Changes in fatty acid composition of cardiac mitochondrial phospholipids in rats fed rapeseed oil.

Male Wistar rats were fed rapeseed oil containing high or low levels or erucic acid for 20 weeks, and changes in the fatty acid composition of cardiac mitochondrial phospholipids were studied. Treatment with rapeseed oil containing 46.2% erucic acid showed incorporation of 22:1 (5.6%) into isolated cardiolipin from heart mitochondria. After high or low (3.7%) erucic rapeseed oil feeding, linolenic acid was slightly incorporated into cardiolipin. Moreover, both of these rapeseed oils induced a significant increase of linoleate-arachidonate ratio in phosphatidylethanolamine and phosphatidylcholine. This ratio was also significantly increased in fatty acids esterified to the beta-position of these phospholipids. On the basis of such results, we have to consider the role of linolenic acid which is present at a high level in the different rapeseed oils used, as a possible inhibitor of heart microsomal enzymes involved in linoleate arachidonate conversion. Such alterations might account for mitochondrial fragility and myocardial lesions obtained in long term rapeseed oil feeding experiments.


Lipid peroxidation: a mechanism involved in acute ethanol toxicity as demonstrated by in vivo pentane production in the rat.

The effect of a single dose of ethanol on lipid peroxidation in three groups of rats fed different amounts of vitamin E was determined by the measurement of pentane in the breath. All rats had increased pentane production above basal levels by 15 min following oral administration of 6 g ethanol/kg body wt. The increase in total pentane production during a 13-hr test period after intragastric administration of ethanol was greater in the rats fed the vitamin E-deficient diet than in the rats fed vitamin E-supplemented diets (alpha = 2P = 0.02). The results support the hypothesis that acute ethanol toxicity involves lipid peroxidation and further demonstrate the usefulness in toxicological studies of monitoring pentane as an index of lipid peroxidation in vivo.


Prostaglandin metabolism by human testis.

Human testis preparations appear to carry out both the synthesis and turnover of prostaglandins. Prostaglandins and prostaglandin metabolites were extracted from whole tissue. Testis microsomes converted both endogenous and exogenous substrate to prostaglandins. Microsomal prostaglandin biosynthesis was inhibited by indomethacin. Prostaglandin E2-9-ketoreductase was present in both the cytosolic and microsomal fractions of human testis. Prostaglandin metabolism by human testis has not previously been reported.


Membranous nephropathy in patients with rheumatoid arthritis: relationship to gold therapy.

Of 90 patients with membranous nephropathy proved by biopsy, 8 (8.9%) had pre-existing rheumatoid arthirtis. Four of these eight patients received systemic treatment with gold. Two others received only token amounts of gold. In two patients who received gold, the renal lesions did not occur until months after discontinuance of gold therapy. We found that clinically significant renal lesions (lesions associated with proteinuria) in patients with rheumatoid arthritis were more likely to be membranous nephropathy than occult amyloidosis or adult lipoid nephrosis. The membranous lesion in patients with rheumatoid arthritis may be difficult to identify by light microscopy, and, although special strains can be helpful, the pathology is frequently sufficiently subtle to require immunofluorescence and electron microscopy for definitive diagnosis. We postulate that chrysotherapy may not be the cause of membranous nephropathy in patients with classic rheumatoid arthritis in whom gold has been used. Whether it merely exacerbates a lesion already present in these patients, or whether it plays little or no role in the development of membranous nephropathy is an unsettled question. Our data lead to think that RA can induce MN and that gold is not the primary inciting agent.


Cardiac risk factors and complications in non-cardiac surgery.

In an attempt to assess cardiac risk in non-cardiac surgery, 1001 patients over 40 years of age who underwent major operative procedures were examined preoperatively, observed through surgery, studied with at least one postoperative electrocardiogram, and followed until hospital discharge or death. Documented postoperative myocardial infarction occurred in only 18 patients; though most of these patients had some pre-existing heart disease, there were few preoperative factors which were statistically correlated with postoperative infarction. Postoperative pulmonary edema was strongly correlated with preoperative heart failure, but 21 of the 36 patients who developed pulmonary edema did not have any prior history of heart failure. Nearly all of these 21 patients were elderly, had abnormal preoperative electrocardiograms, and had intraabdominal or intrathoracic surgery. In the absence of an acute infarction, bifascicular conduction defects, with or without PR interval prolongation, never progressed to complete heart block. Spinal anesthesia protected against postoperative heart failure but not against other cardiac complication. By multivariate regression analysis, postoperative cardiac death was significantly correlated with (a) myocardial infarction in the previous 6 months; (b) third heart sound or jugular venous distention immediately preoperatively; (c) more than five premature ventricular contractions per minute documented at any time preoperatively; (d) rhythm other than sinus, or premature atrial contractions on preoperative electrocardiogram; (e) age over 70 years; (f) significant valvular aortic stenosis; (g) emergency operation; (h) a 33% or greater fall in systolic blood pressure for more than 10 minutes intraoperatively. Notably unimportant factors included smoking, glucose intolerance, hyperlipidemia, hypertension, peripheral atherosclerotic vascular disease, angina, and distant myocardial infarction.


Relationship between the plasma glucose level and glucose uptake in the conscious dog.

In the absence of a change in the pancreatic hormonal milieu, elevations in the normal fasting plasma glucose level have little effect on glucose clearance. In view of these data, and the previously established responsiveness of M to hormones, glucose clearance can be considered to represent a useful index of hormone action on glucose uptake in vivo. Care should be taken, however, when interpreting clearance data obtained under hypoglycemic conditions, since there is a possibility that clearance may spontaneously increase at very low plasma glucose levels.


Biphasic effect of somatostatin on oral glucose tolerance in maturity-onset diabetes.

Oral glucose tolerance was examined in five maturity-onset diabetics during the infusion of somatostatin or saline. Somatostatin inhibited glucose-stimulated insulin release and reduced plasma glucagon by 50%--65%. The rise in plasma glucose after glucose ingestion was initially (at 30--120 min) reduced by somatostatin. However, beyond 3 hr, plasma glucose levels were 50--200 mg/100 ml higher, with somatostatin reaching concentrations at 6 hr that were twofold higher than those observed with saline ( p less than 0.005). The degree of late glucose intolerance was inversely related to postglucose plasma insulin concentrations (p less than 0.01). These findings demonstrate a biphasic effect of somatostatin on oral glucose tolerance in maturity-onset diabetes. The exaggerated later hyperglycemia is related to suppression of insulin secretion. The initial blunting of postprandial hyperglycemia may reflect decreased carbohydrate absorption and/or hypoglucagonemia-mediated enhancement of glucose disposal.


The characterization of antibacterial antibodies in bovine immune sera to Staphylococcus aureus.

Humoral antibody responses to the encapsulated Smith diffuse strain of Staphylococcus aureus were examined in cows immunized with the killed vaccine via different systemic routes. The sequential appearance of the antibody within different immunoglobulin classes in the sera during the  course of immunization was followed by passive hemagglutination (PHA) and precipitation (PC) reactions and the mouse passive protection test. Repeated intravenous injections with the killed vaccine suspended in buffered saline stimulated production of IgM antibody exclusively during the whole period of immunization. On the contrary, following intramuscular administration with the vaccine incorporated in Freund's incomplete adjuvant, the antibodies appeared predominantly in IgG fractions of the sera. Specific antibody to the homologous strain used for vaccination was prepared from bovine immune sera by an absorption and elution process. The mouse passive protective activity of the antibody preparation was removed by absorption with the capsular polysaccharide antigen as well as by the whole cell adsorbent of the Smith diffuse strain, but not by the Smith compact and Cowan I strains of S. aureus. IgM, IgG1 and IgG2 proteins were isolated from the purified antibody and were compared, on a weight basis, with respect to their biological activities. Slightly higher activity of the IgG over the IgM antibody was demonstrated both in the mouse passive protection test and PC reaction, whereas in the PHA reaction, IgM antibody was shown to possess a significantly higher activity than IgG antibody. These studies suggest that IgG as well as IgM antibody might play an important role in protection against infection with encapsulated strains of S. aureus in cows.


In vitro cytotoxicity of peritoneal macrophages activated with Mycobacterium smegmatis.

Incorporation of 3H-TdR into EL4 leukemic cells in vitro was inhibited by peritoneal exudate cells (PEC) harvested from syngeneic C57BL/6J mice given an intraperitoneal (i.p.) injection of 1x10(7) viable Mycobacterium smegmatis ATCC 607 (Smeg) 4 days before. This phenomenon was also observed in the following five systems of PEC from animals and syngeneic tumor cells: C57BL/6J mice and B16 melanoma; DBA/2 mice and P815 mastocytoma; SWM/Ms mice and K5 fibrosarcoma; BALB/c, nu/nu mice and KKN-1 fibrosarcoma; and strain 2 guinea pigs and line-10 hepatoma. The in vitro cytotoxicity of the PEC activated by viable Smeg was much higher than those activated by dead-Smeg, viable BCG or proteose peptone. The activity of the adherent fraction of the PEC was stronger than that of the nonadherent one, and not influenced by either anti-theta or anti-mouse lymphocyte rabbit sera. The PEC induced with Smeg 4 days before contained a large population of mononuclear cells (88.9%) and a significant level of polymorphonuclear cells (PMN) (3.2%), and showed a much higher cytotoxicity than the PEC induced with Smeg 3 hr before, which contained a much larger population of PMN (71.9%), suggesting that PMN were not the effector cells in this system. In vitro and in vivo treatment with macrophage-inhibitors such as carrageenan, trypan blue and cytochalacin B, reduced the activity of the PEC. All of these facts suggested macrophages as the effector. Viable macrophages were required for the growth inhibition of EL4 in vitro: gamma-ray irradiated or freeze-thawed macrophages were ineffective. Kinetic studies revealed that inhibition of 3H-TdR incorporation into EL4 cells started within 3 hr of incubation together with the activated macrophages at an effector to target (E/T) ratio of 5, and the incorporation decreased gradually with the lapse of incubation time. On the other hand, 51Cr release from labelled EL4 was undetected when the E/T ratio was 5 but detected at on E/T of 10 or more. Even at the higher E/T ratio, at least 10 hr were needed until the release of 51Cr, suggesting that the activated macrophages produced growth inhibition of tumor cells followed by cell destruction.


[Biochemical pathways of carbon monoxide assimilation in the carboxydobacterium, Pseudomonas gazotropha].

The incorporation of 14CO into acid-stable assimilation products by Pseudomonas gazotrophia Z-1156 is characterized by a slow rate at the beginning, contrary to the rectilinear kinetics for incorporation of the bicarbonate 14C in the presence of 12CO. The assimilation of 14C-bicarbonate decelerates in the absence of CO. The relative content of 14C is the highest in phosphorylated compounds upon the shortest possible incubation of the cells of P. gazotropha Z-1156 (5 min) in the presence of 14CO and O2, and decreases in the process of incubation. The bulk of radioactivity is found in aspartate and glutamate. The composition of products formed upon the assimilation of 14CO and NaH14CO3 (in the presence of 12CO) during 15 min is similar. The key enzymes of the reductive pentose phosphate cycle have been found in the cell extracts of P. gazotropha A-1156. The specific activity of carboxylating enzymes of the Calvin cycle in the cell extracts increases in the course of proportional growth and sharply decreases when the growth of the culture decelerates. The activity of ribulose diphosphate carboxylase (EC. 4.1.1.39) is always by one-two orders lower than that of ribulose phosphate isomerase (EC. 5.3.1.6) and phosphoribulokinase (EC.2.7.1.19), but is similar to the activity of phosphoenolpyruvate carboxylase (EC. 4.1.1.31). The activity of phosphoenolpyruvate carboxykinase (EC. 4.1.1.32) has not been detected in the cells extracts of P. gazotropha Z-1156.


[Effect of organic acids on the biosynthesis of carotenes by an Actinomyces chrysomallus strain].

Synthesis of carotenes by Actinomyces chrysomallus var. carotenoides was stimulated by citric, acetic, oxalacetic, fumaric, succinic, malic, alpha-ketoglutaric, tartaric, pyruvic, and propionic acids. Acetic acid acts as a precursor of carotene synthesis and also has another stimulating mechanism of action on carotenogenesis of the actinomycete. Acetic, furmaric, malic, succinic, and alpha-ketoglutaric acids stimulate cyclization of lycopene yielding beta-carotene.


[Hydrogenase activity of Chlorella vulgaris cells].

Cell suspensions of Chlorella vulgaris were found to possess the hydrogenase activity as was confirmed by their ability to absorb H2 in the presence of benzyl viologen, azocarmine and other hydrogen acceptors as well as to produce H2 from reduced methyl viologen. Incubation of the cells in the dark under anaerobic conditions in the atmosphere of H2, N2 or Ar stimulated the activity of hydrogenase and induced its de novo synthesis. Treatment of the cells adapted to anaerobiosis with dry ice or liquid nitrogen considerably increased their hydrogenase activity. The enzyme of the adapted cells was more resistant to the inactivation by O2 and temperature.


[Lipolytic activity of osmotolerant yeasts].

The ability to hydrolyse olive oil, cod-liver oil, caviar oil, and yeast oil was studied in osmotolerant yeasts Candida mogii 2, Debaryomyces hansenii 8, and Rhodotorula rubra 9, isolated from salted caviar. The lipolytic activity was manifested at 5, 15 and 26 degrees C and pH 4.0--9.2, even in the presence of high concentrations (0.5--3 M) of such chlorides as KCl, NaCl and CaCl2. The lipolytic activity of S variant of D. hansenii 8 was higher than the activity of its R variant.


[Specific gravity of the dried biomass of pure bacterial cultures].

The weight of wet and dry biomass taken from colonies after growth on MPA was determined in pure bacterial cultures of Pseudomonas denitrificans and Brevibacterium imperiale, and the number and dimensions of bacterial cells in dry preparations of the same colonies were measured by means of membrane filters. The average specific weight of dry biomass was found to be 1.68 and 1.62. In calculating the weight of bacterial biomass in pure cultures and natural cenoses, its volume should be assayed taking into account the number and dimensions of the cells in dry preparations on membrane filters and multiplying by a coefficient 1.6.


[Nucleotide makeup of the DNA of thermophilic bacteria of the genus Thermus].

The nucleotide composition of DNA was determined in extreme thermophilic and obligate thermophilic nonsporeforming bacteria belonging to a new genus Thermus. The GC content (in mol%) in the DNA of exteme thermophilic bacteria varied from 65.3 to 70.8 per cent depending on the strain. The amount of GC (in mol% in the DNA of obligate thermophilic and extreme thermophilic bacteria of the Thermus genus was higher than that in the DNA of sporeforming obligate thermophilic Bac. coagulans. Bac. circulans and Bac. stearothermophilus.


[Naphthalene oxidation by a Pseudomonas putida strain carrying a mutant plasmid].

Naphthalene oxidation by a parent and a mutant strain of Pseudomonas putida was studied. The parent strain contained a plasmid NPL-1 which controlled oxidation of naphthalene to salicylic acid and was capable of oxidizing salicylate. The mutant strain did not oxidize salicylate because of a mutation in salicylate hydroxylase; it contained also a mutant plasmid NPL-41 which determined constitutive synthesis of naphthalene oxygenase. Salicylic acid which accumulated as a product of naphthalene catabolism in the cultural broth of the wild strain was found to undergo further oxidation by the population of growing cells. The content of salicylic acid in the cultural broth of the mutant strain reached maximum and then remained constant. An anion-exchange resin was tested in order to prevent the inhibition of naphthalene oxygenase by salicylate and to increase the yield of salicylic acid. The transmissible character of the mutant plasmid NPL-41 makes it possible, with the aid of conjugation, to construct Pseudomonas strains which would oxidize naphthalene to salicylic acid without further degradation of this compound.


[Virulent and temperate phages of Bacillus licheniformis, the producer of bacitracin antibiotic].

Virulent and temperate bacterial phages were isolated from the cultural broth of Bacillus licheniformis obtained under the industrial conditions when synthesis of the antibiotic bacitracin was interfered with. The following properties of the phages were studied: the fine structure, the morphology of negative colonies, the spectrum of lytic action, the rate of adsorption, the individual growth cycle, as well as the lysogenic state of certain strains of Bac. licheniformis. Some phages were serologically related and morphologically identical whereas others differed sharply in their morphology and antigenic properties.


[Actinomyces thermovulgaris endospores].

It has been established for the first time that autolysis observed when Actinomyces thermovulgaris T-54 is cultivated on liquid media of various composition is caused by the formation of submerged spores. These, in contrast to exospores of the majority of the actinomycetes, are endospores according to their structure and the following criteria: thermostability, the presence of dipicolinic acid, the structure of ultrathin cross-sections studied by electron microscopy, the resistance to novobiocin.


[Variability in the amylolytic thermophilic bacterium, Bacillus diastaticus, induced by ultraviolet rays].

The UV-induced variability of the amylolytic thermophilic Bacillus diastaticus 13 was studied. The biosynthesis of amylase was found to very under the action of UV from 2.2 to 158.7% A "plus" variant referred to as the mutant UV 1 was produced at a dose of UV equal to 41.8-10(2) erg/mm2. Its further selection without using a mutagen made it possible to select a variant UV 1-25 which surpassed the parent strain by 43.3% in amylase biosynthesis. UV-irradiation produced also two mutants with a low activity in amylase biosynthesis. The requirement of growth factors was studied with several mutants.


[Biological activity of the soils of the rice irrigation systems in the southern Ukraine].

The biological activity of soils was studied in the irrigation systems of the Southern Ukraina. Aerobic microorganisms were found to be widely distributed in all these soils. The cell number of Azotobacter and the activity of nitrogen fixation differed among various irrigation systems. Active nitrogen-fixing microbial associations were isolated from the soils; some of them were capable of fixation of 19.4 mg N per 1 g of assimilated glucose. The microbiological processes of certain irragation systems were characterized by reductive processes such as the intensive growth of sulphate reducing bacteria and the high activity of denitrification. The activities of protease, catalase and dehydrogenase differed among various soils, and were the lowest at a level of ground waters being 0.8 m. Flooding is one of ecological factors affecting the biological activity of the soils of irrigation systems.


[Microorganisms that break down alkyl sulfates].

The following bacteria assimilating alkyl sulphates as a sole source of carbon and energy were isolated from various substrates: Pseudomonas, Achromobacter, Flavobacterium, Citrobacter, Enterobacter. The bacteria decomposed sodium dodecyl sulphate at a high rate, and some of them, industrial preparations of alkyl sulphates. The ability to assimilate alkyl sulphates was tested in 257 collection cultures belonging to different taxonomic groups. Alkyl sulphates were found to be decomposed by heterotrophous gram-negative rod-like bacteria belonging to different families and genera. The frequency of bacteria destroying alkyl sulphates at a high rate was found most often in the Pseudomonas genus.


[Thiobacillus ferrooxidans pili].

The surface structures of Thiobacillus ferrooxidans were studied. When growing on a medium containing elemental sulphur, the cells possess peritrichously located filaments (piles) whose diameter varies from 4.5 to 7.0 nm and length, from 0.7 to 3.0 mcm. The cells of T. ferrooxidans do not have piles on a medium with ferrous iron. The physiological role of these structures for thiobacilli is discussed.


[Overall bacterial count in the surface layer of the silt and in the bottom water of Lake Krasnoye].

The total number of bacterial cells containing iron and lacking it was determined daily within relatively short period of time (1--3 weeks) in the course of three years. The total bacterial number and the character of its changes in the surface ooze layer and in the water near the bottom depended on the environmental conditions. The content of oxygen was taken as an index of environmental changes.


[Devices facilitating the preparation of biological specimens for electron microscopy].

The construction of a matrix is described which facilitates the process of placing biological objects into polymer media in order to prepare ultrathin sections without the employment of gelatin, starch and polyethylene capsules that can be used only once. The construction of a reactor for cytochemical assays is presented. The apparatus can be used to locate enzymes within the cell, and to identify microorganisms. A modification of the dialysis technique for microbiological objects is proposed which accelerates and simplifies the process.


[Development of nodule bacteria in soil].

The rate of growth of a population of nodule bacteria in soil and the time it takes for the cell generation depend on the content and accessibility of necessary nutrient substances. The periods of adaptation, active growth, and stabilization of the population number in the course of growth of a population are typical of soddy-podzolic continuous-cultivated soil. The duration of each period is determined by a sum of ecological factors.


[Use of a mass spectrometric method for studying the oxygen demand of suspensions of resting Bacillus anthracoides spores].

Oxygen assimilation by the spore suspensions of Bacillus anthracoides under sterile conditions was continuously registered by means of a modified mass-spectrometry technique using an original reaction vessel. The sensitivity of the technique is 2.10(-2) mcl O2 per 1 mg of dry biomass per hour. The technique made it possible to determine the level of endogenous respiration activity in the spore suspensions of Bacillus anthracoides.


A novel adaptation of the information game for the development of a new drug.

Medical advisers in the pharmaceutical industry have an important function and place in the development and evaluation of new drugs. Although mainly involved in the human and clinical investigations, it is essential that they have the background knowledge and experience to evaluate the results of pre-clinical studies and to apply these safely and effectively to the clinical situation. It is rare nowadays for a medical adviser to obtain direct experience in all areas of drug research due to its complexity. Simulation exercises are a means of obtaining this experience without suffering the results of a wrong decision. An adaptation of the Information Game proved to be a useful and acceptable means of illustrating the decisions that need to be made in a drug development programme and at the same time provided experience in coping with the various problems that might arise in such a programme. The training objectives of the game should be clearly defined at the outset in order to concentrate on the parts of the game that really matter and cover the maximum number of teaching opportunities.


[Problems of protecting complex inventions in the field of microbiology].

Some problems are discussed which are connected with the protection of inventions in the field of microbiology when the invention is complex. The rights of the author are determined when a method and a product are to be protected at the same time. The additional juridical protection of a microbial strain is not necessary. The complex protection of a microbial strain and the method of its utilization is recommended in certain cases since it might prevent conflicts which arise upon the parallel juridical protection of a strain and the method of its utilization.


Toward a clinical orientation in the basic medical biochemistry curriculum.

A re-evaluation of biochemistry in medical school curricula is presented, with reference to designing more effective courses. Responses to a survey conducted among 103 medical students enrolled in two general biochemistry courses indicated that basic biochemistry would be considered more relevant to the medical curriculum if clinical applications were emphasized over basic principles. A majority of students (91%) expressed interest in applying biochemical principles to pathological conditions. They recommended that the biochemistry curriculum should include lectures on the significance of biochemistry in medical practice and its role in the life processes, laboratory comparisons of normal and pathological specimens, and course titles that reflect a more clinical orientation.


[Removal of the RNA from Pseudomonas thermophila cells].

The RNA content in the cells of Pseudomonas thermophila K-2 grown at 50 degrees comprise 13% of dry weight during exponential growth and 5% of dry biomass in the stationary phase. 60% RNA is degraded after 10 min exposure to heat shock at 70 degrees and subsequent incubation at 50 degrees for 2 hours.


Multidisciplinary training in family planning.

A review of 3 years' experience with multidisciplinary training in Family Planning involving representatives from nursing, medical, social work and education professions is presented. The multidisciplinary principle has been shown to be of value in this field, particularly in respect of improved communication.


The relationship between student ratings of course effectiveness and student achievement.

For many years student ratings have been used to assess the strengths and weaknesses of various courses and the teaching abilities of the instructors involved. Investigators have either supported or attacked the validity of this assessment procedure on the basis of the direction and degree of the relationship found between student rating of a course and student achievement in that course. This validation study supplemented correlation analysis with analysis of variance to compare groups at various achievement levels and to control for the possible confounding effects of overall group analysis. Medical students responded to a Likert attitude scale about aspects of an anatomy course. The mean attitude scores for a high and a low course achievement group were significantly different at the 0.005 level; the high achievement group had a more positive course attitude.


Training health workers for primary care in a developing health service.

To provide primary health care in a thinly populated mountainous country with few doctors presents great difficulties. The Royal Government of Bhutan decided to base their primary medical care service on appropriately trained medical auxilliaries. The training programme is described, and the problems of assessing the field activities discussed.


Guidelines for competency-based instruction in psychiatry.

This paper presents guidelines for teachers who wish to design competency-based instructional activities in psychiatry. Developed over a 3 year period, these guidelines outline the methods used by teachers to construct competency-based seminars and clinical rotations. The guidelines describe the process of stating knowledge objectives, performance objectives and experiential objectives for psychiatric trainees to attain prior to completion of training in a given area. Selection of appropriate teaching strategies as well as criteria and conditions for assessment of the residents' abilities are also reviewed. Comments regarding the authors' experience using these guidelines with teachers are offered.


Collusion of information on computerized patient management examinations.

In a computer presented examination the ratio of examinees to computer terminals is generally large. This implies that a computer presented test might span an entire day or several days with different groups of examinees taking the examination at different times. In such a situation, examinees who take the examination later on have the opportunity to gather information from their colleagues who took the examination earlier. This report investigates whether information exchanged between groups of examinees taking a computer presented patient management problem test improves the performance of late takers versus early takers. Results indicate that there is no exchange of information between groups of candidates.


Higher medical and surgical degrees in the University of Sydney.

Three hundred and twenty-six higher medical and surgical degrees were awarded by the University of Sydney between 1883 and 1977. A questionnaire was sent to 209 graduated known to be alive to gather data regarding their prior and subsequent careers. As many of the graduates were in their fourth decade before commencing the research studies for the M.D. thesis, there would appear to be reasons for recommending the Ph.D. degree, with its three years of supervised course work, to prospective higher degree candidates. 286 B.Sc. (Med.) degrees were awarded midway through the medical course between 1949 and 1974. This earlier introduction to research probably does more to encourage and academic or research career than the M.D. degree which currently appears to be a prerequisite to a University appointment. Some concern is raised by the comment of 27% of M.D. graduates who claimed no personal scientific benefit from their studies.


Casualty room presentations and schoolboy rugby union.

For eight years a casualty station has been operating during competition Rugby Union matches at a large Sydney School. During this time, both diagnosis and treatment have been recorded for every presentation. The casualty station was attended by 556 boys over this period, and approximately 50% of these presentations were for trivial injuries. Forty-three severe injuries occurred, of which most were fractures. The rate of presentation, and the pattern of injury, changed as a greater number of both minor and major injuries than did visitors. There was one injury in boys less than 12 years old, and the greatest incidence of injury was in boys aged from 16 to 18 years. It is concluded that there is a place for casualty services at schoolboy competition games, and that the supervised Rugby Union played in this and comparative school competitions is a reasonably safe game for boys less than 16 years old, to whom issues of schoolboy participation are most applicable.


Intracranial aneurysms--a survey of the results of surgical treatment at the Prince Henry Hospital, Sydney, 1972-1976.

In this paper, 124 intracranial aneurysms in 114 patients operated on during a five-year period, are reviewed, and the mortality is analysed in respect to factors of age, sex, duration of preoperative interval, site, and type of operation. A comparison with an earlier comprehensive ten-year cooperative study is attempted.


Systemic vibriosis due to non-cholera vibrio.

A case of extraintestinal vibriosis with septicaemia due to a non-cholera vibrio, from which the patient had recovered, is presented. Diagnostically useful clinical and laboratory data are described together with an outline of the combined medical and surgical treatment regimen which is employed. The association with excessive alcohol consumption and liver diseases is noted.


Australia's potentially most venomous snake: Parademansia microlepidotus.

Studies on the venom of the small-scaled or fierce snake, Parademansia microlepidotus, suggested that its combination of high toxicity and relatively large venom yield make it the most venomous snake in Australia. The species is distinct from the taipan, but its venom is neutralized by taipan antivenom but not other monospecific antivenoms.


Bisolvon and Actifed in the conservative management of glue ear.

Glue ear is a common condition in childhood. In this report treatment by Bisolvon and Actifed is described. In 60 patients, a success rate of 90% was recorded.


An Australian exclusion diet.

Exclusion diets may have a practical place in determining the precipitating dietary factors in certain clinical conditions. We present an exclusion diet which is based on the exclusion of food commonly known to cause food allergies, and the exclusion of food which contains salicylates, benzoates, tartrazine, yeast, and penicillin. This provided a basis for challenge with these additives and natural chemicals. Preliminary information in urticaria suggests a use for this diet in some allergic conditions.


Psychiatric antecedents of myocardial infarction.

Forty consecutive survivors after myocardial infarction (MI) were compared by means of a semistructured interview with a matched sample of 40 controls in respect of various psychosocial factors. The MI group reported a much higher prior occurrence of symptoms of anxiety and depression. The complaints included being tired, irritable, restless, upset and anxious, plus insomnia and anhedonia. Preceding stressful life events were about 2 1/2 times as common with the MI group. However, long-term persanality traits which were not recent additions due to psychiatric change before MI did not strongly discriminate between the two groups, and recognized variables such as cigarette smoking had a lesser association with MI. Similar results were obtained when information about each patient and each control was supplied by a close informant.


Coronavirus-like particles in Aboriginals and non-Aboriginals in Western Australia.

Pleomorphic virus-like particles which resemble coronaviruses in morphology were found in faecal specimens from Aboriginal and non-Aboriginal children in Western Australia. They were equally prevalent in those with or without symptoms of diarrhoea. A much greater proportion of Aboriginal than non-Aboriginal children were found to be excreting the particles. The proportion of children who excreted the virus-like particles increased with age. Coronavirus-like particles, indistinguishable from those found in humans, were found in a number of Aboriginals' dogs.


The Aboriginal population of Victoria.

The basis of epidemiological studies and of health services planning is accurate enumeration of the population at risk. With regard to the Aboriginal population of Victoria there was reason to believe that official census statistics were inaccurate. Interviews were carried out with representatives of Aboriginal organizations, State and federal government departments concerned with Aboriginal affairs and other interested individuals. The best estimate of the Aboriginal population of Victoria arrived at by this method was almost double the census figure. Underestimation was most marked in rural areas.


Cardiological effects of nomifensine, a new antidepressant.

A cardiovascular study of a new antidepressant, nomifensine, revealed no significant cardiac effects in eight ambulant patients who received up to 200 mg of nomifensine per day for three weeks. In an electro-physiological study of cardiac conduction, nomifensine had significantly less effect on cardiac activity than amitriptyline and doxepin. Results of the clinical and the experimental studies suggest that nomifensine may be of value in treating the depressed patient with heart disease.


Preventing unplanned pregnancies.

A two-year study was undertaken in 1975--1976 to plan, implement and evaluate innovatory family planning educational and service delivery pilot projects, among those at-risk in Sydney. The study was done in three stages, described in the three parts of this paper. Part 1 describes the process of analyzing the major factors and outcomes in unplanned pregnancy and determining some characteristics of women experiencing unplanned pregnancies, from abortion and adoption records. The characteristics analyzed are: are, marital status, occupation, socio-economic status, and ethnic group. Part II describes the process of determing acceptable communication channels and services they would use. Twenty-five women were interviewed in each of eight at-risk categories. Recommendations are made about suitable educational methods, and family planning services. Part 3 describes the implementation and evaluation of pilot projects. Four major projects are described: (i) in a two lower socio-economic housing area(s), (ii) among Greek men, (iii) among South Americans, and (iv) in two factories. Recommendations are made about future educational programmes and services.


Holter monitoring in cardiological practice.

Thirty-one patients who presented with the symptoms of palpitations and/or syncope were personally studied by the Holter monitor electrocardiogram method. The method is briefly described. Interesting results were obtained, which are illustrated by five case histories. Of these 31 cases which were studied, five gave entirely negative results. In five cases, there were benign and not very frequent atrial or ventricular ectopic beats. In 21 cases there were significant findings, the most common being frequent and/or dangerous R on T or multifocal ventricular ectopic beats. Additionally, paroxysmal tachyarrhythmias, atrioventricular block, sinoatrial arrest or significant ischaemic changes, which were not detected in the routine electrocardiograms, were recorded.


Non-specific (non-gonococcal) urethritis.

A report is made of a small study of ureaplasmas and chlamydias in 32 cases of non-specific urethritis. Erythromycin was used as a therapeutic agent and found to be reasonably effective.


Consulting rates of general practitioners by demographic groups in a defined community.

The demographic characteristics were recorded of 4798 patients aged from 15 to 69 years who consulted, for any reason, the general practitioners of 97% of the practices in the Perth Statistical Division on one day in 1971. A consulting rate in terms of the population at risk was calculated for patients of different sex, age, marital status, country of birth, and social class. Certain characteristics of the general practitioners were also related to the demographic characteristics of their patients.


Issues with dying patients.

Doctors have the privilege of looking after patients from the moment of birth to the moment of death. Yet, the holistic approach to patients is interfered with by the doctor's role as a warrior against death, where death's everpresent claim on our lives, and its final victory, are ignored. This paper attempts to explore why doctors are in their current position, the mechanisms for ignoring death which are shared by doctors and patients, the nature of the fear of death, and practical implications for the treatment of dying patients. More and more patients die now in medical settings. It is incumbent on doctors to understand the dying process, if much unnecessary suffering is to be prevented.


Erythema infectiosum ("slapped cheeks" syndrome): a little-known entity.

Erythema infectiosum is an uncommon, benign, self-limited disease with a distinctive clinical picture, occurring mainly in children. An inquiry showed that most doctors who deal with children are not familiar with it, and the disease is therefore seldom diagnosed. As recognition has connotations which may sometimes be important, the disease is briefly reviewed, and three cases are reported.


The New South Wales medical registration work force survey 1976.

A medical workforce survey was conducted in conjunction with the 1976 registration of doctors in New South Wales. Its prime aim was to provide information on the number of doctors required to be trained by the medical schools. The main findings of the survey are presented; in particular, current and predicted values of the doctor/population ratio are given. The status of this parameter is discussed.


Clay eating by Aboriginals of the Northern Territory.

Eleven Aboriginal patients from the Northern Territory, in whom radiological examination of the abdomen demonstrated opaque masses of clay in the colon are described. This was due to the eating of white clay which is found only in streams, springs and billabongs of the coastal areas of the Territory. The habit does not appear to be a perversion of appetite, nor is it related to anaemia or pregnancy. The clay is eaten mainly for medicinal purposes or to allay hunger. The results are not always beneficial, since clay caused complications (including obstruction and perforation of the colon) in five of our 11 patients.


Blood pressure and valvular and congenital heart disease in Torres Strait Islanders.

Blood pressure levels were recorded in 1922 Torres Strait Islanders. Comparison with blood pressure levels of an Australian urban community which were recorded in the Busselton survey of 1972 shows that Islanders who are 20 years of age and over hav significantly higher systolic and diastolic blood pressure levels in both males and females. Systolic and diastolic pressure levels also increase in both males and females with age, as in the Busselton patients. Surprisingly, the "urbanized" Islanders have lower blood pressure levels than those who live in village communities in the outer islands. The reasons for this are to be investigated. Comparison with New Guinea Melanesians shows that the Islanders consistently have significantly higher systolic and diastolic blood pressure levels in both males and females in adult age groups. In addition the frequency of congenital and rheumatic valvular heart disease in a group of Torres Strait Islanders is reported. There is no evidence that the incidence of these lesions in the Island population is different from that reported in communities of European descent.


The development of serum immunoglobulins G, A and M in Australian Aboriginal infants.

Serum levels of immunoglobulins G, A and M (IgG, IgA and IgM) were studied in a population of Aboriginal infants from birth to 2 1/2 years of age. Serum levels of all three immunoglobulins were found to be consistently higher than in studies of white children. This is attributed to increased exposure of Aboriginal infants to infectious agents from early in life.


A modified Rutter children's behaviour questionnaire. Its reliability and validity in screening for behaviour disturbances in part-Aboriginal children.

The Rutter Children's Behaviour Questionnaire was completed by the teachers of 108 Aboriginal pupils at two rural schools in the far west of New South Wales. The questionnaire ratings were compared with a contemporaneous psychiatric study of behaviour disturbance for each child. Some modification of the questionnaire was required because of cultural factors. The modified questionnaire was found to be of acceptable reliability and validity in screening for emotional disturbance in Aboriginal children. It is suggested that it would be a useful case finding instrument for teachers of part-Aboriginal children.


[The effect of benzbromarone on fasting-hyperuricemia as a model (author's transl)].

The effect of daily therapeutic doses of 100 mg benzbromarone (Normurat) and 2.0 g probenecid on the purine metabolism of 40 test subjects was investigated. Fasting-hyperuricemia was used as the model and particular attention paid to the mechanisms of renal elimination. Urate concentration remains under the solubility threshold when benzbromarone is administered, in contrast to medication with probenecid. The significantly greater hypouricemic effect of benzbromarone correlates with a significant rise in the excretion and clearance of uric acid in comparison to probenecid, accompanied by a stronger depression of tubular reabsorption. Serum levels, clearances and reabsorption rates demonstrate the prolonged effect of the benzofurane derivative Normurat even during strict fasting. Supplementary allantoin and urea determinations gave no indication of increased enterobacterial uricolysis. Normurat was well tolerated, side effects were not noted.


[Drug treatment of hypercholesterolemia. Experience with a combination of dextrothyroxine and betapyridylcarbinol (author's transel)].

22 patients of our lipid ambulance with hypercholesterolemia received 6 mg highly purified dextrothyroxine (group 1, n = 10) or 900 mg beta-pyridylcarbinol (group 2, n = 12) for 12 weeks and both groups for another 8 weeks a combination of 4 mg dextrothyroxine and 600 mg beta-pyridylcarbinol daily. Most of the patients with an age from 8 to 57 years showed a family history of hypercholesterolemia, some of them suffered from coronary insufficiency. 20 patients completed the therapeutic progrand of 20 weeks. Total cholesterol decreases in both groups during monotherapy significantly, and still more during the combination, singificant in group 1. LDL cholesterol showed greater decrease during mono- and combination therqpy. The frequency of side effects was higher in the monotherqpy periods: increase of preexisting angina pectoris in one case during dextrothyroxine, severe flush in two cases during beta-pyridylcarbinol, gastrointestinal disturbances three times in both groups together. During the combined treatment minimal gastrointestinal symptoms were reported from one patient. The lower incidence and severity of side effects in spite of similar or better effects recommend the combination of dextrothyroxin and beta-pyridylcarbinol for longterm therapy of moderate hypercholesterolemia.


[Clinical pharmacology of Bacampicillin in comparison to Ampicillin (author's transl)].

Equimolecular doses of Ampicillin and Bacampicillin were administrated orally, of Ampicillin also by i.v. injection to 10 healthy adult volunteers (cross over study). By comparison of areas under serum level curves after i.v. and oral administration absorption rate of Bacampicillin which is hydrolysed rapidly to Ampicillin in the body was determined as 95%. Peaks of serum levels after 0.8 g. Bacampicillin administered orally were higher (15,9 microgram/ml) and earlier (after 60 min) than after 0.556 g. Ampicillin administered orally (3.5 microgram/ml after 150 min). Concentrations of Ampicillin in skin blister fluid 1 h after i.v. injection of Ampicillin were 20 times higher than after  oral administration of Ampicillin and 3-4 times higher than after oral administration of Bacampicillin; after 3 and 4 hours skin blister levels after i.v. injection were only a half of skin blister levels after oral administration of Bacampicillin. Determination of antibiotic concentrations in saliva and tears showed similar relations. Since higher peaks in serum resulted in higher concentrations in the extravascular space Bacampicillin which is absorbed compeltely and more rapidly should be prefered for oral administration.


[The antimicrobial activity of amikacin in comparison with three other aminoglycoside-antibiotics (author's transl)].

We report about the in-vitro-sensitivity tests of 1756 Enterobacteriaceae and Pseudomonas strains to amikacin, gentamicin, tobramycin and sisomicin. It was established, that amikacin is more effective than gentamicin, tobramycin and sisomicin in case of infections with Klebsiella, Proteus species, Psuedomonas strains and Enterobacter. The four aminoglycosides are well active against E. coli. Hospital acquired infections with Serratia are a domain of amikacin. Tobramycin is more effective than gentamicin and sisomicin against Pseudomonas infections. Amikacin is the drug of choice against gentamicin-resistent strains, which are also not infrequently resistant to other aminoglycosides. Resistance to gentamicin-tobramycin and gentamicin-tobramycin-sisomicin, is most frequent among Klebsiella strains. The cross-resistance rate is considerably higher among Enterobacteriaceae strains than among Pseudomonas species. The lowest rate of resistance (2.1%) and the high antimicrobial activity are the considerable advantages of amikacin.


[Glucose tolerance and neurogenic muscular atrophies (author's transl)].

Glucose tolerance is reduced in patients suffering from neurogenic muscular atrophies. In a group of 20 patients with myatrophic lateral sclerosis the extent of atrophy correlated significantly with the decrease in glucose tolerance. Creatinine excretion was used as a measure of functioning muscle mass. Insulin secretion was not reduced, on the contrary, it was strongly pronounced in these cases. The observations are not explained by a decrease in distribution volume of glucose. By testing glucose tolerance, functions of sceletal muscles are examined at the same time. In evaluating the results, the functioning muscle mass has to be taken into account.


Determination of IgG, IgM, and IgA antibodies to Mycoplasma pneumoniae by an indirect staphylococcal radioimmunoassy.

An indirect staphylococcal radioimmunoassay (SRIA) has been developed for determination of M. pneumoniae antibodies. This test allows the detection of antibodies in various immunoglobulin (Ig) classes similar to the previously described radioimmunoprecipitation test (RIP). SRIA has two advantages over RIP: first, it uses 100-fold less anti-Ig reagents than RIP; second, bound can be separated from unbound antigen more easily by the relatively heavy staphylococci. SRIA antibodies, belonging to the IgA class of Ig, could be detected in nasal secretions of volunteers infected intranasally with ts H43 of M. pneumoniae. In sera of patients with M. pneumoniae pneumonia antibodies to the IgG or the IgM class of Igs could be determined separately. This is especially important for an early diagnosis of M. pneumoniae disease.


Chemotherapeutic response in metastatic medulloblastoma: report of two cases and a review of the literature.

Metastatic medulloblastoma is a rare clinical phenomenon. Review of the literature and the authors' experience reveals that when it occurs, palliation may be achieved with a variety of single and combination chemotherapy programs. Two objective responses with vincristine-actinomycin-D-cyclophosphamide (VAC) and one each with adriamycin and methyl-CCNU are described.


Clinical trial of nafoxidine in advanced breast cancer.

Forty-nine postmenopausal patients with advanced breast cancer were treated with a nonsteroidal antiestrogen, Nafoxidine. The drug was generally well tolerated with dermatitis being the major toxic effect. A partial response in 12 of 40 patients, or 30%, was achieved with a median duration of response of greater than five months.


Nonbacterial thrombotic endocarditis in cancer patients: comparison of characteristics of patients with and without concomitant disseminated intravascular coagulation.

Thirty-one cases with malignant neoplasm and nonbacterial thrombotic endocarditis (NBTE) were studied. A threefold increase in the incidence of NBTE over the five-year period ending in 1976 was noticed. Seventy-one percent of patients with NBTE had concomitant disseminated intravascular coagulation (DIC). Adenocarcinomas of the lung or ovary were the most common tumors (48%), followed by hematologic malignancies (25%). Five patients had acute leukemia, two of whom had received bone marrow transplantation. Sudden changes in the status of cardiovascular and central nervous systems were the most common manifestations of NBTE and its complications. The possible predisposing factors included disseminated malignant neoplasms and infection with gram-negative bacilli. Identification of high-risk patients and early administration of preventive measures including anticoagulation might decrease the morbidity and mortality related to NBTE.


Relapse of Hodgkin disease after extended-field radiotherapy.

Thirteen relapses occurred among 51 consecutive surgically staged patients with I, IIA, and IIIA Hodgkin disease who achieved complete remission following extended-field radiotherapy. The median disease-free interval was 14 months, but three disseminated relapses occurred at 36, 36, and 39 months. In 6 of the 13 cases, relapses occurred within treated fields. Relapse frequency was greater with advancing stage, but was not related to histology. In 9 of 12 evaluable cases the patients achieved complete remission with MOPP combination chemotherapy. All responders continue in complete remission a median time of 23 months after completing MOPP. This report emphasizes the need for sustained, close follow-up after radical radiotherapy and the excellent response rate of relapsed patients to MOPP combination chemotherapy.


Childhood embryonal carcinoma of testis, report of two unusual cases, and the implication on clinical management.

Primary testicular neoplasms are not common childhood tumors, comprising about 1% of all childhood malignancies [1]. Embryonal carcinoma is the most common childhood testicular neoplasm. It has been described in a variety of histologic variants as embryonal carcinoma of infancy, orchioblastoma, yolk sac tumor, endodermal sinus tumor, Teilum tumor, and adenocarcinoma with clear cells. Because of the rarity of the tumor, there is no general concensus concerning the management. Recently we encountered two children with embryonal carcinoma of testis who had rather unusual clinical courses. We believe that a report of these cases may contribute to further design of the most suitable therapeutic regimen.


Estimation of correlation of lactate dehydrogenase subunits mole quota based on differences in substrate inhibition.

A kinetic method of estimating the mole quota ratios of the human lactate dehydrogenase (LDH) H and M subunits based on differences in substrate inhibition of LDH isoenzymes by lactate is porposed. Stability of kinetic constants for a prolonged period of time is demonstrated. The dependence of the activity ratios on the contribution of the mole quota of the M-subunit of LDH is studied under conditions of low and high substrate concentrations. The experimental and theoretical values show the following correlation: r = 0.998; p less than 0.001. A comparison of the method proposed with the electrophoretic method of LDH subunit estimation is made, the values obtained being in good agreement. No effect of the components of human diploid cell homogenate and only an insignificant effect of the blood serum components on the kinetic constants of LDH isoenzymes are shown. The applicability of the method to the estimation of the quantitative content of both LDH subunits in natural samples is demonstrated. The informational value of the method is compared to that of other standard methods of LDH isoenzyme estimation.


[Relationship between the molecular structure of aqueous solutions of polyethylene glycol and the compactness of double-stranded DNA molecules].

The dependence of viscosity of the water solutions of poly(ethylene glycol) (PEG) on the molecular weight has been studied. It has been shown that there is a "transitional" region in PEG properties which accounts for the formation of fluctuation polymer network of the PEG molecules. It has been shown that the "transitional" region in properties of PEG which appears at a certain concentration of PEG (CtrPEG) is characteristic of the PEG preparations with molecular weights exceeding 600 and dependence of the value of CtrPEG on the molecular weight of PEG was obtained. Compactization of double-stranded DNA molecules in PEG-containing water-salt solutions has been studied and the dependence of the value of CcrPEG, . i.e. the concentration of PEG at which the compact particles of DNA appear in the solution, on the molecular weight of PEG was obtained. The correlation between these two dependences reflecting quite different physico-chemical processes shows that the double-stranded DNA molecules are constrained within the polymer network of the PEG molecules. The influence of ionic strength and ionic composition of the solution on the formation of a compact form was investigated. The transition of the DNA molecules from a linear to a compact state may occur only at a definite value of ionic strength of the solution. This transition may occur at the change of K+ for Na+ cations (at a constant value of CPEG). The extent of compactization of the DNA molecules in PEG-containing water-salt solutions is monitored by the molecular structure and by the ionic strength of the solvent. It is supposed that the peculiarities  of compactization of the DNA molecules in PEG-containing water-salt solutions reflect some characteristics of conformational transitions of the DNA molecules which occur in vivo.


[Changes in the methylated sequences and molecular population of wheat DNA during germination].

The fractions of unique (Cot less than 405), moderately (Cot=0.13--405) and highly reiterated (Cot less than 0--0.13) sequences were isolated from DNA of wheat seeds and 3 day old seedlings, and GC content, amount of 5-methylcytosine and its distribution among various pyrimidine isostichs in the fractions isolated were studied. Different in Cot value DNA fractions from seeds or from seedlings are similar in GC content and in all other characteristics studied. Seed DNA differs from DNA of seedlings in the content of pyrimidine isostichs from the respective fractions of reiterated sequences. Pronounced differences in the amount of pyridmidine clusters with various base composition in the corresponding fractions of DNA from seeds and seedlings were found. These differences in the frequencies of respective pyrimidine clusters from DNA of seeds and seedlings may be considered as being a result of changes in the molecular population of wheat DNA on germination. The seed and seedling DNA differ significantly in the 5-methylcytosine content in the respective pyrimidine isostichs isolated from unique sequences. In the seedling DNA some other nucleotide sequences are to be methylated as compared to DNA of dormat seeds. Thus, on germination some changes occur in DNA methylation as well as in the genome organization.


[Complex of single-stranded phage DNA and protein--a product of bacteriophage fl gene 3. Distribution of gene 3 protein in the DNA molecule].

Upon a 50% isopropanol treatment of phage fl in a 1 M NaCl solution protein A (gene 3 product)--DNA complex is precipitated while protein B (gene 8 product) was still solubilized. After such a treatment the DNA--protein complex containing 10--40% of protein A and less than 0.0025% of protein B was obtained. Evidence was obtained that there was no non-specific rearrangement of protein A during the isolation procedure. The complex was treated with endonuclease R.HAC III, followed by electrophoresis of the  resulted fragments and estimation of the [14C] protein A (labeled with [14C]histidine) throughout the gel. The maximal radioactivity coincided with the DNA bands, being proportional to the DNA content in the respective bands. The data obtained indicate that protein A is iniformly arranged along the DNA molecule.


[Poly(A)-containing RNA from germinating wheat embryos].

Rapidly labelled mRNAs were isolated from informosomes and polyribosomes of imbibed wheat embryos. The distribution of poly(A) sequences in these fractions were studied by poly(U) Sepharose chromatography. It was shown that informosomes contain 11% polyadenylated mRNA while polyribosomes--38%. This fact suggests the important role of poly(A) sequences for translation of mRNA.


[Calculating light scattering when determining "true absorption magnitudes" of virus particles].

Results of the study by V. I. Permogorov et al. (Molecular Biology, 1977, 11, 134--138) on the absence of a deficit of hypochromism in intraphage DNA are discussed. It is deduced that the conclusion of V. I. Permogorov and coworkers is erroneous since it is based on: 1) incorrect interpretation of the results of determination of lightscattering contribution to the absorption of intact phages; 2) not taking into account the lightscattering contribution in the case of disrupted phages; 3) underestimation of the value of hyperchromism of melting of phage DNAs.


[Effect of the state of the lipid phase of the membrane on the effectiveness of photochemical modification of erythrocyte acetylcholinesterase].

Modification of the lipid phase structure of the erythrocyte membrane by phospholipases A2, C and D as well as the partial depletion of cholesterol was shown to be accompanied by the change of the acetylcholinesterase (AChE) UV-sensitivity. The ability of UV-light to change the catalytic properties (Km) of the membrane-bound AChE not observed for free AChE (constant value of Km) and known as the phenomenon of photochemical allotopy, is retained in the cholesterol depleted membranes and disappears after an enzymatic treatment of the membranes by phospholipases. The possible non-photochemical influence of the membrane lipid phase in response to UV-damage of membrane-bound AChE is discussed.


[Renal duplication in childhood. Incidence and clinical significance (author's transl)].

Renal duplication is the most common malformation within the urinary tract system and as such a particular challenge to the pediatrician with regard to diagnosis and therapy. It is discovered either by chance or in relation to chronically recurring urinary tract infections. Urinary tract infection is the main clinical symptom in 2/3 of all the patients with renal duplication. Incidence, age-and sex-distribution, predilection of side or bilateral occurrence, configuration of the ureter and the statistically significant combination with vesico-uretral reflux show systematic regularities and are discussed in connection with the literature. Ureterocele, concrements, obstructions or hydronephrosis often are consequences of renal duplication or, as with hydronephrosis, correlated malformations like aplasia, hypoplasia, malrotation, horseshoe kidney or duplication of the urethra. There is a causative relation between renal duplication and tumors or tuberculosis. Other correlated malformations are particularly heart malformations or myelomeningocele. It depends on the severity of the disease whether therapy will be symptomatic or operative. Between 1968 and 1974 we saw 114 children with renal duplication.


[Embryological aspects of anomalies of the aortic arch (author's transl)].

Various anomalies of the aortic arch have been examined angiographically and discussed in their embryological context. Theoretical concepts are based on Rathke's scheme of the aortic arch system. The importance of developmental aspects for the interpretation of anomalies of the aortic arch in angiography is emphasized.


[Effect of temperature on chymotrypsinogen A hydration in a dynamic system].

The temperature dependence of chymotrypsinogen A was studied by a dynamic method. A gradual exclusion of low adsorbing centers out of the whole number of hydratation centers was observed during the raise of temperature. Differential isosteric heats of hydration were measured at different degrees of hydration. It was shown that at low hydration the heat absorption is connected with the conformational change of the protein molecule.


[The significance of factor VII-deficiency in infancy and childhood (author's transl)].

Prolonged thromboplastin time but normal partial thromboplastin time in coagulation analysis lead to the diagnosis of factor VII-deficiency. The different forms of congenital and acquired factor VII-deficiency and the appropriate therapies are discussed, especially with regard to the recently available factor VII preparation.


[Early diagnosis of Wilson's disease in childhood (author's transl)].

Most of the time Wilson's disease becomes clinically evident in childhood by atypical abdominal symptoms. Therefore early diagnosis is very difficult. In four out of eight patients with Wilson's disease, diagnosed relatively early in the Children's Hospital of Heidelberg University, we could demonstrate that each case of liver disease, which cannot be classified, may be suspicious of Wilson's disease. Even normal levels of ceruloplasmin in serum and copper in urine are not inconsistent with Wilson's disease. There is no screening method in infancy. Fatty liver in school children is very suspicious of Wilson's disease.


[Oriented complexes of nucleic acids with low-molecular weight ligands. I. Anisotropy of the absorbance of DNA complexes with distamycin A and its analogs].

The anisotropy of absorbance (near 320 and 258 nm) of the DNA complexes with distamycin A and two analogues have been studied. Measurements were made along the direction of the flow oreintation of the complexes. The comparison of two orientation effects: deltaA320=(Astop--Aflow)320 and deltaA258=(Astop--Aflow)258, gave the opportunity to estimate the inclination angle of distamycin chromophores with respect to the DNA axis: for all three analogues the angle was lying between 40 and 45 degrees. These results strongly support the model of the complex where the antibiotic is inserted into the narrow grove of the DNA helix.


[Neonatal screening for hypothyroidism. Preliminary results from different methods (author's transl)].

In a regional study 2062 newborns were screened for congenital hypothyroidism by determination of TSH in plasma or dried blood spots on the fifth day of life. Three newborns with congenital hypothyroidism were detected. All of them showed high TSH-levels between 462 and 2192 micromicron/ml. One newborn with a congenital goiter had a TSH-level of 143 micromicron/ml. Additionally, in a follow-up study of 50 newborns with jaundice TSH, T4, T3 and reverse T3 during the first 120 h of life were measured. Efficiency of the different methods concerning their applicability to mass screening is discussed.


[Genetic change in the waxy trait of barley under the influence of wild type DNA. Analysis of the composition of starch and the electrophoretic spectrum of caryopsis hordein from altered plants and the retention of these changes to the fourth generation].

Injection of DNA isolated from the wild type of barley into grains of recipient mutant plants (waxy mutants) at the milk stage of maturity leads to a change in starch synthesis; type of spikes and hordein composition. In the first generation of injected plants the wild type starch synthesis was observed in some separate plants (these observations were made at a haploid level in pollen cells). In the second generation of transformed plants along with the change in starch and hordein synthesis a modification of the type of spikes was also revealed. Recipient plants had six-rowded (hexastichous) spikes, and donor plants--two rowded (distichous) spikes. Disc-electrophoresis of hordeins of the wild type barley (Yuzhny var.), hordeins of the waxy mutant (defected in synthesis of normal starch) and barley plants transformed under the action of wild type exogenous DNA reveals differences in the protein spectrum between donor, recipient and transformants. In the second generation in many of the transformed plants starch synthesis reverted to the recipient mutant type. Simultaneously a reversion of hordein composition to the initial mutant type was observed, and the distichous pikes became hexastichous. Analysis of the components of starch revealed that donor plant that have amilose and amilopectin in starch, and the recipient plants that lack amilose, can be distinguished by the spectra of light absorption of starch. For characterizing these differences the plot of absoprtions at 490 versus that at 590 nm was used. The tangens of angles of these curves for the waxy mutant were equal to 1.05 +/- 0.07 and 1.81 +/- 0.04 for the wild type barley. All transformants have a 1.78 ratio and for revertants this value was 1.02.


[Reaction between synthetic fragment of histone F2al and the protamines iridine and salmine with DNA].

The interaction of basic oligopeptides--F2aI histone, iridine and salmine protamines synthetic fragments with DNA has been studied by the methods of thermal denaturation, circular dichroism and equilibrium dialysis. All the peptides investigated are albe to stabilize the DNA helix and change its conformation. This ability grows with the increase of a number of basic residues in the peptide molecule and decreases when there is a serin residue on the end. The binding of the peptide with DNA obtains a cooperative character if 4--6 arginine clusters are present in the molecule. The comparison of the binding coefficient with the thermal denaturation data allowed to propose an important role of nonelectrostatic forces on the binding of the peptides to DNA.


[Palindromic, repeating and unique sequences in the macronuclear DNA of Tetrahymena pyriformis GL infusoria].

Reassociation kinetics of macronuclear (Ma) DNA of the ciliate Tetrahymena pyriformis GL has been studied. The genome size calculated by the kinetic complexity of DNA constitutes of 2.0.10(8) base pairs, which corresponds to the molecular weight of 1.2.10(11) dalton. About 90% of the Ma DNA fragments of 200-300 base pairs in length reassociate at a rate corresponding to the unique sequences and 3--5% of the nucleotide sequences at a ten times exceeding rate. About 3--5% of the genome consists of sequences reassociating at Cot practically equal to zero. Most of the zero time reassociating DNA seems to be represented by inverted nucleotide sequences. This conclusion was drawn from the study of the at zero time reassociating DNA isolated preparatively by hydroxyapatite chromatography. This fraction shows an approximately 75% resistance to S1-nuclease treatment which is independent from the original DNA concentration. Heat denaturation and reassociation are mutually reversible yielding hyper- and hypochromic effects. The majority of the inverted sequences are likely to be unique, about 20% is repeated scores of time in the Tetrahymena genome. This assumption has been made on the strength of reassociation of the zero time [125I]DNA fraction (after breaks in single-strand hair pin loop with the aid of S1-nuclease) with non-fractionated Ma DNA. According to the equilibrium distribution in a CsCl density gradient the mean nucleotide content of inverted [14C]DNA sequences does not differ from that of non-fractionated DNA. Consequently the largest part of the isolated fraction of inverted nucleotide sequences of the Tetrahymena genome are not fragments of ribosomal genes. The evidence of reassociation kinetics of Ma DNA fragments of various lengths allows to suggest that inverted sequences from large blocks (no less than 6000 base pairs) and scores of times repeated sequences may alternate with the regions of unique sequences.


[A new bile contrast in pediatrics (author's transl)].

Biligram was used for 42 cholegraphies in children aged 2 months to 15 years. A 35% concentration of Biligram was given as intravenous injection in 14 children, a 17% or 3,4% concentration as an intravenous infusion in 16 or 12 patients, respectively. The quality of x-ray films with both Biligram 35% and 17% was equally good whereas Biligram 3,4% gave a weak contrast only. The best time for taking films was 30 and 60 min after injection of Biligram. Allergic reactions or an effect on liver enzymes were not observed.


[Conformational stability of ribonuclease A complexes with specific inhibitors].

Isotermic unfolding of ribonuclease A, phosphopyridoxyl-8Lys41-RNAase A and complexes of the enzyme with cytidine, 2'-CMP, 3'-CMP, 3'-AMP and with the phosphoric ester of 1-(omega-oxypropyl)-cytosine in presence of urea has been studied. The stabilization of the protein structure resulting from the complex formation was shown to be determined by the ligand nucleobase binding. The comparison of the results obtained with those known from the literature suggests, that binding and catalytic zones of the enzyme active site form an integrated network system which is substained by multipoint contacts between the constituents. The change in the state of any part within the enzyme active state affects the energetics of the whole protein globule.


[A new test-strip for the detection of hematuria (author's transl)].

The use of a new test strip for hematuria (Sangur-Test) is suggested for ambulatory and clinical practice. It seems to be reliable and sensitive enough to detect minor degrees of pathological amounts of red blood cells in urine (above 5/microliter). No false negative result was recorded in the present series. The concomitant use of Sangur-Test and Hemastix in 28 children with different degrees of hematuria has shown a higher sensitivity in detecting erythrocyturia with the former.


[Aseptic meningitis following fourth ventricle surgery (author's transl)].

Postoperative aseptic meningitis may occur as a complication of brain neurosurgery, especially after opening of the fourth ventricle. The picture of bacterial meningitis may be simulated. Main symptoms are persistent spiking fever, meningism and pleocytosis of CSF. The usually long lasting course can be dramatically shortened by early steroid therapy.


[Familial paroxysmal choreoathetosis. Clinical course, L-dopa-effect (author's transl)].

The clinical course of two boys with familial paroxysmal choreoathetosis was traced. As far as the medical history could be retrieved, their family has been affected by this disease for three generations. Except for this disorder, the patients' development and psychophysical state are unremarkable. Both boys responded well but at times incompletely to anticonvulsants. Therefore L-Dopa was introduced to the therapeutic regime of the younger, more severely affected boy. L-Dopa caused an appreciable decline of the frequency of the paroxysms.


Colchicine-like effect of diethylstilbestrol (DES) on mammalian cells in vitro.

Diethylstilbestrol (DES), a synthetic estrogen, showed colchicine-like effects in vitro on cells of the cell lines such as Chinese hamster fibroblast of thymus origin (CHT), rat liver (DL), rat erythroblastic leukemia (EDEN-1/TC) and HeLa-S3. Metaphase arrest was induced 3 h after treatment with 15 microgram/ml of DES and polyploid or polynucleated cells were prominently observed more than 24 h after treatment. The arrest, however, was reversible when the agent was removed from the medium. Tetraploid karotypes induced by DES in CHT cells consisted of all double sets of diploid chromosome constitution except one chromosome marker. By clonal selection, several hypotetraploid sublines were successfully isolated from a CHT cell population after the treatment with 15 microgram/ml of DES for 48 h. Some comparative studies of cytological effects of DES with those induced by colcemid indicated that the DES effect was also a mitotic inhibition similar to colchicine.


Chromosome-damaging effect of betel leaf.

The chewing of betel leaf with other ingredients is a widespread addiction in India. The chromosome damaging effect was studied in human leukocyte cultures. There was an increase in the frequency of chromatid aberrations when the leaf extract was added to cultures.


Mutagenicity and cytotoxicity of congeners of two classes of nitroso compounds in Chinese hamster ovary cells.

The induction of mutation by certain nitrosamidines and nitrosamides has been quantitated utilizing the hypoxanthine--guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary cells. Dose--response relationships for cytotoxicity and mutagenicity are presented for N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), N-butyl-N-nitrosourea (BNU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Based on the concentration of each agent required to kill 90% of the cells, the following order of cytotoxicity was observed: MNNG greater than ENNG greater than MNU greater than ENU greater than BNU. This is the same order of potency as observed for mutation induction per unit concentration of mutagen.


Genetic effects of crocidolite asbestos in Chinese hamster lung cells.

Chinese hamster lung cells cultured in the presence of crocidolite asbestos displayed inhibition of cell growth. Cell death was directly associated with the phagocytosis of larger fibres as observed with the aid of trypan blue. Water soluble components of crocidolite did not appear to inhibit cell growth. Chromosomal aberrations were induced by the asbestos. The aberrations were confined mainly to structural aberrations--breaks and fragments. Electron-microscopic preparation indicated that asbestos was readily contained in phagosomes. Phagocytosed asbestos appeared to be a weak mutagen in its ability to induce gene mutation at the hypoxanthine-guanine phosphoribosyl transferase locus.


Sister chromatid exchanges induced by cyclophosphamide in V79 cells cultured in diffusion chambers in mice.

Chinese hamster cells V79 were cultured in diffusion chambers (DC) and implanted into mice. An exponential growth was observed from the 2nd to 4th day after implantation. The maximum growth was reached on the 6th day. After that, cell growth and viable cell counts decreased. Three days after implantation of DC with V79 cells, the hosts received 6 hourly injections of 0.2 ml of 5-bromodeoxyuridine (BUdR) solution at concentrations of 0.125 to 1.0 x 10(-2) M. DC were removed for chromosome and sister-chromatid exchanges (SCE) analyses 24 h after the first BUdR injection. The frequency of metaphases with differentially stained chromatids, with aberrations, and the number of SCE per cell increased with BUdR dose. The frequency of metaphases with differentially stained chromatids was also positively correlated with the duration of BUdR exposure or the number of hourly injections of BUdR-solution. The effects of cyclophosphamide (CY) in V79 cells in DC in mice were studied. Injections of CY at 2.5, 5, 10 and 15 microgram per gram of body weight to the hosts caused an increase in the number of SCE per cell in a linear manner. The results from this study indicate that V79 cells cultured in DC in mice may provide a potential test system for mutagenicity.


Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis.

A specific and sensitive radioimmunoassay was used to measure the levels of antibody to a liver-specific membrane lipoprotein in patients with acute and chronic liver disease. Antibody was detected in 29 of 30 patients with chronic active hepatitis (all of 15 HBsAg-negative and 14 of 15 HBsAg-positive cases), and in 10 of 17 patients with chronic persistent hepatitis but at significantly lower titer. The titer of antibody to the lipoprotein showed a significant correlation with activity of disease as judged histologically and biochemically. Transiently elevated levels were found in 20 of 21 patients with acute viral hepatitis, but there was no correlation with the degree of liver damage. Antibody to liver-specific membrane protein may be part of the final common pathway of liver-cell damage in both HBsAg-positive and HBsAg-negative chronic activite hepatitis, whereas other immune mechanisms determine the liver-cell injury in acute viral hepatitis.


Gynecomastia and gonadal dysfunction in adolescent boys treated with combination chemotherapy for Hodgkin's disease.

We studied 19 Ugandan boys with Hodgkin's disease who had been treated with mechlorethamine, vincristine, procarbazine and prednisone and who survived at least two years to assess testicular germ-cell depletion in pubescent boys on combination chemotherapy, as had previously been demonstrated in sexually mature men. Nine of 13 pubertal boys (ages 11 to 16) had moderate to severe gynecomastia and germinal aplasia, a 10-fold increase in mean (+/- S.D.) serum follicle-stimulating hormone (34.8 +/- 20.5 mlU per milliliter), a threefold increase in mean luteinizing hormone (17.8 +/- 9.8 mlU per milliliter) and reduced serum testosterone levels. Gynecomastia was not associated with an increase in either serum estradiol or prolactin concentrations. By contrast, six prepubertal boys (three to 10 years of age), similarly treated, showed no change in serum gonadotropins, and gynecomastia did not develop. The data confirm germ-cell depletion after combination chemotherapy and indicate further that Leydig-cell dysfunction, manifested by gynecomastia, may be a consequence of treatment in adolescent boys.


Effect of passive smoking on angina pectoris.

The effect of passive smoking on exercis-induced angina in a well ventilated and in an unventilated room was evaluated in 10 patients with angina. Patients exposed to 15 cigarettes smoked within two hours in a well ventilated room or an unventilated room increased their resting heart rate, systolic and diastolic blood pressure, and venous carboxyhemoglobin and decreased their heart rate and systolic blood pressure at angina. Patients exposed to passive smoking in an unventilated room had a larger increase in resting heart rate, systolic and diastolic blood pressure, and venous carboxyhemoglobin  and a greater reduction in heart rate and systolic blood pressure at angina. The duration of exercise until angina was decreased 22 per cent after passive smoking in a well ventilated room (P less than 0.001), and decreased 38 per cent after passive smoking in an unventilated room (P less than 0.001). Passive smoking aggravates angina pectoris.


Selection of medical students for graduate training: pass/fail versus grades.

We analyzed the performance of two cohorts of surgical residents: one from "pass/fail" and the other from "graded" medical schools. A performance index indicates that the group from graded schools performed significantly better (P less than 0.001). No resident from a pass/fail institution ranked above the 87th percentile, and this group accounted for 82 per cent of those ranking below the 15th percentile. A residency training program that seeks excellence among its trainees would do well to select preferentially students who apply from medical schools providing a specific class standing as part of the total evaluation of the student. It is suggested that the pass/fail controversy is symbolic of the erosion of standards that inevitably occurs when the university becomes involved in transient sociopolitical turmoil.


Frozen autologous platelet transfusion for patients with leukemia.

Platelets were removed from 25 patients with leukemia during remission and were frozen for subsequent transfusion. With 5 per cent dimethyl sulfoxide as a cryoprotective agent, we froze 3 to 5 units of pooled platelet concentrate by simply placing the platelets in the vapor phase of a liquid nitrogen freezer. Ninety-one transfusions of platelets stored for 13 to 400 days were administered. The mean freeze-thaw loss was 13 percent, and the corrected one-hour increment in platelet count was 13,700 per microliter, corresponding to a recovery of 53 per cent of the predicted value. In many patients most or all of the transfusion requirements were met with frozen platelets. Our results indicate that frozen platelets can circulate and function hemostatically. Autologous frozen platelets are of particular value in the management of alloimmunized patients and have become an integral part of our transfusion support program.


Relation of education to sudden death after myocardial infarction.

We studied the influence of social and personal characteristics on prognosis among 1739 male survivors of myocardial infarction who had been monitored for one hour at a standard examination and subsequently followed for mortality. Over a three-year period men with little education (eight years of schooling or less) who had complex ventricular premature beats in the monitoring hour had over three times the risk of sudden coronary death found among better educated men with the same arrhythmia (cumulative mortality of 33 per cent and 9 per cent, respectively). No such differential appeared in the absence of complex ventricular premature beats. Neither risk factors for incidence of coronary heart disease nor clinical characteristics affecting prognosis accounted for the differences observed. There was no relation between education level and risk of recurrent infarction.


Hypotension associated with prekallikrein activator (Hageman-factor fragments) in plasma protein fraction.

Thirteen lots of plasma protein fraction made by one manufacturer were implicated in 23 recent reports of hypotension in surgical patients. Four of these patients required resuscitation after rapid administration of the product in the postoperative period. All implicated lots had prekallikrein-activator activity but low levels of bradykinin and kallikrein. The prekallikrein activator was identified as Hageman-factor fragments by molecular weight (35,000 as estimated by gel chromatography), isoelectric point (4.2 to 4.4), and inhibition by antibody to Hageman factor. These data suggest that Hageman-factor fragments are potent hypotensive agents, presumably because they trigger the generation of bradykinin in recipients. Prekallikrein-activator activity, usually at levels lower than those in the initial 13 implicated lots, was frequently detected in plasma protein fraction made by other manufactures. Several of these lots were associated with additional reports of hypotension. Prekallikrein-activator activity rarely occurred in albumin.


Frequency of sexual dysfunction in "normal" couples.

In analyzing the responses of 100 predominantly white, well educated and happily married couples to a self-report questionnaire, this study examined the frequency of sexual problems experienced and the relations of those problems to sexual satisfaction. Although over 80 per cent of the couples reported that their marital and sexual relations were happy and satisfying, 40 per cent of the men reported erectile or ejaculatory dysfunction, and 63 per cent of the women reported arousal or orgasmic dysfunction. In addition, 50 per cent of the men and 77 per cent of the women reported difficulty that was not dysfunctional in nature (e.g., lack of interest or inability to relax). The number of "difficulties" reported was more strongly and consistently related to overall sexual dissatisfaction than the number of "dysfunctions."


Subarachnoid hemorrhage from intracranial aneurysms. Surgical management and natural history of disease.

We analyzed the management of 310 patients with acute subarachnoid hemorrhage from a ruptured intracranial aneurysm, 280 of whom survived to operation, according to preoperative neurologic function, location and size of the aneurysm and timing of operation. Severe initial bleeding, rebleeding (usually within two weeks) and delayed ischemia were major preoperative problems; 10 per cent died, and 13 per cent deteriorated before operation. Operative mortality was 5 per cent, ranging from 1.6 per cent of patients with normal preoperative neurologic function to 35 per cent of severely disabled patients. Intraoperative complications (5 per cent of cases) related chiefly to the size and location of the aneurysm, but postoperative delayed ischemia (minor and reversible in 10 per cent and severe in 5 per cent) related to timing of operation and occurred primarily in patients afflicted within the previous 10 days. The results of surgical treatment, including preoperative deaths, were better than the natural history of the illness, the difference being apparent after one month's observation.


Urinary kallikrein activity in the hypertension of renal parenchymal disease.

To learn more about the regulation of blood pressure in renal parenchymal disease, 57 subjects (18 normal controls, 25 patients with essential hypertension and 14 with renal parenchymal disease and hypertension) were evaluated for peripheral renin activity, 24-hour urinary kallikrein activity and whole-blood volume. Blood volumes were significantly lower in patients with essential hypertension (P less than 0.001) and those with renal disease and hypertension (P less than 0.001) than in normotensive subjects. Renin activities (measured after the subjects were standing) were also lower in patients with essential hypertension and hypertension due to renal disease (P less than 0.01 and P less than 0.02, respectively). Kallikrein activity was similar in subjects with renal disease and those with hypertension (P less than 0.05) but markedly diminished in both groups as compared with normotensive subjects (P less than 0.001 and P less than 0.01, respectively) when glomerular filtration rates were taken into account. The kallikrein-kinin system may be involved in the hypertension associated with renal parenchymal disease.


Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion.

We applied a recently developed and more direct technic to diagnose thalassemia syndromes associated with deletion of particular globin structural genes and to assess a fetus at risk for one of those conditions, deltabeta-thalassemia. The method allows assessment of the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA. Cellular DNA fragments produced by cleavage using two specific restriction endonucleases are separated on the basis of size by agarose-gel electrophoresis, and the distribution of specific sequences among the DNA fragments determined by molecular hybridization. We observed the total deletion of alpha-globin genes in homozygous alpha-thalassemia (hydrops fetalis with hemoglobin Bart's) and the deletion of particular beta and beta-like sequences in cases homozygous for hereditary persistence of fetal hemoglobin and deltabeta-thalassemia. Analysis of amniotic-fluid cell DNA from a fetus at risk for deltabeta-thalassemia demonstrated the feasibility of these improved methods for antenatal diagnosis. The molecular studies confirmed the diagnosis predicted by analysis of fetal blood and established at birth.


A prospective study of sudden death in "high-risk" bundle-branch block.

We prospectively followed 257 patients with bifascicular and trifascicular conduction-system disease and intact atrioventricular conduction who had undergone His-bundle studies. Forty-seven per cent had associated coronary-artery disease, and 23 per cent primary conduction-system disease. His-ventricular interval was moderately prolonged in 43 per cent and markedly prolonged in 12 per cent. During an average follow-up period of 25 months 50 patients died. However, death was sudden in only 27, and 17 of the sudden deaths were not due to bradyarrhythias. Actuarial analysis showed an overall mortality rate (mean +/- S.E.) of 19 +/- 2.6 per cent at two years, mortality from sudden death being 10 +/- 2.6 per cent. Permanent heart block occurred in 12. No clinical symptoms (including syncope), electrocardiographic findings, electrophysiologic data or their combination identified patients at high risk of sudden death. Sudden death due to bradyarrhythmia is uncommon in patients with bundle-branch block and intact atrioventricular conduction. Therefore, routine prophylactic use of permanent pacemakers in all such patients is inappropriate. Pacemaker implantation should be reserved for those with documented symptomatic bradyarrhythmias.


Career choice and performance on state licensing examinations of "Fifth Pathway" students.

Between 1975 and 1977, 340 American citizens trained in foreign medical schools (mostly Mexican) completed a year of supervised clinical training (Fifth Pathway) in New York State before beginning residency training. Analysis of 335 such students revealed a greater tendency to remain in the State for residency training as compared to graduates of New York State medical schools (P less than 0.01). A primary-care specialty was chosen by these students significantly less often than be American graduates (P less than 0.001). Their pass rate on state licensing examinations, although higher than that of other foreign-trained medical graduates, was significantly lower than that of American-trained students (P less than 0.001). Fifth Pathway programs can provide a source of United States-citizen house officers for hospitals currently staffed mainly by alien physicians. Such programs offer foreign-trained United States physicians an opportunity to improve their clinical skills before starting residencies, but evidently do not fully overcome their educational deficits.


Breast self-examination practices and breast-cancer stage.

To determine the relation between breast self-examination performance and the clinical and pathological stage of breast cancer at first diagnosis, we studied 335 patients with breast cancer. Approximately one fourth of the patients reported that they had been practicing monthly breast self-examination, and half that they had never practiced breast self-examination. More frequent performance of breast self-examination was associated with more favorable clinical stage and fewer axillary-lymph-node metastases on histologic examination. On pathological examination, the age-adjusted maximum tumor diameter of patients practicing monthly breast self-examination was 1.97 +/- 0.22 cm (mean +/- S.E.M.) as compared to 2.47 +/- 0.20 for those performing self-examination less often than monthly and 3.59 +/- 0.15 for patients never performing breast self-examination. These data associating more favorable clinical and pathological stages of breast cancer with more frequent breast self-examination need to be extended by determination of the survival rates of the various self-examination groups.


Estimated effect of breast self-examination and routine physician examinations on breast-cancer mortality.

We examined the effects of breast self-examination and breast examination by physicians on the stage of breast cancer at diagnosis. Clinical and pathological-staging information was compared to interview data on method of initial detection of 293 women. Tumors were detected in clinical Stage I 53.8% of the time when the detection method was routine physician examination, 37.7% when it was self-examination and only 27.0% when detection was accidental. Sixty-nine per cent of women practicing self-examination at the time of diagnosis discovered their tumor by this method. Differences were less apparent when pathological stage was considered. Tumors found during routine examination of the breast averaged 6.1 mm smaller in diameter than those discovered accidentally. We estimate that breast-cancer mortality might be reduced by 18.8% to 24.4% through self-examination or routine physician examination, respectively.


Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda.

To investigate the role of uroporphyrinogen decarboxylase in the pathogenesis of the sporadic form of porphyria cutanea tarda, we measured this enzyme in liver, erythrocytes and cultured skin fibroblasts, and also measured coproporphyrinogen oxidase and the total iron concentration in liver. The mean uroporphyrinogen decarboxylase activity was lower in liver from seven male patients (9.0 pmol of coproporphyrin per minute per milligram of protein) than in 12 controls, including seven with alcoholic liver disease (22.3 pmol per minute per milligram; P less than 0.05). Coproporphyrinogen oxidase activities were the same in each group. Liver iron concentrations were lower during remission, but uroporphyrinogen decarboxylase activities were not related to clinical activity for uroporphyrin excretion. Erythrocyte and fibroblast enzyme activities were the same as in normal subjects. A hepatic uroporphyrinogen decarboxylase defect is a prerequisite for the development of porphyria cutanea tarda, but other factors, which probably do not alter uroporphyrinogen decarboxylase activity, determine the clinical onset. In sporadic porphyria cutaneous tarda, the enzyme defect appears to be restricted to the liver.


Scintigraphic detection of pulmonary emboli by serial positron imaging of inhaled 15O-labeled carbon dioxide.

Inhaled radioactive carbon dioxide is retained in pulmonary blood distal to embolic obstruction and appears as an area of increased radioactivity that delineates the site and magnitude of the affected zone. The scintigraphic detection of pulmonary emboli by serial imaging of inhaled carbon dioxide labeled with cyclotron-produced 15O2 was evaluated in 27 patients undergoing conventional pulmonary ventilation/perfusion imaging and pulmonary arteriography. Fifteen patients proved to have pulmonary emboli on arteriography. Sensitivity (87%) and specificity (92%) rates for inhalation imaging were superior to those of conventional ventilation/perfusion imaging (P less than 0.05). Clearance of 15O2 activity was markedly delayed over embolized pulmonary segments (mean half time of 47.0 +/- 11.1 seconds [S.E.M.]) in comparison to normal segments (mean of 3.6 +/- 0.08 seconds; P less than 0.001). Pulmonary imaging by this method provides an approach to the detection of pulmonary emboli that is relatively sensitive and specific and permits analysis of persisting perfusion in embolized pulmonary segments. A major practical limitation, however, is the necessity of a nearby cyclotron.