Cardiovascular and antihypertensive actions of 1-methyl-3-keto-4-phenylquinuclidinium bromide.

The sympatholytic and norepinephrine depleting drug 1-methyl-3-keto-4-phenylquinuclidinium bromide (MA540) possessed significant chronic antihypertensive activity in mecamylamine- and renal-hypertensive dogs. The compound was approximately four times more potent than guanethidine in the former model and three times as potent in the latter. MA540 reduced orthostatic blood pressure responses in unanesthetized rabbits, but was approximately ten times less potent than guanethidine. The quinuclidine derivative did not affect cardiac output, heart rate or stroke volume in anesthetized open chest dogs and moderately increased mean blood pressure and total peripheral resistance. It produced diuresis and saluresis in anesthetized dogs, but did not influence water or electrolyte urinary excretion in conscious rats. In the latter test, guanethidine produced antidiuresis and antisaluresis. It was concluded that MA540 is a potent, orally effective antihypertensive agent acting through adrenergic neuron blockade, that it lacks undesirable effects on cardiac and renal functions, and that compared with guanethidine, it is more potent in lowering blood pressure but less so in interfering with orthostatic cardiovascular reflexes.


Secretion and localization of cathepsin D in synovial tissues removed from rheumatoid and traumatized joints. An immunohistochemical study.

The proteinase cathepsin D which degrades proteoglycan was never demonstrated in extracellular sites in tissues from patients with traumatized meniscoid cartilage, either before or after culture with an antiserum to human cathepsin D. In contrast, in synovia (but not usually cartilage) from the knees of 6 of 11 rheumatoid patients, extracellular cathepsin D was commonly detected by culturing tissues with an antiserum to this enzyme.


Influence of 1-methyl-3-keto-4-phenylquinuclidinium bromide on rat tissue monoamine levels in vivo.

The effects of 1-methyl-3-keto-4-phenylquinuclidinium bromide (MA540) on tissue monoamine levels in male rats have been compared to those of guanethidine. Neither compound influenced norepinephrine (NE) or 5-hydroxytryptamine (5-HT) levels in brain or epinephrine (E) levels in adrenal medulla. MA540 is about twice as potent as guanethidine as a heart NE depleting agent at both 8 and 24 h after drug administration. The durations of action of the compounds are similar. Unlike guanethidine, MA540 does not deplete NE in small intestine, which suggests that the drug may not elicit guanethidine-like intestinal side effects.


The biological disposition of 1-methyl-3-keto-4-phenylquinuclidinium bromide in the rat and dog.

The biological disposition of 1-methyl-3-keto-phenylquinuclidinium bromide (MA540) has been studied in the rat and dog. Gastrointestinal absorption of the drug was considerably different in the 2 species; about 15% and 75% of the dose in the rat and dog, respectively. Tissue distribution after i.v. administration was characterized by generally high tissue/plasma drug ratios in the rat and by low plasma (the only tissue examined) levels in the dog. Drug localization was apparent in the liver and adrenals, and the highest average (24-h) concentration was found in those tissues. The distribution profile and the chemical nature of MA540 suggest that the compound was distributed, at least initially, in extracellular water. MA540 was not extensively metabolized by either species. Excretion, although initially fairly rapid, slowed such that whole body half-lives were estimated to be 21 h and 47 h in the rat and dog, respectively.


The acute and target organ toxicity of 1-methyl-3-keto-4-phenylquinuclidinium bromide (MA540) and guanethidine in the rat and dog.

The effects of acute and repeated increasing oral doses of 1-methyl-3-keto-4-phenylquinuclidinium bromide (MA540) and guanethidine in the rat and dog have been described. On repeated oral administration guanethidine produced histopathological changes in cervical ganglia of rats and dogs which were clearly dose-dependent and reproduced lesions reported in the literature. Repeated oral administration of MA540 resulted in no histopathological changes in either species. The maximum tolerated oral dose for guanethidine was estimated to be 515 mg/kg in the rat and 26 mg/kg in the dog compared with an estimated maximum tolerated oral dose for MA540 of 1750 mg/kg in the rat and 460 mg/kg in the dog. On the basis of these findings it is suggested that subchronic studies with MA540 in the rat and dog should provide evidence which would justify the use of MA540 in man at daily oral doses as high as 9 mg/kg.


Anticatabolic action of formebolone in the castrated rat treated with dexamethasone.

The anticatabolic action of 2-formyl-17a-methylandrosta-1,4-diene-11a,17beta-diol-3-one (formebolone) was demonstrated by assessing the nitrogen elimination in the urine of castrated rats treated with dexamethasone-21-phosphate. The absence of a virilizing action is duly pointed out.


The absorption of [G-3H]-acetylglycyrrhetate after oral administration to rats.

A tritium-labelled form of aluminium acetylglycyrrhetate has been synthesised by catalytic exchange with tritiated water. An oral dose of aluminium [3H]-acetylglycyrrhetate to rats was mainly excreted in the faeces (a mean of 73%). A mean of 4% was excreted in the urine and after five days 17% of the radioactivity was retained in the carcass. The amounts of non-volatile (drug-related radioactivity excreted in faeces and urine during five days were 65% and 3%, respectively, while 6% was retained in the carcass. The total amount of tritiated water produced was 24% of the dose. Experiments in rats with cannulated bile ducts indicated that much of the faecal radioactivity represented unabsorbed drug. 15% of an oral dose was eliminated in bile during 2 days. A minimum value for the extent of absorption of an oral dose was estimated as 21%. Plasma levels of radioactivity were very low and peak levels of drug-related radioactivity were reached at 30 min and represented about 0.2% of the dose in total plasma.


[The influence of orotic acid on the learning process of rats. Short communication (author's transl)].

A genuine water soluble orotic acid, e.g. thiamindisulfide orotate, increases the learning capability and thus the so called "short-time memory" in rats.


[Study on different kinds of animal feed for their adequateness for breeding and rearing beagle dogs. 1st communication: summarizing presentation of results (author's transl)].

Some of the current food mixtures for dogs available on the market and their further development were tested regarding the usage under rational and standardized experimental conditions. Further, it should be clarified which of the two separate modes of nutrition has the better effect on breeding and rearing of dogs. The use of a complete feed for breeding and maintaining (Altromin H) was compared with a special breeding feed (Zahn Z) together with a special maintenance feed (Zahn H). The tests were made at two places (Mannheim and Ingelheim) mainly on Beagle dogs. The food mixtures are described with the kind and quantity of the ingredients and nutrients. The results of the parameters measured in breeding effect, nursing period and rearing phase showed that all the feeds tested were nutritively satisfactory to the animals. Detailed information will be given in the 2nd and 3rd communications. Further investigations should be carried out on food consumption, food wastage, optional usage of the ingredients of the foodstuff and on energy balance.


Behavioral effects of withdrawal of fluphenazine after long-term treatment.

Male Wistar rats were treated i.p. with 10-(3-[4-(2-hydroxyethyl)-1-piperazinyl]-propyl)-2-(trifluoromethyl)-phenothiazine (fluphenazine dihydrochloride, FL, Mirenil) in a dose of 1 mg/kg for 28 weeks, or in a dose of 5 mg/kg for 21 weeks, beginning from the 6th day of life. Withdrawal of the drug caused an abstinence syndrome in the form of increased locomotor and exploratory activity and increased irritability of the animals. Behavioral observation during the period of drug administration indicated the development of tolerance to behavioral effects of FL. Male and female Wistar rats from mothers treated i.p. with 1 mg/kg of FL during pregnancy and lactation period were treated for 32 weeks with 1 mg/kg of FL beginning from the 8th day of life. In males, during the period of withdrawal as well as during renewed treatment, an increase in locomotor and exploratory activity was observed. The behavior of female rats during the withdrawal period was similar to that of control animals. The abstinence syndrome observed after withdrawal of FL is modified by the time of life at which treatment was started and by the sex of the animals.


Absorption and excretion of 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) in man and dog.

The blood levels and excretion of radioactivity administered as 14C- or 3H-4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) have been studied after oral administration to dogs and man. After a single dose of 14C- or 3H-DA 2370 (10 mg/kg) to dogs the daily loss of radioactivity in urine and faeces fell to less than 1% of the dose in 4 days and the plasma levels showed a biexponential decay with mean half-lives of 3.7 and 62 h. When a single 200 mg dose of 3H-DA 2370 was administered to human subjects maximum urinary excretion of radioactivity occurred during day 2 with 4% of the total during day 5. Maximum faecal excretion was on day 2-3 with 0.5% of the dose on day 7. The plasma half-life was 32.5 h. A similar dose three times a day for 3 days had a half-life of 39 h when dosing ceased; radioactivity in the urine and faeces was 2% and 2.5% of the dose, respectively, 4 days later.


[Critical survey on liver microsome test, a system for detecting point mutations (author's transl)].

The host-mediated assay systems and the liver microsome test are compared considering carefully the advantages and disadvantages of the different systems regarding practice. The essay includes methodical problems as well as relevant questions for humans.


[Kinetics of ampicillin, oxacillin and carbenicillin after a short intravenous infusion in man].

Within 5 min 5 g of ampicillin, oxacillin and carbenicillin, respectively, were administered i.v. to patients with normal kidney function. Plasma levels of the antibiotic activity were measured up to 6 h following the injection. Urine was collected at intervals up to 8 h and the cumulative urinary excretion calculated. Furtheron, biologic half-life, volumes of distribution, total and renal clearance and area under the serum level curve have been assessed for the one- and the two-compartment model. For this model the amounts of drug in central and peripheral compartments were simulated. The statistical evaluation resulted in a highly significantly better fit when the data were analyzed according to the two-compartment model. Despite of these differences the physiological consequences of using the parameters of the one-compartment model were not significantly different.


[Studies on the metabolism of l-asparaginic acid (author's transl)].

After infusion of DL-asparaginic acid (Inzolen) during operation the pharmacokinetics of L-aspartic acid were followed by means of enzymatic determinations in serum and urine samples. The level of L-aspartic acid in the serum increases during the infusion of 250 ml of Inzolen-Infusion (18.54 g DL-aspartic acid) from an original value of 2 mg/l to a maximal value of 156 mg/l, reached at the end of the infusion. Two hours after the termination of infusion, the aspartic acid level returns almost to its original value. Only 20% of the infused L-aspartic acid is excreted unmetabolized.


[Bioavailability and pharmacokinetics of 14C-cyproterone acetate after administration as a 50-mg tablet (author's transl)].

Four male volunteers were each given a 50 mg oral dose of methylene-14C-labelled cyproterone acetate in a formulation largely identical to the commercial preparation Androcur Tablets. A further 3 volunteers were each given 10 mg of the 14C-labelled compound by intramuscular injection. Plasma samples were obtained and urine and faeces collected quantitatively from each volunteer up to 10 days post administration. 1. Absorption of the 50 mg of cyproterone acetate administered in the form of Androcur Tablets was largely complete. 2. The maximal plasma level of 400 +/- 40 ng cyproterone acetate equivalents/ml of plasma, calculated from the 14C activity, was found 3,8 +/- 0,5 hours after oral administration. By 10 hours post administration the plasma level had declined with a half-life of 7,9 +/- 2,5 hours (distribution and elimination). The fictitious distribution volume assignable to this process amounted to 140 +/- 40% of body weight. Plasma 14C-activity then decreased with a half-life of 1,8 +/- 0,2 days, which was consistent with elimination. 3. The labelled substance was almost completely extractable from plasma and could be separated by chromatography into 2 fractions of about equal size: cyproterone acetate and one metabolite. 4. Orally administered cyproterone acetate was eliminated with a half-life of 1,6 +/- 0,1 days. By 10 days post administration 33 +/- 6% of the dose had been detected in urine and 60 +/- 8% in faeces. Up to this time total elimination amounted to 93 +/- 5% of the dose. 5. After intramuscular injection of 10 mg of cyproterone acetate the half-life for absorption from the muscular depot was 7,0 +/- 0,2 hours. Between 2 and 10 days post administration there was a uniform decrease in plasma level and urinary elimination with half-life of 2,3 +/- 0,1 days and 2,1 +/- 0,2 days respectively. By the end of the trial 34 +/- 5% of the dose had been eliminated with urine and 57 +/- 6% with faeces.


[The influence of a therapy with vasodilating agents on the sleep EEG of patients with cerebral circulatory disturbances. Results of a double blind study (author's transl)].

In 30 patients (24 men, 6 women) aged from 30-74 years and suffering from ischemic lesions in the cerebral hemispheres all-night EEG recordings before and after a 3 weeks' treatment with vasodilating drugs were carried out. At the same time the development of the clinico-neurological and psychoorganic symptomatology, also using test psychological methods, were studied. The drugs--10 patients received 50 mg raubasin, 6 patients 500 mg bencyclan and the others a salt solution--were administered i.v. Under the treatment no change in the primary sleep EEG findings could be observed, whereas there was an improvement of the clinico-neurological and psychoorganic symptomatology in the drug as well as in the placebo group. The lack of improvement in mood and state of well-being is discussed in its relationship to the sleep behaviour.


[On the effect of colloid sulphur addition to shampoos on the pileous skin of the head (author's transl)].

A group of 16 male test persons was subjected to hair washes with a standard tenside solution over a period of 4 weeks at one-weekly intervals. 1.25% colloidal sulphur were added to the solution for the 3rd hair wash. From the 2nd week onwards quantitative lipid determinations were carried out on the 2nd and 5th day after washing. The samples from the 5th day were also analysed by thin-layer chromatography. We could not demonstrate any influence on the amount of lipid. There was, however, after the addition of sulphur a significant reduction in the free fatty acids to the advantage of the triglycerides. The addition of sulphur, therefore, brings about a decrease in the bacterial lipolysis of the triglycerides on the hair of the head. Apart from this, a significant increase in the free cholesterol and a significant decrease in the wax and cholesterol esters could be demonstrated after the application of sulphur. This could be possibly an expresion of the keratolytic effect of the sulphur.


[Pharmacology of "essential" phospholipids (author's transl)].

In an extensive pharmacological screening of "essential" phospholipids (EPL) antilipemic, hepatoprotective, broncholytic, as well as slight choleretic effects were found and the substance decreased capillary permeability. There was practically no influence on other functions or systems including the vegetative system (heart, circulation, respiration).


[The anti-hyperlipemic and anti-atherogenic effect of "essential" phospholipids: a pharmacologic trial].

To prove antilipemic and antiatherogenic effectiveness several animal species were given "essential" phospholipids (EPL) during different experimental procedures. The following actions were studied: 1. Effect of EPL-substance after prophylactic and therapeutic oral administration (dosage: 50, 150, 450 mg/kg bodyweight daily) in rats with acute and subacute hypelipemia induced by triton. 2. Effect of EPL-substance after prophylactic and therapeutic oral administration (dosage: 50, 150, 450, 1800 mg/kg bodyweight daily) in rats with dietetic hypercholesterolemia. 3. Effect of EPL-substance after daily oral administration (dosage: 50, 150, 450 mg/kg bodyweight) on the development of coronary and aortic atherosclerosis and various biochemical parameters in cholesterol-fed cockerels. 4. Effect of EPL-substance after dialy oral administration (dosage: 50, 150, 450 mg/kg bodyweight) on subacute triton-hyperlipemia in mini pigs. Triton-administration causes a greater or smaller increase in all parameters of the lipid metabolism measured. EPL treatment decreases these parameters during therapeutic and prophylactic administration in some cases even reaching normal values. The effect was clearly dose-dependent. EPL inhibit the increase in total lipids in dietetic hypercholesterolemia during therapeutic as well as during prophylactic administration. The effect was clearly dose-dependent in all doses, being statistically significant at the highest dosage level. In cockerels EPL were effective at all dose levels in counteracting the development of coronary atherosclerosis while the effect in atherosclerosis of aorta was less distinct. Except for non-esterified fatty acids, EPL reduced all biochemical parameters measured.


[Animal experimental studies on the pharmacokinetics of "essential" phospholipids (EPL)].

The pharmacokinetics of orally applied "essential" phospholipids (EPL) (i.e. polyenyl phosphatidyl choline) was investigated in conscious and in anesthetized rats with the aid of radioactively labelled dilinolyl phosphatidylcholines (3H and 14C.). Absorption, distribution and metabolism of EPL were studied using autoradiography and by measuring the distribution of the abosrbed radioactivity in lymph, blood and internal organs, and by determining excretion and expiration.


Chrysotile-induced asbestosis: changes in the free cell population, pulmonary surfactant and whole lung tissue of rats.

Rats inhaling chrysotile asbestos contracted asbestosis and fibrosis of the lungs. Studies of biochemical and morphological changes (between normal and treated animals) show that chrysotile induces an increase in the lung free cell population and pulmonary surfactant levels. Lysosomal enzyme levels are elevated in both the whole lung and free cell population and there are considerable changes in macrophage morphology. It is suggested that the primary response of the lung to chrysotile is an increase in surfactant production coupled with an increase in free cell numbers, in order to prevent the cytotoxic effect of the dust.


Facilitated transport of di- and trinitrophenolate ions across lipid membranes by valinomycin and nonactin.

The conductance of black lipid membranes in the presence of 2,4,6-trinitrophenol (or 2,4-dinitrophenol) is considerably enhanced, if the cation carriers valinomycin, enniatin B or nonactin are added. The effect is, however, largely independent of the cation concentration and is identical for the cations Li+, Na+ and Ba2+. This finding, as well as the sign and magnitude of the diffusion potential in the presence of a gradient of picrate are consistent with the assumption that the transport of picrate anions is facilitated by the above-mentioned macrocyclic compounds, but that cations are not directly involved. A model is suggested which, based on the generation of mobile defect structures by the incorporation of large molecules, allows one to explain facilitated transport without the assumption of stable chemical bonds between a carrier and its transported substrate. If K+ is present in the aqueous phase, the conductance is largely determined by the permeation of the cation complexes of valinomycin and nonactin. The conductance is, however, increases by adsorption of picrate anions to the membrane surface. The negative surface potential generated by the adsorption layer seems to be responsible for the saturation of the conductance at high picrate concentrations in the absence of valinomycin and nonactin.


Combined modality treatment of American Burkitt's lymphoma.

Fifteen American patients with Burkitt's lymphoma were treated in a clinical trial employing chemotherapy, radiotherapy, and immunotherapy. Two patients died during induction, and 13 achieved complete responses. Eight patients relapsed at a median of 11 weeks from initial treatment, and seven of these have died. The remaining patient has enjoyed a prolonged third remission following intensive chemotherapy and bone marrow autograft. Five patients remain in their first remission in excess of 1 year. The major therapeutic goal in the management of Burkitt's lymphoma is the prevention of relapse; the identification of risk factors and various strategies to achieve this goal are discussed.


Luekemic infiltration of the prostate: a case study and clinicopathological review.

A case of leukemic infiltration of the prostate occurring with acute retention of urine is reported. Examination of the blood showed chronic lymphocytic leukaemia (CLL). The number of reported cases of leukemic infiltration of the prostate is updated and a review of the literature on the subject is presented.


The relationship between the ionic composition of the environment and the secretory activity of the endocrine cell types of Stannius corpuscles in the teleost Gasterosteus aculeatus.

The corpuscles of Stannius of threespined sticklebacks contain two glandular cell types of presumed endocrine nature. To elucidate the function of both cell types the secretory activity of the cells was studied in fully adapted seawater and freshwater fishes and in specimens transferred from sea water to fresh water or adapted to media of various ionic composition. The secretory activity was established, in tissue sections and freeze-etch replicas, by estimating the volume of the nuclei, the density of the nuclear pores, and the frequency of exocytotic phenomena. The type-1 cells, ultrastructurally comparable to the predominant or only cell type described in many other teleosts, are more active in sea water than in fresh water. The activity of the type-2 cells, whose ultrastructural appearance is known only for salmonids and eels, is higher in fresh water. Transfer of seawater fishes to fresh water results in reduction of type-1 cells and activation of type-2 cells. The factors responsible for these changes were analyzed by exposure of fishes to solutions of various salts in fresh water and to artificial sea water with a reduced content of one of its components. The high activity of type-1 cells in sea water proved to be related to the high calcium content of this medium. These cells probably produce a substance comparable to hypocalcin, the endocrine factor isolated from the Stannius corpuscles of some other teleost species. The high activity of type-2 cells in fresh water appeared to be connected with the low sodium and potassium levels of this medium. Type-2 cells possibly produce a hitherto unknown hormone involved in the control of sodium and/or potassium metabolism.


Cytological factors and their predictive role in comparative radiosensitivity: a general summary.

Various cytological factors, including interphase chromosome volume (ICV), nuclear volume (NV), cell volume, DNA content per nucleus and per chromosome, have been reviewed to determine their usefulness as indices to predict radiosensitivity. Fourteen topics are discussed. They are: a historical development of the concept of using karyotypic features to estimate radiosensitivity; interrelationships between cellular parameters; relationship of the karyotype to the duration of mitosis and meiosis; relationships between chronic and acute irradiation and ICV using several radiobiological end points for woody and herbaceous species; correlations between dose and cellular parameters ftween chromosome aberrations and cellular characteristics after chronic irradiation; polyploidy and plant radiosensitivity; radiation-induced petal mutations in plants and their relationship to cellular parameters; correlations between mean survival time facter irradiation and cellular parameters in amphibians and higher plants; correlations between radiobiological end points and cellular parameters after whole-body irradiation in amphibians. insects and mammals; correlations between radiosensitivity and cellular parameters in diverse single-cell organisms; correlations between radiobiological end points and cellular parameters in higher plants irradiated with neutrons and the value of cell parameters to estimate relative biological effectiveness (RBE); and energy absorption and trends in radiosensitivity among species and radiobiological end points. It is concluded that ICV is usually the most useful parameter for predicting radiosensitivity.


Lack of effect of acute prolactin suppression on renal water sodium and potassium excretion during sleep.

The possible role of endogenous prolactin (hPRL) in the regulation of renal water, Na and K excretion during sleep was tested in a group of 10 healthy female volunteers. Plasma hPRL and total urinary Na and K excretion were measured at 2- and 4-hourly intervals, respectively, in the control period and after prolactin inhibition with bromocriptin. Despite adequate prolactin suppression, no significant changes were observed in the nyctohemeral excretion rhythms of water, Na and K, suggesting that endogenous prolactin is not instrumental in the control of these parameters.


Urinary excretion of drugs in chronic renal impairment with respect to changes their tubular handling by residual nephrons.

Decrease of the relative value of the renal clearance (the ratio between the value observed and the normal value) of a drug may be slower than the decrease of the relative value of the glomerular filtration rate. A slower decrease of drug renal clearance may be due to an increase in its effective secretion or a decrease in its effective reabsorption by residual nephrons. The mechanisms underlying these changes still remain obscure. One of the factors is assumed to be sodium osmotic diuresis in residual nephrons (associated with functional adaptation).


Articulation in early childhood autism.

Using a standardized articulation test, comparisons were made between the articulation of autistic children and (1) a group of predominantly subnormal language matched controls; (2) developmental receptive dysphasic controls. The autistic children's articulation was significantly superior to that of both control groups. The findings are discussed in relation to differences in the pattern of language impairment in the three groups.


Phonological investigation of verbal autistic and mentally retarded subjects.

A review of the pertinent literature indicates that autistic children are likely to show normal but delayed development of speech sounds. In contrast, atypical phonological development is suggested by experiments demonstrating that autistic subjects are deficient in their ability to extract the components of structured auditory input. A systematic investigation of the speech sound systems of verbal autistic and mentally retarded children reveals a delay in phoneme acquisition, as well as a relative uniformity of error types in both groups. The autistic subjects, however, differ significantly from the mentally retarded in the phonemic substitutions which they make. Autistic subjects are also characterized by a high correlation between frequency of phonological errors and level of overall language development. The findings are interpreted as supporting the hypothesis that the autistic group shows a more global delay in language development.


Biotransformation of ioglycamic acid, iodoxamic acid and iotroxic acid in man.

The biotransformation of the 131I-labeled cholegraphic media ioglycamic acid, iodoxamic acid and iotroxic acid in man is investigated. Plasma, urine and fistular bile were analyzed for unchanged and metabolized constituents of the administered substances using thin layer chromatography. No metabolites were found in plasma, but up to two were found in urine in addition to unchanged contrast media (a total of 50% of the total elimination in 24 hr. urine). A metabolite was only found in the fistular bile after the injection of iotroxic acid.


Reassessment of elevated serotonin levels in blood platelets in early infantile autism.

Blood platelet serotonin content was measured in 30 children with early infantile autism, as defined by Kanner, 30 age-matched normal subjects, and 45 children with various neurological and psychiatric disorders. Serotonin content in the autistic group was 980 +/- 357 ng/mg platelet protein (mean +/- standard deviation), a value significantly higher than that for normal children, 807 +/- 202 ng/mg (p less than .025). Autistic children under school age had higher platelet serotonin concentrations than other older autistic individuals. There was little correlation between age and serotonin levels in the normal children. Elevated serotonin was also seen in some of the non-autistic pathological group, who were disturbed and hyperactive. Elevated serotonin levels are not necessarily a specific biochemical finding for autistic children, but seem to be due to their behavioral distinction.


Neuropathologic aspects of psychosis in children.

On the basis of a search of the literature and extensive inquiries to clinicians, this paper catalogues those cases that contain any information concerning possible neuropathologic changes in cases of childhood autism or psychosis. In all, 33 cases were identified. Twenty-nine cases are from the literature; six of these are sibling pairs. Four cases were folnd by inquiry and have not been reported heretofore. Because of limitations in both the clinical and neuropathologic data in most of the case reports, the paper serves primarily as a source of reference to the 33 cases identified. The information that is available is presented along with some tentative suggestions for further research.


Platelet uptake and efflux of serotonin in subtypes of psychotic children.

The only finding of a metabolic defect in psychotic children which has been replicated in a blind study is the discovery of an elevated efflux of serotonin from the platelets of children with early infantile autism (Boullin, Coleman, & O'Brien, 1970; Boullin, Coleman, O'Brien, & Rimland, 1971). The reported failure of Yuwiler, Ritvo, Geller, Glousman, Schneiderman, and Matsuno (1975) to replicate the Boullin et al. findings is attributable to differences in the method of selecting subjects. The Boullin et al. studies found that only children with classical infantile autism, as diagnosed by the Rimland E-2 check list, manifested the metabolic error. Since only 10% of psychotic children score in the autistic range on the check list, and since all children in the Yuwiler et al. study displayed the syndrome of "perceptual inconstancy," a syndrome inconsistent with "insistence on the preservation of sameness," an integral part of the syndrome of early infantile autism as scored on the E-2 check list, the failure of Yuwiler et al. to find elevated efflux in their sample was to be expected.


Hashimoto's thyroiditis presenting as a solitary functioning thyroid nodule.

A case of hypothyroidism is described in a young woman who on thyroid scan had a discrete functioning "nodule" with homogeneous radioactive iodine uptake, and surrounded by atrophic non-functioning thyroid tissue. Antithyroglobulin antibodies were not demonstrable, but anti-microsomal antibodies were positive at a titer of 1:25,600. Histologically, the "nodule" represented Hashimoto's thyroiditis with more extensive destruction of the remaining gland. Although it is unusual, Hashimoto's disease should be considered in the differential diagnosis of functioning thyroid nodules, and both anti-thyroglobulin and anti-microsomal antibodies should be obtained in such circumstances.


Ovarian refractoriness to gonadotropins in cases of inappropriate lactation: restoration of ovarian function with bromocryptine.

In ten patients with amenorrhea-galactorrhea who had hyperprolactinemia, ovulation could not be induced clomiphene citrate or exogenous gonadotropins. Treatment with bromocryptine in eight of these patients resulted in suppression of PRL in all, cessation of galactorrhea and ovulation in seven and conception in five.


The in vitro suppression of lectin induced 3H-thymidine incorporation into DNA of peripheral blood lymphocytes after the addition of propylthiouracil.

A possible in vitro immunosuppressive role of propylthiouracil (PTU) was investigated by culturing peripheral blood lymphocytes (PBL) from normal subjects with plant lectins in the presence of PTU added at the onset of culture or near the time of peak cell division. When added at the onset of culture PTU caused a dose-related suppression of lectin stimulated 3H-thymidine uptake with an average of approximately 50% suppression at a PTU concentration of 100 mug/ml. When added at the time of peak cell division however, marked suppression was produced by 10 mug/ml of PTU. Prolonged remissions in patients with Graves' disease treated with PTU, and possibly other anti-thyroid drugs, may thus be due to an immunosuppressive role of the drug rather than the natural evolution of the disease.


Electron microscope assessment of fertilization of rabbit ova treated with concanavalin A and wheat germ agglutinin.

Zonaless rabbit ova, exposed to Concanavalin A or Wheat Germ Agglutinin, then to uterine capacitated sperm produce pronuclear, 2 and 4 stage embryos that are indistinguishable from controls. Absence of cortical granules indicates that the ova were fertilized and not merely activated. Survival of lectin-bearing receptors during the period necessary for fertilization was evaluated in ova marked with ferritin-conjugated lectin.


Enhancement of haemolysis by Newcastle disease virus (NDV) after pre-treatment with heterophile antibody and complement.

Pre-treatment of Newcastle disease virus (NDV) with fresh human plasma enhances its haemolytic (HL) capacity by several factors. The effect is due to complement activation by the heterophile anti-chick antibody present in human plasma. All the adult human plasmas tested were effective, also 91/100 human cord blood sera. The antibody was mainly of the IgM class. The enhanced HL was due to integration and transference of the complement 'holed' virus envelope membrane and subsequent leakage of haemoglobin. High concentration of activated complement destroys the integrity of the virus enevelope. Treatment of chick erythrocytes and fibroblasts with human plasma also produced lysis of the cells.


Pregnancy following bromocryptine therapy for the amenorrhoea-galactorrhoea syndrome due to a pituitary tumour.

A woman developed amenorrhoea and galactorrhoea after partial removal of a pituitary tumor during pregnancy. Hyperprolactinaemia was supressed by therapy with bromocryptine (CB 154, Sandoz) resulting in cessation of galactorrhoea in two months, spontaneous menstruation after eight months, and pregnancy after twelve months.


The reaction of Cytembena with cellular thiol compounds.

Cytembena has been shown to undergo a rapid addition reaction with a number of thiol compounds, including glutathione and cysteine, resulting in alkylation of the sulphur. Administration of Cytembena to Yoshida sarcoma cells and to L1210 leukemia cells resulted in a loss of titratable thiol groups within the cells, though the loss of thiol groups caused by pharmacologically active doses of the drug was not sufficient to account, in itself, for the observed toxicity. The addition product of Cytembena and glutathione was isolated and tested for cytotoxicity; it was much less effective than free Cytembena. It is concluded that this reaction acts as a route of detoxification of Cytembena.


Spermatozoal migration and lymphatics: a hypothesis.

The exact mechanism of sperm migration is still unknown. Lymphatics may act as transporting channels for the migration of sperms. The relevant literature is reviewed and it is suggested that myometrial contractions may allow the lymphatics of the uterus to take up the sperms and pump them actively towards the uterine tubes, where they are pumped again by tubal contractions towards their destination at the end of the tube where they fertilize the ovum.


Sequelae of head and neck positions on auditory performance.

Stapedius reflex level, slow auditory evoked potential (AEP), and hearing threshold level of 18 normal adult probands (11 female, 7 male) as well as of 14 normal hearing cerebral palsied children between 4 and 12 years of age (5 female, 9 males)--were determined in different postures which correspond to the influence of tonic reflex activities in supine and prone, and in the so-called "reflex inhibiting pattern" (Bobath) and in a symmetrical relaxed position of neck, trunk and extremities in supine (the last one could only be maintained by the normal volunteers). Influence of the postures was small but significant for all parameters in the volunteers group as well as for AEP in the patients group. In the latter group the influence of tonic reflex activities on auditory evoked potential was independent from their strength. The strength of tonic reflex activity had been graded from 1-5 as judged from clinical impression by observation and palpation.


Bobath-therapy, tonic reflex--activities and processing of acoustic stimuli.

The influence of tonic reflex activities on the slow auditory evoked potential (AEP) as well as the influence of Bobath's reflex inhibiting patterns (r.i.p.) in a group of 14 cerebral palsied children is compared under the same conditions with simulated tonic reflex patterns in 18 adult normal volunteers and 15 cerebral palsied children. In the adult volunteers group the effect of a relaxed symmetrical position of neck, trunk, and extremities in supine on the AEP is also evaluated. There are none but age specific differences in the latence of AEP between both groups but clear cut differences in the amplitudes and in the specific effect of r.i.p. in both groups.


Muscle activity and postural behaviour in newborn infants. A polymyographic study.

In a group of 9 healthy newborns, spontaneous activity of different muscles was studied for 6 or 8 hours by means of surface electromyography on the 5th or 6th day of life. According to the local nursing routine the infants were placed in alternating left and right side positions. Averaged EMG activities were analysed with respect to behavioural states and observed postural behaviour. An improved recording technique and the logarithmic presentation of averaged EMG activities allowed the study of characteristics of tonic activity in state 1. The chin muscles showed the most specific EMG pattern in state 1. Chin muscle quiescence was observed during only 15% of that state. Lack of tonic activity was observed more in the beginning than at the end, but never in the middle of state 1. By visual analysis of 41 patterns of averaged EMG activities from the chin muscle it was found that increases of tonic activity only happen stepwise following concomitant phasic activities. Relaxation of tonic activity is either asymptotic or abrupt or by steps. The latter two are especially characteristic for the transition to state 2. Long periods of sustained tonic activity and low motility were characteristic for a long lasting state 1. The interval between the beginning of state 1 and the first increase of tonic activity varied more than the interval between the end of state 1 and the final drop of tonic activity back to the noise level. Other muscles showed less tonic activity in state 1: the neck area (sterncleidomastoid muscle 48% of state 1 time, trapezius m. 32%) was followed by the muscles of the forearm (extensor carpi m. 18%, flexor carpi m. 16%). These muscles also lead the rank order of the modulation of tonic activity. Tonic activity sustained for more than 30 sec. was not observed in state 2, except during transitions. In state 2 as in state 1 the muscles from chin, neck and upper extremities were more active than the muscles from the lower extremities. Durations of activities ranged from 28% (chin) to 13% (ant. tibialis) of state 2 time. No dominance of flexor muscles, which might account for the observed flexed posture, was found. Systematically changed side positions during the recording had no consistent effect on either motility or presence of tonic activity when corresponding muscles from the upper- and the lower-lying body side were compared during state 1. Likewise in state 2 no consistent effect on the total duration of phasic activity was observed. The results are discussed in relation to other known state dependent motor phenomena. It is suggested that sustained tonic activity results from an increased gain of the gamma-loop which may also contribute to the regularity of respiration. Differences between muscles probably reflect maturational and functional differences.


Communicating hydrocephalus causing aqueductal stenosis.

The cited evidence establishes that the pathogenetic sequence of generalized communicating hydrocephalus followed by various degrees of aqueductal stenosis occurs in many mammalian species. The aqueductal stenosis is caused by compression of the midbrain by the expanding cerebral hemisphere. Therefore the sharp separation of communicating and non-communicating hydrocephalus is no longer tenable.


Benign hereditary non-progressive chorea of early onset. Clinical genetics of the syndrome and report of a new family.

The syndrome of benign non-progressive chorea (of early onset) is described in three brothers and some of their relatives. Clinical genetic study of the family showed an autosomal dominant mode of inheritance and suggested presence of the gene in both sides of the family. Thus, the propositi might be homozygous for the dominant gene (suggested by increased clinical manifestations as compared with other affected members on both sides of the family) which shows relatively high penetrance and variable expressivity. The phenotypic spectrum of the syndrome is differentiated from similar observations in the literature, and genetic implications are discussed. The condition is differentiated from hereditary essential tremor and from paramyoclonus multiplex.


Propanolol treatment of infantile polymyoclonia.

Two infants with the classical involuntary movements of polymyoclonia and opsoclonus were treated with propanolol in a dosage of 2 mg/kg/24 hr. There was a marked improvement in the abnormal movements in both children. No side effects of treatment were encountered.


[5,000 mammography--results and analysis (author's transl)].

Mammography, well performed, is the best method for the differential diagnosis of breast diseases. It is essential for the detection of clinical occult cancer (in some cases thermography can do the same). The earlier breast cancer is diagnosed the lesser is the chance of lymphnode involvement. Therefore women aged over 40 years and belonging to a so-called riskgroup (carcinoma in the family, earlier breast diseases, mastopathies, breast cancer of the other breast etc.) should perform mammography once a year. 90% of the breast cancer patients are over 40 years. In higher ages that mammographic diagnosis is more accurate. Considering the advantage of this method the effect of radiation is to be neglected. The experienced radiologist can obtain 90% correct diagnoses. In combination with thermography and needle aspiration biopsy he can improve to 95%.


[Ventilation mechanics in the premature and the newborn. I. Statistical measurements of the isolated lungs].

On 31 pairs of lungs from still borns and newborns of differing stages of maturation and age (23rd week of gestation up to the 24th week after birth) statical measurements including liquid fillings were performed. On account of the histo-mechanical tests as well as morphological and clinical data, the group could be divided into normal lungs and lungs with decreased surfactant activity. Between the 35th week of gestation and the 5th week after birth a marked increase in pulmonary maturation with unproportional changes of the histomechanical values could be demonstrated. In lungs with decreased surfactant activity the influence of life span upon the mechanical properties of pulmonary tissue could be shown. The high surface tension decreases, presumably on account of surfactant synthesis, while the values of tissue elasticity decrease as a result of overstretching.


[Studies on milk from different species. I. The content of methionine in cow, water buffalo and sheep caseines].

The present paper reports the content of methionine in cow, water buffalo and sheep casein measured according to Maugenet and Coauthors. The following values were obtained: 3,25% in cow; 3,15% in water buffalo; 3,16% in sheep.


[Results of some experiences on modern techniques of vinification of red grapes].

The results of experiences carryed out at the "Istituto di Industrie Agrarie" of the University of Bologna in the last five years, applying the techniques of vinification by carbonic maceration (CM) and by heat treatment of the crushed in the production of Emilia-Romagna wines, are reported. In particular, the evolution of the main organic constituents during anaerobic conditioning of grapes, the possibility of applying the CM to Sangiovese, Merlot and Canina grapes, the different variations of the CM technique, that is, CM followed by information with skins, the rifermentation of wines produced by traditional method with 10-20% of grape juice obtained by CM, the influence of CM on aging of barbera wine, some laboratory tests to explain the mechanism that regulate same interaction phenomena during the "intracellular fermentation", are discussed. The results of technique of heat treatment of the crushed, in the vinification of Sangiovese grapes, in a pilot plant, are exposed. Finally, the effects of some parameters (treatment of the crushed integral or partially dripped, heating temperature, rest time, sulphur dioxide employ, etc.) on the chemical characteristics and on the organoleptic quality, are estimated.


[Chromatographic analysis of water-soluble vitamins. I- Chromatographic behaviour of water-soluble vitamins on Aminex resins (author's transl)].

The most important water-soluble vitamins are quantitatively determined by high pressure chromatography using porous ion exchange resins. Thiamine and Riboflavine are separated by a cation exchange resin Aminex A5 using 0.3 M KCI in 0.1 M potassium phosphate pH 8.0 buffer as mobile phase; pyridoxamine, pyridoxol, pirydoxal and nicotinamide are successfully chromatographated on the same type of cationic resin using a linear gradient both of pH and ionic strength as mobile phase. Anionic vitamins like L-Ascorbic Acid and Nicotinic Acid are separated on Aminex A14 at acidic values of pH, using isocratic conditions of the ionic modifier. Under the described experimental conditions, the reproducibility of VR, RS and peak area are of 2.5% and 3% respectively. The sensitivity relative to the vitamins tested ranges from 100 to 250 ng.


[Search of optimum survival conditions for lactic acid bacteria in powders obtained by spray drying of yoghurt].

The paper reports the results of two spray-drying tests carried out on yogurt as such or previously neutralized. The operating conditions of the drying operation were such that the temperature of the product didn't exceed 80 degrees C, and the residual moisture of the powder was about 10%, slightly higher than the B.E.T. monolayer value. The decrease of total counts was three and two decimal reductions respectively for the natural and neutralized product. This latter gave also much higher viability index as determined in a "fermenting activity" test. Also, the analyses, related to the quality of the protein fraction, strongly support the opportunity of neutralization before drying. In storage tests carried out during 8 months the survival data were higher at 5% relative humidity (corresponding to 7-8% humidity) and at 5 degrees C temperature. In all cases the better results were obtained from the powders of neutralized yogurt, even in comparison with a freeze-dried sample obtained from the natural product. The typical shape of the sorption isotherms of these products suggests that the optimum process as regard to microorganisms' survival consists in drying the neutralized product up to residual humidities of 8-10%, followed by storage, in humidity-proof containers, at temperatures of about 5 degrees C.


[Clinical features of Cryptococcus neoformans infections].

Two cases of infection with Cryptococcus neoformans are presented. The first showed primary localization in the CNS, while the second occurred in connection with lymphoproliferative malignancy and cytotoxic chemotherapy, with the typical sequence of initial lung infection and secondary meningo-encepha-litis. The important clinical features, development and therapy of the disease are discussed in the light of this personal experience.


[Development of a "vortex bed" drying apparatus].

Fundamental parameters in dimensioning a "vortex bed" drying apparatus are the pressure drop across the bed and the higher and lower limit of fluidization velocity. The analysis of the Navier-Stokes equations brings to the following functional relations between dimensionless groups: (see journal). These relations define the fluidization conditions in a "vortex bed" apparatus. Experimental tests carried out on a laboratory scale apparatus will provide us with the unknown constants for industrial scale extrapolation.


[Fine needle biopsy of "cold" struma nodules in 4555 patients of an endemic goiter area. Results and clinical significance].

Over a period of 8 years, thin needle biopsies of hypofunctional, scintigraphically cold goiter nodules were performed in 4555 patients. 1076 underwent surgery and cytological diagnoses were thereby histologically confirmed. In 715 patients with normal or degenerative cytological findings, the diagnosis was correct in 95.1%. On the other hand, 8 malignancies, 13 Hürthle-cell adenomas, and 26 cases of Hashimoto's thyroiditis were misdiagnosed. The 8 diagnostic errors in the malignancies were due to puncturing of the wrong nodule in 3 cases and, in 5 cases, due to highly differentiated, partially degenerated, follicular carcinomas. In 322 cases with suspect or malignant cytological findings, 129 malignancies (40%) were confirmed. In most cases, false positive diagnosis was due to histologically atypical adenomas, e.g. Hürthle-cell adenomas. Hashimoto's thryoiditis could be readily diagnosed only in the advanced stage. The clinical diagnosis of de Quervain's thyroiditis can be verified by cytological examination.


[The sterolic fraction of virgin olive oil and its and its analytical significance].

The influence of the cultivar factor over the composition of the sterolic fraction of virgin olive oil has been verified by G.L.C. Such a fraction is not influenced by either the poor condition of the olives or the auto-oxidation process of oil. The use of many selective stationary phases like OV-17 in comparison with the SE-30 doesn't improve the analitic situation aiming at guarding the genuineness of the virgin oil. The analytic results confirm the value of the official method, even if, in the very few cases of oils with an insufficient level of beta-sitosteroil, blending it is necessary.


[Poly-protein. I- A new process for obtaining leaf protein concentrates].

The authors have devised a new process, called POLY-PROTEIN, for obtaining leaf protein concentrates from alphalpha juice by precipitation with polyelectrolites. The use of steam is avoided and the technology is very simple, making this process more economical than those already employed.


[Microaggregates in preserved blood].

Today it is generally accepted that microaggregates contained in stored blood may be deleterious to the pulmonary circulation if large volumes of blood are transfused. These microaggregates can be eliminated from blood with the help of microaggregate filters. Such filters are expensive and their efficiency and safety has not been tested thoroughly as yet. Alternatively, the use of microaggregate-free blood is advocated to prevent pulmonary complications in massively transfused patients. Fresh blood, fresh frozen plasma and buffy-coat free red cell concentrates do not contain significant numbers of microaggregates and can be used for massive transfusion without microaggregate filtration.


[Influence of technological processes on the extractability of phenols and carbohydrates from sunflower meal and related protein solubility].

A chemical method for the removal of chromogenic phenolic constituents and carbohydrates of the sunflower meal has been investigated. This method uses a nondenaturing polar solvent formed by n-butanol saturated by diluite HCl and allows the preparation of protein isolate off-colour free. Evaluations on the extractibility of phenols, carbohydrates and proteins of sunflower meals from different technological processes have been carried out.


A pathomorphic study of chronic thyroiditis.

The authors studied the pathomorphy of 364 cases of chronic thyroiditis including Hashimoto's thyroiditis (67 cases), Hashimoto's thyroiditis associated with thyroid cancer (21 cases), De Quervain's thyroiditis (10 cases), tuberculous thyroiditis (6 cases), and 260 cases of focal thyroiditis without manifest clinical symptoms appearing in 10% of euthyroid polynodular goitres. A personal classification of chronic thyroiditis is presented. The high incidence (24%) of association between thyroid cancer and the fibrous type of Hashimoto's thyroiditis is emphasized. A morphometric investigation showed the highest sclerosis percentage in De Quervalin's thyroiditis.


The activation of human factor X in sodium citrate: the role of factor VII.

Human factor X was purified by several different procedures yielding products which had varying amounts of factor VII and factor IX. Treatment with CHCl3 during the fractionation of the factor X removed 95% of the factor VII and factor IX activity and the resulting factor X activated more slowly when incubated in 25% sodium citrate. Removal of residual factor VII by DEAE cellulose chromatography yielded a factor X which activated still more slowly and less completely. When the factor VII, removed by chromatography, was added to the chromatographed factor X, the ability to be activated in 25% sodium citrate was restored. Confirmatory evidence for the role of factor VII in this reaction was the inhibition of the conversion of the factor X by both DFP and SBTI.


Bleeding in uremic patients after carbenicillin.

Hemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels greater than 300 mug/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives. This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity. Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenae et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels "only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function".


Platelet adhesiveness and fibrinolysis after recent cerebro-vascular accidents and their relationship with subsequent deep venous thrombosis of the legs.

In fifteen patients with a cerebro-vascular accident resulting in an acute hemiplegia there was a subsequent rise in the platelet count and plasma fibrinogen level. There were no significant alterations in platelet adhesiveness, plasminogen activator, plasminogen, FR-antigen and haematocrit. Patients diagnosed as developing deep venous thrombosis with the 125I-fibrinogen technique had a significantly lower platelet adhesiveness and plasminogen level than those who were not.


Microvascular haemostasis and the effect of local stimulation and inhibition of platelet function. An experimental study in rabbits.

The local stimulation and inhibition of haemostatic plug formation was studied by local infusion and superfusion of different agents - ADP, thrombin, adenosine, heparin, prostaglandin E1 (PGE1) and laster injury. ADP and laser injury shortened venular haemostatic plug formation time whereas adenosine in the superfusate and PGE1 prolonged it. Thrombin infusion had no effect but thrombin in the superfusate significantly stabilised the haemostatic plugs. It is suggested that ADP released from red cells is the most potent stimulator for haemostatic plug formation in the rabbit mesenteric microcirculation.


Molecular size distribution of fibrinogen derivatives formed in vitro and in vivo: a chromatographic study.

Using gel chromatography, fibrinogen derivatives present in purified systems or in biological fluids were separated and partially characterized. Eight groups of fibrinogen derivatives could be separated by gel filtration through 6% agarose in large columns, four with an elution volume smaller and four groups with an elution volume larger than that of fibrinogen. Careful calibration of the column allowed estimation of the diffusion coefficients of some of the derivatives and, thus, comparison with derivatives previously identified. Three, rather than two, groups of intermediate derivatives were observed during the degradation of human fibrinogen by plasmin in vitro or in vivo. One of these had a marked tendency to polymerize. A rather distinct difference in elution pattern was found between plasma obtained during streptokinase administration and from patients with intravascular coagulation.


Low-dose heparin and deep-vein thrombosis after total hip replacement.

The effect of subcutaneous low-dose heparin on postoperative deep-vein thrombosis (D.V.T.) (diagnosed by the 125I-labelled fibrinogen test) has been investigated in a trial of 143 patients undergoing the operation of total hip replacement. Two randomized studies were carried out: in one the scanning for D.V.T. was carried out daily for 7 days postoperatively andin the other for 15 days. In both, the incidence of D.V.T. was significantly lower in the heparin-treated patients (P less than 0.005). Bilateral D.V.T. was also prevented (P less than 0.05), through the extension of D.V.T. to the distal veins of the thigh was not significantly reduced. Heparin treatment was, however, followed by a higher incidence of severe postoperative bleeding (P less than 0.02) and wound haematoma formation (P less than 0.005), and the postoperative haemoglobin was significantly lower than in the control group (P less than 0.005). A higher number of transfused blood units was also needed by the heparin treated patients (P less than 0.001).


Comparison between a modified ethanol gelation test and protamine sulfate test. Experimental studies.

A comparative experimental study has been made to correlate the protamine sulfate test and a modified ethanol gelation test, based on clinical observations of the solubility of a gel formed at 20 degrees C (Godal and Abildgaard procedure) when it was transferred to a bath at 37 degrees C. Two different results were obtained: the gel remained insoluble at 37 degrees C or it became completely soluble, with intermediate degrees of partial solubility. Our studies indicate that this is due to the amount of fibrin monomers formed and the level of fibrinogen: the first are responsible for the insolubility of the gel and the second for its solubility. This furnishes us with useful information for diagnostic purposes. We found the protamine sulfate test more sensitive than the ethanol gelation test, and its sensitivity increased when fibrinogen level decreased. An insoluble gelation test is a sure indication of the presence of fibrin monomers, but a soluble gel calls for the protamine sulfate test to confirm this or the existence of high fibrinogen level.


Platelet preservation. II. The response of human platelet suspensions to hypotonic stress.

1. Platelet suspensions were exposed to hypotonic stress. Several parameters of the changes in light absorbance were investigated i.a. the initial decrease in absorbance (A min), the maximal rate of the recovery process (V max), and the value of the absorbance two hours after mixing the platelet suspension with the hypotonic solution. 2. The ratio V max/A min appeared to be independent of both platelet concentration and, within a specific range, decrease in osmolarity. 3. Cryoprotectants appeared to disturb the response to hypotonic stress. 4. Cryopreservation caused a decrease in the light absorbance of the platelet suspension, of A min, and of the recovery process.


Platelet preservation. III. The influence of dimethylsulfoxide and cooling conditions on serotonin uptake velocity and response to hypotonic stress of human platelets.

1. Serotonin uptake velocity of human platelets was found to be reversibly inhibited by the presence of dimethylsfulfoxide (DMSO). 2. Incubation of platelet concentrates in the presence of DMSO for 90 minutes at room temperature decreased serotonin uptake velocity and response to hypotonic stress. 3. The serotonin uptake velocity was not substantially influenced by the temperature of incubation with DMSO. 4. The best recovery of serotonin uptake velocity after cryopreservation in the presence of DMSO was observed when DMSO was added quickly before cooling and removed quickly after thawing. 5. No significant differences were observed in serotonin uptake velocity and response to hypotonic stress cryopreservation in the presence of DMSO when cooling rates were varied from 2 to 10 degrees C/min.


Newborn platelet dysfunction: a storage pool and release defect.

Per cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to highdose ADP (20 muM), strong collagen suspensions, and thrombin; however, when compared with PRP from the mothers or from normal adults, per cent aggregation in response to lower concentrations of ADP (2 muM), weak collagen, and part particularly epinephrine was markedly reduced. Nucleotide release after stimulation of the newborns' PRP with the latter two inducers was also impaired. ATP and ADP content of the newborns' platelets was also significantly less than that of their mothers or of normal adults, but specific activity was normal. The data suggest that the impairment of ADP release in the platelets of newborn infants is due to decreased sensitivity to external stimuli. Since metabolic ATP is necessary for the platelet release reaction, it is postulated that the platelet dysfunction results from a lack of metabolic ATP.


The prothrombin time test: effect of varying citrate concentration.

Blood samples from 12 normal subjects and 46 patients on oral anticoagulants were divided so that each was anticoagulated with four concentrations of trisodium citrate solution in the range 0.09-0.15 M, 9 vol blood being added to 1 vol citrate solution in each case. Citrated blood haematocrit and plasma prothrombin time was measured on each subsample; 0.025 M CaCl2-solution was used for recalcification throughout. Three laboratories participated, each using a different prothrombin-time technique.


Fibrin formation: the role of the fibrinogen-fibrin monomer complex.

The process of fibrin formation using highly purified fibrinogen and thrombin was studied using laser fluctuation spectroscopy, a method that rapidly determines particle size in a solution. Two periods in fibrin clot formation were noted: an induction period during which no fibrin polymerization occurred and a period of rapid increase in particle size. Direct measurement of fibrin monomer polymerization and fibrinopeptide release showed no evidence of an induction period. These observations were best explained by a kinetic model for fibrin clot formation incorporating a reversible fibrinogen-fibrin monomer complex. In this model, the complex serves as a buffer system during the earliest phase of fibrin formation. This prevents the accumulation of free polymerizable fibrin monomer until an appreciable amount of fibrinogen has reacted with thrombin, at which point the fibrin monomer level rises rapidly and polymerization proceeds. Clinically, the complex may be a homeostatic mechanism preventing pathological clotting during periods of elevated fibrinogen.


Analysis of the disappearance curve of labelled fibrinogen at the time of hyperfibrinogenemia in rabbits with acute or chronic intravascular coagulation.

In order to study fibrinogen metabolism, the disappearance curve of 125I-abelled homologous fibrinogen was investigated in the rabbits with experimentally induced acute or chronic intravascular coagulation by injection of Lycopodium spores or thromboplastin. The results obtained were as follows. 1. Using haemolysate, an intermediate phase with upward convexity was clearly recognized between the early rapid-decay phase and the late slow phase in each radioactivity decay curve obtained in groups of rabbits. This convexity was most marked with acute intravascular coagulation induced by injection of Lycopodium spores, and was less marked, although higher, with chronic intravascular coagulation induced by injection of thromboplastin than that in the normal control. 2. The disappearance curve with the intermediate phase could be expressed, in approximation, as a sum of 2 equations--the initial exponential decay equation and the late parabolic one. 3. From the results obtained by separate examinations of the disappearance curve of plasma, fibrin clots and serum in rabbits with acute intravascular coagulation induced by injection of Lycopodium spores, the intermediate phase appears to be influenced more by the secondary increase of labelled non-clottable part tahn recirculation of the labelled fibrinogen. 4. The half time (27.4 hours) of the radioactivity in fibrin clots at the late phase observed in the group of rabbits with acute intravascular coagulation induced by injection of Lycopodium spores was shorter than that in the normal rabbits (50.2 hours). This fact may indicate that the increase of fibrinogen in the group of rabbits with acute intravascular coagulation induced by the injection of Lycopodium spores is due to overproduction of fibrinogen. 5. The half time of labelled fibrinogen should be calculated from disappearance curve of fibrin clots, instead from that of haemolysate or plasma.


The recovery of factor VIII from fresh-frozen indated and outdated human plasma.

The availability of factor VIII concentrates is frequently a limitation in the management of classical hemophilia. Such concentrates are prepared from fresh or fresh-frozen plasma. A significant volume of plasma in the United States becomes "indated", i.e., in contact with red blood cells for 24 hours at 4 degrees, and is therefore not used to prepare factor VIII concentrates. To evaluate this possible resource, partially purified factor VIII was prepared from random samples of fresh-frozen, indated and outdated plasma. The yield of factor VIII protein and procoagulant activity from indated plasma was about the same as that from fresh-frozen plasma. The yield from outdated plasma was substantially less. After further purification, factor VIII from the three sources gave a single subunit band when reduced and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. These results indicate that the approximately 287,000 liters of indated plasma processed annually by the American National Red Cross (ANRC) could be used to prepare factor VIII concentrates of good quality. This resource alone could quadruple the supply of factor VIII available for therapy.


Failure of immunosuppression in a severe haemophilia B patient with specific antibody.

Prevention of a secondary response to factor IX by cyclophosphamide was attempted in an 11 year old patient with severe Christmas disease. An antibody to factor IX had been present for 4 years before immunosuppressive therapy was tried. Despite profound lymphopenia, synthesis of factor IX antibody was not depressed. The difficulties of modifying the anamnestic response to factor IX by chemical immunosuppression may be as real as has been reported for factor VIII in classical haemophilia.


Comparison of the actions of thrombin and the thrombin-like venom enzymes ancrod and batroxobin.

Thrombin acts on several coagulant proteins to produce products with physiologic, pharmacologic and pathologic potential. The most sensitive thrombin substrate seems to be factor VIII. Some thrombin dependent reactions studied in vitro and proposed as control reactions seem too insensitive to the action of thrombin to be of in vivo significance. The only enzymic reaction the thrombin-like venom enzymes, Ancrod and Batroxobin, have in common with thrombin is the removal of fibrinopeptide A.


Properties of human tissue thromboplastins from brain, lung, arteries, and placenta.

Properties of purified and delipidated human tissue thromboplastins (TTPs) from brain (BTTP), lung (LTTP), arteries (ATTP) and placenta (PTTP) were studied. The extinction coefficients were closely similar with a mean value of 8.3 +/- 0.01 (SD). The molecular weights were 200,000 +/- 3,000 (SD) BTTP), 90,000 +/- 2,000 (SD) (LTTP), 110,000 +/- 3,000 (SD) (ATTP) and 250,000 +/- 4,000 (SD) (PTTP). The maximum activity of each delipidated TTP after relipidation was obtained when phospholipid-delipidated TTP ratio was 2.0, and the maximum specific activity was 440 units per mg BTTP, 270 units per mg LTTP, 80 units per mg ATTP and 600 units per mg PTTP. Ouchterlony analysis with anti-delipidated PTTP antibody showed the reaction of partial identity between delipidated TTPs and the antibody. Studies of the reactivity of I-125-delipidated TTPs with the antibody gave the following average values for % bound I-125-TTPs in 2 hours: 3.6 +/- 0.2(SD) % (I-125-BTTP), 11.0 +/- 0.3 (SD) % (I-125-LTTP), 4.4 +/- 0.2 (SD) % (I-125-ATTP) and 13.7 +/- 0.3 (SD) % (I-125-PTTP). It was also found that the antibody markedly neutralized the coagulant activity of saline extracts of brain, lung and placenta. These results indicate that delipidated BTTP, LTTP, ATTP and PTTP are different while being similar in some aspects and that complete TTPs are not coated with lipids in a manner inaccessible to anti-delipidated PTTP antibody.


Some observations on the preparation of platelet-rich plasma.

In order to prepare platelet-rich plasma a constant height and volume of citrated whole blood was centrifuged at different gravity forces and times. The supernatant plasmas were examined for platelet concentrations, plasma volumes and optical densities. Results are described showing that gravity force and time have an important influence on the platelet numbers and the plasma volumes recovered. The light attenuation by different concentrations of platelets in plasma, using light path lengths of 5 mm and 10 mm, was compared. The shorter light path provides greater linearity between optical density and platelet numbers especially at higher concentrations.


Effects of matrix contact during gel filtration of human platelets in plasma.

When gel filtration is used to transfer platelets from plasma into an established environment, alterations in platelet characteristics may result from the change in environment or from the effects of platelet contact with the gel matrix. To approach the problem of evaluating the relative contributions from these sources, a Sepharose 2B matrix was employed and platelets transferred from citrate anticoagulated PRP into autologous PPP to yield plasma-GFP. Platelet recoveries averaged 93%. PRP: plasma-GFP pairs were found to be indistinguishable with respect to: morphology; ADP, thrombin or collagen-induced aggregation response; uptake of 5-hydroxytryptamine (5-HT) or adenosine; and thrombin or collagen-induced release of accumulated 5-HT or adenosine. Pairs are distinguishable by prostaglandin E2 synthesis assayed immediately after filtration.


Platelet dysfunction in migraine: effect of self-medication with aspirin.

Circulating microembolic index (CMI) was determined by drawing one blood sample into EDTA-formalin and the other into DTA alone in patients with migraine and compared with matched normal controls. Platelet aggregates, if any, are fixed in EDTA-formalin but disaggregated by EDTA. Ratios of these two counts approximate "unity" in normals and are proportionately less than unity, depending on the number of platelet aggregates. 26 untreated migraineurs and 19 migraineurs with history of self-medication with aspirin taken within 72 hours of the test, were studied in headache-free intervals. Results were compared with those from 20 healthy, age and sex matched volunteers, without migraine, who were medication-free for at least one week. Mean CMI in untreated migraineurs (0.77 +/- 0.03 SEM) was significantly lower than the mean in normal controls (0.94 +/- 0.02, p. less than 0.002). Migraineurs with self administration of aspirin had mean CMI of 0.88 +/- 0.02, differing significantly from untreated migraineurs (p less than 0.01) but not from normal controls (0.1 less than p less than 0.2). Results suggest excessive platelet aggregation in migraineurs which tends to be corrected by treatment with platelet inhibitors such as aspirin.


Effects of fasting on plasma and platelet-free fatty acids and platelet function in healthy males.

10 healthy male volunteers fasted for 72 hours. Their plasma concentration of free fatty acid increased more than two-fold, to 1.8 mmol/l. The number of reversible venous "in vivo" platelet aggregates increased significantly (p less than 0.01); this figure correlated with the concentration of long-chain saturated free fatty acid in plasma (p less than 0.02). The correlation with the amount of long-chain saturated free fatty acid plus oleic acid (18:1) was even better (p less than 0.01). Plasma PF-4 concentration increased, suggesting increased platelet release reaction. In spite of the plasma increase, total platelet FFA concentration was reduced and there was a change in the distribution of platelet free fatty acid which correlated with the degree of aggregation.


Sedimentation and adhesion of platelets onto a horizontal glass surface.

An experimental method for measuring platelet adhesion to a glass surface and platelet sedimentation rate is described. Anticoagulated platelet-rich plasma is placed on a horizontal glass slide for various contact periods. The number of platelets adhering to the slide per unit area is recorded as a function of time. The experimental results are used to verify theoretical predictions which account for the effect of the slow sedimentation rate of the platelets and for their escape over the potential barrier between them and the solid surface. By a least-squares fit of the theoretical equation to the experimental data, both the platelet adhesiveness, in terms of P the probability to overcome the potential barrier, and the platelet sedimentation rate V are evaluated. A range of values of P and V for healthy humans is presented.


Inhibition of ADP-induced platelet aggregation by adenosine tetraphosphate.

In contrast to previous reports, highly purified adenosine tetraphosphate (AP4) does not induce the aggregation of platelets but inhibits the aggregation and release reaction in platelet-rich plasma promoted by ADP. The inhibitory action of AP4 on the aggregation by ADP is compared with that of AMP and ATP. The data presented suggest a competitive manner of inhibition of the ADP-induced aggregation by AP4.


Effect of platelet age on adhesiveness to collagen and platelet surface charge.

Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (less than or equal to 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets showed a moderate but statistically significant increase in adhesivity to collagen but old platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.


Inhibition of human and animal platelet adhesiveness to glass bead columns by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid.

The differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.


Platelet aggregation following defibrination with ancrod.

In vitro platelet aggregation was studied in dogs following defibrination with Ancrod. There was marked inhibition of aggregation immediately after defibrination. A gradual return toward normal aggregation was observed over the 96 hours study period, but aggregation was still abnormal at 96 hours after defibrination. There was an inverse and highly significant correlation between aggregation and fibrin degradation product level. Fibrinogen was not measurable after defibrination for the entire study period. Aggregation was thus independent of fibrinogen concentration in this study.


Physico-chemical explanation of blood cell adhesion in thrombus formation.

A model is suggested which assumes that the rate of deposition of cells is determined both by hydrodynamic factors and by Brownian motion over the potential barrier caused by London and double-layer forces in the immediate vicinity of the deposition surface. The height of the barrier in the potential energy of interaction between blood cells and various surfaces is analyzed in relation to the physical properties of the cells, surfaces, and solutions. Based on this analysis, the adhesion of platelets to injured blood vessel walls and to non-biologic materials, the lack of adhesion of red blood cells under the same conditions, the mechanism of ADP induced aggregation and the interaction with blood flow are explained. The qualitative predictions of the model are substantiated by available experimental information. Quantitative results are presented in terms of a time constant, which typifies a period of contact with a surface, during which appreciable deposition occurs.


An immunological method for detection of the carrier of hemophilia B.

This paper presents the results of an immunological study of hemophilia B and its carriers which used two kinds of antibodies, a heterologous antibody of high specificity and a homologous antibody developed in a patient with severe hemophilia B. 1. The factor IX related antigen for hemophilia B could be determined by a neutralization test and not by a precipitation reaction. 2. The activity of factor IX in a definite carrier of hemophilia B was significantly lower than that of factor VIII in a definite carrier of hemophilia A. 3. In hemophilia B, there were no differences between the factor IX antigen determined by either the heterologous rabbit antibodies or the homologous antibodies. And there was no discrepancy between the factor IX antigen and the factor IX activity. Therefore, we cannot use this discrepancy for the detection of a carrier of hemophilia B. 4. However, there was a discrepancy between the factor IX antigen determined by the neutralization test and the factor IX procoagulant activity in the patients of both hemophilia BM and hemophilia B+. The identical results were obtained in the cases of carriers of both hemophilia BM and hemophilia B+. These facts are very useful for the detection of carriers of hemophilia BM and hemophilia B+.


Enhancement of fibrinolytic and thrombolytic potential in the rat by treatment with an anabolic steroid, furazabol.

The effect of long-term ingestion of an anabolic steroid, furazabol, was studied on coagulo-fibrinolytic systems in the rat. During the administration of furazabol at the daily dose of 0.04, 0.2 or 1 mg/rat for 3 months, the most remarkable changes were increase in the plasminogen activator activity in blood and the lung tissue and decrease in plasma fibrinogen level as well as decrease in plasma cholesterol. It was a very important finding that in most of the rats the furazabol treatment was effective in reducing susceptibility to lactic acidosis-induced pulmonary thrombosis. No meaningful changes were observed in other parameters tested including ADP-induced platelet aggregability, plasma recalcification time, plasma plasminogen, plasma antiplasmin activity, plasminogen activator content of tissues other than the lungs and the release of vascular activator induced by venous occlusion. One month after cessation of the furazabol treatment, these altered parameters tended to return to normal. Independently on the furazabol treatment, highly significant positive correlation existed between the plasma activator activity and the pulmonary tissue activator content. This indicated that the major source of plasma activator in the rat was the lung tissue and that the furazabol treatment increased the circulating activator activity through enhancing activator content in the lungs.


[The influence of straw, particularly rice straw, together with calcium-cyanamide on the microbiological activity of two Portuguese soils (author's transl)].

The influence of calcium-cyanamide upon the microbiological activity was tested in pot experiments under controlled conditions in two Portuguese soils (sandy and loamy) after the addition of rice or wheat straw (rice straw 0.275% N, wheat straw 0.307% N). The amount of straw was equalled to 100 dz/ha, the application of calcium-cyanamide to 25, 50 and 100 kg N/ha. In the containers treated with straw the total amount of microorganisms (Koch-method) was higher in sandy than in loamy soil after 30 days, but after 70 days it was higher in loamy soil. The content of active nitrogen (NH4 + NO3) increased, when calcium-cyanamide was added, but decreased after the application of straw. After 70 days sandy soil again showed an increase of active nitrogen. Straw increased the rates of CO2-production considerably, wheat straw was superior to rice straw. Calcium-cyanamide increased the CO2-production more in sandy than in loamy soil or German loess, which was also used for this experiment. Only in the case of rice straw higher doses of calcium-cyanamide had a positive effect. After 70 days the CO2-production rose only when rice straw was applied. The dehydrogenase-activity was increased in both soils, but a superiority of wheat straw occurred in sandy soil only. The microbiological activity in the pots with straw was higher in sandy than in loamy soil, the addition of calcium-cyanamide accelerated it. Doses of 25-50 kg N/ha are sufficient generally. The period of the formation of insoluble organic N-compounds, usually connected with the application of organic matter with a wide N:C-ratio, seems to be reduced by the addition of calcium-cyanamide.


[Chemotherapy of the inoperable lymphosarcoma (author's transl)].

By means of chemotherapy it is not possible to heal the lymph osarcoma but to obtain remissions lasting up to 5 years in about 20% of the cases. The mode of therapy is discussed with regard to the generalized lymphosarcomatosis.


The histological structure of dog knee menisci with comments on its possible significance.

Knee-joint menisci are poorly understood terminologically, structurally and functionally in spite of their almost universal occurrence in mammals and their considerable clinical significance in man. A study was therefore undertaken of dog knee menisci utilizing several histological techniques. Terminologically, it is proposed that the part of the meniscus extending between the anterior and posterior horns and exclusive of them be called the meniscal "body." Structurally, the horns and body differ in anumber of ways. The horns are oval in cross section, the body triangular. Hyalinized areas are much more frequent in the body than in the horns. The collagen of the horns is organized into discrete bundles that are separated from one another by loose connective tissue septa, while that of the body is arranged in a "herringbone" pattern; no septa are present in the body. Finally, the meniscal horns are richly supplied with blood vessels are nerves (including large myelinated fibers which apparently terminate in the horns) while the body is almost completely devoid of blood vessels and nerves. Functionally, it is hypothesized that knee-joint menisci may serve important sensory functions.


Anemia of azaribine in the treatment of psoriasis.

Azaribine is an effective agent in the treatment of psoriasis. In this investigation the extent of clinical dermatologic remission appeared to correlate with the degree of metabolic block induced by 6-azauridylic acid, as quantitated by the urinary excretion of orotic acid and orotidine, and the development of anemia. Following azaribine therapy there was a coordinate rise of the specific activities of erythrocyte orotate phosphoribosyltransferase and orotidine-5'-monophosphate decarboxylase. There was no correlation between the pretreatment activity of these enzymes and the clinical response to azaribine. The anemia of azaribine therapy was mile and of a megaloblastic type. Uridine effectively corrected the azaribine-induced anemia, but led to exacerbation of the patients' psoriasis. Following uridine therapy there was a reduction in the urinary excretion of orotic acid and orotidine, presumable reflecting end-product inhibition or repression of the first steps of a repeated pyrimidine biosynthesis.


Ultrastructural study of testis in testicular feminization.

Testicular tissue was investigated by electron microscopy in a case of testicular feminization. The seminiferous tubules were lined by spermatogonia and by Sertoli cells. Spermatocytic maturation was not observed. Leydig cells were numerous and contained well developed, abundant vesicular smooth-surfaced endoplasmic reticulum and large mitochondria with tubulovesicular cristae. Reinke crystalloids were absent. The ultrastructural findings were consistent with the assumption that Leydig cells were under adequate stimulation and were in a stage of active secretion. Hence, the results seem to indicate that testicular endocrine function was maintained in the studied case.


[Study of the HL-A system in Basedow's disease (author's transl)].

HL-A typing has been carried out in 100 caucasians with Graves' disease and compared with 270 healthy controls. 25 HL-A antigens were characterized using a lymphocytotoxicity microtechnique. Analysis of the results reveals an increased incidence of HL-A8 antigen (35% in patients as compared to 16,3% in controls), with a high degree of statistical significance: p=0.0002 and corrected p X 25) = 0.005. We did not observe a clearcut correlation between the presence of HL-A8 and different characteristics of the disease: sex, age of onset, familial history, exophtalmia, goiter, severity. The knowledge of the relationships between the HL-A8 gene and several auto-immune diseases is a strong argument in favor of the auto-immune nature of Graves' disease. The association between HL-A8 and Graves' disease could be explained by a close linkage between the second HL-A locus and one or several Ir-IgG loci occupied in predisposed individuals by predisposing alleles. In these subjects, an antigenic contact with an exogenous etiological agent would induce a pathological immune response, with production of thyroid stimulating IgG.


The ultrastructure of the interstitial cells in human fetal ovaries.

Steroid-active interstitial cells (stromal lutein cells) in human fetal ovaries of 12, 15 and 22 weeks of gestation were studied by means of electron microscope. The large cells, which are predominantly situated in the vicinity of capillaries, show high structural similarity to Leydig cells (type A) of the fetal testis. Both are characterized by extensively development of smooth endoplasmic reticulum, accumulation of lipids, and numerous mitochondria of the tubular type containing osmiophilic inclusions. Whether the interstitial cell system of the fetal ovary has any specific function in developmental physiology of the genital system cannot be decided on the basis of the present results. Its differentiation may only indicate adequate response of competent mesenchymal cells to gonadotropic stimulation.


[Morphological study of a prolactin-secreting pituitary adenoma after therapy with 2-bromo-alpha-erogocryptine (CB154) (author's transl)].

After treatment with CB 154 of a prolactin-secreting pituitary adenoma a morphological study reveales that many cells present a positive immunofluorescent reaction with anti-ovine prolactine antibody. At the ultra structural level, many granulations and vacuolated dense bodies can be observed.


[The ratio birth-weight, placental weight and the term of delivery. A contribution to the problem of a relative placental insufficiency in late pregnancy (author's transl)].

It is suggested, that a relative placental insufficiency in late pregnancy is one of the releasing factors of childbirth. Under this assumption 1027 deliveries in term pregnancy (266th-294th day of pregnancy) were inquired on the interrelationship between the ratio brith-weight: placental-weight and the duration of pregnancy. The average birth-weight increases slighly but significantly with the duration of pregnancy just as the average placental-weight. The average ratio birth-weight: placental-weight decreases significantly: The more unfavorable the ratio birth-weight: placental-weight is, the shorter remains the fetus in utero. This underlines the assumption of a relative placental insufficiency as one of the releasing factors of childbirth.


[Experimental candida vaginitis in the mouse (author's transl)].

Manifest Candida albicans infection of the vagina of mice was achieved only after oestrogen treatment. Histologically, different phases of vaginal candidiasis could be observed: the mycotic infection began with a massive colonization of Candida albicans in the horny layers of the vaginal epithelium and an early immigration of granulocytes. Abscess-like changes followed when high number of yeast cells were used for infection. One to two weeks after onset the inflammatory changes decreased and fungi were no longer identifiable in epithelial micro-abscesses by the methods employed. In contrast, yeast cells could be detected within the vaginal skin exhibiting weak inflammatory lesions up to the 57th day. Chemotactic studies showed that the fungi considerably stimulated the migration of mouse granulocytes in the presence of serum. Since mannan isolated from the Candida cell wall also possesses strong chemotactic activity, certain components of the fungal cell wall may play a pathogenic role in Candida colpitis.


[Histological diagnosis, DNA-content and chromatin pattern of breast cancer cases with positive and negative 17-beta-oestradiol receptor binding (author's transl)].

The DNA-concent of cell nuclei of 45 breast cancer cases of various histological structure has been determined cytophotometrically. With the exception of two gallert carcinomas no DNA-histogram of peridiploid range was found. The average DNA-content was 2--3 times higher as in the control tissue. The standard deviation of undifferentiated solid mammary tumors was the highest measured in this series. 24 of 45 cases had a negative oestrogen receptor binding. This was true in 60% of the undiffierentiated solid breast cancer cases, in 69% of the adenomatous and in 89 respectively 67% of the ones of special histological structure. The heterochromatin content of nuclei was lowest in the group of differentiated mammary cancer (50--60%). In the group of undifferentiated tumors it was 60--70%. So much for now is known about the mechanism of cellular action of 17-beta-oestradiol and the function of eu- and heterochromatin of cell nuclei it is discussed that positive or negative oestrogen hormone receptor binding in mammary tumor cells is probably a biochemical parameter of cytological desintegration. From this point of view these hormon receptors could be of the same value as the index of Barr bodies in breast cancer cells with respect of selection of cases for hormonal therapy. But this has to be analyzed in further studies extensively.


Investigations into the preservation of human ovaries by means of a cryoprotectivum.

Human ovaries in the phase of follicular ripening were treated by means of a cryoprotectivum immediately after their removal. They were kept at --18degrees C for up to 8 weeks. After having gradually been thawed the ovaries were in vitro connected to a perfusion system. When completely revitalized they were examined in the steady-state for their metabolic behaviour. It was found that in comparison with the untreated controls, depending on the period of preservation, the oxygen consumption and the estrogen secretion had decreased, while the glucose absorption and lactate production had increased. As a morphological substrate a minor oedema was established in the tissue in the histological control after a preservation period of 2 months. This was mainly localized around the arteries. The method can be regarded as suitable for the preservation of ovaries for a limited period of time. It is possible to maintained a metabolism that can still be regarded as functioning.


[Asteroid plastic surgery as optimum management of complete and partial vaginal occlusion (author's transl)].

Opinions differ about the type of surgical procedure to be applied in cases of complete or partial vaginal occlusion. The large percentage of postoperative vaginal stenoses and functional disorders necessitated a search for a new technique. The mucous membrane of the introitus vaginae is incised in the shape of a lying cross and the four flaps thus made are detached. Then an exactly lateral incision is made on each side of the crossing point described above resulting in a broad access to the vagina. Once the opening is wide enough, a second group of triangular flaps is formed vertically to this horizontal incision; the dimensions of the triangular flaps in the inner and outer group must be identical. Then the outer four flaps are turned inward and the four inner flaps are turned outward and interlinked so that a zig-zag line is formed which encircles the vagina in the area of the former stenosis. Thus far this surgical technique has been applied five times and yielded satisfactory results in every instance.


A trend in the therapy of Amanita phalloides poisoning.

Recent experimental evidences have been produced on the protection afforded by penicillin G in rats poisoned by Amanita phalloides extracts. A therapeutic trend which combines penicillin G infusions to the classical supportive measures was applied to 33 cases of severe A. phalloides poisoning, with 100% survival rates. The possible mechanism of the protective effect of penicillin G in A. phalloides poisoning is discussed.