Relationship between addict crime and drug treatment: two cohorts examined. Patient samples from methodone maintenance and detoxification programs are examined for their patterns of criminal activity before, during, and after treatment. Demographic, sociological, and criminal history variables are tested for their ability to account for changes in arrest patterns over time. While the number of arrested decline after entering treatment, certain groups remain at high risk of arrest and/or confiction. Patterns of crime as measured by official arrest statistics do not appear stable over time for the treatment cohorts.


Self-concept and completion of treatment for heroin and nonheroin drug abusers. One hundred sixty-one veterans with a history of drug abuse were administered a battery of background questions as well as self-concept measures prior to entering a Substance Abuse Unit at the VA Hospital in Miami. Significant interaction effects were found whe a 2 X 2 analysis of variance was run using heroin/nonheroin as one factor and completer/dropout as the other. Nonheroin drug abusers who subsequently completed treatment entered the program with the lowest self-concepts, highest ideals (with respect to the self), and were most often high school dropouts. Nonheroin drug abusers who eventually dropped out of treatment entered with relatively high self-concepts, low ideals, and were more often high school graduates. On the other hand, heroin users showed the opposite trend. Heroin users who eventually completed treatment began with higher self-concepts, lower ideals, and more education than the heroin users who became dropouts. It is suggested that a generalized feeling of optimism and motivation surrounds the completer, while the dropout seems to lack such drive.


On the reality of hierarchy in a drug-free program. This paper sets forth qualitative and quantitave indicators of hierarchy as presumably experienced by members of a drug-free program. We argue that the staff's expectations concerning such hierarchy and its role in rehabilitation may be given an objective rendering without necessarily distorting members' views or treating them as mere reflections of the staff's.


Drug abuse and suicide.

Drug abuse and suicide. This paper examines the relationship between drug abuse and suicide. It attempts to assess the extent of suicidal thoughts or behaviors among a group of drug abusers. The research examines variables related to self-destructive or self-endangering behaviors, such as accidental overdoses, arrests for driving under the influence, and auto accidents in which the subject was the driver. These data were examined in relation to reports of suicidal thoughts and actual suicide attempts. The results indicate a suicide attempt rate at least 12 times greater than expected for the general population. The results also indicate significant correlations between suicidal thoughts and suicide attempts, suicidal thoughts and nonsuicidal overdoses, and arrests for driving under the influece of drugs or alcohol and nonsuicidal overdoses. The implications of these results along with the role of depression as discussed.


The ethnic variable and problem drinking in a select sample of southwestern two-year multicultural college students. Five hundred and ninety-two Anglo, Mexican American, and American Indian students from nine selected 2-year colleges in the Southwest were given a self-administered questionnaire with items related to problem drinking (dependent variable) and various social psychological and demographic information (independent variables). Analyses included discriminant analysis, chi square, and eta. While ethnicity per se contributed little to the discrimination of problem from nonproblem drinkers, several other variables provided an overall correct classification (discrimination) rate of 79.73%. There variables were, in order of discriminating power: neighborhood people drink, veteran status, live life differently, close friend with drinking proble, drink because acquaintances drink, and age. It is hypothesized that the psychological principle of individual differences, and the significance of some other study variables, may haver overshadowed any ethnic effect. Measurement problems in this area are discussed as well as some potential research directions.


Staff drinking patterns and approach to patient drinking problems within a psychiatric hospital. Previous studies at this VA hospital had indicated considerable evidence of "serious problem drinking" among the psychiatric patients. Mailed questionnaires to 344 treatment staff members assessed their attitudes toward and recommended approach to this problem as a function of job classification and personal drinking patterns. Results indicated that physicians, psychologists, and social workers favored a "therapeutic" approach to the problem, while nurses and nursing assistants advocated "punitive" measures. Interestingly, staff members who reported light or moderate personal drinking recommended additional therapy for these patients, while staff members who reported personal abstinence or heavy drinking generally suggested punitive actions.


The effectiveness of a treatment program for the alcohol-involved driver. The Don't-Drink-and Drive Program (3-D) is a classroom and behind-the-wheel, 3-day curriculum designed for court-referred drinking drivers, mostly first offenders. The curriculum is not an abstinence program but designed for the so-called social drinker, most of whom will in all probability continue to drink. The 1-year driving record of 876 3-D graduates was compared with 802 drivers exposed only to the usual court procedures of probation and fine. It was found that the "no-treatment"groups had 78% more alcohol-related violations, 23% more moving violations, 40% more suspensions of licence, and 34% more accidents. The importance of quasi-experimental designs in accident research is discussed.


Carisoprodol dependence: a case report.

Carisoprodol dependence: a case report. Although known to have central nervous system effects comparable to those of meprobamate, carisoprodol has not previously been reported to be a dependence-producing drug. This case report is of a woman, previously addicted to other drugs, who became dependent on carisoprodol.


[Determination of metal dusts in aerosols using x-ray fluorescence. Comparison with other analytical methods]. Determination of metals in aerosol collected as thin layer on membran filters has made employing X-ray fluorescence. Standards are prepared in suitable chambers: dust collected on membran filter is weighted. The problems of methodology are discussed. Calibration curves have been prepared for Pb - Fe - Cd - Si; comparisons have been made with other methods employing atomic absorption spectroscopy.


[Control of occupational exposure to benzene in a chemical plant]. Later on detection of several cases of acute myelotoxic intoxications the use of benzene as a solvent has been banned in Italy since 1963 (Law n. 245). Its consumption has therefore been confined to synthesys processes in petrolchemical industry. The hazards arising from the operations performed in an open air chemical plant which produces alkylbenzene were monitored by the AA. The synthesis occurs in a closed system which provides opportunities for benzene exposure during filling, control and maintenance operations. Nine environmental samples out of 10 showed benzene concentrations above 10 ppm with peaks up to 110 ppm. Long term air sampling showed values ranging from 12 to 75 ppm. Urinary phenol elimination has been measured showing values above 50 mg/1 for approximately 20% of workmen. The difficulties pertaining to an adequate control of benzene exposure in chemical plants are discussed. Being skin contact a mode of entry of apreciable concern, the AA. stress out that priority in exposure monitoring should be given to biological tests such as urinary phenol level and benzene concentration in expired air measurements.


[Industrial pollution by solvents with special reference to limited values for mixtures]. The report concerns the AA. experience in the field of pollution due to solvents, particularly in the following industries: shoe manufacturing, graphics and the production and application of paints. The exposure risk in these 3 indutries is quantitatively and qualitatively defined based on data obtained from the gas--chromatographic analysis of 238 work environment samples. The data are evaluated with reference to limit values established by the ACGIH, the Italian Society of Occupational Medicine and the Italian Society of Industrial Hygiene. In additon to the evaluation with respect to the TLV and VLP, the hygiene parameter of TLVs for mixtures is evaluated in the field of industrial hygiene.


[Risk of absorption of fluoride in electrode arc welding]. The AA. in order to investigate the risk of fluoride absorption examined two factories in which arc-welding electrodes were used. They measured: a) fluoride content in two most used electrodes; b) airborne fluoride concentrations and dustness in the presumed respiratory area of welders with or without fume and dust capture devices; d) airborne fluoride concentrations and dustness three meters away from the welding place during unprotected work with basic electrodes; e) concentrations of fluoride in urine during a workweek in welders (n = 63) and in a control group (n. = 25). The AA. conclude that, in spite of the high teoretical risk of breathing fluoride, the intake of this compound is very low if welders are protected by easy devices.


[Cadmium as an air pollutant].

[Cadmium as an air pollutant]. Daily concentrations of airborne cadmium has been determined for a year in three italian urban areas presenting different characteristics. Results obtained are in the following ranges: Rome, 0,0017--0,0194 micrograms/m3; Venice, 0,0012--0,2234 micrograms/m3 and Marghera, 0,0037--0,704 micrograms/m3. Some data for urban inciniretors emissions are also presented. Origin, effects and legislation concerning airborne cadmium are briefly discussed.


[Risks due to chemical agents in agriculture]. After a few notices about the contribution that chemistry has given for the development of the agriculture in this last century, we give a short description, with a classification supposition, of the main chemical agents used in the agricultural field, for the development and the defence of animal productions and crop-farming. Then, we present national statistical information about the use of chemical means of agrarian interest. We give also a short description of risks caused by chemical agents in agricolture (with hygienic implications concerning consumers also) prefiguring, in conclusion, some hypoteses for the substitution of the chemical mean with alternative techniques and methods.


[Environmental health risks in a marble-working shop]. With regard to the "Inquiry industrial accidents and respiratory pathology of marble workers", promoted by the "Regione Toscana" and being made by the preventive medicine services for workers acting in Massa Carrara and Lucca Provinces, the AA. relate about the sanitary environment conditions in a modern marble manufacture workshop and compare them with the ones in other workshop less advanced from the technological point of view.


[Proposal for threshold limit values for organic solvent concentrations in alveolar air]. The n-hexane concentration was determined in upper factory environmental air and in worker alveolar air. The relationship between the hexane alveolar concentration, and the hexane environmental concentration (Ca/Ci) was found to be steady during the 4,5 hours exposure and independent of the alveolar ventilation and hexane environmental concentration. These results suggest the hypothesis that alveolar TLV's can be fixed for hexane and other solvents.


[Circadian rhythms in urinary coproporphyrin and delta-aminolevulinic acid]. The circadian rythm concerning the excretion of urinary metabolites ALA and CP was investigated. More ALA and CP are excreted in the urine during the day than the night. This phenomenon is more evident with CP. The sampling of urine for biochemical control of saturnism is discussed and the sample collected after 24 h was chosen.


[Chromium concentrations in urine of persons non-occupationally exposed to chromium and its compounds]. The investigation on 316 samples of urine from persons that are not professionally subject to the action of chromium or its compounds, demonstrated the following: - chromium is absent in the 8% of tested people; - average chromium concentration is 6.6 micrograms/l; - maximum chromium concentration is 36.6 micrograms/l. The average chromium concentration with regard to tested people living in the districts of Bergamo, Bolzano and La Spezia (4.21 - 4.16 - and 5.32 micrograms/l respectively) is 40% lower than chromium concentration observed in people living in the districts of Agrigento and Milan. The high rate of chromium elimination in people living in Milan (10,39 micrograms/l) depend upon the high chromium concentration in drinking water of this city (10.40 micrograms/l). In the 78% of urine samples a chromium concentration was found corresponding to or lower than 10 micrograms/l.


[Relation between environmental concentration, urinary elimination and body burden of chromium in occupationally exposed workers]. Biological and environmental monitoring of chromium exposure was carried out on 20 welders working with special electrodes in the manufacture of tank-cars. The workers were divided in groups, according to the different degree of chromium accumulation, which was determined by renal clearance of diffusible chromium. A closed linear relationship between TWA concentration of hydrosoluble chromium in air and urinary excretion of the metal at the end of exposure was observed. The parameters of regression lines in welders with more (clearance 10 ml/min) or less (clearance 5 ml/min) accumulation of chromium suggest that the renal burden influences not only the basal excretion, but also the excretion at the end of exposure. We underline the difficulty in the determination of correct biological limits if we take them from TLV in air. We must at least consider the degree of accumulation in exposed workers too.


[Use of functional telethermography in the diagnosis of some occupational diseases (due to vibrating tools; carbon disulfide; polyvinyl chloride]. The AA. have considered occupational technopathies due to vibrating tools, carbon disulphide and polyvinyl chloride. The functional or organic involvement in the peripheric vascular system, attributable to the disease, has been evaluated by thermographic examinations, carried out in 35 patients, in basal conditions and, when possible, after cold-test. The results have demonstrated that functional thermography may be a reliable tool both in the early diagnosis and in the prognosis of occupational vascular diseases, especially when it can replace more traumatic methods (such as angiography) in the periodic controls: in fact, it can be sufficient to carry out a simple thermoscopy and to compare the result with the previous photo-thermogram.


[Continuous monitoring of polycyclic hydrocarbons in an industrial urban zone: preliminary data]. Polynuclear hydrocarbon pollution is controlled sistematically in an industrial area in Genoa town. Quantitative and qualitative evaluation was carried out by gas chromatographic technique. First results show a remarkable intake of such pollutants in the air. The used sample collection allowed also the evaluation of polynuclear hydrocarbon levels according to the day hours.


[In vitro effect of asbestos fibers on short-term cultures of human lymphocytes]. The endocellular incorporation of asbestos fibres seems to be capable to induce on Chinese hamster cell cultures numerical and structural chromosome aberrations. In the present study asbestos fibres have been added at different concentrations to human cultured lymphocytes which have been harvested at 48 and 72 h, respectively. The results do not show significant difference in the distribution of chromatid and chromosome-type aberrations between the control cultures and the cultures treated with asbestos.


[Industrial hygiene and improvement of the work environment]. The AA. report a series of practical experiments in the following industries: textiles, ceramics, graphics and heavy industry, in order to demonstrate the necessity and utility of industrial hygiene in which an occupational hazard is not simply identified, but rather an improvement of the work environment is undertaken and the results of such a programme are again controlled and evaluated. The data presented lend themselves to a discussion of a preventive nature since, from a comparison of the data before and after modification, the efficacy of the modification itself is evaluated. The efficacy may vary from simple maintenance of equipment to environmental purification procedures and necessity of applying corrective modifications directly by the raw materials.


[Control of refractory dust in the continuous casting of steel]. Dusts from refractory material are indicated as determining steel plant work site pollutions. To reduce the danger from the dustiest operation--the demolition of coating--the A. examines the possibility of technical prevention based not on the individual protection, but on the use of lower content in free silica materials, on operative ways that underexpose the workers and on the aspiration at source of the produced dust.


[Preventive intervention during the planning of a new factory: contribution of an occupational medicine service on installation of a ceramic dye-producing plant]. The control during the planning of a factory is a sort of prevention. For instance, we suggested industrial hygiene standards for a new chemical plant, which have been into account. According to our suggestions they set up a closed factory process, a dust and fumes filtering plant and the water recycle. After some controls outside the factory, lead and dust concentrations were below the maximum allowed levels (30 and 5 mg/Nmc).


[Selection of suitable individual respiratory protective devices in relation to workroom environment]. Adopting individual respiratory protective equipments, even if in those limited situations in which they are justified, must be consequent to a selection related with the nature of the pollutants to which the operator is, or may be, exposed, with the peculiarity of the workroom environment and, lastly, with the degree of security to be achieved. This statement is not to be neglected even if all respiratory protective equipments are fit to meet the suggestions of qualified standard making institutions. The same is to be considered of capital importance in Italy where the lack of legislation as far as omologation is concerned, allows products not fit to guarantee the request for security which are, consequently, not only superfluous, but dangerous for wearers. For these reasons it has been considered useful to illustrate the characteristics and proper application-fields of the most widely spread respiratory protective equipments referring, as far as possible, to the recommendations being prepared on the matter by the CEN (European Committee for Standardization).


[Factors of contagiousness in the epidemiology of hepatitis type B (author's transl)]. Since morbidity of viral hepatitis B is increasing, the causes of diffusion of this infection have been studied. There are several routes of transmission and undoubtedly apparent non-parenteral routes have a great importance. In a study performed on 32 families of HBsAg carriers, familial aggregation of infection has been acquired through close personal contact. Transmission of infection from mother to infant may occur transplacentally for vertical transmission, or, after the birth, for horizontal transmission, so that a high percentage of children is infected. Percutaneous transmission of hepatitis B in families affected by scabies is evident. The presence of infectivity markers is of major importance for transmission of virus: these are HBeAg and specific DNA-polymerase activity of serum. Well, when the carrier exhibits the markers, the contacts are involved in the infection in a high percentage. From this point of view the carriers with chronic liver disease are more dangerous than the asymptomatic ones. The problem of carrier exists: nevertheless it is possible to carry out a better prophylaxis, if we take into account the presence of the infectivity markers.


[Virological and serological study in the herpetic gengivostomatitis (author's transl)]. Virological and serological investigations to verify herpetic etiology have been performed on 24 children and 1 adult with acute gengivostomatitis. Viral isolation and detection of antibodies against HSV, carried out by neutralization, complement fixation, and indirect immunofluorescence techniques, have confirmed this etiology in the 88% of cases.


[Serum and skin surface lipids relation in the hepatic subjects (author's transl)]. The Authors studied a relation interlinking the abnormal groups of the serum lipids on the skin surface. They concluded that in liver disease there are two distinct classes of lipids and they are totally independent each other.


[Study on 190 strains of "staphylococcus aureus" isolated  in a department of ophthalmology (author's transl)]. Biochemical features and sensitivity to chemotherapeutic agents of 190 strains of Staphylococcus isolated from pharinx and conjunctiva of ophtalmological patients and staff were studied. Each strain was investigated for: pigment, coagulase, hemolysis (alpha-toxin), phosphatase and penicillinase production and mannite fermentation. Twentyfour chemotherapeutic angents were used for sensitivity tests. The Authors emphasize that a positive coagulase test is the best laboratory evidence for pathogenicity of a given strain of Staphylococcus, and that the site of isolation of the examined strains is not related with their biochemical features and sensitivity to chemotherapeutic agents.


[Malignant pustule in province of Milan, Italy (author's transl)]. Preliminary the statistical data are reported about human malignant pustule denounced in Italy in different Districts, in Lombardia and in Province of Milan. Correlatively the outbreaks and cases of haematic anthrax in animals declared in Italy, in different Districts, in Lombardia and in Province of Milan. Then the outbreaks of malignant pustule in Province of Milan are related in 1975-1977 period in the resident population where is considerable concentration of the leather manufactures. The epidemiological and microbiological researches have determined the relation among the outbreak of malignant pustule and the working of the hides imported from African Countries (Nigeria, Tanzania, Ethiopia, South Africa, Burundi-Kenya, Uganda) containing the spores of b. anthrax. The spores besides to cause infections of the workmen employed in the hide manufacture (industrial anthrax) through the effluents and solid refuses from the tanneries, are dispended upon the tiled ground and determine outbreak the haematic anthrax in the animals and agricultural coutaneus anthrax in the men.


The toxicological properties of impurities in malathion. During a malaria eradication programme in Pakistan in 1976, out of 7,500 spraymen, 2,800 became poisoned and 5 died. The major determinant of this poisoning has been identified as isomalathion present as an impurity in the malathion. It seems almost certain that the isomalathion was produced during storage of the formulated malathion. The quantitative correlation found between isomalathion content and toxicity of many field samples of malathion has been confirmed by an examination of mixtures of pure compounds. Addition of known amounts of isomalathion to technical malathion indicates that other active substances are present. These impurities have been identified (trimethyl phosphorothioates) and have been shown to behave like isomalathion in potentiating the toxicity of malathion. Some preliminary work on their toxicological properties is reported. The mechanisms involved in the potentiation of the toxicity of malathion are discussed.


[Factor XII deficiency - Hageman trait. Report of 2 cases]. For the first time in our literature we have described the two cases of hereditary deficiency of factor XII (Hageman trait), a very rare disorder. It was discovered when a long clotting time was found in our patients during the course of a preoperative evaluation. Abnormal thrombelastogram, with a picture typical for hemophilia, gave as a reason to continue with laboratory investigation. The laboratory findings showed us a very low value of factor XII in one case, and total absence of factor XII in the other.


[Erythropoietin in sideropenic anemias]. The erythropoietic activity in the sera of 18 patients with sideropenic anemia was investigated. The ex-hypoxic mouse bioassay was used and the 48 hour incorporation of radioiron into the peripheral blood was measured. The level of erythropoietin found was compared to the hemoglobin concentration and the PCV values in those patients. The statistically significant correlation was found between erythropoietin in the patients sera and the degree of anemia. Higher erythropoietin values were found in men as compared to women with the same severity of anemia. It was concluded that the results obtained in this study can be used as control values when erythropoietic activity in the sera of patients with different hematological disorders is measured.


[Role of the virologic laboratory in the diagnosis of subacute sclerosing panencephalitis. Report of 12 cases studied between May, 1977 and March, 1978]. Measles h.i.a. and c.f.a. were titrated in serum and cerebrospinal fluid of 12 SSPE patients. Specific IgM h.i.a. in the same specimens were also determined. Pretreatment of the sera by monkey red blood cell absorption, by kaolin or by heparin MnCl2, did not significantly affect h.i.a. titres, but h.i.a. were no more demonstrable in cerebrospinal fluids after kaolin and titres were somewhat lowered by heparin-MnCl2 treatment. By both h.i. and c.f. tests measles antibody were found at much higher titres in sera of SSPE patients than in controls of the same age. H.i.a. and, with one exception, c.f.a. were found in each of the 9 available cerebrospinal fluids from patients, but in none of the 6 specimens from non-SSPE cases. Ratio GM titers h.i.a. over GM titers c.f.a. in sera of SSPE patients was about 1, a value far from that found under different immunization conditions. In control sera, for instance, the ratio was 5.3. Specific IgM were never found in the cerebrospinal fluids and in only 2 out of the 10 sera examined.


The state of antitetanus protection in the commune of Perugia. A serological survey was carried out on the population in the Perugia district to assess the protection level against tetanus. The antitoxin titre was evaluated by indirect haemagglutination test in 983 sera from healthy subjects of both sexes and all age-groups. Only 285 males and 144 females, 33.47% of the subjects, had been immunized prior to the investigation. The research made it clear that the serological antibody level does not always correspond to the anamnestic data on previous immunization. Therefore, it appears that prophylactic treatment against tetanus should be based on objective data, that is, serum antibody titre, in all subjects at risk. This information, thanks to the indirect haemagglutination test, is not difficult to obtain.


Haemagglutination antibody titre levels which give certain protection against tetanus toxin. The lowest haemagglutination titre which gives safe protection against tetanus toxin, in sera of vaccinated subjects of both sexes and of all age groups has been assessed, by comparative haemagglutination and neutralization tests. It was established that sera with 1/32 haemagglutination antibody titre have a toxin neutralizing capability of greater than or equal to 0.1 I.U./ml. Lower haemagglutination titers do not assure protective capacity against tetanus toxin.


[Changes in serum immunoglobulin levels in aged subjects]. Serum immunoglobulin G, A, M levels have been determined on serum samples from 97 healthy elder subjects aged from 60 to 92. No qualitative changes were detected by electrophoretic analysis. The results show a significative increase with age in IgG and IgA concentrations; the IgM concentration results unaffected.


[Rosette formation test with mouse erythrocytes in chronic lymphatic leukosis: correlation with other membrane receptors]. The lymphocyte subpopulations of CLL patients have been studied. IgM and IgD membrane-associated immunoglobulins alone or in combination have been found, IgG being present in only one case. A marked increase in mouse-complement receptors (as shown by the EACt rosettes) as compared with human complement receptors (as shown by the EACa rosettes) was observed. The population of SIg-bearing lymphocytes was significantly greater than that of complement bearing lymphocytes. Moreover a mean percentage of 60.7 +/- 17 of the leukaemic lymphocytes formed rosettes with mouse red blood cells. In a significant number of patients the E-rosettes forming cells were also increased.


[Chromosome aberrations studied in short and long-term cultures of lymphocytes from patients with chronic hepatitis]. Chromosome aberrations of short and long-term cultured lymphocytes have been studied in 12 subjects with chronic hepatitis B. Short-term cultures show "stickiness", aneuploidy, and fragmentations. Long-term cultures show minor damages, made up almost totally of "lacunae" and sporadic fragmentations. Major size chromosomes appear to be more affected, among the latter those containing sites for the interferon. This latter findings would suggest that the interferon decrease in patients might be bound, even only partially to the virus-linked chromosome alterations.


[Brucella sacroiliitis in a West African]. A brucelian sacro-iliitis is reported in a 33-year-old West African man recently arrived from Mali. Thus, clinical, biological, radiological, and isotopic aspects could be precisely observed, and were found very similar to brucelian sacroiliitis in Europeans. Major information is required about the interest of technetium scintigraphy. The treatment included Rifampicin, in association with Doxycyclin and the theoretical bases of this choice are explained. Tolerance was good and a complete recovery was obtained after three months.


[Treatment of Lobo's disease with clofazimine (B 663)]. The author studies the three first cases of Lobo's mycosis treated with oral clofazimine. That is a curious tropical disease, which only occurs in neotropical region, particularly in the Brazilian Amazon. Without any known effective treatment, the mycosis has however responded well to clofazimine in the three cases, the results being significant regression of lesions by reabsorption of their content and disorganization of fungal structures.


[A dengue epidemic at Futuna].

[A dengue epidemic at Futuna]. During an outbreak occuring in Futuna (Horne Islands) from October 1976 to January 1977, II strains quite similar to dengue virus type I were isolated from blood of patients in acute phase. Immunitary responses were noted on 8/12 paired sera submitted to IH test; 4/17 serum samples showed antibody titer presumptive of a recent infection. Entomological survey gave evidence that virus was transmitted by Aedes polynesiensis and confirmed that Futuna is free of A.E. aegypti; other species found were: Culex annulirostris, C. pipiens fatigans, C. sitiens. A viral strain was isolated from Ae. polynesiensis only.


[Presence of a prokaryote of the genus Haemobartonella Tyzzer and Weinman, 1939, in the blood of Nigerians in the Niamey region]. The hemograms of 97 bed-riddens in very bad conditions reveal the presence (74 more or less infected but 6 heavily) of cocci, rots, rings, commas, coloured by May-Grünwald and Giemsa stain against the cell membrane wall of the erythrocyts and sometimes free in the blood plasma. This procaryotic element is the same agent of the canine, feline, equine and cuniculine haemobartonellosis in Niger. Principal symptoms are general weariness, anaemia, arthralgies, dizziness, anguish, suffocation crisis. It is a disease of the deficient and underfed men in Sahel.


[2d case of cutaneous leishmaniasis with mucous involvement in Senegal]. A 6 year-old-girl of a village along the Senegal River presented cutaneous lesions with a nasal nodule, both infected with Leishmania amastigotes. This is the second case of cutaneous leishmaniasis with mucosal involvement described in Senegal (West Africa).


[Treatment of giardiasis with tinidazole]. Fifty patients stricken by giardiosis were treated by a single dose administration of Tinidazole -- 50 mg./kg. for children and 2 g. for adults per os. Fifteen days after treatment, 84 0/0 of the patients had negative coprologic exams for giardiosis. The product was well-tolerated by the digestive tract as was demonstrated by a coprologic examination for digested food reside; however, minor digestive inconveniences were noted in 87 0/0 of the patients. There were no perturbations of hematologic or hepatic tests. This product would thus appear to be a treatment of choice in the management of giardiosis.


[1 case of autochthonous strongyloidiasis]. About one case of massive strongyloidosis becoming out of any immunosuppressive treatment and without travel out of France in a 40 year-old-woman, the authors study the different possibilities of contamination and set the problem of a drug-resistance to Thiabendazole.


[Sergentomyia berentiensis N. sp. (Diptera, Psychodidae). Description of a female specimen collected in Madagascar]. The authors describe, from a single female caught in Madagascar, a new species of sandfly: Sergentomyia berentiensis. They give mensurations and specific features (spermatheca, cibarium, pharynx). They note some similitudes with American species.


Bond graph models for plant biosystems.

Bond graph models for plant biosystems. Computable dynamic models for plant biosystems permit the study of effects of environmental variables on plant growth and productivity. Using bond graphs, a comprehensive phenomenological model of a plant biosystem may be developed and used in computer simulations. Elements of a model studied in this papaer include a gas diffusion network between the atmosphere and leaf cytoplasm, intracellular chemistry, and the translocation networks of the phloem. Bond graphs are shown to provide a conceptual basis for the development of biological subsystem and system models and lead to computable representations.


Bond graphs and the exploitation of power conserving transformations. Use is made of the guaranteed energy conservation property of any bond graph model (presuming that consistent energy variables are used). Thus power transformations are power conserving, and this property is exploited with respect to multiport transformers where many effort and flow variables may be involved. In these cases the relationship among the effort (flow) variables across the transformer may be easier to derive than the relationship among the flows (efforts). The power conserving nature of the transformer permits immediate derivation of the alternate variable relationship. This formulation procedure is applied to the reflex reaction of the arm.


Network representation of reaction--diffusion systems far from equilibrium. This paper develops the network theory of chemical reaction systems from first principles. The network approach is then used to derive a canonical set of differential equations for reaction--diffusion systems, and an analysis of the Brusselator is presented as an example.


A computer program for multivariate ratio analysis (MISCAT). Analysts must deal frequently with missing data in multivariate analysis. In such cases, estimating the covariance maxtrix V of the dependent variables usually involves initial estimation and iterative adjustment of imputed missing data values, and/or smoothing of an estimate V which is not necessarily positive semi-definite. This paper presents an alternative procedure for computing estimates of relevant multivariate parameters in situations where missing data occur at random and with small probability. MISCAT is a computer program which computes multivariate ratio estimates of the means and a corresponding positive semi-definite estimate of the covariance matrix. It is an extension of GENCAT, which is a program for the generalizaed least squares analysis of categorical data. Thus, one advantage of dealing with missing data in this manner is that variation among the ratio estimates may be conveniently analyzed within MISCAT using asymptotic regression methodology, provided that sample sizes are sufficiently large. An example is given to illustrate such analysis for longitudinal data from a multicenter clinical trial.


A computer program for the generalized chi-square analysis of competing risks grouped survival data (CRISCAT). CRISCAT is a computer program for the analysis of grouped survival data with competing risks via weighted least squares methods. Competing risks adjustments are obtained from general matrix operations using many of the strategies employed in a previously developed program (GENCAT) for multivariate categorical data. CRISCAT computes survival rates at several time points for multiple causes of failure, where each rate is adjusted for other causes in the sense that failure due to thes other causes has been eliminated as a risk. The program can generate functions of the adjusted survival rates, to which asymptotic regression models may be fit. CRISCAT yields test statistics for hypotheses involving either these functions or estimated model parameters. Thus, this computational algorithm links competing risks theory to linear models methods for contingency table analysis and provides a unified approach to estimation and hypothesis testing of functions involving competing risks adjusted rates.


On the stationarity and normality of the electroencephalographic data during sleep stages. In this paper, we show techniques to examine the stationarity and the normality of time series as well as results obtained by applying these techniques to EEG data during sleep stages. Many statistical analyses of the EEG data are based on the assumption that the EEG data are stationary and normally distributed. However, the problem is to know the length of data which is most appropriate for the statistical analysis. From the analysis, it is found that a decreased length of data implies an increased degree of stationarity and normality in each stage of sleep. However, for the practical stationary analysis of EEG data, it is shown that it is appropriate to take about 5 s during sleep state. Stationarity is fulfilled to a relatively large extent in REM but more seldom in stage 2. In the case of short data, asymmetric distribution occupies the large parts of non-normal distribution. As the length of data increases the proportion which is symmetric but sharper or flatter than the normal distribution increases.


The computation of EEG bispectra.

The computation of EEG bispectra. This paper presents a FORTRAN program for computation of bispectra of multichannel EEG on a PDP-11/55 computer. Input data are already digitized and file-structured. Output of power spectra, bicoherence and biphases is produced in synoptic form on a line printer.


Computer techniques for the processing of evoked potentials. A computer technique is described for the systematic characterization of brain evoked potentials. Preprocessing of the data by a causal digital filter is followed by a peak search and identification procedure. A latency histogram of the peaks found is constructed to determine the ranges or clusters of peaks within the single evoked potential. Peaks found within the clusters are then corrected to the mean latency of the cluster and a latency corrected average version of the evoked potential constructed.


Evoked potential measurement and analysis on a small laboratory computer. A program is described for the collection and subsequent analysis of somatosensory evoked potentials using a LINC-8 computer. The program allows simple evoked-potentials analysis in centers where a small laboratory computer may be available but sophisticated instrumentation such as a computer of average transients is not available. This program provides an efficient method of easily obtaining information concerning the conduction pathways of the nervous system as well as the cerebral function; the program can be implemented on small laboratory computers which most hospitals currently own, without the associated cost or complexity of additional hardware in the laboratory. Combining utilization of a small laboratory computer with an easily programmable method provides an approach for evoked potential analysis which is well within the financial and technical scope of most neurophysiology laboratories.


A minicomputer system for display and rate analysis in vectorcardiography. A system has been constructed for recording vectorcardiographic signal with a FM taperecorder. Off-line AD-conversion and analysis of rates and magnitudes of partial vectors are made with a minicomputer. The reason for studying particularly initial vectorrates is that according to our hypothesis these contain valuable information for classification of certain cardiac arrythmias according to supraventricular or ventricular impulse focus. Preliminary results confirm the hypothesis. In vectorcardiography one difficulty is to give an easily comprehensible presentation of the vectorloop. In this study a method for '3-dimensional' display has been developed, using a graphic display processor and varying intensities of the beam. The system is to a high degree man-machine interactive.


Automatisation of chronic toxicities.

Automatisation of chronic toxicities. Automatisation of collection and processing of chronic toxicity tests are presented in a 'pharmaceutical research center environment'. The data are either analog signals or numerical values transmitted to the computer, from terminals posted in various laboratories. The minicomputer works under time-sharing system which allows many users to access to the programs in the same time. This system controls about 3000 results a day and prints complete reports in less than two days. Rewriting is then avoided thanks to this system, and in such a way, the reports are more reliable.


Use of a clinical laboratory computer to warn of possible drug interference with test results. Using a clinical laboratory computer system, software has been developed which checks to determine if the result of any test performed on a patient specimen may be affected by any drug administered to that same patient. If possible interference is detected, a comment is automatically attached to the result on the patient's computer-generated report warning the attending physician the result may be falsely elevated or lowered.


BANDSCAN--a computer program for on-line linear scanning of human banded chromosomes. BANDSCAN, an interactive program for on-line linear scanning of human G-banded chromosomes quantitative analysis is described. This program was written for a Wang 720 C programmable desk calculator associated to the Zeiss scanning photometer MP01. The system can detect up to a maximum of 24 densitometric band peaks found along banded chromosome arms or chromatids, estimate the total arm length and localize bands in terms of their relative positions. The scanning stage under control is always returned to the pre-fixed scanning starting point (centromere) which allows a user to scan the specimen repeatedly at different sensitivities and thus to reject minor bands or suspected chromosome artifacts. This facilitates a better visualization of major bands and chromosome landmarks. A fully formated print-out on band localizations and their relative positions is obtained at the end of each scanning. The possibilities of the application of this program to band mapping of human chromosomes and to the study of small chromosome band aberrations is discussed.


Readers' forum: experiences with a system. The implementation of a completely operational computer system in a cardio-thoracic department. Wythenshawe Hospital is a large general district hospital with more than 1000 beds, situated approximately 9 miles south of Manchester. The Cardio-Thoracic department, housed in the new section of the hospital which was completed in 1973, is the major centre for cardiothoracic surgery in the greater Manchester area. It also receives any major accident cases which require treatment within the Intensive Therapy Unit. This paper describes a Patient Data Display System and the methods used to introduce the concept of such a system, to doctors, nurses, laboratory and paramedical staff, and the manner in which these staff were trained in the use of computer terminals. Principles underlying the need for and requirements of such a system are also discussed. Six months after hardware commissioning the system was fully operational throughout the whole department.


Endocytic mechanisms of the digestive cells of Hydra viridis. 1. Morphological aspects. The endocytic mechanisms of the digestive cells of Hydra viridis were examined by transmission electron microscopy. Algae which form a stable intracellular symbiosis are phagocytosed by uncoated plasmalemma, as are large (greater than 0.5 micron) food particles. Discoidal coated vesicles apparently effect the endocytosis of smaller particles, including macromolecules. Competition experiments indicate that the uptake of algae and larger food particles utilize similar endocytic membrane.


The process of wound repair in Udotea petiolata (Siphonales). The process of wound repair is examined in the multiaxial thallus of Udotea petiolata. In response to cutting, the injured siphons form a plug, which quickly seals the wound surface. This plug is composed of a fibrillar substance, and of roundish bodies; the latter in unwounded siphons are present in the vacuole. A wound-wall is formed inside the plugs in every tested part of the thallus. Only the apical terminations of the fringe siphons are unable to form a complete wound repair. The composition and function of the two components are discussed.


Initiation of bends in the microtubular axostyle of Pyrsonympha. The motile axostyle of Pyrsonympha, a symbiotic protozoan occupying the hindgut of termites, is a cytoplasmic bundle of microtubules capable of initiating and propagating bends. In vivo, bends are always initiated at the anterior end of the cell. The early events to bend initiation are described using quantitative data from cinemicrographic recordings. In addition, the conplicated array of structures at the site of bend initiation is described using electron microscopy of serial thin sections through the anterior end of the cell. Bend initiation is postulated to represent a mechanical event associated with one or more of the specialized structures associated specifically with the anterior end of the axostyle.


Time of appearance of cellular antigens on chicken RBC. At least twelve genetically distinct systems of RBC membrane alloantigens have thus far been detected in the chicken. Earlier studies have indicated that some of these are 'latent' in that the full development of surface antigen appears only gradually during ontogeny. The present experiments show that the alloantigens B2, B19, E1 and I2 are among those which develop more slowly in the RBC plasma membrane system. These might be utilized as indicators of the state of membrane differentiation during various experimental treatments or disease states.


Histopathological and cytochemical studies on the 5-fluorouracil treated gonads of Locusta migratoria (L.). 5-Fluorouracil caused necrosis in ovary only whereas testis remained unaffected even with higher doses. In ovary the ooplasm shrank; some follicular epithelial cells became pycnotic, and the nuclei of others showed an abnormal fragmentation of chromatin material; the cytoplasm of follicular epithelial cells was drawn into the peripheral empty space formed by the contraction of the ooplasm, and ultimately the follicular epithelium disintegrated. The interoocytal bridge is some oocytes was lost. The yolk formation was inhibited, and maturation of eggs was prevented. Most of the mature oocytes were also damaged. Inhibition of DNA and RNA synthesis, and decreases in proteins, carbohydrates and lipids was observed. With increased doses and post-treatment periods the effects mentioned above were increased.


Reconstruction of mammalian heart tissue from embryonic heart cell suspension with reference to the aggregation of adult heart cells. Aggregations of isolated embryonic and adult heart cells were studied so as to examine in detail the formation of cell contacts, the assembly of cells into multicellular systems, and cell co-operation in forming organized and differentiating tissues. At selected intervals after initiating rotation cultures, aggregates were examined microscopically for evidence of contractility, and subsequently processed for scanning and transmission electron microscopy (TEM, SEM). By continuous accretion of single cells, and the joining of small clusters, the aggregates increased in size. Cells within the aggregates exhibited rhythmic and synchronous contractility by 3--12 h of culture, suggesting the formation of low-resistance inter-cellular junctions between apposed cells. Two populations of cells could be recognized by 9--12 h with SEM. One was spherical in surface view and the other was flattened. Spherical cells possessed myofibrils, and were classified as cardiac myocytes which occupied the core of the aggregate. The flattened cells were devoid of myofibrils and non-muscle in nature. They covered the surface in a multilayered epithelium. At 12h the aggregates were round to oval, covered by flattened cells, but individual round cells could still be recognized. Intercalated discs were frequently observed in 12 h aggregates. The junctional complexes observed in 12--72 h aggregates include desmosomes, fascia adherens and gap junctions. Most of the aggregation was completed by 24 h, and at later time periods, i.e. 48--72 h, the external surface of the aggregates was smoothed out with epithelial investment. In these aggregates myofibrils and intercellular junctions became reconstructed in less than 24 h. Unlike embryonic myocardial cells, adult cells did not form aggregates of numerous cells. Instead, they formed irregular clusters of 2--5 cells during 3--48 h of culture. Intercellular contacts and suggestive desmosomal materials were observed between adherent cardiac muscle cells. When culture continued for 48--72 h, the cells underwent supercontraction and became non-viable, suggesting that the terminally differentiated adult myocardial cells are incapable of regenerating constituents obligatory for histogenetic reconstruction.


A comparison of alcoholics and heroin abusers: computerized transaxial tomography and neuropsychological functioning. A number of conclusions may be drawn from the present neuropsychological and neuroanatomical assessment of alcoholic and heroin abusers: (1) Heroin abusers display deficits on the Category Test, TPT (Time and Localization) and Raven's Progressive Matrices (Set I and II) when compared to controls. (2) Alcoholics show significantly greater deficits than heroin abusers on these tests. (3) Duration of heroin and alcohol abuse are positively related to the extent of the observed deficits. (4) Observed deficits on the Progressive Matrices and Category tests appear to be reversible in the heroin abuser, but not the alcoholic, after comparable periods of remission. (5) The same proportion (1/15) of alcoholics and heroin abusers showed evidence of cerebral atrophy based on enlarged ventricular size.


Sympathetic nervous function and renin activity in hypertensives on long term drug treatment with propranolol, methyldopa or bendrofluazide. Plasma noradrenaline and plasma renin activity were measured as indices of sympathetic activity and renin angiotensin system in similar groups of hypertensive patients receiving either propranolol, bendrofluazide or methyldopa. Plasma renin activity was similar in the propranolol and methyldopa groups and significantly lower (p less than 0.01) in both these groups than the diuretic treated subjects. Plasma noradrenaline was significantly lower (p less than 0.01) on methyldopa than either propranolol or bendrofluazide. These different effects on the renin angiotensin system and the sympathetic nervous system of these drugs may be relevant in the choice of long term therapy in hypertension.


Effects of R-28935 on sympathetic nervous activity in anesthetized cat. Intravenous administration of erythro-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-Et]-4-piperidyl)-2-benzimidazolinone (R-28935) (25--100 microgram/kg) produced a dose-related decrease in spontaneous electrical activity recorded in the splanchnic and renal nerves. Reductions in sympathetic nerve activity were paralleled by hypotension and bradycardia. R 28935-induced depressor responses were not affected by baroreceptor denervation, piperoxan, yohimbine or phentolamine. Results support the idea that R-28935 decreased resting blood pressure and heart rate through a reduction in central sympathetic outflow which does not involve alpha-adrenergic receptor activation.


Influence of angiotensin antagonists on renal vascular resistance and prostaglandin E release. Blood pressure (BP), renal arterial pressure and renal blood flow (RBF) were measured and blood samples were removed for determination of prostaglandin E (PGE) content in pentobarbital anesthetized dogs. Analysis of PGE with prior column separation was by radioimmunoassay utilizing a PGF antiserum and PGE specific anti-serum. The angiotensin antagonists 1-Sar-8-Ala-angiotensin II (saralasin) and 1-Sar-Ileu-angiotensin II (1-S-8-I A) were infused intraarterially to the kidney achieving concentrations of 20 and 50-60 ng/ml and 10 and 20 ng/ml, respectively before and during partial occlusion of the renal artery (RAO). 1-S-8-I A, 20 ng/ml, caused a small increase in renal vascular resistance (RVR) before RAO, but saralasin exerted no effect prior to RAO. Arterial and renal venous PGE levels were not affected by the antagonists. RAO caused a decrease in RVR and gradual increase in BP which ranged from 29-38% and 12-15 mmHg, respectively at the 20 min interval. The concentration of PGE in renal venous blood was found to be increased and the AV difference was significant when measurements were made using PGF antiserum, but no change was detectable when using PGE antiserum. The infusion of saralasin, but not 1-S-8-I A in the above concentrations caused a significant decrease in RVR during RAO; however, no changes in PGE levels were obtained with either agent. These results indicate that 1-S-8-I A has a more potent agonistic renal vasoconstrictor effect than saralasin as found before RAO, and saralasin exerts a renal vasodilator action only during RAO, which is due to angiotensin antagonism and not to PGE release.


Depression of sympathetic preganglionic neurons by clonidine: evidence for stimulation of 5-HT receptors. In unanesthetized spinal cats, clonidine HCl (5-50 microgram/kg, i.v.) rapidly and markedly depressed excitatory transmission through two spinal pathways to sympathetic preganglionic neurons. Depression through either pathway was dose-dependent and persisted for more than 3 hr but could be rapidly antagonized at any stage by tolazoline HCl in a dose-ratio of about 1:100. The two spinal pathways were also depressed transiently by L-dopa and for prolonged periods by 5-HTP; both precursors were shown to act by releasing 5-HT from bulbospinal 5-HT terminals and their depressant effects were also antagonized by tolazoline. In the absence of 5-HT-induced depression, L-dopa only enhanced transmission through both pathways by inducing release of catecholamines from bulbospinal NE terminals. These results indicate that clonidine depresses sympathetic activity by stimulating inhibitory 5-HT receptors on sympathetic preganglionic neurons, a mechanism that adequately accounts for its central vasodepressor effect.


Plasma volume, blood volume and transcapillary escape rate (TER) of albumin in young spontaneously hypertensive rats (SHR) as compared with normotensive controls (NCR). A detailed comparison of blood and plasma volumes and of the transcapillary escape rate (TER) of albumin was performed in SHR and matched NCR, particularly during the phase of rapid pressure rise in SHR. Throughout this early phase of life, the relative plasma and blood volumes tend to be lower, and TER higher in SHR, as would be expected when neurogenic mechanisms dominate the initiation of hypertension. Only in late established SHR hypertension, with increasing signs of cardiovascular complications, blood volume tends to be higher in SHR than in NCR. These results are in general agreement with most observations in early essential hypertension in man. They are of interest in contrast to recent findings in another variant of primary hypertension in rats, MHS. Also the apparently quite different initiating mechanisms in SHR and MHS primary hypertension are discussed.


Clinical assessment of sympathetic tone: orthostatic blood pressure responses in borderline primary hypertension. Orthostatic changes of systolic, diastolic and pulse pressure, and pulse rates were evaluated as clinical indicators of sympathetic nerve tone in 28 patients with uncomplicated primary hypertension. After sixty minutes in the upright position, systolic blood pressure increased in 13 and decreased in 15 of the patients, while pulse pressure diminished in 19, was unchanged in 4 and increased in 5 of the patients. The changes of both systolic blood pressure and pulse pressure showed a significant positive correlation with basal (supine) levels of norepinephrine (r = 0.40, p less than 0.05 and r = 0.54, p less than 0.01, respectively). In the total sample of patients, 25% had basal plasma norepinephrine concentrations above the normal range. Of the patients with increased systolic blood pressure after standing, 38% had elevated basal norepinephrine. Similarly in patients with increased orthostatic pulse pressure or in those with pulse pressure reductions less than 10 mm Hg, 45% had elevated basal norepinephrine. On the other hand, of patients with reductions of pulse pressure of more than 10 mm Hg, only 6% had elevated basal norepinephrine. Of the patients with similar systolic blood pressure reductions, none had increased plasma norepinephrine. Both diastolic blood pressures and pulse rates always rose during orthostatic stress, but they did not correlate with basal sympathetic tone. In conclusion, hypertensive patients with orthostatic increases of systolic and pulse pressure are more likely to have elevated basal sympathetic tone than unresponsive patients. The former may comprise a subset of hypertensives who have a causal neurogenic component. They may be more sensitive to drugs which suppress sympathetic nerve function.


Reduction of plasma renin activity by centrally-administered angiotensin II in anesthetized cats. Cerebroventricular administration of angiotensin II elevated arterial pressure and reduced plasma renin activity (PRA) in renal venous blood in anesthetized cats. Further, there was an increase in the concentration of urinary sodium, as well as the rate of Na+ excretion. Acute renal denervation significantly reduced the effects of central angiotensin II on the PRA and on the natriuresis. The data suggested involvement of a neurogenic component in these effects. Further, it appears that there may be a reciprocal relationship between CSF renin activity and PRA.


Differential development of renal, DOCA-salt, and spontaneous hypertension in the rat after neonatal sympathectomy. The development of hypertension was studied in rats after neonatal sympathectomy by s.c. injection of 6-hydroxydopamine HCl. Three different types of hypertension were investigated: renal hypertension in the two-kidney Goldblatt model, steroid hypertension produced by deoxycorticosterone (DOCA) implantation and saline as drinking fluid, and genetic hypertension in the spontaneous hypertensive rat (SHR). Blood pressure was measured directly in conscious animals via the iliac artery. Mean blood pressure of conscious sympathectomized (SX) normotensive rats was not significantly different from that of normotensive controls. Renal hypertension reached the same level in controls and SX rats four weeks after application of a renal artery clip. DOCA-salt hypertension developed faster and to a higher level in SX rats than in control rats. The hypertension in SX DOCA-salt hypertensive rats was accompanied by a marked tachycardia. In contrast hypertension did not develop in SX SHR. Up to 12 months of age mean blood pressure was markedly lower than that of control SHR, but slightly higher than that of SX normotensive Wistar Kyoto rats. These differential effects of neonatal sympathectomy on the development of hypertension in the rat may point to differences in the pathophysiological mechanisms. It is concluded that an intact sympathetic nervous system is essential for the development of hypertension in SHR. In DOCA-salt hypertension the intact sympathetic nervous system appears to protect against a rapid rise in blood pressure.


The hypertensive response to injection of physostigmine into the hypothalamus of the unanesthetized rat. Microinjection of physostigmine (3-30 nmoles) into the posterior hypothalamic nucleus of freely-moving, unanesthetized rats elicited a dose-related hypertensive response. This effect was significantly reduced by prior central injection of hemicholinium-3. The direct acting cholinergic agonist, carbachol, also evoked an elevation of blood pressure following intrahypothalamic injection; however, this response was unaffected by prior administration of hemicholinium-3.


Central cardiovascular actions of histamine in rats: involvement of histamine H2-receptors. Centrally induced pressor effects, associated with tachycardia have previously been demonstrated after intraventricular (i.c.v.) injections of histamine. The selective histamine H2-receptor agonists dimaprit (1--500 microgram) and 4-methyl histamine (1--10 microgram), and the histamine H1-receptor agonist 2-methyl histamin (1--10 microgram) elicited rises in blood pressure and heart rate after i.c.v. administration in urethane-anaesthetised rats. Metiamide (400--800 microgram, i.c.v.) antagonised the cardiovascular responses induced by dimaprit and 4-methyl histamine, but not the responses induced by 2-methyl histamine. In contrast mepyramine (100 microgram, i.c.v.) failed to antagonise the dimaprit-induced effects. It is concluded that histamine H1 and H2-receptors are present in the central nervous system of rats. Selective stimulation of either H1- or H2-receptors can lead to pressor effects associated with tachycardia after i.c.v. administration of specific agonists in urethane-anaesthetised rats. These responses are selectively antagonised by the respective receptor antagonists.


The effect of an acute or chronic treatment with indomethacin on the blood pressure of DOCA/salt and spontaneously hypertensive rats. The intravenous infusion of indomethacin (5 mg/kg/min) for 10 min did not modify the systolic blood pressure of conscious, unrestrained doca/salt hypertensive, spontaneously hypertensive (SH) and normotensive Wistar (NW) rats. However, this dose of indomethacin was sufficient to prevent completely the hypotensive action of arachidonic acid in these animals. The chronic administration of indomethacin to doca/salt treated- and young SH rats was without any effect on the development of hypertension in these animals. These results suggest a limited role for endogenous PGs during the development of these two types of hypertension.


Cardiovascular changes in anaesthetised rats after the intra-hypothalamic administration of adrenaline. Bilateral injections of adrenaline (0.01-10.0 microgram) into the anterior hypothalamic (AH) region, in urethane-anaesthetised spontaneous hypertensive (SH) rats, elicited dose-dependent falls in blood pressure and heart rate. The bradycardia was immediately in onset while the hypotension was preceded by a short-lasting rise in blood pressure. Bilateral injections of adrenaline into the anterior preoptic area (POA) and areas surrounding the AH had little or no effect on blood pressure and heart rate, while injections into the posterior hypothalamus (PH) induced tachycardia and hypertension followed by a smaller fall in blood pressure. Pretreatment with dl-propranolol (25-100 microgram bilat. AH) appeared to potentiate the hypotension induced by adrenaline (1 microgram bilat. AH) in a dose-dependent manner, but did not affect the falls in heart rate. On the other hand, pretreatment with metoprolol (25-100 microgram bilat. AH) effected a dose-dependent antagonism of the adrenaline-induced hypotension and bradycardia. Pretreatment with 1-propranolol (25 microgram bilat. AH) also antagonised the adrenaline-induced cardiovascular depressor effects, while pretreatment with d-propranolol (25 microgram bilat. AH) abolished the initial hypertensive effect. Pretreatment with piperoxan (25-100 microgram bilat. AH) antagonised adrenaline (1 microgram bilat. AH) induced hypotension and bradycardia only at the highest dose used. The results give further support to the concept that hypothalamic adrenaline receptors may be involved in the central regulation of blood pressure and heart rate. Furthermore, while an involvement of hypothalamic alpha-adrenoceptors cannot be ruled out, it is suggested that hypothalamic beta-adrenoceptors may be involved in mediating the cardiovascular depressor effects of adrenaline injected into the AH.


[Parthenium hysterophorus allergy. A weed problem in India (author's transl)]. Parthenium allergy is caused by direct and indirect contact with Parthenium hysterophorus L. of the Compositae family, accidentally introduced into India from the USA 20 years ago. Its distribution was supported by the optimal environmental conditions of this country. It causes severe contact dermatitis in a lot of people, which becomes chronic after longer exposition. The source of the epidemic are the strong sensitizing sesquiterpene lactones parthenin, ambrosin and others, which are highly concentrated in the trichomes of the plant. During the dry season in India the mature plants crumble to a fine dust, that is scattered by the wind and becomes disseminated throughout the countryside. Permanent contact with this dust is the source of this socalled "airborne contact dermatitis". About 12 deaths occurred in severely affected persons due to intercurrent infection. Control of Parthenium hysterophorus is possible with Ansar-529, a weed-killer containing arsenic. Recently the weed has been introduced into Central-Australia too.


The prevalence of nickel allergy among women. An epidemiological study in hospitalized female patients. Through an interview examination among hospitalized female patients the prevalence of nickel allergy has been found unexpected high. 241 patients have been invesitgated, of them 20 gave history compatible with nickel allergy. Five of them had had hand eczema, the four of them only for short periods. The study concludes, that larger epidemiologic studies are necessary to evaluate the frequence of hand eczema in nickel sensitive patients and its prognosis in relation to environmental factors.


[Photochemotherapy and cataract formation]. According to the literature combined treatment with 8-MOP and UVA has induced ocular damage in animals. Similar changes in humans on photochemotherapy have not yet been reported and therapeutic doses are considerably lower than the doses that proved toxic for the animal eye. The present paper reviews pertinent literature on the subject and discusses the conditions under which photochemotherapy for psoriasis seems acceptable in view of present day knowledge.


[Relationship between accidental injuries and the course of malignant melanoma]. On a case report the possible role of traumatisation in acceleration of progress of malignant melanoma was demonstrated. The factors determining the clinical course of malignant melanoma are in the majority unknown. In the individual case with a provable causality of trauma on the acceleration of tumor progress a pretension for insurance es legal. This decision takes into consideration the special aspects of each particular case.


[Erosions caused by crystalline substances. Report of 3 iatrogenic cases]. Three examples demonstrate how therapeutics (potassium permanganate and silver nitrate), improperly applied, can lead to erosions the determination of which is difficult if a relatively low water solubility causes a prolonged latency between impact and perceptible consequence. This latency can be considerably extended by a slight development of subjective symptoms of such erosions. Two of the cases show that the prescription of granulated potassium permanganate requires an accurate information of the patient.


Acute and subacute toxicology and safety evaluation of hexahydro-1,3,5-triethyl-S-triazine. Acute and subacute toxicology and safety evaluation was determined for hexahydro-1,3,5-triethyl-s-triazine (Vancide-TH), a bacteriostatic and fungiastatic agent proposed for industrial use by R. T. Vanderbilt and Co., Inc. Single dose oral toxicity, subacute 14 day dermal toxicity and eye irritation studies were conducted on either the rat or the rabbit. The data obtained indicate that Vancide-TH should be classified as a "toxic, corrosive and an eye-irritating" substance as defined under the "Regulations" of the Federal Hazardous Substances Act. Since the acute dermal LD50 closely approximated the acute oral LD50 in rats, this route might constitute the most serious hazard involved with V-TH and special precautions should be exercised when handling or using this substance. Because of the severe eye-irritating action, precautions should be taken to protect the eyes when handling or using the compound; the ocular damage produced may be irreversible. The "in use" concentrations (1,000 to 10,000 ppm) produced a much lesser toxocity in animals and could be without hazard if precautions are taken.


A multi-generation toxicity evaluation of P,P'-DDT and dieldrin with Japanese quail. II. Tissue residues analyses. Selected tissues and egg yolks of Japanese Quail fed diets containing DDT or dieldrin in a four-generation (parental, F1, F2 and F3) study were analyzed for residues of parent compound and/or specific metabolites. Diets containing DDT (5 and 50 ppm) or dieldrin (0.1 and 1.0 ppm) were fed to each generation for 10 wks followed by a 12-wk recovery period in order to determine generation-accumulative effects, maximum residue levels and decline of residues during recovery. Tissue-residue storage and intergeneration transmission for DDT and dieldrin were generally similar and were related to dietary levels. Tissue residues in newly hatched birds were elevated initially for each generation subsequent to the parents, but any cumulative effects between generations were transitory, as residues after 5-to-10 wks were similar in each generation. Tissue residues in all groups showed a decline during the 12-wk recovery period. Decline during recovery was greater for females than males, probably attributable to egg production. Egg yolk residues for birds fed 5.0-ppm DDT declined to near control levels during the recovery period; at 50 ppm, residues declined but remained elevated above controls. For the quail fed dieldrin, residue levels were above those in controls; as with DDT the subsequent decline was more marked in the females.


Serum enzymes as indicators of chemically induced liver damage. Rats were dosed with CCl4 or diethylamine to induce liver injury. The time and magnitude of peak liver injury were assessed by histopathological examination of liver specimens taken at intervals after dosing. Serum enzymes were measured at the same intervals. Serum ornithine carbamyl transferase (SOCT) activity increased at least 6-fold in animals that showed liver damage by histopathology, and fell again as the injuries resolved. Measurements of other enzymes were less sensitive. SOCT measurements appear to be as sensitive a method as histopathology for detecting liver damage caused by administering xenobiotics. Since serum enzyme measurements do not require that the animals be sacrificed, they can be used for repeated examinations of the same animals, thus increasing the likelihood of detecting transient injury.


Hair dyes and aplastic anemia.

Hair dyes and aplastic anemia. Reports linking the use of hair dyes with bone marrow suppression and aplastic anemia have appeared sporadically over the past 45 years. For the most part these clinical cases are difficult to evaluate but appear to rely heavily for support on a single report in 1935. The infrequency of these reports and the wide-spread use of hair color products argue strongly against a primary toxic action on bone marrow in humans. The results of studies in three species of animals support this conclusion, giving no indication that chronic exposure to hair dyes causes adverse effects on hematopoiesis. Although it cannot be dismissed as a possibility, invoking idiosyncrasy seems on equally shaky grounds since any rational basis for continued association of a substance with individual sensitivity should find increasing numbers of cases with increasing population exposure. Clearly this has not been the case.


Interaction of parathion and malathion with hepatic cytochrome P-450 from rats treated with phenobarbital and carbon disulfide. Alterations in the activity of drug-metabolizing enzymes and the concentration of cytochrome p-450 from liver microsomes of rats pretreated with phenobarbital for enzyme induction and later given a single oral dose (0.4 ml/kg) of carbon disulfide (CS2) have been examined. In vitro incubations of these microsomes with parathion and malathion showed no significant change in the amount of cytochrome p-450 from that present in the corresponding controls. This inhibition of oxidative desulfuration of these insecticides by microsomes from CS2-treated animals could be attributed to the prior binding with cytochrome p-450 of sulfur released from CS2 as confirmed from the results of spectral binding of SKF 525-A, parathion and malathion. These results lead to the conclusion that CS2, parathion and malathion undergo oxidative desulfuration in an analogous manner and that the metabolism of the insecticides is impaired in liver previously exposed to CS2.


Enhancement of 1,1-dichloroethylene toxicity by pretreatment of fasted male rats with 2,3-epoxypropan-1-ol. The efficacy of pretreatment with various low molecular weight epoxides in increasing the toxicity of orally administered 1,1-dichloroethylene (1,1-DCE) has been determined in fasted male rats. Rats were dosed ip with either 2,3-epoxypropan-1-ol (EP), 1,1,1-trichloropropane-2,3-oxide (TCPO), styrene oxide (SO), cyclohexene oxide (CHO), butadiene monoxide (BMO) or the sulfhydryl reagent, diethylmaleate (DEM) 1 hr before intubation with 1,1-DCE. Increases in plasma aspartate transaminase (AsT) 24 hr after 1,1-DCE intubation were used as a measure of toxicity. In rats pretreated with 278 mg of EP/kg the acute LD50 of 1,1-DCE was reduced by a factor of 5 (to less than 40 mg/kg) and doses of 1,1-DCE as low as 12.5 mg/kg increased AsT levels. While 25 mg of 1,1-DCE/kg did not increase plasma AsT activities in naive rats, this dose did increase AsT levels in rats pretreated with 30 mg of EP/kg. The severity of 1,1-DCE toxicity in EP pretreated rats was greater in large, mature rats than in small, immature rats. On a molar basis the abilities of these various epoxides and DEM to exacerbate 1,1-DCE toxicity were related as follows: EP greater than SO greater than TCPO greater than CHO greater than DEM greater than BMO. These epoxides appeared to increase the toxicity of 1,1-DCE by interfering with the metabolism of a toxic product of the microsomal oxidation of 1,1-DCE.


Reproductive and teratologic studies with isoflurane. The volatile anesthetic, Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), was investigated at anesthetic concentrations to determine its effects on reproduction in rats treated prior to mating, on fetal development in rats and rabbits when administered during various stages of gestation, and on fetal survival in rats treated during late pregnancy. No adverse reproductive effects were observed, and no evidence of teratogenic activity was obtained. Fetal survival was low in rats exposed during late pregnancy but whether or not this finding is related to Isoflurane exposure requires confirmation.


Acute mitochondrial toxicity of caffeine in cultured heart cells. The cytotoxic effect of caffeine on heart cells was evaluated in primary cultures of rat heart muscle (M) and endothelioid (E) cells. The cultures were exposed to 5, 10, or 20 mM caffeine for 6, 12, or 24 hours. As an index of cytotoxicity produced by the treatments, in situ changes in mitochondrial membrane fragility were measured by a sensitive cytochemical technique. The 24 hr treatment with 20 mM caffeine was lethal to both E and M cell cultures; only the 12 hr treatment of M cell cultures with 20 mM caffeine produced significant labilization of mitochondrial membranes. The results of tests with other concentrations and durations of treatment were not statistically significant.


Acute toxicity of tetramethylbenzenes: durene, isodurene and prehnitene. Oral LD50 (rat), primary skin irritation (rabbit), cutaneous sensitization (guinea pig) and eye irritation (rabbit) studies were conducted on the three tetramethylbenzene isomers: durene , isodurene and prehnitene. The order of oral toxicity was isodurene greater than prehnitene greater durene. Durene was not a skin irritant, while isodurene and prehnitene each produced a mild positive skin response (erythema). None of the tetramethylbenzenes were skin sensitizers or eye irritants. Durene, isodurene and prehnitene are only slightly toxic on an acute toxicologic basis and only pose an acute health hazard when injested in excessive quantities.


Continuous monitoring of temperature in laboratory animals during inhalation exposure. An automatic system was developed to monitor continuously the colonic temperature of laboratory animals during inhalation exposure to toxic chemicals. It includes: an automatic switchbox, a control circuit, a recorder and a digital voltmeter. The system was calibrated for different temperature ranges and used for a year to assess the effects of household solvents on temperature of Sprague-Dawley rats. Reliable monitoring of temperature in 16 rats was carried out in a sequential manner in the manual mode or in the automatic mode for several consecutive days. Very slight changes (.01 - .02 degrees C) in temperature can be measured with this system.


Effect of long term heparin administration in dogs. Because several literature reports suggested that heparin could sequester calcium from body tissues and one could reason that prolonged therapy might lead to osteoporosis, the effect of long term heparin administration was studied in dogs. Eight dogs (four males and four females) received subcutaneous injections of heparin at 250 units/kg bid, seven days a week. The female dogs were euthanatized after one year and the male dogs after two years. Pre and post-drug radiographs of the forelegs (radius, ulna, metacarpal bones) did not reveal any evidence of osteoporosis. As expected, the heparin did produce increased recalcification times and the development of occasional subcutaneous hematomas. But no effects were noted on various hematologic and blood chemistry parameters or on gross and microscopic tissue examinations.


The determination of the irritancy potential of surfactants using various methods of assessment. Several animal irritancy test methods whose criteria include sensory response, pain/discomfort or tissue damage were evaluated as to their ability to assess relative irritancy potential of the following surfactants: sodium lauryl polyether (12) sulfate (SLES), Miranol C2M (MC2M), Miranol MHT (MMHT), sodium coco methyl tauride (SCMT), triethanolamine lauryl sulfate (TEALS), ammonium lauryl sulfate (ALS) and sodium lauryl sulfate (SLS). Data from the mouse upper respiratory tract and mouse writhing tests indicated that SLES, MC2M and MMHT were the least irritating and SLS, ALS and TEALS were the most irritating. The blepharospasm test did not lend itself to this type of evaluation because sequential instillation of the surfactants produced eye anesthesia. Data from the Draize eye test indicated that SLES was the least irritating while MC2M was slightly more irritating. All other surfactants were equally irritating. The Draize skin test results showed that SLES again was the least irritating at all concentrations tested and that SLS and ALS along with TEALS and SCMT were the most irritating.


Pulmonary excretion of hydrogen sulfide, methanethiol, dimethyl sulfide and dimethyl disulfide in mice. Neither hydrogen sulfide nor any other volatile sulfur metabolites were found in the expired breath of mice given sodium sulfide intraperitoneally in doses up to the LD50. The detection system was sensitive to less than 0.1% of the sulfur in the given dose. The intraperitoneal administration of dimethyl disulfide resulted in its appearance in the expired breath of mice as well as much smaller amounts of both methanethiol and dimethyl sulfide. The intraperitoneal administration of methanethiol resulted in its pulmonary excretion as well as that of dimethyl sulfide. Administration of dimethyl sulfide led to its appearance alone in expired breath. Mice pretreated with ammonium acetate and then injected with dimethyl disulfide excreted the same three compounds via the lungs as above, but there were complex changes in the proportions and in the time sequence of their appearance. The absolute amounts of all three were increased, and the peak excretion for each was delayed. The amount excreted as dimethyl sulfide was particularly increased.


Behavioral and neuropharmacological toxicology of the macrocyclic ether 18-crown-6. 18-CROWN-6 was assessed for neurologic effects in rats, mice, and rabbits by intravenous (IV) and intraperitoneal (IP) routes of administration. Male rats and mice exhibited no effects with IV doses to 20 mg/kg. Given IP doses of 20 to 160 mg/kg/day, rats and mice exhibited numerous signs, including aggression, tremors, muscle weakness and a degradation of some reflexes. All signs faded after four days when dosage levels were kept constant, but returned when the dose was doubled. All signs disappeared upon discontinuance of exposure. Treatment with PCPA (p-chlorophenylalanine) or dibenzyline caused most signs to disappear. Rabbits given 6.0 mg/kg/day IV displayed tremors, hyperactivity, unsteady gait and stereotypic behavior, with acclimation as in rats and mice. 18-CROWN-6 had no activity in isolated tissue preparations unless it was first incubated with tissues. PCPA and dibenzyline reversibly blocked the actions of incubated 18-CROWN-6 on isolated tissue. 18-CROWN-6 is hypothesized to be metabolized to a serotonergic agonist.


Effects of pyridostigmine and cholinolytics on cholinesterase and acetylcholine in Soman poisoned rats. Soman reduced blood and brain cholinesterase (ChE) activity to less than 15% and increased cerebral acetylcholine (ACh) levels to 137.4% of control. When pyridostigmine (P) was used as a prophylactic adjunct, it reduced blood ChE activity to 31.6% of control, failed to significantly alter brain ChE activity, and protected more than 70% of the blood (but not brain enzyme) from phosphonylation by soman. Benactyzine (B) was more effective than atropine (A) in reducing cerebral ACh concentrations, while a combination of the two was more effective than either alone. A prophylaxis of P + A + B was effective in controlling ACh levels in rats poisoned with one LD50 dose of Soman. Since P did not diminish the effects of the cholinolytics on cerebral ACh, this (together with the enzyme data) suggests that the two cholinolytics alone provided the central protection.


The influence of concentration, exposure duration, and patch occlusivity upon rabbit primary dermal irritation indices. The Primary Rabbit Dermal Irritation Assay as described in the Federal Hazardous Substances Act (FHSA) is used by the Consumer Products Safety Commission (CPSC) to determine the labeling requirements of household products. One of the more obvious deficiencies of this assay is the descriptive imprecision for preparing the form in which solid materials are applied. Our experimental findings show that form and concentration of test material as well as the length of contact with the skin and the degree of patch occlusivity are prime factors influencing the degree of skin change. Four detergent granular products are evaluated. In the dry powder form with 4 hour exposure all the detergents were non-irritating. The paste at 24 hours under total occlusion was the most irritating.


Effects of lead on temporally-spaced responding in rats. The effects of lead acetate and aging on temporally-spaced responding (differential reinforcement of low rate or DRL-20 seconds) were studied. Three groups of animals were considered along with their respective controls. Neonate-treated Long-Evans rats were orally intubated with 200 mg/kg lead acetate from the third to 30th day after birth. Some of these animals were tested at 3 months (adult group) and some at 21 months (geriatric group) of age. A continuously treated group was exposed to 250 ppm lead in utero and throughout their life after birth and was treated at 8 months of age. Lead-treated animals exhibited a more variable response to d-amphetamine and a more pronounced number of IRTs in the first class interval. Aging shifted the pentobarbital dose-response curve to the left in both control and lead-treated animals and flattened interresponse time (IRT) distributions.


Effect of undernutrition on the regional development of transmitter enzymes: glutamate decarboxylase and choline acetyltransferase. The effect of undernutrition on the activity of glutamate decarboxylase (GAD) and choline acetyltransferase (ChAc) (markers for the GABA-ergic and the cholinergic transmitter system, respectively) was studied in various parts of the rat brain at the age of 10, 15 and 21 days, and at day 54 following 33 days of rehabilitation. The brain regions investigated were the olfactory bulbs, cerebellum, pons-medulla, hypothalamus, colliculi, cerebral cortex hippocampus and the residual brain. Undernutrition resulted in a marked retardation of the developmental rise of the activities of both enzymes, expressed in terms of either total brain part or unit weight or protein. The effect diminished with age even during the period of nutritional deprivation. In most brain regions the enzyme activities were restored to normal after rehabilitation. In the cerebral cortex the total activity of both enzymes was persistently reduced, although the concentration of GAD exceeded the control levels. A negative correlation was manifested between the activities of GAD and ChAc in the different brain parts (except the cerebellum) during development. The correlation became significant by day 21 in the controls, but only after postweaning rehabilitation of the undernourished rats. The results showed therefore that undernutrition caused a reversible retardation in the development of these two transmitter enzymes, and they suggested that even the balance of the GABA-ergic and cholinergic systems throughout the brain can be restored to normal by rehabilitation.


The electroencephalogram in a case of pituitary dwarfism before and after eight years of treatment with human growth hormone. The EEG of an 11-year-old hypopituitary dwarf was investigated to determine whether the disorder was accompanied by a disturbance in cortical maturation. By means of a previously derived equation relating age and the first four central moments of the EEG interval histogram in normal children, the dwarf's developmental age was estimated from his EEG to be only about 6 1/2 years. After 8 years of treatment with human growth hormone, age estimated from the EEG was 8 2/3 years - an increase of barely more than 2 years.


Distribution of Thy-1 differentiation alloantigen in the rat nervous system and in a cell line derived from a rat peripheral neurinoma. The expression of the Thy-l 'differentiation alloantigen' was analyzed in rat tissues of two strains. Cerebrum was shown to express an amount of Thy-l equivalent to the thymus. The cerebellum, brain stem and spinal cord expressed approximately one-half this amount, and the olfactory bulb expressed 10- to 15-fold less. Of the peripheral nervous system tissues examined, only cauda equina expressed substantial amounts of Thy-l, although minor amounts were found on the lumbar roots and trigeminal nerve. Kidney, spleen, liver, salivary gland and testes expressed little or no Thy-l. Several cell lines derived from nervous system tumors were also examined. RN-l, a line established from a rat peripheral neurinoma, expressed Thy-l at levels comparable to thymus.


Cell junction and ultrastructural development of reaggregated mouse brain cultures. The morphological development of reaggregated embryonic mouse brain cells was followed by scanning and transmission electron microscopy. Initially, the reaggregated cells are loosely packed and lack specialized cell junction; however, after 2-4 days puncta adhaerens junctions are numerous. The first immature synapses are seen at 8-9 days of culture. These synaptic complexes mature in appearance and increase approximately 3-fold in number during the next 3 weeks of culture. Two distinct, electron dense, intercellular specialization, apparently unique to neural cell cultures, are observed in these older cultures. Brain cell reaggregates observed at 2, 3, and 5 months of culture show signs of aging, i.e., a gradual decrease in the number of synapses, myelin degeneration and increased lipofuscin granules.


Neuronal cells from chick embryo cerebral hemispheres cultivated on polylysine-coated surfaces. Dissociated cells from 5- to 12-day-old chick embryo cerebral hemispheres were cultivated in polylysine-coated plastic Petri dishes. The polylysine substrate was observed to be favorable for the growth of neuronal cells, whereas glioblast proliferation was inhibited. The optimal conditions for the production of a predominantly neuronal culture were to use cerebral hemispheres from 7-day-old chick embryos, to dissociate the brain tissue mechanically and to seed the cells at a concentration range between 1.5 and 5 X 10(6) cells/ml. The cultures were observed by phase contrast microscopy. Most cells grew fibers and differentiated into bipolar and multipolar neurons. These neurons were stained by thionine, which demonstrated the presence of Nissl bodies. The silver impregnation revealed the presence of neurofibrils within the nerve fibers. Acetylcholinesterase was found to be present in the neuronal cells, but absent in the glioblasts. Under our culture conditions the neurons survived for 10-12 days. This system should allow further studies on the effects of growth factors on the differentiation of isolated neurons as well as investigations on neuron-glial interrelationship.


Kinetic studies of cytoplasmic and mitochondrial aconitate hydratases from rat liver. The kinetic properties of the cytoplasmic and mitochondrial aconitate hydratases of rat liver have been studied by measuring the formation of the two products from each of the three tricarboxylic acids used as substrate. The kinetic properties of the two enzymes are very similar; the similarity of the Km values for each of the three substrates is particularly remarkable. The results are discussed with particular reference to a possible role of the cytoplasmic aconitate hydratase in the process of gluconeogenesis. With both aconitate hydratases, substrate activation by citrate and D-isocitrate has been observed.


Developmental changes of rat liver cytoplasmic and mitochondrial aconitate hydratases. The developmental patterns of the activity of cytoplasmic and mitochondrial aconitate hydratses of rat liver have been studied. Both activities are low in foetal liver, with respect to adult levels, and begin to increase after birth. The activity of the mitochondrial enzyme reaches a maximum about two days after birth, then decreasing gradually to adult level. The activity of the cytoplasmic enzyme reaches its maximum level, nearly equal to adult level, about ten days after birth. The developmental pattern of the activity of the cytoplasmic aconitate hydratase may suggest a possible role of this enzyme in gluconeogenesis.


A conformational model for the action of general anesthetics at the membrane level. I. Theoretical considerations. The first paper of this series describes a working hypothesis for the action of general anesthetics. According to such hypothesis, anesthetics, by inducing a labilisation of lipid-protein interactions in biomembranes, affect the conformation, and hence the activity of membrane-bound catalytic proteins. It is conceivable that such changes in ionic channels in neuronal membranes will abolish the transmission of nervous impulses and give rise to anesthesia. The hypothesis is discussed on the basis of previously known experimental data and of theoretical considerations. Thermodynamic considerations are in favour of the idea that a rupture of lipid-protein interactions will expose protein groups to water destabilising helical structures. A large decrease of alpha-helical content after lipid removal had been previously found. Furthermore lipids affect the kinetics of membrane-bound enzymes, suggesting that conformational changes occur in the catalytic site after lipid removal or perturbation.


A conformational model for the action of general anesthetics at the membrane level. II. Experimental observations on the effects of anesthetics on lipid fluidity and lipid protein interactions. We have investigated the effect of general anesthetics (the normal alcohol series up to pentanol, halothane, pentrane, ether, chloroform, and ketamine) on lipid fluidity of phospholipid vesicles and mitochondrial and erythrocyte membranes by using spin labels and fluorescent probes. The spin labels used (5- and 16-doxyl stearic acids) show that all anesthetics tested have a slight fluidizing effect on lipid vesicles but induce a very strong increase in mobility of spin labels in mitochondria and lower in erythrocyte ghosts. These results are interpreted as a labilization of lipid protein interactions at all depths in the bilayer. The fluorescent molecules ANS and NPN, which probe the glycerol region and the core of the bilayer respectively, show a decrease of fluorescence induced by alcohols, halothane, ether, chloroform in both lipid vesicles and membranes. The decrease of fluorescence is due to decreased quantum yield as shown by double reciprocal plots of probe fluorescence against membrane concentration. The fluorescence decrease is interpreted mainly as an increase in fluidity of the lipid bilayer and not as an increase of polarity of the probe environment. The effect of ketamine is that of fluidization in the bilayer core (NPN) but of increased rigidity in the glycerol region (ANS) perhaps due to the amphipathic character of this anesthetic, that is supposed to bind in the polar region of the bilayer. Pentrane also induces fluidization in the bilayer core (NPN) but has a peculiar effect near the surface (ANS): in lipid vesicles it induces a fluorescence decrease, whereas an increase is seen in mitochondrial membranes. These complex effects are considered as the result of some specific change in the lipid protein interactions in the region probed by ANS. The effects of anesthetics on maximal NPN fluorescence (Fo) have been usually found to be stronger in mitochondrial membranes than in lipid vesicles, thus confirming the results of the spin label studies, showing a labilization of lipid protein interactions induced by anesthetics. The effects on Fo of ANS, however, appear to be stronger in lipid vesicles than in membranes. These findings indicate that the presence of the proteins counteracts the perturbation induced by anesthetics at the level of the membrane surface, in contrast with the disruption of lipid protein interactions observed in the membrane hydrophobic areas.


The significance of "positive" margins in surgically resected epidermoid carcinomas. Sixty-two patients with epidermoid carcinomas of the head and neck (excluding glottic larynx and skin), in whom surgical-resection margins were classified as "positive", were studied to determine the incidence of local recurrence, the subsequent clinical course, and survival. The recurrence rate in this group was compared with that of patients who had "negative" margins. Four histologic findings are classified as positive margins: (1) margin closeness (tumor within 0.5 cm), (2) premalignant change in the margin, (3) in-situ cancer in the margin, and (4) invasive microscopic cancer at the margin. Patients with these variants showed a significant increase in local recurrence and in mortality when compared to those with negative margins. A review of the literature is presented, and recommendations are made for this clinical setting.


Malignant melanoma of the head and neck. Sixty-nine patients with head and neck melanoma were prospectively evaluated from 1971 to 1977. Patients presenting for initial therapy underwent wide excision of their primary tumor, and those with deeply invasive melanoma also underwent regional lymphadenectomy, whether their nodes were clinically positive or negative. The results suggest that the prognosis of this tumor is similar to that of melanoma arising at other sites. Clinical stage and primary-tumor histopathologic microstage both correlated with disease recurrence. At 1 to 75 months, patients with clinical Stage I disease had a 13% recurrence rate, while 58% of those with Stage II disease developed recurrence. Patients with superficially invasive melanoma had a 10% recurrence rate, while 17%-33% of those with deeply invasive disease developed recurrence. However, the presence of node metastases, rather than the microstage of the primary tumor, appeared to be the dominant indicator of outcome. Radical excision of the primary tumor may reduce the incidence of local disease recurrence. We believe that regional lymphadenectomy is indicated for deeply invasive melanoma.