Induced mutagenesis in Ustilago maydis. II. An in vivo biochemical assay.

UV gamma radiation-induced reversion to nar+ in a nar1-m nir1-1 strain of Ustilago maydis was found to occur under nongrowth conditions by performing the in vivo assay for functional nitrate reductase described by Resnick and Holliday (1971) who previously demonstrated that nonviable cells may still synthesize normal or near-normal levels of activity. Reversion frequencies of a signle gamma-irradiated culture were estimated in two cell populations by different methods: (A) among surviving clones after plating, and (B) among all cells (viable and nonviable) in suspension in the absence of postirradiation cell division. At gamma doses (300, 500 krad) corresponding to considerable cell killing (35%, 2% survival), reversion frequency by either method was the same. This supports the conclusion that mutation induction by gamma rays and its expression occur in nonviable cells with the same frequency as among survivors. If an error-prone repair system is assumed to be responsible for the observed gamma revertibility, then it is argued that this process is constituitive rather than inducible and that it is recombination-independent.


The isolation of IS1 and IS2 DNA.

DNA of the IS-elements IS1 and IS2 was prepared by digestion of appropriate heteroduplex molecules with endonuclease S1, followed by sucrose gradient centrifugation or gel electrophoresis. The material obtained is homogeneous with regard to size. The length of IS1 DNA is 820 +/- 65 nucleotides, the length of IS2 DNA is 1,350 +/- 70 nucleotides. IS1 DNA is not cleaved by the restriction endonucleases Eco R1, Hind II or Hind III. IS2 DNA is cleaved once by each of the two latter enzymes. The buoyand density determined by equilibrium centrifugation of Hg-complexes in Cs2so4 corresponds to a GC content of approximately 50%. Labelling with polynucleotide kinase indicates that both IS DNA's have a guanosyl residue at both of their 5'-termini.


Octopine and nopaline synthesis and breakdown genetically controlled by a plasmid of Agrobacterium tumefaciens.

Several nopaline degrading strains and one octopine degrading strain are shown to loose oncogenicity as well as the ability to utilize these guanidine compounds when they are cured of their TI plasmid. To investigate whether the specific genes involved in the utilization of one or the other compound are located on the plasmid, plasmid-transfer experiments have been performed. The plasmid from a nopaline degrading strain has been transferred to a naturally non oncogenic Agrobacterium namely A. radiobacter. Furthermore, the plasmid from an octopine degrading strain has been transferred to a plasmid-cured strain which originally had the capacity to utilize nopaline. Both kinds of experiments prove that the TI plasmid determines the strain specificity with regard to the utilization of either octopine or nopaline. They also demonstrate that the synthesis of either octopine or nopaline in crown gall cells is also determined by genes located on the TI plasmid harboured by the transforming A. tumefaciens strains.


The influence of DNA binding protein on the substrate affinities of DNA polymerase from Ustilago maydis: one polymerase implicated in both DNA replication and repair.

The DNA polymerase of Ustilago maydis is stimulated by a DNA binding protein from the same organism. Analysis of this stimulation shows that there is an increase in affinity for both substrates of the reaction. The apparent Km for deoxynucleoside triphosphates is decreased 3 fold, and that for denatured DNA by 4 fold. In both cases the maximum velocity (Vmax) is increased 1.2 to 1.4 fold. It is suggested that the variability in the affinity of the enzyme for deoxynucleoside triphosphates mediated by the binding protein may provide the basis for the UV sensitivity of pyrimidine auxotrophs in this organism.


[A new (brachymelic) type of primordial dwarfism (author's transl)].

Second report of an apparently new type of primordial dwarfism characterized by severe intrauterine and postnatal growth retardation, striking craniofacial deformities and a peculiar osteochondrodysplasia. The major clinical findings are microcephaly, hypotrichosis, bulging eyes, prominent nose, micrognathia and short extremities. The osteochondrodysplasia is characterized by short and bowed humeri and femora with absent ossification of the femoral necks, small and dysplastic iliac wings, strikingly retarded ossification of the epiphyses and shortened metacarpal I and middle phalanges II-V. Possible this condition is caused by the homozygous state of mutant gene. The brachymelic type of primordial dwarfism differs from other forms of primordial dwarfism (particularly from case I of Seckel) by its skeletal abnormalities. The cases described by Seckel (and sometimes referred to as Seckel or bird-headed dwarfism) are heterogenous: Seckel dwarfism apparently does not exist as a nosologic entity.


[Transcutaneous oxygen tension measurement in pediatrics (author's transl)].

The development of a new electrode by A. Huch, R. Huch, and D. Lübbers to measure the arterial oxygen tension transcutaneously (tcPo2) has provided the opportunity for continuous monitoring in critically ill children. For the first time it is possible to monitor oxygen therapy and to minimize considerably the risk of oxygen therapy. With this technique respirator therapy can be managed much more critically and effectively. Changes in PaO2 are recognized within seconds and dangerous hyper- and hypoxias can be corrected immediately. We demonstrated that there exist different heart rate patterns with hypoxemia; these changes normally are not recognized with convential methods. The significance of the silent heart rate pattern has not yet been established. As there are no problems now with the manufacturing of the electrodes, we hope that this excellent method will be used wherever critically ill children are treated.


[Pyelonephritis in patients with congenital malformations of the urinary tract after corrective operation and under antibiotic therapy (author's transl)].

398 (otherwise unselected) children with certain types of congenital urinary tract malformation were followed up for a period of not less than three years for evaluation of the infection rate after surgical correction (the latter performed in 1968 to 1972). During a six month course post op., all patients received appropriate antibacterial drugs, thereafter cessation of medical treatment depending upon normal findings in urinalysis. The over-all cure rate was 77% after six months, 85% after twelve months, 95% after two years and 97% after three years. No recurrence of urinary tract infection was observed three years after surgery of in frapelvic ureteral stenosis/hydronephrosis (n=86; Anderson-Hynes procedure) in 100%; of distal ureteral stenosis/megaureter (n=76; Politano-Leadbetter or occasionally Boari approach) in 92%; and of primary reflux (n=236; Lich-Grégoir technique) in 98%. The incidence of infectious relapse following any normal cytological and bacteriological control was 1% resp. 7% resp. 2%, with an average of 3% for all three groups.


[Ballooning mitral valve in tricho-rhino-phalangeal syndrome (author's transl)].

The ballooning mitral valve defect has been repeatedly found in hereditary disorders of connective tissue such as the Marfan syndrome, osteogenesis imperfecta and the Ullrich-Turner syndrome. The present report concerns a nine year old girl with tricho-rhino-phalangeal dysplasia type I and this peculiar anomaly of the mitral valve. Since a literature review disclosed two more cases with tricho-rhinophalangeal dysplasia I and mitral insufficiency, the association may be more than fortuitous. Apparently the mesenchymal changes in tricho-rhino-phalangeal dysplasia I are not limited to the skeletal system.


Dose-response data for X-ray induced translocations in spermatogonia of Rhesus monkeys.

The yields of translocations in spermatocytes after irradiation of spermatogonia of Rhesus monkeys with doses of 100, 200 or 300 rad X-rays were low, and consistent with a humped dose-response curve with a peak at about 200 rad. Such a curve would agree well with earlier results on the marmoset and man, but the yields at any dose in the Rhesus monkey were lower.


The effect of changes in dose rate on the yield of chromosome aberrations in human lymphocytes exposed to gamma radiation.

The yield of chromosome aberrations was studied in Go human peripheral blood lymphocytes following in vitro exposure to 100, 250 and 500 rad of caesium-137 gamma radiation. The doses were given at various rates up to 400 rad per h with the longest exposures lasting for approx. 50 h. At 500 and 250 rad the dicentric yields fell by 66 and 64% when the dose rate was reduced from 400 to 10 rad per h whereas at 100 rad the reduction was only 29%. Reductions were also noted in frequency of acentric aberrations. At the higher dose rates (greater than 150 R/h) the aberration yield was constant and agreed with data published elsewhere for 3000 R/h. The dose rate at which the decline in aberration yield became apparent was dose dependent and, for dicentrics, occurred at about 150, 100 and 25 rad/h respectively for the 500-, 250- and 100-rad doses. The data are interpreted in terms of the quadratic model of aberration induction in which the dose-squared term represents dose rate dependent two-track aberrations which constitute an increasingly important component of yield as dose increases. The implications of this work for cytogenetic dosimetry are discussed.


Factors affecting the growth of Chinese hamster cells in HAT selection media.

Factors affecting the efficiency of selection of "revertants" of salvage pathway mutants in media containing amethopterin have been examined. Our V79 Chinese hamster cell line was found to require a significantly higher level of thymidine for optimal growth in such media than has been reported for other cell lines. Hypoxanthine (but not glycine) was also required for reversal of amethopterin toxicity, but levels did not differ significantly from those reported elsewhere. Growth in HAT was also dependent on plating density and serum batch. Our modification (VHAT) was compared with published HAT recipies in back selection reconstruction experiments. A sharp fall in EOR (efficiency of recovery) of wild type cells from  mixtures with mutants at plating densities greater than 3500 cells/cm2 (10(5) cells/6 cm dish) was observed for VHAT. EOR with other HAT recipes was lower still, and was affected also by the particular mutant used in the mixture. EMS induced "revertants" were isolated from three 8AZr mutants by plating in VHAT. All revertants were however amethopterin resistant, they were also 8AZ resistant and the mobility of residual HGPRT (as measured by polyacrylamide gel electrophoresis) was similar to that of their 8AZr parents i.e. dissimilar from that in wild type. The modal chromosome number of V79 wild type cells was 21. No significant deviation from this mode was detected in any of the mutant lines examined. The data indicate that the recovery of colonies in HAT from 8AZr mutants does not necessarily indicate that a back mutation in the structural gene for HGPRT has occurred. Thus, the frequency of HAT+ colonies cannot be taken as a direct indication of reversion frequencies.


Factors affecting the efficiency of purine analogues as selective agents for mutants of mammalian cells induced by ionising radiation.

In the Chinese hamster cell line V79-4, the frequencies of the cells selected for their resistance to purine analogues do not always reflect the true frequencies of resistant mutants. The frequency of cells resistant to 8-azaguanine varied widely, especially when different sources of serum were used in the selective medium. Even with the more efficient analogue, 6-thioguanine, small colonies arose in the selective medium at a frequency which was strongly dependent upon analogue concentration and viable cell seeding density. These colonies were shown to have a phenotype which was indistinguishable from wild type. Hence with irradiated cells, where the viability of the cell population is reduced to an extent varying with the dose and the interval allowed for mutant expression, the counting of all colonies arising in selective medium  can lead to spuriously variable, and sometimes very high, "mutation frequencies". Although the frequency of wild type colonies selected in thioguanine was diminished by the use of high concentrations of the analogue, a loss of induced mutants also occurred at these concentrations. Further, the V79-4 line contained two distinct types of mutant with different levels of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity, and only of these types (HGPRT-negative mutants) increased in frequency with radiation dose. These results can account for many of the anomalies encountered in previous studies with purine analogues as selective agents, and show that some care has to be taken to characterize the mutants selected by resistance to purine analogues before meaningful dose-response relationships can be established.


A new statistical evaluation of the dominant-lethal mutation test.

A multivariate statistical method for evaluation of the dominant-lethal mutation test is outlined which takes into consideration the dependence among the dimensions of the test. It can also be fitted into a computer programme as is necessary with dominant-lethal tests which often give a large number of data. This article describes a multivariate statistical method and gives an example of an experiment evaluated with the method.


The effect of insecticides on Chinese hamster cell cultures.

The effect of p,p'-isomers of DDT and its derivatives DDD, DDE and DDA on Chinese hamster cells in culture was studied. At different concentrations and various times of treatment the proliferation rate was inhibited most strongly by DDD and DDT, whereas DDE exhibited a markedly weaker influence. DDA was the least toxic compound of the four. The cytogenetic effects were also different. Again, DDA induced the least damage. Only enhanced gap rates but no chromosome breaks were observed. DDE was more active, and higher break rates occurred. DDD and DDT were by far the most damaging compounds, and they raised the gap and break rates markedly. However, no induction of configuration anomalies was found in any experiment. Chronic treatment of the cells for 3 months with DDT at 8 ppm did not alter the proliferation rate, the sensitivity to acute treatment with higher DDT concentrations or the chromosomal aberration rates. The results are discussed in relation to the relevance of differential pesticide effectivity in organs of higher animals and man.


Mutagenic effect of sodium nitrite on cultured mouse cells.

Effect of sodium nitrite on cultured FM3A cells, a C3H mouse mammary carcinoma cell line, was examined. The chromosomal preparations demonstrated that severe aberrations were induced in more than 80% of the mitotic plates at 10(-2) M and in nearly 40% at 10(-25) M after 24 and 48 h treatment. According to the results of alkaline sucrose gradient analysis sedimentation profiles of cell DNA treated at as high as 10(-1) M for 24 h scarcely changed from that of control cell DNA. Induction of 8-azaguanine-resistant mutation was demonstrated above 10(-3) M sodium nitrite.


Chromosome analyses in cell cultures of the Chinese hamster after application of cadmiumsulphate.

Cell cultures of a Chinese hamster cell line were treated with CdSO4 in concentrations of between 10(-4) and 10(-8) mol/l for different time periods. After a treatment of 16 h the mitotic index was reduced. Strong stickiness and pycnosis of chromosomes occurred at the highest concentrations. A treatment period of 3 h with concentrations of 10(-5) and 10(-4) mol/l without additional application of Colcemid and hypotonic solution yielded a stathmokinetic effect. The mitotic index increased, mitoses were blocked in metaphase stage and "initial C-mitoses'' and "C-mitoses'' were present. Structural chromosome aberrations were present in the recovery period of more than 12 h following a treatment of 1 h with 10(-4) mol/l CdSO4. The observed aberrations were mainly of the chromatid type.


Cytogenetic study of DDT on human lymphocytes in vitro.

The cytogenetic effect of DDT on human blood cultures, in vitro, was investigated. Two types of experiment were carried out: one, in which the DDT concentrations found in the culture media were similar to those found in the plasma of individuals of the Brazilian population (0.06--0.20 mug/ml); in the second experiments, doses ranging from 1 to 15 mug/ml were used. No correlation was found between DDT doses and cells with chromosomal aberrations. The Poisson test of comparison between means showed that at certain DDT concentrations (0.20, 4.05 and 8.72 mug/ml) the proportion of cells with structural aberrations was significantly greater than in the controls.


Lymphocyte chromosome studies in humans exposed to chemical mutagens. The validity of the method in 67 patients under cytostatic therapy.

Eighty-three lymphocyte cultures from 67 patients exposed to high therapeutic doses of chemical mutagens and from 10 healthy controls were examined for structural aberrations of the chromatid type (gaps, breaks and exchanges) and chromosome type (rings, dicentrics, acentric fragments and abnormal chromosomes) in order to evaluate the reliability of this testing system. Most of the patients had received several drugs; a few had radiotherapy as well. Owing to insufficient yields of mitoses at shorter incubation periods a culture time of 72 h had to be chosen. Whenever possible, 100 mitoses were analyzed. Because evaluation is highly subjective, gaps (i.e. interruptions of the chromatid structure not clearly exceeding a chromatid's width) were not included in the results. The incidence of chromatid breaks was 0--2% in the controls and 0--4% in most of the patients. In 6 cases containing 5--15% mitoses with chromatid breaks and exchanges, these values did not correlate with increased incidences of chromosome type aberrations. The incidence of chromosome type aberrations was 0--1% in the controls as well as in 19/20 patients who had received anti-metabolites and spindle poisons only and in 22/53 patients who had received therapeutic irradiation and/or well-known clastogenic agents. From these findings it is concluded that an increased incidence of chromatid breaks and exchanges is not a typical finding in lymphocyte cultures of persons exposed in vivo to chromosome breaking agents, and that a normal incidence of chromosome type aberrations does not exclude exposure to massive doses of clastogens. This testing system is therefore judged to be inadequate for monitoring weak or questionable mutagens in exposed populations.


Hyperuricosuria due to high-dose pancreatic extract therapy in cystic fibrosis.

Dysuria, uric acid crystalluria and hyperuricosuria developed in a child with cystic fibrosis and normal serum uric acid. Hyperuricosuria in this patient and two other children was directly related to ingestion of large amounts of pancreatic extract. In these three children, reducing pancreatic extract dosage by 85 percent lowered their purine intake by 307, 225, and 148 mg, respectively; urinary uric acid excretion decreased by 245, 239, and 158 mg. Overmedication resulted from parents' decisions to increase enzyme dosages. In our cystic fibrosis clinic, 15 of 32 patients screened at random were taking higher than the prescribed dose of pancreatic enzymes, and 14 of these 15 children were hyperuricosuric. On the basis of this information, we suggest that the minimal effective dose of pancreatic extract should be determined and adhered to for each child with cystic fibrosis to avoid potential renal injury from hyperuricosuria.


Lack of efficacy of thermography as a screening tool for minimal and stage I breast cancer.

In a study of thermograms of 42 patients with Stage 1 or smaller carcinomas of the breast, 44 confounding cases and 64 randomly selected subjects being screened, we found that the ability of expert thermographers to identify the patients with carcinoma correctly (true positive = 0.238) varied little from the ability of untrained readers (true positive = 0.301). Furthermore, in the expert group, the indexes of suspicion were so high (0.436) and the true-positive levels were so relatively low (0.238, P = 0.0005) that thermography may well have a very limited role as a screening or pre-screening modality for the detection of minimal or Stage 1 breast cancers.


Low thyroid hormones and respiratory-distress syndrome of the newborn. Studies on cord blood.

To investigate the relation between thyroid function and respiratory-distress syndrome we determined thyroid hormone in cord serum from 39 term and 120 premature newborns. In groups matched for gestational age (33 to 37 weeks) and body length, after exclusion of newborns with birth asphyxia, maternal diabetes and delivery by cesarean section, the newborns with respiratory distress syndrome had significantly lower cord tri-iodothyronine index, higher ratio of thyroxine to tri-iodothyronine and higher thyrotropin concentration than those without syndrome (P less than 0.05 or less). Conversely, the frequency and severity of respiratory-distress syndrome were higher in newborns who had low cord tri-iodothyronine and thyroxine concentration, low free tri-iodothyronine index and high thyrotropin levels. These observations show an association between low thyroid activity at birth and respiratory-distress syndrome and are in accord with animal studies showing accelerated lung maturation due to thyroxine administration.


Obesity in young men after famine exposure in utero and early infancy.

In a historical cohort study of 300,000 19-year-old men exposed to the Dutch famine of 1944-45 and examined at military induction, we tested the hypothesis that prenatal and early postnatal nutrition determines subsequent obesity. Outcomes were opposite depending on the time of exposure. During the last trimester of pregnancy and the first months of life, exposure produced significantly lower obesity rates (P less than 0.005). This result is consistent with the inference that nutritional deprivation affected a critical period of development for adipose-tissue cellularity. During the first half of pregnancy, however, exposure resulted in significantly higher obesity rates (P less than 0.0005). This observation is consistent with the inference that nutritional deprivation affected the differentiation of hypothalamic centers regulating food intake and growth, and that subsequent increased food availability produced an accumulation of excess fat in an organism growing to its predetermined maximum size.


The stereoselective interaction of warfarin and metronidazole in man.

Because of the known interaction of warfarin and disulfiram and the "disulfiram effect" of metronidazole, the interaction with metronidazole of commercial racemic warfarin and its separated enantiomorphs was evaluated in eight normal subjects. Single oral doses of racemate, S(-)-warfarin, and R (+)-warfarin, were administered in the amounts of 1.5, 0.75 and 1.5 mg per kilogram of body weight, respectively, with and without metronidazole, 750 mg by mouth, beginning seven days before the warfarin dose and continuing seven days before the warfarin dose and continuing daily throughout the hypoprothrombinemia. Daily plasma samples were analyzed for warfarin in content and one-stage prothrombin time. A highly significant (P less than 0.01) augmentation of the mean warfarin level and hypoprothrombinemia with metronidazole occurred for racemic and S (-)-warfarin; none occurred with R (+)-warfarin. Thus, the interaction of racemic warfarin and metronidazole is stereoselective and can be lessened or even avoided by use of R (+)-warfarin alone for long-term therapy.


Pharmacokinetic aspects of theophylline in premature newborns.

To characterize further the pharmacokinetics of theophylline in premature infants, its concentraion in blood was measured by high-pressure liquid chromatography after intravenous infusion given to six apneic premature newborns three to 15 days of age. Theophylline's apparent volume of distribution was 0.690 +/- 0.095 liters per kilogram (mean +/- S.E.), a value similar to that of children, but the half-life (30.2 +/- 6.5 hours) was nine times longer. Blood clearance rate (17.6 +/- 2.3 ml per kilogram per hour) was lower than plasma clearance rate (100 ml per kilogram per hour) of young children. At a total plasma concentration of 17 mg per liter, 56.4 +/- 3.8 and 36.4 +/- 3.8 per cent of the theophylline was bound to adult or full-term cord plasma proteins, respectively. Bilirubin and theophylline did not compete for plasma protein. Calculations suggest that a loading doses of 5.5 mg per kilogram and a maintenance dose rate of 1.1 mg per kilogram per eight hours would achieve and maintain a mean blood concentration of 8 mg per liter (about 10 mg per liter in plasma).


Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus.

We studied the increased levels of hemoglobins AIa+Ib and AIc in five hospitalized diabetic patients to determine whether changes in diabetic control would cause parallel changes in the levels of these hemoglobins. Before control of diabetes the mean fasting blood sugar for all patients was 343 mg per deciliter (range, 280 to 450), and hemoglobin AIc concentration 9.8 per cent (range, 6.8 to 12.1). During optimal diabetic control the blood sugar concentration was 84 mg per deciliter (range, 70 to 100), and hemoglobin AIc concentration 5.8 per cent (range, 4.2 to 7.6). Hemoglobin AIc concentration appears to reflect the mean blood sugar concentration best over previous weeks to months. The periodic monitoring of hemoglobin AIc levels provides a useful way of documenting the degree of control of glucose metabolism in diabetic patients and provides a means whereby the relation of carbohydrate control to the development of sequelae can be assessed.


Search for B-1 aflatoxin and similar fluorescent compounds in 'misso'.

Following previous studies on the investigation of B-1 Aflatoxin in food samples (4,5) we report in this paper the results obtained using thin layer chromatography (TLC) with three different solvent systems and spectrophotometric analysis in order to differentiate actual B-1 Aflatoxin and Aflatoxin-like substances. Twenty 'Misso' samples were studied and we could detect Aflatoxin in 3 of them. An Aflatoxin-suspected substance was also isolated. No Aflatoxin-producing Aspergillus was isolated from the samples analysed.


[Systematic study of Saccharomyces: oxidases and vitamin requirements].

A study of the genus Saccharomyces by new biocharacters demonstrates indirectly the genotype of each species; intracellular osidases (lactose - maltose -cellobiase - melibiase - invertase - trehalase) and vitamin requirements (biotin-folic acid-inositol-niacine-pantothénate-para-aminobenzoic acid-pyridozine-thiamine) reveal some phylogenetic links between the species. It appears that Van der Walt's group I is very homogeneous and must be restricted to only 7 species. The torulospora group seems very similar to the genus Debaryomyces when vitamin needs and osidases are considered; the relations between the 2 groups are discussed. When other biocharacters are studied (nitrite reductase-immunological properties, etc. ...) the value in the GC content (4-5% lower in Debaryomyces) will be established. These results confirm that intracellular oxidases and vitamin needs are very valuable tools for systematic criteria.


Effect of acetone on production of aflatoxins and versicolorin pigments by resting cell cultures of Aspergillus parasiticus.

Resting cell cultures of Aspergillus parasiticus were grown in medium containing four different concentrations of glucose, with and without acetone. In addition, the effect of different equimolar concentrations of acetone, acetic acid, ethanol, and sodium acetate was compared at two glucose levels. Aflatoxin and versicolorin pigment production increased in resting cell medium containing increasing concentrations of glucose. In the presence of glucose high concentrations of acetone (1.0 and 0.25 M) inhibited secondary biosynthesis and low concentrations of acetone (0.1, 0.025 and 0.01 M) stimulated secondary biosynthesis of aflatoxins and versicolorin pigments.


Ex vivo determination of potentially virulent Sporothrix schenckii,.

Hyphae from 30 isolants of Sporothrix and Ophiostoma species were washed, dried and pyrolyzed at 350 degrees C. Pyrolysis products were separated on a Carbowax column heated 7.5 degrees C/min to and maintained for 50 min at 160 degrees C. Hydrogen flame detector responses were recorded graphically. Fifteen clinical isolants of S. schenckii from geographically separated sources produced qualitatively identical pyrograms. S. foliorum, 8 avirulent S. schenckii and other Sporothrix species isolants from soils, and Sporothrix states of 6 Ophiostoma species yielded pyrograms readily distinguished from each other and from those of virulent S. schenckii. Taxonomic and clinical implications of the pyrograms are mentioned.


Mycoflora of activated sewage sludge.

Thirty-eight species of fungi were identified in pure culture after isolation from activated sewage sludge by serial dilution. Nine species and genera were identified that had not been previously reported. In 1963, Cooke (1) published an excellent laboratory guide on the identification of fungi from polluted water, sewage, and sewage treatment systems; of approximately 30 papers cited only one (2) dealt with fungi from activated sewage sludge. Later (1970), Cooke & Pipes (3) enumerated 47 fungi consisting of 4 genera of yeasts and 33 genera of filamentous fungi that had been isolated from activated sludge. This paper reports the mycoflora of anaerobically digested sludge from a residential area in Auburn, Alabama.


Pathogenesis of paracoccidioidomycosis: a model based on the study of 46 patients.

Forty-six Paracoccidioidomycosis patients were studied with emphasis on lung pathology. It was found that the greatest clinical involvement of the reticuloendothelial system occurred in younger individuals. On the other hand, the frequency of tegumentary lesions was low in young patients and increased with age. Lung involvement was nearly always demonstrated when searched for and showed no relationship to the patient's age. In the young patients the disease was acute while in the older individuals its course was chronic. The findings from this study permitted formulation of a model for the pathogenesis of paracoccidioidomycosis in which the respiratory tract is accepted as the primary site of infection. Based on this model, a classification of the various forms of the entity is proposed.


[Study of the contamination by dermatophytes of a population of small wild mammals in Alsace].

Mature fruit-bodies of Coprinus congregatus grown on modified Bille-Hansen medium were obtained with concentrations of glucose ranging from  5 to 40 g/l and asparagine from 0 to 4 g/l; the carbon/nitrogen ratio varying from 13 to 100. When the ratio C/N is too high (above 100), no visible primordium is formed; when this ratio is under 13, numerous primordia are produced, but they never reach maturity. A positive correlation exists between the C2/N ratio and the time required for producing mature fruit-bodies. The best yield for basidiocarps production is reached when the C/N ratio value is around 30 and glucose concentrations range from 10 to 20 g/l.


Simple mathematical models with very complicated dynamics.

First-order difference equations arise in many contexts in the biological, economic and social sciences. Such equations, even though simple and deterministic, can exhibit a surprising array of dynamical behaviour, from stable points, to a bifurcating hiearchy of stable cycles, to apparently random fluctuations. There are consequently many fascinating problems, some concerned with delicate mathematical aspects of the fine structure of the trajectories, and some concerned with the practical implications and applications. This is an interpretive review of them.


Structural patterns in globular proteins.

A simple diagrammatic representation has been used to show the arrangement of alpha helices and beta sheets in 31 globular proteins, which are classified into four clearly separated classes. The observed arrangements are significantly non-random in that pieces of secondary structure adjacent in sequence along the polypeptide chain are also often in contact in three dimensions.


Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides.

The microsomal fraction of horse and human platelets contains an enzyme which converts prostaglandin cyclic endoperoxides (PGG2 or PGH2) to a substance which is much more potent in contracting strips of rabbit aorta. This substance has the same characteristics as thromboxane A2, and can be distinguished from other products of arachidonic acid metabolism by differential bioassay.


4S oop RNA is a leader sequence for the immunity-establishment transcription in coliphage lambda.

oop RNA, which is initiated at the po promoter and is 81 nucleotides long, can function as a leader sequence for the lambda immunity establishment transcription, previously believed to originate at a special promoter pre located in the y region. Thus, oop RNA seems to have a dual role, either favouring the lytic cycle as a primer for the initiation of lambda DNA replication, or leading to the establishment of lysogeny when elongated into the imm transcript, which directs synthesis of the repressor.


Model consideration for the origin of life. Environmental structure as stimulus for the evolution of chemical systems.

In an attempt to understand the origin of living systems we encounter the following problems: How can we conceive the origin of the first self-reproducing forms, and by means of what stimuli could a constant increase in the complexity of such forms commence? How can a translation apparatus for genetic information develop? One cannot imagine that such an apparatus for the synthesis of enzymes can function alone without the interference of enzymes themselves, which, however, could only become available after the construction of the apparatus itself. What stimulus mechanism is conceivable that leads to the division of the genetic apparatus into a replication system, and an enzyme-synthesis system? The main problem therefore, is not the search for basic theoretical concepts. It is not a question which can be answered by means of specific experiments. One should rather explore the principal possibilities of how molecules combine to produce more and more complicated functional units. We look for the fundamental structural changes in the organizational systems and the driving forces initiating these developments. Questions concerning the detailed chemical realization are of secondary importance. In trying to solve the puzzle of how the genetic apparatus is gradually built up as complex aggregates of molecules, we consider a consistent causal chain of simple and transparent physiochemical model steps. The driving force for the self-organization of matter is seen in a specific environmental structure to be found on the surface of the earth. By this structure, which is periodic in time and heterogeneous in space, evolution is initiated and driven towards a continuously increasing degree of complexity correlated with a continuous expansion of the accessible living space. This process is a necessity under proper environmental conditions. Accidental events initiate each step but do not determine the general course of evolution which is determined by the selection mechanism.


[Use of microalgae for nutritional purposes].

Mass cultures of planktonic microalgae can render large quantities of proteinaceous matter. The good nutritional quality of microalgal protein has been proven both for animals and for human. The toxicologic safety of microalgal biomasses is, however, not yet sufficiently established. This requires further toxicologic studies, before cultivated mocralgae can commercially be utilized as ingredients of animal feed, or as food additives. Both types of nutritional application may become economically feasible.


Hypothalamic superfusion with muscarinic drugs: their effects on pressor responses to hypothalamic stimulation.

The posterior hypothalamus of cats anaesthetized with pentobarbital sodium was superfused with artificial cerebrospinal fluid through a push-pull cannula and electrically stimulated with the noninsulated tip of the cannula. The effects of muscarinic drugs on the pressor response to stimulation of the hypothalamus were investigated. Superfusion with muscarine, oxotremorine or N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602) decreased the pressor responses to hypothalamic stimulation. Superfusion with methylatropine did not influence the pressor responses to hypothalamic stimulation; however, superfusion with methylatropine 60 min prior to and during superfusion with the muscarinic drugs abolished the inhibitory effects of muscarine and oxotremorine and temporarily reversed that of AHR 602 on the pressor responses. Superfusion of the posterior hypothalamus with arecoline enhanced the rise of blood pressure elicited by hypothalamic stimulation. When the hypothalamus was superfused with hexamethonium 60 min prior to and during superfusion with arecoline, arecoline reduced the pressor responses to electrical stimulation of the hypothalamus. Superfusion with methylatropine prior to and together with an ineffective concentration of arecoline increased the rise of blood pressure elicited by hypothalamic stimulation. From the drugs studied here only oxotremorine caused a fall of the "resting" arterial blood pressure; it was abolished by the intravenous injection of methylatropine. From these results it was concluded that superfusion of the posterior hypothalamus with muscarinic drugs impairs the pressor responses to hypothalamic stimulation. Drugs possessing both nicotinic and muscarinic properties either enhance or diminish the pressor responses according to their relative potencies on the two types of receptor.


Peptide and acetylcholine action on neurones of the cat subfornical organ.

Angiotensin II, related oligopeptides and acetylcholine were tested on neurones of the cat subfornical organ (SFO). Angiotensin II activates SFO-neurones by local administration onto the surface, by i.v. injection or with the aid of microiontophoretic techniques. Application of related oligopeptides, bradykinin, physalaemin and eledoisin showed no comparable results. Activation of neurones similar to those observed after angiotensin II was obtained with acetylcholine. About 30% of the cells tested were excited by both substances, 56% of tested SFO-cells responded only to angiotensin II, but not to acetylcholine. Atropine sulphate prevents specifically the acetylcholine excitation. Since angiotensin II is involved in regulatory mechanism of thirst, these results suggest the possibility that the SFO is one of the sites, where dipsogenic receptors for this circulating peptide are located.


Effect of theophylline on calcium exchangeability in ventricular myocardium.

The effects of theophylline on contractile force and myocardial calcium exchangeability were studied in isolated, electrically driven Langendorff perfused guinea-pig hearts. Following a 30-min exposure to 45Ca, total cellular calcium and 45Ca activity were measured in right ventricular samples. "Nontoxic" theophylline concentrations (5 x 10(-5) -10(-3) g/ml) which augmented contractile force without producing arrhythmias or contractures had no effect on total tissue calcium and did not alter the size of the fraction of cellular calcium exchangeable under steady-state conditions. A "toxic" concentration of theophylline (2 x 10(-3) g/ml) induced contractures and increased the amount of exchangeable cellular calcium. The latter effect was due to an increase in total calcium; the unlabelled cellular calcium fraction remained unchanged under the influence of all theophylline concentrations studied. The results suggest that theophylline increases the steady-state calcium exchangeability in ventricular myocardium only when the total calcium concentration is also increased.


On the relation between release of prostaglandins and contractility of rabbit splenic capsular strips.

Rabbit splenic capsular strips release prostaglandins E and F when contracted by noradrenaline or methoxamine. Contractions and prostaglandin release are dose-dependent. Cocaine increases significantly the effect of noradrenaline, but not that of methoxamine, on contraction of the strips and release of prostaglandin E. Release of prostaglandin F was increased by the addition of cocaine not only when noradrenaline was used as an agonist but also at two of three dose levels of methoxamine. When indometacin is added to the bath fluid, it inhibits prostaglandin release and at the same time potentiates the contractile effects of noradrenaline and methoxamine on the rabbit splenic capsular strips. The prostaglandin-synthetase blocker 5,8,11,14-eicosatetraynoic acid also potentiates the contractions induced by noradrenaline and methoxamine. Both the effects on prostaglandin synthesis and on contraction exerted by indometacin can be reversed, when indometacin is washed out. Exogenous prostaglandins E1, E2 and F2alpha in concentrations up to 150 ng/ml do not influence contractions of the strips induced by either noradrenaline or methoxamine. At higher concentrations prostaglandin E1 decreases, but prostaglandins E2 and F2alpha increase the contractions induced by both agonists. The potentiation of the effects of noradrenaline and methoxamine on rabbit splenic strips by indometacin and 5,8,11,14-eicosatetraynoic acid cannot be explained by inhibition of uptake1 or uptake2, release of endogenous noradrenaline or inhibition of metabolism of the agonists. It is suggested that the potentiation is caused by inhibition of synthesis of endogenous prostaglandins, although an undefined sensitizing effect of indometacin and 5,8,11,14-eicosatetraynoic acid cannot be completely exclused.


The fate of phenylhydroxylamine in human red cells.

Phenylhydroxylamine added to human red cells under aerobic conditions and in the presence of glucose was partly reduced to aniline. About half the hydroxylamine was recovered as amine after a 2-hr incubation. The aniline, after acetylation, was identified as acetanilide by melting point, Rf-value in TCL as well as UV, IR, and NMR spectroscopy. The fate of the remaining phenylhydroxylamine was followed by use of 14C-labeled phenylhydroxylamine. About 30% of the total radioactivity was bound to hemoglobin or other proteins and about 20% was found in highly polar low-molecular substances which were insoluble in organic solvents. The elucidation of the sites at which phenylhydroxylamine was bound to hemoglobin was complicated by the lability of the bonds. When purified human hemoglobin had reacted with radioactive phenylhydroxylamine, large proportions of the radioactivity bound to hemoglobin were removed by treatment with acid or with PMB for separation of alpha- and beta-chains. The radioactive compound liberated from hemoglobin by acid was found to be aniline. After reaction with phenylhydroxylamine the number of SH groups titrable with PMB was found to be diminished. Pretreatment of hemoglobin with N-ethylmaleimide or PMB decreased the amount of phenylhydroxylamine bound to hemoglobin but did not fully prevent the reaction. Tryptic digestion of hemoglobin after reaction with radioactive phenylhydroxylamine yielded tryptic peptides with lower specific activity than that of hemoglobin. Chymotryptic digestion of the tryptic core yielded a core with specific activity much higher than that of hemoglobin. Fingerprinting of the tryptic or chymotryptic hydrolyzates showed the presence of peptides with high and other ones with low or no radioactivity and of radioactive compounds which did not react with ninhydrin. In the covalent binding of phenylhydroxylamine to globin the SH group beta93 plays an important role, but other yet unknown sites are also reactive.


Release of creatine kinase by antigen, histamine, and catecholamines.

In mepyramine treated, ovalbumin sensitized anaesthetized guinea pigs protracted anaphylactic shock was produced by i.p. injection of antigen, and serum creatine kinase (CK) activities were determined 4, 6, or 17 hrs thereafter. Significant increases above nonsensitized controls were obtained. In nonanaesthetized guinea pigs shock course and serum CK increase were considerably accelerated. Histamine increased the serum CK only when given in high amounts (10 mg/kg) s.c., in the presence or absence of mepyramine. I.p. injection of histamine in mepyramine treated animals had no effect. Adrenaline (1 or 10 mg/kg) given as a s.c. depot in oil produced a significant increase of serum CK, as well as noradrenaline (0.1, 1, or 10 mg/kg). Dibenamine reduced the effect of adrenaline. In isolated perfused guinea pig hearts a significant CK liberation occurred already within the first hour after eliciting anaphylaxis. Nonanaphylactic hearts released CK too, but significant amounts were obtained only in the total 4 hrs after ovalbumin administration. Isolated anaphylactic hearts incubated in Tyrode solution liberated significantly more CK than did nonsensitized control hearts. The findings are discussed in view of a possible myocardial damage in anaphylaxis.


Methylxanthines and intestinal drug absorption.

1. Jejunal loops of anaesthetized rats were filled with buffered isotonic solutions of tritiated water (HTO), urea, antipyrine and salicylic acid at pH 6-8. The venous outflow and the appearence rate of the substances in the intestinal venous blood were determined. Blood pressure was kept constant by adjustable supply of blood from donor rats throughout the experiment. 2. The absorption of urea, antipyrine and salicylic acid was, in concentrations from 0.001 to 1.0 mg/ml found to be directly proportional to the intraluminal concentration. 3. Theophylline and caffeine (2 mg/ml), when injected into the lumen, increased the blood flow to 188% and 166% of controls. 4. The theophylline induced increase in blood flow caused an enhancement in the absorption of antipyrine to 153%, HTO and urea to 135% and salicylic acid 123% of controls. 5. Caffeine influenced the absorption of HTO and salicylic acid similar to theophylline.


Evidence for the possible formation of a toxic tyrosine metabolite by the liver microsomal drug metabolizing system.

The toxicity of tyrosine in the mouse was found to be affected by agents which interact with the liver microsomal drug metabolizing system. Pretreatment of mice with SKF 525A or cobaltous chloride, two different types of inhibitors of the drug metabolizing system, afforded a marked protection against tyrosine toxicity. Pretreatment with phenobarbital or 3-methylcholanthrene, two inducers of the drug metabolizing system, potentiated the toxic effects of tyrosine. Toxicity, as determined by lethality, was also found to be correlated with a depletion of liver glutathione levels. It is concluded that the liver microsomal drug metabolizing system is capable of converting tyrosine to a toxic metabolite, conceivably a 2.3 epoxide of tyrosine. The present results are discussed in relation to the human disease tyrosinemia (tyrosinosis).


Effects of pretreatment with spironolactone of pharmacokinetics of 4'''-methyldigoxin in man.

Pharmacokinetics of 3H-4''' -methyldigoxin (md) were studied in three paired experiments with and without pretreatment with spironolactone (7 mg/kg/day for 7 days) and in one additional test person after pretreatment only. The results were compared with controls after oral (n equals 6) and intravenous (n equals 6) administration of md. In addition the biliary excretion of md and its metabolites was investigated in biliary fistula patients with and without pretreatment with spironolactone. After pretreatment of normal persons maximum plasma levels of tritium were approximately 35% lower and they were reached on average 60 min after oral administration as compared with approximately 15 min without pretreatment. Already 12 hrs after oral administration the plasma concentrations, with and without pretreatment, no longer differed and the biological half lives of radioactivity in plasma were equal. With or without pretreatment, the cumulative excretion of tritium in urine and faeces was nearly identical in the paired experiments within 7 days. It was in the range of the controls which eliminated 55.2 +/- 2.8 and 28.6 +/- 5.7% of the dose in urine and faeces, respectively, after oral, and 62.2 +/- 2.1 and 28.9 +/- 5.2%, respectively, after i.v. administration. Accordingly after pretreatment the radioactivity excreted in bile within 48 hrs (14.9% of the dose) did not differ from controls. Examination of the composition of labelled compounds excreted in urine and bile revealed no significant alterations in the metabolic degradation of md under the influence of spironolactone. Thus the profound effects of spironolactone upon pharmacokinetics of md previously observed in rats are without any significance for human conditions.


Preferential deamination of dopamine by an A type monoamine oxidase in rat brain.

The effect of graded doses of clorgyline, a preferential inhibitor of MAO A, and of deprenil, a preferential inhibitor of MAO B, on the activities of serotonin-deaminating MAO (MAO A) of dopamine-deaminating MAO, and of phenethylamine-deaminating MAO, (MAO  B), in rat corpus striatum were compared with the effects of the drugs on striatal levels of homovanillic acid(HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC). The dose-response curves for the two last-mentioned dopamine metabolites closely follow those for MAO A and dopamine-deaminating activity, whether clorgyline or deprenil was used as MAO inhibitor. In addition, the effect of these drugs on dopamine levels and on the accumulation of 3H-dopamine + 3H-methoxytyramine formed from 3H-DOPA in rat whole brain was analysed. In contrast to the marked increases caused by clorgyline, the effects of deprenil were negligible. In reserpinized rats, clorgyline potentiated the effect of L-DOPA on motor activity; deprenil did not. These results suggest that the deamination of dopamine in vivo is almost entirely effected by MAO A.


Inhibition of the reuptake of serotonin by tryptoline.

Tryptoline, a metabolite of tryptamine, competitively inhibits serotonin accumulation in nuclei-free homogenate of rat "forebrains". After intraventricular injection the drug elicits an increase of serotonin levels in the same part of the brain whereas the monoamine oxidase activity is not altered.


Nucleoli of lymphocytes in the peripheral blood of patients with bronchogenic lung and gastrointestinal cancer.

Patients suffering from bronchogenic and gastrointestinal cancer without, as well as with metastases, were investigated to provide more information on the number of morphology of lymphocytes in their peripheral blood particularly in respect to the frequency of various nucleolar types in these cells. The decreased number of lymphocytes in the peripheral blood of the cancer patients was due to the decline of lymphocytes with ringshaped nucleoli representing resting cells which can be stimulated in respect to the RNA synthesis and blastic transformation. The decreased number of such cells was apparently more pronounced in the peripheral blood of the patients suffering from gastrointestinal cancer with metastases. The increased frequency of lymphocytes with compact nucleoli or nucleoli with nucleolonemas representing immature or stimulated cells was noted in most patients suffering from bronchogenic cancer without, and with metastases in lymph nodes, as well as in some patients with gastrointestinal cancer and, without metastases. On the contrary, the decreased number of these cells was observed in the peripheral blood of patients suffering from gastrointestinal cancer with metastases. All these changes provide further information on the changes of the lymphocytes in the peripheral blood of the patients suffering from malignant disease. The possible interpretation of these changes presented in the discussion is in accordance with the present conception on the relationship between the malignant growth and lymphocytes.


Multiple myeloma in two brothers. Immunoglobulin levels among their relatives.

The reports on the occurrence of myeloma in two or more members of the same family are very scanty, and until present, only about twenty observations of the familial occurrence have been reported. In this paper the observation of multiple myeloma in two brothers is described. The clinical diagnosis was confirmed by the bone marrow biopsy which showed an infiltration of abnormal plasma cells. X-ray examination of the skeleton revealed typical osteolytic changes in one patient and diffuse osteoporosis in the other. Moreoever both patients had a massive monoclonal protein fraction in serum and Bence-Jones protein in urine. In one case the monoclonal serum protein was of the IgG-K type and in the other, of the IgA-K type. Thus the antigenic determinants were different in the class specificity. Immunoglobulin studies among healthy relatives of the two brothers demonstrated much higher incidence of the polyclonal increase in one immunoglobulin class than could be expected in the population. Without evidence of monoclonal serum protein, unusally high IgA serum levels, more than 500 mg/100 ml, were observed in seven of seventeen healthy family members. This could be explained on genetic basis in connection with the familial occurrence of myeloma either by an abnormal distribution of plasma cell clones or by their abnormal activity. However, a defective control mechanism in protein synthesis may also be taken into consideration.


Metastases into the cervical lymph nodes from unknown primary focus.

The analysis bears on 33 patients with histologically verified metastases into the cervical region from an unknown primary tumor, which was found intra vitam in 7 cases and by resection in 2 of the cases (i. e. 27.2%) only. The best form of treatment is a surgical-radiological combination. The search for the primary focus is often difficult and necessitates the use of ORL investigation and the other diagnostic methods. Emphasis is laid on the need of regular and frequent check-ups in case the primary focus is not detected. An early detection of the origin favourably affects the results of treatment.


Carcinoma cervicis uteri. Treatment results from the period 1953--1968.

During the course of 16 years, i. e. from 1953 to 1968 inclusively, a total of 2111 patients with carcinoma of the uterine cervix were treated at the Oncological Institute in Brno. Of these, 1829 patients, i. e. 86.6% were irradiated, 282, i. e. 13.4% underwent primarily a radical excision and subsequently were irradiated. During the past years, approximately 95% of all such patients are being given radical irradiation. The mean age is 52.7 years, the sixth decade being numerically the highest in incidence -- 27.4%. The distribution pattern according to the tumor stage: I -- 29.3%, II -- 14.3%, III -- 48.2%, IV -- 8.2%. This distribution remained practically unchanged over the follow-up period of 16 years. The fundamental method treatment of practically 87% of all the patients was actinotherapy consisting in a combined application of radium and X-rays. Of the total number of 2111 patients, 1298, i. e. 61.5% have survived 5 years without any symptoms of the disease, 966 patients, i. e. 59.0% (out of a total of 1671 patients) survived 10 years. The five-year survival symptom-free period for the various stages ia as follows: I -- 82.5%, II -- 77.1%, III -- 52.8% and IV -- 9.8%. A comparison of the results of treatment in patients radically irradiated and those primarily operated upon then subsequently irradiated, i. e. in 619 patients of stage I showed the 5-year recovery to be superior by almost 4% in the former than in the latter group --84.1% as against 80.3%. Over the last 6 years of the follow-up, i. e. 1962--1968, this difference went up to 6.0% in favour of those radically irradiated--85.1% as against 79.2%. An increasing mortality rate due to carcinoma is noted with advancing age.


New potential cytotoxic and antitumor substances. II. Effect of hydroxyanthraquinones and their glucosides on Ehrlich ascites carcinoma cells in vitro.

Mono and dihydroxyanthraquinones and their derivatives affected the utilization of 14C-labeled precursors nucleic acid and protein synthesis into Ehrlich ascites carcinoma (EAC) cells. Inhibitory effect of the substances markedly increased when one acetyl group was introduced into the basic molecule. As the tested substances inhibited mainly incorporation of 14C uridine into the cold TCA insoluble fraction of EAC cells, their mechanism of action can be explained by the inhibition of RNA synthesis.


Abnormal hydroxyproline polypeptides in the urine of patients with chronic uremia.

An abnormal peak of hydroxyproline polypeptides has been observed when the polypeptide fraction from the urines of patients with advanced chronic uremia was subjected to gel chromatography. This abnormality was apparently related to the degree of uremia and to the presence of uremic osteodystrophy. The abnormal peak was not observed in patients with high turnover bone disease without renal insufficiency and in patients with nephrotic syndrome and normal glomerular filtration rate.


Acute renal failure due to radio-contrast agents.

Over a 2-year period, acute renal failure following radio-contrast studies was observed in 25 patients after intravenous urography in 13, angiography in 10, oral cholecystography in 1, and cholangiography in 1. 20 had impaired renal function prior to the study. Renal failure, oliguric in 16 patients, occurred within 24 h. Serum creatinines reached levels of 5.3-13.3 mg% in 3-10 days. Recovery occurred in 20 patients within 5-37 days. Among the 5 patients in whom renal failure function was not restored, 1 died of progressive underlying renal disease and 4 of other causes while still in acute renal failure. These observations demonstrate the not infrequent occurrence of severe oliguric renal failure following radio-contrast study in patients with preexisting renal disease.


Lipid composition of the rat kidney.

The lipid fractions free fatty acids, triglycerides, cholesterol, cholesterol esters and phospholipids of rat kidney cortex, outer and inner medulla were analyzed by thin-layer chromatography. The concentrations of 23 individual fatty acids in the lipid fractions of each zone were determined by gas chromatography; 14 of them were evaluated by an analysis of variance. For most of the lipid fractions a corticomedullary concentration gradient was found, the highest concentrations occurring in the cortex. The lipid classes primarily determined the pattern of individual fatty acid concentrations. A significant concentration difference between the three zones only existed for 4 of 14 fatty acids. Long chain fatty acids were found in a higher concentration in the phospholipids of cortex and outer medulla (about 95%) in comparison to the inner medulla (65%).


Intrarenal hemodynamics in acute myohemoglobinuric renal failure.

Renal blood flow (RBF) and its distribution were measured in acute renal failure induced by glycerol injection to water-drinking rats and to rats chronically loaded with NaCl solution. Mean RBF and intracortical blood flow distribution of both water-drinking and saline-loaded rats at 24 h after glycerol injection were not different from those of control rats. Although chronic saline loading blunted the impairment of renal function caused by glycerol as evidenced by serum creatinine values, no differences in renal hemodynamics were noted. This suggests that changes in glomerular arteriolar resistance or glomerular permeability might be of greater importance in the reduction of glomerular filtration rate than are alterations of blood flow.


Influence of middle-sized molecule aggregates from dialysate of uremic patients on lymphocyte transformation in vitro.

It was found that middle-sized molecules obtained from dialysate of uremic patients caused suppression of PHA-induced lymphocyte transformation. This was expressed by the lowering of labeled leucine incorporation and by the suppression of lymphocyte transformation as morphologically assessed. In view of the presented data middle-sized molecules seem to be biologically active substances.


Cerebral dermoid tumours.

Four cases of cerebral dermoid tumour with an intraventricular, occipital and sellar location are reported, representing 0.04% of the verified cerebral tumours in the authors' statistics. A recurrence occurred after one year in the first case of intraventricular dermoid tumour; after the second operation aseptic meningitis developed and the patient died. In the second case microscopic examination revealed aspects of malignant transformation of the tumour. The symptoms did not differ from those of other cerebral tumours. Operations should be radical whenever possible, avoiding dispersion of the tumour contents in order to prevent a recurrence or aseptic meningitis.


Multiple meningiomas. Two patients with a spinal and an intracranial meningioma. Radiological diagnosis.

We report two patients with a spinal and intracranial meningioma without evidence of von Recklinghausen's disease. The radiological and scintigraphical findings are demonstrated. Certain implications with regard to the examination and follow-up of patients with a meningioma are indicated.


Traumatic intracerebral haematoma: complication of skull caliper traction. Case report.

Recently, a unique case of traumatic intracerebral haematoma complicating the insertion of skull calipers, has been observed. It is assumed it was due to: 1. the accidental penetration of the burr into the skull, while making the insertion hole for the caliper; 1. the failure to grip the skull with the special metal sleeve, the Blackburn skull caliper is provided with, so that the end plates were free to move in and out of the skull in this restless patient. The correct diagnosis was made only after severe uncal herniation had developed. The reasons for missing the correct diagnosis within useful time for proper treatment are considered to be: 1. carotid angiography performed too early in the process of haematoma formation: 2. the vascular displacements were only slight and not fully diagnostic; 3. a recognized complication, extradural haematoma, had already been excluded.


Complications of skull caliper traction.

During a period of 20 years 88 patients with fracture dislocation of the cervical spine were treated by attaching Crutchfield tongs to the skull. Sixty-seven per cent of all patients had some complications. The different types of complications are reported and discussed in order of frequency.


Massive cerebellar abscess due to candida albicans.

A case of a previously healthy 51-year-old man, who was diagnosed clinically as having a posterior cranial fossa tumour. At operation this proved to be an abscess which was radically removed. Histological investigations showed the presence of a fungus which was identified as Candida albicans.


[Clinical significance of encycling clips in neurosurgery].

It is reported how, in 5 cases of arterial haemorrhage, the ligature of an artery was avoided by the use of Heifetz encircling clips with teflon liner. Two of the five patients had aneurysms. The remaining 3 were suffering from brain tumours. Postoperative computer tomography together with neurological follow up examinations indicated, that in two cases there was no disturbance of cerebral circulation. With a carotid angiography it was possible to show that in the other three cases normal flow through the arteries was maintained, 2, 11 and 45 days after emplacement of the clip.


Direct effects of estradiol and progesterone on pituitary graft gonadotrophs and their differential response to median eminence extract.

The direct effects of median eminence extract (MEE), estradiol (E) or progesterone (P) or combinations of these hormone preparations on the structure of the adenohypophysis and its secretion of gonadotrophins were examined in female rats bearing pituitary homografts obtained from long-term ovariectomized (LTO) donors. Preliminary investigation had shown that the pars distalis of LTO animals retained large numbers of hypertrophied gonadotrophs for several weeks even when homografted under the kidnay capsule of hypophysectomized recipients. Homografts from vehicle-treated controls contained many gonadotrophs at 24 days. Treatment with E or P resulted in complete disappearance of gonadotrophs at 24 days, but not at 10 days. E produced depletion of gonadotrophs even in the presence of MEE, while P + MEE treatment resulted in retention of gonadotrophs. In general, ovarian morphology correlated well with changes in pituitary cytology. These results suggest that the ability of MEE to stimulate release (and probably synthesis) of gonadotrophic hormones depends on the steroid sensitization of pituitary tissue and the differential effect of E and P on gonadotrophin release in the presence of MEE.


Basal and stress-induced adrenal cortical activities in the chronic thalamic pigeon.

The plasma corticosterone level was determined in chronic thalamic pigeons. Basal resting adrenocortical activity did not show any diurnal variation and kept a steady intermediate level. The peak and nadir in the morning and in the evening were completely suppressed. Neurogenic stress (restraint) resulted in a sharp increase in the plasma corticosterone concentration 15 min after immobilization. This response was as important in magnitude (three-fold the resting level) in thalamic pigeons as in intact birds. These results can be compared with data obtained after complete or partial deafferentation of the hypothalamus, and after hippocampal or archistriate lesions, and are discussed in terms of sleep-walking alternation in these various experimentally-prepared pigeons.


Effect of suckling on serum follicle-stimulating hormone and luteinizing hormone in nursing women.

The effect of breast feeding on serum FSH and LH concentrations was studied in 13 puerperal women. Despite the collateral increase in serum prolactin levels, nursing was not followed by significant changes in serum FSH or LH levels during a 30-min observation period. Our data indicate that nursing has no significant effect on pituitary FSH and LH release.


Neurosecretory axo-axonic synapses in the median eminence of the turtle, Geoclemys reevesii.

Neurosecretory axo-axonic synapses were found in the median eminence of the turtle. Most of the presynaptic axons contain granules approximately 95 nm in diameter, and the postsynaptic elements have granules approximately 110 nm in diameter. The functional significance of axo-axonic synapses in the median eminence is discussed in relation to the discharge of releasing hormones from the axon terminals.


Effect of electrical stimulation of the hippocampus upon corticosteroid levels in the freely-behaving, non-stressed rat.

The influence of the hippocampus upon pituitary release of adrenocorticotropic hormone (ACTH) was studied in male Sprague-Dawley rats which had concentric bipolar stainless stell electrodes chemically implanted in the dorsal and ventral hippocampus. Blood samples were withdrawn at half-hour intervals from a cannula in the right atrium. Plasma corticosterone levels reflected ACTH release. 30 min of 25 or 250-cps electrical stimulation of the hippocampus in the freely-behaving, non-stressed rat resulted in significant increases in basal plasma corticosterone levels evident at the end of stimulation. In afternoon experiments, after stimulation at either hippocampal site with 25 cps only, the increase was followed by a delayed inhibitroy phase and temporary inhibition of the circadian rise in corticosterone levels. The inhibitory effect was more pronounced with ventral than with dorsal hippocampal stimulation. The basis for these differential effects is discussed in terms of the anatomical organization of the hippocampus.


Radiographic measurements of the normal spinal cord in childhood.

110 normal air myelograms of children were reviewed and the ratio of the spinal cord width to the subarachnoid space width (cord/SAS ratio) was calculated in the sagittal and transverse planes. This ratio proved to be independent of age and sex. The mean values at different vertebral levels are in close agreement with those previously reported for adults. The cord/sas ratio is helpful in evaluating changed cord dimensions, especially that of cord atrophy.


A technical contribution of the exact angiographic localization of carotid cavernous fistulas.

A better visualization and localization of carotid cavernous fistulas may be achieved by selective angiography of the vertebral artery with simultaneous digital compression of the ipsilateral carotid artery, if the posterior communicating artery is patent.


Angiotomographic study of the normal cerebral circulation. II. The vertebrobasilar system.

Simultaneous tomography applied to normal vertebral angiography has, by the dissociation of the vascular planes, made a selective and spatial study of the vertebrobasilar circulation possible, and therefore, the identification of the vessels which are partly or totally hidden by other vascular structures. This technique has also led to a better delimitation and sometimes a direct observation and spatial localization of some anatomical structures above and below the tentorium.


The potential of vertebral phlebography for the diagnosis of tumours in the posterior cranial fossa.

The diagnostic value of the vertebral phlebogram is emphasized. A practice orientated principle is recommended for the classification of infratentorial veins. A total of 132 phlebograms taken from patients with intratentorial tumours is analyzed for local diagnosis, general diagnosis, venous circulatory disorder, and pathologic veins. An example is given to underline the importance of tomography in vertebral phlebography.


The petrosal vein and its demonstration in the normal vertebral angiogram.

The great variability of the petrosal vein in terms of position, shape, and course was established by vertebral phlebography in 100 normal subjects and by metric studies. Knowledge of this variability is essential to any assessment of phlebographs and adds to the possibility of differentiating between normal and pathological findings.


Morphogenesis of the spinal canal, normal and stenotic.

The closest formative developmental dependence of the axial skeleton upon the morphogenesis of the intraspinal nervous structures is reflected in the roentgen features of the individual vertebrae as well as of the vertebral column in its entirety. The vertebroneural developmental events are characterized by a steady relative decrease in size of the nervous structures (the first to be laid down and huge in the embryonic period) under a corresponding increase in size of the skeletogenic tissues. There exists experimental evidence that the maintenance  of the necessary developmental balance between the two tissues, the bony and the skeletogenic, is a function of the nervous substance. The tight spinal canal appears to result from a failure of the latter neural function leading to overgrowth of the bony structures, viz., to massive vertebrae and laminae encroaching upon the neural contents. Morphogenesis of the normal and tight lumbar spinal canal is discussed with special reference to the developmental interrelations between the cauda equina complex and the lumbar vertebrae.


Measurement of effective atomic number and electron density using an EMI scanner.

Computed tomography, employing an EMI scanner at two beam energies, can be used to obtain information about the electron density and the effective atomic number of materials. The theory which is discussed has been verified experimentally and then applied in the investigation of some brain tumours in vivo. It is anticipated that, as techniques improve, the ability to carry out chemical and physical analysis of pathological processes in vivo will be an important application of computed tomography.


X-ray energies for effective atomic number determination.

The measurement of the effective atomic number of a piece of material in vivo can be achieved using computed tomography. The precision of measurement of this parameter depends on the precision of measurement of the X-ray absorption coefficient at two energies and the separation of these energies. With the assumption of a fixed photon flux, it is shown that two optimum energies exist for the measurement of effective atomic number. The analysis indicates that if energies of 40 keV and 80 keV are employed, a precision of at least 1 part in 400 in the measurement of effective atomic number may be achieved.


The limitations of definition of blood vessels with computer intravenous angiography.

Using a polystyrene phantom and various concentrations of iodine contrast material, the discrimination of blood vessels by the EMI scanner was studied. Although a 2 mm tube can be delineated using high concentrations of iodine, smaller tubes are not seen due to noise inherent in the system.


The influence of atherosclerosis and ectasia on cerebral blood flow.

Of 65 patients with neurological disorders examined with rapid serial angiography of the carotid artery, 24 had normal cerebral arteries, 17 atherosclerosis, 11 arterial ectasia and 13 both kinds of vascular changes. These patients were examined for hemispherical rCBF determination on the same occasion, using the 133Xenon clearance method. Primarily, the patients were examined without general anaesthesia, and they did not have acute illness, trauma, or angiographic evidence of a focal intracranial lesion. In addition, other parameters such as arterial size, ventricular size, cerebral circulation time, age, and sex were determined. All these data were studied statistically in a series of multiple regression analyses with a computer. No significant differences in rCBF could be found between cases with ectasia, atherosclerosis and without any kind of vascular changes. However, the mean value of rCBF in patients with atherosclerosis and in patients with intracranial ectasia was below the normal mean value, although it did not differ significantly from this value. Nor was any influence on the rCBF found in patients with marked stenosis of the internal carotid artery and those with slight stenosis.


Delineation of pituitary adenomas by angiotomography.

The supra sellar extension of even small sized pituitary adenomas can be delineated with accuracy by angiotomography. This technique avoids the discomfort of pneumoencephalography in many patients. Angiotomography is also useful for the differential diagnosis of empty sellae.


Topographic measurement of the superior vermian vein by lateral vertebral phlebography.

The position of the superior vermian vein (SVV) has been defined by means of an easily constructed triangular system with two fixed points and by determination of quotients of measured lengths or angles. 100 normal lateral vertebral phlebograms with well outlined SVV and accurate projection were thoroughly measured and calculated. Since SVV was found to occupy a constant position in the reference system used, certain quotients and angles might be suitable for diagnosis.


Calibration and response of an EMI scanner.

Computed tomography provides a measurement of the linear absorption coefficient of material in vivo. The precision and accuracy of the measurements of this parameter made by the EMI scanner have been investigated at all three recommended voltage settings of the machine. The relationship between the EMI number and the linear absorption coefficient was found to be linear despite the polychromatic nature of the X-ray beam. The spatial resolution of the machine and the response to materials at different depths within the section have also been investigated.


[Changes in blood sugar, and insulin levels induced by somatostatin in normal, diabetic and acromegalic subjects].

The effect of somatostatin on plasma sugar and insulin levels was determined in 8 normal, 7 diabetic and 5 acromegalic subjects. An absolute fall in blood sugar values on the order of about 20% was noted, though during administration of the drug only, in all cases. Normal and diabetic subjects also showed an approximately 40% decrease in blood insulin, whereas no such fall was observed in the acromegalic. In spite of the simultaneous fall in insulin levels, it was clear that the reduction in blood sugar was ascribable to a drug-induced block of glucagon secretion. The part possibly played by somatostatin in the regulation of glucide homeostasis is examined in the light of these results.


[Isoproterenol in the emergency treatment of cardiac stimulus conduction].

Continuous infusion with isoproterenol (mean dose 2 mug/min) was carried out for periods of a few hours to a few days in 22 patients recurrent Adams-Stokes syncope. In all cases, an improvement leading to or in the direction of physiological cardio-circulatory conditions was noted. Undesired side-effects foreseeable as the result of beta-adrenergic stimulation were not observed. Isoproterenol is more active than metaproterenol and is to be preferred on this account. It is indicated in Adams-Stokes crises due to conduction disturbances when pacemakers cannot or should not be fitted, or as a prelude to their application.


[Use of a new water-soluble aldosterone-antagonist in surgery. Early clinical results].

A new i.v., water-soluble aldosterone antagonist (potassium canrenoate) was employed for the first time in a series of patients operated for various forms of abdominal disease. The pharmacological and clinical effects of the drug were constantly reproduced and a marked anti-aldosterone activity was noted. The drug is felt to be specifically indicated in the management of secondary hyperaldosteronism typical of the immediate postoperative period.


[The apexcardiogram in acute myocardial infarct].

The relation between intracardial haemodynamics and apicocardiogram (ACG) parameters is explained. A wave (amplitude and duration), A/H ratio, true and total TCI, total systole, total expulsion, RIV, RFW, TE/TCI (total) and TE/TCI (true) findings in 22 patients with acute myocardial infarct are presented. Attention is also given to clinical and radiological signs of cardiac insufficiency and the infarct site. Constant and significant increases in the A wave, A/H ratio and RIV, together with a decrease in total expulsion, were noted, particularly in cases with clinical evident insufficiency. In the pre-expulsive stage, ACG Data could not be taken as a reliable index of myocardial contractility in cases where insufficiency was not manifest. It is felt, therefore, that ACG may be of assistance in the evaluation of changes in myocardial performance, even where clinical and radiological signs of decompensation are absent.


[Difficulties in the electrocardiographic diagnosis of a previous posterior myocardial infarct].

A retrospective study was carried out of 39 cases of posterior m.i. from 8 months to 6 years after acute episode. In each case the diagnostic reliability of the standard derivations of a series of parameters was evaluated (duration of Q D3 and Q aVF, Q.100/R ratio in aVF, R/S ratio in V1 and R V1/R V6) and of the following accessory derivations: De Maria, III P of Pescador (classical and in two personal modifications), dorsal and sternal derivations. It is concluded that in many cases, standard derivations do not enable previous posterior m.i. to be diagnosed. The De Maria and III P of Pescador derivations (with the proposed personal modifications) are advisable. In isolated cases, the sternal derivation may also be very useful.


[Myocardial infarct. Dimensions of the problem and its local aspects].

World statistics of infarction are given in brief from the viewpoints of incidence, mortality and prevalence. The results of analysing admittances for m.i. to the Imperia Hospital in the period 1960-1972 are then reported. The series is considered from the general and local standpoints, with reference to the organizational and welfare problems created by the high number of admittances and their high annual increment.


[Identification of corpses in mass disasters].

Reference is made to an air disaster causing considerable loss of life near Palermo. The type of lesions noted on the bodies is described and the criteria adopted for identification and recognition in accordance with the present legislation are explained. The reasons for mistaken identification, some of them of a most unusual nature, are listed and their prevention is discussed. An examination is also made of some recent proposals concerning the avoidance of such errors in disasters involging large numbers of persons.


[Radiothermolumiscent dosimetry in plesioroentgenotherapy].

The employment of thermoluminescence dosimeters in the evaluation of X-rays emitted by a plesiotherapy apparatus was investigated. It was found that lithium fluoride microdosimeters gave good linearity of response in function of the energy involved. This response was also repeatable as required.


[Incidence of hepatic metastases of breast cancer. Scintigraphic study with radiocolloids in 111 patients].

The anatomical and physiological premises of liver scintigraphy with radiocolloids as a useful study in patients suffering from various stages of breast cancer are analysed. A series of 111 cases is then reported. The technique was used on these cases one or more times and revealed the presence of a scintigraphic picture suggesting liver metastasis in 36% of cases (27.5% at first observation). These data proved higher than those previously reported in the literature by other workers. The technique is therefore proposed as a routine investigation in patients suffering from breast cancer.


[Modern views concerning surgical treatment of psychogenic chronic hepatic abscesses].

A case of paracholecystic pyogenic abscess of the liver discovered intraoperatively in a patient with calculous cholecystitis is reported. Successful management was obtained by means of extensive resection of the protruding cap, scrapping of the wall and suture of the parenchyma, coupled with cholecystectomy. The literature on treatment of liver abscesses is reviewed. The conclusion is drawn that radical removal, with respect for the parenchyma, is best employed in chronic, restricted forms. The pus must, of course, be cultured and an antibiogram run on the germs isolated, as a prelude to planned antibiotic management after surgery.


[An unusual complication of calculous cholecystitis: transparietal migration of a calculus into a circumscribed peritoneal sac without a fistulous passage].

A rare complication of calculous cholecystitis (calculous that had migrated from the gallbladder and held in a circumscribed peritoneal sac with no fistula between this and the gallbladder) was observed in a woman who had been suffering from dropsy of the gallbladder with calculi for some 13 years. The most recent literature on acute and chronic perforations of the gall bladder and on known pathogenetic mechanisms regarding transparietal migration of calculi and the establishment of bilio-digestive and bilio-biliar fistulas is reviewed. A number of hypotheses are put forward to explain the unusual operative finding but the impossibility of formulating any precise preoperative diagnosis is recognized and it is stressed that many cases are recognized only following surgery.


[Hemi-agenesis of the thyroid gland].

The paper is based on the observation of two cases of thyroid hemiagenesis, not so much for the rarity of the findings as for their diagnostic ambiguity. These aspects are discussed along with the consequent therapeutic problems. The concept of "no clinical significance" expressed elsewhere on the question of hemiagenetic thyroids is not shared because of possible development into goitre, myxoedema, Basedow's disease and, particularly, neoplastic degeneration. The congenitally incomplete organ is called on to sustain the entire functional burden from birth and even earlier. Where hemiagenesis is identified, this means careful supervision because it is precisely as a result of the organ's mutilated condition and the duration of the functional burden involved that the danger lies.


[Hyperglycemic, hyperosmolar nonketotic diabetic coma in the pediatric age].

A case of non-ketotic hyperglycaemic-hyperosmolar diabetic coma in a 8 yr. old boy after a severe mental trauma is reported. This joins the 18 similar cases of paediatric age published up to now. On the basis of the results of virological and immunological investigations, insulinogenic function and psychodiagnosis, the diagnosis, aetiopathogenesis and therapy of this unusual event are discussed. The desirability of measuring plasma osmolarity in children diabetic coma is stressed.


[The vanishing testis syndrome. Considerations on a case].

The aetiopathogenesis and clinical and diagnostic features of bilateral absence of the testicles in 46XY subjects are briefly reviewed. A eunuchoid 25-yr-old patient with male sex chromatin, 46 XY genotype, plasma testosterone slightly below normal, normal urinary 17-KS unaltered by gonadotropin stimulation, and bilateral absence of the testicles is presented. Examination of the inguinal canal showed a funiculus and ductus deferens residue terminating in an adipose mass. Section of the fibrous duct showed that this mass was full of capillaries and venules. Lesion between the 14th and 16th week of pregnancy is postulated.


[Use of cloridarol in coronary insufficiency].

The therapeutical activity of a new oral drug with a coronaric and myocardiotrophic action of choice, 2-benzofuryl-p-chlorophenyl-carbinol (Menacor, Menarini) in 20 patients with chronic coronary insufficiency was studied by administering 750 mg/day for at least 20 days. General and gastroenteric tolerance was excellent, while good or fair therapeutic results were obtained in 16 cases (80%). It is felt that the drug can be usefully employed in the management of coronary insufficiency.


[Selective angiography and transcervical exeresis in mediastinal parthyroid adenoma with anomalous drainage].

A personal case of hyperparathyroidism due to parathyroid adenoma is reported: selective angiography enabled the neoplasia to be precisely localized in an unusual site and made it possible to identify its abnormal venous drainage. Transcervical surgery was used to remove the adenoma and the patient cured with no relapse up to the present. In the light of this expecience and a review of the recent literature on diagnostic techniques, emphasis is laid on the effectiveness of angiography in the localization of parathyroid adenoma, a localization which should always be sought preoperatively to avoid the risk of pointless surgical exploration.


[Bleeding fibroma of the small intestine].

A case of serious, recurrent enterorrhagia is reported. The cause could not be identified with normal diagnostic tools and was discovered only after explorative laparotomy. The finding was benign ulcerated tumour of the small intestine, histologically defined as fibroma with fluorishing cellularity.


["Very slow" cholangiography in hyperbilirubinemias and in chronic liver diseases].

The "ultra-slow" method for cholangiography in serious icterus due to chronic heptopathy is described. The results are related to different icterus stages. A comparison is drawn between this and conventional methods for examination of the bile ducts, assuming equal degrees of blood bilirubin.


[Problems of gastrointestinal angiography].

The subject of abdominal angiography is discussed, for informational rather than technical reasons, on the basis of seven years personal experience. The method used to prepare the patient for angiography and emergency treatment of the various episodes of reaction to the contrast medium or of complications of arterial catheterism are illustrated and some of the most significant aspects of abdominal angiographic symptomatology described.


[Frequency of lung asbestos bodies in autopsy material at Udine].

Following chemical digestion of the pulmonary tissue, asbestos bodies were sought in 50 random necropsies carried out at Udine. The age of the subjects examined, 24 men and 26 women, was between 23 and 90, and 43 cases were older than 50. A positive finding was observed in 44 cases (88%).


[Clinico-statistical studies on 700 cases of lymphatic diseases of various kinds. Laboratory parameters].

Statistical assessment of laboratory data relating to about 700 cases of lymphopathy of various kinds was used in the elaboration of material to be used in diagnosis in the very early stages of the disease. Diagnostic tables giving a high degree of probability were prepared.


[Cardiovascular disorders in young military personnel. Treatment and readjustment].

The vascular disturbances most commonly encountered in conscripts are examined and the features leading to their diagnosis and the consequent differentiation of organic heart diseases are described. Rhythm variations, auscultation abnormalities (systolic, diastolic and vascular murmurs, additional tones) and ECG alterations thus detected are seen as instances of functional disorders, of a non-dangerous nature that will regress or disappear in the course of time.


[Behavior of the ventricular gradient under hypoxia conditions in applicants for officer pilot training schools].

Two ECG traces were taken to measure the value and orientation of the QRS, T wave, and ventricular gradient areas in 18 applicants for places in flying officer schools subjected to hypoxia by inhalation of a poor mixture. A significant reduction was noted in the T and ventricular gradient areas, whereas there was no appreciable change in the QRS. The significance and usefulness of this form of examination is discussed, particularly with respect to subjects with abnormal ECG responses in hypoxia.


[Chromosome studies of personnel exposed to electromagnetic radiation at radar centers].

The possibility that chromosome alterations take place in personnel exposed to electromagnetic radiation in radar centres has been studied. The study was carried out "blind" on short-term cultures of peripheral blood, some 450 metaphases being analysed for each case. No aberrations were found in either radar operators or controls and there was no statistically significant difference between them.


[Various pulmonary lesions induced by high-pressure oxygen].

Hyperbaric oxygen may provoke lesions in various organs and tissues depending on the dose and application time. The toxic action mechanisms of oxygen are manifold. The pulmonary lesions that occur in mice submitted to various oxygen pressures are investigated. Anatomo-pathological examination revealed numerous alterations of various kinds depending on pressure used. Emphysema, pulmonary oedema and enormous inflammatory processes in the lung are the most frequent findings encountered in research.


[Health education campaign conducted among Air Force personnel in relation to visual refraction defects].

A permanent health education campaign was begum some months ago among air force personnel designed to persuade men of all functions and ranks and suffering from refraction defects, to use prescribed corrective means permanently. The causes of failure to use them on the part of many subjects are analysed and the desirability of the health education campaign and the most suitable means of conducting it are illustrated.


[Development of the internal ear in albino rat embryos subjected to transverse acceleration at + 3 G.  Note 3: First observations on the ultrastructural picture of the labyrinth. 1st ultrastructural studies of the labyrinth].

Marked body size reduction (minus 50.5%), and delayed head and body skeletal development were noted in albino rat embryos following exposure of the mother to +/- 3 G acceleration for 3 hr/day between the 10th and 19th day of pregnancy. In addition, electron microscope examination of the inner ear showed signs of greater functional activity of the labyrinth, unaccompanied by reduction of development. Semicircular canal cells and size, in fact, were normal in the crests and at a distance from the latter. There was a marked increase in the number of mitochondria in the cells, in ER area and volume, and A and B glycogen granule richness compared with the controls, these being all signs of considerable activity. The findings substantiate prior histological and histochemical observations: the physiological stimulus offered by acceleration is highly specific for the inner ear structure, particularly that of the labyrinth, to the point where the handicap imposed by the circulatory hypoxia caused by such acceleration, by disturbing the mother-foetus circulation, is overcome.


[Biological effects of radiomimetic compounds: quantitative studies of changes in the urinary excretion of creatine and creatinine in rats treated with HN-2].

Urinary creatine and creatinine excretion in rats treated by HN-2 ("bb'-dichlorodiethyl-N-methylamine") has been studied as function of dose and time from administration. Experimental results obtained in treated animals show an increased urinary excretion for creatine and decreased urinary excretion for creatinine. The variations are correctly related with the dose. Observed modifications are compared with the informations about urinary creatine and creatinine excretion after ionizing radiations exposure. Within research bounds, experimental results let to regard studied compounds as a possible biological dose indicators in the HN-2 intoxication.


[Normal echogram of the mitral valve. Study of 50 normal, military-age subjects].

The mitral echograms of 50 normal subjects of military age were studied and basic parameters compared with anthropometric data and heart frequency; unlike what has been found by other workers, no significant statistical correlation was observed. Mean values of the parameters used are not substantially different to those reported in the literature consulted although deeper statistical studies are required if more valid standards are to be found.


[Our experience with peripheral vascular contrastography].

The Authors are showing here come of the most significant clinical instances of lumbar aortography and upper & lower limbs arteriography and flebography. As the work comes from the cooperation between a civilian and a Navy medical staff, the Authors hope the'll be allowed by their own respective Authorities to go further on cooperating.


[Personal experiences of immunotherapy using the transfer factor].

Six subjects, four suffering from chronic mucocutaneous candidosis, one from ataxiatelangiectasia and one from partial combined immunological deficiency with ongoing pulmonary tuberculosis, were treated with transfer factor. The deficient immunological situation normalized in all subjects after treatment. Clinically, all showed improvement excepting one candidosis case.


[Nosological classification of headaches].

The problem of headache classification is still open. As a mention of all the attempts to classification is not possible, the Author proposes the scheme of work adopted at Turin Headache Unit (referring himself to the best known classifications). The most important idiopathic headaches are described and it is also suggested that they should be kept separated, one from the other, at least up to now. This criterium makes also easier their differential diagnosis from other head pains. Anyway, is has to be emphasized the actual tendency to group together an ever larger amount of headache types.


[Exploration of extra-cephalic pain induced in essential headaches].

The deep pain threshold and migrainous patient's tolerance were investigated by different methods such as: the post-ischemic stasis, muscular exercise in an ischemic condition, sural pressure, comparing them with the cold pain test employed to assess the superficial pain threshold. The tests were carried out simultaneously and symmetrically to both extremities in order to check the possible asymmetry of the pain threshold. Migrainous patients showed a reduced threshold and a lower tolerance to deep pain, while this is not evident when testing the superficial threshold. The simultaneous measurement of both extremities showed higher differences in migrainous patients than in control patients. The meaning of the change of systemic pain is discussed, with special reference to the possible correlation with the hypothesis of a central origin of pain in essential headaches.


[Diagnostic and therapeutic studies using the cryoprobe in various forms of facial pain, not of the migraine or trigeminal type].

The application of cold in neurosurgery (cryosurgery) has already clearly shown that it acts on the nervous structures in two opposite directions, depending on the temperature: i.e., at temperature from 0 degrees to --10 degrees, it stimulates the nervous fibres, and, at lower temperatures (below--80 degrees), it causes their destruction. On these bases we started our diagnostic researches and the treatment of certain forms of non-migraine nor trigeminal facial pain.


[Changes of testosterone levels in the cluster headache syndrome. Preliminary study].

In a preliminary study, plasma testosterone values were obtained by the RIA method from 2 groups of cluster headache males at separate laboratories. Within each group the mean testosterone levels were compared between normal control and cluster patients in active and remission periods. Significantly lower values were consistently obtained from the active cluster patients when compared to either cluster-remission or normal control. The results of this preliminary study are interpreted as revealing a possible association of lowered plasma testosterone levels with the active cluster period in cluster headache syndrome.