Effects of beta2-sympathomimetic on histamine-stimulated gastric acid secretion in dogs.

The effect of a selective beta2-adrenoceptor agonist on histamine-stimulated gastric acid secretion was studied in conscious gastric-fistula dogs. A dose-dependent inhibition was found, most pronounced for the lowest doses of histamine. The inhibition was on the volume, whereas the acidity was unchanged. The pulse rate was increased by the beta2-agonist and by histamine. Propranolol prevented the inhibition of acid secretion as well as the increase in pulse rate. Practolol had no effect on the inhibition of acid secretion but reduced the increase in pulse rate. Dose-response experiments with six doses of histamine and two doses of the beta2-agonist showed unchanged calculated maximal response and an increase in D50. It is concluded that the beta2-agonist inhibits histamine-induced acid secretion in the dog, but to a lesser degree that pentagastrin-induced acid secretion, as found in earlier experiments. The inhibition follows competitive kinetics, and beta2-receptors are probably involved. The influence of beta2-sympathomimetics on the mechanism of gastric acid secretion is discussed.


Coexisting malignant lymphoma and adenocarcinoma of the stomach.

The fourth case of malignant lymphoma coexisting with an adenocarcinoma in the stomach is presented. Although an increased incidence of systemic malignant lymphoma in association with gastrointestinal tumors has recently been emphasized, primary gastric lymphoma and adenocarcinoma coexisting in the same stomach is still rare.


Acquired pulmonary stenosis.

A patient with acquired pulmonary stenosis due to lymphocytic lymphoma is presented. Three further patients with acquired pulmonary stenosis have been seen in our department in the past 15 years. A review of published cases reveals that there are more causes of this condition than have previously been enumerated.


The gastric aspirate foam test in the prediction of hyaline membrane disease.

The gastric aspirate foam test was performed on 99 infants of low birth weight. In 59 of 61 infants with no respiratory distress, the test was positive. All infants who developed hyaline membrane disease (HMD) had negative or intermediate foam test results. There was no consistent relationship between the foam test result and the development of wet lung syndrome. Infants who were small for gestational age had a significantly lower incidence of HMD, as did infants with amniotic fluid infection syndrome. These data indicate that the gastric aspirate foam test is a reliable index of neonatal lung maturity.


Reemergence of thyroidectomy as treatment for Graves' disease.

Hyperthyroidism of Graves' disease may be treated very effectively by antithyroid pills, such as PTU and Tapazole, by radioactive iodine therapy, and by subtotal thyroidectomy. Each form of therapy has advantages and disadvantages, and thus treatment should be individualized. While therapy with radioactive iodine would appear to be ideal since it does not require an operation and is less expensive than surgical management, it suffers from a high rate of progressive hypothyroidism and from the fact that the time until a euthyroid state is obtained is often prolonged. In addition, the long-term carcinogenic risk of the therapy for thyroid neoplasia has never been completely defined since the data most often quoted have a mean follow-up time of only eight years. Furthermore, new "low-dose" radioiodine regimens may be more dangerous in this regard. Subtotal thyroidectomy, while not totally without complications, remains a rapid, safe, and effective treatment for Graves' disease. The careful use of propranolol has facilitated the preparation of some patients and has lessened the risk of operation. Thyroidectomy should remain the treatment of choice for young adults with this disease.


Chemical analysis of linseed meal produced in Egypt.

Representative samples of linseed meal were collected from the productive nineteen oil mills of Egypt. The averages of nutrients in the mentioned samples were 6.55 +/- 0.22, 93.45 +/- 0.22, 11.19 +/- 0.60, 26.97 +/- 0.59, 11.18 +/- 0.43, 36.10 +/- 0.60, 8.00 +/- 0.38, 0.39 +/- 0.03 and 0.89 +/- 0.04 for moisture, dry matter, ether extract, crude protein, crude fiber, nitrogen-free extract, ash, calcium and phosphorus respectively. The average of the calculated calorific value was 435.81 +/- 3.16 kcal per 100 gram of the meal.


[Etiology of RDS in infants weighing more than 2500 g (author's transl)].

Between 1974 to 1977, 7005 infants were born live at the I. University Clinic of Obstetrics and Gynecology, Vienna. 55 of these infants weighed at birth more than 2500g and developed RDS (Respiratory Distress Syndrome) as a result of which 16 died. All infants showing either malformations, icterus gravis (malignant jaundice) or infants delivered by insulin dependent diabetic mothers were excluded. The remaining 48 infants were compared with two control groups selected at random. The mortality rate for infants with RDS weighing more than 2500g (29,1%) was identical with those weighing less than 2500g (28,7%). The significant finding in the RDS group was the high incidence of primiparae, mothers with abnormal obstetrical histories, imminent abortion, cerclage operations and EPH gestoses. On three women in this group extragenital surgery which was performed during pregnancy appeared noteworthy. Time of labor, prolonged delivery time or surgical interference at time of birth did however not seem to make any difference. The RDS group showed in the 1 minute as well as in the 5 minute Apgar-Value distinctly worse results, whereby the missing recuperation after 5 minutes is typical and prognostically unfavourable for RDS. Of decisive importance for the development of RDS in infants weighing more than 2500g was birth induction before the end of the biological term.


Infective endocarditis during the first decade of life. An autopsy review of 33 cases.

Twenty-six cases of infective endocarditis seen at autopsy during the first decade of life, between 1911 and 1944, are compared with seven fatal cases between 1944 and 1977. The incidence of infective endocarditis at autopsy in this age-group has decreased since 1944 (0.60% to 0.23%). Before 1944, Gram-positive cocci were most frequently responsible. Rheumatic heart disease (31%) more often predisposed to infective endocarditis than did congenital heart disease and left-sided valves were most frequently involved. Peripheral septic foci and penumonia were the most frequent sources of infection. The introduction of penicillin and advances in cardiology and cardiovascular surgery have had considerable impact of the spectrum and evolution of the diseases. Fungi and uncommon opportunistic bacteria are now frequently encountered. Rheumatic heart disease rarely predisposes to infective endocarditis in this age-group, congenital heart disease being the major underlying disease.


Recognition and differential diagnosis of enlarged extraocular muscles in computed tomography.

We found enlargement of the extraocular muscles in 70 patients out of 603 orbit studies, of whom 310 had exophthalmos. The majority (46 of 70) had the eye signs of Graves' disease. Arteriovenous malformations and carotid cavernous fistulas can cause enlargement of the extraocular muscles by a diffuse increase in orbital venous pressure, Acute orbital myositis can be distinguished from other forms of pseudotumor by the presence of a single enlarge extraocular muscle with associated inflammatory findings which responds to corticosteroid therapy. Neoplasms may invade extraocular muscles or compress their venous drainage causing secondary muscle enlargement. In all these patients the presence of a mass was correctly identified. The ability of the computed tomography scanner to recognize abnormalities of the extraocular muscles represents a significant advance in classification and diagnosis of the causes of exophthalmos.


Alkaline phosphatase isoenzyme patterns in hyperthyroidism.

Fifteen of 36 hyperthyroid patients had elevation in serum alkaline phosphatase activity. There was no difference in mean thyroxine (T4), triiodothyronine (T3), age, or duration of illness between the groups with high alkaline phosphatase and normal alkaline phosphatase levels. After treatment, serum alkaline phosphatase levels rose as T4 levels declined; at 3 months, the mean serum alkaline phosphatase value rose from 7.1 Bodansky units to 10.3 Bodansky units (P less than 0.005), while the mean T4 value fell from 18 microgram/dl to 7.2 microgram/dl (P less than 0.005). In some patients, serum alkaline phosphatase values have remained elevated for more than 1 year, despite continued normality in thyroid variables. Before therapy, isoenzyme patterns analyzed by polyacrylamide gel electrophoresis were qualitatively normal. As therapy was instituted, the isoenzyme patterns changed markedly, with increased amounts of bone alkaline phosphatase appearing in the serum as T4 levels were declining and total alkaline phosphatase was rising. Thyroid tissue homogenates from patients with Graves' disease were found to have very low levels of alkaline phosphatase activity and an isoenzyme pattern quite distinct from that found in the serum.


Cyclophosphamide in the management of advanced Graves' ophthalmopathy. A preliminary report.

Three patients with advanced Graves' ophthalmopathy were treated with cyclophosphamide. All had proptosis and diplopia. One patient had disabling iatrogenic Cushing's syndrome from steroid treatment of the ophthalmopathy and had undergone bilateral orbital decompression before cyclophosphamide therapy; steroids could not subsequently be withdrawn. When cyclophosphamide was administered to the cushingoid patient, withdrawal of glucocorticoid therapy was then possible. Diplopia completely resolved in two patients and improved in the third coincident with administration of cyclophosphamide. Deteriorating visual acuity resolved in one patient. Chemosis improved in the two affected patients. Proptosis was unchanged in all three patients. Cyclophosphamide deserves further study as a therapeutic agent in Graves' disease.


Effect of environmental conditions on the production of two extracellular proteolytic enzymes by Vibrio SA1.

The production of two extracellular proteases, an endopeptidase and an aminopeptidase, by the marine bacterium Vibrio SA1 was studied in batch cultures. The production of the proteases was induced during growth of the organism in peptone media and by several amino acids during growth in minimal media. It was repressed by easily metabolisable carbon compounds such as glucose, lactate and succinate during growth in peptone media. During growth in a lactate basal medium, phenylalanine was one of the best inducers and this amino acid was therefore used in further experiments. That lactate did not repress the synthesis of the proteases during growth in the lactate basal medium supplement with 2mM phenylalanine as an inducer, appeared to be a consequence of the low iron content of this medium. Growth curves of Vibrio SA1 on such media showed a period of linear growth during which protease production was observed. When the iron concentration was made sufficiently high to prevent linear growth, the synthesis of the proteases remained repressed. Apparently by imposing an iron limitation on the organism, catabolite repression by lactate was relieved. Similarly, when growth was limited by very low values of the dissolved oxygen tension in the medium, a high rate of protease synthesis was found which was immediately repressed when the oxygen limitation was released. The results indicate that the growth rate and/or a factor associated with the energy metabolism play a role in the regulation of the synthesis of the enzymes.


A continuous culture study of the regulation of extracellular protease production in Vibrio SA1.

During growth of Vibrio SA1 in a lactate-limited chemostate in the presence of 2mM phenylalanine as an inducer, the rate of production of two proteolytic enzymes, namely an endopeptidase and an aminopeptidase, was dependent upon the dilution rate. An optimum in the rate of synthesis of both proteases was observed at a dilution rate of 0.23 h-1 and enzyme production only occurred between dilution rates of 0.06 and 0.45 h-1. Without inducer a low rate of aminopeptidase production was found with an optimum at 0.19 h-1, but only trace amounts of endopeptidase were detectable in the culture. In the presence of inducer the rate of enzyme production increased with increasing dilution rates over the range 0.06 to 0.23 h-1 which was explained by an increase in saturation of inducer sites. The progressive decrease in the rate of protease production at higher dilution rates was ascribed to an increasing effect of catabolite repression by the increasing concentration of the growth substrate. It was shown that 5 mM cyclic AMP could not relieve catabolite repression caused by glucose or lactate. Repression of protease production also occurred in the presence of higher concentrations (5 mM) phenylalanine and other amino acids and by ammonium ions. It is suggested that the energy-status of the cell may play an important role in the regulation of protease synthesis in Vibrio SA1.


Conversion of p-nitrophenol to 4-nitrocatechol by a Pseudomonas sp.

A strain of Pseudomonas sp. ATCC 29354, isolated from parathionamended flooded soil, converted p-nitrophenol to 4-nitrocatechol which persisted in pure culture. In unsterilized flooded soil, not previously treated with parathion, 4-nitrocatechol was further metabolized by other microorganisms.


Translocation of an ampicillin resistance determinant within an R-factor aggregate in Salmonella panama.

The molecular properties of the plasmids of a natural isolate of Salmonella panama have been studied. This strain, Sp477, harbours 5 different plasmids: the conjugative plasmid pRI477TF (molecular weight 20 megadaltons), the two non-conjugative plasmids, pRI477A and pRI477S, coding for ampicillin and streptomycin plus sulfonamide resistance respectively (molecular weights of both 5.6 megadaltons) and two cryptic plasmids with molecular weights of 1.0 and 2.7, megadaltons respectively. After conjugal transfer to Escherichia coli the ampicillin resistance determinant was frequently found to be integrated into pRI477TF or pRI477S. The translocatable sequence on pRI477A, designated as Tn901, resembles the TnA sublcass transposon TnA(1).


Enterobacteria of emerging pathogenic significance from clinical cases in man and animals and detection of toads and wall lizards as their reservoirs.

A total of 416 samples comprising faecal samples from diarrhoeic cases of man, calves, sheep and goats, and urine samples from patients with urinary tract infections, were examined for the presence of enterobacteria of emerging pathogenic significance. Citrobacter freundii from 20, C. intermedius biotype-a from four, Serratia marcescens (serotype 05:H13, bactericin type 16) from one and Erwinia herbicola from two human stool samples were isolated. Only two urine samples yielded C. freundii. Citrobacter freundii was isolated from 10 and C. intermedius biotype-a from two calves. From sheep and goats, two isolates of C. freundii and three of C. intermedius biotype-a were obtained. None of these samples yielded Edwarsiella tarda or Yersinia enterocolitica. The examination of 99 toads and 145 wall lizards revealed that toads were reservoirs for C. freundii, C. intermedius biotype-a and Salmonella brijbhumi, whereas wall lizards were reservoirs for C. freundii, C. intermedius biotype-a, E. herbicola, Enterobacter cloacae and Salmonella spp. These bacteria were present in the range of 2.0 x 10(6) to 6.0 x 10(11) organisms per gram of intestinal contents. In addition, toads were carriers for Edwardsiella tarda (new serotypes 04167:H1 and 05159: non-motile). None of the toads and wall lizards proved positive for C. intermedius biotype-b (C. koseri), S. marcescens and Y. entercolitica. C. freundii, C. intermedius biotype-a, E. herbicola and S. marcescens were resistant to penicillin and erythromycin whereas E. tarda isolates were also resistant to gentamycin, neomycin, colistin and sulfamethaxazole.


Liquid nitrogen storage of yeast cultures. I. Survival, and literature review of the perservation of fungi at ultralow temperatures.

All 20 yeast strains of 17 species tested survived 75 days (the length of the experimental period) in liquid nitrogen at -196 C. The components of the more protective of the two freezing media used were (w/v) malt extract 2.5%, yeast extract 0.25%, peptone 0.5%, calf serum 15% (v/v) and dimethyl sulfoxide 10% (v/v). Viability of the cells in this medium after rapid uncontrolled freezing and thawing in selaed plastic ampoules ranged from 2% to 98% (average 67%) compared with the viability of the cultures before freezing. In only 4 strains was survival lower than 50%. (90 references).


Influence of sympathetic nervous system on surfactant production. An ultrastructural study.

The influence of the sympathetic nervous sytem on pulmonary surfactant was investigated in an ultrastructural study of normal and chemically sympathectomized rat lungs. Chemical sympathectomy was accomplished by administration of 6- hydroxydopamine (6-OHDA). The 6-OHDA did not have any systemic influence on the experimental animals. These animals grew normally and were killed at intervals of three, four, six, and seven weeks. The mean weight of the controls at three weeks was 41.75 +/- 3.12; at four weeks, 77.00 +/- 2.68; at six weeks, 169.25 +/- 11.29; and at seven weeks, 182.25 +/- 4.94. The mean weight of the 6-OHDA treated group at three weeks was 48.50 +/- 1.04; at four weeks, 76.25 +/- 1.93; at six weeks, 171.75 +/- 3.40; and at seven weeks, 180.25 +/- 2.36. The body/ lung weight ratio was about the same in both groups. In the control animals, the alveolar capillary membranes were intact, the alveoli were well expanded, and epithelial cells appeared normal. The cytoplasm of the granular II pneumocytes contained their characteristic osmiophilic lamellated bodies as well as multiple transition forms between the multivesicular and lamellated bodies. It is these lamellated bodies that are the suspected site of surfactant production in the lung and they appear to migrate towards the alveolar lumen. In addition to the lamellated bodies, multiple lattice-like tubular myelin figures were abundant in the alveoli of the normal rat lung. Following sympathectomy, structural alterations occurred within the cytoplasm of the granular II pneumocytes, involving mainly the lamellated bodies. There was a decrease of osmiophilic content as well as loss of organization of the bodies. This change was quantitated by scoring the degree of osmiophilia in the control and sympathectomized animals. The mean score in the control animals was 4.43 +/- 0.03 S.E., whereas in the sympathectomized group it was 3.77 +/- 0.16 S.E. It was concluded that the lamellated bodies, the site of phospholipid synthesis in the granular II pneumocyte, arise from the multivesicular bodies and are extruded into the alveolus. They then participate in the formation of the alveolar acellular lining layer. Sympathectomy alters the structure of the lamellated bodies, thereby influencing the development of the surfactant system.


Acute toxic delirium. Neurotoxicity of intrathecal administration of amphotericin B.

A patient with coccidioidal meningitis was treated with intrathecally administered amphotericin B, and an acute toxic delirium with EEG abnormalities developed. Clinical recovery followed discontinuation of therapy and paralleled EEG resolution. This complication was dose related and argues for caution when initiating intrathecal therapy with amphotericin B at doses greater than 0.025 mg.


Tuftsin and its analogues. III. Modification of basic amino acid residues in the peptide chain.

Five tuftsin analogues, containing one or two of the basic amino acid residues, respectively in position: 2, 3, 2 and 4, 2 and 3--of the peptide chain, were synthesized and tested for biologic activity by the Najjar test.


[Synthesis and physico-chemical parameters of clanobutin (author's transl)].

Synthesis and physico-chemical parameters (pKa, partition coefficient, permeability coefficient, critical micelle concentration, surface pressure, etc.) of 4-[4-chloro-N-(4-methoxy-phenyl)-benzamido]-butyric acid (clanobutin) are described.


Comparative study of oxaflozane urinary metabolism in man, the dog and the rat. Identification of the principal metabolites.

The urinary metabolites of isopropyl-4-(trifluoromethyl-3-phenyl)-2-morpholine (oxaflozane) were compared in man, the dog and the rat using thin-layer chromatography and gas chromatography. In the dog, the tritiated molecule on the morpholine ring was administered to a certain number of animals. The principal metabolites were isolated, purified and identified by IR, RMN spectrometry and mass spectrometry. The principal metabolite in man and the rat was obtained by osaflozane N-dealkylation. In the dog, 2 metabolites formed by cleavage of the morpholine ring were also observed.


Inhibition of platelet aggregation by a new synthetic compound: 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid (K 3920).

The effect of the new synthetic compound 2-[p-(1-oxo--2-isoindolinyl)phenyl] butyric acid (K 3920) on platelet aggregation was assessed in vitro on human platelets. ADP, epinephrine and collagen at different concentrations were employed as inducing agents. From the results of the present study it appears that K 3920 inhibits human platelet aggregation in vitro, probably by acting on the release reaction.


Absorption in rats, dogs, pigs, and humans of nicotinic acid after oral administration of phosphatidyl inositol pentanicotinate hydrochloride (PIN).

Bound nicotinic acid in feces after oral administration of phosphatidyl inositol pentanicotinate (PIN) was determined by chromatographical isolation from acid hydrolysate and UV absorbance of the eluted nicotinic acid. With all species tested, the absorption of nicotinic acid after administration of PIN was found to be incomplete, proportions from 5 to 25% of the amount of nicotinic acid administered with PIN being recovered from feces. Humans absorbed about 75% of the nicotinic acid administered with 700 mg PIN, i.e. 230 mg. It is concluded that the presence of bound nicotinic acid in feces is due to slow absorption of the PIN or slow hydrolysis of the nicotinic acid ester. Rabbit liver homogenate, human blood plasma, and human duodenal juice were found to liberate nicotinic acid from PIN.


[Serum concentration and kinetics after i.v.-infusion of 3 g lincomycin (author's transl)].

The pharmacokinetics of lincomycin (Albiotic) were studied in ten healthy male and female volunteers after administration of 1 X 3 g and 2 X 3 g lincomycin i.v., respectively, infused over 60 min. After discontinuing the infusion a mean serum value of lincomycin of 97.5 microgram/ml was measurable. 5 h later the mean serum values were 13.5 microgram/ml and 24 h later 1.6 microgram/ml. After 24 h 72.5% of the drug had been eliminated in the urine of 4 volunteers. The mean serum half-life was 286.3 min with the one-compartment model. The volume of distribution was 78.7 l with the one-compartment model and 25.9 l with the two-compartment model. The area under the curve has the value of 14 805.39 microgram . min . ml-1 and 44 418.9 microgram . min. ml-1 with the one- and two-compartment model, respectively. The mean values for the total renal clearance with the two models were 204.8 and 75.5 ml/min. The importance of high-dose therapy with lincomycin is discussed with respect to the tissue penetration of the substance and possible bactericidal effects, whereas lincomycin in general only acts bacteriostatic.


[Structure-activity studies on carboxyflavone derivatives with antianaphylactic activity (author's transl)].

The passive cutaneous anaphylaxis (PCA) activities of a number of new A- and B-ring carboxyflavone and carboxyflavonol derivatives with planar and without planar orientation of the B-ring--synthesized in relation to baicalein and 2-carboxyxanthone derivatives as antianaphylactic prototypes--are recorded. From the investigated compounds A-ring carboxylic acids are more active than B-ring carboxy derivatives and flavonols are less active than flavones. Problems resulting from the correlation of the PCA activity of a number of chromone derivatives with the substitution of the 3-position are discussed.


[Preliminary pharmacokinetics of metoclopramide in humans. Plasma levels following a single oral and intravenous dose (author's transl)].

A quantitative thin-layer chromatographic method is discribed for the determination of metoclopramide in human plasma for the 40--320 ng/ml range. Similar plasma levels were observed after single oral dosing with capsules (5 X 11.62 mg metoclopramide X 2 HC'L X H2O) and i.v. injection (2 X 11.62 mg metoclopramide X 2 HCl X H2O). The shape of the plasma level curve after i.v. administration indicates the presence of an open two-compartment model for metoclopramide in humans. Following a very short distributive phase an elimination phase is observed with a half-life of 3--6 h over the period studied. The present data suggest that under the conditions employed in this study metoclopramide is bioavailable by only about 50%; a "first-pass" metabolism is indicated.


[Determination and comparison of the plasma and urine concentrations in men given tranylcypromine stereoisomers].

The (+) and (-)isomers of DL-trans-2-phenylcyclopropylamine (tranylcypromine, Parnate, Jatrosom) were tested under cross-over conditions on 10 volunteers. (-)Tranylcypromine entered blood circulation more rapidly, reached significantly higher concentrations and was metabolized more slowly than (+)tranylcypromine. These results indicate a difference in the pharmacokinetics of the tranylcypromine isomers. In the urine collected over a period of 24 h the excretion of unmetabolized (4)tranylcypromine was lower probably resulting from the greater metabolization rate of this isomer. There is a conformity between the findings in plasma and urine.


Gas chromatographic determination of amitriptyline, nortriptyline and perphenazine in plasma of schizophrenic patients after administration of the combination of amitriptyline with perphenazine.

A specific and sensitive gas-chromatographic technique using a common extraction procedure for the quantitative determination of amitriptyline, endogenous nortriptyline and perphenazine in plasma of schizophrenic patients receiving therapeutic doses of a combination of amitriptyline and perphenazine (Etrafon) has been developed. The lower limits of detection are 20 ng/ml for amitriptyline, 1 ng/ml for nortriptyline and 5 ng/ml for perphenazine. Amitriptyline is estimated with a flame ionization detector. Nortriptyline is quantitated using an electron capture detector after converting it to its heptafluorobutyryl derivative by reaction with the appropriate anhydride. Perphenazine is also determined using an electron capture detector after forming its stable, trimethylsilyl derivative by reaction with N,O-bis-(trimethylsilyl)-acetamide. In individual patients, the steady-state plasma levels ranged from 44 to 215 ng/ml for amitriptyline, from 49 to 270 ng/ml for nortriptyline and from less than 5 to 20 ng/ml for perphenazine. Steady-state plasma levels data on amitriptyline, nortriptyline and perphenazine in 23 patients treated with Etrafon are presented.


[Chloroquine enantiomers. Activity against P. vinckei and binding on DNA (author's transl)].

(+)-Chloroquine is more active against P. vinckei than (-)-chloroquine. No correlation has been observed between antiplasmodial activity and DNA-binding of the chloroquine enantiomers.


[Are there pseudophototropic reactions in biology? Part 3: The pseudophototropic behaviour of the cell membrane of halobacteria (author's transl)].

The behaviour of coloured membrane portions of "halobacteria" is studied with respect to spectral response and reversibility. The results are in good correlation with colour generating effects of pseudophototropic reactions. The disclosed and dicussed systems are in the range from purely synthetic to purely biological.


Lack of hypotensive and brain catecholamine depleting effects by erythro- and threo-alpha-methyl DOPS.

An investigation was carried out to ascertain whether erythro- and threo-alpha-methyl-dihydroxy-phenyl-serine were able of depleting cerebral and peripheral norepinephrine (NE) through their metabolization to alpha-mNE. The results show that the alpha-methyl-aminoacids were decarboxylated only at the periphery and that the threo-form caused depletion in cardiac NE. In any case, both isomers were unable to cross the blood-brain barrier leaving the cerebral NE unaffected. Consequently the use of alpha-mDOPS as alternative tool to alpha-mDOPA in the therapy for hypertension seems unlikely to occur. The results also provide evidence for differences in the pharmacokinetics of the two isomers.


Amidantel, a potent anthelminthic from a new chemical class.

N-(4-[(1-(Dimethylamino)-ethylidene)-amino]-phenyl)-2 methoxyacetamide hydrochloride (amidantel, BAY d 8815) is a new aminophenylamidine with an interesting anthelminthic spectrum. In rodents the compound is active against nematodes, filariae and cestodes. Of special interest is the high efficacy in dogs against hookworms and large roundworms. Amidantel was well tolerated by all animals tested and did not show teratogenic effects.


[32P-incorporation in adenosine phosphates of the rat brain after oral application of vincamine for 2 weeks (author's transl)].

The 32P-incorporation into the adenosine phosphates AMP, ADP and ATP of the rat brain after an oral administration of a daily dose of 20 mg/kg 14,15-dihydro14 beta-hydroxy-(3 alpha,16 alpha)-eburnamenine-14-carbonic acid methylester (vincamine; Vincapront) during two weeks was determined. The concentrations of the three adenosine phosphates did not change. After the administration of vincamine the increase in the 32P-incorporation into AMP and ADP was statistically significant. The results obtained are discussed in regard to an acceleration of the pentose phosphate shunt and an activation of adenylate kinase.


[The tissue distribution of racemic S-(+)- and R-(R)-(-)-MPPB (1-methyl-5-phenyl-5-propylbarbituric acid) in the rat].

Distribution of racemic 1-methyl-5-phenyl-5-propyl-barbituric acid (= racem. MPPB), of the S-(+)- and R-(-)-enantiomer (= (+)- and (-)-MPPB) between serum and several tissues was investigated after i.v. administration of the substances to rats. Anesthesia produced by the racem. MPPB--(+)-MPPB causes convulsions whereas (-)-MPPB is anesthetically active--cannot be explained by a stereoselective difference of the MPPB-concentration measured in serum and brain when giving the enantiomers. Reversely as expected in the brain MPPB-concentration is significantly higher after administration of (+)-MPPB than after that of (-)-MPPB during the appearance of the CNS symptoms.--Significant stereoselectively different MPPB-concentrations, which are time dependent, could also be detected in liver, spleen and fatty tissue; however, in contrast to the brain in these tissues MPPB-concentration is higher after administration of (-)-MPPB than after that of (+)-MPPB. Concentration differences which are measured in liver, spleen and fatty tissue already 1--10 min after i.v. administration of the enantiomers cannot be explained by a stereoselectivity of the metabolism and/or renal elimination. However, a stereoselective metabolism and/or renal elimination of the enantiomers can be responsible for concentration differences which are observed during the late period of 60--180 min after administration: in serum, brain, liver and fatty tissue MPPB-concentration is lower if (4)-MPPB is administered. For that reason it can be supposed that (+)-MPPB is faster eliminated than (-)-MPPB.


[The influence of treatments with a quinine-lithium-salicylate combination or acetylsalicylic acid on hematopoiesis in mice (author's transl)].

The effects of an 8-week treatment with the quinine-lithium-salicylate combination Togal and sole acetylsalicylic acid (ASA) on the hemopoietic bone marrow cells of mice were studied. In general, both substances caused only minor changes. A slight leukopenia caused by higher doses as well as a transitory erythropenia observed a little bit more distinctly in ASA treated animals than in Togal treated animals need more detailed discussion, especially so because after a short two-week Togal treatment some animals showed an increase of hemopoietic cell colonies which a sole ASA dose did not cause. On the other hand, these results indicate a lower toxicity of Togal in comparison with acetylsalicylic acid as has been already shown in several other publications. It was proven that after a several weeks' treatment with therapeutic doses no pernicious influence on blood producing organs or pathological processes of the blood picture occurred. Only doses that border on the toxic region lead to insignificant bone marrow changes. As these over-doses are ten times the highest therapeutical dose the use of Togal does any damage to the blood forming tissue or pathological changes in the blood count are not likely. This has also been proved by other authors by means of long-term tests on humans.


Effect of steroids and diethylstilbestrol on cocaine toxicity, plasma concentrations and urinary excretion.

Comparative experiments were performed on female rats given pregnenolone-16 alpha-carbonitrile (PCN), spironolactone, triamcinolone, estradiol or diethylstilbestrol to study correlations between the toxic effect of cocaine, its blood clearance and its urinary excretion. PCN and estradiol significantly reduced the toxicity of the drug as well as its plasma levels and urinary excretion. Diethylstilbestrol and spironolactone, unlike triamcinolone, also diminished cocaine toxicity and plasma concentrations.


[Experimental protection with tyrothrizin against herpes simplex virus infections in mice].

Using 12-day old baby mice, strain NMRI, the LD50 of a Herpes simplex virus type 1 was calculated. Intragastric inoculation of the mice was carried out applying a stomach tube. Lethality of the mice was reduced from 67% to 23% by pre-incubation of the virus suspension for 30 min at 37 degrees C in the presence of 0.2 mg tyrothricin/ml. The effect was statistically significant and could be produced only after direct contact between tyrothricin and virus. Under the same conditions there was no effect of lysozyme against virus infectivity.


Interaction of indolmycin in the metabolism of tryptophan in rat liver.

When compared with other tryptophan analogues, indolmycin is a potent inhibitor of tryptophan pyrrolase and tryptophan decarboxylase, both enzymes involved in tryptophan catabolism. Otherwise the decarboxylation of 5-hydroxytryptophan is only slightly affected by indolmycin. The indolmycin derivative, 2-methylamino-5-(1-naphthylmethyl)-oxazolidin-4-one (YX-CX 22 XX) demonstrates only a slightly weaker inhibitory effect in the tryptophan-tRNA-ligase system in E. coli but does not show any significant action on the tryptophan metabolism in the eukaryotic system.


[Effect of the liver protecting compound ES 914 on D-galactosamine induced experimental hepatitis in the rat].

The i.p. application of 400 mg/kg D-galactosamine to rats induces liver damage which histologically resembles hepatitis. As also shown in the present investigation, the transaminases SGOT and SGPT in the serum of the damaged animals strongly increase already within 24 h. In the present investigation part of the animals (rats) was treated with 15, 30, 60, 125, 250 and 500 mg/kg of a new hepatoprotective preparation alpha,alpha-dithio-dicapronic acid (ES 914, Lipexal Berna) 2 h before and 6 h after the application of the liver damaging substance D-galactosamine (dose 400 mg/kg). ES 914 was applied p.o. whereas D-galactosamine was injected i.p. The transaminases were estimated at the beginning of the experiments as well as 24 h after the injection of D-galactosamine. The statistical evaluation of the results showed an increasing protective effect depending on the increasing dosage of the preparation ES 914. The protective effect begins at the latest with the dose of 30 mg/kg ES 914 and with 60 mg/kg it is highly significant (p less than or equal to 0.001). With a dosage of 500 mg/kg ES 914 the increase of SGOT and SGPT values is virtually abolished.


[Studies on the competition of several antibiotics for binding sites to serum protein (author's transl)].

Protein binding of benzylpenicillin, acidocillin, ampicillin, oxacillin, tetracycline and clindamycin was determined in vitro by equilibrium dialysis with and without combination. Concentrations of labelled drugs were measured by scintigraphy, of non-labelled drugs by agar diffusion technique using a test strain resistant against the second antibiotic of the combination. Percentage of protein binding of the different penicillins decreased somewhat in higher concentrations, whereas with tetracycline there was found a significant increase of protein binding in higher concentrations. There was no inhibition of protein binding when combining two penicillins or tetracycline with clindamycin at lower concentrations. If very high concentrations of oxacillin of flucloxacillin were used in combination with benzylpenicillin protein binding of benzylpenicillin was reduced by about 20%.


[Dibekacin--a novel aminoglycoside antibioticl. Antimicrobial activity  and parallel resistance in vitro].

Dibekacin (Orbicin) is a new aminoglycoside antibiotic which chemically differs from tobramycin only by lack of an OH-group. The activity of dibekacin against E. coli, Klebsiella, Enterobacter, Serratia, Proteus indol-negative and indol-positive and Pseudomonas aeruginosa was compared with that of gentamicin, sisomicin, tobramycin and amikacin by tube dilution procedure. Dibekacin showed a high activity against P. aeruginosa including gentamicin-resistant strains. The development of resistance and cross-resistance in vitro in E. coli, Klebsiella, Proteus and P. aeruginosa to the five aminoglycosides was investigated. The experimentally produced resistance under increasing aminoglycoside concentrations was developing by multiple-step mutation. The frequency of cross-resistance is of great importance for the first choice of an aminoglycoside antibiotic in the hospitals. These in vitro studies have yielded that dibekacin and gentamicin are well suited for the first choice of an aminoglycoside in P. aeruginosa infection.


[Are there pseudophototropic reactions in biology? Part 4: On the reversibility of biologic/synthetic polymere systems (author's transl)].

In further research on pseudophototropic behaviour in cellular membranes of halobacteria the reversibility of vinylmethylethermaleic anhydride-copolymeres with biological liquids is tested and the basic principles of different colour generating reactions are studied.


[On the technique of applying drugs in solid form to rats (author's transl)].

A method is described which allows the oral administration of drugs in solid form by hardgelatin mini-caps to rats with a simple device. The method is especially suitable for the administration of solid, radioactively labelled drugs.


gamma,gamma'-(4,4'-Diamino-3,3'-biphenylylenedioxy)dibutyric acid (dicarboxidine) a safer substitute for benzidine type chromogens.

gamma,gamma'-(4,4'-Diamino-3,3'-biphenylylenedioxy)dibutyric acid (dicarboxidine) is a new chromogen developed as a safe substitute for conventional benzidine type reagents. The compound is water soluble and has a low distribution ratio organic phase/aqueous phase, which makes it superior for use with automatic analytical instruments. The stability of both dicarboxidine and its coloured oxidized form are better than and their sensitivity equal to that of o-dianisidine. Dicarboxidine is not mutagenic in Ames test. Studies in mice for two years failed to reveal any carcinogenic activity, studies in rats indicated only a marginal effect.


Synthesis and pharmacological activity of befuraline (N-benzo[b]furan-2-ylcarbonyl-N'-benzylpiperazine), a new antidepressant compound.

The methods of synthesis and the pharmacological evaluation of a new non-tricyclic antidepressant drug, N-benzo[b]furan-2-ylcarbonyl-N'-benzylpiperazine (befuraline), are reported. The chemical structure of befuraline is clearly different from that of the tricyclic antidepressant drugs. While the gross behavior in animals remains unaffected, the central nervous system depressed by reserpine, tetrabenazine or perphenazine is activated by even small doses of this novel compound. Exploratory activity is prolonged, and performance in operant behavior tests and in the conditioned avoidance response is improved by befuraline, indicating increased alertness, attentiveness and the capacity to react to environmental stimuli. High doses stimulate the CNS, causing EEG desynchronization. Befuraline displays an aggression-inhibiting activity; without having a sedative effect on the animals' normal behavior, it inhibits fighting behavior. The central anticholinergic effect of befuraline is negligible. No apomorphine or tryptamine potentiation is observed and hexobarbital anesthesia is not influenced. The peripheral autonomic nervous system, with the exception of the nictitating membrane in cats, is not affected by befuraline. It has a biphasic effect on the norepinephrine induced contraction of isolated guinea pig seminal vesicle and of isolated cat spleen slices. Although the mechanism of action is as yet not clear, it is assumed that, in addition to a direct influence on the central adrenergic structures, the inhibition of norepinephrine and serotonin uptake and the inhibition of phosphodiesterase are responsible for the drug's effect. Befuraline has no undesirable effects on either the peripheral autonomic nervous system or the cardiovascular system, and it does not affect the normal gross behavior of animals. Because these favorable therapeutic aspects are coupled with low toxicity, befuraline may provide a new alternative in the treatment of depression.


Alphaxalone distribution in rat tissues.

A method for the extraction and gaschromatographic determination of 3alpha-hydroxy-5alpha-pregnane-11,20-dione (alphaxalone, main active component of Althesin) in microgram amount in plasma and tissues is described. The slow i.v. infusion of Althesin in the rat gives uniform alphaxalone distribution in tissues, slight localization in the fat and brain levels comparable to plasma concentration.


[Studies on DNA content of tissues and organs. 1st communication: changes in cell content of some mesenchymal and parenchymatous rat organs during development, maturation, and in part aging (determinations of DNA) (author's transl)].

In this study the cell content was analyzed by means of the DNA content of certain mesenchymal and parenchymal organs of the rat. The main aspects were the postnatal stages of development and maturation. Their correlation to aging was examined only on examples, so was their correlation to the prenatal development (on 2 examples: liver and skin). One important result of this research is that a gradual reduction in the exponential growth takes place with increasing maturation and development. The "growth by production" prevails over the "growth by division" (of cells). This is the explanation for the "relative" (= apparent) decrease in the cell content of the tissues and organs analyzed during the decisive postnatal development and maturation phases. In this period the complete differentiation of the cytoplasmic structures and of the differentiation products of the tissues and organs here analyzed occurs. This leads to a shift in their relative amounts to the disadvantage of the cell nuclei, which prevailed in the total weight of tissues and organs during the early phases of development. This concerns determinations of the DNA content related to wet weight even more than such of the DNA content related to dry weight. As already shown clearly, the different tissues and organs of the mammalian organism (here on the example of the rat) grow, mature and age differently. During growth different phases can be distinguished, too, by analysis of the DNA content which partly correlate with phases of growth which were differentiated morphologically. Determinations of DNA contents are necessary as parameters for determinations of the production metabolism (e.g. activities of enzymes, products of formation and differentiation) of the different tissues and organs during their development, maturation and aging.


[Studies on DNA content of tissues and organs. 2nd communication: findings on DNA content in various rat organs 1. during maturation and aging and 2. during experimental pathological models and their therapy (author's transl)].

In this paper the DNA content as a quantitative parameter of the cell content was analyzed on selected rat organs. Aging changes in parenchymatous and connective tissue (= mesenchymal) organs were examined. Further, some pilot studies on experimental animal models of human diseases (experimental shock and liver fibrosis) and their therapy were carried out. In these simulations of human diseases only some preliminary indications about changes in cell or DNA content, resp., of the various organs could be obtained. The results show that these pilot studies justify intensified continuation (in larger series).


[Inhibition of the slow-response action potential of mammalian ventricular myocardium by etafenone (author's transl)].

In isolated papillary muscles of guinea pigs the effect of etafenone on both Na-dependent action potential and slow-response action potential and on isometric contractile force was analyzed. Etafenone (3 mg/l) reduced contractile force to 46.1% of control accompanied by a loss of plateau of the Na-dependent action potential whilst its rate of rise and overshoot remained unchanged. In contrast to this, etafenone significantly diminished upstroke velocity and overshoot of the slow-response action potential and, in some cases, even induced a complete blockade. This inhibition of the slow-response action potential could be overcome by either excess Ca (4 mmol/l) or the beta-adrenergic compound isoproterenol (1 mg/l). Consequently, contractile force increased thereby attaining or even surpassing the control values obtained prior to the etafenone treatment. The results strongly suggest an inhibition of the Ca carried slow inward current that seems to be the reason for the negative inotropic action of etafenone.


[The influence of the ester function on the vasodilating activity of 1,4-dihydro-2,6-dimethyl-4-nitrophenyl-pyridine-3,5-dicarboxylates (author's transl)].

In the series of 1,4-dihydro-2,6-dimethyl-4-nitrophenyl-pyridine-3,5-dicarboxylates the vasodilating action (increase of O2-saturation in the coronary sinus of the dog) is found to be dependent on the position of the nitro function (ortho and meta superior to para) and on the nature of the ester group. One representative, niludipin (BAY a 7168, No. 17; bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate) was selected for further pharmacological studies.


[Comparative studies on the basic Ca2+ antagonistic activities of niludipine (Bay a 7168) and nifedipine (Bay a 1040) on the myocardium, myometrium and vessels of smooth muscles (author's transl)].

Niludipine (bis(2-propoxyethyl)1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate; Bay a 7168) with respect to its specific actions on mammalian myocardium, sino-auricular or atrio-ventricular pacemakers, myometrium, and vascular smooth muscle has to be considered one of the most potent representatives of the new group of calcium antagonists. The pharmacodynamic effects of niludipine strikingly resemble those of nifedipine both qualitatively and quantitatively. Interestingly enough, niludipine is also a powerful coronary vasodilator. This is made particularly evident by the present experiments on potassium- or glycoside-contractured smooth musculature originating from large extramural coronary stem arteries.


Effects of tocainide on normal and myotonic mammalian skeletal muscle.

The effects of the lidocaine derivative 2-amino-2',6'-propionoxylidide hydrochloride (tocainide, W-36095) on the contraction force and on membrane resting and action potentials of rat diaphragm were tested in vitro. In a concentration of 5 x 10(-4) mol/l, tocainide reduced the amplitude of the twitch by about 25% within 15 min. This reduction was reversible on washout of the drug. Tocainide had little effect on the membrane resting potential, but considerably affected the action potential: rate of rise, maximum amplitude and rate of fall were reduced, the duration increased. The conduction velocity of the action potential was reduced by 20%. Experimental myotonia produced in excised diaphragms or in anesthetized whole animals by anthracene-9-carboxylic acid was completely abolished by low doses of tocainide.


[The effect of thyroid hormone on the absorption of L-proline, chloramphenicol and digitoxin].

Using the method of the perfused small intestine preparation in situ, the influence of triiodothyronine on the absorption was investigated. The absorptions of L-proline and digitoxin were disturbed by the thyroid hormone in different ways, in contrast to chloramphenicol, where it is unaltered. The effects of triiodothyronine on the absorption of these substances are dose dependently different. Obviously the thyroid hormone can influence the absorption of proline and digitoxin in both ways, increase or decrease. The behaviour of digitoxin different from that of chloramphenicol points to this drug making use of active mechanisms concerned in the absorption.


The antitussive activity of a novel compound RU 20201.

A novel compound, 1,2,3,4,4a,9b-hexahydro-8,9b-dimethyl-4-[3-(4-methylpiperazin-1-yl)propionamido]dibenzofuran-3-one dihydrochloride (RU 20201), has been shown to have comparable antitussive activity to that of codeine phosphate in animal experiments after oral administration. RU 20201 was also shown to have local antitussive activity when given by aerosol. This effect took place immediately. Initial observations suggest that RU 20201 is an antitussive compound that exerts its activity in the lungs, probably by direct inhibition of superficial receptors in the respiratory tract.


Anticonvulsant properties of some new derivatives of phensuccinimide.

Anticonvulsant properties of two new derivatives, of phenylsuccinimide, N-morpholinomethyl-3-bromophenyl-succinimide(IL-7) and N-amino-3-bromophenylsuccinimide (IL-16), were studied. It was stated that both compounds have similar acute toxicity and act longer than phensuximide. They are especially active in maximal electroshock seizure (MES) test. Their effectiveness against convulsions produced by pentetrazole is less than that of phensuximide. Their effectiveness against procaine and strychnine is similar, only one of tested compounds has very high potency against strychnine. This compound, IL-16, has also a different pattern of effect-time which is probably due to its different pharmacokinetic behaviour.


[Hydroxylation of testosterone and induction of steroid hydroxylases by phenobarbital in genetically obese mice (author's transl)].

In spite of the profound alterations in lipid metabolism in the liver of genetically obese mice (strain C57 BL/6J) the activity of the hepatic hydroxylases with testosterone as substrate does not differ from that of their litter mates of normal weight. However, when the increased liver weight of the obese animals is taken into account their total capacity for steroid hydroxylation exceeds that of their litter mates by a factor of more than 2. Moreover, the inducibility of the membrane-bound enzyme system is not affected: application of phenobarbital (20 or 40 mg/kg body weight twice daily for 4 days) leads to a 2--3fold increase of the activity.


[Study on the induction of chronical trichophytosis in small experimental animals for screening antimycotic agents. 3rd communication: the effect of cyclophosphamide on experimental trichophytosis in guinea pigs (author's transl)].

Elevated doses of the cytostatic cyclophosphamide (Endoxan) given daily for 6 weeks, resulted in a prolonged course of experimental trichophytosis in guinea-pigs. From this phenomenon, it may be concluded that the short self-healing course of this disease is due to a rapid triggering of immunoreactions. The fractionated treatment with cyclophosphamide at defined intervals (50 mg/kg initially and 30 mg/kg at 4-day intervals) did not result in any effect.


Disposition rate of proscillaridin A in man after multiple oral doses.

After multiple oral doses, the disposition rate constant (beta) of proscillaridin was studied in 4 young healthy volunteers and 33 elderly patients with congestive heart failure. Glycoside activity in plasma was assayed by the 86Rb-technique. In the volunteers the beta averaged 0.0299 corresponding to a half-life (t 1/2) of 23 h. beta could be determined in 24 patients and was 0.0139 +/- 0.0077 (mean +/- SD). The SD of beta due to biological factors was estimated to be 0.0072. The total variation of beta was 10fold. The mean beta corresponded to a t 1/2 of 49 h with a range from 19 to 209 h. It is concluded that the great variation of beta means difficulty in obtaining adequate plasma levels of proscillaridin and that a rapid elimination of the glycoside cannot be presumed.


Steady-state pharmacokinetics of sulfamethoxazole and trimethorprim in man after rectal application.

The pharmacokinetics of a combination of 800 mg sulfamethoxazole (SMZ) and 160 mg trimethoprim (TMP) were studied in 5 healthy male volunteers after repetitive rectal administration at constant 8-h dosing intervals. The average serum concentrations measured in steady-state between the fourth and seventh days showed a range for total SMZ of 47.86 to 63.38 microgram/ml. Free SMZ was between 40.04 and 51.42 microgram/ml and TMP between 1.44 and 2.20 microgram/ml. The ratio of total SMZ to free SMZ did not change during the course of the investigation. The pharmacokinetic parameters were derived from a simultaneous curve fitting of the Bateman function on the basis of the multiple dose equation. The values thus found for V0 and t50% correlate essentially with those found in the literature for oral administration. In addition, the final serum minimums and maximums were calculated. Extrapolation from t leads to infinity gave a serum minimum for total SMZ of 51.7 microgram/ml and 1.8 microgram/ml for TMP. The course of the curve fitting did not show an accumulative trend so that, in fact, it can be assumed that a steady-state was present.


Comparative pharmacokinetics of paracetamol in men and women considering follicular and luteal phases.

The pharmacokinetics of paracetamol administered in a single dose were investigated and compared in young male and female subjects, considering follicular and luteal phase of the menstrual cycle. The mean AUC for paracetamol in the blood of female subjects was significantly increased by 39% and 51%, respectively, taking into account the follicular and luteal phase, in comparison with the AUCs of male volunteers. The peak plasma concentration revealed significantly higher values in women in both phases, by 48% and 66%, respectively. The time to reach the peak concentration was shorter by 8% in follicular phase than in males. The difference was statistically insignificant. Elimination constant decreased in follicular phase by 15% and in luteal phase by 21% in comparison with males (the difference--statistically insignificant). The paracetamol half-life was longer (although not significantly) in women than in men: in follicular phase by 29 min, i.e. 15%, and in luteal phase by 65 min, i.e. 33%. The apparent volume of distribution was found to be significantly lower in the female group by 35% and 40% in follicular and luteal phase, respectively. Comparing data obtained in the follicular and luteal phase, it was shown that the AUC was larger, peak plasma concentration was higher and biological half-life was longer in luteal phase. It is likely that the differences in some pharmacokinetic parameters between men and women, as well as in women considering both phases of menstrual cycle, might be of clinical significance.


An ultrasonic study of the thermotropic transition of dipalmitoyl phosphatidylcholine.

The acoustic absorption of sonicated and unsonicated suspensions of dipalmitoyl phosphatidylcholine has been studied as a function of temperature at frequencies between 0.6 and 4.0 MHz. The absorption at a fixed frequency passes through a maximum at a temperature which is dependent on the sample preparation and history and somewhat dependent on the frequency of observation, with sonicated vesicles exhibiting a temperature of maximum absorption 2--3 degrees C below that found for unsonicated dispersions. The temperature dependence of the absorption at fixed frequency suggests a cooperative process while the frequency dependence of the absorption at fixed temperature indicates that more than a single relaxation time is required to describe the acoustic absorption.


Structural studies on lamellated osmiophilic bodies isolated from pig lung. 31P NMR results and water content.

1. Lamellated osmiophilic bodies are intracellular organelles in which pulmonary surfactant is stored prior to secretion. They contain about 85% phospholipid (per dry weight) and dipalmitoyl phosphatidylcholine is a major constituent, and although their ultrastructure is uncertain it is generally supposed that they resemble liposomes. However, liposomes are stable because layers of water are interposed between the lipid bilayers whereas an essential aspect of the function of lamellated bodies is that, subsequent to their secretion, they are rapidly disrupted to form a surface-active film which covers the respiratory epithelium of the lung. 2. A new method for isolating lamellated bodies from pig lung is described which has the advantage of speed and simplicity and which results in increased yields. The homogeneity of the preparation is similar to that obtained by other methods. 3. 31P NMR spectra of lamellated bodies showed that at 40 degrees C about 95% of the phospholipid was present as extended bilayers and that about 5% was present in a phase exhibiting isotropic head group mobility (tau R less than 10(-5) s). It is suggested that this phase may be due to apolar proteins which are present both in lamellated bodies and in liposomes prepared from lipids extracted from them. 4. The internal water content of lamellated bodies has been measured gravimetrically and the hydration of the phospholipid head groups has been examined by 31P NMR. The two methods gave results in good agreement and show that there are about seven molecules of water/molecule of phospholipid. It is concluded that although the phospholipid head groups in lamellated bodies are fully hydrated, there is no zone of free water. 5. Lamellated bodies are osmotically insensitive to NaCl whereas liposomes prepared from lipids extracted from them behave like perfect osmometers. It is suggested that the osmotic insensitivity and restricted water content of lamellated bodies are important to their function and dependent upon polar proteins in the outer limiting membrane.


Follow up of patients with hepatitis B surface antigen.

One hundred and five patients attending clinics for sexually transmitted diseases were found to carry hepatitis B surface antigen (HBsAg). Of these, 87 patients had liver function tests performed of which 44 gave abnormal results. Fifteen patients underwent liver biopsy, which showed chronic hepatitis in eight cases.


Critical evaluation of the venereal disease control campaign in Poland 1970-76.

A comprehensive campaign to control venereal diseases was undertaken in Poland in 1970. During the eight-year period of the campaign a significant decrease in the morbidity rate of gonorrhoea and syphilis was achieved. The number of cases of primary and secondary syphilis decreased by 85% and the number of cases of gonorrhoea by 30%. This paper presents the main guidelines of the campaign and a critical evaluation of the various epidemiological methods applied, such as mass screening for syphilis and gonorrhoea, epidemiological treatment, contact-tracing, improvement of treatment methods, improvement of methods of health education, and training of physicians and laboratory staff in venereology.


Graves' disease, follicular thyroid carcinoma and functioning pulmonary metastases.

We present a case with the unusual association of Graves' disease and functioning pulmonary metastases of follicular thyroid carcinoma. Unlike other reports of thyroid cancer and thyrotoxicosis, this patient's hyperthyroidism was related to a hyperfunctioning primary thyroid neoplasm and not merely to large amounts of functioning metastatic tumor. Thyroidectomy cured her hyperthyroidism. A lung biopsy confirmed the impression of metastatic thyroid cancer. Following therapeutic radioactive I131 pulmonary metastases completely disappeared.


[Juvenile goitre (author's transl)].

Clinical, cytological, serological and endocrinological examinations were performed on 50 previously untreated children and adolescent with goitre. Three girls were found to have the cytological picture of Hashimoto's thyroiditis, in one instance associated with Turner's syndrome and hyperthyroidism. Two other girls presented with hyperthyroidism. In the remaining 45 patients thyroid aspirates and thyroid hormone levels were normal. The girl with Turner's syndrome, hyperthyroidism and Hashimoto's thyroiditis had thyroglobulin antibodies. It is the authors' experience that the diagnosis of Hashimoto's thyroiditis can be made only by needle biopsy of the thyroid. If iodination of cooking and table salt were to become widespread in the Federal Republic of Germany, and increased incidence of Hashimoto's thyroiditis is to be expected amount children with goitre.


A case of Turner's syndrome with hyperthyroidism.

A female patient with classical gonadal dysgenesis associated with Graves' disease is reported. The karyotype was mosaicism of 45,X/46,X,i(Xq). The relationship among Graves' disease, Hashimoto's thyroiditis and Turner's syndrome is discussed along with a review of the reported cases.


Local hormonal modulation of neural activity in Aplysia.

The abdominal ganglion of Aplysia provides a convenient experimental system for cellular studies on the roles of peptides as chemical messengers in the nervous system. There are indications that the bag cells, a group of neuroendocrine cells, synthesize and release egg laying hormone (ELH), a peptide with an apparent molecular weight of 6000. Our recent investigations indicate that a burst of impulse activity in the bag cells produces five types of long-lasting responses, some excitatory, others inhibitory, in 26 identified neurons and 2 identified cell clusters located near the bag cells in the abdominal ganglion. The responses have slow, smoothly graded onsets, and many of them result in modulation of neuronal activity for 3 hours or more. Physiological and ultrastructural data support the hypothesis that they are induced by a bag cell hormone (or hormones) that is released into vascular and interstitial spaces of the ganglion to act on the target neurons. Local application of purified ELH to one of the target neurons provides evidence that the bag cell effect is mediated by ELH. Many of the target neurons are known to be parts of neuronal circuits that control specific behavioral and homeostatic processes. Since egg laying is initiated by the bag cell discharge and is associated with a stereotyped behavior pattern lasting several hours, the actions of these peptide-secreting neurons on the central nervous system may serve to regulate certain elements of behavior and homeostasis during egg laying.


Action of cobra venom phospholipase A2 on the gel and liquid crystalline states of dimyristoyl and dipalmitoyl phosphatidylcholine vesicles.

The activity of phospholipase A2 from cobra venom toward phospholipid in single-walled, sonicated vesicles was analyzed, particularly with respect to its activity toward the saturated phosphatidylcholines in the gel and liquid crystalline states. When egg phosphatidylcholine vesicles are used as substrate, the phospholipase has an apparent Km of 4.4 mM, an apparent Vmax of 100 mumol min-1 mg-1 of protein, and a pH optimum of 5.0 at 40 degrees C. The phospholipase hydrolyzed the gel state of dimyristoyl phosphatidylcholine vesicles and dipalmitoyl phosphatidylcholine vesicles at a rate 2 to 3 times greater than the liquid crystalline state, taking into account temperature effects on the enzymatic reaction itself. The results suggest that, toward sonicated vesicles, there is no specific enhancement of the rate when the both liquid crystalline and gel states are present together, as has been suggested to occur for multibilayers studied with other phospholipases. An apparent stimulation of activity as the reaction proceeded was observed above the phase transition temperature. This might be attributed to an increase in the phase transition temperature caused by free fatty acids so that, in the presence of reaction products, the enzyme is actually hydrolyzing gel state phospholipid which was found to be the preferred lipid state for phospholipase activity.


Deamination of glumatic and aspartic acids by Geotrichum candidum.

Strains of Geotrichum candidum were isolated from the surface of a commercial sample of Limburger cheese and from raw milk. Growth of the isolates in an acidified tryptone-yeast extract medium was accompanied by a rise in the pH of the medium from 3.5 to above 7.0 Ammonia production, as indicated by Nesslerization, was associated with the deamination of glutamic and aspartic acids. The first reaction in the production of ammonia from glutamic acid, isomerization to beta-methylaspartic acid, required vitamin B12 and the second reaction, the deamination of beta-methylaspartic acid to mesaconic acid and ammonia, was dependent on magnesium and potassium. The conversion of aspartic acid to fumaric acid and ammonia required magnesium. These minerals were in sufficient amounts in the Limburger cheese for optimum deaminase activity.


Organotypic cultures of diploid type II alveolar pneumonocytes: surfactant associated esterase activity.

Organotypic cultures, established from enzymatically dispersed day 19 fetal rat lung, are comprised primarily of cells which are morphologically similar to type II alveolar pneumonocytes, the cells involved in surfactant synthesis. To further characterize these cultures, the nonspecific esterase pool was examined to determine if these cultures contained certain nonspecific esterases previously shown to be enzyme markers for the surfactant system. The results of biochemical, electrophoretic and cytochemical studies indicate that these organotypic cultures contain the same nonspecific esterases already demonstrated in surface active fractions derived from rat and mouse lung homogenates and pulmonary lavage fluid. As in whole lung, the major site of esterase activity in the organotypic cultures is the type II cell lamellar body, the putative site of surfactant synthesis and storage. These findings support the concept that the organotypic cultures derived from fetal rat lung are comprised predominantly of type II cells which retain surfactant associated functions in vitro.


Naturally occurring antibodies to liposomes. I. Rabbit antibodies to sphingomyelin-containing liposomes before and after immunization with unrelated antigens.

Liposomes were prepared from a mixture of sphingomyelin, cholesterol, and dicetylphosphate or L-alpha-dimyristoyl phosphatidylcholine, cholesterol, and dicetylphosphate, in the presence of glucose. The amount of trapped glucose released from these liposomes was monitored after incubation with a variety of normal and immune sera in the presence of guinea pig complement. All normal rabbit sera tested were found to release, in the presence of complement, detectable amounts of trapped glucose from sphingomyelin-containing liposomes. After immunization with a variety of unrelated antigens, the anti-sphingomyelin liposome activity increased signficantly and in direct proportion to the number of injections, despite the fact that the liposomes used in the assay did not contain the relevant antigen used for immunization. Liposomes prepared from dimyristoyl phosphatidylcholine showed only marginal release of their trapped marker when assayed with the same rabbit sera and complement. These liposomes, however, were fully reactive when the appropriate antigen was inserted in their bilayer structure. The antiliposome activity was associated mainly with the IgM antibody class. These results raise the interesting possibility that antigenic stimulation may trigger the activation of lymphocyte clones directed against autologous cell-membrane components that cross-react with artificial model membranes containing sphingomyelin.


Effect of nonsteroid anti-inflammatory drugs on subarachnoid hemorrhage in dogs.

The effects of two long-acting anti-inflammatory agents on behavioral changes and cerebral vasospasm were evaluated in a canine model of chronic subarachnoid hemorrhage (SAH). The agent with the longest half-life, sudoxicam, clearly reduced both the incidence and the magnitude of the vasopasm, and prevented the usual behavior changes caused by the stimulated SAH. The results obtained with the other agent, naproxen, suggested that it was better than the administration of saline. These agents were studied because of reports indicating that prostaglandins and thromboxane may play a role in the pathogenesis of the effects of SAH and because of nonsteroid anti-inflammatory agents exert pharmacological effects by reducing an excessive synthesis of these lipids. The findings suggest that some of these agents may afford an alternative treatment for the deterious consequences of SAH.


[Transverse symptomatics in lymphosarcoma patients (author's transl)].

We report about two patients with compression of the spinal cord caused by lymphosarcomas. In the first patient the tumour was localized in the lumbal region and destroyed two vertebrae. In the second patient the lymphosarcoma also infiltrated the meninx, the cord, and some internal organs. Both children died.


Early tissue distribution of therapeutic 131I in a patient with thyrotoxicosis.

A therapeutic dose of 131I was given to a 53-year-old man with thyrotoxicosis three and one-half hours prior to death. The distribution of 131I in the thyroid gland was studied by autoradiography, and the radioactivity in various fresh tissues was measured. Radioactivity was distributed evenly throughout the colloid; small amounts were present in follicular cells. Radioactivity was not localized to the periphery of colloid follicles as observed in an earlier report. Papillary projections were associated with increased radioactivity. Decreased radioactivity was associated with oxyphilic cells. Measurement of 131I in individual tissues showed that per gram of tissue the thyroid gland contained approximately 50 times that of intestine and spleen and approximately 100 times that of liver and bone.


Thyroid peroxidase activity in euthyroid and mild hypothyroid patients with Hashimoto's thyroiditis.

Thyroid peroxidase (TPO) activity was measured spectrophotometrically according to Hosoya's guaiacol method. The mean TPO activity in ten patients with Hashimoto's thyroiditis was 19.8 +/- 7.6 (mean +/- SE) in an arbitrary unit, which was not significantly different from the normal value in seven normal thyroid tissues (33.7 +/- 5.4). The ten patients were divided into two groups, euthyroid and mild hypothyroid, on the basis of their basal serum TSH. In the euthyroid group, TPO activity (8.17 +/- 1.3) was significantly less than the normal tissue (p less than 0.01). In the hypothyroid group, TPO activity (27.64 +/- 13.8) was almost similar to the normal tissue. A positive correlation was obtained between TPO activity and serum TSH in ten patients with Hashimoto's thyroiditis (r = 0.85, p less than 0.01). It was concluded that TPO activity is significantly decreased in Hashimoto's thyroiditis even when the thyroid function was still within normal range, but the activity might be restored to normal in hypothyroid patients by the stimulation of elevated TSH.


Production of anti-rubratoxin antibody and its use in a radioimmunoassay for rubratoxin B.

Rubratoxin B was coupled to ovalbumin using 1-ethyl-3-(3-dimethyaminopropyl) carbodiimide HCl (ECDI) in high concentration at pH 8.0. Under these conditions it was possible to couple 13 moles of rubratoxin B per mole of ovalbumin. The conjugate was used for immunization of rabbits, and anti-rubratoxin antibody was produced. A radioimmunoassay for rubratoxin B was developed which could detect 0.1 microgram to 10 microgram of toxin using 0.21 microgram of [14C] rubratoxin (0.47 Ci/mole, 2.0 x 10(9) dpm/microgram) and 0.125 ml of anti-rubratoxin antibody.


Production of [14C]rubratoxin B.

[14C]rubratoxin B was produced by culturing Penicillium rubrum Stoll for 13 days at 22 degrees C in medium containing [14C]glucose. The most efficient incorporation of glucose into rubratoxin occurred when Raulin-Thom medium enriched with 2.5% malt extract was supplemented with 2.5% added glucose. The presence of 1.0 mCi of radioactivity in 50 ml of medium with 2.5% added glucose resulted in the production of 38 mg of labeled, chromatographically pure rubratoxin with a specific activity of 0.47 Ci/mole.


[Immunological reactivity of rats exposed on the Kosmos-605 and 690 biosatellites].

Immunological reactivity of rats flown aboard the biosatellites Cosmos-605 and Cosmos-690 was compared with respect to the complementary activity of serum and frequency antibodies to sheep red blood cells. Cosmos-605 rats showed changes that rapidly returned to the normal whereas Cosmos-690 rats irradiated inflight with a dose of 800 rad exhibited significant and stable changes in immunological reactivity. Those latter seemed to be associated with the combined effect of ionizing radiation and other space flight factors.


Retraction of the lower eyelid.

Retraction of the lower eyelid is a useful sign of disease. It is an early manifestation of weakness of the facial muscles, occurring with myopathies, myasthenia, and upper and lower motor neuron facial paresis. Rarely, lower and upper lid retraction occur without proptosis in patients with Graves disease. Lower lid retraction occurs in proptosis and varies directly with the degree of proptosis. It is also seen with senile entropion or ectropion, after eye muscle or orbital surgery, and with contraction of lid tissues. Apparent retraction results when the contralateral lower lid is pathologically elevated, as in Horner syndrome, in enophthalmos, or with vertical deviations of the eye.


Knee arthrography.

Knee arthrography done with the double contrast and spot film technique is a highly accurate method of evaluating the knee of a patient suspected of having an internal derangement. Its greatest value is in the evaluation of the menisci. The modern radiologist is frequently capable and interested in performing the examination. The modern radiologist is frequently capable and interested in performing the examination. The technique is safe and has a high degree of reliability. It should prove useful to the referring surgeon.


Abnormal lung surfactant related to essential fatty acid deficiency in a neonate.

A low-birth-weight infant, suffering from chronic bronchopulmonary dysplasia following hyaline membrane disease and recurrent episodes of necrotizing enterocolitis, developed biochemical evidence of essential fatty acid (EFA) deficiency in the plasma. Fatty acid composition of phosphatidylcholine and phosphatidylglycerol in the lung lavage fluid was abnormal. Plasma changes included a decrease in the level of linoleic acid and an increased level of palmitic, palmitoleic, oleic, and 5,8,11-eicosatrienoic acid to arachidonic acid being greater than 0.4:1. A lower than normal level of palmitic acid and an increased level of palmitoleic and oleic acids were seen in pulmonary sufactant phospholipid components. Upon treatment and recovery from EFA deficiency, the fatty acid pattern both in plasma and surfactant phospholipids returned to normal along with clinical improvement. An association between EFA deficiency and altered fatty acid composition of pulmonary surfactant phospholipids is suggested.


Arthrography of the knee: a comparative study of the accuracy of single and double contrast techniques.

Single and double contrast arthrographic techniques were compared in 951 patinets with suspected meniscal injuries. Exploratory surgery of the knee was performed in 384 of these patients and good clinical follow-up was obtained in 135 patients. In the latter two groups of patients, the single contrast technique was 97% accurate in assessing the medial meniscus and 96% accurate in assessing the lateral meniscus. Double contrast arthrography was 97% accurate in assessing the medial meniscus and 93% accurate in assessing the lateral meniscus. Numerical differences in the results from the two techniques were not statistically significant. Therefore both techniques can be considered equally effective diagnostically.


Plasma levels of apomorphine following intravenous, intraperitoneal and oral administration to mice and rats.

Clinical use of the potent dopaminergic partial-agonist apomorphine (APO) in a wide variety of neuropsychiatric disorders is hampered by a lack of data concerning tissue/plasma levels following various routes of administration. In the present experiments, plasma levels were assessed at various times up to 4 hours after APO administration IV, IP, and PO to mice and rats. Plasma levels of total radioactivity after PO administration of [3H]-APO were 50 to 65% of those seen after IV administration, but brain levels were almost undetectable after PO administration. Organic solvent-extractable concentrations of tritium-labelled material after IV and IP administration of [3H]-APO to mice were significantly lower than the levels of total radioactivity, while after PO administration, these concentrations were minimal. Similar results were observed in rats following IV and PO administration of [3H]-APO.


Lung maturation in the fetal rat: acceleration by injection of fibroblast-pneumonocyte factor.

Fibroblast-pneumonocyte factor, produced by the fetal lung fibroblast in response to glucocorticoids, was partially purified by column chromatography on Sephadex G-75. The resulting preparation showed two major and two minor bands on sodium dodecylsulfate-polyacrylamide gel electrophoresis. When fetal rats were injected on day 17 of gestation with 1 microgram of this material, they showed on day 20 biochemical evidence of accelerated lung maturation as compared to littermate controls. There were no differences between the two groups in body weights, organ weights, or circulating corticosteroid levels.


[Use of hypothermia after operations on the knee joint].

The author applied a continuous cooling (for 72 hours) in 40 patients after operations on the knee joint. A favourable effect has been noted. The author concludes that the local hypothermia lessens the inflammatory process activity in the joint.


[Effect of preoperative preparation on the state of the surfactant in chronic pneumonia].

A complex of physico-chemical, biochemical and morphologic methods was used to study the surfactant state in resected lungs of 44 patients with chronic suppurative processes. A possibility of correction of some surface--active properties of the surfactant through the effect of the preoperative management with the use of intrapulmonary electrophoresis of antibiotics, hydrocortisone and heparin was established.


[Atrophy of the hippocampus of vascular origin. Clinico-pneumoencephalographic study].

Among 20 patients with symptoms of cerebrovascular insufficiency, dissociation between memory disturbances and cognitive functions, and PEG studies, there were 13 cases showing atrophy of the hippocampus. The neurological and psychological studies included memory functions tests, IQ, and the analysis of language and praxia. Complementary tests included standard EEG records, EEGs obtained with nasopharingeal electrodes and PEG tomography with selective filling of both temporal horns, in order to demonstrate the inner and lower surface of the temporal lobes. The volume of the Ammon horn was reduced in 13 cases. Hippocampal atrophy was unilateral in 11 patients and bilateral in 2. The fact that hippocampal atrophy was demonstrated by PEG studies in 13 out of 20 cases, appears to be highly significant. This clinico-neuroradiological correlation seems to indicate that hippocampal atrophy, following ischemia in the deep distal vertebro-basilar-posterior cerebral territory, disturbs the function of axial structures (Papez circuit or limbic system) apparently leading to the disturbances of memory functions observed in this group of patients.


[Epilepsy and neural science. Critical review].

The nature of, and the knowledge about epilepsy, still under discussion is based upon clinical and experimental data, gathered from the last century until the present date and accepted now as scientific knowledge. The epileptic phenomenon interpreted as the outcome of a disturbance of the central regulation, of neuronal excitation and of the cerebral electric and biochemical equilibrium, is still subject of permanent study and review. From a cybernetic point of view, the epileptic fit can appear as the first expression of an abnormal organization process, or as the outcome of an electrical disturbance within a neuronal regulation circuit. This article is an attempt to review such concepts and to analyze their clinical implications.


[Cerebral potentials related to visual stimulation. Pattern inversion and flash].

Distinguishing between electroencephalogram (EEG) and event-related potentials (ERP) as indicators of brain electrical activity, methodological considerations pertaining to the recording of ERP to visual stimulation (evoked potentials, EP) are presented. Visual EP may be either steady-state or transient, depending upon stimulation used (repetitive versus transient) and method of analysis (frequency domain versus time domain). While both have diagnostic applications, this paper concentrates on transient visual EP. Based on the contention that intra and interindividual EP variability is the single most important issue in clinical practice, it presents data comparing two widely employed techniques (checkerboard reversal and flash stimulation) with respect to their stability in normal populations and their diagnostic sensitivity in demyelinating disease.


Brainstem auditory evoked response (BAER): Clinical perspectives and normative data.

Research pertaining to the physiological mechanisms involved in the generation of brainstem auditory evoked responses is reviewed emphasizing the current status of its clinical applications, pointing out present gaps in knowledge and delineating avenues for further inquiry. Some work conducted in our laboratory aimed at statistical description of BAER parameters relevant to clinical practice is presented, along with assessment procedures that are deemed promising for routine work. Relevant implementation procedures are described.


Human cortical pO2.

A human cortical pO2 rhythm similar to that described in cats was demonstrated. It bears close correlation to behavioral states such as weaking and slow wave sleep. Induced changes in cerebral blood flow, through carotid compression, has been detected as qualitative variations in local oxygen availability, at the oxygen cathode tip.


[Ocular diskinesia].

The clinical findings and the electro-oculogram were correlated in four cases (3 postinfectious, 1 vascular) with ocular dyskinesias, of a mixed type in two of them. This correlation led to a more precise recognition of the pattern of opsoclonus, flutter and ocular dysmetria. Ocular dyskinesias have certain resemblances with voluntary saccadic movements; the effects of ocular following and optokinetic stimulation are described. The role of brainstem and cerebellar structures in relation with the physiopathology of these dyskinetic ocular movements is discussed.


[Campimetric changes in optic radiation lesions].

Visual field defects may be congruous or not in lesions affecting the optic radiation. This fact, and the macular sparing found in some cases, can be explained if the optic radiation is envisaged as formed by three layers, the superficial corresponding to homolateral peripheral vision, the intermediate to contralateral peripheral vision, and the deepest to central vision from both hemimaculae. The fibers of all these layers fan out sequentially, first the more superficial, then the deeper, around the posterior part of the lateral ventricles, following a longitudinal plane of divergence in their way to area 17. The progressive displacement, upwards and downwards, of the thick fibers transmitting peripheral vision, leave out finally the thin fibers for central vision as the sole constituents of the central and terminal part of the optic radiation. As supporting evidence of this conception we have the fact that if the optic radiation is encroached on from its outer side (as it generally happens for reasons stated in the full text) visual field defects tend to be larger in the homolateral field. This holds true for temporal and parietal lesions, and to a lesser degree for occipital lesions. Deep lesions (for instance intraventricular tumours) tend to affect first the deeper strata of the optic radiation (macular vision and/or contralateral quadrants of peripheral vision). The schematic drawings presented allow us to understand how a temporal lesion may produce: a) no visual field defect, b) an upper homonimous quadrantopsia, c) a lower homonimous quandrantopsia, d) a homonimous hemianopsia; and that these field defects can be either congruent or uncongruous. Deep parietal lesions will produce visual field defects in the lower quadrants, which may be congrous or not. As the visual fibers for macular vision are deeply located in the optic radiation, forming a thin but wide layer in the vertical plane, they cannot be affected to a significative extent without the more superficial fibers for peripheral vision being also affected to an even greater extent. Due to the width and depth of this macular layer even in extensive lesions of the optic radiation some of its fibers can escape injury. This can explain macular sparing in some cases without resorting to hypothetical bilateral macular representation which is deemed unacceptable. Anatomical data and clinical examples are given which lend support to all these contentions.


[Ischemic cerebral vascular pathology. History and updating].

This is a contribution to the memory of Professor Román Arana Iñíguez. He, with Professor Néstor Azambuja made possible our participation, in the Joint Study of Extracranial Arterial Occlusion from the National Institutes of Health, with 23 U.S. Universities. This research was started on March 1963 and ended on June 1971. It was directed by Dr. Arana, who gave impetus to our work and to our active participation on the subject at meetings held in Uruguay and abroad. A brief historiography of the subject is made, with emphasis in the chronology of our advances as compared to those of other leading countries.


[In the boundaries of aphasia].

The anatomical boundaries of those structures whose lesion leads to the disturbances of language are indistintic and largely exceed the classical "areas of language", including subcortical structures as the thalamus and the non-dominant hemisphere. It is equally indistinct the possibility of definition of aphasic disturbances. On one hand aphasia can be seen within the realm of decodification, as a failure of a mental rather than of a verbal process, close to dementia, while among the codification mechanisms motor aphasia can appear a syndrome of phonetic desintegration with component of apraxic, dystonic and paretic nature. Esquizophasia and agrammatism are two examples of those peculiar disturbances of language. The correlation between disturbances of language and of intelligence is another frontier of aphasies where a causal relationship appears to be well established. Aphasias, interpreted in the beginnings as anatomically localized well defined disturbances of function, are now seen both anatomically and functionally, as a process with indistinct and mixed boundarie related to other equally illimited and indistinct functions.


[Alexia without agraphia (clinicotomographic correlation)].

Two cases of alexia without agraphia, one due to a cerebrovascular accident which improved spontaneously and the other in a cerebral abscess partially recovered after surgical treatment are presented. Both were anatomically verified by computed tomography. The second was also verified at surgery. A small well localized lesion of the fusiform and lingual gyri in the dominant hemisphere can lead to alexia without agraphia. The lack of involvement of the optic radiation and calcarine fissure explain the abscence of visual field defects and hence the purest type of this syndrome as shown in our first case. The involvement of the splenium of the corpus calosus and related forceps majors seems essential for a long lasting reading defect. The integrity of the dorsal or superior splenium is responsible for the abscence of the color warning defect found on about 30% of the cases of pure word blindness. The severity and ultimate progression of the alexia will depend not only upon the extension of the dominant occipital lesion but of its association with the damage of other possible pathways. A slowly growing and potentially treatable expanding lesion, as in our second case, can also produce an almost pure form of the syndrome. It appears to us that the wider use of CT will allow on the near future will lead to a better knowledge of the anatomical lesions and a better understanding of this fascinating syndrome.


Pregnancy following treatment with human gonadotropins in primary unexplained infertility.

Six patients with primary unexplained infertility of 2 to 9 years duration, and who failed to conceive after repeated trials of clomiphene treatment, were treated with human gonadotropins; 3 of them became pregnant following one or two courses of treatment. Three patients failed to conceive in spite of 3 courses of human gonadotropins, 2 of them had high titers of sperm-agglutinating antibodies found in their sera, which may explain their infertility. None of the 13 treatments resulted in hyperstimulation syndrome or multiple births. This preliminary result seems encouraging but awaits further study.


Peliosis hepatis. Report of nine cases.

Nine cases of peliosis hepatis are reported: five of these were associated with the administration of androgen or anabolic androgenic steroids and a sixth with large doses of medroxy-progesterone acetate. In five instances, neoplasm was present as an underlying disease. Antemortem evidence of liver disease was detected in six of seven cases but was not severe and had not contributed to death. The pathogenesis of blood-filled cystic cavities is discussed and the literature reviewed. Angiopathy of hepatic sinusoids in patients with wasting diseases or in those receiving androgens in coexistence with passive congestion of the liver appear to be factors in the pathogenesis of pleiosis hepatis.


A socio-epidemiologic survey of veneral diseases among national servicemen attending a VD hospital in Singapore.

Between September 22 and October 29, 1976, a socio-epidemiologic survey of venereal diseases (VD) was carried out at a hospital for VD and skin diseases in Singapore. The study subjects comprised 401 national servicemen from the Singapore Armed Forces who were selected by periodic stratified random sampling from among army patients at the hospital. These subjects were divided into two groups, one consisting of those suffering solely from venereal diseases and the other from non-venereal skin diseases only. Studies were made to compare the personal characteristics, educational and social backgrounds and sexual behavior between these two groups. On the basis of the results, a profile of a soldier likely to contract venereal diseases was made. The study showed that soldiers have inadequate knowledge of venereal diseases. Suggestions are made to improve education as to venereal diseases and to reduce risk of infection in the armed forces.


Opposition to "coercive continuing medical education and mandatory recertification".

A district branch survey on attitudes toward obligatory continuing medical education (CME) and mandatory recertification indicated that most respondents approved the concept of lifelong learning. However, proposed methods of implementation of CME were criticized on grounds of commercialization, bureaucratization, poor quality, wasting time and money, excessive external control over learning, and flawed requirements. Objections to mandatory recertification centered mainly on an abhorrence of Board-type examinations. The author offers suggestions to program directors and sponsors, educational researchers, and CME administrators as to ways to answer these criticisms of CME and recertification.


Surgical management of diseases of the adolescent female breast: a clinicopathologic study.

Sixty-three patients, ages 10 to 20 years with diseases of the breast were operated on during a 10 year period. A variety of pathologic entities were found. The most common were diagnoses fibroadenoma, cystic disease, and cellulitis with abscess formation. Malignancy was found in three patients: lobular carcinoma in situ in one, angiosarcoma in the second, and lymphosarcoma in the third.


Pulmonary sporotrichosis in Oklahoma in susceptibilities in vitro.

Six cases of pulmonary sporotichosis were observed in 2 institutions in Oklahoma City, Okla. Three of the patients were treated with iodides with or without surgery. Although one patient required a second course of iodides, the patients have remained well after at least 34 months of follow-up. Three patients treated with amphotericin B, single course as well as multiple courses, and other antifungal agents (hydroxystilbamidine and miconazole) have all relapsed. These cases and a reviewed of more than 40 cases of pulmonary sporotrichosis susceptibilities of Sporothrix schenckii that we observed in vitro suggest that amphotericin B is not an effective agent for the treatment of pulmonary sporotrichosis. It is our opinion that the treatment of choice for pulmonary sporotrichosis is a supersaturated solution of potassium iodide. If the patient is allergic to the medication or fails to respond, then a combination of amphotericin B plus flucytosine may be tried.


Bacterial breakdown of benomyl. I. Pure cultures.

With different soil and water samples as inoculum and the benzimidazole fungicides benomyl (either as Benlate or as the pure compound) and thiabendazole as selective agents, a large number of, mainly fluorescent, Pseudomonas strains were isolated which nearly all were able to grow in a mineral medium with benomyl as the sole source of carbon. However, no growth occurred with any of a series of other benzimidazole compounds, viz. benzimidazole, 2-aminobenzimidazole (2-AB), thiabendazole and fuberidazole. Although benomyl--or rather its non-enzymatic breakdown product methyl benzimidazol-2-yl carbamate (MBC)--was partially degraded to 2-AB, most probably n-butylamine, which arises after splitting off of the butylcarbamoyl side chain, was the actual carbon source for the Pseudomonas isolates. When incorporated in a lactate medium, 2-AB markedly inhibited the growth of Pseudomonas spp. at a concentration of 250 microgram/ml, with complete inhibition being attained at 500 microgram/ml. For Bacillus spp. grown in liquid peptone media benzimidazole compounds were inhibitory at concentrations of 500-1000 microgram/ml, with a toxicity increasing in the order: benzimidazole less than thiabendazole less than MBC less than 2-AB.


Cardiovascular effects of benzquinamide.

The cardiovascular effects of benzquinamide were evaluated in anesthetized dogs. Intravenous benzquinamide, 0.5 to 5 mg/kg, caused tachycardia, elevated blood norepinephrine levels, frequent ventricular arrhythmias, and brief hypotension. Ganglionic blockade by hexamethonium prior to administration of benzquinamide prevented the tachycardia and alterations in norepinephrine levels but prolonged the period of hypotension. In isolated mesenteric arterial preparations benzquinamide interfered with contractile force generated by potassium chloride, norepinephrine, and prostaglandin F2 alpha. It is concluded that benzquinamide directly relaxes vascular smooth muscle thereby producing in vivo reduced peripheral vascular resistance and hypotension, which are compensated for by reflex sympathetic activation.


Does cough increase the spread of subarachnoid anesthesia?

Two matched groups of eight patients were given hyperbaric tetracaine (12 mg) intrathecally. One group was instructed to cough vigorously three times after injection. The mean upper level of analgesia by pinscratch technique was the sixth thoracic dermatome in both groups. We conclude that three vigorous coughs do not influence the spread of spinal anesthesia.