[Method for the determination of alpha radiation potential energy of radon decay products occurring as free ions].

The paper presents a simple method of measuring the concentration of alpha radiation potential energy of radon decay products occurring as free ions in the air. This method consists in deposition of free ions of radon decay products on the surface of metal plates in so called impactor, which is constructed by an appropriate selection of shapes and mutual arrangement of the plates. The paper presents an improved system of calibration of impactor, which continuously produces free ions in the tube, through which the filtered air containing radon is being passed. The least concentration of alpha radiation potential energy of radon decay products free ions, detactable by this method, when 1 liter of air is passed through the impactor, is 10(3) MeV liter-1). This method may be applied in laboratory and environmental measurements.


[Contemporary problems of industrial toxicology].

The author presents the present -- day position and developmental trends of industrial toxicology studies, relating this specialty to other hygiene branches, especially to natural environment protection. Disproportions in the development of this line of studies was indicated, as opposed to the progress in technique and technology. These disproportions are most evident when we compare the number of chemicals for whose some data determining their biological effects have been collected, with over 4 mln. chemical compounds used in our economy. The main general problems to be solved in the nearest future are: scientific and technical information and establishment, at an international level, of basic definitions, criteria of toxicity evaluation and occupational risk, related classification and bases constituting a starting point for establishing the hygienic standards (MAC). In addition, current orientation of studies in narrower specialties within industrial toxicology was discussed, i.e. experimental toxicology, chemical air analysis, toxicological biochemistry, chemical substances metabolism in organism, pathology of acute and chronic intoxications. The development of new narrow specialties and new problems was pointed out, in view of their perspective significance for the health protection of workers occupationally exposed to chemicals. Among those problems are: remote effects of exposure to chemicals, especially the problem of industiral carcinogenesis, combined effects of poisons, and so called behavioral toxicology. It was noted that the present knowledge of carcinogenic effects of chemicals permits to gradually set up efficient preventive measures, conditioned by implementation of systems of occupational risk control and the control of health effects of exposure.


[Spinal pain syndromes in coal miners].

The paper presents an evaluation of spinal pain syndrome prevalence in miners of a Mining Industry Corporation, employing 45 thous of manual workers. The observed population included 34.487 underground workers, and 9.507 surface workers. The distribution of workplaces was based on the degree of the spine load. The number of examined sick workers during one year amounted to 1.600. The authors noted, that the morbidity among underground workers with considerably loaded spine is 1/3 higher and they begin to complain about 5 years earlier than surface workers -- which obviously results from the type and environment of the work. On the other hand no difference was found in the morbidity between underground and surface workers engaged in the work with a middle load of spine, because the type of work is similar in this case and the effects of environment are not significant.


[Thermographic functional test in the diagnosis of vascular changes in the vibration syndrome].

Contactant thermometry of fingers' skin in thermal functional test is a routine examination common now in vascular changes diagnosis. The sensitivity of this test is increased by the use of a linear thermograph, averaging the temperature of the skin area being examined. In order to ensure correct measurement results, conditions and principles of the test performance must be observed carefully, as indicated by the authors. Evaluation of time thermograms of fingers' skin should involve three types of thermoregulating reaction: homoiothermic, poikilothermic and amphithermic. The first type may be numbered among absolute, whereas the other two among relative physiological standards. Evaluation should include: fingers' skin temperature before cooling, the rate of temperature rise between the 1st and the 5th minute after cooling and the temperature taken at the 15th minute after cooling. Repeated measurements allow to differentiate changes in fingers' skin temperature, resulting from a damage to vessels due to vibration, as well as a relative physiological standard.


[Ear protective plugs].

The authors present results of studies of application of polyurethane foam to produce individual sound-absorbing ear plugs. In addition to physico-mechanical properties of the foam, the authors present its optimum prescribed composition, ensuring appropriate attenuation qualities, flexibility, softness and long -- lasting strain relaxation -- i.e. the conditions resulting in excellent filling of external auditory meatus, masking effect and utilization comfort. The efficiency of attenuation of sounds by the plugs, tested audiometrically by the method of auditory threshold shift in otologically healthy subjects ranges from 12.25 dB (250 Hz) to 29.75 dB (4000 Hz). No significant inflammatory reactions in external ear skin were found after 8 hrs of continuous wearing of ranges under the work conditions typical for the textile industry. The results demonstrate that the polyurethane foam, developed by the authors, are valuable ear protectors, of advantageous functional qualities.


Influence of acetylsalicylic acid on plasma glucose, insulin, glucagon, and growth hormone levels following tolbutamide stimulation in man.

The effects of acetylsalicylic acid (ASA), a known inhibitor of prostaglandin (PG) synthesis, on plasma glucose, insulin, glucagon and growth hormone (GH) responses to tolbutamide were examined in ten normal volunteers. Treatment with 3.2 g ASA daily for 3 days caused a significant reduction in basal plasma glucose levels (p less than 0.05); by contrast, basal insulin rose from 23 +/- 2 to 31 +/- 2 microU/ml (p less than 0.01). No significant changes in the basal concentrations of glucagon and GH were found after ASA. Insulin response to tolbutamide was significantly augmented after ASA (p less than 0.01) while GH response to hypoglycemia was reduced (p less than 0.05). The pattern of plasma glucose and glucagon was not significantly modified by the treatment. Since ASA seems to have an action opposite to PGE on insulin and GH secretion, it is possible that the ASA may work through inhibition of PG synthesis.


Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated with hypertriglyceridemia.

Hypertriglyceridemia is common in untreated diabetes mellitus. An abnormality in the interaction of lipoprotein lipase with endogenous circulating plasma lipoprotein triglyceride has been demonstrated in untreated diabetes. These diabetics have a decreased maximal removal capacity for plasma triglyceride (27.0 mg TG/kh/hr) and increased Km (390 mg/dl) for endogenous plasma triglyceride-lipoprotein lipase interaction compared to that found in nondiabetic hypertriglyceridemic subjects (Vmax, 32.0; km, 157). Diabetics treated for at least two months have a maximal removal capacity and Km similar to that of nondiabetic subjects (Vmax, 32.7; Km, 192). No evidence for an increase in triglyceride production due to diabetes per se was found. When diabetic subjects with triglyceride levels over 400 mg/dl were selected for study, most were found to have an independent familial form of hypertriglyceridemia.


Failure to demonstrate stimulatory effect of prolactin on vitamin D metabolism in vitamin-D-deficient rats.

The effect of administration of bovine prolactin in vivo on renal 1 alpha-hydroxylase (1 alpha-OHase) activity was investigated using thyroparathyroidectomized and sham-operated vitamin-D-deficient male rats. A high dose (1.5 IU/hr) and a low dose (0.3 IU/hr) of bovine prolactin was constantly infused into the cannulated femoral vein for 6 hr or 30 hr. The accumulation of 1 alpha, 25-hydroxyvitamin D3 [1 alpha, 25-(OH)2-D3] in plasma produced from 25-hydroxy-vitamin D3 (25-OH-D3) was calculated from the 6-hr conversion of intravenously injected [3H]-25-OH-D3 to [3H]-1 alpha, 25-(OH)2-D3. Both high dose and low dose of prolactin administration caused no significant stimulatory effect on 1 alpha-OHase activity in TPTX animals. Also, in sham-operated rats the prolactin treatment produced no significant change in the 1 alpha-OHase activity. Plasma calcium concentrations showed a tendency to increase slightly. These results suggest that prolactin has no direct stimulatory role on renal 1 alpha-OHase activity in rats. Its effect on calcium metabolism may be mediated by a different mechanism(s).


Impact of hemodialysis on the abnormal glucose and alanine kinetics of chronic azotemia.

Rates of alanine and glucose turnover and precursor-product interrelationships were determined in patients on chronic hemodialysis and in matched controls using simultaneous primed injection-continuous infusions of [U-14C] alanine and [2-3h] glucose. In eight chronically dialyzed patients studied before their first dialysis of the week, glucose turnover was 866 +/- 120 micromole/min (mean +/- SE); after their last dialysis of the week, glucose turnover was 880 +/- 63 micromole/min. These rates were 35% (p less than 0.05) and 37% (p less than 0.01) greater than rates observed in ten normal volunteers (642 +/- 28.3 micromole/min). Fasting glucose and insulin levels in dialyzing patients were unchanged from normal. Alanine turnover was increased predialysis (318 +/- 55.2 micromoles/min; p less than 0.01) and postdialysis (248 +/- 32.4 micromole/min; p less than 0.01) as compared to normal (168 +/- 14.3 micromole/min). In patients pre- and postdialysis, gluconeogenesis from alanine was increased to 34.6 +/- 10.9 micromole/min (p less than 0.05) and 39.0 +/- 6.33 micromole/min (p less than 0.05) compared to 20.9 +/- 1.63 micromole/min in normal subjects. We conclude that neither acute nor chronic hemodialysis corrects the increased glucose and alanine production and utilization and gluconeogenesis observed in chronic renal failure.


Role of endogenous somatostatin in the secretion of parathyroid hormone and calcitonin.

Our previous in vitro and in vivo studies demonstrated that exogenous somatostatin inhibited secretion of both parathyroid hormone (PTH) and calcitonin (CT). This study evaluates the possible role of endogenous somatostatin in PTH and CT secretion. Rats receiving somatostatin antiserum i.v. had significantly greater circulating levels of serum immunoreactive PTH (iPTH) and CT (iCT) than rats receiving normal rabbit serum. In in vitro studies with bovine parathyroid tissue, the addition of somatostatin antiserum to the medium significantly increased PTH secretion from basal, low calcium-stimulated and high calcium-suppressed parathyroid tissue. These combined observations strongly suggest that endogenous somatostatin must have a suppressive effect on PTH and CT secretion. The in vitro observations with isolated parathyroid tissue suggest that somatostatin is synthesized by cells within this tissue. These data strongly suggest that somatostatin is a locally-synthesized hormone that has a role in modulation of both PTH and CT secretion.


Difficult intubations.

Six cases of difficult intubation are presented and their management discussed. Routine practice of blind nasal intubation and fiberoptic laryngoscopy is recommended for improved dexterity. Elective tracheostomy should be considered in cases where the airway is compromised and cricothyroidotomy should be recommended.


The treatment of severe pancreatic pain.

The management of four patients with severe pancreatic pain is discussed. Bilateral coeliac plexus block with alcohol gave effective pain relief to the three patients with pancreatic carcinoma and the one patient with acute pancreatitis. The treatment of the pain of acute and chronic pancreatitis is reviewed.


Biochemical characterization of H2S-positive Salmonella sendai strains isolated in Hong Kong.

The biochemical properties of 8 H2S-positive variant strains of Salmonella sendai isolated from patients and carriers in Hong Kong were studied. Apart from the production of H2S, all these strains showed typical properties of S. sendai and a dependence on tryptophan. Their capacity to utilize different forms of sulphur sources varied, ranging from being capable of utilizing SO4, SO3, S2O3 and cystein to only cystein as the sulphur source.


UV survival of human mycoplasmas: evidence of dark reactivation in Mycoplasma buccale.

The inactivation by ultraviolet (UV) light irradiation of mycoplasma cells of five human strains was monitored by investigating the colony-forming ability. The survival curves of five strains tested indicated that the cells of Mycoplasma buccale only are single and homogenously susceptible to UV light. The effect of the repair inhibitor, caffeine, on the colony-forming ability of UV-irradiated cells was investigated with M. buccale because of its homogenous susceptibility to UV light. The colony formation of irradiated cells was markedly depressed by post-irradiation treatment with caffeine at concentrations that had little or no effect on the colony formation of unirradiated cells. The colony-forming units (CFU) of UV-irradiated cells which were kept in broth without caffeine in the dark increased without a lag as the time in the dark increased. The colony-forming ability of the irradiated cells completely recovered after 3 hr in the dark. However, when irradiated cells were kept in the presence of caffeine, no increase in their CFU was observed. The mode of action of caffeine on UV-irradiated cells closely resembles that described for other organisms which possess dark reactivation systems for UV-induced damage in deoxyribonucleic acid (DNA). Thus, the results obtained provide evidence for the existence of a dark repair function in M. buccale.


[Elimination of nitrous oxide by a combined bacterial culture].

The ability of bacteria to eliminate nitrous oxide (N2O) from a gaseous phase containing 20% O2 was studied. Representatives of the following physiological groups were found to be incapable of removing N2O: denitrifying bacteria (Paracoccus denitrificans), nitrifying bacteria (Nitrosospira briensis), carboxydobacteria (Pseudomonas carboxydoflava), methane oxidizing bacteria (Methylosinus trichosporium), and nitrogen fixing bacteria (Bacillus polymyxa). Five corynebacteria-like strains were isolated from soil samples actively eliminating N2O under oxidative conditions. None of the strains could remove considerable amounts of N2O in pure culture. The rate of N2O elimination was much higher than that of the initial cultures if a combined culture comprising five strains was used. Three strains of the combined culture formed H2O2 and possessed a low catalase activity whereas the remaining two did not produce H2O2 and decomposed hydrogen peroxide at a high rate; this suggests that the catalase mechanism is involved in the elimination of N2O.


[Glycerin metabolism in purple sulfur bacteria].

The purple sulfur bacteria Thiocapsa roseopersicina, strains BBS and SL-4, and Lamprobacter modestohalophilus assimilate glycerol when grown in the light under the anaerobic conditions or in the dark under the aerobic conditions. Apart from glycerol, the bacteria require for their growth reduced sulfur compounds (thiosulfate) and bicarbonate. The 14C from 1-14C-glycerol is incorporated into the cells of T. roseopersicina and L. modestohalophilus at a lower rate in the presence of thiosulfate under the phototrophic conditions. In the presence of glycerol, all the studied purple sulfur bacteria produce more reserve carbohydrates of the glucan type than on the mineral medium. Glycerol metabolism in purple sulfur bacteria, like that in nonsulfur purple bacteria, involves glycerokinase and the pyridine nucleotide independent alpha-glycerophosphate dehydrogenase. The activity of these enzymes does not depend on the conditions of the cultural growth and the presence of glycerol in the medium.


[Effect of formate on the respiration of different microorganisms].

The cells of methylotrophic bacteria (Achromobacter parvulus 1, Pseudomonas methylica 2 and 20, Ps. fluorescens 45, Ps. oleovorans 52) and Candida methylica 101 grown in a medium with methanol take up oxygen in the presence of formiate. A. parvulus is most resistant to formiate (KM = 2.3 +/- 0.5) X 10(-3) M; Ki = 4 x 10(-1) M). When grown on Cn substrates, these microorganisms cannot oxidize formiate (with an exception of A. parvulus). Formiate also serves as a respiration substrate for E. coli K-12 and the purple bacterium Rhodopseudomonas palustris, disregarding the composition of a medium on which the cells are grown. When the cells cannot oxidize formiate, it inhibits the respiration of the cells and cell extracts in the presence of other substrates, including TMPD + ascorbate. The respiration is completely inhibited at a concentration of formiate of 10(-3)--10(-2) M. It follows therefore that formiate acts on the terminal cytochrome oxidase, regardless of whether it is cytochrome a or o.


[Lipid component of Streptomyces levoris membranes].

The total composition of membranes is characterized in Streptomyces levoris producing the polyene antibiotic levorin in the course of its growth; the lipid component has been studied in detail. The membranes contained protein (50--55%), lipids (37--40%), carbohydrates (3--4%), and RNA (2--3%). The ratio between the main components hardly changed with age and only the content of total phosphorus in the membranes decreased noticeably. The lipid component was represented mainly by polar lipids (80--90%); phosphatidyl ethanolamine, phosphatidyl inositolmannoside and cardiolipin prevalied. The content of phospholipids in the fraction of polar lipids gradually decreased. The possibility of substituting phospholipids by analogues containing no phosphorus is discussed. The fatty acid spectrum of membranous lipids was represented mainly by saturated fatty acids with a branched chain of the iso and anteiso series, and changed with age only to a minor extent.


[Growth of a Propionibacterium shermanii culture under varying aeration conditions].

The effect of aeration of growth of Propionibacterium shermanii BKM B-103 was studied. Aeration was found to stimulate growth of the culture in a complex medium containing sodium lactate as a source of carbon and energy. When the concentration of oxygen in the medium was raised, the economic coefficient increased, the Ks value for lactate assimilation decreased, and the value of mum did not change.


[Structural changes in Mycobacterium rubrum cells under the influence of chloroethylamine].

Chloroethylamine was used to differentiate the membranous structures of bacterial cells whose physiological role becomes more pronounced under the action of this substance. The following changes were found: in the synthesis of the cell wall as a result of modifications in the structure of mesosomes which control the correct orientation of growth and cell division; in the nucleoid and nucleoidosomes; in the analogues of mitochondria characterizing the level of energy metabolism and in the analogues of the endoplasmic reticulum accompanied with changes in the synthesis of metabolites and reserve substances in the cells. Changes in the structure and ultrastructure of the bacteria under the action of irradiation and the radiomimetic substance chloroethylamine are analyzed.


[Respiratory cyanide resistance in Candida lipolytica and the supersynthesis of citric acids].

The interrelationship between the cyanide resistance of respiratio and the process of citric acid synthesis was studied with various strains of Candida lipolytica. When the synthesis of citric acids was intensive, the respiration of cells was almost entirely inhibited by cyanide. The respiration became cyanide resistant only when the biosynthesis of citric acids was over. Induction of the cyanide resistance of respiration with antimycin A stopped the biosynthesis of citric acids. The cyanide resistance of respiration in yeast cultures incapable of considerable production of citric acids was displayed when the growth ceased. There was a strong direct correlation between the rate of citric acid synthesis and the degree of inhibition of the respiration by cyanide. It was concluded therefore that the process of citric acid overproduction could reset the reduction equivalents, thus making unnecessary the cyanide resistant pathway of electron transport.


[Spheroplast study of Thiobacillus ferrooxidans].

Spheroplasts were prepared, under the action of lysozyme (200 and 400 mcg/ml) from the cells of Thiobacillus ferrooxidans grown on the Waksman medium with elementary sulfur after their treatment with 0.5M NaCl solutions and exact exposure to sucrose (0.5M). Intracellular structures were revealed on the spheroplasts which could not be detected on intact cells.


[Dynamics of the accumulation of adifferentiated variants in a submerged culture of Streptomyces roseoflavus var. roseofungini].

When Streptomyces roseoflavus var. roseofungini is grown as a submerged culture in a chemically defined medium with stirring, it yields a number of variants in which the capacity to form the aerial mycelium is disturbed. Inoculations of the submerged mycelium of different age into a solid medium give rise to both "tomentose" variants (TV) with the aerial mycelium and "naked" variants (NV) lacking the aerial mycelium. The latter variants comprise Nocardia-like variants (NLV) with the fragmenting mycelium. The following change in the variants occurs in the inoculations of the submerged mycelium in the course of the cultural growth: TV leads to NV leads to NLV or (more rarely) TV leads to NLV. The dynamics of accumulation of the variants depends, to a considerable extent, on the source of carbon in the medium: NLV first appear on the medium containing fructose; NV are detected first on the medium with glucose; NV are rarely found on the medium with mannitol. In aged cultures, the number of NLV can reach 80--90%, the content of TV is 20--10%, and NV are absent. The above results suggest that the formation of NLV from S. roseoflavus var. roseofungini is the result of stepwise selection.


[Bacteriocin-like factor in Bacillus thuringiensis].

The paper describes Bacillus thuringiensis var. galleriae strains possessing a bacteriocin-like factor (factor K) which inhibits the cultures of a number of serotypes of Bac. thuringiensis. The K+ cultures exhibit no antibacterial effect on other gram-positive and gram-negative microorganisms. The maximal level of factor K is found by the 8--9th hour of cultivation. No correlation has been established between the strucutred elements in the preparations of K+ cultures and the antibacterial activity. Apparently, factor K can be transferred to other strains.


[Proteolytic system of Aspergillus ochraceus studied in relation to its plasma-coagulating and fibrinolytic activities].

The culture of Aspergillus ochraceus HP-19 accumulates two types of proteolytic enzymes in the cultural broth. One group of proteases coagulates blood while the other has the fibrinolytic activity. The enzymes can be separated by gel filtration on Sephadex G-100. The first group of enzymes consists of several proteases with the coagulase activity and an inert protein.


[Electron microscopy study of the microorganism topography on plant roots].

The topography of microorganisms in the root cap zone and in the absorption zone was studied with 7-day-old wheat seedlings. No microorganisms were detected in the root cap zone. Individual microorganisms as well as their accumulations were registered in the absorption zone. The topography of microorganisms in this zone was characterized. Different morphological forms were present among microorganisms. Types of interaction between these microorganisms and the cells of root epidermis are discussed.


[Possibility of the nonbiological binding of CO2 and CO by the components of Martian soil].

A mixture of carbon dioxide and carbon monoxide was irradiated in the presence of limonite and hydrogen peroxide at 340 nm. As has been demonstrated by gas chromatography, chemical reactions occurring in this case yield organic compounds which could be synthesized in the experiments conducted by the Viking stations. Consequently, this method cannot discriminate between the chemical and biological processes which possibly accounted for positive signals registered in the experiments of the Viking stations.


[Ultrastructural organization of Sulfobacillus thermosulfidooxidans cells and spores].

The ultrastructural organization of Sulfobacillus thermosulfidooxidans cells and spores was studied by electron microscopy using the techniques of negative contrasting and thin sections. The cell wall was found to be 20--25 nm thick and to consist of a rigid layer bound to the cytoplasmic membrane with crosspieces. A microcapsule about 20 nm thick having an ordered structure is closely associated with the cell wall. A layer of slime which can reach 0.2--0.3 mcm and more in thickness is located at the outside. The flagellar apparatus is absent. The membranous apparatus has a peculiar structure. On thin cross-sections of intact cells, the cytoplasmic membrane profile is stained sharply asymmetrically. Numerous membrane invaginates located in the cytoplasm are morphologically simple vesicular formations and structures of a rather complicated unusual configuration. Lamella-like structures are also encountered, which divide, as it were, the cytoplasm into compartments. The contours of the intracellular membranes look thicker as compared with the cytoplasmic membrane. Small vesicular formations are occasionally encountered in the periplasm. Vast areas with inclusions of unknown chemical nature having a fine granular structure are located in the cytoplasm. The process of sporogenesis comprises the same stages as in Bacillus, and spores have a strucutre typical of the endospores.


[Microbial cenosis in the initial stage of spruce needle decomposition].

The formation of saprophytic microbial cenosis at the primary stage of decomposition of spruce needles was studied by the method of scanning electron microscopy with parallel inoculations into growth media. The composition of the cenosis was found to differ depending on whether the needles were decomposed on the surface of the forest floor or on the soil without any flooring. The characteristics of the formation of the saprophytic microbial cenosis are described. The cenosis is formed from individual species of the soil microbial complex and from some representatives of the epiphytic microbial cenosis which change here becoming saprophytes instead of biotrophs. Yeasts and yeast-like organisms predominate at the primary stage of decomposition of spruce needles.


[Nitrogen-fixing fungal associations with bacteria].

Nitrogen-fixing associations of fungi and bacteria have been isolated from the soil and flooring of coniferous forests. The special composition and the nitrogen-fixing activity of components in associations were determined. Pure fungal cultures did not possess the nitrogen-fixing activity. The nitrogen-fixing activity of pure bacterial cultures was always lower than that of their associatons with fungi. The possibility of existence and the specificity of species composition in the nitrogen-fixing associations of fungi and bacteria are discussed.


[Bacterial plankton study of the shallow inlets of Possiet Bay (Sea of Japan)].

A summer-autumn maximum and a winter maximum are typical of the seasonal bacterioplanktonic developmental cycle. The minimal concentration of bacteria (biomass, 16--26 mcgC/l; production, 5 mcgC/l . day) is observed in early winter. As the water gets warmer by July, this concentration reaches its maximum (biomass, 70--75 mcgC/l; production, 70--85 mcgC/l . day). The activity of microflora in half-open bays is similar to that of the open bay the Road of Pallas. The high level of bacterial activity is evidently supported by dissolved organic matter transferred from the detrital pool of eelgrass.


An analysis of behavioural objectives in the teaching of anatomy from the results of marks in MCQs.

Since 1972 behavioural objectives have been presented to the students in the Department of Anatomy, University of Cape Town, for certain sections of their course but not for others. Questions set to students in certifying multiple choice examination from 1972 to 1976 were divided into two categories (a) those set on sections of the course with objectives and (b) those set on sections of the course without objectives, and analysed in terms of (i) student performance, (ii) discriminative ability of the questions. Significant differences are noted in student performance in these two categories which support the setting of student objectives. Student discrimination however is noted to be less effective in the category of questions on objectives, but not significantly so.


Ongoing evaluation of a behavioural sciences course for medical students: uses, methods, limitations.

This paper describes a system of ongoing student evaluation of a behavioral sciences course for medical students. Student opinion about all aspects of the course is tapped, using a variety of methods including formal and informal discussion between staff and students; and written evaluations of lectures, tutorials, textbooks, assignments, and methods of assessing students' performance. The evolution of the evaluation programme into its present form is described, together with the way in which student evaluations are used, and the limitations of these methods of evaluating a course.


A factor analytic study of branching patient management problems.

This study was undertaken to determine the factor analytic structure of patient management problems (PMPs) and to determine whether such factors are stable for different groups taking the same examination and for the same group over time. Two examinations were administered to a group of medical students, the first during their junior year and the second during their senior year. The second examination was also administered to a second class of students during their junior year. Factor analyses results indicated there are two components to medical problem-solving as measured by PMPs-data gathering and management. Both factors were stable over groups and over time.


Videotapes in psychiatry: their use in teaching observation techniques.

In order to assess the effectiveness of videotapes in teaching mental state examination, two groups of medical students, one who had received videotape teaching and one not exposed to videotapes, are compared in their ability to observe accurately the mental state during a live interview. Accuracy of observation was assessed by obtaining a measure of the students' ability to shift from an incorrect opinion about a patient to a more accurate assessment following the live interview. Students who had received videotape teaching were able to make more accurate judgements than those who had not. This ability was not related to certain personality attitudes measured, nor to an ability to detect subjective elements in the interview, nor is it reflected in their examination results. The only significant variable found to influence this ability was whether or not the student had received videotape teaching.


[Product of second-stage riboflavin biosynthesis in Pichia guilliermondii].

Dialyzed extracts of the mutants of Pichia guilliermondii RG80 (rib3, his-) and RA39 (rib3, ade-) in which the third step of flavinogenesis was genetically blocked converted GTP into 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine phosphate and 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine in the presence of NADPH2. Apparently, 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine phosphate is a true precursor of riboflavin whereas 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine is formed upon its hydrolysis.


The use of television in the assessment of home and foreign postgraduate groups during an introductory course in psychiatry.

Videotapes were developed for testing the ability to detect psychiatric phenomena, methods of questioning and interview technique. These were capable of discriminating between the performance of home graduates (HGs) and foreign graduates (FGs) and were consistent with other test results. These were significant differences between HGs and FGs on all tests before and after teaching. HGs started with high scores on all tests and these remained high, although no significant improvement occurred with teaching. FGs started with lower scores and showed improvement on the videotape test only, after teaching. HGs and FGs were exposed to video teaching methods but FGs rated video demonstration as a more helpful teaching mode.


Criteria for acceptance of reports in experimental laboratory courses (an examination of the cook-book experiment in physiology and its relation to the scientific process).

The purpose of this paper is to solve a practical problem through a theoretical analysis based on concepts from another scientific field. A new hypothesis emerges from this 'hermeneutical' approach, namely that the criteria derived are a set of useful tools in improving instruction in laboratory course work of the Cook-Book-Experiment type in physiology and related subjects. The hypothesis has been empirically tested only to an extent that deems it worthy of further testing by other teachers.


[Evaluation of neck bruits by directional Doppler sonography (author's transl)].

Neck bruits were noticed 86 times in 60 patients. A hemodynamic obstruction of the carotid artery was diagnosed in 22% by Doppler sonography of the supratrochlear artery. The diagnostic directions in case of neck bruits are suggested: 1. In patients with a history of neurological symptoms a pathological Doppler test will be the indication for cerebral angiography. If obstruction of the carotid artery is suspected by clinical examination cerebral angiography should be done in spite of a normal directional Doppler sonography. 2. Cerebral angiography must be done in patients with asymptomatic neck bruits and a pathological Doppler sonography if the patient will undergo a great operation.


[Survey after correction of carotid stenosis (author's transl)].

Since 1962 until 1976 we have performed 335 operations on the carotid artery in 268 patients. In 1977 we were able to obtain information from 265 patients. The early mortality in stage I, II and IV was one to three percent, in stage III 40 percent. The cumulative survival rate after four years was 74 percent. The main causes of death were cardiac diseases. Often the patients also had heart failure, peripheral arterial diseases, hypertension, and diabetes. Following the operation at least one third of the patients had an improvement of their symptoms.


[The resorption of cotrimoxazol from preparations produced by different manufacturies (author's transl)].

In a pharmacokinetic study with healthy test persons we compared the forte-tablet form of cotrimoxazol produced by 4 different manufacturers. We were able to show that 3 of the tested products (2 well known standard products I and II as well as a new comparative product) achieved nearly equal high serum concentrations of sulfamethoxazole and trimethoprim. The serum concentrations of a fourth product, a generic product, were lower for sulfamethoxazole and trimethoprim. As the difference is of no statistical significance and the serum concentrations of the last product are within the therapeutic range this product is also qualified for therapeutic use. When the dose is given after a standard breakfast the serum values of sulfamethoxazole were slightly higher than if given on an empty stomach. However, the serum values of trimethoprim given on an empty stomach were higher.


[Atrial double-rhythm with total intraatrial block (author's transl)].

Report about a 52-year old patient with hypertension, who showed a transitory atrial double-rhythm and a total intraatrial block. The actions of one atrium with a frequency of 55--60/minute were transmitted regularly to the ventricles; the actions of the other atrium had a frequency of 90/minute and were not transmitted. In later controls of the ECG this phenomenon could not be seen again; at this time the rhythm was changing between a sinusrhythm with polytope ventricular extrasystoles and an absolute arrhythmia due to atrial fibrillation.


[Psychological and psychopathological aspects of cardiac pacemaker implantation (author's transl)].

Several examinations made clear that patients with cardiac pacemakers are able to react in the three following ways: In most cases we see a regain of joy of living and mental performance caused by the regulation of heart-action and the normalization of the physical strength. Most patients seem to be anxious and labile in the first postoperative phase until some weeks later the previous state of emotional stability is obtained again. Many other patients are not able to adapt themselves to the pacemaker in a satisfactory manner; depressions, fears, dependences, lability, and uncomfortable feelings continue. In some cases we see intensive affective reactions even to a psychotic degree. An accurate and continous psychological care based upon an intact doctor-patient-relation might lead to an accelerated and improved adaptation to the pacemaker.


Slipped capital femoral epiphysis following radiotherapy and chemotherapy.

There may be an increased frequency of slipped femoral epiphysis in pediatric patients who have received radiation to the pelvic area and combination chemotherapy. Previous reports include bilateral slipping of the epiphysis, eight years after radiation, in a patient with a pelvic neuroblastoma and the occurrence in a patient who had received radiation for Hodgkin disease, with a primary site in the pelvic region. No direct correlation was established in either case. This is a report of two patients who received pelvic radiation and combination chemotherapy who subsequently developed slipped femoral epiphysis. Our purpose is to heighten the suspicion in patients who have received radiation and chemotherapy for pelvic tumors. It is recommended that the femoral heads and acetabula be shielded when their inclusion in the treatment fields is not crucial to the treatment of the underlying disease.


Inapparent infiltrations associated with vindesine administration.

Vindesine is des-acetyl vinblastine amide sulfate (Eldisine, Eli Lilly and Co), an investigational derivative of the vinca alkaloid, vinblastine. Initial phase I results with vindesine have determined that myelotoxicity is dose-limiting and that, contrary to preclinical studies in animals [1], a neurotoxic potential is indeed present [2]. Another phase I study also observed a rather high incidence of phlebitis (16%) and of cellulitis (10%), however, myelosuppression remained the dose-limiting toxicity [3]. Because good clinical responses have been noted in lymphomas, leukemias [4] and some solid tumors including breast cancer [5], the drug has a potential for wide utility. However, while we have noted several clinical responses with vindesine, injections of the drug have been complicated by serious infiltration with atypically delayed presentation. The purpose of this communication is to briefly describe the incidence and course of these infiltrations.


Action of cytosine arabinoside on human tumor cells isolated from malignant effusions: in vitro phosphorylation and inhibition of DNA synthesis.

Tumor cells were isolated from malignant effusions of three patients with disseminated solid tumors of different origin. Intracellular accumulation of nondiffusible cytosine arabinoside (ara-C) nucleotides was used to measure phosphorylation. Mouse leukemia L 1210 and L 1210/CA, and ara-C-resistant subline, were used as reference cells. Phosphorylation activity was similar in the cells from all three solid tumors and showed a linear increase with drug concentrations of 0.1--100 micograms/ml. In contrast to activity in L 1210 cells, the in vitro activity was not saturable at drug levels up to 100 micrograms/ml. Ara-C inhibited the incorporation of thymidine into DNA 84%--90% in the solid tumor cells at a concentration of 10 micrograms/ml. Higher drug concentrations did not result in further inhibition. In one patient, DNA synthesis of tumor cells isolated before and after intraperitoneal instillation of 1,000 mg ara-C was measured. The in vivo inhibition was found to correspond to the in vitro data. Solid tumor cells isolated from malignant effusion have no greatly reduced capacity for cellular formation of ara-C/nucleotides, but higher drug levels than achieved with conventional therapy are necessary for sufficient ara-C nucleotide synthesis.


An exploration of cancer staff attitudes and values.

A multidisciplinary team involved in the care of patients with advanced cancer including physicians, nurses, social workers, physical therapists, nutritionists, clergymen, enterostomal therapists, biostatisticians and administrative personnel were studied over a period of eighteen months. A prospective study of staff attitudes and values about life, disease, and medical care which focused particularly on cancer, cancer treatment and patients with cancer was undertaken. Data were gathered from the staff by written responses to the following instruments: 1) Rokeach Value Survey and 2) a Personal Attitudes Toward Illness Questionnaire. This longitudinal prospective study demonstrated the reliability of scrutinizing individual and collective staff characteristics in a cancer care team. Although most team members had minimal previous contact with clinical research or with patients with advanced cancer, increased exposure did not result in changes in staff attitudes and values over the period of seventeen months.


Adenocarcinoma of unknown primary site: a clinico-pathological study.

An analysis of the clinico-pathological findings in 49 patients with adenocarcinoma of unknown primary origin indicates a short survival time. No factors were identified that influenced survival. Thromboembolic episodes and second primary tumors commonly complicate the clinical course. Metastases in widespread organs are common autopsy findings. Immunological mechanisms may explain these findings.


A megavoltage MTF measurement technique for metal screen-film detectors.

A technique to measure the MTF of metal screen-film detectors at megavoltage x-ray energies has been devised. It employs an exposure through a slit 25 micron wide and a method to average numerous line spread functions from a single film image. That the slit is wide compared to those used at diagnostic x-ray energies serves two purposes: it facilitates the use of a laser alignment procedure designed to ensure correct orientation of the slit-forming tungsten blocks in the x-ray beam, and it also increases the contrast in the slit image, thereby reducing the data analysis problems caused by film noise. Further reduction in the effects of film noise is accomplished by the averaging method. A correction is made to account for the effect of the wide slit on the MTF. The validity of this correction, the laser alignment, and the averaging method have been confirmed by simulations.


Examination of the factors Ac and Aeq for cylindrical ion chambers used in cobalt-60 beams.

The calibration of a cobalt-60 beam in a phantom with an ion chamber, which has been calibrated with respect to exposure, requires the use of a displacement correction factor which essentially corrects the photon fluence for the attenuation and scatter when the chamber with buildup cap is removed and replaced by phantom material. To determine the displacement factor, Ac, a special set of cylindrical ionization chambers with various volumes were constructed out of polystyrene. Tissue-air ratios were measured with these chambers for cobalt-60 gamma rays in a polystyrene phantom, and the ratio Ac/Aeq was experimentally determined. In order to calculate Ac from this ratio, Aeq was determined also. It was found that Ac depended on chamber diameter only, and not on field size or depth. A value of 0.990 for Aeq is recommended and a table of Ac for chambers of different outer diameters is included.


The laser microprobe mass analyzer (LAMMA): a new instrument for biomedical microprobe analysis.

After a short review of the general state of the art of microprobe analysis, recent achievements of a new system, the laser microprobe mass analyzer (LAMMA) are presented. The LAMMA-instrument, which was primarily developed for biomedical purposes, has recently been used on a large variety of specimen, biological, technical, organic and inorganic in nature. Detection limits, mass resolution and reproducibility were improved such that for many elements measurements could be extended down to the subppm range. For bulk analysis, a separate version of the LAMMA-instrument is under development. The examples of LAMMA-applications given in this paper include muscle tissue (physiological cations), uterine tissue (Fe), retina tissues (Na, Mgmg, K, Ca and Ba!), airborne particles (Pb, Fe, Al, Ti, Mn, Ca, Zn), cerebral tissue (Li), and pure cristalline organic materials.


Dose distribution from a Delta-25 head scanner.

The dose distribution pattern from a Delta-25 head scanner was evaluated experimentally in a 17.5-cm-diam cylinder water phantom for different scan speed and slice thickness combinations. TLD chips were used to measure the dose at different points across the scan section. The isodose curves thus obtained were found to be asymmetric, with the regions of maximum and minimum dose near the surface on the opposite sides of the phantom. The effect of changing the scan thickness and speed on dose was evaluated and a linear increase in dose with the increase of slice thickness was observed. This was consistent with the design of the line focus and the beam collimators used in this system. The effect of multiple slice scan on the dose was also evaluated.


Fast and economic conversion of images to a tactile presentation for blind people.

A new procedure for the conversion of binary black and white images to a tactile presentation perceptible by the blind is described. Conventional procedures are very time-consuming and expensive and are not adapted to produce the required low editions of tactile displays, e.g., for schools for the blind or individual applications. The procedure recently developed allows the fast, economical conversion of even single drawings to a tactile display with high resolution. An account of the investigations and valuations of all possible physical procedures of optical-to-tactile conversion is given. The new procedure, based on a slightly modified Xerox copying process in a first step and gumming tactile material with the tone powder at the darkened regions in a second step, is described in detail. The device realised is presented. It allows the conversion of one page of a drawing to a tactile display with a resolution of 0.3 mm within 1 min. Various applications of the system and experiences with blind users are reported. The implement proved to meet most of the requirements of blind people. It is easy to handle and produces tactile drawings of excellent quality. As it is based on commercial subsystems it promises an economical production even at small series.


Monte Carlo advice.

The generation of long, high quality random number sequences for Monte Carlo simulations using minicomputers is considered. The importance of the thorough testing of Monte Carlo random number generators is emphasized. A recommendation is given to authors of Monte Carlo papers to specify their random number generator and to describe the randomness testing which that generator has undergone.


Discrimination of phantom hand sensations elicited by afferent electrical nerve stimulation in below-elbow amputees.

The necessity for a sensory feedback system that would enhance patient acceptability of motorized hand prostheses is now generally acknowledged. Afferent electrical stimulation of the nerves in the amputation stump can convey sensory feedback from prostheses with the advantage of eliciting sensations in the phantom image of the lost hand. Experiments with percutaneous nerve stimulation of the amputation stump in below-elbow amputees showed that with stable electrode conditions, amplitude modulated stimulation was better than frequency modulated stimulation in terms of accuracy, delay, and transinformation both with intermittent and uninterrupted stimulation. With unstable electrode conditions, different results were noticed, since amplitude modulated stimulation is very sensitive even to minor changes in electrode position. It is concluded that afferent electrical nerve stimulation with adequate training and stable electrodes had characteristics of accuracy, transinformation and delay which are good enough to make it a suitable method of conveying information in a prosthesis feedback system.


Calculating dose from remaining body activity: a comparison of two methods.

Two methods for calculating the radiation dose from remaining body activity have been suggested. One requires correction of the cumulated activities so that they reflect the activity uniformly distributed in the total body. The other method requires correction of the S values so that a value of S for the target organ from the remainder of the body is obtained. These two methods give the same answer. We have examined these methods and the number of steps required to calculate the radiation dose in each case. Our results show that the method of correcting the cumulated activities is preferred, especially if the number of source and target organs is large and a computer equipped with the necessary software is not available.


The development of consensus standards for medical devices in Canada.

The Canadian Standards Association Health Care Technology Program is a new, innovative program initiated by the Canadian Standards Association four years ago in response to the great increase in technology which has innundated our health care facilities. The goal of the program is to develop consensus standards in the medical engineering field and to help in implementing those standards across Canada through education, input to professional societies, and input to provincial or federal legislation.


A video-recording system for evaluating the clinical interview--a simple, inexpensive method.

A simple, inexpensive video-recording system was designed to provide raw data for the evaluation of therapist interview behaviors in the out-patient clinic. The system uses a combination of commercially available cameras, lenses, and recording equipment which do not require technical audio-video expertise to operate. Video-cassette recordings are produced that contain full-face, head-and-shoulders images of both the therapist and the patient. An automatic search control terminal rapidly locates any point on the video-cassette for review. Using normal clinic lighting and little space, the system is easily installed in any existing clinic examination room. A description of the system's use in examining the counseling and interviewing skills of a medical clinic staff is presented.


Computerized patient contours using the scanning arm of compound B-scanner.

Full utilization of the precision of newer radiation therapy devices requires patient contours drawn with greater accuracy than is possible with the conventional lead wire technique. Polaroid photographs can introduce large errors due to distortion and small image size. Techniques including electromechanical or optical devices and CT scans offer improved accuracy, but often at added expense. A method for obtaining contours has been developed which utilizes a treatment planning minicomputer (equipped with an analog-to-digital converter and plotter) and a commercially available ultrasound B-scanning arm. Voltages corresponding to the X-Y position of the tip of the scanning arm are fed from the scanner to the A/D interface, smoothed, scaled, and plotted. The resulting drawing is a full scale external patient contour. The accuracy of this method is compared to alternative techniques.


Feedback control dynamics for glucose controlled insulin infusion system.

Miles Laboratories has developed a Glucose Controlled Insulin Infusion System (GCIIS) designated by the Trademark (BIOSTATOR) as a tool to investigate the physiologic control parameters of carbohydrate metabolism and regulatory deficiencies in diabetes. It consists, in principle, of a rapid on-line glucose analyzer, a computer/controller for the calculation and control of insulin or dextrose infusion, and a multichannel infusion system. A silent printer records, on a minute-by-minute basis, the glucose value measured, the insulin and/or dextrose infusion rates, and the cumulative total of the insulin infused. The on-line glucose analyzer employs an electrochemical sensor with immobilized glucose oxidase and measures the hydrogen peroxide produced. Its linearity extends beyond 700 mg/dl glucose; it permits a rapid two-point calibration of the sensor and the overall calibration of the on-line analyzer without disconnecting the catheter from the patient. The system's response time, including blood sample transport from the patient, is less than 90 seconds with a blood loss of approximately 50 ml per 24 h. The insulin and dextrose infusions are governed by control algorithms; various mathematical models have been developed and employed toward improved feedback control dynamics. The rapid glucose analyzer eliminates the need for the calculation of a "predicted" glucose value and permits, instead, the use of a derivative function for dynamic control. A multichannel infusion system combines the principles of a peristaltic pump with the advantages of a precision pump performance and individual computer control for each of the pump channels.


The development of an artificial beta cell system and its validation in depancreatized dogs: the physiological restoration of blood glucose homeostasis.

An instrument for the control of blood glucose in a closed-loop fashion has been developed. This artificial beta cell consists of 4 subunits: a Glucose Monitor, a Microcomputer, an Insulin Infusion Pump and a Printer. Its internal control algorithm was derived from the modeled dynamics of glucose-induced insulin secretion, and includes the effects of both the proportional and derivative actions of blood glucose concentration, and is expressed as: IIR = Kp . BG + Kd . deltaBG + Kc, where IIR is insulin infusion rate, BG and deltaBG are blood glucose concentration and rate of change in glycemia, respectively. Kp and Kd are individual coefficients and Kc is a constant of basal insulin secretion. The performance of this system was studied with various kinds of glucose challenges on anaesthetized depancreatized dogs. Its notable characteristics were: 1) the insulin infusion rate was such as to maintain physiological insulin levels, and 2) dextrose or glucagon infusions were not required.


Action of staphylococcal alpha-toxin on membranes: some recent advances.

Recent developments in the area of Staphylococcal alpha-toxin studies are presented which modify the concepts previously held with respect to both biological and physical properties of alpha-toxin. New data concerning the nature of the binding site for alpha-toxin on rabbit erythrocyte membranes and a model to explain the various observed complexes of alpha-toxin and membrane receptor are discussed. Finally, evidence suggesting that Staphylococcal alpha-toxin is a potent demyelinating agent is presented.


Purification and structural properties of isozymes of isocitrate dehydrogenase from the mouse.

Cytoplasmic and mitochondrial isozymes of NADP+-dependent isocitrate dehydrogenase were purified from kidney and heart tissue of an inbred strain of mice. The cytoplasmic isozyme was purified from kidney of DBA/2J mice by means of a four-step procedure which included affinity chromatography with an 8-(6-aminohexyl)-amino-NADP+-Sepharose column. The heart mitochondrial isozyme of DBA/2J mice was purified by a two-step procedure involving the use of 8-(6-aminohexyl)-amino-AMP-Sepharose and 8-(6-aminohexyl)-amino-NADP+-Sepharose columns. The specific activity of the homogeneous cytoplasmic and mitochondrial isozymes was 40 units/mg and 45 units/mg, respectively. Native and subunit molecular weights of these two isozymes were determined by chromatography on Sephadex G-100, G-150 and G-200 Superfine and polyacrylamide gel electrophoresis. Both isozymes were found to be dimers with the subunit molecular weight of approximately 35,000. The sedimentation coefficients were determined to be 5.9 and 6.1 for the mitochondrial and cytoplasmic isozyme, respectively. The amino acid compositions of these two isozymes revealed distinct differences in arginine and proline contents. A modified procedure regarding the use of affinity columns for the purification of the weakly bound enzymes is also discussed.


Mutants of Staphylococcus aureus deficient in recombinational repair. Improved isolation by selecting for mutants exhibiting concurrent sensitivity to ultraviolet radiation and N-methyl-N'-nitro-N-nitrosoguanidine.

Recombination-deficient (rec) mutants of Staphylococcus aureus strains 152 and Ps29 were sought by initially screening mutagenized cultures for mutants exhibiting increased sensitivity to both ultraviolet (UV) radiation and N-methyl-N'-nitro-N-nitrosoguanidine (NG). Mutants thus isolated were analyzed for recombinational ability by transduction, and further characterized in terms of sensitivity to UV, NG, ability to repair UV-irradiated bacteriophage, and spontaneous and UV-induced DNA degradation. Mutagenesis of strain 152 yielded three isolates, one of which was rec, the second potentially lex, and the third possessing an undetermined repair deficiency. Mutagenesis of strain Ps29 resulted in the isolation of one mutant, which exhibited a rec genotype. In searching for rec mutants of S. aureus, the value of initially screening mutagenized cultures for mutants exhibiting concurrent sensitivity to UV and NG, as opposed to screening for UV sensitivity alone, is discussed.


Vitamin C is positive in the DNA synthesis inhibition and sister-chromatid exchange tests.

Ascorbate caused a dose-dependent increase in sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells and in human lymphocytes. Moreover, in the DNA synthesis inhibition test with HeLa cells, ascorbate gave results typical of DNA-damaging chemicals. Catalase reduced SCE induction by ascorbate, prevented its cytotoxicity in CHO cells, and prevented its effect on HeLa DNA synthesis. Ascorbate reduced induction of SCE in CHO cells by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by direct inactivation of MNNG.


Spontaneous and mitomycin-C induced sister-chromatid exchanges. Comparison of in vivo and in vitro systems.

Frequencies of sister-chromatid exchanges (SCE) were measured in vitro in mouse fibroblasts and in vivo in mouse bone-marrow cells. SCE levels in these cell systems were measured in response to varying concentrations of bromode-oxyuridine (BrdU) and mitomycin-C (MMC). Although BrdU was found to induce SCE in both cellular systems, baseline SCE levels were 2- to 3-fold higher in vitro than in vivo. SCE induction was found to be a linear function of MMC concentration in vivo and in vitro; however the slope of the vivo curve was 5-fold higher. The interaction of BrdU substituted DNA and MMC was examined by administering a fixed dose of MMC with increasing concentrations of BrdU. The induced SCE frequencies appeared to be additive. In addition to measuring drug-induced SCE, the BrdU differential staining technique allows concomitant measurement of the inhibition of cellular replication by the test drugs.


Frequency changes with time in vivo of radiation-induced chromosomal aberrations in skin fibroblasts.

5 Syrian hamster litter mates were each irradiated with X-rays on one flank to 300 rad. Skin biopsies were taken from both the irradiated and unirradiated (control) flanks of each animal at one day and at about 6 months after irradiation. The cells cultured from these biopsies were used to determine the frequencies of chromosomal aberrations. During the 6-month period there were significant reductions in the frequencies of both reciprocal translocations and terminal deletions. Translocations involving the short arm of the Y-chromosome, however, showed a significant increase during this period. It is possible that while the latter phenomenon was due to cell selection in vivo the general fall off in translocations and deletions was the result of a long term in vivo repair mechanism or perhaps the results of certain aberrations proving to be lethal with prolonged expression times.


Mutagenicity of 8-methoxypsoralen and long-wave ultraviolet irradiation in V-79 Chinese hamster cells. A first approach to a risk estimate in photochemotherapy.

The effect of 8-methoxypsoralen (8-MOP) and long-wave ultraviolet irradiation (UVA) on cell killing and mutation induction was studied in V-79 Chinese hamster cells. No effect was observed after treatment with 8-MOP alone (50 microgram/ml, 4 h), UVA alone (9000 J/m2), or 8-MOP metabolized by rat-liver microsomes. Combined treatment with 8-MOP and UVA induced both cell killing and mutation. This was also observed under conditions approaching patient treatment with PUVA photochemotherapy with respect to the concentration of 8-MOP in the skin and the amount of UVA received by the epidermal cells. A simple relation proved to apply for mutation induction under different treatment conditions: 5.5 X 10(-8) per J/m2 per microgram 8-MOP/ml. On this basis the mutation induction in dividing cells per session of PUVA-photochemotherapy amounts to 12.4 X 10(-5), which is probably an over-estimation.


gamma-Ray mutagenesis in bacteriophage T4 is not enhanced by oxygen.

As in the induction of r mutants in bacteriophage T4 by gamma-rays, the radiation-induced reversion of T4 amber mutants to wild-type was found to depend on the product of the DNA-repair gene x of the phage. Neither the efficiency of induction of r mutants nor the efficiency of reversion of ambers was enhanced by the presence of oxygen during irradiation. T4 differed in this respect from phage T7, for which no indication has been found that gamma-ray mutagenesis results from error-prone repair of DNA damage. Notwithstanding the substantial contribution of misrepair to mutation induction in T4, the efficiency of induction per base-pair observed for irradiation under oxygen was lower than that found previously for T7.


Aberrations of holokinetic chromosomes and associated lethality after x-irradiation of meiotic stages in Tetranychus urticae Koch (acari, tetranychidae).

Chromosomes of the holokinetic organization type were irradiated with X-rays in various stages of meiosis in unfertilized eggs of Tetranychus urticae Koch. Visible cytological aberrations, lethality and sterility were investigated in subsequent generations. Chromosome fragments are the most frequently occurring light-microscopically visible chromosome aberrations; bridges are not formed. Contrary to expectations, the presence of fragments appears to be positively correlated with the occurrence of lethality; loss of fragments, mis-segregation and the measure of damage to the broken chromosome parts are involved. In contrast with monokinetic chromosomes the earliest lethality occurs only after about 10 divisions. The ratios between different embryonic lethality types (early vs. late) differ depending on the stage irradiated: in more compact chromatin, more serious damage (i.e. more early lethality syndromes) is induced than in less compact chromatin. In the progeny of the surviving males, neither translocations nor independent fragments are found; indirect evidence indicated the occasional presence of inversions. The presumptive inversions are induced more frequently in a chromatin-compact stage (metaphase I) than in a less compact one (telophase I).


Induction of lethal mutations in female mice by 9 generations of gamma-irradiation during foetal development.

Female CBA mice were chronically gamma-irradiated in utero during either of two periods, the 10th to 14th days or the 14th to 18th days of gestation. The doses administered were 34 rad/generation in the earlier group and 160 rad/generation in the latter with dose rates of 0.3 rad/h and 1.7 rad/h, respectively. The doses were given through 9 generations. The effect of the irradiation was expressed as an increased frequency in the rate of recessive lethal equivalents by just above 4%. This corresponds to a mutation rate of 1.5 X 10(-4) mutation/rad/genome in the animals irradiated during the 10th to 14th gestational days and 0.3 X 10(-4) mutation/rad/genome in the 14th to 18th day group. As in earlier investigations, neither dominant mutations nor dominance effects of induced recessive lethal equivalents were found.


The effect of oxygen concentration on the X-ray induction of chromosome aberrations in human lymphocytes.

In vitro dose--response curves, for unstable chromosome aberration induction in human lymphocytes under conditions of full oxygenation or of anoxia, have been obtained using 250 kVp X-rays. Dicentric yields have been fitted to the quadratic function Y = alpha D + beta D2. An Oxygen Enhancement Ratio (OER) ranging from 7.2 to 2.7 was calculated from the coefficients of these curves possibly indicating that the data do not fit to the dose-modifying model of the oxygen effect although the differences are not statistically significant. A similar analysis of total aberration data yields an OER of 3.6 to 2.7 fitting much more satisfactorily to the dose-modifying model. Variations in dicentric yield induced by 3.0 Gy and 0.75 Gy of X-rays with increasing oxygen concentration were plotted and for each dose a constant dicentric yield was observed at oxygen levels of 2 and 250 ppm. Above 250 ppm yields increased steeply up to about 1% oxygen and then more gradually to a maximum at 100% oxygen.


Facilitation by pyrimidine deoxyribonucleosides and hypoxanthine of mutagenic and cytotoxic effects of monofunctional alkylating agents in Chinese hamster cells.

Hypoxanthine (Hx), thymidine (TdR) and deoxycytidine (CdR), at concentrations of 10(-5) M increased the yield of 8-azaguanine-resistant (AzGr) mutants induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in cultured Chinese hamster V79 cells. The cytotoxicity of MNNG was increased 2-fold in the presence of Hx, and more than 10-fold in the presence of TdR. This cytotoxic effect of TdR was abolished by equal concentrations of CdR, which by itself did not increase the cytotoxicity of MNNG. However, the yield of MNNG-induced AzGr colonies was increased 2--10-fold in the presence of both CdR and TdR. The AzGr colonies displayed phenotypes characteristic of hypoxanthine: guaninephosphoribosyltransferase-deficient (HGPRT-) mutants, or indicative of mutant HGPRT with altered substrate affinities. The nucleosides did not affect the growth or expression time of the HGPRT- mutants; the same extent of alkali-labile DNA damage occurred in cells treated with alkylating agents in the presence and absence of TdR and CdR; and the increase in mutation frequency in the presence of these nucleosides occurred not only with MNNG, but also with ethylating agents. Nucleosides treated with MNNG were not mutagenic, and treatment of the cells with TdR and CdR only prior to treatment with MNNG or only during selection with AzG did not increase the induced mutation frequency. Therefore, the interpretation is proposed that CdR, TdR and Hx produce nucleotide-pool imbalances that increase lethal and mutagenic errors of replication of alkylated DNA.


The recovery of mammalian cells treated with methyl methanesulfonate, nitrogen mustard or UV light. I. The effect of alkylation products on DNA replication.

CHO cells were synchronized in G1 phase and treated with MMS or HN2. The subsequent rate of DNA replication was found to be reduced in a dose-dependent manner. In addition, 2 X 10(-3 M and 3 X 10(-3) M MMS resulted in a 3--4 h delay prior to the initiation of S phase. If the cells were held for 8 h in hydroxyurea after MMS treatment, no subsequent lag in DNA synthesis was seen after removal of the hydroxyurea. The entry of confluent cells into S phase was found to be delayed 7 h upon trypsinizing and replating. Treatment of these cells with MMS resulted in a reduced rate of DNA replication, but no further delay in its initiation. Repair replication was found to continue at a constant rate for at least 12 h following MMS treatment of cells under all of these conditions. At the concentrations used in these experiments MMS severely inhibited the rate of protein synthesis, but HN2 had little effect. By comparing both the kinetics of repair replication and recovery of protein synthesis with the rate of DNA replication, it was concluded that the initial, severe reduction in rate following MMS treatment was probably due to an inhibition of protein synthesis.


The recovery of mammalian cells treated with methyl methanesolfonate, nitrogen mustard or UV light. II. The importance of DNA repair prior to the initiation of S phase.

CHO cells were synchronized 2 G1 phase and treated with UV light or HN2. These treatments resulted in a dose-dependent reduction in the rate of DNA replication and cell survival. Holding UV-irradiated cells in G1 phase (in HU medium) for an additional 10 h prior to their release into S phase did not assist recovery as measured by either of these criteria. The survival of cells treated with HN2 was also not enhanced by this recovery period. However, following 2 X 10(-5) M HN2 the rate of DNA replication increased from 30% to 70% of the control level when the period in HU medium was extended to 14 h. The induction of cross-links following HN2 treatment of asynchronous cells was shown to be dose dependent. Subsequent incubation in fresh medium resulted in complete recovery within 20 h at concentrations of HN2 up to 10(-5) M, and at 2 X 10(-5) M HN2, 75% of the cross-links were removed at 14 h post treatment.


Superoxide dismutase and catalase activities in Ataxia telangiectasia and normal fibroblast cell extracts.

Superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) are important enzymes involved in protection of the cell from harmful effects of oxidative degradation. The respective substrates for these enzymes, superoxide anion and hydrogen peroxide, can be generated within the cell either by normal metabolism or by ionizing radiation. The hypothesis that the inherent radiosensitivity associated with the human autosomal recessive disease Ataxia telangiectasia is due to decreased levels of SOD and/or catalase was tested. The results suggest that fibroblast cells derived from ataxia patients are normal with respect to these two enzymes.


Induction of 8-azaguanine- and ouabain-resistant mutants by cyclophosphamide and 1-(pyridyl-3)-3,3-dimethyltriazene in Chinese hamster cells cultured in diffusion chambers in mice.

A host-mediated assay is described for induction of 8-azaguanine-resistant (azgr) and ouabain-resistant (ouar) mutants in Chinese hamster V79 cells cultured in diffusion chambers (DC) in C3H mice. Injection of the hosts with the indirect mutagen/carcinogen cyclophosphamide (CPP) or 1-(pyridyl-3)-3,3-dimethyltriazene (PyDT) caused a dose-dependent increase in mutation frequency at the loci of azgr and ouar in the V79 target cells. Plating efficiency of V79 cells in DC in mice was decreased depending upon the dose of CPP or PyDT given to the hosts. In addition, the relationship between expression time and mutation frequency was examined and discussed. The data support the use of this system as an effective screening procedure for suspected environmental mutagens or carcinogens, especially those that need to be metabolically activated in vivo.


Inducibility of chromosomal aberrations by metal compounds in cultured mammalian cells.

Metal compounds were tested for their ability to induce chromosomal aberrations in cultured mammalian cells. Chromosomal aberrations were induced by the application of some Cr, Mn and Ni compounds. Among 6-valent Cr compounds, K2Cr2O7 and CrO3 induced high levels of aberrations, at rates which were similar for Cr-equivalent doses. The perchromate compounds were more efficient in producing chromosomal aberrations than was a chromate compound, K2CrO4. A 3-valent Cr compound, Cr2(SO4)3, was less toxic and failed to induce a demonstrable increase in chromosomal aberrations. KMnO4 induced aberrations, but at a low rate. As to Ni compounds, NiCl2 and (CH3COO)2Ni induced few aberrations. Administration of K2Ni(CN)4 induced only gaps. NiS induced a low but definite increase in chromosomal aberrations. The rate of these aberrations increased with an increase in treatment time from 24 to 48 h, indicating a time-dependent increase in the hereditable toxicity of metal compounds. CdCl2 and HgCl2 were somewhat toxic, but failed to induce chromosomal aberrations in the present study.


Chromosomal aberrations and sister-chromatid exchanges in Chinese hamster cells treated in vitro with hexavalent chromium compounds.

Chinese hamster cells (CHO line) were treated in vitro for 30--39 h with hexavalent chromium compounds (K2Cr2O7 and Na2CrO7), at concentrations ranging from 0.1 to 1.0 microgram of Cr6+ per ml, in medium containing BUdr. Chromosomal aberrations and sister-chromatid exchanges were scored on BUdr-labelled 2nd division metaphases, collected at the end of treatment and stained with Giemsa. Treatment with mitomycin C 0.009--0.030 microgram/ml) was carried out as a control for the responsiveness of the cell system to chromosomal damage. Both chromium compounds induced marked mitotic delays. Chromosomal aberrations were increased about 10-fold by exposure to Cr6+ (1.0 microgram/ml). The principal aberrations observed were single chromatid gaps, breaks and interchanges, whose frequencies increased proportionally to the concentration of chromium. Dicentric chromosomes, isochromatid breaks, chromosome and chromatid rings were also induced. The frequenyc of sister-chromatid exchanges was hardly doubled 30 h after exposure to Cr6+ at 0.3 microgram/ml, whereas it was trebled 39 h after treatment, in the cells whose division cycle had been slowed down by chromium.


Cytogenetic activity of some common antioxidants and their interaction with x-rays.

Experiments were designed to investigate the cytogenetic activity of some commonly used phenolic antioxidants, namely BHA, BHT, BMP and PG, all used widely to preserve and stablize food products rich in fats and oils. Barley and onion were used as test systems. The treatments reduced seed germination and induced a significant amount of seedling injury. Only PMP treatments produced a moderate amount of chromosomal aberrations while others failed to do so. Being strong antioxidants it was expected that these compounds would reduce the cytogenetic damage caused by the radiations. Contrary to expectations, however, a significant increase was observed in the radiation damage measured as seed and seedling lethality and chromosomal aberrations. Chemical post-treatments also increased the radiation damage. The damage was, however, reduced with ATP post-irradiation treatment.


Chromosomal aberrations induced by maleic hydrazide and related compounds in Chinese hamster cells in vitro.

The cytotoxic effects and chromosomal abnormalities induced by maleic hydrazide (MH) and its salts were investigated in cultured V79 cells. MH, and its potassium (K-MH) and diethanolamine (DEA-MH) salts were tested. MH was 5--14 times more cytotoxic than its salts and almost 4.5 times less toxic than the related compound, hydrazine dihydrochloride (HDC). MH salts had very weak cytotoxicity; the LD50 values on V79 cells on exposure for 3 h in vitro were (in microgram/ml) 1100 (MH), 12 000 (DEA-MH), 20 000 (K-MH), 230 (HDC) and 10 000 (NaCl). Both MH and its salts--but neither HDC nor NaCl--caused chromosomal aberrations in cultured V79 cells. The maximal frequencies of aberrant cells in cultures exposed to the compounds for 3 h in vitro were 18% (mh at 100 microgram/ml), 18% (K-MH at 20 000 microgram/ml) and 13% (DEA-MH at 20 000 microgram/ml). Maximal frequencies observed in cultures treated with HDC or NaCl were 10% (HDC at 400 microgram/ml) and 5% NaCl at 10 000 microgram/ml). Those of positive groups were 97% (N-methyl-N'-nitro-N-nitrosoguanidine, MNNG, at 5 microgram/ml) and 16% (ethyl methanesulfonate, EMS, at 400 microgram/ml). These frequencies of MH and its salts were 3.25--4.5 times those in untreated control cells. These results suggested that MH and its salts had weak inducibili


Mutagenicity, cytotoxicity and DNA crosslinking in V79 Chinese hamster cells treated with cis- and trans-Pt(II) diamminedichloride.

The mutagenicity and cytotoxicity of cis- and trans-Pt(II) diamminedichloride (PDD) were examined in V79 Chinese hamster lung cells and compared with effects on DNA measured by alkaline elution. DNA--protein crosslinks and DNA interstrand crosslinks were detected following doses of cis-PDD which reduced cell survival 80--90% and which produced a mutant frequency of 3 X 10(-4) at the HGPRT locus. Equitoxic doses of trans-PDD were much less mutagenic than cis-PDD. At equitoxic doses, trans-PDD produced more DNA-protein crosslinking than did cis-PDD, but interstrand crosslinking for the two isomers was comparable. Hence, the interstrand crosslink could be the cytotoxic lesion produced by these Pt compounds whereas neither of these DNA lesions are necessarily mutagenic. The mutagenesis produced by cis-PDD could be due to crosslinks of a different type than those produced by trans-PDD or it may be due to monofunctional damage.


Absence of genotoxic effects of metronidazole and two of its urinary metabolites on human lymphocytes in vitro.

The antiprotozoan agent metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) and two of its major human urinary excretion products, 2-methyl-5-nitromidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole were tested for genotoxic activity in human lymphocytes in vitro by analysis of chromosome aberrations, sister-chromatid exchanges and DNA-repair synthesis. The positive control compounds methyl methanesulphonate (MMS) and nitrogen mustard (HN2) showed significant genotoxic activity in these tests. No such activity of metronidazole and its two metabolites was detected in concentrations up to 1000 microgram/ml (5.8 X 10(-3) M). Nor did these 3 compounds influence DNA-repair synthesis induced by MMS and HN2. These results suggest that metronidazole, 2-methyl-5-nitroimidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole have no direct genotoxic effect on human lymphocytes in vitro.


Sister-chromatid exchanges and chromosal breakage in patients treated with cytostatics.

The frequency of structural chromosomal rearrangements and sister-chromatid exchanges (SCEs) was investigated in short-term phytohemagglutininstimulated lymphocyte cultures by means of bromodeoxyuridine substitution and fluorescence plus Giemsa (FPG) staining technique. Both these parameters were significantly increased in patients treated with comparatively low doses of cyclophosphamide, busulphan and adriamycin. The increased SCE rate was proportional to the number of chromosome breaks, the ratio of SCE to breaks being about 100:1. The increase in the SCE number was maintained for several months after the termination of cytostatic therapy, when the conventional analysis of chromosome breaks yielded normal results. Normal SCE values were obtained in two patients treated with low doses of fluorouracil.


Urethane and hydroxyurethane induce sister-chromatid exchanges in cultured human lymphocytes.

Both urethane and hydroxyurethane induced sister-chromatid exchanges (SCE) in cultured human lymphocytes. Aroclor-induced rat-liver microsome fraction deactivated rather than activated these two agents in the lymphocyte system.


Activity of citrinin metabolized by rat and human microsome fractions in clastogenicity and SCE assays on Chinese hamster V79-E cells.

The mycotoxin citrinin is a potent inducer of chromosomal aberrations in the clastogenicity assay on V79-E cells when metabolized by rat and human liver microsomes. Rat and human liver microsomes, standardized on protein content, activate citrinin at equal levels. 5 X 10(-4) M citrinin induces complex translocations in a high frequency as well as defects of chromosomal coiling. Higher concentrations are cytotoxic, lower ones are almost inactive. After metabolization of mycotoxin by rat-kidney microsomes or an S9 mix fraction containing rat liver and kidney microsomes, toxic effects predominate and chromosomal aberrations are diminished. Clastogenic citrinin concentrations do not induce an increase of SCE frequency. Although the mode of action of this mycotoxin on chromosomal structure remains obscure, possible explanations are discussed.


Rubber solvent: a clastogenic agent that fails to induce sister-chromatid exchanges.

Rubber solvent was tested for its ability to induce chromosome aberrations and sister-chromatid exchanges in human whole blood cultures. Following exposure to relatively low rubber solvent concentrations (0.0125% and greater) significant increases in the frequencies of chromatid gaps and breaks were observed. At higher rubber-solvent concentrations (0.05% and greater) there were also significant increases in the frequency of chromosome breaks. In contrast to the increase in chromosome aberrations following rubber-solvent exposure, rubber-solvent concentrations up to the toxic level failed to produce increases in the sister-chromatid exchange frequency.


The effect of a tumor promotor, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), on sister-chromatid exchange formation in cultured Chinese hamster cells.

The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) does not increase the sister-chromatid exchange (SCE) frequency in either Chinese hamster ovary (CHO) or lung (V 79) cells which are cultured in the presence of 5-bromodeoxyuridine. Moreover, TPA does not alter the induction of SCEs in CHO cells by mitomycin C during the first 3 cycles following addition of the alkylating agent. These SCE induction data do not by themselves support the hypothesis that tumor promotion by TPA depends on the enhancement of mitotic recombination.


A prospective study of spontaneous fetal losses after induced abortions.

The incidence of spontaneous abortions was observed among 31,917 women followed from their first prenatal visit. Life-table analysis showed that losses in the first trimester were not significantly affected by previous induced abortions, nor was any change in the risk of second-trimester losses detected among the 1493 parous women who reported having had induced abortions after childbirth. There was, however, an increase in the incidence of midtrimester losses among the 2019 nulliparous women with previous induced abortions; the age-adjusted rate of loss was 59.9 per 100,000 women at risk per day, as compared with 24.2 among the 12,042 control nulliparous women (P less than 0.001). The relative risk increased with the number of previous induced abortions and was not explained by the distribution of demographic and social variables. The risk decreased from 3.27 (95 per cent confidence limits, 1.72 to 6.23) after abortions induced before 1973, mainly by dilation and curettage, to 1.42 (0.76 to 2.65) after those done since 1973, when the more gentle technic of cervical dilation by use of laminaria was introduced. These findings indicate that there is little or no risk of spontaneous abortions after induced abortions when performed by current technics.


Circulating and urinary catecholamines in pheochromocytoma. Diagnostic and pathophysiologic implications.

Three biochemical tests for the diagnosis of pheochromocytoma were evaluated in 24 patients with proved tumors and 40 patients whose clinical picture was suspect but who had no evidence of the disease. Measurement of resting, supine plasma catecholamines (by radioenzymatic assay) was more useful than either 24-hour urinary vanillylmandelic acid (VMA) or metanephrines or both. In only one of 23 patients with pheochromocytoma were plasma catecholamines within the range of those in patients without pheochromocytoma, as compared with urinary VMA in 11 of 22, urinary metanephrines in five of 22 and both metabolites in three of 22. These studies reaffirm the value of plasma catecholamines in the diagnosis of pheochromocytoma and indicate that urinary catecholamine metabolites are less useful. The poor correlation between the height of arterial pressure and circulating levels of catecholamines suggests that the regulation of arterial pressure in pheochromocytoma is complex.


The chemotherapy on plasma-cell myeloma and the incidence of acute leukemia.

Previously untreated patients with myeloma were randomized to initial treatment with melphalan and prednisone (and to cyclophosphamide or carmustine if relapse or progression occurred)(Group A, 125 patients), melphalan, cyclophosphamide, carmustine and prednisone in alternating (Group B, 123 patients) or concurrent (Group C, 116 patients) schedules. The groups were similar with respect to known prognostic factors. Response rates and survival were also similar. We were unable to identify a subgroup of patients who responded or survived better on melphalan-cyclophosphamide-carmustine and prednisone than on melphalan and prednisone. We conclude that the combination of the four drugs is not better than melphalen and prednisone for inducing responses or prolonging the survival of patients with myeloma. Myelomas producing only gamma chains have a poorer prognosis (P greater than 0.001) than IgG, IgA, or kappa myeloma. Acute leukemia has developed in 14 patients. The actuarial risk of developing acute leukemia, has increased rapidly to 17.4 per cent at 50 months.


Streptokinase in acute myocardial infarction.

In a controlled trial of streptokinase in acute myocardial infarction, 512 of 2338 patients at 11 European centers were stratified according to clinical severity. Three hundred fifteen patients allocated to medium-risk and high-risk groups were randomized to a 24-hour infusion of streptokinase or glucose. There were no essential differences in the severity of illness in the two groups before infusion. The overall mortality rates within six months were significantly lower (P less than 0.01) in the streptokinase group (15.6 per cent) than in the control group (30.6 per cent). Bleeding complications were more frequent in the streptokinase group; except for two nonfatal cerebral hemorrhages these complications were clinically unimportant. The treatment was generally well tolerated. We tolerated. We conclude that streptokinase given under the conditions of this trial -- to medium-risk patients admitted to a coronary-care unit within 12 hours of onset of symptoms -- reduces mortality at six months. (N Engl J Med 301:797-802, 1979)


HLA-DR specificities among black Americans with juvenile-onset diabetes.

To study the association of histocompatibility (HLA) genes in black persons with juvenile-onset diabetes, we determined HLA-A, HLA-B, HLA-C and HLA-DR specificities in 40 black Americans with this disease and in 67 unaffected black Americans. Marked increases in the frequencies of HLA-DRw3 and HLA-DRw4 were found in the patients as compared with the unaffected persons: DRw3 was found in 72.5 per cent of patients versus 29.9 per cent of unaffected persons and DRw4 in 72.5 per cent versus 25.4 per cent (corrected P values each less than 0.0007). DRw2 was not found in any of the patients but was present in 26.9 per cent of unaffected persons (P corrected less than 0.035). There is thus a negative correlation between this specificity and juvenile-onset diabetes. By contrast, no meaningful differences were found in the frequencies of A, B, or C locus antigens. Studies in white persons with juvenile-onset diabetes have suggested that the reported HLA-B associations are due to HLA-D region specificities, and our results also support the premise that D region specificities are the primary associations with juvenile-onset diabetes.


Competition in the delivery of medical care.

One approach to reform of the medical-care-delivery system emphasizes the development of constructive competition among providers of health care. In this article we describe competition among providers in Minneapolis-St. Paul, one of the few areas that can provide information concerning the practicality of this type of reform. We have found that competition has helped to reduce hospitalization, contain costs and improve access to medical services. At the same time it has focused attention on consumer satisfaction with medical services, increased the range of consumer choice and given consumers better information about providers. Certain public and private measures could facilitate the development of similar competition in other communities.


A neutrophil disorder induced by capnocytophaga, a dental micro-organism.

We recovered capnocytophaga, a gram-negative anaerobe implicated in the pathogenesis of periodontal disease, from two patients with a history of dental infections. Neutrophils from both patients failed to acquire the asymmetric shape characteristic of normal neutrophils. Fluorescein staining of the patients' living neutrophils remained diffuse and patchy instead of showing the normal pattern in which the fluorescence is swept into the rear of the cell. The locomotion of one patient's neutrophils in vitro was less than 50 per cent of that of normal neutrophils, and migration of this patient's neutrophils into dermal abrasions was reduced, although phagocytosis and nitroblue tetrazolium reduction were normal. All abnormalities of neutrophil morphology and function disappeared after eradication of the capnocytophaga infections. Sonicates and culture medium of capnocytophaga contained a dialyzable substance that caused normal neutrophils to behave like neutrophils obtained from the infected patients.


The infant of the diabetic mother: correlation of increased cord C-peptide levels with macrosomia and hypoglycemia.

C peptide is secreted by pancreatic beta cells in amounts equimolar with insulin, and its levels provide a direct indication of endogenous fetal levels of insulin despite the presence of maternal insulin antibodies. To determine the presence of hyperinsulinemia and its relation to the development of complications in infants of diabetic mothers, we measured cord serum levels of C peptide in 79 infants of diabetic mothers and 62 infants of nondiabetic mothers. Infants of diabetic mothers had higher cord levels of C peptide, which were significantly associated with neonatal hypoglycemia and macrosomia (P less than 0.001) but not with hyaline-membrane disease. Cord levels of C peptide in infants of diabetic mothers were elevated at the earliest gestational age studied (less than 34 weeks) and were directly related to the severity of maternal diabetes, as assessed by the White classification. We conclude that hyperinsulinemia is present in infants of diabetic mothers and that it is related to some major complications in such infants.


The Ph.D. to M.D. program: the seven-year mark.

The Ph.D. to M.D. Program, a two-year, accelerated medical curriculum for Ph.D. scientists, has been in operation at the University of Miami for over seven years. Two hundred and nine students from a broad range of scientific disciplines have been admitted, and attrition has been remarkably low (less than 1 per cent). One hundred and thirty-five of the entering candidates (65 per cent) were nonbiologists, but their achievements in the curriculum were virtually equivalent to those of their biologically oriented peers. All graduates have commenced house-staff training, the vast majority at university or university-affiliated hospitals. Of the 46 graduates who have completed some aspect of postgraduate training, 22 are in private practice, 20 are in teaching and research positions and four are scientific administrators in industry. The record indicates that through intensive medical education, the program is able to bring a group of scientists with unusual talents to the theory and practice of medicine.


Protection of granulocytes by vitamin E in glutathione synthetase deficiency.

The administration of vitamin E (alpha-tocopherol) was found to improve polymorphonuclear leukocyte function in an infant with congenital deficiency of glutathione synthetase activity. Before therapy with vitamin E the abnormal leukocytes exposed to phagocytic challenge showed oxidant damage. They released 60 per cent more hydrogen peroxide than did normal leukocytes, iodinated only 20 to 25 per cent of the normal number of particles, and were unable to kill bacteria as effectively as normal leukocytes although the rates of phagocytosis were normal. These functional abnormalities disappeared when the patient was placed on 400 IU of alpha-tocopherol daily for three months. Associated with the functional improvement was a normalization of microtubule assembly during phagocytic challenge.


Natural occurrence of the mycotoxin penitrem A in moldy cream cheese.

The occurrence of the mycotoxin penitrem A in refrigerated cream cheese that was involved in the intoxication of two dogs is described. Penitrem A and the fungus Penicillium crustosum were isolated from the cream cheese and identified. This is believed to be the first definitive case of the natural occurrence of penitrem A.


Toxic aspergilli from pistachio nuts.

Pistachio nut samples taken during various stages of development from orchards in Iran, showed that contamination with fungi occurred mainly during the later stages of nut development. Members of the genera Aspergillus and Penicillium occurred most frequently. Of the Aspergilli, the species A. niger, A. flavus and A. fischeri var. spinosus occurred most frequently, followed by A. terreus, A. tamarii and A. nidulans. Twenty-two isolates comprising 13 species were tested for toxicity to ducklings. Isolates of known toxic fungi included A. flavus, A. niger, A. parasiticus, A. ochraceus, A. versicolor, A. nidulans and A. terreus. The toxicity of A. fischeri var. spinosus is reported. Chemical analysis showed that all isolates of A. flavus and A. parasiticus produced aflatoxin B1, the isolates of A. versicolor and A. nidulans produced sterigmatocystin while the toxic isolate of A. ochraceus did not produce ochratoxins.


Experimental paracoccidioidomycosis in the Syrian hamster: morphology, ultrastructure and correlation of lesions with presence of specific antigens and serum levels of antibodies.

Male hamsters (134) received intratesticular injection of a live cerebriform culture of Paracoccidioides brasiliensis and were sacrificed from 6 hours up to 123 days onwards. Tissues from testis, lymph nodes, lungs, liver, spleen, kidneys and intestines were examined microscopically; presence of specific antigens was saught in lesions of testis, regional lymph nodes and liver by indirect immunofluorescence (IF); inoculation site lesions were studied electron microscopically and circulating specific antibodies measured by complement fixation and IF tests. Up to 24 hours inoculation site lesions showed fungi surrounded by PMNs; 48 hours latter macrophages accumulated forming loose nodules; epithelioid granulomata appeared after 5 days. Fungi, scarce in early lesions, increased in numbers up to the time when epithelioid granulomata dominated the picture; in young granulomata fungi were abundant and small; older granulomata contained rare, vacuolated fungi. Ultrastructurally the space between fungi and host-cells was larger around reproducing forms decreasing in size as the parasites grew larger and being a virtual slit around old degenerated fungi. Immunofluorescence studies revealed that fungal walls were brightly fluorescent; in early lesions macrophages surrounding fungi or free in the intersticium contained fluorescent antigenic material in the cytoplasm; similar macrophages were observed in draining lymph nodes as early as 18 hours after inoculation, and latter, in macrophage nodules and Kupffer cells in the liver; epithelioid and giant cells appear to block diffusion of antigens, since in epithelioid granulomata fluorescence was limited to fungal walls. Disseminated paracoccidioidomycosis occurred in 100% of animals after day 5 of infection. Besides specific lesions (containing fungi), antigens were identified by immunofluorescence in 'non specific' lesions in the liver (diffuse or nodular Kupffer cell hyperplasia) and in the lymph nodes (histiocytic hyperplasia). Serum antibodies appeared in low titers, up to day 20, increasing onwards. From day 70 on, titers decreased and lesions changed from confluent epithelioid to loose granulomata infiltrated by PMNs; fungi that before were large and quiescent now were small and in active reproduction. Secondary amyloidosis was present in 85% of the amimals. In the hamster, Paracoccidioidomycosis develops as a chronic progressive disease and the lesions are related both to fungi and its antigens.


Dermatophyte species, microscopic and cultural examination.

The dermatophytes Epidermophyton floccosum, Microsporum canis, Trichophyton mentagrophytes var. interdigitale, T. rubrum, and T. verrucosum were compared with respect to the direct microscopic examination of a clinical material and the number of colonies obtained by culture. It was found that the results of microscopy as well as of culture depended to a marked extent upon which species were the cause of the mycosis. The extremes were E. floccosum and T. mentagrophytes var. interdigitale which showed 7.5% and 32.5% isolates with negative microscopic findings and 45.5% and 5.0% isolates with larger than or equal to 10 colonies.