Comparative effects of glycerol and dextrose on porphyrin precursor excretion in acute intermittent porphyria. The effects of dietary manipulations on excretion of the porphyrin precursors, delta-aminolevulinic acid (ALA), and porphobilinogen (PBG) were studied in eight patients with acute intermittent porphyria. Three diet periods of 9-17 days comprised each study. In each patient, a "baseline" protein, fat, and carbohydrate intake was kept constant throughout. In addition, during the first diet period each patient received 150 g dextrose; during the second, this was replaced by an isocaloric amount of neutral fat; and during the third, the fat was replaced by 150 g glycerol. In each of the patients, three comparisons of the effect of diet on both ALA and PBG excretion were made: (1) 300 g carbohydrate versus 150 g carbohydrate (dextrose versus fat), (2) 150 g carbohydrate + 150 g glycerol versus 150 g carbohydrate (glycerol versus fat), and (3) 300 g carbohydrate versus 150 g carbohydrate + 150 g glycerol (dextrose versus glycerol). For each of these three diet comparisons, there are sixteen individual comparisons possible for the effect of diet on porphyrin precursor excretion, eight for ALA and eight for PBG. Thus, the mean values for ALA and PBG excretions during each of the diet periods are statistically compared internally within each individual patient. Increasing carbohydrate intake from 150 g to 300 g by isocaloric substitution of dextrose for fat produced a significant (p less than 0.05) decline in eight of the sixteen comparisons of ALA and PBG excretion. Addition of 150 g glycerol by isocaloric substitution for fat caused a significant (p less than 0.05) decline in nine of the sixteen possible comparisons. In the sixteen comparisons of isocaloric dextrose and isocaloric glycerol-substituted diets, dextrose produced significantly (p less than 0.05) lower porphyrin precursor excretion in four cases and glycerol produced significantly (p less than 0.05) lower values in five. One patient showed no significant change on any of the diets. Of the four patients having symptoms believed referrable to porphyria during the study, three reported an improvement in symptoms during the high glycerol intake. The effects of dietary perturbations on porphyrin precursor excretion in acute intermittent porphyria are variable, but glycerol appears to be capable of decreasing the excretions and may prove useful in treating some of these patients.


Amino acid uptake and output by the sheep hind limb. Arteriovenous differences across the hind limb of fed sheep show release of alanine, glutamine, and tyrosine and uptake of serine, glutamate, and possibly lysine. In starved animals there is a net output of most amino acids, although the amount of alanine released, 26 nmol/ml blood, is much lower than reported for human muscle and is less than the cumulative release of valine, leucine, and isoleucine. Since it has been argued that the carbon of alanine is derived from glucose and the nitrogen from the deamination of branched chain amino acids, we suggest that either nutrient availability is limiting alanine output or else sheep muscle has an impaired ability to degrade the branched chain amino acids.


Renal hemodynamics and water excretion in Addison's disease. Patients with Addison's disease have impaired ability to excrete free water. The mechanism of this defect is still not clear. These experiments were designed to help clarify the role of altered renal hemodynamics in the genesis of the defect. Six patients with Addison's disease were studied. Enough salt and water was administered to maintain adequate hydration throughout the study but no hormonal replacement was instituted. After a water load, the urine output (V), free water clearance (CH2O), sodium excretion (UNaV), total solute clearance (COsm), inulin clearance (CIn), and para-aminohippurate clearance (CPAH) were measured by standard clearance techniques. In the control studies V and CH2O were abnormally low. The studies were repeated after administration of DOCA, 2.5 mg daily, for a week. This medication decreased UNaV and improved the plasma electrolyte profile but did not cause a significant change in V, CH2O, GFR, or RPF. The same studies were repeated once more after administration of prednisone, 5 mg daily in divided doses, for a week. This drug induced a marked water diuresis while GFR and RPF remained unchanged. It is concluded that hypovolemia and altered renal hemodynamics are not the only mechanisms of the impaired water excretion in Addison's disease. A severe defect remains after normalization of hypovolemia and this is corrected by prednisone but not by DOCA, through mechanisms which do not involve changes in GFR or RPF.


Muscle nitrogen metabolism in chronic hepatic insufficiency. Whole blood arterio-venous (A-V) differences for ammonia (NH3) and amino acids were determined across the forearm in 14 patients with decompensated alcoholic cirrhosis and hyperammonemia. NH3 was extracted by the forearm in all patients; however, the fractional extraction of NH3 was significantly less in five individuals with gross muscle wasting (13.3% versus 25.3%). There was neither a significant uptake nor release of NH3 in normal control subjects. The arterial concentrations of 12 out of 20 amino acids were strikingly diminished in the patient group. In contrast to normal subjects, in whom the release of alanine exceeds that of glutamine, the A-V difference for glutamine in the patients was threefold greater than that for alanine. The A-V differences for all other amino acids were not significantly different from zero. The results suggest that (1) muscle plays an important role in disposing of NH3 in patients with hepatic insufficiency and (2) a major fraction of NH3 taken up by muscle is released as glutamine.


Free and total insulin levels in a patient with insulin-resistant diabetes mellitus and chronic lymphatic leukemia: effect of prednisone therapy. An insulin-resistant diabetic patient who also has chronic lymphocytic leukemia and very high plasma levels of free and total insulin along with high levels of insulin antibodies is described. In response to prednisone therapy, his insulin requirement decreased, but the total and free insulin concentrations increased as insulin antibody measured as the maximal insulin-binding capacity of plasma remained unchanged. In insulin resistance, persistent hyperglycemia, in spite of high levels of immunoreactive free insulin, presumably reflects peripheral tissue unresponsiveness to insulin. The beneficial effect of prednisone treatment in this patient is discussed, and it is postulated to be the result of either increased availability of free insulin or an increased responsiveness of the tissues to insulin or both.


Effect of protein intake and dialysis on the abnormal growth hormone, glucose, and insulin homeostasis in uremia. To evaluate the role of protein intake in the altered growth hormone (GH) secretion of chronic renal failure, GH responses to mild exercise and to an oral glucose tolerance test were measured in ten uremic patients ingesting both low and normal protein diets. To delineate the effect of uremia on any interaction between GH and protein intake, tests were performed before dialysis, after daily dialyses for 3-4 days and after withholding dialysis for 3-4 days. Results were as follows: (1) exercise-stimulated GH release was increased compared to controls; (2) protein intake did not alter GH secretion, (3) basal GH concentrations were significantly correlated with creatinine levels and were significantly lower after dialysis, (4) dialysis did not improve the oral glucose tolerance test, (5) there was no correlation between glucose tolerance and exercise-stimulated GH levels, basal GH concentrations, or the sum of GH values after glucose, and (6) dialysis significantly increased the insulin response to glucose. In chronic renal failure enhanced GH secretion is not affected by protein intake, does not cause glucose intolerance, and may be related to the degree of uremia. Dialysis does not improve glucose tolerance, but does increase glucose-stimulated insulin release suggesting that insulin antagonism is not ameliorated.


Thyrotropin levels in hyperlipidemic survivors of myocardial infarction. In an earlier investigations, the prevalence of hyperlipidemia in a group of patients who survived myocardial infarction was determined, and family studies were performed to allow genetic classification of patients with hyperlipidemia. Radioimmunoassay for thyrotropin (TSH) has now been performed on plasmas from most of these hyperlipidemic survivors. Elevated TSH values were found in five of the 18 hyperlipidemic women over age 60, and in seven of the remaining 104 hyperlipidemic subjects. Among the various genetically defined types of hyperlipidemia, the highest prevalence of TSH elevations was seen in women with sporadic (nonfamilial) hypertriglyceridemia; four of the ten had an abnormal TSH level, and two of the remainder were receiving thyroid medication. Hypercholesterolemia was not strongly correlated with TSH abnormalities. These data support the hypothesis that clinically inapparent thyroid damage may be associated with coronary artery disease.


Brain tryptophan, plasma free tryptophan and distribution of plasma neutral amino acids. Although rat brain tryptophan is strikingly elevated following portacaval shunt, plasma total tryptophan is unchanged and plasma free tryptophan is not elevated to the same degree as brain tryptophan. Investigation of the concentrations of the neutral amino acids (phenylalanine, tyrosine, methionine, threonine, leucine, isoleucine, and valine) revealed that their distribution and the sum of their concentrations were altered following portacaval shunt, and that this pattern was similar to that seen in humans with cirrhosis of the liver. It is suggested that both the elevation in plasma free tryptophan and the decrease in the competing neutral amino acids, act together to increase the transport of tryptophan into brain when portal blood is diverted around the liver. The implications of these findings in therapy of hepatic coma is discussed.


Parathyroid hormone and vertebral osteosclerosis in uremic patients. Six out of 30 patients with chronic renal failure showed osteosclerosis in the lateral radiograph of the lumbar spine. When two groups with a similar degree of renal impairment were compared, the patients with osteosclerosis were younger and had a significantly higher level of circulating PTH (p less than 0.05) and total hydroxyproline excretion (p less than 0.02), than patients without overt osteosclerosis. The metacarpal cortical thickness was significantly reduced in patients with vertebral osteosclerosis. The results suggest that in patients with chronic uremia endogenous hypersecretion of PTH is one of the most significant factors responsible for the development of osteosclerosis. The mineral released from other skeletal sites could be utilized in the mineralization of the newly formed trabecular bone without any external calcium gain.


Hyperprolactinemia influences renal function in man. Renal handling of solute and water following oral water loading was determined in six subjects with small pituitary adenomas associated with nonsuppressible hyperprolactinemia. Compared to control subjects, urine volume and solute excretion were significantly diminished in the hyperprolactinemic group. This was attributable to a decrease in osmolar clearance. Free water clearances were not different from control subjects. Hypothyroidism and adrenal insufficiency as an explanation for the antidiuresis were excluded in each patient. The data supports the suggestion that prolactin influences renal function in man.


Utilization of oxidizable substrates by the sheep hind limb: effects of starvation and exercise. Measurements of substrate uptake by the sheep hind limb show a pattern similar to human and other monogastric animals. Thus free fatty acids (FFA) are the principal substrates at rest and during exercise while beta-hydroxybutyrate and acetoacetate are major nutrients in starved animals. The hind limb has arteriovenous differences for glucose and lactate which indicate that glucose supplies about 27% of the fuel of respiration during exercise, but the hind limb in resting, fed, and starved animals returns essentially all of the glucose carbon to the blood in the form of lactate. This finding is consistent with a conservation of glucose in aminals which obtain very little dietary glucose. Although some acetate is extracted from the blood in fed sheep, the utilization of this nutrient can account for only 2% or less of the oxygen uptake in the hind limb of starved or exercising animals. Thus, while acetate is the major product of the sheep rumen it is not used directly as a major energy source. We propose that most of the actate is converted to FFA which can be stored as triglyceride or oxidized in muscle.


Renal excretion of uric acid during prolonged fasting. Serum and urine uric acid were evaluated during prolonged therapeutic fasting in 15 obese patients. With increasing ketonemia the serum uric acid rose from a control value of 5.9 +/- 0.4 to 12.5 +/- 1.0 mg/100 ml at 7 days and then decreased progressively to 7.7 +/- 1.3 mg/100 ml by 28 days despite sustained ketonemia. The uric acid clearance were 5.5 +/- 0.9, 1.8 +/- 0.2, and 4.4 +/- 1.5 ml/min at days 0, 7, and 25 of fasting. At the same times the creatinine clearances were 114 +/- 11, 80 +/- 6, and 64 +/- 6.3 ml/min. There was no evidence of a renal tubular abnormality as assessed by glycosuria, bicarbonaturia, or increased phosphaturia. Urate binding to plasma proteins remained unchanged. Acute studies of the renal handling of uric acid revealed a uricosuric response to the administration of sodium lactate or sodium bicarbonate by intravenous infusion and low-dose acetylsalicylic acid orally. This renal tubular response departs significantly from that observed during the overnight fasted state and could not be accounted for by extracellular fluid volume expansion or the induced acid-base changes.


Human leukocyte peroxidase: activity of a soluble and membrane-bound enzyme form in normal persons and patients with neuronal ceroid-lipofuscinosis. Human leukocytes contain a peroxidase fraction soluble in 0.1 M phosphate buffer and an insoluble peroxidase component with 10--15 times higher specific activity which can be extracted by 0.1 M phosphate buffer + 0.2% Triton X-100 + 0.2% sodium taurocholate and sonication. Both enzyme components have been estimated spectrophotometrically with the substrate hydrogen peroxide (final concentration 1 mM) and the hydrogen donor p-phenylenediamine (final concentration 28-55 mM) within the first 60 sec. The pH-optimum of the soluble and membrane-bound leukocyte peroxidase is at pH 7.0 with a second smaller peak at pH 5.5. Using 0.2 M boric acid/0.05 M sodium borate buffer (pH 7.6) instead of phosphate buffer a 40%-50% increase of enzyme activity can be achieved. In two patients with the juvenile form of neuronal ceroid-lipofuscinosis (type Spielmeyer-Vogt) the activity of soluble leukocyte peroxidase was considerably reduced, in one patient with the late infantile form (type Jansky-Bielschowsky) the activity was just below the normal range, and in two patients with the adult form (type Kuf) activity was normal. In all patients the activity of membrane-bound leukocyte peroxidase was not significantly altered. Only one of four heterozygotes for the juvenile type had deficient values of the soluble enzyme. The variability of the peroxidase findings in patients and carriers with neuronal ceroid-lipofuscinosis make it uncertain whether this represents the primary enzymic defect.


Effect of hypophysectomy on weight gain and body composition in the genetically obese yellow (Ay/a) mouse. In order to investigate the role of the pituitary in yellow obesity, genetically obese yellow mice (Aya) and normal nonyellow siblings (aa) were either shamoperated or hypophysectomized by a paraphyarngeal method at 45--50 days of age. The operated animals were weighed for 13 wk and their carcasses subsequently were analyzed for fat, water, and lean body mass content. Completeness of hypophysectomy was assessed by microscopic examination of stained serial sections of the brain and attached hypophyseal capsule. Completely hypophysectomized Aya mice still gained more weight than hypophysectomized nonyellow siblings and showed the excessive accumulation of fat characteristic of the yellow obesity. We conclude that the pituitary and the endocrine pathways it controls are not primarily involved in the expression of yellow obesity.


Self-descriptions of applicants to medical school. An analysis of self-descriptive essays by applicants who successfully gained entry to medical school shows that five sub-types of entrant can be differentiated. Medical schools have not yet deliberated on the sort, or sorts, of person most needed in the medical profession, but doubtless individual selectors exercise personal if undeclared preferences.


A partially self-instructional system that any teacher can develop and implement. Some authors have suggested that the teacher has two basic choices of style which can be used to influence learning: he/she can manage learning resources or he/she can function as such a resource. Part of the appeal for the authors of the course format described here is the blurring of that distinction. Functioning both as a manager and a resource appears to us a near optimal role for the teacher.


Medical student evaluation in the absence of examinations. Traditional examination systems achieve a high degree of pseudo-precision, producing relatively little information that is constructively useful for student or teachers, and conveying it in the form of scores and marks that appear falsely accurate. The rationale and methodology of a structured evaluation system, in the absence of formal examinations, and based on validated self-assessment, are described. An account of the organization and uses of such a process, and a description of some new evaluation techniques used, is based on the system currently being evolved in the McMaster University M.D. Programme.


Multiple choice questions: to guess or not to guess. Multiple choice question papers in which the student has a 'don't know' option are widely used in undergraduate and postgraduate examinations in Medicine. In the present study students' performance in papers with a 'don't know' option has been compared with their performance when they are instructed to answer all the questions. By completing questions left unanswered (i.e. 'don't know' options) students were able to increase their score significantly and the rank order of the students in class is changed. Answers omitted may indicate complete ignorance or various degrees of knowledge. It is concluded that the 'don't know' option in multiple choice question papers favours the bold and test-wise student and in consequence their validity as a measure of achievement may suffer. Papers in which the student is instructed to answer all the questions are to be preferred to those in common use where there is a 'don't know' option.


Upstairs, downstairs: medical students in their first clinical year and their previous experience of work in hospitals. In a study of Edinburgh students in their first clinical year it was found that a sizeable proportion had had some prior experience of hospital life and work from vacation jobs--such as being porters, auxiliary nurses and so on. Students' retrospective accounts of such experience are reported. The most salient aspect of hospitals seen from this vantage point concerned the division of labour between grades of staff, and the hierarchical organization of hospital personnel. Students saw the experience primarily as a chance to see medicine 'from the other side'. It is suggested that such experiences can be drawn on in the teaching of sociology to undergraduate students.


A performance-based method of student evaluation. A method of medical education has been developed which emphasizes audit of student performance in terms of behavioural traits (thoroughness, reliability, analytic sense, and efficiency) rather than in terms of memorized knowledge. This method is dependent upon the Problem-Oriented Medical Record. The tools developed for the audit and some preliminary results are presented.


Methods of attitude assessment for medical teachers. A variety of methods to assess attitudes toward patient care, the medical profession and medical education have been described. Direct, written methods have been most widespread; they are most useful with anonymous respondents when group, rather than individual, data are sought. Examples of disguised, written and audio-visual methods were also presented to stimulate readers to experiment with these approaches. Finally, observational methods were reviewed to capture behaviours in real and simulated situations that reflect attitudes.


Trainees assessment of vocational training in psychiatry: a pilot study at the Maudsley Hospital. The adequacy of postgraduate trainees is assessed rather more frequently than that of the teaching process. A survey was therefore undertaken of the views of sixty-two junior psychiatrists regarding the clinical units they had worked on during their 3-year rotational training programme at the Maudsley Hospital. The quality of the training experience was felt to be related to work load (not too light), to the number of trainees attached to each consultant, and to the attention given by the consultant to instruction on practical management. The factors felt to need most attention were feedback from consultants on the trainee's performance, and the standards of academic instruction and of interdisciplinary teamwork.


Medical education in France, Germany, Italy and the United Kingdom compared. 1. The purpose of the visit was to compare postgraduate medical education and training in the United Kingdom with that in France, the Federal Republic of Germany, and Italy. 2. Except in Italy, there appeared to be widespread agreement that specific postgraduate training for general practitioners was essential to improve the quality of practice and to relieve the undergraduate curriculum from the necessity to provide comprehensive medical training to prepare a graduate for independent practice. The main difficulty appeared to be the development of good 'teaching' practices. 3. Direct comparison between training programmes for specialist practice is not straightforward in view of the different staffing structure in continental hospitals and the existence of private specialist practice to which patients have direct access. Training appears to be generally longer in the United Kingdom, possibly due to the necessity of passing postgraduate diploma examinations, but outside the university hospitals the fully trained specialist (consultant) enjoys a higher status and independence than most hospital specialists in other countries. The absence of equivalent bodies to the Royal Colleges and Faculties places responsibility upon universities for specialist training on the continent; standards are not coordinated nationally, and vary significantly from region to region. 4. The need for continuing medical education for all doctors is accepted; this is essentially voluntary, although there are variable direct and indirect incentives. Programmes are organized on a local or regional basis in most countries, but in Germany and the U.K. there is a growing trend towards national coordination of both training programmes and the provision of continuing education. 5. The recent reorganization of the National Health Service in the United Kingdom provides opportunities for 'public health' doctors to become involved in the coordination of clinical services and to relate these to the needs of the public at large, as well as to provide preventive health services. These opportunities do not exist in France, Germany and Italy, where public health services remain discrete from clinical medicine, and postgraduate training is largely confined to formal teaching at designated institutes which are university based only in Italy. Opportunities for university staff to become involved in the organization and delivery of health care appear to be greater, therefore, in the United Kingdom than in other countries.


Correlation between students' results in pre-clinical and final surgery examinations. The results obtained in each subject of the first 4 years of a 6 year course in medicine were assessed and compared with the final result obtained in surgery together with the result from a class test in surgery at the beginning of the fifth year. Two hundred and thirty-five students graduating between 1969 and 1973 were assessed, the correlations being tested with regression techniques. There was a highly significant degree of correlation between the final surgery result and all the previous records. However, there was a wide scatter of results, and the predictive value for the individual student was imprecise.


The final examination in United Kingdom medical schools, 1974. The structure, character and results of the final M.B. examinations held in United Kingdom medical schools in 1974 were investigated by postal questionnaire. The mean failure rate (10-5%, range 0-24-6%) was significantly higher in the student sample from the London medical schools compared with those in the periphery. No significant sex difference in total failure rate was noted. Wide variations were observed in the length and character of the examinations.


The effect of a spaced sex education course on medical students' sexual knowledge and attitudes. This paper reviews the literature and emphasizes the rapid expansion of medical sex education, which has created a diversity of course content, curriculum timing and strategies. One variable of medical sex education programmes is whether they are massed or spaced courses. The authors conducted testing on 159 first year medical students who took a spaced sex education course. Significant changes in cognitive knowledge as well as attitudinal tolerance of others is reported. No changes were found in styles of thinking as measured by the Rokeach Dogmatism Scale.


Doctor-patient communication in general practice consultations. Detailed study of a series of tape-recorded interviews enabled the author to carry out a critical self-audit of his consultations. The analysis of categories of verbal interaction in doctor-patient consultations proved to be a practical and reliable method of studying the doctor-patient relationship. The methods and techniques used in this research could, with advantage, be employed in the fields of undergraduate and postgraduate teaching. Since a satisfactory doctor-patient relationship is of great value, study in depth of the verbal interaction between doctor and patient in general practice consultations can provide guide lines to those who seek an improvement in doctor-patient communication.


What should be taught in anatomy?

What should be taught in anatomy? The aim of the undergraduate course in topographical anatomy should be to enable the student more meaningfully to carry out a physical medical examination, and to become familiar with the normal, thus providing the intellectual and technical background for later study of the abnormal. Attendance at postgraduate courses should be compulsory for admission to postgraduate surgical examinations; such courses should be complementary, not supplementary, to undergraduate courses.


The value of ordinary and advanced level British school-leaving examination results in predicting medical students' academic performance. This paper examines the correlation between students' school-leaving examination results and medical school examination results, and discusses the usefulness of O and A level examination results as predictors of a student's ability to pass pre-clinical examinations in anatomy, physiology and biochemistry.


Student test type preference and its relation to personality and achievement. 1. Test type preference of 227 medical students was investigated by means of a questionnaire. 2. A majority of students believed that MCQ examinations gave rise to less advance anxiety than other forms of examination. 3. There was a highly significant correlation between preference and performance, probably as a result of reciprocal reinforcement between them. 4. A multiple linear regression analysis revealed than the scales stability/neuroticism, extraversion/introversion, general mental ability and native language had a significant influence on test preference. There was a significant trend for confident, stable students to demonstrate preference for MCQ while tense, anxious students tended to prefer other test types. 5. We conclude that a mixed examination format is desirable not only on theoretical grounds, but was also preferred by these students.


Patient monitoring in the operating room--an anesthetist's viewpoint. The spectrum of patient monitoring techniques and equipment presently available in the operating room is reviewed from the anesthetist's viewpoint. Although electronic monitoring instruments are becoming more sophisticated with self-contained microprocessors or computer interfaces, few are designed for performance specifically within the hostile environment of the operating room. Intraoperative patient monitoring equipment lacks interchangeable transducers, facilities for automatic collection of physiological data, and methods for the display of trends in the patient's condition. Event recording during anesthesia depends upon the time-honored but inefficient handmade record of the anesthetist. Within the context of developing a computer-assisted monitoring and display system, this commentary presents the physician's perspective of instrumentation limitation and successes.


Future trends in neurosurgical instrumentation--a speculative approach. The neurosurgeon is confronted with a cumbersome array of sophisticated instrumentation with which he must cope. A multitude of tubes, wires, and cables spill about his feet and operative field, cluttering his work area and limiting his mobility. In this communication, the consolidation of power sources, improvement in the power delivery systems to the operative site, and the creation of an equipment console incorporating built-in lights, microscope, power sources, vital-sign monitors, and instrumentation are considered. The physiological condition and milieu of the surgeon are also examined. An attempt is made to outline some of the complex and provocative problems involved in improving the surgeon's physical work environment and in improving his instrumentation.


Improving radiology in surgery.

Improving radiology in surgery. The time has come to reevaluate the use of films of substandard quality obtained from outdated radiography equipment. The authors recommend that surgical subspecialists, orthopedic surgeons, emergency room physicians, gastroenterologists, or whoever employs radiology in the operating room ensure that technological progress in radiology be transferred to the surgical area. The mobile C-arm image amplifier with television fluoroscopy and single-image storage device should be considered for orthopedic surgery and ER rooms. More sophisticated equipment is required for operative cholangiography and operative angiography.


Design hazards of electrosurgical devices. The tremendous lifesaving value of adjunct electrosurgery to the medical profession is not without potential hazards. The hazards, which can be classified as radio-frequency burn hazards, shock hazards, electrocution hazards, and explosion hazards, may result from equipment design circuitry, possible failure modes, or operator error. The three basic electrosurgery systems currently being marketed--grounded output systems, referred-to-ground output systems, and floating output systems--are described, and the hazard potential of each system, as well as the hazard potentials of modifications of these systems, are identified. The authors propose a safety system to eliminate most of the hazards cited for the other systems, recommend minimum circuit performance requirements, and evaluate an electrosurgery standard.


Trends in operating room devices.

Trends in operating room devices. Although trends in the use of operating room devices have generally followed advances in technology, the trends are not always influenced as much by surgical need as they are by industrial expediency and commercial promotion. Nonetheless, a broad view of trends in OR devices definitely points to efforts at greater compatibility between devices made by different manufacturers. To mention a few examples, operating tables are being made more compatible with OR X-ray equipment; surgical lighting is being designed for greater compatibility with air-handling systems and video equipment; power consoles have reduced the clutter of tubes, hoses, and wires in complicated operations, and have become more functional in keeping with the trend away from electrical power and toward nitrogen power for driving surgical tools; cabinetry is being designed to employ clean-air principles; and surgical apparel and barrier materials are undergoing close scrutiny for their effectiveness against moist bacterial strike-through in lengthy wet operations. Operating room devices form an important segment of the devices classified by the FDA, and are expected to benefit by the application of standards in performance and safety. This trend will affect not only the devices themselves, but all other facets of operating room design and engineering.


Laser medical instrumentation.

Laser medical instrumentation. In spite of inadequate budgets, significant research and development studies have been made on laser medical instrumentation applications for both diagnosis and treatment. Diagnostic instrumentation includes the laser microprobe for cation microanalyses, cytofluorometry, interferometry, transillumination, holography and acoustical holography, and communications and information handling. Laser investigative surgical instrumentation includes lasers of argon, carbon dioxide, neodymium-YAG, and ruby, which are used as optical scalpels. Advantages of laser surgical instrumentation include precision, color absorption for lasers in the visible light range, and hemostasis.


Management of ruptured abdominal aortic aneurysms. If an abdominal aortic aneurysm causes symptoms, surgical replacement is mandatory. Once frank rupture has occurred, the outlook is grave, but immediate surgery and intensive general care can allow survival in up to 50% of patients.


Nose and throat: occupational hazards.

Nose and throat: occupational hazards. Recent reports on the effects of occupational factors in disorders of the nose and throat are reviewed. Chemical irritation is usually responsible for immediate effects, which are transitory but unwelcome. Allergic responses may be more troublesome. The more insidious carcinogenic properties of some industrial irritants are now being recognized.


Treatment of intestinal parasites in Australian aboriginal children. Five to nine-year-old Aboriginal children on Mitchell River Community maintained a satisfactory growth rate in the presence of multiple infections with intestinal parasites. Intensive treatment was successful in eliminating Giardia lamblia, Entamoeba histolytica, and Strongyloides stercoralis infections, but reinfection with G. lamblia was rapid. Treatment failed to produce any growth spurt in the group. This may have been due to the rapidity of reinfection, but raises the question of whether intestinal parasites contribute significantly to growth retardation or whether growth retarded children have  an immune deficit rendering them more susceptible to parasitic infections.


Cadmium exposure and renal accumulation in an Australian urban population. An indication of the degree of cadmium exposure and renal accumulation in an Australian population (Brisbane) has been obtained from cadmium determinations of urine from 98 patients and post-mortem kidney specimens from 91 patients. Urinary excretion of cadmium from normal or unexposed adults and lead exposed adults was consistent with normal values from other developed countries. There was no apparent relationship between cadmium and lead excretion levels for individual urine specimens. Renal cadmium concentrations were used to estimate the average total cadmium content for a "standard man" and renal cortex concentrations. The results were similar to reported studies from the United Kingdom and Europe, but lower than those from Japan. Daily intake of cadmium was estimated to be 30 to 50 mug, which compares favourably with the FAO/WHO1 "provisional tolerable weekly intake" of 0-4 to 0-5 mg cadmium per adult per week. It is concluded that Australian populations exposed to potential sources of industrial and environmental cadmium contamination should be investigated.


Cancer research for small countries: why and how? Small countries can, and in fact have a duty, to carry out cancer research. To be effective research must be carried out by teams of no fewer than eight to 10 full-time professional research workers, adequately funded on a relatively long-term basis.


Beclomethasone dipropionate in paediatric asthma. An investigation into the use of beclomethasone dipropionate aerosol in the management of 42 severe asthmatic children, ranging in age from two-and-a-half to 16 years with a mean age of seven years is presented.


Histological appraisal of ulcerative colitis fibreoptic colonoscope biopsy specimens. The availability of the fibreoptic colonoscope with biopsy facilities has created new opportunities for the investigation of ulcerative colitis. Morphological assessment of the disease, which has hitherto been limited to observing changes in the mucosa of the sigmoid colon and rectum, can now be made on biopsy material obtained under direct vision from the large bowel above the level of the sigmoid. On the basis of 157 colonoscopic biopsies taken from 38 patients with endoscopic appearances of the disease is proposed. The classification is as follows: (i) active chronic phase without ulceration; (ii) active chronic phase with ulceration; (iii) quiescent chronic phase; (iv) healed chronic phase; (v) precancerous phase. Three degrees of severity (mild, moderate and severe) for each phase are recognized.


Perforated peptic ulcer long-term follow-up. A series of 349 survivors of perforated peptic ulcer was followed for periods of up to 23 years. Almost nine out of every 10 patients suffered from dyspepsia during follow-up. Subsequent elective gastroduodenal surgery was required in more than a quarter of the cases. The surgery rate for gastric ulcer was more than one and a half times that for pyloroduodenal ulcer, and for females almost double that for males. The highest rate of all was for females with gastric ulcer, of whom almost one half came for surgery. One in five patients bled during follow-up. One in eight developed stenosis of the stomach of duodenum, and one in 11 perforated again. There was a significantly increased incidence of subsequent perforation and stenosis in those with an initial perforation of 5 mm or more in diameter. Gastric carcinoma occurred in less than 2% of cases and was restricted to cases of pyloroduodenal perforation. When complications occurred, the majority did so within five years. Only 15% of the 262 patients about whom complete information was available had no complications on follow-up. The indications for definitive surgery at perforation should be extended to include perforated gastric ulcer in the female, particularly if the ulcer is large.


Vitamin B12 malabsorption associated with a normal Schilling test result. A patient with vitamin B12 deficiency and a true normal Schilling test result is presented. This patient could absorb chemically pure vitamin B12 normally but could not absorb protein-bound vitamin B12.


Management of asymptomatic abdominal aortic aneurysms. The decision whether to operate on a patient with an asymptomatic abdominal aortic aneurysm is difficult. It depends on balancing the risk of its future rupture against the risk of the operation. A large aneurysm (greater than 7 cm in diameter) should certainly be replaced. A small aneurysm (less than 5 cm across) should simply be observed. The need for surgery on an aneurysm between 5 cm and 7 cm in diameter is doubtful.


Gastrointestinal endoscopic polypectomy. Recent advances in the field of gastroenterological endoscopy have now embraced endoscopic polypectomy. Experiences at the Royal North Shore Hospital over a period of one year include 42 colonic and three gastric polypectomies. Rectal bleeding was the main presenting feature in the patients with colonic polyps. All colonic polyps were situated between the sigmoid and transverse colon. Eighteen polyps were under 1 cm in size, 15 between 1 and 2 cm and nine over 2 cm. There was one carcinoma detected in each of these groups. No significant complications were encountered with any of these patients. The high yield of malignancy, none of which could be suspected on clinical or radiological grounds, more than justifies the introduction of this endoscopic procedure which will offer considerable saving from both the point of view of economic factors and personal discomfort.


What does the intern do?

What does the intern do? A minute-by minute professional work study was undertaken on three interns at the Royal Adelaide Hospital from Monday to Friday of three consecutive working weeks in December, 1972. The clinics studied were general medical, general surgical and urological. There are obvious major limitations in extrapolating the results of this study beyong the hospital involved at the time of year concerned. Nevertheless, allowing for this factor, it is probably a matter of general principle that there is excessive disproportion between the time spent by an intern in clinical work, contrasted with the time spent in clinical activity, transit, and waiting time. It is suggested that the work of an intern needs more support by better secretarial and similar facilities.


The paediatric surgeon-operating physician or surgeon. To elucidate a child's symptoms one must understand the child. A wide range of medical conditions may present to the consultant paediatric surgeon, so that he must be qualified by training to recognize them. Within a children's hospital he is aptly trained and placed to act as a focal point whenever disease or injury involves a number of surgical specialties.


Rotaviruses and acute gastroenteritis of infants and children. By means of electron microscopy and ultracentrifugation techniques rotavirus-like particles have been found in 84 of 269 specimens of faeces collected from infants and young children admitted to the Royal Alexandra Hospital for Children, Camperdown, N.S.W. during the usual winter outbreak of infantile gastroenteritis. Morphologically intact viruses were also found in faecal specimens stored at -20 degrees C for up to nine years. Rotaviruses were found in specimens collected from five newborn infants with diarrhoea, and in a subsequent survey of the nursery when 23 neonates without diarrhoea were present, 12 (52 %) were found to be excreting virus. Morphologically similar viruses were found in six of 16 faecal specimens from newborn calves with gastroenteritis (scours), and an antigenic relationship between the rotaviruses of human and bovine origin has been demonstrated.


New virus associated with diarrhoea in neonates. Since December, 1974, there has been an increase in the incidence of acute diarrhoea in the neonatal nurseries of five Melbourne metropolitan hospitals. Four of these have had epidemics, and the incidence of endemic diarrhoeal disease has increased. Extracts of faeces from 148 patients from the five hospitals were examined by electron microscopy. "Duovirus" particles were detected in 82 of these extracts, including at least one from each hospital. No bacterial pathogens were isolated. It seems likely that "duovirus" is an important cause of sporadic and epidemic acute diarrhoeal disease in neonates. It is important to note that the absence of a recognized bacterial pathogen does not exclude an infective cause, especially when sugar intolerance is present. Appropriate measures to minimize the spread of infection must be employed.


Triage in civilian practice.

Triage in civilian practice. A triage area for the assessment and treatment of acutely ill patients on their admission to hospital was created. Four groups of patients were defined who were to be sent to this area rather than be treated in the casualty department. The area was contiguous with the hospital intensive care unit rather than the casualty department as the ease of providing trained staff members and equipment on a 24-hour basis outweighed the disadvantage of geographical separation from the casualty department. The increase in workload created for the intensive care members of staff was small, while the reduction in delay for seriously ill patients was considerable.


Accuracy of blood glucose measurements using a reflectance meter. The performance of a stock reflectance meter for measuring blood glucose levels with glucose oxidase test strips has been assessed. Glucose values obtained were spuriously high, and the response of the instrument was non-linear. The instrument could not be recommended as an accurate means of determining glucose levels, but may be useful for detecting hyperglycaemia and hypoglycaemia.


Reuse of a disposable dialyser for home dialysis. A disposable parallel flow plate dialyser (Gambro Lundia) has been evaluated. It is comparable in surface area and efficiency to the standard Kiil dialyser and can be regularly reused six times, combining the reliability and convenience of a prefabricated, factory-tested unit with the low cost of the Kiil dialyser.


Cerebellitis in glandular fever.

Cerebellitis in glandular fever. Cerebellitis as an unusual manifestation of infectious mononucleosis is reported for the first time in Australia. Complete recovery occurred, as has been the rule in previously described cases. The difficulty that may be encountered in early diagnosis is discussed, and screening for infectious mononucleosis is suggested for elusive neurological illnesses. The possible significance of cerebrospinal fluid antibodies is considered.


Treatment with the artificial kidney (dialysis). For patients with chronic renal disease, haemodialysis can provide reasonable rehabilitation and, in most cases, a life expectancy in excess of 10 years. However, dialysis is unable to provide for any loss of the kidneys' endocrine or metabolic activities and the kidneys' excretory capacity is only replaced suboptimally. Recent well controlled studies on the frequency, time and techniques of dialysis, instigated mostly as a consequence of recent hypotheses, such as the "middle molecule" theory and consideration of the potential importance of residual renal function, have resulted in a complete reassessment of the nature of adequate dialysis. Developments such as sorbent-based dialysis are leading to a wearable dialyser. Theoretical and hardware developments are providing not only more adequate treatment, but improved rehabilitation for those patients on chronic dialysis therapy.


The heart attack and doctor/patient communication. In patients with recent proven or suspected myocardial infarction, understanding of the nature of a heart attack was explored. A wide range of misconceptions, some of them frightening, was revealed; there was a poor understanding of some terms commonly used in discussion with patients; the potential for creation of new misconceptions by doctors and nurses was highlighted.


Post-pill anovulation.

Post-pill anovulation. Basal temperature records were maintained by 346 women after ceasing to take oral contraceptives; 167 had ceased using combined and 179 had ceased using low-dose sequential formulations. In the first cycle after withdrawal of low-dose sequential pills, 11 (6%) women failed to ovulate and ovulation was delayed in five cases. Short luteal cycles occurred in 14 subjects. In 83% of the subjects there was no disturbance of ovulation. In the first cycle after withdrawal of combined oral contraceptives, 49 (30%) women failed to ovulate and ovulation was delayed in 29 cases. A short luteal phase was observed in 26 subjects. In only 38% of the subjects was there no disturbance of ovulation. The minimal disturbance to ovulation in the cycle after the withdrawal of low-dose sequential formulation indicates that this type of oral contraceptive carries little risk of producing post-pill infertility. Women under the age of 21 years were anovulatory nearly twice as frequently as older women after ceasing to use combined oral contraceptives.


Post-pill infertility.

Post-pill infertility. One hundred and fifty-one nulligravid women and 63 parous women stopped taking low-dose sequential oral contraceptives in order to become pregnant. During the first post-Pill cycle, 39% of the nulligravid and 54% of the parous women conceived. These figures have been compared with data from the Royal College of General Practitioners survey in England, in which 13% of nulligravid and 17% of parous women conceived in the first cycle after ceasing to take combined oral contraceptives. The percentage of nulligravid women not pregnant six months after withdrawal of low-dose sequential formulations was 19% compared with 32% after withdrawal of combined oral contraceptives. The corresponding figures for parous women were 5% and 21%. Available data suggest that after withdrawal of low-dose sequential oral contraceptives, the incidence of post-Pill infertility is lower than that after withdrawal of combined oral contraceptives. The extent of this difference is 16% three months after withdrawal of the Pill and 10% six months after attempting pregnancy.


Cerebral tumour with intracranial angioma. This paper concerns the simultaneous occurrence of tumours, a meningioma and intracranial angioma, of diverse histological characteristics. Their clinical radiological and pathological implications are discussed.


Facial and cervical injuries.

Facial and cervical injuries. It is not commonly appreciated that mandibular and maxillary fractures are occasionally associated with fractures of cervical vertebrae. An incidence of 1-6% in a three-year survey at the Royal Brisbane Hospital is reported and the implications are discussed.


[The normal range of the pulmonary artery pressure during ergometrical exercise (author's transl)]. In healthy subjects the pulmonary artery pressure was measured during exercise tests with the aid of the flow guided catheterisation. The work load was determined on bicycle ergometer in recumbent position in form of a multistage exercise test with relative steady state periods till exhaustion was reached. In this way, during the highest work load (200 Watt) the systolic pulmonary artery pressure was 33.9 +/- 5.5 mm Hg, the diastolic pressure 17.5 +/- 3.6 mm Hg and the pulmonary mean pressure 24.7 +/- 4.0 mm Hg. The factors influencing the pulmonary artery pressure during work are discussed.


[Diagnostic application of external electrical impulses in form of an overdrive for the influence of an implanted QRS inhibited demand pacemaker system (author's transl)]. The possibility of influencing an implanted demand pacemaker system by means of an external electrical impulse has already been described by several authors. In this paper further clinical applications of this method are discussed in relationship to patients who have a pacemaker of the QRS inhibited type. Electrodes are applied externally over the regions of the pacemaker generator and the catheter tip. Electrical impulses are then given at a higher frequency than those of the implanted pacemaker, thus enabling the impulses of the internal pacemaker to be inhibited, and consequently the spontaneous action of the heart to be observed. Further possible clinical applications with the aid of examples are discussed: the identification of persistent arrhythmias, digitalis intoxication, fresh cardiac ischaemias, as well as evidence of the need for temporary stimulation during generator change.


[Acute myoglobinuria accompanied by renal failure in high febril infection (author's transl)]. A 41 year old man developed a myolysis with myoglobinuria during a period of high fever. The clinical signs were severe myalgia with general muscular weakness without manifest localized paresis. Electromyographically a diffuse generalized floride myopathy was found. Besides the extreme increase of CPK, a myoglobinuria was already macroscopically visible, which caused an acute renal failure. The treatment included corticosteroids and hemodialysis. An illness of several weaks was followed by complete recovery. As other known factors leading to myoglobinuria have been excluded, and the complement fixation reaction for Herpes simplex was more than 1:80, a viral-toxic etiology of this disease might be considered.


[Treatment of peripheral occlusive vascular disease with pentoxifylin (author's transl)]. 102 patients suffering from peripheral occlusive vascular disease were treated with Pentoxifylline (Trental) parenterally (i.v. infusions) and orally (dragees). Surprisingly good therapeutic response was obtained not only in patients stage II but also stage III (after Fontaine), in total 84% of the patients showing improvement. These favourable results can only be explained by increase of nutritious circulation indicating an improvement of blood-flow-properties in the microvasculature. The observed particular efficacy of Pentoxifylline necessitates a more differentiated valuation of the systemic (intravenous) administration of vasoactive drugs all the more so as the majority of patients with occlusive vascular disease are accessible to conservative treatment only.


[Anabolic steroids: damages, effect on performance, and on metabolism (author's transl)]. 10 normal persons (age: x=22 years) and 15 weight lifters (age: x=27 years) were studied before and three months after taking Nandrolone danoate (ND). Strength exercises, hear rate during ergometer work, physical working capacity and certain biochemical variables were measured in the experimental group, as well as in a controll group of 7 weight lifters. Six weight lifters in the experimental group who had been taking ND for at least 3 years were also studied to determine whether there were any deleterious effects on their health. In addition, 75 athletes who had been taking anabolic steroids were investigated to determine the possible effects. It was found that: 1. In spite of an 7% increase in performance, the maximal heart rate was not higher when the subjects took ND. During submaximal work loads the heart rate (p less than 0.025) and the blood lactate level (p less than 0.05) were lower. During physical work, there was essentially no effect of ND on glucose or total lipids in serum. 2. The results from the three-months study, from the weight lifters taking ND for 3 years, as well as from 26 of the 57 athletes who had been taking ND showed no evidence of a deleterious effect of ND (based on 26 biochemical measurements). It would appear, therefore, that the general suggestion of a detrimental effect of anabolic hormones is not justified. 3. Damages or functional disturbances were found in 31 athletes and 3 weight lifters of the experimental group after oral application of anabolic alkyl-steroids. After a period of time without alkyl-steroid administration, all investigated biochemical parameters returned to normal levels; thus it appears that the aforementioned pathological findings are reversible changes in liver function.


[Embolia cutis medicamentosa (author's transl)]. A rare secondary effect of intramuscular injections is reported in three own observations: This embolia cutis medicamentosa has been relatively often found in former times as result of bismuthe and mercury injections during lues therapy and today is only occasionally found, especially after intramuscular injections of phenylbutazone-containing antirheumatics. The question is discussed whether this medicamental embolism is really due to an embolic occlusion of small skin arteries. The typical clinical picture of the infarct-resembling skin necrosis in livid skin area could also be explained by vessel necrosis or thrombosis in the site of injection itself.


[Tricyclic psychotropic drugs: complications and therapy of Choloprothixen-intoxication (author's transl)]. The broad use of tricyclic psychotropic drugs demands from the physician to take in account the side effects of these drugs. These side effects relate primarily to the cardiovascular system. We describe a suicidal Chlorprothixen(Taractan-)intoxication of a 27 year old female patient. The progress of this intoxication was characterized by severe arrhythmias, mainly ventricular tachycardias. The pathogeneisis of the cardiotoxic reaction is discussed. Since there is no specific antidot against these drugs, therapy of side effects is limited to symptomatic treatment including administration of cholinergic drugs. Severe cardiovascular reaction also can be found, when the drugs are used in therapeutic doses. The cardiodepressive effect of tricyclic psychotropic drugs may lead to considerable complications, especially in older patients.


[Complications of the sternal puncture (author's transl)]. The case of a 57 year old female patient suffering from plasmocytoma with a sternal fracture after local puncture characterized by a late healing tendency is reported. According to the literature the complications of this diagnostic method, known up to now, are described with special emphasis to the pathomechanism and the clinical course of the mostly fatal sternal perforation with cardiac tamponade. Puncture of the iliac crest instead of the sternal region is recommended in cases with serious osteoporotic or osteolytic defects of the sternal bone.


[Telemetry of blood pressure in healthy subjects and patients with tachycardia and hypertension under Prindolol treatment]. The effect of 0.4 mg i.v. Prindolol on arterial blood pressure and heart rate was investigated with continuous measurement by telemetry. The 19 healthy subjects and 13 patients were controlled at rest supine, standing and finally during exercise. Following Prindolol a significant decrease of blood pressure and heart rate was observed, in particular in the group suffering from hypertension and tachycardia and under conditions of exercise, when compared with the pretreatment values. No side effects were noted.


[Early mobilization after myocardial infarction. Hemodynamic and metabolic studies]. In a controlled study two groups of patients with acute myocardial infarction were compared. One group consisted of 75 patients who were early mobilized; a control group of 38 patients was treated conservatively. Although the early mobilized patients showed a slightly increased stress on the hemodynamics these findings had no clinical significance: the complication rate in this group was not higher than in the conservatively treated patients. The main advantage of early mobilization however as compared to conservative treatment seems to be the prognostically and psychologically favourable effect especially with respect to rehabilitation.


[Appearance of anaerobic vibrionen species (vibriones) in cases of chronically recurrent vaginal fluor (author's transl)]. In 480 patients suffering from chronically recurring and/or therapy-resistant fluor of the outer female urogenital tract, a vaginal virbiosis was stated in 54 cases as cause of the fluor complaints lasting, for the most part, longer than five years. Aspects of vaginal vibriosis and respective therapy are discussed.


[Severe course of an infection with Leptospira grippotyphosa (author's transl)]. In a 22 years old female patient severe jaundice, renal failure and myocarditis developed 3 days after the onset of fever and other uncharacteristic symptoms. In dark-field microscopy leptospires were found. Inspite of high-dose penicillin therapy exitus letalis occurred in myocardial and circulatory failure, due to a severe interstitial myocarditis. Leptospira grippotyphosa could be proven serologically as the causative bacterium. It is pointed out, that leptospirosis inspite of their rare occurrence should be included in the differential diagnosis of infections of undetermined origin, especially if jaundice develops. The demonstration of leptospira in blood, cerebro-spinal fluid or urin by means of darkfield microscopy may quickly support the diagnosis. Since the course of severe leptospirosis can be influenced significantly only up to the 4th day after the onset, high-dose penicillin G or tetracycline therapy should be initiated already when the clinical suspicion is present.


[Clotrimazol in the treatment of candida infections in premature and newborn children (author's transl)]. The early infancy is especially affected by moniliasis in pediatrics. The causes are: broad spread of Candida albicans in the environment of these children, a growing immunity, the immaturity of the skin and an insufficient candida-static activity of the serum. The prematures and the newborns with an irregular birth are especially endangered. This danger is increased by simultaneous antibiotic therapy. The arising mycosis can reach from the relative harmless mouth- and diaper-thrush to serious septic diseases. An effective therapy therefore is very much desired. As new efficacious medicaments the derivates of imidazol, Clotrimazol, have proved satisfactory for the treatment of mycoses. It is as Canesten marketed. The drug possesses a strong activity against numerous fungi, some protozoa, and bacteria. In this paper it is reported on own pharmacokinetic and therapeutic investigations with Clotrimazol. The substance has been very useful for the treatment of mouth- and diaper-thrush. Clotrimazol was administered as BAYb 5097 peroral and local as Canesten -solution 1% and -cream 1%. There were 171 treatments carried out. Essential side-effects were not observed.


[Surgical treatments of kinking of the internal carotid artery (author's transl)]. 20 per cent of all patients we operated due to stenoses of the internal carotid artery were found to have kinking of the artery. Several methods of surgical treatment, among these resection of the kinking end-to-end anastomosis, and myoplasty using the digastric muscle are described. Angiography pre- and postoperatively is performed. Cerebral blood flow is measured by the 133 Xenon clearance.


[Results of the treatment of diaphragmatic lesions (author's transl)]. During the period of 1959 to 1975 34 patients were operated at the Chirurgische Universitatsklinik Koln-Lindenthal because of lesions of the diaphragm. From the survivors 20 patients were examined again 2 to 15 years after operation. 15 patients (75%) stated subjective complaints. On these patients cicatrizations in the sinus phrenicocostalis, higher position of the diaphragm, axial hernia of the hiatus, restricted flexibility of the diaphragm, flattened diaphragm and paralysis of the diaphragm were found. More than 50% of the patients showed a significantly restricted total and vital capacity. Most important was the fact that in 25% of the reexamined patients there existed an axial hernia of the hiatus caused by the trauma.


[One-stage resections in cases of carcinoma of the sigma and rectosigmoid (author's transl)]. 210 one-stage resections of the sigma and 69 resections of the rectosigmoid were performed without a temporary proximal colostomy. Anastomotic leakage occurred in 4,7 and 2,9% respectively. Operative mortality was 3,5%. Comparing the results with the corresponding literature, it is shown, that the chosen operative procedure is a safe way of treatment.


Characterization of aberrations in image-intensified fluoroscopy. A procedure is developed for characterizing and measuring the distortion and intensity variations which are present in x-ray image-intensifier systems. These effects often seriously limit the usefulness of such systems, and the results here make possible an evaluation and comparison of competing intensifier instruments.


Biomedical probe using a fiber-optic coupled scintillator. A high-sensitivity biomedical radiation probe which employs a fiber-optic coupled NaI(Tl) scintillator as a detector is described. It was developed for in vivo counting of low-energy 239Pu photons from material located in the tracheobronchial lymph nodes.-This probe is 20 times as sensitive as a solid-state probe (avalanche diode) previously developed for this application. Tests with 99mTc show a sensitivity more than 90 times greater than biomedical probes using DcTe of GaAs; however, the improved sensitivity is largely due to an increased sensitive volume. Probes were evaluated in animals and phantoms for detection of 239Pu and for location of lung tumors labeled with 111In.


Unequal weighting of given doses in opposed fields in treatment of cancer of the tonsillar region using 60Co, 4-, 8-, 15-, 24-MVp photons. Weighting of given doses from parallel opposed fields is a widespread practice in radiation therapy of cancer in the tonsillar region. In order to determine when weighting is useful, dose distributions on the central axis were calculated for various energies (60Co, 4-, 8-, 15-, and MVp photons), weighting factors, and field separations. Criteria for judging the usefulness of weighting were (i) that variation in the dose across the tumor volume not exceed 10%, and (ii) that the dose to critical tissues outside the target volume be at least 20% less than target volume dose. The clinical situation that met these criteria was a lateral lesion that extended to less than one-third of the transverse diameter of the head, treated with either 60Co, 8, or 4 MVp with 4:1 weighting. Under these conditions, weighting was considered to be justified.


Reduced output of orthovoltage radiotherapy units. Three causes of reduced output of orthovoltage radiotherapy units have recently been reported in this journal, each being due to faults external to the tube insert. A further incident is now reported where the output was reduced by 30% due to the tungsten foil becoming partially detached from the anode, while the unit continued to operate normally. The possible cause and the prevention of a repeat occurrence are discussed.


Dosimetry of 137Cs sources with the Fletcher-Suit gynecological applicator. Measurements were made in water about the tandem and ovoid structures of the Fletcher-Suit applicator loaded with a 137Cs source. The dose rate was found to vary as much as 25% as a result of differential absorption in the ovoid. Empirically based trigonometric expressions are suggested which provide the absorption correction as a function of the two angles of a spherical coordinate system. Computer calculated dose rates, with and without the absorption corrections, are compared.


Size distribution of human albumin microspheres by forward scattering of monochromatic light. Optical diffraction is used to study the structure of the Fourier transform of a thin suspension of human albumin microspheres. The intensity profile in the transform plane is then used to derive information about the particle size distribution.


Line-focusing x-ray monochromator for the analysis of trace elements in biological specimens. A line-focusing x-ray monochromator has been designed and developed to be used with an energy dispersive detection system for the quantitative analysis of trace elements in biological specimens. This instrument uses a cylindrically curved Johansson-type crystal to monochromatize and focus the excitation radiation into a line 0.5 mm wide and 40 mm long. The excitation radiation chosen for these experiments was Mo Kalpha and the total intensity of the line-focused beam was estimated to be 2 X 10(7) cps. Because of the narrow width and high power density of the excitation between beam, small tissue specimens 1 X 1 X 12 mm in size along with a single strand of hair were analyzed for trace elements from Al through Sr. For the transition elements, concentrations of a few parts per million were easily detected with this analyzer.


Demonstration of whole blood analysis using proton-induced x-ray emission. The elemental variations in whole blood following gamma-radiation injury of mice have been studied. the trace-element analyses were performed using the proton-induced x-ray emission technique, and the results were compared with the red blood-cell count. It is shown that, by using this method, the variation of the six elements, K, Ca, Fe, Cu, Zn, and Rb, can be studied simultaneously.


Micro-scale two-dimensional polyacrylamide gell electrophoresis of ribosomal proteins. A specially designed apparatus and conditions are described for the rapid analysis of ribosomal proteins by two-dimensional gel electrophoresis on a micro scale. The resolution of proteins in electropherograms is comparable to that obtained with other systems, but because of miniaturization, only 0.5 to 1 mug of each protein is required, and the entire procedure, including electrophoresis in both dimensions, and staining and destaining can be completed in 6 to 7 hours.


Genes inhibiting senescence in the ascomycete Podospora anserina. Senescence occurs in all wild strains of Podospora anserina after continued growth. This syndrome can be inhibited by a synergistic interaction of two linked genes, incoloris and vivax. Whereas the wild strain starts to become senescent after 26 d and the mutants incoloris and vivax after 42 and 66 d respectively, the double mutant shows no signs of aging after culture for more than one year.


Extrachromosomal inheritance in Schizosaccharomyces pombe. I. Evidence for an extrakaryotically inherited mutation conferring resistance to antimycin. In crosses of [ANTr8] with auxotrophic strains, resistance to antimycin segregates almost 50:50 in random spore analysis with a slight preponderance for the sensitivity allele. Tetrad analysis, however, shows all possible types of tetrads (2:2; 3:1; 1:3; 4:0; 0:4 resistant versus sensitive) with an excess of 2:2 segregations and sectoring of colonies on antimycin medium indicating an extrachromosomal mode of inheritance. The overall ratio of resistant versus sensitive spores is the same as compared with random spore data. Using a mutant blocked in meiosis (mei 1) mitotic segregation of stable diploids is achieved, leading to a ratio of 20% resistant to 80% sensitive clones. Possible reasons for the bias in transmission of the resistance determinant is discussed.


Extrachromosomal inheritance in Schizosaccharomyces pombe. II. Evidence for extrakaryotically inherited respiratory deficient mutants. In contrast to the wild-type, mutant [ANTr8] is able spontaneously to throw off stable respiratory deficient mutants. The frequency of these mutants is considerably enhanced by treatment with ethidium bromide (EB) or the azo-dye Janus green (JG). An unstable cell state with a petite-like phenotype is found in both mutant [ANTr8] and wild-type after EB-treatment. However, only in the mutant is this unstable cell state followed by the appearance of stable respiratory deficient (RD) mutants. Formation of microcolonies is observed both in [ANTr8] and wild-type. RD mutants were isolated after EB treatment. Three of them (mit-12, mit-25, and mit-30) were analyzed and mit-25 characterized in more detail.


Partial reversible inactivation of enzymes due to binding to the human erythrocyte membrane. Hypotonic human erythrocyte ghosts, devoid of the original glyceraldehyde-3-phosphate dehydrogenase content of the red cell, bind added glyceraldehyde-3-phosphate dehydrogenases, isolated from human erythrocytes, rabbit and pig muscle, as well as rabbit muscle aldolase. There are only slight differences in the affinities towards the various glyceraldehyde-3-phosphate dehydrogenases. On the other hand, glyceraldehyde-3-phosphate dehydrogenases are bound much stronger than aldolase; in an equimolar mixture the former can prevent the binding of the latter, or replace previously bound aldolase at the membrane surface. Binding is always accompanied by the partial inactivation of enzymes, which can be reverted by desorption. Unwashed ghosts rich in hemoglobin seem to have a more pronounced inactivating effect on bound glyceraldehyde-3-phosphate dehydrogenase. In isotonic media ghosts, whether white or unwashed, reseal and do not interact with the enzymes.


[Significance of diagnostic parameters in recurrent urinary tract infection in children. I. The history (author's transl)]. Comparison of the history of 136 children with recurrent urinary tract infection (UTI) with their follow up in a special urologic service (260,6 patient years)  showed marked differences in symptoms of recurrent UTI prior to follow up (769 "anamnestic" recurrent UTI) as compared to true significant bacteriuria (278 recurrent UTI during follow up). Therefore parents statements about time of first UTI and incidence of further recurrences should be considered with caution. Only 10% of the physicians proved their diagnosis "UTI" bacteriologically. Anamnestic data, however, are of great importance for the follow up of children with recurrent UTI: children with many recurrences in their history have a greater risk of further recurrences despite careful follow up, and tend to have more pathologic findings on first radiologic examinations.


Lipid-F1 nucleohistone interactions.

Lipid-F1 nucleohistone interactions. High concentrations of phospholipids determine destabilization of F1 histone-DNA complex at the weight ratios, histone:DNA, 0.8:1 and 1:1, but low concentrations cause only negligible destabilization. Cholesterol at high weight ratios has little effect on nucleohistone stability. Only linolenic acid of the fatty acids used reproduces similar changes in the thermal stability of F1 histone-DNA complex as phospholipids. The type of interaction of phospholipids with the F1 histone-DNA complex is analyzed, and the involvement of phospholipids in DNA replication in vivo is discussed.


[Hyposensitization with extracts of house dust and mites adsorbed on aluminium-hydroxyde (allpyral) in children with bronchial asthma (author's transl)]. Since the year 1971 the authors have treated 39 asthmatic patients with Allpyral house dust vaccins containing Dermatophagoides farinae extract. 16 of these children previously had similar treatment, but without mite extract, and this was changed because of the poor results. Patients allergic only to house dust and mites were selected according to the skin tests. Skin reaction to mite extract did not change even in symptomfree children in contrast to the decrease or disappearance of skin sensitivity to house dust. 23 out of 39 patients had no symptoms or only mild and short wheezing occasionaly in the last 3-6 months of treatment. There were six patients whose symptoms remained unchanged during the treatment. These children were all among the 16 asthmatics who previously had an unsuccessful house dust hyposensitization. So every patient whose treatment was started with the combined house dust-mite Allpyral has imporved, only 5 of the 23 still had yet a few asthmatic attacks.


[Pre-, peri- and and postnatal prevention of major neuropediatric handicaps in Sweden (author's transl)]. The actual distribution and panorama changes of neuropediatric handicaps in Sweden as well as modern aspects on prevention are presented. The following conclusions are drawn. Preventive programs directed towards brain damaging factors occurring after the neonatal period are more or less completed. Further gains, however moderate, should be attainable perinatally. The largest number of unsolved problems and today the most challenging, refer to secondary fetal brain dysfunction during the prenatal period, particularly the 3rd trimester.


[Distance and velocity standards for head circimference growth before and after term until 18 months--results from a longitudinal study (author's transl)]. Standards for head circumference growth (distance and velocity) from the perinatal period until the age of 18 months have been based on repeated measurements at short intervals (longitudinal) in 60 appropriate for gestational age (AGA) preterm infants of very low fetal age, and 68 full term infants. Moreover the growth of 32 small for gestational age (SGA) preterm infants has been evaluated. Before term the extrauterine head growth curve is similar to that of "intrauterine curves". At term and until the age of 18 months the growth curves of AGA preterm infants agree well with those of the full term controls, without statistically significant differences (p greater than 0.1). If the age is not corrected for prematurity ther is a significant difference between preterm and full term infants until 17 months (p less than 0.05). With decreasing velocity of head circumference growth this difference becomes non-significant at the age of 18 months (p greater than 0.1). Out of the heterogenious group of 32 SGA preterm infants 15 have shown a catch-up growth in head circumference until the third month, whereas 17 infants remained significantly below the growth curve of the AGA. Growth velocity of head circumference, calculated in cm/month, in the last 10 weeks before term is significantly higher (p less 0.025) than later on, with a mean peak of 4.3 cm in the 34th postmentstrual week. After term, the velocity curve of the AGA preterm infants agrees with that of the full term controls. A period of rapid head circumference growth -- a growth spurt -- extends from the 31st postmenstrual week until the 6th month after term. In the following months the velocity curves flatten. If the age is not corrected for prematurity, the peak of the velocity curve becomes flat and spread with a mean growth velocity of 3.0 cm in the first, of 3.4 cm in the second and of 2.5 cm in the third month.


[The longitudinal increase of the internal jugular vein and the upper v. cava as measured between the mastoid to the heart: parameter for timing the re-operation after ventriculocardiostomy (author's transl)]. Some time after ventriculo-cardiostomy in children with hydrocephalus the cardiac catheter is retracting out of the right atrium into the upper veins due to the increase of body length during growth. This might endanger proper functioning of the valve. Therefore most authors are in favour of a prophylactic elongation of the catheter by re-operation. In order to roughly predict the time for re-operation we measured course of the catheter in 4120 children. As a basis for long time supervision of children with this shunt operation we thus propose a curve of length increase of the blood vessels concerned, based on our data, in connection with the known curve of length increase of the body.


[Heredo familial areflectoric dystasie. Roussy-Lévy-Syndrome (author's transl)]. The Roussy-Lévy-Syndrome in a 12 years old girl is described and its relation to other heredofamilial ataxias is discussed. The kindred of our patient was studied as well. Information about 21 family members could be collected; 11 of them also suffered from RLS. Additionally for the first time in literature, dermatoglyphic patterns in these patients have been investigated.


[Unviable micromelic dwarfism: a syndrome with dystrophy of the thorax and polydaktyly type Saldino-Noonan (author's transl)]. Besides classical achondroplasia various severe osteochondrodysplastic disorders have been differentiated in recent years. Their most important features include obligatory perinatal mortality, severe dystrophy of the thorax and shortening of tubular bones. Additionally some of these syndromes present visceral malformations, cleft-lip, and malformations of the genitals. A detailed case report of a patient is given. Various features: dystrophy of the thorax, micromelia, postaxial polydactyly, metaphyseal dysplasia, malformations of the great vessels, and polcystic kidney suggest the classification as short rib-polydactyly syndrome, type Saldino-Noonan.


[Possibilities of extension of blood group determination in cases of disputed paternity]. Results of the blood-group testing carried out in 1966-1974 in cases of discussed paternity are described in detail. Until 1970 only blood groups A1, A2, BO, MN and systems of Hp Rh and Gm (a) were tested (so called fundamental-testing). Maximal chance of exclusion of paternity on the base of these systems 70%. From 1970 on, the investigation have been extended to systems Gm (b), Gm(x), INV (1), Ss, Kell-Cellano, Duffy and during the last two years to systems of Gc, acid-phosphatase of erythrocytes and glutamat-pyruvat-transaminase. Thus the maximal chance of exclusion of paternity increased to 90%. Chances of exclusion on the base of every system are discussed separately also in detail. Fundamental-test were carried out in 10 200 cases, extended-tests in 278 cases. On the base of fundamental-tests exclusion of paternity could be achieved in 32, 85% of the cases. In 1974 in 374 (32, 21%) cases out of 1161 by fundamentaltesting, in further 100 (8,61%) cases by extended testing altogether in 474 (40,82%) cases- could be achieved exclusion of the paternity. These data indicate effectivity and reasonableness of the extension of blood-grouping-testing.


[Anthropological studies as a possible tool in disputed paternity cases]. Author on the base of the material investigated in the Department of Forensic Medicine of Semmelweis Medical University discusses importance of anthropological investigations as a valuable, additional to serology test. Data obtained by the investigation of 2000 families demonstrate the hereditary features and their value as an evidence in a filiation cases. Author emphasizes the importance of the chromosome-investigations as one of the most reliable methods in paternity cases.


[The work at the Toxicology Laboratory of the Institute for Forensic Medicine]. The author gives an account on the work of the department laboratory of the Department of Forensic Medicine of Semmelweis Medical University. The laboratory was founded 15 years ago. The work, consist of a large number of routine investigations, inspite of that manysided, sometimes complicated. Author emphasizes the necessity of the use of principally different chemical methods in the solution of the same problem and importance of parallel measurements for the sake of reliability and accuracy.


[Various problems concerning maternal mortality during pregnancy]. In the autopsy material of the Department of Forensic Medicine of the Semmelweis Medical University--90,000 cases in 25 years (1950-1975)--508 cases of death in the period of gestation have occurred. Author have analysed this material and have established, that in every second case the death occurred due to criminal abortion, in every fifth case due to the complications of the pregnancy and in every third case due to the complications of delivery. By means of trend-calculations it was further established that in the autopsy material of the Department the number of the sudden natural death of women in the reproductive age during the 25 years remained on the same level, but the number of death cases connected with gestation decreased. In the latter group: the number of death cases due to abortion and complications of pregnancy decreased significantly, number of lethal cases due to complications of delivery remained at the same level. Data of the analysis are compared to the data reported in the literature. Some questions--the cause of the death, the criminality when abortions are concerned, questions of the treatment and the responsibility of physicians are also discussed. These investigations seem to evidence that on the base of the evaluation of a large autopsy material the legal medicine can reveal valuable data for the preventive medicine.


[Topo-optical demonstration of lineal arrangement of vicial OH radicals by means of aldehyde bisulfite toluidine blue (ABT) reaction]. Topo-optical reaction with aldehyd-bisulfit-toluidinblue (ABT) suitable for the demonstration of lineal arrangement of vicinal OH-radicals is described. On the base of double refringement brought about by the orientated dye-binding, this reaction is suitable for the study of molecular arrangement of carbohydrate components of biological structures (glycoproteins, glycolipides and polysaccharides). Double refringement brought about by the reaction ABT optically is negative to the length of polysaccharide-chains. Practical use of the method is demonstrated on several biological structures. Findings show, that reaction ABT opens new possibilities for the study of ultrastructure of carbohydrate components of various tissue elements.


[Demonstration of bacteria and fungi in tissues by topo-optic aldehyde bisulfite toluidine blue (ABT) reaction]. Reaction with aldehyd-bisulfit-toluidinblue (ABT)--as a selective topo-optical reaction for vicinal OH-and amino-OH groups, appears to be suitable for demonstration of bacteria in tissues. Cell membranes and capsules of bacteria and fungi contain large quantity of carbo-hydrates, therefore they show strong basophilic staining after ABT reaction. Double refringement brought about by orientated dye-binding seems to be the sign of the linear arrangement of polysaccharides composing cell membranes and capsules of bacteria. Practical importance of the reaction is shown on examples. Diagnostic advantages of it are also discussed.


[Selective demonstration of amloid deposits and methodical possibilities for the analysis of ultrastructural differences]. In preparations stained by congo-rot and covered with arabic gumm amyloid deposits reveal intensive, positive bi refringement, collagen is isotrop, or shows a mild bi refringement. This method is most suitable for selective optical demonstration of amyloid deposits. On the base of investigation of ultrastructural stability of amyloid deposits (resistency to performiat and induced proteolysis) two types of them may be distinguished: I. amyloid deposits of labile structure (generalized, secondary amyloidosis) and 2. amyloid deposits of stabile structure (generalized primary amyloidosis, local and senile amyloid deposits).


[Electron microscopic changes in the myocardium in experimental carbon monoxide poisoning]. Effect of coal-gas poisoning on the myocard was studied by the aid of electron microscope and electronmicroscopic histochemistry. Alterations revealed can not be regarded as specific ones, they seem to be of hypoxic origin. Activity of the cytochromoxidase--as revealed by electronmicroscopic histochemistry--in cases of coal-gas poisoning decreases. Specificity of the cytochromoxidase method and the leadsalt method of the demonstration of calcium are discussed.


[Possibilities of the use of electron microscopy in forensic medicine]. Author deals with possibilities of application of scanning electron microscopy in the medico-legal practice. After a short review of the literature methodological problems are discussed and the author's experiences are reported. Author have investigated various injuries of hair, bonetissue, and skin specimens. It was established that they reveal characteristic changes which can be easily observed by scanning-electron-microscope. Various injuries of hair-cutting, tearing, breakage, burning etc.-have distinguishable characteristics. Scanning electron microscopy is suitable for the study of vital and postmortal injuries.


Critical periods of the mitotic cycle: influence of aminopterin and thymidine on production of chromosomal aberrations by radiation in Crepis capillaris. The influence of aminopterin (AP), tritiated thymidine ([3H] TdR) and "cold" thymidine (TdR) on production of chromosomal aberrations in meristematic cells of Crepis capillaris irradiated in different stages of the mitotic cycle with 300 rad of 63Co gamma-rays was studied. All the chemical treatments increased most of all the frequency of aberrations induced during two "critical periods" localized before the stage of DNA synthesis (fixation 9 h after irradiation) and before that of mitosis (4 h). Treatments with TdR and [3H]TdR increased most of all the frequency of chromatid aberrations when irradiation was performed in G1, and the frequency of gaps when irradiated in G2. Treatment with AP increased the yield of different types of aberration more uniformly. The modifying effect of the chemicals tested appeared to be independent of replicative synthesis. The "critical periods" are suggested to be the stages when regular "proof reading" and correction of spontaneous errors takes place [9,13]. In addition to this regular mechanism, radiation induces an "emergency" mechanism of repair. AP inhibits the mechanism of regular repair; in addition TdR and [3H] TdR suppress the lateral spread of primary injuries across the chromosome.


Clastogenic effects of methylnitrosourea and ethylnitrosourea on chromosomes from human fibroblast cell lines. Human fibroblast cell lines were pulse-treated for 1 h with either methylnitrosourea (MNU) or ethylnitrosourea (ENU) at various time intervals before harvesting for chromosome analysis. Cells treated with 1 X 10(-3) M, 5 X 10(-4) M, and 1 X 10(-4) M final concentrations of MNU and ENU during the G2 or M phases of the cell cycle showed a significant increase in chromatid-type abnormalities over controls. Cells exposed to MNU or ENU 23 h before harvest showed some chromosome-type abnormalities, reflecting probable damage induced during the G1 phase of the cell cycle or derived from chromatid damage induced during the previous cell cycle. The mitotic indices and incidences of abnormalities suggested a dose response effect when cells were treated with the two higher concentrations and the three concentrations, respectively, of MNU or ENU. Chromatid abnormalities were observed in MUN and ENU-treated cells from each of four cell lines. From this investigation, it was concluded that MNU and ENU treatment of human diploid cell lines in vitro induced both chromatid and chromosome aberrations. MNU and ENU, both of which had previously been shown to be mutagenic in experimental animals, are, therefore, also considered to be mutagenic at the chromosome level in human fibroblasts grown and treated in cell culture.


Analysis of intercellular distributions of chromatid aberrations. 59 intercellular distributions of chemically induced and spontaneous chromatid aberrations were analyzed for goodness of fit in respect of the Poisson (PD), the geometrical (GD), and the negative binomial distributions (NBD). The data are excellently described by the NBD. This distribution can be deduced from a model out of the queueing theory and is based on the hypothesis of restitution. Estimators are obtained for the ratio of restitution and induction processes involved in the origin of chromosomal aberrations.


Chromosome aberration yields in human lymphocytes induced by fractionated doses of x-radiation. Unstimulated (G0) human peripheral blood lymphocytes were exposed at 37 degrees C to doses of 200 or 500 rad of X-rays delivered in two equal fractions. The dose fractions were separated by intervals of up to 7 h in the 200 rad study and up to 48 h for 500 rad. In both studies the mean levels of dicentrics and total unstable aberrations began to decline when fractions were delivered with intervals of greater than 2 h. With 200 rad the yield had decreased to an additive baseline (i.e. equal to only twice the yield of a single 100-rad fraction) by an interval of 4 h. Following 500 rad the yield declined until 8 h and then remained 20% above the additive baseline even when 48 h separated the fractions. Possible explanations for this discrepancy are discussed. In a second experiment PHA  stimulated lymphocyte cultures were exposed to 2 doses of 125 rad of X-rays up to 7 h apart in an attempt to demonstrate the late peak in aberration yields originally reported by Lane [5]. Control cultures received unsplit doses of 250 rad at the time of the corresponding second 125-rad fraction. No evidence of a late peak in dicentric yield was observed. The yield remained approximately the same irrespective of the time interval between fractions but these split dose yields were significantly different from the accompanying unsplit controls.


X-ray-induced mutants resistant to 8-azaguanine. I. Effects of cell density and expression time. Asynchronous Chinese hamster ovary cells were irradiated and colony survival in Alpha MEM medium with dialyzed serum was determined with or without 15 mug/ml 8-Azaguanine (AG). Data indicated that a reproducible assay for the system was dependent upon controlling cell density at least two days prior to induction as well as throughout the expression period. Generally, spontaneous and radiation-induced mutant frequencies decreased when cell densities exceeded a critical density of 3-6 X 10(4) cells/cm2. Infrequently, the critical density was exceeded by a factor of two with no observed decrease, possibly correlated with a longer cell doubling time. Drug depletion artifacts can occur because of drug degradation, or because wild-type cells utilize the drug or produce conditions which reduce uptake of the drug. Thus, as the effective drug concentration is lowered, the observed mutant frequency increases because a spectrum of mutants resistant to only low concentrations can now survive. In fact, refeeding with AG at intervals during the incubation period lowered spontaneous and radiation-induced frequencies approx. 5-fold. Therefore, to standardize conditions, cells were trypsinized at the end of the expression time and replated at a constant cell number for mutant selection by AG. Over two generations of growth during the expression period were required for optimal manifestation of induced mutants, and when densities were kept below 4 X 10(4) cells/cm2 at all times, observed mutant frequencies did not change significantly over a period between 80 and 140 h post-induction (over 4 generations for irradiated cells and over 6 generations for controls). Previous reports of observed mutant frequencies decreasing beyond three generations may be due to cell interaction prior to mutant selection.


X-ray-induced mutants resistant to 8-azaguanine. II. Cell cycle dose response. Synchronous Chinese hamster ovary cells were irradiated in G1 or S phase. Colony survival in Alpha MEM medium with dialyzed serum was determined with or without 15 mug/ml 8-azaguanine (AG). An expression period of over three generations (multiplicity of 20) was utilized, with expression times ranging from 58 to 114 h. Both G1 and S phase were practically identical in sensitivity to X-ray-induced mutations, with mutant frequency/viable cell/rad ranging from 1 X 10(-7) (75-100 rad) to 8 X 10(-7) (1000 rad). The spontaneous mutation rate, shown by Luria-Delbruck fluctuation analysis, was 5 X 10(-7) per generation. Thirty-three mutants, isolated at random and grown for over 30 generations in the absence of AG, were analyzed for plating efficiency (PE) in different concentrations of AG or in hypoxanthine-aminopterin-thymidine (HAT) medium. Of these, 64% were resistant (PE greater than 0.1) to 7.5 mug/ml AG, 85% to 5.0 mug/ml, and 91% to 3.5 mug/ml. Only 42% showed possible hypoxanthine-phosphoribosyltransferase (hprtase) deficiency as evidenced by HAT sensitivity (PE less than 0.1). Wild type controls exhibited PE's in 3.5 mug/ml AG of less than 0.001 and in HAT of greater than 0.5. Of ten mutants studied, all demonstrated survival response to radiation similar to wild type cells (D0 of approx. 120 rad). For radiation protection standards, the radiation dose required to induce mutations at a rate equal to that occurring spontaneously is called the doubling dose. The doubling dose observed for acute irradiation was about 3 rad and was estimated to be 10-60 rad for chronic irradiation, similar to that often reported for in vivo studies.


Ethyl methanesulphonate mutagenesis with L5178Y mouse lymphoma cells: a comparison of ouabain, thioguanine and excess thymidine resistance. Complete inhibition of growth of sensitive L5178Y mouse lymphoma cells in culture was obtained with 10(-3)M ouabain, 1.65 X 10(-3)M thymidine, 1.8 X 10(-4)M thioguanine and 10(-6)M cytosine arabinoside. The toxicity of methotrexate was dependent upon cell density and this compound was excluded from further study. The expression time before addition of the selective agent was important for detecting EMS induced resistant variants. Ouabain-resistant variants appeared immediately after treatment and were present over a broad time span. No excess thymidine- or thioguanine-resistant variants were seen initially; a peak in variant numbers was seen for excess thymidine resistance at 48-96 h and for thioguanine resistance at 144-192 h. Using induced mutation frequencies at optimum expression times, equal EMS treatments yielded substantially more variants resistant to thioguanine than to ouabain. It is suggested that this difference may have origin in possible constraints in the classes of mutants which are permissible in a vital function, maintenance of the Na+/K+ balance, when compared with a non-vital function, salvage purine biosynthesis. Some data are presented on the stability in culture of resistant variants. A limited number of observations were made following treatment in the peritoneal cavity of the mouse which were in broad agreement with the above results.


Effects of childhood leukemia and chemotherapy on puberty and reproductive function in girls. Longer survivial in childhood leukemia prompted this study of pubertal development and reproductive function in 35 girls and women. Twenty-eight patients (80 per cent) had normal pubertal progression during a median of 74 months after diagnosis of leukemia and 49 months of chemotherapy. Seven patients were abnormal: four exhibited hypothalamic-pituitary dysfunction with suppression of circulating serum gonadotropins (less than 6 mlU per milliliter); three others had evidence of primary ovarian dysfunction - reversible in two - with inappropriately elevated circulating serum gonadotropins (follicle-stimulating hormone greater than 20 mlU per milliliter). Normal sexual development correlated best with pubertal status at onset of leukemia; only one of 17 patients with diagnosis before puberty experienced altered pubertal progression, whereas abnormalities appeared in six of 18 with onset during puberty or after menarche. Thus, most girls with aggressively treated child-hood leukemia have an excellent prognosis for normal hypothalamic-pituitary-ovarian function; normal development is further enhanced in patients who are prepubertal at onset of leukemia.