The relationship between tissue fluid and lymph. II. Enzymes in tissue fluid and lymph. In rabbits both under normal conditions and after burning the activity of intracellular enzymes (LDH, GOT) is higher in tissue fluid than in the peripheral (leg) lymph. The relationship between tissue fluid and lymphatic enzyme concentrations is non-linear. The observations suggest the presence of at least two distinct compartments in tissue fluid. The first compartment forms the pathway taken by the fluid and protein leaving the blood capillaries and is directly drained by the lymphatics. The second compartment is the 'true' tissue fluid, contains the extravascular protein pool and it is in dynamic equilibrium with the first compartment.


Relative rates of absorption of fluid and protein from the peritoneal cavity in cats. The relative rates of fluid and protein absorption from the peritoneal cavity of anesthetized cats were measured over 6 hours at an intraperitoneal pressure of 15 mm Hg and with intraperitoneal protein concentrations from 1-8 g%. The fractional absorption rates of fluid and protein did not change significantly over the 6 hours and were not significantly different from each other within each one hour period. In addition both fractional absorption rates were unaffected by the protein concentration of the fluid within the peritoneal cavity. Although the absolute rate of absorption is greatly increased by elevation of the intraperitoneal pressure, these data indicate that the process remains iso-oncotic as would be expected for lymphatic rather than transcapillary absorption.


Lymph flow mechanism of the subperitoneal diaphragmatic lymphatics. Inorganic corpuscles like Indian ink and latex particles as well as erythrocytes penetrate via stomata on the peritoneal surface of the diaphragm into the subperitoneal lymphatics when injected intraperitoneally. Electronmicroscopic examinations showed that stomata are formed by intercellular gaps between neighbouring mesothelial and endothelial cells. In these areas there is a lacunar dilatation of the lymphatics, and a basement membrane as well as collagenous fibres are absent. The back flow of the lymph fluid from the stomata into the peritoneal cavity is prevented by overlapping of mesothelial and endothelial cells during inspiration as well as valve like cell processes of endothelial cells. The lymph flow is particularly affected by anchoring filaments of the lymphatics and the respiratory movement of the diaphragm.


Investigations on the uterine lymphatics of juvenile mice, up to the onset of sexual maturity. By means of orthograde and retrograde application of dyestuffs (using patent blue violet and Japan ink) one can successfully demonstrate the uterine lymphatics in juvenile mice, up to the onset of sexual maturity. However, the three subgroups used here do not show the typical features of the cyclical events of nulliparous and parous mice. However, the morphological changes already present, allow one even now to recognize, that with the increasing sequence of individual sexual cycles, cyclical changes in the uterine lymphatics of the mouse were identified.


Lymphography in surgically unresectable adenocarcinoma of the exocrine pancreas. Bipedal lymphograms were performed on 28 consecutive previously untreated patients with biopsy proven and surgically unresectable carcinoma of the pancreas. Four of these patients had findings indicating lymph nodes metastases. In three of these 4 patients, the lymphogram provided the only evidence of metastatic disease. The information provided by bipedal lymphography may be useful in treatment planning.


Analysis of the semantic structures of medical languages: part 1. A framework for the semantic power of reference languages. A model for analysis of medical reference languages, based on Saussure's distinction between paradigmatic and syntagmatic relations in language is proposed. Non-structural components, i.e. the size of the reference language and its ability to absorb new concepts are further considered.


The computerized medical record in gastroenterology: part 2. Morphological (descriptive) data. The linguistic problems involved in the communication of morphological (descriptive) data resulting from investigations performed by physicians were solved by the use of an artificial English language based on: (a) the Systematized Nomenclature of Medicine (SNOMED) completed by a set of semantic modifiers (mainly adjectives), (b) an elementary syntax using some prepositions and conjunctions, (c) a few simple rules of punctuation and lay-out.


The computerized medical record in gastroenterology: part 3. Numerical laboratory data. The main difficulty with numerical laboratory data is the risk of ignoring significant results scattered in a multitude of normal results. The universal scale of measure attempts to provide an answer to this problem. It reduces every abnormal value of similar severity to the same number.


The computerized medical record in gastroenterology: part 4. Health curriculum vitae. The health curriculum vitae consists mainly of a chronological sequence of diagnoses, which are the mainstays of the medical record. Each diagnosis is connected vertically in the health curriculum vitae with its aetiological factors and its medical or surgical treatments in a casual concatenation; and horizontally throughout the other three parts of the record with its relevant functional, morphological (descriptive) and numerical laboratory data in a diagnostic association. The health curriculum vitae uses the Systematized Nomenclature of Medicine (SNOMED), the International Nomenclature of the Diseases of the Gastrointestinal Tract (CIOMS) and the International Standard Classification of Occupations of the Internationl Labour Office.


Computer-assisted system for a mycobacteria tuberculosis laboratory using MUMPS. A Laboratory Information System (LIS) has been developed and the main part of LIS is an on-line system with auto analysers. In April 1976, the Biochemistry Laboratory was computerized in Osaka Prefectural Habikino Hospital. This LIS uses a PDP 11/40 minicomputer system using MUMPS language. At present a Mycobacteria Tuberculosis Laboratory (MTL) is computerized using the same computer and MUMPS. In this laboratory, there is no auto analyser, so this computerization aims at saving on labour in paper work and increasing the reliability of test results. This paper shows that the computerization of MTL with no auto analyser can be effectively achieved using MUMPS.


Processing medical records: data related problems. Computer processing of medical data can sometimes give a poor result. This can be due to several reasons. First, medical data may be heterogeneous, sometimes inacurate and often subjective. Secondly, the complex process of codification, data capture and validation is rarely carried out as carefully as possible. Finally, the processing itself can be the cause of some inaccuracy when it does not correspond to the defined objectives for which the data have been collected.


A preliminary report of an out-patient systems study in Sri Lanka. Out-patient medical clinics in Sri Lanka often have long queues of patients waiting to see a doctor partly due to a shortage of doctors. To apply operational research techniques to optimize the functioning of the clinic, an initial step is to determine the distributional pattern of patient arrival times and the doctors' service times. The results showed that the arrival times of patients were time dependent. However, analysis of half-hourly data of inter-arrival times showed a negative exponential distribution. The doctor's service time varied from doctor to doctor and whether new or follow up patients were being seen. Each of the service times seemed to fit into an Erlangian distribution.


Exploitation of medical records.

Exploitation of medical records. The difficulties in fully exploiting correct and valid medical data held in a computer system are presented. The requirements for such a system to answer a physician's request are detailed and related to the clinical user, the computer interface and the technological interface, in particular that relating to adequate software. The technical aspects of hardware and software govern the progress of change and a degree of long-term compatibility is required, to ensure adequate exploitation of clinical data. The various economic aspects of such changes are considered including the importance of economy in supporting harmonious technical changes.


[Effects of contraceptive pills in the field of otolaryngology? (author's transl)]. Besides the wellknown alterations of the Eustachian tube and membrana mucosa nasi there will be discussed the effects of the contraceptive pills on salivarian glands and on inner ear. The influence of gestagen and estrogen on the regulation mechanism of the above mentioned organes is demonstrated. Especially the erectile tissue of the submandibular and parotic glands and recidiving sudden deafness and discussed. To solve the about mentioned problems the interaction of medical statistics with clinical experiences is desirable.


[Kaposi's sarcoma. Pharyngo-laryngeal manifestation, treatment (author's transl)]. Kaposi's sarcoma involvement of the ENT region develops normally years after the onset in the skin. Reports on Kaposi's sarcoma in the ENT literature are therefore very rare. Until now by no kind of treatment including X-ray irradiation satisfactory results could be obtained. The recently introduced longterm-treatment with vinblastine sulfate is very effective reducing the size and extension of the tumorous infiltrations. In the ENT-region the plate, the pharynx, the larynx and the trachea are most frequently involved. We report on a patient with extensive pharyngeal and laryngeal involvement who had to be tracheotomized. While still on treatment with vinblastine-sulfate the decanulement was possible, the patient could resume his profession as bassoonist. This successful treatment regimen has not been mentioned in the ENT-literature previously.


[Rhabdomyoma of the soft palate (author's transl)]. A case of a rhabdomyoma of the soft palate of a 50-year-old woman is reported. The histological characteristics of this rare tumor are demonstrated by light and electron microscopic studies. The findings are compared with the criteria of extracardiac rhabdomyoma cases described in the literature.


[Cor pulmonale due to upper airway obstruction by hypertrophied tonsils and adenoids (author's transl)]. A case of cor pulmonale is reported, due to chronic nasopharyngeal obstruction by hypertrophied tonsils and adenoids. This syndrome is characterized by stridor, somnolence, arterial hypoxia and hypercarbia, pulmonary and right heart failure. The pathogenesis of this syndrome is due to pulmonary hypoventilation. After tonsillectomy and adenoidectomy the symptoms disappeared.


[A new method for haemostasis by tonsillectomy by use of infrared radiation (author's transl)]. Using infrared radiation tisssue is coagulated by infrared radiation and not by electrical current. Main purpose for this procedure is to apply mechanical pressure and radiation. No crust will stick to the artificial tip of the infrared apparatus to open up wounds once more. Infrared radiation for coagulation has been used in the clinic for 2 1/2 years, mainly in parenchymatous haemostasis during tonsillectomy. The method seems to be very effective and should enlargen the different means of dealing with haemorrhage.


[Dynamic range of acoustic reflex and its importance for hearing aid evaluation (author's transl)]. It is reported on the dynamic range of acoustic reflex in the case of normal hearing. Stimulation is carried out with speech noise under free field conditions. The sensitivity of impedance measurement is increased by using an averager, which enables acoustic reflex measurements at sound pressure levels of about 70 dB. Further an exact evaluation of input-output-characteristics becomes possible by this procedure. Basing on this consideration the possibility of objective hearing aid evaluation is discussed. The fundamental point of this technique should be the compensation of pathological input-output-characteristics by suitable hearing aids.


[Auscultatory detection of respiratory responses to olfactory stimuli. Approach to feigned anosmia (author's transl)]. The auscultation of breathing noise facilitates the detection of responses to smelled stimuli. In addition the noise of respiration may be recorded. The phenomenon has been used during the evaluation of nonorganic anosmia.


[Verrucous acanthosis (verrucous carcinoma) of the larynx (author's transl)]. Verrucous carcinomas are lesions occurring mainly in the buccal mucosa but sometimes they arise also in the larynx. The disease is characterized by a cornifying verrucous proliferation of the squamous epithelium, without atypias or metastases. The clinical and histological pictures of six observations are described and the differential diagnosis from hyperkeratotic papillomas and benign keratosis of the larynx are discussed. In one of these cases, 13 years after the beginning of the disease a focal cancerisation could be observed. The authors consider this disease not as a carcinoma and are not sure whether it is a true tumor at all. They propose therefore the name "verrucous acanthosis" instead of verrucous carcinoma and classify these lesions as facultative precanceroses.


[Cervical-lymph node metastasis of unknown primary tumour (author's transl)]. The therapeutical results of 39 patients with cervical lymph node metastasis of unknown primary tumour are presented. 34 patients received radiotherapy, 2 chemotherapy, and in 2 cases the metastasis was only excised. In 22 patients the radiotherapy consisted of homogenic irradiation of the neck, in 12 patients the area of tumour manifestation was irradiated with a dosis ranging from 4000 to 6000 rad. The cumulative survival rate of all the patients was 64% after one year and 30% after 4 years. Ninety one per cent of the patients who were without symptoms after the therapy, survived this time interval. All patients without therapeutical success died. The median survival time of all patients was 20 months. In 21 patients the primary tumour was found later. In 13 cases (62%) the tumour was located in the head and neck region. In 7 patients the histology of the tumour had to be changed.


[Parasitological diagnosis of onchocerciasis. A critical review of present methods (author's transl)]. The different methods used for the parasitological diagnosis of onchocerciasis are compared to test their reliability, sensitivity and practicability under field conditions in the Sudan-Savanna area. Two skin snips taken from both iliac crests with a sclerocorneal punch give the best results during large scale field surveys. The incubation of biopsies in normal saline solution is the most sensitive technique and the results may be further improved by filtration on millipore filter-paper and collagenase digestion. However, counting microfilariae emerged after 30 minutes in distilled water is the easiest method and gives a reasonably good reliability for comparison of the results in space and time. The lack of sensitivity can be compensated for by incubation of the negative specimen during 24 hours in saline solution.


[The question of anhaptoglobinemia in immigrants from West Africa (author's transl)]. Studying the plasmatic level and the phenotype of haptoglobine (Hp) in 71 West Africans living in France, the authors did not record any case of absence of Hp (Hpo) and did not see any significant correlation between the Hp and the duration of stay in France. They conclude that Plasmodium falciparum likely does not play any role in the origin of the Hpo peculiarity in West African immigrants.


[HBs antigen in rural population of Senegal (author's transl)]. The prevalence of HBs Ag has been determined by counter-immuno-electrophoresis among 16,006 Africans of all ages and both sexes living in 132 villages chosen at random in whole Senegal. 8,83 +/- 0,5 p. 100 of the examined people were positive for HBs Ag. HBs Ag is much more frequent among males (11,1 p. 100) than females (7,0 p. 100). Almost non existent before the age of 1, prevalence increases during childhood and reaches its summit between 10 and 14 years for boys (14,7 p. 100) and between 20 and 24 for women (10,1 p. 100), then it decreases regularly with old age and become negligible over 60. Ethnic factors and way of living are more important than geographical factors. Subtyping demonstrated the importance of contamination inside families and consequently the preponderance of oral over percutaneous transmission.


[Effect of new technologies in the coke industry on aromatic polycyclic hydrocarbon concentrations in the ambient air]. Concentractions of aerosols, amount of polycyclic hydrocarbons, in terms of soluble in benzene fraction and benzo(a)pyrene concentration were determined in coking plant air. Air was sampled on the roofs of modern coke batteries and on old-type batteries prior to, and following, modernization and major reapir. Aerosols were determined by passing 10--100 m3 of air through a 26 X 18.5 cm filter. After a weight determination of aerosol content the filter was subjected to benzene extraction and aromatic polycyclic hydrocarbons were isolated from the extract, using thin-layer chromatography. Quantitative determination of these hydrocarbons was done using ultraviolet spectrophotometry. Results of determinations on work-posts in modern and old-type coke batteries prior to, and following, modernization were comapred. Average concentrations of aerosols in the air, amounts of polycyclic hydrocarbons soluble in benzene and concentration of benzo(a)pyrene determined on the roofs of old coke batteries before modernization were as follows: 11.26 mg/m3, 6.37 ug/m3 and 112.28 mg/m3, and after modernization: 0.88 mg/m3, 0.25 mg/m3 and 1.29 ug/m3, respectively. On the roofs of modern high chamber coke batteries average concentrations of aerosols, polycyclic hydrocarbons--benzo(a)pyrene amounts were: 4.21 mg/m3, 0.79 mg/m3 and 5.72 ug/m3, respectively. The results clearly demonstrate that work conditions in modernized coking plants are much better than those in old non-modernized coking plants.


[Control of arthropod vectors of human diseases in intertropical Africa: its importance (author's transl)]. Intertropical Africa is the first area in the world for the frequency of arthropod born human diseases, such as malaria, trypanosomiasis, viral infections (f.i.yellow fever), various filariasis and chiefly onchocerciasis. Control of arthropod vectors is very important indeed in this area. It requires a closed collaboration between entomologists, biologists, hygienists and tropical physicians. Chemical control is still preponderant but it must be associated, as often as possible, with physical, biological and genetic means of control.


[Bases for control of arthropod vectors: II--Present means (author's transl)]. A review of the present means of control of arthropod vectors in which the authors consider:--individual means aimed at the prevention of bites by utilizing clothes, repellents, mosquito nets and insecticide sprays,--collective means which are either physical, biological or chemical. Physical means are specially used for water control either in "peridomestic actions" or in large scale campaign's related to rural or industrial development scheme. Actually biological means are represented only by larvivorous fishes. The chemical control is the most important, its various requisites, and techniques are given.


[Correlation between changes in lungs caused by industrial dusts and the composition of amino acids in blood plasma. I. Experimental animal studies]. Animals, used for experiments, were intoxicated intratracheally with a suspension of grinding, ceramic or welding dust, in a NaCl solution. These studies demonstrated that the ceramic and welding dusts, used in the experiment, showed a rather great biological activity. This has been proved by the increased weight of dried lungs, and increased total content of some aminoacids in lungs, e.g. hydroxyproline, which is thought to be a reliable index of fibrosis of the pulmonary tissue, as well as of the change in the morphological structure of lungs. Parrallel to the mentioned changes of the lungs, the content of free aminoacids in the animals blood plasma has been remarkably reduced. The results described in this paper prove that there is a dependence between the content of aminoacids in the blood plasma and the changes in lungs caused by dust.


[Multistage studies aimed at early detection of chronic effects of vinyl chloride and mercury vapors]. 168 persons occupationally exposed to vinyl chloride and 236 persons exposed to mercury in plants electo two-stage medical and laboratory examinations. Workers exposed to vinyl chloride in average concentrations of 133 mg/m3 were found to show megalohepatia and abnormal enzymatic tests results (transaminic, A1AT, AP). The frequency of disturbances in workers exposed to vinyl chloride, average concentration 17.9 mg/m3, was considerably lesser. The second stage of studies involved those exposed to vinyl chloride for more than 10 years, with megalohepatia and at least 1 abnormal enzymatic test. No angiosarcoma was found. An analysis of the diagnostic value of biological tests used, indicated a great usability of liver scintigraphy and vascular system examinations for early diagnosis of vinyl chloride intoxications. In the plant where workers were exposed to mercury the Hg concentrations were found to range from 0.05 to 0.07 mg/m3. No significant differences between these workers and the control group were found, in respect to medical and laboratory examinations. The second stage of studies involved 118 persons exposed to mercury in concentrations above 20 mg/m3 of air, no matter how long the exposure lasted. The second stage of studies consisted of extensive biochemical studies, examinations of the liver using isotopic scintigraphy, psychological, psychiatric examinations and encephalographic determinations. Psychological, psychiatric and encephalographic examinations were said to be of great importance in early diagnosis of chronic mercury intoxications.


[Changes in lysosomal activity of beta-glucuronidase in leukocytes of rats exposed to benzene under selenic protection]. The authors demonstrated that a chronic exposure to benzene caused in rats a reduction in the number of lymphocytes in peripheral blood, decrease in beta-glucoronidase (BG) activity in neutrophils and increase in BG-positive lymphocytes fraction. In addition, a failure was found in lysosomes of lymphocytes, revealed by scattering of a given enzyme in cytoplasma. Administration of 1.0 microgram/kg for 10 consecutive days before benzene exposure, did not prevent lymphocytopenia but hampered BG activity decrease in neutrophils as well as a damage to lymphocytic lysosomes. Administration of 5.0 microgram/kg for 10 successive days prior to benzene exposure, prevented lymphocytopenia and caused a reactive increase in the amount of neutrophils and resulted in an increase of BG-positive lymphocytes fraction, especially those with cytoplasmatic localization of enzyme. The results obtained demonstrate that only a smaller dose of selenium protected lysosomal membrane of lymphocytes from toxic effects of benzene, whereas both selenium doses protect BG in neutrophils.


[Influence of carbon disulfide on hemostasis in rabbits. I. Studies on coagulation and fibrinolysis]. Rabbits were exposed to carbon disulphide vapours in the toxicological chamber. Fibrinogen level, antiplasmin activity and soluble fibrin monomer complexes in the blood were increased, fibrinolysis time was prolonged. These disturbances in hemostasis depend on the concentration of carbon disulphide in the inhaled air and on the intoxication time. The authors suggest that these findings depend on the changed lipid metabolism and on the direct antagonistic influence of CS2 on coagulation and fibrynolysis agents.


[Control of vectors of human onchocerciasis in intertropical Africa (author's transl)]. First the authors make short comments on the two Simuliidae species complexes vectors of African human onchocerciasis (S. damnosum s.l. and S. neavei), as well as on the reasons for renewed interest in the control of those vectors; then they review the various possible methods of control (ecological, biological, genetical and chemical methods) and they finally detail the methodology of anti-S. damnosum chemical larviciding which is the only kind or large scale control presently used against onchocerciasis vectors. The experiences and results of the previous campaigns resulted in the large Onchocerciasis Control Programme in Volta River Basin (O.C.P.) which now appears as a model for present and future control measures against S. damnosum. This Programme is briefly described, together with its results, problems (reinvasion) and orientations. As a conclusion, the excellent level of control of the vectors and onchocerciasis transmission which is obtained is emphasized and it is expected that in the future new large scale campaigns using O.C.P. experience may be initiated.


[Bases for control of arthropod vectors: III--Insecticides and questions they raise (author's transl)]. Insecticides are still nowadays our main way of control of arthropod vectors. Their use raises many important question, resistance of the vectors, toxicity, risks of pollution and costs of spraying campaigns. These various drawbacks are considered with special regard to the problem of resistance its world wide spreading, its mechanisms, its meaning. The various types of toxicity are also detailed.


[The chemical control of disease vectors. Evaluation of new insecticides. Operational insecticides. New insecticides (author's transl)]. The chemical control of disease vectors which has been very successful during about 15 years is now faced with some difficulties due to the resistance of insects to the insecticides, to the decreasing number of candidate insecticides, to the increase of their price and to the legal restrictions concerning their safe use and their environmental inocuity. Since 1960, W.H.O. has carried out an evaluation programme to define the properties of new insecticides and to access their usefulness for public health. Through this programme several alternative insecticides have been selected and are now used in vector control operations. Although research continues on organophosphorous compounds and carbamates, it also includes the promising groups of pyrethroids and insect growth regulators. The present trend of vector control is to integrate various control techniques and to limit the use of insecticides to the control of the epidemiologically dangerous part of the vector population. This approach might prevent or delay the development of resistance.


[The control of the vectors of the sleeping sickness caused by Trypanosoma gambiense Dutton (author's transl)]. In this review on tsetse control, the authors particularly stress the methods used at the present time against riverine species vectors of "Gambian sleeping sickness". The different kinds of insecticidal treatments, the means of ground and aerial application of residual or non-residual compounds as well as the planning of control campaigns are described. Besides, the authors show the present trends of the research on tsetse flies ecology, new insecticides, methods of spraying, biological control and the impact of tsetse control operations on the environment.


[Acute toxic effects of trimethyl and triethyl phosphites]. The studies on toxic properties of trimethyl and triethyl phosphities involved: determination of acute general toxic effect on white rats following intragastric and intraperitoneal administration of these compounds, based on DL50 test, determination of damaging effect direction, by histopathological examination of animals' internal organs, determination of intensity of primarily irritating action on the skin, eye and conjunctiva, as well as sensitizing effect on guinea-pigs. DL50 value for trimethyl phosphite following intragastric administration was found to be 2.45 g/kg and following intraperitoneal administration--2.25 g/kg; for triethyl phosphite these values were: 4.00 g/kg after intragastric administration and 1.50 g/kg after intraperitoneal administration, respectively. In local action both phosphites mildly irritate the skin, eye and conjunctiva. A weak sensitizing effect of triethyl phosphite was found. Trimethyl and triethyl phosphites have general toxic effects. A particular direction of their action is demonstrated by acroparalysis. Apart from general action they were found to show systemic action and induce parenchymatous degeneration of the liver and kidneys, whatever route of administration. Administered intragastrically, they result in mucosa necrosis, ulceration and fibrino-purulent exudate, exfoliating the mucosa.


[Method of determination of hydrogen and chloride ions in the air]. The turbidimetric method of determination of hydrogen chloride and chloride ions has been elaborated. The determination range of the method is 20--100 microgram Cl-in solution. The precision error is +/- 3.28%.


[Determination of vinyl chloride in the air by the gas chromatography method]. The purpose of the paper was to work out a gas chromatographic method for determination of vinyl chloride in the air at work places in the chemical plants. The best results have been obtained at 50 degrees C on 3-meter column containing 10% SE-30 on Chromosorb W AW DMCS, 80--100 mesh. Two methods of sampling have been considered: that of collecting samples in vacuum pipettes and that of adsorption on charcoal. In the former method stability of collected samples has been investigated (Fig. 3). A slight decrease in concentration of the vinyl chloride (approximately 3%) was found in four hours. In the latter method two ways of determination of vinyl chloride desorption coefficient from charcoal have been investigated. Since no essential difference in values of desorption coefficient has been observed, both ways for determination of desorption coefficient may be employed. A modified device for preparation of standard concentrations of vinyl chloride in the air has been utilized in our research (Fig. 2). The relative standard deviation resulting from analysis of samples was +/- 0.075. The minimum determinable amount of vinyl chloride was found to be 10 ng per injection.


[Problems of formal organizational structure of industrial health care complexes]. The author formulates the thesis that the description of organizational structure of industrial health care complex calls for isolation of the following aspects:--structure of territorial links--systemof organizational units and divisions--organization of basic functions--structure of management--structure of supervision of middle and lowe-level personnel--composition of health care complex council--system of accessibility ranges. Each of the above aspects has been considered on the basis of operative rules of law, using organizational analysis methods.


[Hearing impairment in operators of motor saws]. An otolaryngological and audiometric examination was performed among 901 motor-sawers occupationally exposed to motor-saw noise, and among 177 persons in a non-exposed control group. Hearing impairment of various degrees was found in 83.7% of motor-sawers examined. In 63.5% of motor sawers hearing impairment was due to noise exposure. The hearing impairment found, was in 88% a reciprocal receptive loss, more intensified in the left ear. It was positively correlated with motor-savers' age, duration of employment in exposure to motor-saw noise, and the amount of wood cut. The average hearing impairment in both ears was significantly higher among motor-sawers with hearing damage due to various causes, than among those with damage due to the motor-saw noise only, which proves a simultaneous overlapping of different factors inducing impairment, including motor-saw noise.


[Classification of degenerative bone lesions in operators of motor saws]. Results of radiological examinations of hands, cubital and acromial articulations of 360 motor-sawers in forestry were analysed. A 4-degree distribution of degenerative lesions of bones in view of their progression was suggested. The authors consider their classification of radiological pictures helpful in prevention and diagnosis of vibration disease.


The mode of production of endotoxin-induced interferon in rabbit tissue cells. I. Development of priming by pretreatment with interferon. In vitro production of endotoxin-induced interferon in rabbit tissue cell cultures could be enhanced by pretreatment with interferon. The enhancible state developed from the first hr of incubation at 37 C and a maximal priming effect was attained at 6 hr of incubation. Yields of interferon from unprimed cultures were usually 20-200 units/ml. In contrast, the primed cultures constantly yielded 1,000-2,500 units/ml of interferon. The pretreatment with interferon seemed to cause an earlier appearance of detectable interferon and the primed cells became more sensitive to endotoxin. It turned out that 10--30 units/ml of rabbit interferon were enough to develop the maximal priming. Even when cells were pretreated with higher doses of rabbit interferon such as 1.0 x 10(4) - 1.0 x 10(5) units/ml, the same level of priming effect was always observed without diminution. Various types of homologous (rabbit) and heterologous (human and mouse) interferon preparations showed similar dose-dependent enhancement of interferon production in proportion to the antiviral titers of these preparations as tested with RK-13 cells of rabbit origin.


[Effect of a stimulating factor formed by Aspergillus wentii on exoprotease biosynthesis by a culture of Aspergillus kanagawaensis]. The object of this work was to study the composition of proteases synthesized by an active culture of Aspergillus kanagawaensis (I) as well as that in the presence of a cultural broth of Asp. wentii (II) which did not produce exoproteases. Enzyme complexes I and II are similar in qualitative composition but complex II has a higher proteolytic activity. The preparation containing the stimulating factor produced by Asp. wentii has been separated by gel filtration and ultrafiltration. Biosynthesis of exoproteases is stimulated by low molecular weight fractions of the cultural broth of Asp. wentii.


[Formation and utilization of lactate during methane fermentation of cellulose]. The role of lactate was studied in the course of methane formation from cellulose by a mixed bacterial association. Lactate was accumulated in the medium during intensive degradation of cellulose and was assimilated in the period of active gas production. Glucose added to the medium was converted into lactate within 30 min. If lactate served as a substrate for a methane forming association which was previously cultivated in a medium containing cellulose, it was almost completely converted into methane; the lag phase was shorter than in the case of cellulose, while the rate of methane formation was higher. In the presence of sulfate in the medium, sulfate reduction preceded methane production from lactate. The combined culture Desulfovibrio vulgaris+Methanosarcina grew in the medium containing lactate, and completely converted it into methane. The formation of methane from lactate by the mixed microbial association can be attributed to the interaction between sulfate reducing and methane producing bacteria.


[Deuterated membranes of Micrococcus lysodeikticus: production and several biochemical properties]. A technique has been elaborated for preparation of deuterated membranes from deuterated cells of Micrococcus lysodeikticus containing 85--90% of deuterium according to the data of IR and PMR spectroscopy. Normal lysis of the deuterated cells of M. lysodeikticus requires a concentration of lysozyme which is eight times higher than for usual cells (8 mg per 1 g of wet deuterated cells) and an addition of the lytic enzymes E-2 (2 mg per 1 g of wet deuterated cells). Preparations of deuterated membranes purified from ribosomes and proteins can be obtained by treating of the lysate with RNAase and washing in 0.5 M NaCl. The purity of the deuterated membranes was evaluated by the evidence of electron microscopy, IR spectra and enzyme activities. After hydrogen atoms were substituted by deuterium, the secondary structure of the total membrane protein, the ratio between the activities of the respiratory chain enzymes, and the relative content of the lipid and protein components of the deuterated membranes remain at the same level as in the protonated ones.


[Study of the dynamics of the uptake and utilization of a hydrocarbon in Mycobacterium paraffinicum cells by means of IR-spectroscopy]. The dynamics of uptake and further utilization of hexadecane in different regions of the cells of Mycobacterium paraffinicum was studied using spectroscopy of Attenuated Total Reflection (ATR) in the IR range during the whole period of their growth. The outer layers of the cells were found to be rapidly saturated during their growth on a medium containing hexadecane. Oxidation of the hydrocarbon resulted in accumulation of a large amount of triglycerides whose active biosynthesis started at the end of the logarithmic growth phase. The bulk of triglycerides concentrated in the cytoplasm. Later, the content of triglycerides decreased almost twofold, this suggesting assimilation of these compounds by the cell. After 13 days of cultivation, all parameters were stablized; therefore, the metabolic processes decelerated and the state of dormancy occurred. No degradation of the culture was observed.


[Effect of metal ions on the lipolytic activity of Rhizopus microsporus]. Various metal ions have different effect on the lipolytic activity of Rhizopus microsporus in the course of cultivation on nutrient media having diverse composition. The fungus particulary requires metal ions for the production of lipase on a mineral medium. Additional introduction of microelements into a medium containing maize extract has no significant effect on the lipolytic activity. Active biosynthesis of lipase by the culture requires zinc.


[Population composition of Actinomyces tumemacerans and Actinomyces albus var. fungatus]. The population analysis of Actinomyces tumemacerans and Actinomyces albus var. fungatus has revealed identical homologous series of spontaneous variants, this suggesting the genetical relationship of the cultures. Variants of the same type (basic, oligosporous, asporogenous and proactinomycete-like) are identical not only according to their individual properties (Kuznetsov, 1973) but also in total characteristics typical of the variants of a given species. Populations of the studied cultures comprise variants synthesizing several antibiotics, i.e. albofungin, albonursin and tetraene (basic and oligosporous variants), albofungin and tetraene (asprogenous green variants), as well as variants producing only one tetraene antibiotic (proactinomycete-like variants). Therefore, the population analysis based on the law of homologous series in hereditary variability of actinomycetes can be used as a new approach to the taxonomy of these microorganisms.


[Participation of nitrifying bacteria in the disintegration of serpentinous ultrabasic rock]. Nitrifying bacteria were found to be widely distributed among the products of the weathering crust of ultrabasite rocks. Nitrosospira briensis and Nitrobacter winogradskyi involved in the first and second phases of nitrification, respectively, were detected and isolated as pure cultures. In experiments conducted with a pure culture of Nitrosospira briensis, a correlation was established between degradation of serpentinite by this culture and an increase in the content of nitrites in the growth medium. The presence of nitrogen compounds in the deposits, as well as wide distribution of nitrifying bacteria, suggests that this bacterial group along with other, in particular, heterotrophic microorganisms participates in weathering of serpentinized ultrabasite rocks, leaching of elements, and formation of the weathering crust.


[Effect of nitragin on alfalfa yield in the chernozem-poor zone of northen Siberia]. The presence of nitragin in soil on which lucerne was cultivated increased the yield of green biomass as well as the content in it of protein, essential amino acids, nitrogen-less extractive substances and ash, and decreased the content of cellulose. Nitragin increased the yield of green biomass by 44--51% in the absence of spontaneous nodule bacteria in soil and by 10--19% in their presence; the content of protein in the crop increased respectively 2.1--2.4 and 1.4--1.8 times. The most active strains of the lucerne nodule bacteria were 435a, 441a and a "local" one; the least active strain was 422a.


[Determination of carbon dioxide released from soil at different humidities]. The detection of soil microorganisms by their evolution of carbon dioxide does not always correlate with the number of microorganisms and the rate of biochemical processes in soil. New microbial populations appear in the incubation chamber as the concentration of carbon dioxide increases; this results in an increase in the activity of such processes as photosynthesis, chemosynthesis and heterotrophic assimilation of carbon dioxide. Life detection on other planets by determining carbon dioxide evolved from the ground may lead to erroneous conclusions on the presence of microorganism in the ground.


[Sequence of formation of gaseous products during anaerobic decomposition of cellulose in the presence of several electron acceptors]. The course of anaerobic cellulose decomposition by a mixed microbial association was studied in the presence of nitrate and sulfate ions in the medium. The succession of reductive processes was evaluated by the formation of gaseous products, i. e. nitrogen, hydrogen sulfide, and methane. The sequence of processes in the course of cellulose degradation was determined by the energy yield of oxidative-reductive reactions. Sulfate reduction predominated if lactate was assimilated by the same microbial association, while denitrification prevailed when the association used acetate.


[Utilization of aromatic compounds by yeasts of the genus Debaryomyces]. The ability to utilize phenol, catechol, resorcinol, hydroquinone, p-hydroxybenzoic acid, m-hydroxybenzoic acid, 2,4-dihydroxydenzoic acid, protocatechuic and gentisic acids was studied among 61 strains of 23 yeast species belonging to the Debaryomyces genus. All species characterized by active fermentation did not utilize these aromatic compounds. If fermentation was absent or weak, some of the aromatic compounds were utilized. This fact suggests an ecological difference between the two above yeast groups, justifying the subdivision of the Debaryomyces genus by some authors into two genera Debaryomyces and Torulaspora. No correlation could be established between the utilization of certain aromatic compounds and the yeast species classified on the basis of their behaviour toward carbohydrates. Therefore, classification of yeasts belonging to the Debaryomyces genus is artificial. It would be expedient to isolate a small number of typical species unless a more accurate relationship is established between cultures of the Debaryomyces genus referred to as different species.


Automated family classification in ambulatory arrhythmia monitoring. A system to analyze ambulatory arrhythmia monitoring has been developed which is highly specific and sensitive. It has been used to process seven tapes per day (comprising clinical caseload and data for antiarrhythmic drug studies) in a clinical environment. This system has also been used to investigate two-channel ambulatory electrocardiograms, where the additional information provided is expected to improve the ability to deal with artifact and the problem of isoelectric premature ventricular contractions. A correlation of QRS complexes with operator-selected decisions has also been tested. While time-consuming, it is reliable and amenable to optimization solutions.


[Respiratory system of Pichia guilliermondii yeasts with different levels of flavinogenesis]. The yeast Pichia guilliermondii was grown on media with different content of iron and its respiration system was studied. When the yeast was cultivated on a complete medium, its respiratory chain operated at the maximum rate in the exponential growth phase, i. e. all the three points of phosphorylation were involved; cytochrome oxidase was the only terminal oxidase. When the growth was decelerated and at the stationary phase, the alternative autooxidable cyanide-resistant pathway inhibited with salicyl hydroxamate partly functioned. Iron deficiency in the medium resulted in a two-three-fold decrease in the content of total and non-hemin iron in the cells, changes in the character and rate of growth, a decrease in the biomass yield, a high rate of flavinogenesis, a slight decrease in the respiration activity, though no drastic changes in the respiration system occurred. This system is represented, as in the case of cells grown on a complete medium, by a typical cytochrome system and an alternative autooxidable pathway. The absence of principal differences in the respiration systems of normal and iron-deficient cells, as well as the operation of the first point of coupling in flavinogenic cells, makes it doubtful that Fenh-proteins of the first segment of the respiratory chain are involved in the regulation of flavinogenesis.


High-speed Holter ECG analysis--what we have learned. A system for high-speed quantitative analysis of continuous ECG (Holter) recordings has proved effective in maintaining a measured specificity of 99.67 percent and sensitivity of 99.74 percent. Practical difficulties with common ECG signal artifact, and with unusual QRS complexes, have proved that online operator monitoring of classification accuracy is required. Because of artifactual and physiological variability among patients, Holter analysis of individual recordings is meaningless unless accompanied by an indication of the degree of accuracy of the specific recording. Common definitions of specificity and sensitivity based on results from sample recordings are not sufficient to describe the characteristics of an automated ECG performance on any given recording. A quality assurance program that evaluates both the machine and its operator is discussed.


Bromocriptine in lieu of levodopa for Parkinson's disease. Thirteen patients with Parkinson's disease, whose disability was increasing and on long-term levodopa therapy (both with and without carbidopa), had the levodopa fully replaced by bromocriptine. At three months, eight of the 13 patients (62%) were less disabled on bromocriptine and none became worse. The present indications for the use of bromocriptine are discussed.


Prematurity and height of ventricular ectopic beats as criteria for detection in rapid Holter scanners. Automatic ventricular ectopic beat (VEB) counters attached to rapid Holter scanners, currently available commercially, should be examined for accuracy and cost-effectiveness. The author, by using permaturity and height as criteria for detection of VEBs, found an average error of 23 percent; at times the error was higher than 50 percent. The Medical Decision Making Theory was applied in an attempt to reduce the error by more sensitive adjustment of the detectors, but this resulted in only minimal improvement. The author has concluded that automatic VEB counters using prematurity and height as detection criteria are potentially very inaccurate and, therefore, not cost-effective.


Medical management of acromegaly with bromocriptine. Effects of continuous treatment for over three years. Eighty-seven patients with active acromegaly were treated with bromocriptine for periods of up to 42 months. On treatment, 82 of these patients noted a rapid alleviation of one or more symptoms of their disease. In 67 patients, the mean growth hormone level of four values taken through the day fell by 14 mu/L or more, or became undetectable. Eighty patients have been treated for over 12 months and this suppression was maintained. Improvement in abnormal glucose tolerance occurred in 25 out of 29 diabetics and tolerance became normal in 19. Bromocriptine is of great value in cases in which surgery or radiotherapy has not been completely effective or as interim treatment until the full effect of other therapy has taken place. However, the long-term effect of high doses of bromocriptine is not yet known.


Noninvasive ambulatory monitoring of physiologic data: recording systolic time intervals. Adding physiologic data to ambulatory electrocardiographic monitoring data yields information with great potential for diagnostic and therapeutic use. The ear densitogram's stability, demonstrated during exercise and under laboratory conditions, indicates its applicability to ambulatory monitoring as a source of systolic time intervals. Circuitry has  been developed to feed the output of an ear densitogram pickup into one channel of a two-channel Holter monitor. Baseline studies in different postures are used to establish pulse transmission time, which permits the ear densitogram pulse to be used as a delayed aortic pulse in measuring systolic time interval. Feasibility and field studies have shown that systolic time intervals can be precisely determined by this method.


Bromocriptine in treatment of acromegaly: Australian experience. Ten acromegalics, 6 females and 4 males, aged 24 to 75, have been treated with bromocriptine (CB). Six patients responded clinically to CB: two subsequently escaped control, three have been treated continuously for from 14 to 32 months, and one withdrew because of side effects. Four patients failed to respond: one at 60 mg/day, two at only 20 mg/day and the fourth at 5 mg/day when treatment was ceased because of side effects. Three patients had severe illnesses during treatment and four patients were troubled by side effects. CB is useful in the treatment of acromegaly where other modalities are unsuitable.


An adaptive algorithm for noise rejection. An adaptive algorithm for the rejection of noise artifact in 24-hour ambulatory electrocardiographic recordings is described. The algorithm is based on increased amplitude distortion or increased frequency of fluctuations associated with an episode of noise artifact. The results of application of the noise rejection algorithm on a high noise population of test tapes are discussed.


Transvenous catheter defibrillation: comparison of a half-sinusoidal and trapezoidal waveform. This study compares transvenous electrode catheters' defibrillation effectiveness when using the trapezoidal waveform and when using the damped half-sinusoidal waveform, at comparable energy levels. Five greyhounds were used in some 272 fibrillation/defibrillation trials. Neither total energy, peak current, nor peak voltage could be absolutely correlated with percent effectiveness for transvenous defibrillation. However, for a given waveform, an increase in delivered energy was associated with a large and statistically significant increase in percent success.


Treatment of acromegaly with bromocriptine. Twelve patients with acromegaly were treated with bromocriptine for periods from nine to 23 months. All showed some clinical improvement. There was no significant difference in plasma growth hormone levels before and after therapy with bromocriptine, but a significant fall in plasma prolactin levels was observed after the bromocriptine therapy was commenced. The release of other pituitary hormones was not affected by bromocriptine.


Meningeal seeding from rhabdomyosarcoma of the head and neck with base of the skull invasion: recognition of the clinical evolution and suggestions for management. Rhabdomyosarcomas of the head and neck may spread by diffuse local invasion, resulting in erosion of the base of the skull with possible extension to the leptomeninges, brain, and cranial nerves, as well as invasion of the ventricular system with possible intradural, extramedullary metastases anywhere along the neuraxis. Meningeal spread of tumor is difficult to eradicate, and nearly all patients reviewed died soon after meningeal disease was evident. Patients with erosion of the base of the skull or abnormal cranial nerve findings seem to have a risk of seeding the meninges with tumor. The clinical evolution of this pattern of metastatic spread is reviewed, diagnostic studies are recommended, and therapeutic considerations are discussed. Tentative treatment guidelines are also offered.


Radiation myelitis following craniospinal irradiation with concurrent actinomycin-D therapy. Two patients are presented who developed radiation myelitis as a complication of treatment for medulloblastoma. These patients had been entered onto a pilot study to evaluate the therapeutic efficacy of combined treatment with radiation therapy and actinomycin-D (AMD). AMD is a known radiation enhancer in all tissues but the nervous system. Both of these patients received a full course of cranio-spinal irradiation plus AMD 15 mcg/kg for the first five days of therapy. One patient developed myelitis at 4 months, and the other at 12 months after treatment. Both patients are surviving three years posttreatment without any evidence of recurrent disease. The myelitis in one patient has improved, and it is stable in the other patient. It is concluded that AMD enhances the effect of radiation therapy on the central nervous system. This has never been reported but is important to note now, since radiation enhancers are included in multimodal treatment regimens for a variety of malifnant conditions. Reduction of radiation dose may be necessary when large volumes of the nervous system are treated.


Steroid receptors study in breast carcinoma. Estrogen receptors (ER) were measured on specimens taken from 27 patients with benign breast conditions and 109 patients with breast cancer. Using sucrose gradient assay, 15% (4/27) of benign lesions and 56% (61/109) of malignant tumors were estrogen receptor-positive (ER-positive means 8S or 8S+4S levels more than 7 fmoles/mg cytosol protein). Progesterone receptors (PR) were tested on specimens from 28 patients and 39% (10/26) of the cancers were PR-positive. ER protein activity was not correlated with stage, histology, size of primary lesions, or extent of axillary or distant metastasis. Tumors with low ER levels are more likely to recur, and recurrent tumors after longer disease-free intervals are more likely to be ER-positive. Detailed analysis showed that ER levels did correlate with age and serum albumin levels. Concentrations of serum alpha1-globulin were decreased, while IgG and IgM were significantly increased among patients with positive ERs. Eighteen evaluable patients with advanced breast cancer had endocrine therapy, 13 had objective response. Twelve of these 13 had 8S receptor above 10 fmoles/mg, or 4S above 15 moles/mg, or 8S+4S above 25 fmoles/mg. The one exceptional patient had tumor with high PR but without detectable ER.


Cisplatin pharmacokinetics in a patient with renal dysfunction. Plasma and urine platinum concentrations were measured by atomic absorption spectrophotometry during a three-day course of cisdiamminedichloroplatinum (DDP, cis-platinum, cisplatin) therapy in a patient with acute renal failure who was being treated with hemodialysis. Twenty-four hour urine collections, obtained during the oliguric phase, accounted for only 0.36--0.56 percent of the daily DDP dose. The plasma t1/2beta of platinum was approximately 240 hours after the last DDP dose. Platinum could be measured in the dialysate only during the first two hours after DDP administration. Although the data show that the t1/2beta of DDP is prolonged three fold in a patient with profound renal failure, the clinical implications of these findings await further studies.


Septicemia in acute leukemia.

Septicemia in acute leukemia. We have surveyed septicemic episodes occuring in individuals with acute leukemia and have found two factors favorably influencing survival, mainly granulocyte counts over 1,000 mm3 and gram-positive bacteremias. In contrast, blood cultures persistently positive for longer than 48 hours were a bad prognosticator. Significantly, patients with gram-positive bacteremia had received less antibiotics in the week prior to septicemia than had patients with gram-negative bacteremia.


Plasmacytomas and mesothelioma.

Plasmacytomas and mesothelioma. A patient is reported who developed five plasmacytomas over a four-year period and developed a pleural mesothelioma 12 years later. The relationship of these two entities is discussed and the question of a common environmental carcinogen is raised.


Increasing incidence of Gram-positive sepsis in cancer patients. A review of the agents causing septicemia in cancer patients during a nine-year period (1968--76) revealed that Gram-positive organisms (especially S aureus) have become the most frequent isolates during the last two years. This unanticipated increase (P less than 0.001) in the number of Gram-positive isolates could not be related to horizontal transmission nor to changes in patient characteristics or therapy.


Metastatic Ewing sarcoma to the heart simulating adriamycin cardiotoxicity. A 20-year-old man with metastatic Ewing Sarcoma developed severe congestive heart failure. Because he had been treated with a large amount of Adriamycin, the diagnosis was initially thought to be Adriamycin cardiotoxicity. However, ante- and post-mortem studies revealed the presence of massive cardiac metastases. At post-mortem, there was no evidence of Adriamycin cardiotoxicity. This case emphasizes that cardiac metastases must be considered in the differential diagnosis of heart failure in patients treated with Adriamycin.


Electrocardiographic changes following adriamycin treatment. Two hundred and fifty-six patients with a wide variety of advanced neoplasms who were treated with adriamycin at Roswell Park Memorial Institute were studied for electrocardiographic changes. All the patients had pre- and posttreatment electrocardiograms (ECG's) and changes were found in 85 (33.2%). In the group of 1-8 patients with normal pretreatment ECG's, changes occurred in 51 (30.3%). In the group of 88 patients who had abnormal pretreatment ECG's, 34 (38.6%) developed further changes following treatment. Twenty-five patients received cytoxan concomitantly and ECG changes developed in 12 (48%); however, this and the above difference were not statistically significant. Frequency of ECG changes was higher and the extent of histologic abnormality in the myocardium was greater in those patients who received high doses of adriamycin. Arrythmias were rather benign and only a small number of patients required treatment. ECG changes following adriamycin treatment occurred more frequently than previously reported.


Electron microscopic analysis of in vitro transcriptional complexes: mapping of promoters of the coliphage T5 genome. Transcriptional complexes formed in vitro with coliphage T5 DNA as template were analyzed by electron microscopy and the number and location of starting sites utilized by E. coli RNA polymerase were determined. Of the 40 promoters characterized in this way, 6 map in the two terminal "pre-early" regions, 29 in the "early" and 5 in the "late" region. The direction of transcription within the different regions determined in this study agrees with earlier findings derived from RNA synthesized in vivo.


Phosphorylation of the Ca2+ pump intermediate in intact red cells, isolated membranes and inside-out vesicles. Ca2+-entry into intact red cells containing [32P]-ATP increases the phosphorylation of the 150 000 dalton polypeptide of the membrane. This phosphorylation occurs even in Mg2+-depleted red cells. Extracellular lanthanum applied during ATP-depletion further increases the Ca2+-induced phosphorylation. In fragmented membranes or resealed insideout vesicles (IOVs) membrane bound Mg2+ is sufficient to catalyze the phosphorylation of spectrin 2 and Band 3 polypeptides with low concentrations (less than micron of [32P]-ATP. In Ca-EDTA buffers one single polypeptide is phosphorylated which is located in the 150 000 molecular weight region. KmCa for phosphorylation is much lower (0.2 micron) than for active Ca2+ transport (40 micron) in IOVs. Lanthanum induced phosphorylation (up to 250 micron Lafree) is significantly greater than Ca2+-induced phosphorylation. Hg2+ inhibits both Ca2+ and La3+ induced phosphorylation. Ca2+-induced labelling can be rapidly "chased" by unlabelled ATP+Mg2+, but not with EGTA+Mg2+. Dephosphorylation in Ca2+ phosphorylated membranes and IOVs is significantly inhibited by La3+. It can be concluded that the mechanism of La3+ and Hg2+ inhibition of the Ca2+ pump is different in intact cells and isolated membranes or Iovs.


Hepatic gluconeogenesis in chickens.

Hepatic gluconeogenesis in chickens. Gluconeogenesis by isolated hepatocytes resulted in glucose release but insignificant rates of glycogen synthesis. The effectiveness of precursors was similar for hepatocytes from fed and starved chickens except for impaired gluconeogenesis from pyruvate when compared to lactate in lactate starved chicken hepatocytes. The impairment was caused by limitations in cytosolic NADH production as a result of the mitochondrial location of phosphoenolpyruvate carboxykinase in chicken liver. The order of effectiveness of precursors on hepatic gluconeogenesis was generally similar to the effects of precursors on increasing the plasma glucose concentration in vivo. The exceptions were caused by interactions with other precursors in vivo. The alteration of the NADH/NAD+ ratio by ethanol and ATP/ADP ratio by adenosine could play significant roles in the control of precursor conversion to glucose. Physiological glucagon concentrations stimulated gluconeogenesis from precursors entering the pathway both above and below the level of triose phosphates, and its effect were mimicked by dibutyryl cyclic AMP. Previous results on the effects of precursor and glucagon injection on the plasma glucose concentration of chickens in vivo can largely be explained by effects at the hepatic level. Isolated chicken and rat hepatocytes share many common features. Qualitatively the ordering of gluconeogenic effectiveness was similar but quantitive differences existed as a result of differing activities and cellular locations of enzymes. Neither preparation readily synthesised glycogen and the sensitivity to glucagon was similar.


The drug metabolism systems of liver and liver tumors: a comparison of activities and characteristics. Transplantable rat liver tumors 5123 t.c., 7288 ct.c., 5123 t.c.(H) and the Novikoff hepatoma have active mixed function oxidase systems capable of metabolizing a variety of drug and polycyclic hydrocarbon substrates. The tumor drug metabolism systems are at best 20% as active as rat liver. The tumor drug metabolism activities are induced by pretreatment with phenobarbital or beta-naphthoflavone and can be inhibited with specific inhibitors such as carbon monoxide or 7,8-benzoflavone. Tumor drug metabolism systems appear to consist of cytochrome P-450 and cytochrome P-450 reductase. The properties of the two protein components from tumors are highly similar to the corresponding components of the liver drug metabolism system. Cytochrome P-450 reductase has been at least partially purified from the Novikoff hepatoma and hepatoma 5123 t.c.(H). The kinetic and physical properties of the tumor reductases are similar to those of the liver reductase except that the Km of hepatoma 5123 t.c.(H) reductase, but not of the Novikoff hepatoma reductase for NADPH, is elevated an order of magnitude over the Km of the liver reductase. The mechanism for the interaction of electron donor and electron acceptor with liver or tumor reductases seems to be a sequential reaction mechanism. Experiments on the NADP-inhibition of the interaction of NADPH and cytochrome c with liver reductase indicate that NADP is competitive with NADPH and noncompetitive with cytochrome c. This result is consistent with the postulate of a sequential reaction for NADPH-cytochrome P-450 reductases of liver and tumors. These data support the conclusions that an active drug metabolism system is present in liver tumors and that the tumor systems are constituted like the liver system.


[Three levels of structural organization of the eukaryotic chromosomes]. Three levels of structural organization of eukaryotic DNA in the cell nucleus are considered in this paper: (i) the chain of nucleosomes; (ii) the solenoidal or superbead (nucleomere) model of compactization of the nucleosomal fiber; (iii) the mode of suprasolenoidal DNP-packing--loops or domains. Recent results bearing on the relation of these three levels to functional activity of chromatin are also discussed.


[Charge separation in bacterial photosynthetic reaction centers]. The physical aspects of the primary charge separation process in bacterial photosynthesis are discussed. The donor-acceptor model of electron tranfer through proteins is used. The kinetics of the processes of the photosynthetic reaction centers are considered and their energetic scheme is constructed by means of the nonequilibrium density matrix method. It is shown that the theory is in good agreement with experiment if one takes into account the influence of vibrational sublevels of states which take part in transitions.


[Soluble complexes of bovine serum albumin with linear polyelectrolytes]. Interaction of bonive serum albumin with copolymers 2-methyl-5-vinylpyridine, acrylic and methacrylic acids in different proportions in aqueous solutions was studied. It was shown, that in a wide range of ration of the components soluble cooperative complexes were formed. Ability of amphotheric copolymers to form complexes with bovine serum albumin depend both on the composition of the copolymers and on the pH of the medium. The non-polar interactions of the protein globules with hydrocarbonic 2-methyl-5-vinylpyridine chain fragments of the polyampholyte play an important role in the association of similarly charged particals. It was shown that besides this effect of chain fragments of 2-methyl-5-vinylpyridine a significant contribution in the association is made by non-polar interactions, created by methyl groups in copolymer 2-methyl-5-vinylpyridine and methacrylic acid. The association mechanism and structure of the formed complexes was studied. It was shown that complex formation is accompanied by non-equal distribution of the chain copolymer between the protein globules and appearance of asymmetric particles of the complex. A correlation between the ability of polyampholytes to bind protein and their physiological action was found.


[Single copy and repetitive DNA sequences of Echinodermata. I. Arrangement of DNA sequences of different multiplicity]. Arrangement of repetitive and single copy DNA sequences in the DNA of 8 Echinodermata species (sea urchins, starfishes and sea-cucumber) has been studied. Comparison of the reassociation kinetics of short and long DNA fragments assayed by hydroxyapatite binding indicates that the pattern of DNA sequence organization of all these species is similar to the so called Xenopus pattern found in genomes of most animals and plants. Interspecies differences consist mainly in the quantities of sequences of various repetition degrees and their interspersion with each other and with single copy sequences.  Measurements of the size of S1 nuclease resistant reassociated repetitive sequences show variability in the relative quantities of long and short repetitive sequences of different species. Difference in the arrangement of single copy and repetitive sequences between Echinodermata species are not related to their evolutionary proximity.


[Structural peculiarities of the nucleic factor from ascitic fluid of tumors]. Several characteristics of the nucleic factor of tumors which is thought to play an important role in suppression of tumor immunity was investigated. This nucleic factor differs from native double-stranded DNA of eukaryotic nuclei by base composition (A: T: G : C = 1: 1.44 : 0.91: 0.69); its affinity to GAP and hyperchromic effect were lower than those in native DNA. Heating above 80 degrees in 1 N KOH destroyed the nucleic factor to fragments that could not be detected in 8% PAK electrophoresis. The results of this and previous reports lead us to a hypothesis that the nucleic factor is a DNA molecule consisting of single- and double-stranded regions, as well as short insertions of RNA. The double-stranded regions in this molecule possess non-parrallel breaks.


[Simulation of DNA conformation possibilities by means of nonbonded interaction energy calculations of complementary dinucleoside phosphate complexes]. Nonbonded interaction energy calculations were performed for complementary deoxydinucleoside phosphate complexes dApdA with dUpdU and dUpdA with dUpdA. All dihedral and bond angles but nitrogen base angles were the variables in minimization of energy. Complex conformations resembling A- and B-family double-helical conformations were recieved as a result of calculations when intramolecular interaction energy approach minima. Dihedral angles of one molecule of the complex may differ from corresponding angles of another by several degrees. Energy optimal complex conformations in other space regions of conformation parameters were found. Biological consequences of possible dihedral and bond angle changes of double stranded nucleic acids at interactions with other molecules are discussed.


Pathology of adult respiratory distress syndrome. The morphology and sequential evolution of the pulmonary lesions in respiratory distress syndrome have been reviewed. Reasons have been presented to support the conclusion that these lesions are in the main produced by toxic effects of oxygen rather than the underlying disease process which initiated the episode of respiratory failure. The mechanism of oxygen toxicity has been briefly reviewed. The implication of these considerations is that in any patient with acute respiratory impairment, oxygen should be used as therapy only if it is required to prevent death from hypoxia and should be used in the lowest possible effective dose. As the patient improves and arterial oxygen tension rises this dose should be promptly reduced.


[A comparative study of Dicrostonyx torquatus chionopaes Allen DNA with different numbers of B-chromosomes]. In order to elucidate the possible relationship between the karyotype and the polynucleotide sequence organization in DNA, comparison was made between DNA from the liver of Dicrostonyx torquatus chionapaes Allen with different numbers of B-chromosomes (2n = 47-49, 1-3 B-chromosomes; 2n = 52-54,6-8 B-chromosomes). The reassociation kinetics patterns for denatured DNA fragments (about 300 nucleotides long) were obtained by the batch hydroxyapatite method. The analysis of these patterns showed a approximately 10% increase in the proportion of reiterated nucleotide sequences in the DNA of animals with 6-8 B-chromosomes. The increase in the proportion of reiterations in DNA correlated with increase in the number of B-chromosomes can be regarded as an indirect confirmation of the heterochromatic nature of B-chromosomes. The individual fractions of reiterated nucleotide sequences (C0t = 1.0) were isolated from studied DNas. The reassociation kinetics of these fractions and the thermostability of resulting duplexes were examined. The revealed differences are indicative of a certain dissimilarity in the polynucleotide sequences organization that correlate with variation in the number of B-chromosomes. The heterochromatic and euchromatic. DNAas from the liver cell nuclei of animals carrying different numbers of B-chromosomes were studied by thermal denaturation analysis and neutral CsCl equilibrium centrifugation. In the heterochromatic DNAs from livers of D. t. chionopaes with 6-8 B-chromosomes additional components enriched with AT-pairs were revealed. The specific features of DNA correlated with increase in the number of B-chromosomes are discussed in connection with peculiarities of B-chromosomes behaviour and their evolution in Dicrostonyx torquatus chionapaes.


[Investigation of the structure of magnesium and lithium salts of T2 phage DNA by the method of x-ray diffraction. The possible mechanisms of the participation of cations in the structural transformation of double-stranded DNA]. The secondary structure of DNA is known to be largely determined by the kind of counterion bound to it. We have used the X-ray diffraction method to study the structure of magnesium and lithium salts of T2 phage DNA in oriented fibres. The structural behaviour of this glucosylated DNA in the form of magnesium and lithium salts was shown to be identical to the behaviour of the same salts of "normal" calf thymus DNA throughout the studied range of relative humidities (44-95%). However these two DNAs in the form of sodium salt are known to behave quite differently. One can presume that Mg2+ and Li+ influence the structural behaviour of double-stranded DNA so effectively as to be able to "ignore" the fact that T2 phage DNA contains glucoside residues. The results of this work and the already known facts concerning the structure of DNA in the form of various cation salts (in solution and in "solid" fibres) indicate that the structural behaviour of double-stranded DNA is mainly determined by the cation located in the region of the narrow groove of the double helix. If cations are graded according to the efficiency of their influence on the structural behaviour of DNA in fibres, the scale will coincide with that of their DNA-binding strength in water solution, that is: Mg2+ greater than Li+ greater than Na+ greater than K+ greater than Rb+. A qualitative consideration of electrostatic interaction between the cations and the negatively charged DNA strands leads one to suppose that this interaction must obstruct the transition of individual DNA molecules from the B-form to the A-form. Aggregation of self-aggregation of DNA molecules is presumed necessary to enable them to adopt the A-conformation.


Comparative studies of chromosomal aberration and mutagenicity of the trivalent and hexavalent chromium. The comparative cytogenetic and mutagenic effects between trivalent and hexavalent chromium were investigated. Five chromium compounds, K2Cr2O7  and K2CrO4 containing Cr6+, and Cr(CH3COO)3, Cr(NO3)3 and CrCl3 containing Cr3+, were examined for their ability to induce chromosomal damage in cultures of human leukocytes, for their reactivity with DNA by a rec-assay system and for mutagenicity in the E. coli Hs30R test system.  Chromosome-breaking activity was significantly higher for the compounds with hexavalent than trivalent chromium, the efficiency being in the decreasing order K2Cr2OM greater than K2CrO4 greater than Cr(CHCOO)3 greater than Cr(NO3)3, CrCl3. In the rec-assay and mutation assay, hexavalent (K2Cr2O7 and K2CrO4) and trivalent Cr(CH3COO)3) compounds gave positive results, their mutagenic potential being higher in the same order of clastogenic magnitude.


[Structural organization of the genome of bacteriophage T5 by specific endonucleases]. The DNA of Bacteriophage T5+ has been treated with restriction endonucleases EcoRI, HindIII, BamI, SmaI, PstI, SalI, KpnI and the electrophorectic pattern obtained in agarose gel has been analyzed in order to localize the specific cleavage sites on the T5 DNA. The localization of cleavage sites has been resolved from the electrophoretic pattern of double and partial digests, the digests of isolated restriction fragments and the digests of deletion mutant T5 st(O) DNA. Four BamI cleavage sites have been found and localized on the physical map of T5 DNA at 0.225; 0.68; 0.715 and 0.725 fractional lenght. Endonuclease PstI cuts T5 DNA at 11 sites: 0.095; 0.215; 0.320; 0.510; 0.635; 0.675; 0.710; 0.770; 0.810; 0.840; 0.875 fractional length. Six KpnI cleavage sites have been mapped at 0.140; 0.160; 0.530; 0.720; 0.760; 0.840 fractional length. 14 out of 17 HindIII cleavage sites have been localized at 0.10; 0.24; 0.255; 0.345; 0.40; 0.52; 0.54; 0.57; 0.70; 0.76; 0.80; 0.84; 0.87; 0.89, fractional length of T5 DNA. Complete cleavage map of the phage genome is presented for seven restriction enzymes.


[Kinetics and equilibrium of reactions between nucleotides and methylol derivatives of beta-alanine]. The rate constants of forward and reverse reactions between methylol derivatives of beta-alanine and deoxycytidine 5'-phosphate, deoxyadenosine 5'phosphate and deoxyguanosine 5'phosphate and the equilibrium constants of these reactions were determined by the spectrophotometric method at 39,5 degrees C and pH 6,95. Besides, the equilibrium constant of the reaction between beta-alanine and formaldehyde was determined. Unlike deoxycytidine and deoxyadenosine 5'-phosphates, interaction of deoxyguanosine 5'phosphate with methylol derivatives is more complicated. A model proposed for the interaction of deoxyguanosine 5'phosphate with methylol derivatives explains the behavior of this nucleotide in the reaction. The kinetic and equilibrium constants of the interaction of methylol derivatives with nucleotides investigated exceed by two or three orders of magnitude the corresponding constants of the interaction of formaldehyde with these nucleotides.


[Electronic-conformational interactions of molecular-biological systems. I. Quantum-chemical aspect of the theory of electronic-conformational interaction]. Electronic-conformational interactions (ECI) are the main causes of enzymatic catalysis and other biological processes, occuring at the molecular and super-molecular levels. For the studies of several problems, related to ECI the qualitative methods of quantum chemistry can be used, in particular the method of intermolecular orbitals. The possibilities of this method are shown in some simple cases.


Cytogenetic toxicity of gentian violet and crystal violet on mammalian cells in vitro. The cytogenetic toxicity of gentian violet in Chinese hamster CHO cells in vitro has been studied by analyzing (1) squash preparations from direct fixation for recording mitotic anomalies and (2) air-dried preparations (with colcemid--hypotonic pretreatments) for recording metaphase chromosome aberrations. It was concluded that this compound is a mitotic poison as well as a clastogen in vitro. Its clastogenic property was confirmed in 5 other different mammalian cel types. 10 samples of different gentian violet and crystal violet were surveyed and all were shown to be clastogenic. Unless in vivo studies prove otherwise, gentian violet and crystal violet should be regarded as biohazardous substances.


Cytogenetic effects of styrene and styrene oxide. Styrene and styrene oxide induce various cytogenetic effects, similar in both human lymphocytes in vitro and onion root-tip cells in vivo. Styrene appears to cause chromosome breakage in both systems, and in Allium it shows a strong c-mitotic effect. Styrene oxide, on the other hand, seems to destroy the tertiary folding of the chromatin. Cytotoxicity of styrene oxide is very high (complete mitotic inhibition occurs on 0.03% v/v) in human lymphocytes, whereas, in Allium, styrene is slightly more toxic than styrene oxide. Styrene glycol, a further metabolite of styrene oxide, does not cause mitotic inhibition.


Cytotoxic effects of toximul MP8 in human lymphocytes in culture: a preliminary investigation. Toximul MP8, a commercial emulsifier formulation, has been used for a number of years to spray forest trees infested with spruce budworm with the organophosphate insecticides, Fenitrothion and Phosphamidon. To assess its cytotoxic effects on human lymphocytes varying amounts of Toximul MP8 were added to human whole blood (0--50 ppm) and cultured along with phytohaemagglutinin for 52h. At the end of the culture period cytotoxicity to human lymphocytes was assessed by (1) mitotic index, (2) DNA labelling index and (3) the frequency of chromatid breaks. The cytotoxic effects were apparent even at the lowest concentration tested, i.e., 10 ppm. A significant dose-dependent decrease in the mitotic and DNA-labelling indicies was observed. Toximul MP8 also produced a significant level of chromatid breaks even at 10 ppm.


Cytogenetic effects of inhaled ozone.

Cytogenetic effects of inhaled ozone. We have repeated as closely as possible the experiments of Zelac et al., who observed significantly elevated levels of chromosome aberrations in short-term cultures of peripheral lymphocytes from Chinese hamsters that had inhaled ozone. Unlike Zelac et al., we observed no increase in chromosome-type aberration levels, though a small increase in chromatid-aberration levels similar to that reported for exposed human subjects by Merz et al. was seen. No increase in the levels of any chromosomal aberration type was seen in parallel direct bone-marrow preparations. Sister-chromatid exchange (SCE) levels and cell-replication rates, which were determined in the Chinese hamster peripheral lymphocyte cultures and also in bone-marrow samples from similarly treated mice, failed to show any ozone-induced changes.


Chromosome studies on blood lymphocytes of men occupationally exposed to cadmium. Chromosome studies were carried out on peripheral blood lymphocytes from a population of 40 men occupationally exposed to cadmium salts for periods up to 34 years, and on 13 on-site controls. Although four chromatid interchanges were observed in 3740 cells from the exposed workers and none in the 1243 cells from controls, there was no significant difference in aberration frequency between the two groups. Possible reasons for contrasting findings on the chromosome-damaging effects of cadmium in other published reports are discussed, and the possibility that heavy metals might act synergistically to enhance the mutagenicity of other compounds present in the environment is considered.


Retinoids induce sister-chromatid exchanges in human diploid fibroblasts. Vitamin A palmitate, retinoic acid and an aromatic retinoic acid analogue (Ro 10-9359) induced sister-chromatid exchanges (SCE) in human diploid fibroblasts. The same SCE level was reached with the 3 compounds tested, when the concentration of vitamin A palmitate was 10 times higher than those of retinoic acid and Ro 10-9395. No correlation was found when the dose-related SCE induction of a retinoid was compared with the respective antineoplastic activity as reported by others.


Sister-chromatid exchanges induced in rabbit lymphocytes by 2-aminofluorene and 2-acetylaminofluorene after in vitro and in vivo metabolic activation. Because short in vitro treatments of Chinese hamster cells with 2-aminofluorene and 2-acetylaminofluorene did not increase SCEs even in the presence of a metabolic activation system, experiments were carried out with rabbits to see if in vivo activation occurred. Rabbits injected with 2-AF could activate the compound and a transient dose-dependent increase in SCEs was found in peripheral lymphocytes cultured at various times after the injection. With 2-AAF, however, the response was more variable: some rabbits showed an increase immediately, but one showed an increase only after a subsequent injection. This indicated that among rabbits differences exist in their ability to detoxify 2-AAF. Because rabbits could activate the compounds, in vitro experiments were carried out to see if their lymphocytes responded differently from Chinese hamster cells and to see if the metabolic changes brought about by PHA stimulation affect the ability of the cells to activate the chemicals. The addition of PHA and the consequent metabolic stimulation do affect the induction of enzymes involved in the activation of 2-AF and 2-AAF. Benzo[alpha]pyrene, in contrast, can be activated by rabbit lymphocytes independently of PHA stimulation.


Role of opportunistic fungi in ocular infections in Nigeria. The importance of opportunistic fungal pathogens in causing ocular infections is emphasized. A study was conducted over a period of 4 years (1974--1977) to investigate the role of opportunistic fungi in causing mycotic keratitis and to elucidate certain aspects of epidemiology of this disease in Nigeria. Fifty-nine cases of corneal ulcers of suspected mycotic etiology were investigated. Fungal etiology was confirmed in 42 of these cases. The predominant etiological agent was Fusarium solani in 14 cases (33.33%) followed by Penicillium citrinum in 8 cases (19.04%) and Aspergillus fumigatus in 5 cases (11.90%). The yeasts were responsible for only 3 cases (7.14%) i.e. one each caused by Candida albicans, C. parapsilosis and C. guilliermondii. Among the remaining 12 cases, one was caused by F. moniliforme, 3 by A. flavus, 2 each by A. niger, Penicillium expansum and Penicillium sp., and one each by Cladosporium cladosporioides and Cladosporium sp. The clinical features of the cases are briefly described. The incidence of mycotic keratitis in relation to sex, age, occupation, trauma and other factors has been analysed. Corneal trauma appeared to be an important predisposing factor as 27 (67.28%) of the patients gave a history of injuries to the eye. Notably, a large number of patients were farmers and trauma was most often from palm tree leaf, thorn, kernel or other plant objects. Topical application of corticosteroids or broad spectrum antibiotics did not seem to play an important role in the etiology of keratomycosis. Cases were recorded throughout the year although the number of cases was higher in the months of March--May, and November--December than that during the rest of the year. The isolates of the causative agents were studied in detail for their morphological and cultural characters. The isolates of F. solani grew well at 37 degrees C and survived at 40 degrees C for more than 3 weeks. In vitro drug sensitivity tests indicated good antifungal activity of pimaricin and econazole for F. solani, clotrimazole and econazole for Aspergillus fumigatus. A. flavus and Penicillium citrinum, and 5-fluorocytosine for Candida spp. Investigations on the incidence of fungi in normal healthy eyes of 450 persons comprising 204 adults and 246 children yielded 204 isolates belonging to 21 genera of fungi. Cladosporium was most frequent (12.88%) followed by Penicillium (10.22%) and Aspergillus (6.66%). Another important fungus was Fusarium represented by 10 isolates, viz. 4 of F. solani, 2 of F. moniliforme, 1 of F. exysporum, and 3 of Fusarium sp. The yeasts were represented by two isolates each of Candida tropicalis, C. pseudotropicalis, C. krusei, Trichosporon sp and Cryptococcus albidus, and one of Candida guilliermondii. Successive culturing of fungi from normal eyes in a small group indicated that fungi occur in the outer eye generally as transients. The epidemiology of mycotic keratitis has been discussed in relation to the present findings and in comparison with observations of other investigators.


Mycotoxicoses of animals.

Mycotoxicoses of animals. Mycotoxicoses are intoxications caused by ingestions of foodstuffs contaminated with mycotoxins, i.e. toxic secondary metabolites of microscopic filamentous fungi (moulds). By field observations and by experimental testing, toxins or toxic strains of more than 100 species of fungi have been encountered. However, causal associations have so far only been established for a small number of mycotoxicoses in farm animals, and the more important mycotoxicoses are aflatoxicosis, facial eczema, mycotoxic nephropathy, and estrogenic syndrome. A full assessment of the impact of mycotoxins on the health of farm animals can hardly be made at present, because the amount of surveillance data from mycotoxicoses is very limited, due mainly to inadequate diagnostic criteria. A new set of criteria for the diagnosis of mycotoxicosis is proposed, which has been successfully applied in the causative study of mycotoxic porcine nephropathy.


Renin release and the refractoriness to acute renal failure of rats recovering from prior renal failure. Renin substrate concentrations and the release of renin in response to the rapid removal of 15 ml/kg weight blood or subcutaneous administration of 500 microgram/kg body weight isoproterenol were measured in control rats and animals recovering from prior myohemoglobinuric acute renal failure (recovery rats). Blood for these assayas was drawn from chronically implanted aortic catheters, obviating the need for animal handling and anesthesia. Baseline plasma renin titers of recovery rats were modestly elevated but renin substrate concentrations were the same as in controls. Hemorrhage produced equivalent changes in blood pressure and plasma renin titer in the two groups. Isoproternol injection in recovery rats caused a somewhat greater blood pressure fall and almost twice the rise in plasma renin concentration observed in control rats. The marked resistance of recovery animals to a second bout of acute renal failure thus cannot be attributed to impaired renin release or inadequate plasma renin substrate.


Lack of inhibition of hog renin by heparin. These experiments were performed to test if heparin inhibits the production of angiotensin I from rat renin substrate acted upon by either rat or hog renin. Substrate was prepared from the plasma of nephrectomized rats; commercially prepared hog renin and heparin (0-50 units/ml, final concentration) were added and angiotensin I production was measured by radioimmunoassay following incubation of the mixture at 37-38 degrees C for 30 min. Heparin had no effect on the radioimmunoassay for angiotensin I, nor on the Vmax nor the Km of the renin-renin substrate reaction. Heparin (0 and 50 units/ml, final concentration) was added to rat plasma which contained renin and renin substrate. No effect of heparin on the rate of production of angiotensin I was observed in this system. In conclusion, rat and hog renin are not inhibited by heparin within the range of concentrations used.


Normotensive hyperreninemia in systemic lupus erythematosus. An indicator of tubular dysfunction. High plasma renin activity (PRA) was found in 16 of 42 randomly selected nonuremic systemic lupus erythematosus (SLE) patients. Mild hypertension was present in 3 of the 16.6 high-PRA and 10 normal-PRA patients were admitted to a metabolic ward. Salt restriction produced a disproportionate rise in both PRA and aldosterone, a decrease in glomerular filtration rate (GFR) and a slightly greater negative sodium balance in the group with high PRA. Potassium excretion was less than intake in both groups. Balance studies were performed in 6 additional high-PRA patients before and during indomethacin administration (150 mg/24 h). PRA and aldosterone were markedly suppressed by indomethacin. UnaV was significantly greater than in the control period despite of the 28% reduction in GFR. These results suggest that high PRA is secondary to impaired distal tubular sodium reabsorption. Such a defect could be responsible for the relatively low frequency of hypertension in lupus nephritis.


Middle molecules re-examined.

Middle molecules re-examined. Evidence for and against the presence and pathophysiologic importance of middle molecules in uremia is reviewed. The evidence favors both their presence and importance.


Effects of ultrafiltration of diffusion and convection in two newer coils. Clearances of sodium and B12 were measured with increasing ultrafiltration in two newer coils with new types of membrane support. In all other coil studies previously reported, clearance increases with ultrafiltration did not equal predictions from contributions of convection implying simultaneous decreases in diffusive solute transport with increasing transmembrane pressure. Such deterioration was attributed to masking of membrane surface area by the membrane support, widening of blood channels, and/or channeling of dialysate flow. In these newer coils, clearance increases were very near to predicted enhancement by convection while diffusion was stable in one type and decreased only modestly in the other. Coil volumes assessed with the kerosene technique increased with higher transmembrane pressure similar to findings in previous coils studies. Thus, although coil blood path dimensions are altered with increasing pressure as in older coils, diffusive clearances remain stable and increases in total clearances equal that predicted from convective solute transport. These results suggest that membrane masking is probably the major mechanism for decreases in diffusion with ultrafiltration in other coils and that the problem has been minimized with improved membrane supports.


Stenosing renal artery disease in children: clinicopathologic correlation and results of surgical treatment. From 1955 to 1977, 27 pediatric patients underwent surgical treatment for renovascular hypertension. Renal artery disease was most commonly caused by intimal or perimedial fibroplasia and occurred bilaterally in 7 patients. Overall results were 16 patients cured (59%), 5 patients improved (19%) and 6 failures (22%). The best results were obtained in children with unilateral renal artery stenosis. In recent years, ablative surgery has been largely supplanted by reconstructive vascular procedures in the treatment of this disease in children. Autogenous vascular bypass grafts have been most successful and aortorenal reimplantation may occasionally be employed. Renal autotransplantation should be reserved for children with the middle aortic syndrome or multiple lesions involving the branches of the renal artery. Splenorenal bypass and segmental resection with renastomosis have yielded poor results and are best avoided in this age group. Primary nephrectomy should only be performed in patients with renal atrophy or uncorrectable branch vessel disease. Renovascular hypertension in children is a potentially curable disease and revascularization with preservation of renal function should be the combined objectives of surgical therapy in the most cases.


Bacterial populations of the small intestine in uremia. The small intestinal bacterial flora of 15 patients with chronic renal insufficiency was compared with that of subjects with blind loop synDROME. 9 patients were on regular hemodialysis with high protein intake and 6 (serum creatinine 7.5 to 12.5 mg/dl) were maintained on low protein diet. The chronic renal patients harbored a greatly increased microbial flora of both anaerobes and aerobes in the duodenum and jejunum, quantitatively comparable to those in blind loop subjects. The composition did not differ significantly in the two groups. Some organisms may have the potential to metabolize substrates which reach the intestinal lumen from the diet and bile, and perhaps to generate toxic metabolites that could contribute to uremic toxicity or malabsorption.


Endocytosis: a property of the glomerular visceral epithelial cell. The sequential intravenous injections of protamine and heparin into rats results in the deposition of protamine-heparin aggregates along the lamina rara externa of the glomerular basement membrane. Morphologic studies indicate that these foreign aggregates are removed from the glomerular basement membrane by virtue of phagocytic activity by the glomerular visceral epithelial cells. We have studied the disappearance rate of protamine-heparin aggregates from the glomerular basement membrane in animals given a single dose of these compounds and in animals receiving chronic administration. The disappearance rate was measured utilizing a computerized morphometric technique to determine the numerical density of protamine-heparin aggregates per 100 micrometer glomerular basement membrane in sequential biopsy specimens taken from 15 to 600 min post-injection. The disappearance rate described a linear function in both acute and chronic animals, with a half-disappearance time of approximately 120 min. Disappearance of the aggregates appeared to be due to epithelial cell phagocytosis. This model provides a method of studying this function in the intact glomerulus in both normal and disease states.


Lysine in treatment of hyperornithinemia. A metabolic study in a case of hyperornithinemia with gyrate atrophy of choroid and retina is presented. It is demonstrated that the lysine-ornithine antagonism is a physiological, safe, easy to handle therapeutic tool in hyperornithinemia. A lysine load was invariably associated with a reduction of plasma ornithine concentration. This happened at any level of protein intake. It was also shown that diets containing a low protein intake are invariably associated with negative nitrogen balance.


Hypothalamic dopamine-beta-hydroxylase activity: fluctuations with time of day and their modifications by intracranial surgery, adrenalectomy, and pinealectomy. Hypothalamic and plasma dopamine-beta-hydroxylase [DBH, EC 1.14.2.1] activites were measured by a coupled radioenzymatic method. Animals representing five experimental groups [intact controls, adrenalectomized, pinealectomized, adrenalectomized pinealectomized, doubly sham-operated] were killed and sampled at 8 times through the 24-hr daily cycle, 15 days postoperation, and at 50-52 days of age. Hypothalamic DBH in intact control animals had statistically significant fluctuations in relation to time of day. These changes were lost or dampened in groups that had had intracranial surgery and were characteristically shifted by adrenalectomy, either alone or with pinealectomy. Plasma DBH fluctuations in the same animals resembled those in hypothalamus in some features (e.g., peak near mid-dark; shift in daily maxima and minima after adrenalectomy) and differed in others [e.g., no effect of intracranial surgery or of sham operation; adrenalectomized pinealectomized animals resembled the solely pinealectomized]. Although temporal patterns in hypothalamic DBH activity thus differed in the experimental animal groups, the daily means of hypothalamic DBH activity were similar.