[Presence of endogenous inhibitors of the respiratory chain in organs and tissues of rat]. 14 organs and tissues of the rat were tested for inhibitors of the respiratory chain. Electron transfer particles (ETP) from beef heart mitochondria served as test object. The respiratory measurements were carried out in the presence of serum albumin to avoid the reversible inhibition by fatty acids. Inhibition of the NADH oxidase system was observed with testicle, ovary, placenta, amnion, mammary gland, sceletal muscle, skin, liver, kidney, spleen, lungs and brain; the succinate oxidase system was inhibited by preparations from testicle, placenta, amnion, mammary gland, sceletal muscle and skin. Moreover, a self-inhibition of the succinate oxidase activity of the homogenates was observed with brain, liver and placenta. The respiration of the homogenates was inhibited by the respiratory inhibitor RF from rabbit reticulocytes in any case tested. With some objects besides inhibitions also stimulatory effects on the respiration of ETP appeared (vesicular gland, sceletal muscle, spleen, lungs). The inhibitory activities of the rat organs and tissues disappeared in most cases by heat treatment (10 min, 60 degrees C). A part of the inhibitors was sensitive against storage as well as freezing and thawing. They might be lipids (e.g. slow irreversible inhibition by fatty acids not relieved by serum albumin) or inhibitory proteins like RF and enzymes (proteinases and phospholipases). A protein nature is likely for the NADH oxidase inhibitors from liver, kidney, lungs, brain, sceletal muscle and placenta as well as for the succinate oxidase inhibitor from testicle. The results presented suggest the universal distribution and action of endogenous respiratory inhibitors. Presumably they occur in all mitochondria-containing cells. Their primary biological importance may be the triggering of the degradation of mitochondria. High inhibitory activities are present in cells with a high rate of renewal of the mitochondria and furthermore in maturation, differentiation and involution processes which are accompanied by a decline of the number of mitochondria.


Reversible changes in the testes and epididymides of dog treated with alpha-chlorohydrin. 1. Chronic administration of alpha-chlorohydrin (8 mg/kg body wt for 30 days) caused lesions in the testis of dog. The changes in the germ cells were degenerative. The seminiferous tubule and Leydig cell nuclear diameter were reduced. 2. Epididymal cell height was greatly reduced and the stereocilia had disappeared completely. The lumen was devoid of spermatozoa. 3. Alpha-chlorohydrin administration inhibited the RNA and sialic acid contents in the testes and epididymides of dog. Total cholesterol and lipids/g of testes were increased significantly after alpha-chlorohydrin administration. 4. These effects were reversible. Repopulation of testis tubules occurred following a period of 100 days recovery in dog. Numerous spermatogonia and sperm develop and traverse the epididymides. The RNA, sialic acid, cholesterol and total lipids of testes and epididymides returned to subnormal levels. 5. The possibility of using alpha-chlorohydrin as male contraception is indicated.


[Significance of different social factors active in the course of ontogenesis, for the effectiveness of chronic stress influences upon cerebro-visceral regulation processes of albino rats]. Fifty male albino rats were used to study how social factors (animals kept in large groups with playing-cage character, or in social isolation by solitary maintenance) are reflected in the responsiveness of cerebro-visceral regulation processes to chronic stress exposure. The following results were obtained: Animals kept from the 12.-30. week of life in social companionship and, additionally, exposed to chronic stress influences, proved to be greatly resistant to permanent load. This effect is referred to the rich supply of social afferentations and to the pronounced stimulation of proprioreceptive reafference as a result of social communication and motor activity. Animals kept, after preceding large-group maintenance, in social isolation from the 17.-30. week and simultaneously being exposed to the same stress influence as the animals in the playing cage, showed symptoms of an early stage of neurotically induced, arterial hypertension. Here, the chronic lack of socially determined, adequate environmental afferentation and of proprioreceptive reafference, as was typical of solitary maintenance, proved to be a factor enhancing the pathological predisposition of the organism under extreme environmental conditions.


[Influence of feed mixtures supplemented with animal fat on milk yield and milk composition]. Animal fat was administered in fat-supplemented mixtures of concentrates in amounts varying from 0%, 5%, to 10%. The trials were carried out on 12 dairy cows. The best results were obtained with mixed concentrates containing 5% of animal fat. Animals on these food rations produced 6.75% more milk (expressed in units of fat-corrected milk (FCM) and 9.87% more milk fat. Additions of animal fat affected the composition of milk fat in such a way that the milk contained smaller portions of short-chain fatty acids and higher proportions of stearic and oleic acid.


[Influence of thermal and mechanical treatment of animal feed on the true digestibility of amino acids. 1. True digestibility of amino acids in soy bean meals treated by varying heat]. Thermal treatment inactivates harmful components in some feedingstuffs such as extracted soy bean meal. The true digestibility of amino acids from untreated and heat-treated extracted soya bean meal had been determined in order to investigate the great variety of ways in which thermal treatment might affect food proteins, e.g. in producing a decomposition of inhibitors or damaging the amino acids. The trials were carried out with young pigs.


[Studies on the various sugar-urea and sugar-starch-urea relationships with reference to the fermentation in the rumen and the digestibility of nutrients in fattening cattle]. Recommendations are given saying that sugar-to-crude fibre rations of not more than 1.7:1 and sugar-to-urea ratios of 12:1 should be used in the fattening of cattle fed urea-supplemented rations of roughages in which 40% to 50% of the crude protein content of the ration had been replaced by urea. The amount of sugar per kg live-weight should not exceed 4 g. Higher quantities reduce the digestibility of crude fibre and, additionally, decrease the NH3 level and the pH in the rumen. At the same time the amount of volatile fatty acids is increased while the content of ruminal acetic acid decreases. Variations in the sugar-to-starch ratio had no statistically significant influence on the nitrogen balance whereas it was found that increasing quantities of sugar significantly decreased the digestibility of crude fibre. The proportional content of sugar in the readily metabolisable carbohydrates contained in the ration should not exceed 20% to 50%.


[Studies with ammonized straw pellets used as a sole basal diet in the feeding of ruminants. 1. Feeding trials with dairy cows fed ammonized straw pellets as a sole basal diet]. Feeding trials were performed with two groups of dairy cows receiving ammonized straw pellets supplemented with varying levels of concentrates as sole basal diet. The trials were carried out over periods of 546 days and 120 days. An annual milk production of 4217.9 kgs (calculated on the basis of 3.5% of milk fat) per cow was achieved in group I by feeding 3060.6 kgs of straw pellets and 2014.7 kgs of concentrates per animal. After subtracting all additives an amount of 2641.1 kgs of pure straw (= 52%) and of 2434.2 kgs of concentrated food (= 48%) remained so that the resulting amount of dry feed consumed per 100 kg of milk was 120.3 kg. A total of 6309.6 kgs of milk was produced per cow over a period of 546 days of trial. During this period the average weight gain per cow was 98.4 kgs. 1517.3 kgs of milk (calculated on the basis of 3.5% milk fat) per cow were produced in group II (56 cows) over a period of 105 days by feeding 892.5 kgs of straw pellets and 682.5 kgs of concentrate pellets. The concentrate pellets contained 50% of ammonized dried sugar beet chips but not extracted meals.


[Excretion of zinc in lactating cows receiving various supply of zinc]. Studies were carried out with 5 lactating cows receiving a semisynthetic diet to trace the pattern of zinc excretion in the faeces, urine and milk under conditions of Zn depletion and repletion. Faecal Zn concentrations were found to be drastically reduced during a 6-week period of Zn depletion. The Zn supply to the animals at different levels of Zn repletion (varying between 22 mg and 436 mg Zn per kg) was well reflected in the corresponding faecal Zn concentrations. Similarly, faecal Zn excretion expressed as the percentage of Zn supplied with the diet was shown to change with the level of Zn supply. In the range between 6 mg and 54 m Zn per kg of dietary dry matter the level of relative faecal Zn excretion increased from 42% to 56% whereas with higher Zn supplements (up to 436 mg/kg) only slight increases (up to 60%) were observed. This indicates that the organism exhibits a strong tendency to maintain a physiological balance; this tendency is all the more pronounced with increasing Zn depletion; thus after 19 weeks of Zn depletion as little as 25% of the administered amount of Zn was excreted in the faeces. The average minimum of urinary Zn concentrations was 0.25 mg Zn per litre. The Zn concentrations in urine were not found to be dependent on the Zn supply. The level of relative Zn excretion in the milk was markedly increased despite the reduced concentrations of milk Zn during the periods of Zn deficiency. At the beginning of Zn depletion rather more zinc was released with the milk than was taken up with the Zn deficient diet. The mean proportion of milk Zn in the total amount of dietary Zn over the 6-week depletion period was 91%. With Zn amounts of 22 mg, 54 mg, 87 mg, 108 mg, 130 mg and 436 mg per kg of diet 23.7%, 13.1%, 12.9%, 5.7%, 4.3%, and 1.7% of the dietary Zn were excreted with the milk. Thus, a relative decrease of Zn excretion in the milk was observed, i.e. relative to the level of Zn supplementation.


[Studies using labeled urea on lactating ruminants. 4. Incorporation of 15N-urea into the basic amino acids of goat milk]. Goats were used in a trial to investigate the rate of 15N incorporation from labelled urea into the basic amino acids of the milk (excess of 15N = 24.9 atom%). As early as 20 minutes after administration of the first dose of 15N urea nitrogen labelling in arginine and lysine was observed. The highest level of 15N labelling was noticed for lysine and arginine 24 hrs after start of the trial. The peak values of labelling for histidine were essentially lower. Reference is made to peculiarities of the ruminal metabolism of histidine.


Radioactive antigen suicide of an anti-DNP (2,4-dinitrophenyl) clone. I. Recovery and escape from clonal dominance by suicide resistant precursors. An anti-2,4-dinitrophenyl (DNP) clone line, maintained in vivo by serial passage through irradiated syngeneic recipients, was exposed to 125I-labeled dinitrophenylated L-Tyr-L-Glu-L-Lys copolymer antigen of high specific activity. Hapten-specific suicide was obtained, though with more difficulty than for a heterogeneous secondary response. The recovery was followed and was shown to occur either with the same clones or with new clones, depending on conditions. After suicide at a late passage of the clone, recovery by new clones occured very rapidly. This indicated that there was a background heterogeneity in the clone system, normally suppressed by clonal dominance and that some of these new clones were suicide resistant.


Characteristics of immunological memory in mice. II. Resistance of nonrecirculating memory cells to antigen-mediated suppression of the secondary antibody response. Mice were primed and subsequently challenged at various times with subcutaneous injections of sheep erythrocytes, and some characteristics of the secondary responses in the draining brachial and axillary lymph nodes were investigated. It was found that the secondary response within primed nodes was resistant to immunological preemption, a competition-like phenomenon which severely depresses primary responses. Since it was also shown that circulating memory cells could be inhibited by preempting injections of antigen, it was concluded that the resistance of primed nodes to preemption was due to the presence within them of a nonrecirculating subpopulation of memory cells. The size of this population was dependent both on the amount of priming antigen and the time after priming. The observation that the response given by these cells remained unaffected by doses of antigen which could depress a primary response does not favor the view that suppression of immune responses by preemption or antigenic competition is due to a factor which acts directly and indiscriminately on all immunologically competent cells.


Radioactive antigen suicide of an anti-DNP (2,4-dinitrophenyl) clone. II. Follow-up of clones relatively resistant to radioactive antigen suicide when initially selected. After suicide of the anti-dinitrophenyl (DNP) clone E21 in a previous experiment (Eur. J. Immunol. 1975. 5:58) several new clones (S clones) appeared promptly in the recipients. There was compelling evidence that they were then resistant to suicide, relative to E21. We now report further studies on these S clones and their antibodies. The antibodies of half of the S clones had affinities ten to one hundred times higher than E21 (3 x 10(-7) M); none was lower. The four tested were also able to bind DNP on the particular conjugate used for the suicide procedure. Three of the S clones were serially propagated, they showed a very great capacity for proliferation, transferring into 510, 85 and 110 recipients each. When their cells were tested at subsequent passages, they recovered early after inhibition by radioactive antigen. Two S clones may still have been somewhat refractory to suicide but, probably in all three, rapid proliferation was largely responsible for the recovery of the few cells escaping suicide, and helped them to appear suicide resistant.


Bispecific cells among IgM and IgG producers during the early phase of primary and secondary responses. Simultaneous immunization of mice with sheep (SRBC) and horse (HRBC) erythrocytes regularly resulted in the appearance of hemolytic plaque-forming cells (PFC) specific for each type of erythrocyte and also of PFC lysing both types of erythrocytes. After primary stimulation the highest number of bispecific cells (42/10(6) cells) was found among PFC as revealed by the direct procedure (IgM producers). Among PFC enhanced with anti-mouse Fab serum (IgG producers), bispecific cells were less numerous (8/10(6) cells). In preparations enhanced by anti-mouse-gammaFc serum which reveals IgG producers without inhibiting IgM antibody, the number of bispecific PFC equalled the sum of bispecific cells revealed by direct and anti-Fab enhanced procedures. The number of direct bispecific PFC during primary and secondary response was approximately the same, whereas the number of IgG-producing, bispecific PFC increased considerably during the secondary response. Another difference was the time limitation of the appearance of bispecific cells: after primary immunization direct bispecific PFC were detected only on days 3, 4 and 5, but enhanced bispecific PFC were present from day 4 up to day 12. However, during the secondary reaction, bispecific PFC were detected by all three procedures only between days 3 and 6. Studies on the cross-reactivity between SRC and HRBC gave negative results at the humoral level, even when the mice were primed with a minimal amount of both erythrocytes and then two months later, boosted with one of them. Studies at the cellular level showed that after immunization with one antigen, only 0.4 to 0.7 direct or enhanced PFC/10(6) cells could simultaneously lyse both erythrocyte types. Thus, a hundred times more bispecific PFC were constantly found after double immunization of the animals. Moreover, sudden disappearance of all bispecific PFC on the 7th day after secondary stimulation makes it unlikely that all bispecific PFC are simply cross-reacting cells.


Angiogenic tumor in the small intestine. A case report and review of the literature published in Japan. 1) A rare case of such angiogenic tumor in the duodenum as presumed to be hemangioblastoma was reported in detail. 2) Cases of angiogenic tumor in the small intestine reported in Japan were reviewed and summarized.


Lithium and amphetamine hyperactivity in rats. Differential effect on d and l isomers? The author contended opposite pharmacological effects resulting from lithium and amphetamine. Three groups, each one consisting of four rats, were put on chronic lithium condition to measure its effects on amphetamine hyperactivity. This condition was effected after appropriate handling and saline control periods and the baselines for drug activity were measured. In young rats (150-200g), lithium significantly decreased d-amphetamine hyperactivity (and probably other effects, like anorexia) while producing little effect on amphetamine stereotyped behavior (ASB). If confirmed, this fact may prove of marked importance in further localizing and studying the pharmacology of lithium. However, this observation was true in only three rats of the first group. All other rats, of the older group or of the other strain, showed only ASB,  a fact that also deserves further study because it seems to contradict previous important reports.


Studies on cartilage formation. XVIII. Changes of the composition of glycosaminoglycans in the regenerating articular surface. The cartilaginous articular surface of the distal part of the femur of adult dogs was removed and the composition of GAGs was determined in the granulation tissue adhering to the bone wound and in that adhering to the articular capsule 7, 33, and 70 days after operation. The articular cartilage and the synovial layer of the articular capsule of intact adult dogs were also studies. The materials were digested with papain and the released GAGs were fractionated according to Svejcar and Robertson's method. The articular cartilage of non-operated dogs contained, on the average, 65.3% ChS, 13% KS, 5.8% HA and 15.8% GAG of lower molecular weight. The synovial layer of the capsule contained 41.1% HA, 15.3% Ch4-S and Ch6-S, 13.7% DS, 21.7% KS, 2% H and 6% GAG of lower molecular weight. The granulation tissue of the articular surface and that adhering to the capsule show a different developmental course. The former differentiates into cartilage, whereas the latter is simply added to the tissue of the capsule. The two tissues are different in GAG composition as early as on the 7th postoperative day. With time an increase of Ch4-S, Ch6-S and KS can be observed in the tissue of the articular surface. The tissue adhering to the capsule is characterized by a high HA and an increasing DS content. From the study of the composition of GAG's (proportion of GAG building stones) a deeper insight can be obtained into the details of GAG biosynthesis characteristic of cartilage than from the analysis of quantitative data of ChS. In the development of GAG composition characteristic of the tissue, the epimerase reactions participating in GAG biosynthesis, and the mechanisms regulating their activities seem to play a primary role.


Effects of various denervation techniques on the ATP of the rat vas deferens. Postganglionic denervation of the vas deferens of the rat by surgical means or pretreatment with 6-hydroxy-dopamine results in a substantial decrease in the concentration of ATP in the tissue. The loss of ATP cannot entirely be accounted for by the loss of neuronal ATP nor by a compromised blood supply. The results suggest that the postganglionic nerve plays an important role in the regulation of the ATP of the effector cells.


An investigation of helminth parasites in well-cared for dogs in Accra. A survey of a relative prevalence of helminth parasites in pet dogs has been conducted in the Accra metropolitan area. Carcass examination revealed a high incidence of Ancylostoma caninum (58%), Toxocara canis (40%), Dipylidium caninum (24%), Spirocerca lupi (18%) and a low 2% of Taenia pisiformis. Stool examination revealed hookworm ova in approximately 39% stools, ascarid ova in 4%, tapeworm in 1.3% and Spirocerca in 0.24; a low incidence of Strongloides (0.03) and trichurid ova (0.1%) were also encountered. It appears that anthelmintic treatment of dogs is relatively ineffective and indirect transmission of hook-worm and ascarids in children may occur in Accra.


Potentiating effect of lithium chloride on aggressive behavior induced in mice by nialamide plus L-DOPA and by clonidine. Effects of acute administration of LiCl on aggressive behavior and alterations in brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents induced by nialamide plus L-DOPA and by clonidine were examined in mice. Effects of LiCl on turnover and metabolism of brain NE were also investigated. LiCl potentiated the aggressiveness induced by both nialamide plus L-DOPA and by clonidine. Increase in levels of brain NE, DA and 5-HT by nialamide plus L-DOPA was not affected by LiCl. The potentiating effect of LiCl on clonidine aggression was not observed in mice pretreated with disulfiram. Although LiCl did not alter the steady state levels of brain NE, DA and 5-HT, it increased the turnover of NE and decreased the content of endogenous normetanephrine. These results favour the assumption that lithium reduces the ability of nerve terminal vesicles to store NE leading to an increased turnover and decreased concentration of NE at receptor sites.


The monoamine oxidase B inhibitor deprenyl potentiates phenylethylamine behaviour in rats without inhibition of catecholamine metabolite formation. The drug l-deprenyl has been reported to have antidepressant properties, and in the present study three possible mechanisms of action were investigated in animal experiments. l-Deprenyl, which is a type B monoamine oxidase (MAO) inhibitor, was compared to clorgyline, an MAO A inhibitor with regard to its inhibitory effect on the formation of three major catecholamine metabolites, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MOPEG) in the rat brain in vivo. Apart from a difference in dose levels the two drugs showed no difference in the dose--response pattern of all three metabolites. Clorgyline inhibited the formation of HVA, DOPAC and MOPEG with an ED50 of about 0.2 mg/kg s.c. and l-deprenyldopamine and noradrenaline are formed by the same type of monoamine oxidase(s), probably type A, in the rat brain in vivo. Antidepressant properties of l-deprenyl therefore seem to be independent of catecholamine deamination. l-Deprenyl but not clorgyline (2 or 8 mg/kg s.c.) potentiated the stereotyped sniffing behaviour induced by beta-phenylethylamine, a specific substrate for type B monoamine oxidase. This result is discussed in relation to a new hypothesis of phenylethylamine and dopamine involvement in depression. l-Deprenyl was 10,000 times less potent than DMI as inhibitor of noradrenaline uptake in crude synaptosomes from the occipital cortex of rat brain. Inhibition of noradrenaline uptake was therefore excluded as a possible mechanism for the antidepressant action of l-deprenyl.


[A new diphasic serotype of S. egusi:=41:d: [1,5]-sub genus I]. Description of a new serotype of Salmonella: S.egusi, var. diphasic=41:d:[1,5], belonging to Subgenus I, from the lizard Lacerta sicula sicula, Raf., captured in Messina, Sicily, Italy.


[The immune response to cryotherapy of prostatic carcinoma]. The Authors look for the theoric process by which an immunological response can occur after cryosurgery of prostate carcinoma. The theories about the development of this hypothetic response are explained and thoroughly considered also in the light of personal results.


Effect of triiodothyronine (T3) thyroparathyroidectomy and mercaptoimidazole treatment on enchondral bone growth. II. Growth dynamics in the proximal growth organ of the tibia in young rats. The 24 hour growth rate of the tibial proximal growth organ was investigated in triiodothyronine or mercaptoimidazole-treated, and in thyroidectomized male rats. Longitudinal growth of the tibia of the same period was also studied. After one week treatment, the 24 hour rate of growth in the triiodothyronine-treated rats was retarded as compared with the controls, whereas at the end of the 3rd and 5th weeks the growth rate of the treated animals exceeded that of the controls. The tibia was somewhat longer in the treated rats than in the untreated controls, though the difference was not significant. The growth rate in the growth organ of mercaptoimidazole-treated and thyroidectomized animals was generally higher than that measured in the controls. The length of the tibia was less than in the controls, but the difference was not significant. The phenomenon is attributed to the altered hormonal conditions.


Individual tuna trolling strategies and transmission of fishing skills in a local community of Shimokita Peninsula. Trolling techniques and strategies of fishermen of Oma in northern Japan to catch blue-fin tunas Thunnus thynnus are described. Usage patterns of fishing devices revealed to have ecological, psychological, and social implications. Choice of fish baits depended not only on the environmental factors relevant to the ecology of fish, but also on fishermen's skills which were different among different age groups and individuals. Younger fishermen preferred live baits to dead baits or lures whereas middle-aged or older ones chose them significantly less frequently. Moreover, the combination of a bait and a line by the latter denoted particular differences and specializations in terms of fishing strategies. Large differences in tuna landings indicating individual variations of skills were apparently related to techniques of trolling gear operation. In spite of an individual-based work. alternating work exchanging baits, and gifting were important in compensating physiological and technical handicaps through fishermen's interpersonal relationships based on genealogical, generational, and neighboring bondages. The exploitative difference between the coastal and the off-shore fishing grounds, use of baits being more varied in the latter, which were lately developed area, was also referred to as a problem of transmission in a local community of technical and mental skills.


Soybean virus Z: its characteristics and taxonomy. Soybean virus Z is a hitherto undescribed virus of soybeans found in Australia. It has a limited host range, attains a low concentration in plants and has a thermal inactivation point of 65 degrees. It has flexuous filamentous particles with a modal length of 610 nm and forms amorphous inclusions, but no pinwheels, in infected cells. It has not been transmitted by aphids or by seed. Its genome is RNA with the composition G23, A26, C25, U26, and its coat protein weights about 2.7 X 104. This virus seems to be unrelated to previously described viruses of soybeans, and does not fall into any of the described virus groups with similar particles.


[Functional state and reactivity of the adrenal cortex in rats with hereditarily conditioned hypertension]. Investigations conducted by the authors have made it certain that biosynthesis of cortico steroids from progesterone-C14 in rats of Ocamoto (SHR) line with hereditary-conditioned hypertension at chronic stage of the disease does not experience any substantial changes. At the same time, an acute emotional (immobilization) stress results in greater changes in the biosynthesis of corticosteroids, metabolism of aldosterone and its blood content in the SHR rats as compared to control, normotensive ones of the Wistar line. Hyperaldosteronism revealed in the SHR rats becomes particularly intensive in response to an additional neurogenic stimulation. An important role in the mechanism of its development plays reduced metabolism of aldosterone in the liver of the SHR rats, especially in response to a stress.


Development of polylactic/glycolic acid delivery systems for use in treatment of narcotic addiction. Implantable polylactic/glycolic acid matrix systems have successfully provided the sustained release of naltrexone to mice for periods of up to 200 days. In vitro and in vivo release rates have been determined by measuring chemical concentrations in pH 7 buffer solution and urine, respectively, and in vivo efficacy has been measured by direct challenge with morphine (Dewey-Harris mouse tail-flick test). Dosage forms of small inplantable cylinders, 1/16 inch diameter, (25 mg/rod, one rod/mouse) containing 33 per cent by weight naltrexone pamoate in 90 L(+)/10 polylactic/glycolic acid have sustained the delivery of chemical for 200 days. Delivery of chemical from dosage forms of 1/16 inch diameter spherical beads (3 mg/bead, 3 beads/mouse) containing 33 per cent by weight naltrexone base in 90 L(+)/10 polylactic/glycolic acid was sustained for 60 days. Earlier a similar bead type dosage form of 75 L(+)/25 polylactic/glycolic acid containing 50 per cent by weight naltrexone base and coated with the pure polymer provided controlled release for 25 days. Polymerization conditions which incorporate the use of pharmacologically suitable catalysts and yield products reproducibly have beendelineated. Techniques for sterilization of the final implant have been screened.


Development of injectable microcapsules for use in the treatment of narcotic addiction. Injectible microcapsules containing narcotic antagonists have been prepared with dl-poly (lactic acid) as the coating material. The encapsulation technology has been developed to the point that high yields of less than 180 mu capsules can be prepared routinely. Such capsules with an initial payload of 50 wt. per cent naltrexone pamoate provide 60-90 per cent antagonism to the action of morphine 28 days after injection into mice as a peanut oil/aluminum monostearate suspension at a dose level of 40 miligrams naltrexone pamoate/kg. mouse.


Notes on prediction of behavioural change in evaluation of drug education. Much drug education has, rightly or wrongly, been concerned, implicitly or explicitly, with affecting the probability of drug use. This note is concerned with the assumption, often underlying both the application of educational methods and their evaluation, that behaviour change is somehow caused by changes in attitude and can be predicted on the basis of changes in response to attitude scales. Evaluation results are discussed to demonstrate that attitude and behaviour do not necessarily co-vary as one might expect. A model of choice is outlined as a step towards a more adequate formulation that recognises the situational context of verbal and non-verbal behaviours.


The influence of early lead exposure on morphine reinforcement in the rat. The effect of early lead burdens on morphine-seeking behavior was investigated in the albino rat. Several concentrations of lead acetate were administered to nursing mother starting at 0,7 or 14 days after birth, or provided directly to the pups in the drinking water after weaning, so that lead exposure was continous for 3 successive weeks in each group. The offspring were later tested for acquisition and maintenance of a goal-box preference based on morphine reinforcement. High lead burdens imposed before the second week of age resulted in a mild but significantly greater incidence of morphine-seeking responses, as well as retarded growth, compared with placebo-treated controls or animals treated at a later age. The data support the proposition that lead, introduced at a critical stage of development via the lactating mother, increases the potency of morphine reinforcement as a result of changes in cerebral dopaminergic activity. This effect may be mediated directly by the high lead burdens in the offspring, or indirectly by interfering with the mother's nursing capacity.


[Cortisol metabolism in paroxysmol disorders of cardiac rhythm]. In 37 patients with paroxysmal disorders of the cardiac rhythm cortisol metabolism was studied. Investigations showed an increased excretion of 17-OCS at the time of paroxysmal arrhythmia. It was found to be the highest in patients without any organic lesions of the myocardium and also in cases of microfocal infarctions. The cortisol excretion proved greatest in the hours of vasovagal attacks. The latter were attended by the most pronounced disorders of the cortisol metabolism, particularly significant in patients with ischemic heart disease accompanied by congestive failure of circulation.


[Use of tritium oxide for the study of metabolism during development of experimental arteriosclerosis]. Theoretical grounds are presented for some methods (administration of isotope and time of sacrifying the animal, estimation of radioactivity in ther material examined, and mathematical processing of the data obtained) with which radioactive water is used as a universal precursor for the study of the integral rates of metabolism in various organs and biochemical components of the body. An analysis of the dynamics of tritium inclusion into the water of the blood and urine of the control animals and of those with experimentally induced atherosclerosis permitted to establish that the development of hypercholesterinemia is accompanied by a decrase (by 26%) of the rate of autorenuewal of the water phase of the macroorganism, one of its causes consisting in an enhanced hydrophility of the tissues in cases of this pathology. A monthly periodicity was noted in the changes of the tritium concentration in the body waters of rabbits, as well as its correlation with the periodical changes in the concentration of serum cholesterol during the development of experimental atherosclerosis. It is suggested that the water and cholesterol metabolism have a joint centralized regulation in the body which essence consists in maintaining the rhythm of each separate kind of metabolism for its synchronization with the other kinds of metabolism in unfavourable outer and inner situations for the macroorganism.


The properties of bird feathers as converse piezoelectric transducers and as receptors of microwave radiation. II. Bird feathers as dielectric receptors of microwave radiation. The characteristics of bird feathers as receptors of microwave fields were investigated in the 10- to 16-GHz region. Experiments were conducted coupling the specimen (feather) to a length of waveguide which served, together with other microwave components, as a primary detector. Microwave power radiation patterns were measured both in the presence and in the absence of the specimen. Results indicated a substantial increase in the microwave power collected in the forward direction and a decrease of the radiation pattern beam width when the feather was present. Fruthermore, some experiemental evidence indicated the possibility of inducing piezoelectric effects in the specimen by audiofrequency pulse-modulated microwave fields. These results are important in view of (i) the fundamental role that feathers play in the life of birds and (ii) the influence of environmental factors on bird behaviour.


Contact hypersensitivity to some perfume materials. Some recent publications concerning perfume contact sensitivity are briefly reviewed. Japanese workers have identified some perfume sensitizers and have devised an allergen replacement system. Costus absolute of perfumery has been found to sensitize guinea-pig and man; sesquiterpene lactones are responsible for cross-sensitivity with some other plant products. Balsam of Peru is a useful screen for perfume sensitivity; terpenoids of balsams require study.


Merthiolate testing in twins.

Merthiolate testing in twins. Positive and negative patch tests to merthiolate occur with the same frequency in monozygotic and dizygotic twin pairs. There is no correlation to strong or weak reactions to primary irritants. Consequently, the positive merthiolate reactions should be considered allergic rather than irritant.


Situs inversus totalis associated with subaortic and subpulmonic stenosis. The unusual occurrence of total situs inversus and idiopathic hypertrophic subaortic stenosis with the demonstration of right and  left heart dynamic obstruction in one patient is presented. The fact that the patient was known to have a rare abnormality (total situs inversus) and the presenting symptom being angina pectoris, may have obscured the diagnosis of IHSS and emphasized the value of comprehensive evaluation of patients. The documentation of right ventricular dynamic obstruction, in addition to obstruction of the left side of the heart, was facilitated by the use of simultaneous pressure recordings in the pulmonary artery and in the body of the right ventricle. The angina-like pain was secondary to left ventricular outflow obstruction, rather than to coronary disease.


Idiopathic hypertrophic subaortic stenosis in a patient with mirror-image dextrocardia. A 42-year-old man with mirror-image dextrocardia was found to have idiopathic hypertrophic subaortic stenosis. The coexistence of these uncommon congenital cardiovascular anomalies was previously reported in only one patient.


Impairment of active avoidance in rats with unilateral hypothalamic lesion. Male albino rats with unilateral hypothalamic (ULH) lesion on either the right or left side were trained to acquire active shock avoidance in a two-way shuttle box. With 20 trials in a session per day, either group scored responses below 50% by the 8th day, while intact rats attained the criterion of 80% correct responses by the 5th day. It is concluded that intact lateral hypothalamic areas are essential for successful learning of active shock avoidance.


Bladder explosions during transurethral surgery. Gases liberated during transurethral electrosurgery are common to all tissues with hydrogen produced in high concentration. We postulate that the majority of hydrogen is derived from electrolysis of intracellular water. Only with the addition of outside oxygen does the gaseous mixture become potentially explosive.


The endocrinology of human chorionic gonadotropin-secreting testicular tumors: new methods in diagnosis. Serum from 59 men with testicular masses was examined for the presence of human chorionic gonadotropin-beta. Results indicate: 1) In patients with testicular tumor human chorionic gonadotropin-beta serves as a sensitive and specific marker of tumor activity with an incidence of 28%. 2) Because human chorionic gonadotropin-beta levels correlate with response to therapy this test will be useful in selecting men for adjunctive irradiation or chemotherapy. 3) Radioimmunoassay for human chorionic gonadotropin-beta is far more sensitive and specific than conventional methods for detecting human chorionic gonadotropin production. 4) After unilateral orchiectomy for carcinoma of the testis elevated serum luteinizing hormone levels are common and may be unrelated to the presence or activity of residual tumor. 5) Human chorionic gonadotropin-beta-producing tumors were associated with increased estradiol and testosterone levels and significantly depressed  serum follicle stimulating hormone levels in this series. 6) The prognostic implications of the presence of human chorionic gonadotropin-beta are not yet fully understood. The importance of this study is the fact that men with testicular tumors have a high incidence of human chorionic gonadotropin-beta secretion and this fact provides the physician with a powerful new tool for examining the various aspects of tumor activity. It also shows the feasibility for prospective screening of patients with a wide variety of neoplasms of differing histologic types.


Eye injury during transurethral surgery. An injury to a surgeon's cornea, which resulted in permanent damage, is reported. The accident could have been prevented if there had been no exposed metal in the telescope eyepiece and if the surgeon had been wearing glasses. Any telescope with exposed metal in the center of the eyepiece should be returned to the manufacturer for replacement with a more protective and insulated type of eyepiece.


Septum-lesioned rats in pharmacological investigations: a re-evaluation. An objective and quantitative method has been developed for measuring the hyper-reactivity of septum-lesioned rats. Twenty drugs belonging to various classes have been investigated as to their influence on this hyper-reactivity. Seventeen compounds inhibited septal hyperreactivity. One drug (methylphenidate) augmented it, while metamphetamine and physostigmine were ineffective. It has been concluded that the use of septal rats in pharmacological investigations does not fulfil expectations. The model cannot differentiate between depressants of various kinds, antidepressants, narcotics or central cholinolytics any more than do the much more simple procedures routinely used in pharmacological laboratories.


Globin synthesis in fibroblasts fused with erythroblasts. II. Human fibroblasts. Fusion of human (diploid) fibroblast monolayers with erythroblasts from 3-day chick embryos resulted in cultures containing on the average 14% heterokaryons and 8% fibroblast homokaryons. When these heterokaryon-containing cultures were labeled with radioactive amino acids during the first 24 h after fusion, the proportion of labeled proteins found in the globin region of analytical polyacrylamide gels showed a 40-fold increase compared with fibroblast homokaryons (0.08% vs. 4% of protein synthesized). Incorporation of radioactivity into globin decreased sharply during the second 24 h. Purified 35S-methionine-labeled globin from heterokaryon cultures gave rise to a tryptic fingerprint containing peptides characteristic of chick embryonic globins as late as 4 days after fusion. While fibroblasts in the fusion culture continue to go through the cell cycle normally, heterokaryons stop cycling almost completely soon after fusion.


Production of mammalian somatic cell hybrids by means of polyethylene glycol treatment. Polyethylene glycol (PEG) is known to promote fusion of plant protoplasts. Various adaptations of this treatment to mammalian, including human, cell cultures are reported here. PEG is very effective in producing hybrids capable of indefinite multiplication even in cases, such as early passage human skin fibroblasts and lymphocytes, known to be highly recalcitrant to other treatments.


Human intelligence: sex differences.

Human intelligence: sex differences. An extensive review of the literatureon sex differences in human intelligence leads to the conclusion that there is stron evidence for sex differences in processing both verbal and spatial information. The few genetic studies that there are all point toward a sex-link mode of inheritance of certain spatial abilities.


School achievement, intelligence, and personality in twins. A sample of 47 MZ and 49 DZ pairs of Brazilian twins was investigated in relation to school achievement in six specific areas of study, as well as performance in the test of Dominoes, the Differential Aptitude Tests (DAT) and Grieger's Characterological Qur the school grades obtained in five of the six areas considered, as well as for their general average; the same being true for the results on the indicated measure of general intelligence, six of the eight DAT tests, and two of the characterological elements. There is a clear positive relationship between the grades earned by the twins and their performance in the Dominoes test. Achievement in Portuguese and foreign language correlates positively with DAT's Numerical Ability, Abstract Reasoning, and Clerical Speed and Accuracy. The results show an agreement with previous estimates of the genetic determination of these variables, which is to a certain extenet surprising if we consider the differences in sample sizes, age, and degree of schooling of the subjects, environmental differences, and the dissimilarities which exist between the homes and school systems of USA, Europe, and Brazil.


A contribution to the psychological study of interpersonal relations in twins. A sample of 71 pairs (32 MZ, 39 DZ), of mean age 9.7 years, has been studied through various techniques in order to better understanding the interpersonal relation of twins, both within the pair and with repect to the members of the family group, and especially the mother. Zygosity, dominance, and birth order have been taken into account. The relation between MZ twins appears to be somehow less special than believed, whereas a special triadic relation appears to exist with the mother. A differentiated research of identity in MZs and autonomy in DZs is also noted (which contributes to a better understanding of problems of schizophrenia in twins). Finally, the relation between MZ cotwins shows mutual similarity and attachment to be lower than foreseen and, anyhow, of a far from mysterious nature.


[Possible role of the cytoplasm in the course of morphogenesis, namely, in the case of twinning]. A number of facts that cannot be interpreted in terms of nuclear genes would seem to be interpretable in terms of cytoplasmic heredity. The hereditary role of the mitochondria has already been demonstrated in molds. The role of the cytoplasm (matrilineal heredity) has also been shown in some phanerogams, and analogous facts have been noted in insects and molluscs. In amphibians, the influence of an alteration of the egg cortical cytoplasm has been shown to reappear in the following generations. This cortical cytoplasm includes the morphological plan of the organism with its bilateral symmetry. In Tatusia novemcincta the twins may be morphologically or chemically different, which may only be explained by an unequal subdivision of a heterogenic cytoplasm. Similar facts are observed in human twinning. Monozygotic twins are usually discordant with respect to congenital malformations (especially symmelia and anencephaly), which may only be interpreted in terms of unequal distribution of cytoplasmic properties.


Correlation matrices for palmar dermatoglyphic traits in twins. Intraclass correlation values have been studied in a sample of 50 MZ and 50 DZ twins with respect to fourteen palmar dermatoglyphic metric traits in binary combinations. The results confirm the general trends already shown in singleton studies. The shape of the palmar surface does not appear to be significantly correlated with other metric traits. Generally speaking, a large independence has been found between the various traits.


Inclination of longitudinal axis of palmarprint with intertriradial distance a-d, PMPC, and DWC. The wide fluctuations of the three angular measurements, a-d, PMPC, and DWC with longitudinal axis make palmar projective breadth (PB) the ideal standard axis for any work involving the quantitative estimates of longitudinal and transverse trends of palmar triadii.


Twinning in India.

Twinning in India. The incidence of twinning in India, as estimated on the basis of data from the various types of maternity centers, so as to include both urban and rural population, appears to be 15.97 per thousand (12.6 DZ, 3.3 MZ). The incidence is significantly higher in rural than urban populations (18.1 vs. 11.8 per thousand). It is suggested that this may be accompanied with a higher production of DZ, possibly opposite-sexed twins.


Determination of triplet zygosity with the use of serological and anthropological characters. This paper discusses briefly some problems involved in zygosity determination in triplets, such as the calculations of the probability of the three zygosity types, as well as the use of serological and other anthropological characters.


[Canine leptospirosis in the state of São Paulo (author's transl)]. In this paper the occurrence of leptospirosis was studied by the search of agglutininis antileptospira, in 10 dogs with symptoms of the disease. Another group of 22 animals with hepatic or renal insufficiency was also studied for the correlation between both insufficiency and leptospirosis. Finally, a third group of 40 dogs, clinically normal, was also included in this study. In 60% of suspected cases the clinical diagnosis was confirmed by the presence of specific agglutinins to serotypes icterohaemorrhagiae, canícola, grippotyphosa and bataviae. Among animals with renal or hepatic insufficiency it was found 36.3% of reagents while in the normal group the rate was only 7.5%. The serotype butembo was detected serologically in dogs for the first time in Brazil.


Purification and characterization of rabbit testicular androgen binding protein (ABP). Testicular androgen binding protein (ABP) was purified from the epididymis of 1500 adult rabbits by the sequential use of ammonium sulphate precipitation, ion exchange chromatography on DEAE cellulose, gel filtration on Sephadex G-200, hydroxyl-apatite chromatography and preparative polyacrylamide gel electrophoresis. This procedure yielded a 1000-fold increase in specific activity compared to that of the 1500,000 x g supernatant, and the recovery of active ABP was about 3-5%. ABP is acid glycoprotein with a molecular weight of 65-68,000 daltons. Antisera to rabbit ABP raised in quinea pigs inhibit 3H-DHT binding to ABP as measured by SS-PAGE. When diluted rabbit serum containing TeBG is treated with the same dilutions of these antisera, identical binding inhibition curves are found. Thus, ABP and TeBG in rabbits appear to possess identical immunological determinants.


Nuclear-magnetic-resonance studies of carboxypeptidase B. Binding of inhibitors to the manganese enzyme. Longitudinal and transverse proton relaxation rates of water in solutions of porcine manganese carboxypeptidase B have been measured in the presence of various competitive inhibitors by pulse nuclear magnetic resonance (NMR) spectrometry. The inhibition constant of Mn-carboxypeptidase activity by L-argininic acid and acetyl-L-arginine was in agreement with the equilibrium constant obtained by the NMR method, indicating similar and specific binding of the inhibitors to the active site of the manganese enzyme. Titration of the water boound to the metal ion revealed the presence of one water molecular which could be displaced from the sphere of the managenese ion by various inhibitors. The structural features of the inhibitors required for this displacement as well as the mode of interaction is described.


Kinetics of binding of bovine trypsin-killikrein inhibitor (K unitz) in which the reactive-site peptide bond Lys-15--Ala-16 is cleaved, to alpha-chymotrypsin and beta-trypsin. Equilibrium measurements of the binding of reactive-site-cleaved (modified) bovine trypsin-kallikrein inhibitor (Kunitz) to alpha-chymotrypsin and beta-trypsin show a stoichiometric 1:1 association with high binding constants. At least in the case of chymotrypsin much evidence is presented that the reaction with modified inhibitor leads to the same complex as the reaction with virgin inhibitor does. The association rate constant of modified inhibitor with chymotrypsin at pH 7, 22.5 degrees C is 15.8 M-1 S-1. This is about 2 x 10(4) times slower than the binding of virgin inhibitor to that enzyme. In the analogous reaction of modified inhibitor with beta-trypsin, however, the association rate constant (1.2 x 10(4) M-1 s-1 at pH 6.9, 22.5 degrees C) is of about the same order of magnitude as it is in the reaction of virgin inhibitor and trypsin. These and analogous phenomena observed in the reactions of virgin and modified soybean trypsin inhibitor (Kunitz) with alpha-chymotrypsin and beta-trypsin suggest that the specificity of both inhibitors to trypsin is strongly reflected in the association rate constants of the modified forms. The dissociation rate constants of the complexes of trypsin-kallikrein inhibitor with chymotrypsin or with trypsin towards the modified inhibitor are estimated to be unmeasurably slow (half-life times of 45 or 1.5 x 10(4) years, respectively).


The effect of cleaving the reactive-site peptide bond Lys-15--Ala-16 on the conformation of bovine trypsin-kallikrein inhibitor (K unitz) as revealed by solvent-perturbation spectra, circular dichroism and fluorescence. Spectroscopic measurements of virgin bovine trypsin-kallikrein inhibitor and its modified species (in which the reactive-site peptide bond Lys-15--Ala-16 is split) indicate a conformational difference between both proteins. The inhibitor contains four tyrosines but no tryptophan. In the modified inhibitor a tyrosyl blue shift is seen in the difference absorption spectrum of modified against virgin inhibitor. The solvent perturbation spectra show an increase of the fraction of exposed tyrosyls from 0.45 in the virgin inhibitor to 0.59 in the modified form. Comparison of the circular dichroism spectra of the modified and virgin inhibitors reveals a decrease of the mean residue ellipticity in the tyrosine and peptide bond region of the modified inhibitor. In the fluorescence spectra a 50% increase in the quantum yield of the tyrosine fluorescence is observed in the modified inhibitor. All these spectroscopic data support the idea, which is also evidenced by the X-ray crystallographic model, that in the modified inhibitor up to five residues from Ala-16 to Arg-20 gain rotational freedom.


The effect of oestrogen and progesterone on maternal behaviour in rats. Treatment or implantation of oestrone, oestradiol or progesterone on the third day postpartum into the ventromedial-arcuate region of the hypothalamus produced a complex pattern of changes in established maternal behaviour in rats. Progesterone implanted into the ventromedial-arcuate region of the hypothalamus increased the time spent nursing. In contrast, it was shortened by oestradiol given subcutaneously or implanted hypothalamically or extrahypothalamically, or by oestrone implanted into the hypothalamus. Oestradiol by an route used oestrone implanted into the hypothalamus caused marked reduction of pup weight and retrieval frequency. Progesterone had no such effect. Maternal care involving retrieval, sniffing, licking and nursing, expressed in seconds care, declined after hypothalamic and systemic oestradiol treatment. However, oestrone implanted into the hypothalamus increased seconds of care on days 9 and 10. Progesterone did not affect this function.


[Multiple gastrointestinal familial poliposis (Peutz-Jerghers syndrome). Report of a clinical case]. The authors review a single case history of intestinal polyposis (Peutz-Jeghers syndrome) of a patient followed by them for eleven years. The paper includes a review of the pertinent literature. The present case was diagnosed as a result of the clinical observation of pigmented spots in the oral mucosa and crises of spasmodic abdominal pain accompanied by bowel movements containing mucus and blood. In other members of the family only a younger sister had slightly pigmented spots in the oral mucosa. None had radiologic findings suggestive of the syndrome of Peutz-Jeghers. Recently the patient under study suffered an intestinal intussuception which led to the surgical resection of a segment of small intestine and permitted pathologic confirmation of the diagnosis. Surgical resection of nodules in both breasts resulted in diagnoses of sclerosing adenosis in the left and an epidermoid cyst in the right.


Microthrombocytosis and platelet fragmentation associated with idiopathic/autoimmune thrombocytopenic purpura. Platelet volume distribution curves were obtained in 20 control subjects and in 21 patients with idiopathic/autoimmune thrombocytopenic purpura. A striking increase in microthrombocytes as well as megathrombocytes was noted in 86% of patients on one or more occasions, particularly in the prsence of severe thrombocytopenia. The entire spectrum of platelet volume distribution curves noted in patients could be reproduced experimentally in rabbits following intravenous injection of anti-platelet antibody. Differential centrifugation studies with control subjects revealed that microthrombocytes were light platelets and megathrombocytes were heavy platelets. Electron microscopy in patients with thrombocytopenia revealed that microthrombocytes were composed of intact small platelets as well as platelet fragments. It is concluded that severe peripheral destruction of platelets is associated with an increase in microthrombocytes as well as megathrombocytes.


[Evaluation of the antibody anti-insulin titer using Christiansen's radioimmunoelectrophoresis in clinical diabetology]. On the basis of personal experience concerning 2020 consecutive determinations, the radioimmunoelectrophoretic method of Christiansen for 125I-Insulin-Binding to IgG (= IB, significant limits = mU/ml) has been proved as a reliable tool for the evaluation of insulin antibody titer in clinical diabetology. After a critical review of the recent literature about insulin antibodies both without and after exogenous immunization, the following results are presented and discussed. 1) - In 163 diabetic subjects, never previously treated with insulin, the mean value of IB was X = 0,008 mUml (sigma = 0,023 . Sx = 0,002). 2) - In 221 longterm insulin-treated diabetics the mean value of IB was X = 1,50 mU/ml (sigma = 2,15 . Sx = 0,145). 3) -In 46 insulin-dependent diabetics, serial determinations of IB allowed to follow the insulin antibody production during a 5 years treatment with monocomponent insulin )Lente MC). No or slight antibody formation was observed in newly diagnosed patients, never previously treated with insulin. High antibody starting levels showed tendency to a gradual reduction, after switching from conventional insulin treatment to the monocomponent one. These modifications in the IB values have been studied in correlation with the clinical course of conditions possibly referred to an immunologic pathogenesis, such as: brittle diabetes, high insulin requirement, insulin allergy, insulin lipoatrophy, diabetic microangiopathy. No significant variations in IB values were observed after viral infections.


Relation between changes in plasma calcium in first week of life and renal function. (1) Of 71 infants fed on reconstituted dried or evaporated cow's milk, 31 showed a fall in plasma calcium between the 1st and 6th days of life, whereas in 35 breast-fed infants this occurred in only 5. (2) Those artificially-fed infants who had shown a rise in plasma calcium over this period had significantly lower plasma creatinine values and significantly higher excretion of creatinine than those infants who showed a fall in calcium levels. (3) Artificially-fed infants who had shown a rise in calcium had significantly lower plasma osmolality and significantly higher osmolar excretion in the urine than those infants who showed a fall in plasma calcium. (4) It is suggested that a delay in the normal increase in glomerular filtration rate during the first week of life in some infants leads to phosphate retention. This, together with a higher dietary intake of phosphate, leads to a decrease of the plasma calcium to hypocalcaemic levels.


Stimualtion of glycerolphosphate phosphatidyltransferase activity in fetal rabbit lung by cortisol administration. Phosphatidylglycerol is an important component of pulmonary surfactant. Previous studies have shown that direct administration of corticosteroids of thyroxine to the fetus during the latter part of gestation results in accelerated lung maturation with increased surfactant production. We have shown that administration of cortisol to fetal rabbits at 24 days' gestation results 3 days later in a significant increase in the activity of pulmonary glycerolphosphate phosphatidyltransferase, an enzyme involved in the synthesis of phosphatidylglycerol. The activity of the liver enzyme was not affected. Choline phosphotransferase, CDPdiglyceride-inositol phosphatidyltransferase, lysophosphatidic acid acyltransferase and lysolecithin acyltransferase activities were not altered significantly by cortisol treatment. Thyroxine treatment had no effect on any of the enzymes of phospholipid or fatty acid biosynthesis studied.


Bilayers of dipalmitoyl-3-sn-phosphatidylcholine. Conformational differences between the fatty acyl chains. Dipalmitoyl-3-sn-phosphatidylcholine is specifically deuterated at the C-2 position of the fatty acyl chains. Using deuterium magnetic resonance it is then possible to probe the chain conformation in the vicinity of the polar head groups. Three separate quadrupole splittings are observed for bilayers of 1,2[2'-2H2]palmitoyl-3-sn-phosphatidylcholine, indicating that the two chains behave differently. The synthesis of phosphatidylcholines each deuterated in only one chain allows the assignment of the three resonances. It is concluded that the beginnings of the two chains have orientations parallel and perpendicular to the bilayer normal. The data further suggest the possibility of two long-lived conformations of the glycerol constituent.


Differential scanning calorimetry and 31P NMR studies on sonicated and unsonicated phosphatidylcholine liposomes. 1. Phase transitions in sonicated (vesicles) and unsonicated liposomes composed of various synthetic phosphatidylcholines are monitored using differential scanning calorimetry and 31P NMR. 2. The temperature (Tc), heat content and width of the phase transition are comparable in both vesicles and liposomes prepared from 1,2-dipalmitoyl phosphatidylcholine and 1,2-dimyristoyl phosphatidylcholine. In vesicles composed of a (1 : 1) mixture of 1,2-dipalmitoyl phosphatidylcholine and 1,2-dioleoyl phosphatidylcholine phase separation occurs as in the bilayers of the unsonicated liposomes. 3. The linewidth of the 31P resonances in vesicles is not greatly dependent upon the fatty acid composition when the lipids are in the disordered liquid crystalline state (above Tc). When the lipids are in the gel state (below Tc), however, there is a marked increase in linewidth, demonstrating a reduction in motion of the phosphate group. 4. The ratio of the amounts of phosphatidylcholine present in the outside and inside monolayter of the vesicle membrane was determined with 31P NMR using Nd3+ as a non-permeating shift reagent. 5. The outside/inside ratio is dependent upon the hydrocarbon chain length. Increasing chain length gives a lower outside/inside ratio and a larger vesicle. Introduction of cis or trans double bonds in the chain influences the outside/inside ratio slightly. 6. The incorporation of cholesterol decreases the outside/inside ratio and increases the size of 1,2-dimyristoyl phosphatidylcholine vesicles. The cholesterol concentration in the outside and inside monolayer is approximately the same. The size of the 1,2-dioleoyl phosphatidylcholine vesicles is also increased by cholesterol incorporation but the outside/inside distribution is also increased, especially between 30 and 50 mol% cholesterol. In these vesicles cholesterol is asymmetrically distributed and strongly prefers the inside monolayer of the vesicle.


Lymphosarcoma of the breast.

Lymphosarcoma of the breast. A case of lymphosarcoma presenting as a breast tumour in a 68-year-old woman is described and the condition briefly reviewed.


A 31P NMR study of the thermal transition of dipalmitoyl lecithin vesicles. Phosphorous-31 nuclear magnetic resonance (31P NMR) was used to study the liquid crystalline transition of sonicated dipalmitoyl lecithin vesicles in D2O. Linewidths were dependent upon temperature and changed dramatically through the transition region. The potential usefulness of 31P NMR spectroscopy for probing the thermal behavior of phospholipid membranes is evaluated and discussed.


Solvation of oxygen in lecithin bilayers. The solubility of oxygen in dipalmitoyllecithin (DPL) and paraffinc C19 has been investigated by measurement of the enhanced proton relaxation rates under the influence of oxygen pressure. The paraffin shows a noticeable effect in the rotator phase, but not so in the crystalline phase. tin contrast to paraffins, both phases of DPL-bilayers dissolve oxygen, but the solubility in the liquid-crystalline phase is greater than in the crystalline state by a factor approximately equal to 3. Furthermore, the experiments indicate a distribution of electron relaxation times in the crystalline phase in contrast to the liquid-crystalline phase. A possible explanation of this behaviour is a multiphase structure of the "crystalline' lamellae. The biological relevance of thbse results could be a triggering of the gas-transport by the alveolar lining of lungs, if cyclic phase transitions occur during the breathing-cycle.


[Ciguatera: neurophysiological demonstration of toxicity of several ciquatoxic fractions]. Raw extracts from one Polynesian, frequently ciguatera-inducing fish were submitted to fractional distillation by means of a chromatographic process using a silicic acid column. Three out of the seven fractions split this way exhibited either anticholinesterasic properties, or directly toxic properties at the muscle-cell level: fraction 5, which is not antagonized by atropine, presumably accounts for this direct action, as it competes with calcium at membrane sites. Fraction 6 appears to be more specially responsible for the anticholinesterasic action. It revealed a quaternary ammonium ion in its 6-2 sub-fraction. Fraction 7 shows the same properties as fraction 6, but on a smaller scale.


Effects of CB-154 (2-Br-alpha-ergocryptine) on prolactin and growth hormone release in an acromegalic patient with galactorrhea. An acromegalic patient with galactorrhea was treated with an ergot alkaloid, 2-Br-alpha-ergocryptine (CB-154). Serum prolactin decreased rapidly to normal level by CB-154 and the complete cessation of galactorrhea was noted. The inhibitory effect of CB-154 On growth hormone (GH) release was also noted, but slight. The mechanism of inhibitory action of CB-154 on both prolactin and GH secretion was discussed in connection with the experimental model of pituitary tumors, in which both hormones were produced by a single type of tumor cells. The discontinuation of CB-154 treatment was associated with the return of both prolactin and GH levels to the initial high values with resumption of galactorrhea.


[Do the eosinophilic granulomas observed in Brittany represent a form of anisakiasis? The larvae of Thynnascaris aduncum do not produce these granulomas experimentally]. To explain the enigmatical origin of gastric eosinophilic granulomas prevailing among patients in Brittany (France), we have tried to experiment with the larvae of Thynnascaris (Thynnascaris aduncum (Rud.)), a Nematode found in the sardine (Sardina pilchardus (Walbaum)), a fish sometimes eaten raw in our country. In a preliminary experiment, larvae of Thynnascaris were observed to penetrate the mucosa of the rabbit stomach in vitro at room temperature. But in vivo, whatever the means, the ways and the experimented mammals of our study, we have failed to experimentally reproduce such tumours. We think that this result belongs to the fact that the larvae of Thynnascaris in the conditions of our experimentation could not perform an evolution in homeothermal animals.


[Preparation of a standardized antigenic extract from several strains of African trypansomes]. The preparation of a soluble antigen from african trypanosomes is described below. It is important to observe the following steps: --minimal dose of the phytohemagglutinin must be placed in rapid contact with the trypanosomes; --the standard speed of the different centrifugations must be strictly observed; --a thorough washing of the trypanosomes must be carried out to eliminate the hetero-antigens, but caution should be excercised, as over washing is harmful to the Trypanosomes.


Morphological conversion of 13 strains of three dimorphic fungi in tap and stream water. Various strains of Sporotrichum schenckii, Histoplasma capsulatum and Paracoccidioides brasiliensis show partial to complete (ca 70%) conversion to yeast when the mycelial culture is grown on Sabouraud's dextrose agar at 25degreesC and palced in tap or stream water at 37degreesC. Conversion (ca 70%) to mycelial phase occurs when the yeast culture is grown on brain heart infusion agar at 37degreesC and then placed in tap or stream water at 25degreesC. It was observed that, with the dimorphic organisms and strains tested, enriched medium is not necessary for partial conversion to either phase because it occurs in tap and stream water. The change in morphology is assumed to be principally due to temperauture change, as reported for Blastomyces dermatitidis and H. capsulatum by other workers.


Additives in fibers and fabrics.

Additives in fibers and fabrics. The additives and contaminants which occur in textile fibers vary widely, depending on the type of fiber and the pretreatment which it has received. Synthetic fibers such as nylon and polyester contain trace amounts of contaminants such as catalysts and catalyst deactivators which remain after the synthesis of the basic polymers. In addition, there are frequently a number of materials which are added to perform specific functions in almost all man-made fibers. Examples of these would include traces of metals or metal salts used as tracers for identification of specific lots of fiber, TiO2 or similar materials added as delustrants, and a host of organic species added for such special purposes as antistatic agents or flame retardants. There may also be considerable quantities of residual monomer or small oligomers dissolved in the polymer matrix. The situation becomes even more complex after the fibers are converted into fabric form. Numerous materials are applied at various stages of fabric preparation to act as lubricants, sizing agents, antistats, bleaches, and wetting agents to facilitate the processing, but these are normally removed before the fabric reaches the cutters of the ultimate consumers and therefore usually do not constitute potential hazards. However, there are many other chemical agents which are frequently added during the later stages of fabric preparation and which are not designed to be removed. Aside from dyes and printing pigments, the most common additive for apparel fabrics is a durable press treatment. This generally involves the use of materials capable of crosslinking cellulosics by reacting through such functions as N-methylolated amides or related compounds such as ureas and carbamates. These materials pose some potential hazards due to both the nitrogenous bases and the formaldehyde which they usually release. There is usually also some residual catalyst in fabrics which have received such treatments. Other types of chemical treatments which are often applied to fabrics to achieve special effects include flame retardants, soil release agents, antistatic agents, softeners, water and/or oil repellents, ultraviolet absorbers, bacteriostats, and fungistats.


Plasma level studies on different brands of sodium diphenylhydantoin (DPH) and primidone. Comparative plasma level studies on different brands of sodium diphenylhydantoin (DPH) and primidone are described. Steady state plasma levels of both drugs were measured in epileptic patients who were chronically maintained on this medication. Simultaneous measurements of phenobarbital, primidone and diphenylhydantoin were carried out by gas chromatography. Drug product equivalence and clinical significance of plasma levels of DPH and primidone are discussed.


Studies on the intrathecal pharmacotherapy. Part I: CDP-choline. A study was made of the intrathecal infusion as a route of administration of drugs for the CNS, by giving due consideration to the presence of blood-brain and CSF-brain barriers. CDP-choline was used as the brain activator, and the effect of the drug intrathecally infused was investigated both clinically and by experiments on animals. Seven patients with a disturbance of consciousness due to primary brain lesion received a total of 19 intrathecal infusions of CDP-choline, and were examined for the effect of the treatment neurologically and electroencephalographically. Wistar rats were infused either intravascularly or intracisternally with 14C-CDP-choline, and the distribution in the body was investigated by whole body autoradiography.


[Gastric lesions caused by potassium permanganate tablets. Measures to be taken after ingestion]. Potassium permanganate tablets are caustic and it has been suggested that they should be removed straightaway by gastrostomy, immediately after swallowing. Some operators have been impressed by the macroscopic appearance of the stomach and have carried out gastrectomy. However, the lesions were only fairly superficial on pathological examination. In the light of a new case and 21 similar cases, treated at the Fernand Widal hospital, the authors discuss other cases in the literature. They conclude: the extreme rareness of digestive perforation; the absence of toxicity of breakdown products of potassium permanganate. They propose treatment of neutralisation of the permanganate with sodium hyposulphite, gastric lavage and supervision on a surgical unit. In case of perforation, they believe that the operation should be conservative.


A sensitive and precise radioimmunoassay for human thyroid-stimulating hormone. A high-sensitivity radioimmunoassay for human thyroid-stimulating hormone (hTSH) has been developed utilizing a highly specific rabbit antibody (developed by AFP) to hTSH with an affinity constant of 4.4 x 10(11) M-1. Optimal conditions which minimized both 125I-hTSH radiation damage and 125I dissociation included storage at -60 C in 0.25% albumin. Repetitive freezing and thawing did not cause loss of structural integrity or of full immunochemical reactivity of 125I-hTSH. Effects of human and calf sera on the precipitation of first antibody-bound 125I-hTSH by second antibody have been tabulated; the addition of TSH-free human serum to the standard curve is necessary to compensate for the serum effect. The minimum detectable amount of TSH in the new assay at a 1:1,000,000 final dilution of the hTSH antibody is 0.02 muU/tube. The mean normal hTSH value of 1.5 +/- 1.0 muU/ml (mean +/- SD) fell within the central one-third of the logit (B/Bo) plot where antigen concentrations are measured with highest precision. This assay gives good precision and reproducibility of measurements throughout the normal range of serum TSH concentrations.


The dietary status of "new" vegetarians. A study of fifty well educated young adults, average age twenty-eight years, living in a metropolitan area of New England, who were followers of Zen macrobiotics, revealed that none was below his/her desirable weight although all were at the limit of the normal range. Average triceps skinfold thickness of the men and women fell in the 15th percentile, while arm circumference for members of both sexes was in the 5th percentile (24). Their ten-day dietary records indicated that the base of their diet was grains interspersed with a wide variety of vegetables, fish, cheese, and eggs and that nutrient intakes of the adults were limiting in energy, calcium, and riboflavin--and additionally in iron for the women. Improvement in the nutritional value could be achieved by greater consumption of foods common to macrobiotic dietary practices. Calcium and energy intakes of ten young children were low, especially for a period of rapid growth and development. Because of the bulk necessary to achieve nutritional adequacy with respect to calcium, increasing the children's consumption of macrobiotic food would not be advisable. Consequently, it is suggested that milk be included in their diets.


Neuropathologic effects of intrathecal water. In attempting to control the pain of disseminated carcinoma, a variety of agents has been injected intrathecally.  This report deals with the neuropathologic changes in spinal roots and spinal cord of four patients into whose lumbar sacs 100 to 285 ml of distilled water was infused. Survival following the procedure ranged from 9 to 50 days. In most severely affected case (285 ml instilled 50 days prior to death) the abnormalities were: (1) severe breakdown of axons and myelin sheaths of the lower cauda equina and to a lesser extent of other roots at levels as high as the eighth cervical segment, (2) severe central chromatolysis of anterior horn cells in lumbo-sacral spinal cord with milder degrees of change in the thoracic and lower cervical spinal cord, and (3) striking vacuolar change and axonal swelling, primarily in the lateral columns ascending as high as the lower cervical spinal cord. A second case (140 ml instilled 24 days prior to death) showed similar but milder changes. The remaining cases (100 ml instilled 34 days prior to death: 100 and 200 ml instilled 27 and 9 days prior to death) showed no changes referable to intrathecal water. Infusion of distilled water intrathecally is capable of producing distinctive lesions of spinal root and cord.


Bone mineral content determined by functional imaging. Quantitation of bone mineral by photon absorptiometry is a simple and accurate method for determining changes in bone volume and mineral content in serial studies. An extension of the scintillation camera method for studying such changes in the calcaneous is described. This technique is applicable to large areas of bone, thereby minimizing the effect of repositioning errors. Using a 40-mCi 241Am sheet source, a 2.1% reproducibility in bone phantoms and a 2.4% reproducibility in normal patients was achieved. Several case studies are presented to illustrate sensitivity and clinical application of the method. Although bone mineral determinations are now performed in a limited number of health care facilities, the scintillation camera method described in this report could increase the availability of these determinations significantly.


The effect of intestinal distension and of section thickness on counts of epithelial nuclei in the rat small intestine. (1) A method is described for counting nuclei in wax-embedded histological sections of epithelium. The counts are independent of section thickness over a wide range (4-10 mum). (2) counts of nuclei were made in villi and crypts of rat small intestine fixed either collapsed or distended by a hydrostatic pressure equivalent to 350 mm of water. There was no significant difference between the counts of nuclei in collapsed or distended gut. (3) Distension reduced the absolute height of villi, and increased their absolute width at the base. (4) The implications of these findings for studies of the morphological basis of intestinal adaptation are discussed.


Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus. Plasma glucose and glucagon responses to standard meals containing carbohydrate, fat, and protein as in normal diets were studied in 12 subjects with insulin-dependent diabetes and 12 normal subjects. Diabetics had two to three times greater glucagon responses than did normal subjects. Fifteen units of insulin injection did not normalize these excessive glucagon responses, although postprandial hyperglycemia was reduced. Infusion of somatostatin at a dosage of 500 mug/hr prevented glucagon responses and diminished postprandial hyperglycemia by 60%. The combination of insulin and somatostatin caused a progressive fall in plasma glucose levels despite meal ingestion. Somatostatin and insulin, administered subcutaneously in the same syringe, also abolished postprandial hyperglycemia. These studies indicate that excessive glucagon secretion participates in the genesis of diabetic postprandial hyperglycemia. Somatostatin, an inhibitor of glucagon secretion, may thus prove useful as an adjunct to insulin in the treatment of diabetes mellitus.


Myxedema ileus. A form of intestinal pseudo-obstruction. Myxedema ileus uncommonly complicates the hypothyroid state. It is a rare cause of intestinal pseudo-obstruction that can be reversed with thyroid hormone therapy. Our two patients with myxedema ileus had concurrent infection. Intestinal ileus was completely reversed with the administration of thyroid hormone.


Hypercalcitonemia in bronchogenic cancer. Evidence for thyroid origin of the hormone. Retrograde venous catheterization in a hypercalcitonemic patient with adenocarcinoma of the lung demonstrated that the thyroid gland was secreting a very large amount of hormone (14-fold higher than the peripheral level), while the venous drainage from the tumor deposits was similar in concentration to that of the periphery. Conceivably, the calcitonin is being elaborated in response to metastatic and humoral bone resorption or both. Radiotherapy resulted in a decrease in the calcitonin level. Further studies are needed to determine the diagnostic or prognostic implications of serum calcitonin in bronchogenic cancer.


High altitude pulmonary edema. A rare disease? Since its original description in the English literature 15 years ago, high altitude pulmonary edema (HAPE) has been the subject of many reports. The clinical and hemodynamic features of HAPE are now well recognized, but its underlying pathophysiology remains unclear. In this article, a case of HAPE is described and the clinical features, proposed pathogenesis, and treatment are discussed. (JAMA 234:491-495, 1975).


Smoking, oral contraceptives, and obesity. Effects on white blood cell count. Data from 14,961 healthy women were analyzed to determine the relative importance of factors that alter the white blood cell (WBC) count. The effects of smoking, oral contraceptive use, and obesity were most striking. A total leukocyte count greater than 10,00/cu mm was found in 44% of obese, heavily smoking women who took oral contraceptives (central 95% of the distribution was 5,800 to 14,200/cu mm) as compared to 2% of women without these attributes (3,500 to 9,400/cu mm). Other factors such as age, time of day, phase of the menstrual cycle, and red blood cell variables were of lesser significance. The use of noncontraceptive estrogenic hormones did not affect the WBC count. Recognition of these findings is important because excessive laboratory studies, lost physician time, and patient inconvenience may thereby be avoided.


Phencyclidine poisoning.

Phencyclidine poisoning. Phencyclidine hydrochloride abuse has become increasingly common and should be considered in patients with unexplained acute psychosis, dystonic reactions, status epilepticus, or coma. Two phencyclidine-intoxicated patients had bizarre combinations or disorientation, hallucination, agitation, and dyskinetic motor activity. Supportive care and reduction of sensory stimulation are the basis for management of the symptoms.


Phencyclidine. Nine cases of poisoning.

Phencyclidine. Nine cases of poisoning. In nine cases of phencyclidine hydrochloride poisoning, early signs of overdose included drowsiness, nystagmus, miotic pupils, blood pressure elevation, increased deep tendon reflexes, ataxia, anxiety, and agitation. In more severe cases, seizures, spasticity, and opisthotonos were seen in addition to deep coma and respiratory depression. Treatment included removal by emetics or lavage, hydration, and a quiet, reassuring environment. Spasticity, agitation, and ocular manifestions responded to diazepam. Psychiatric intervention was instituted after the patients were stable and no longer agitated.


Fallibility of the clinical diagnosis of venous thrombosis. Doppler ultrasound examination confirmed the diagnosis of acute venous thrombosis in only 194 (37%) of 527 patients. Of the remaining 333 patients, 245 (74%) had some other evident cause of the limb complaints. The postphlebitic stasis syndrome; symptomatic varicose veins; congestive heart failure; leg trauma; venous or lymphatic obstruction by malignancy; cellulitis or lymphangitis; arthritis; and pregnancy were etiologic factors in these patients. The proved inaccuracy of the bedside diagnosis of leg vein thrombosis stresses the need for accurate objective verification of venous disease before committing the patient to a full course of anticoagulant therapy. For most clinicians, a contrast phlebogram is the most available and reliable diagnostic procedure.


Pneumonia associated with measles.

Pneumonia associated with measles. Thirty-three children were hospitalized for pneumonia associated with measles. Eight did not have rash but had serologic evidence of measles infection and an otherwise compatible clinical picture. Lung puncture and tracheal aspirations were performed on 21 of the patients. Mortality was 15.2% (five patients) and was not associated with the use of these procedures.


Cephalexin-related nephropathy.

Cephalexin-related nephropathy. Hematuria and eosinophilia developed in two patients being treated for bacterial endocarditis with 20 or 24 gm/day of cephalexin given orally together with probenecid (Benemid). One patient had a concurrent transient increase in serum creatinine; both patients had a history of penicillin allergy and had previously received cephalexin intravenously. All abnormalities promptly remitted following discontinuation of therapy.


Ophthalmic Graves' disease.

Ophthalmic Graves' disease. Ophthalmic Graves' disease is a peculiar clinical condition, characterized by ocular symptoms, without thyrotoxicosis. A survey of 22 observed cases is discussed. This condition is 25 times less frequent than classical Graves' disease. The eye symptoms include upper lid retraction, exophthalmos, and severe ophthalmopathy. Unilateral symptoms are frequent (16 out of 22). A negative T3 suppression test was found in half of the patients. LATS was detectable in 3 out of 17 of the cases. The stimulation of TSH secretion by TRH was normal in 3 out of 6 of the cases. When the tests were combined and repeated, a positive response was found in 8 out of 9 of the exophthalmic patients, and in 3 out of 9 of the patients with lid retraction. Appreciation of the course of the disease necessitates a prolonged follow-up; transformation into classical thyrotoxicosis have been observed. Our clinical studies bring into focus the relationship of ocular symptoms with Graves' disease and Hashimoto's disease.


Congenital muscular dystrophy: a clinico-pathological and follow-up study of 15 patients. Fifteen patients with a presumptive diagnosis of congenital muscular dystrophy were followed for up to 15 years. The diagnosis was based on clinical, enzyme, histological and neurophysiological examinations. The group formed nine per cent of the 160 children suffering from neuromuscular disorders seen at the same hospital during a period of ten years. The muscle weakness was generalized and also involved respiratory muscles and the face. 60 per cent of the children had congenital contractures; these were well amenable to treatment. However, there was a strong tendency for new contractures to form from the second to third year onwards. There were also other signs indicating that the disease process was changing with time. The deep tendon reflexes were present in the beginning but later were usually lost. The serum creatine kinase was raised even to high levels in the first one to two years and gradually sank to normal or near normal values. The histopathological findings changed with time from relatively slight changes compatible with a muscle destroying process to inactive type lesions characterized by fibrotic and particularly adipose tissue replacing muscle fibres. On the basis of these findings it can be assumed that the active disease process is at its height during intrauterine and early postnatal life and then wanes leaving an outburnt or cicatrical state in which new contractures easily develop causing possible deterioration with time. Active treatment is thus of great importance both to overcome neonatal contractures and to prevent new ones to develop.


Peripheral nerve maturation in premature infants. The association of peripheral nerve conduction velocity and conceptional age in premature infants is well established. However, the impact of premature birth on the rate of maturation of peripheral nerves is unclear. In this study a group of 119 premature infants and 32 term infants had nerve conduction velocity determinations. The correlation of velocity and conceptional age is significant. There appears to be no effect upon nerve conduction velocity by the occurrence of prenatal or postnatal events. It is unclear whether extrauterine rates of increase of velocity in prematures are comparable to intrauterine rates, but testing of prematures after they have reached their expected date of birth shows them to have identical mean values to term infants tested at term.


[Juvenile spongy dystrophy of CNS with necrosis of the medulla. A. complication of hydroxyquinoline therapy (author's transl)]. A girl of 10-5/12 years is described, who had diabetes mellitus from the age of 5 years on and who developed bilateral ptosis, pigment degeneration of the retina and bilateral impairment of hearing at the age of nine years. A few weeks before death she suffered from an acute gastrointestinal infection which was successfully treated by a hydroxyquinoline derivative. In the days following a severe encephalopathy and signs of cardiac involvement appeared. A month later the girl died of bulbar paralysis and acute heart failure. Histology showed remnants of a granulomatous inflammation in the heart, the kidneys, the pancreas and the skeletal muscles. Furthermore there was a widespread spongiosis in the white substance of the brain, with large astrocytes, and partly also in the basal ganglia, the brain stem and the cerebellum. Foci of sudanophilic tissue necrosis resembling Wernicke's Encephalopathy were found in the medulla oblongata and the spinal cord. The peripheral nerves appeared partially demyelinated and showed axonal lesions. This case is classified as a Juvenile Type of so-called Canavan's Disease. It shows some resemblence to the "Progressive Chronic Ophthalmoplegia with Spongiform Encephalopathy described by Daroff, Kearn and Sayre. The possible neurotoxical effects of the hydroxyquinoline therapy are discussed.


Micronodular encephalitis and acute leukemia treated with immunosuppressives in a child. The present paper is the study of a micronodular encephalitis with inclusions occurring in a child suffering from acute leukemia treated with antimitotics and immunosuppressives. The role of the immunosuppressive treatment in the onset of the encephalitic syndrome is discussed.


Latent Haemobartonella muris infection: its transmission and decline in an inbred, ectoparasite-free strain of Wistar rat. Ectoparasite-free, SPF Italian Wistar rats were consistently found to carry a latent infection with Haemobartonella muris, activable by splenectomy. In an inbred line this diminished and eventually ceased in six generations. Experimental infection from wild rats demonstrated that this was not apparently due to immunity.


The choice of antibiotic for treating infective endocarditis. The bacteriological spectrum of infective endocarditis is very different when the disease occurs spontaneously from when it follows shortly after cardiac surgery or is associated with narcotic abuse or haemodialysis. It is therefore suggested that two categories of the illness, naturally occurring and extraneous, are recognized. The great majority of cases of naturally occurring infective endocarditis are caused by organisms highly sensitive to penicillin. Oral therapy is nearly always effective in such cases and amoxycillin given with probenecid is recommended as the regime of choice. Extraneous infective endocarditis is most often caused by staphylococci, with Gram-negative bacilli and fungi also quite frequent infecting agents. Intravenous and oral therapy with a variety of antibiotics is discussed in the management of this group.


The significance of alveolar geometry and surface tension in the respiratory mechanics of the lung. It is customary to describe alveolar respiratory mechanics in terms of a bubble-shaped model alveolus, using the Laplace equation. The coexistence of alveoli of different radii cannot be satisfactorily explained by this model, even if hypotheses as yet unconfirmed by experiment are taken into account. Moreover, this model requires the assumption of extremely low surface tensions, near 0 dny/cm, to explain the absence of atelectasis with very small alveolar radii and the maintenance of alveolar fluid balance. On the basis of investigations of the dynamic surface tension of lung alveolar surfactant from rat lungs, however, the minimal surface tension of alveoli is 18-20 dny/cm. In addition, the lung does not consist of isolated and spherical alveoli but a dense packing of polyhedral air spaces separated by alveolar septa. This paper is an attempt to analyze the recoil forces of the lung due to surface tension on the basis of the polyhedral alveolar structure and the minimum surface tension mentioned above. It is demonstrated that several geometrical parameters are able to guarantee the stability of the alveolar structure of the lung to a greater extent than a variable surface tension. It is concluded that not a single (and fictive) alveolus but the septal intersections and the "peripheral" septa (limiting only one air space) are the smallest morphological units of the respiratory mechanics. Some consequences concerning the pressure-volume behavior of the whole lung, the above mentioned coexistence problem and the alveolar fluid balance are discussed.


Lymphosarcoma, cold urticaria, IgG1 monoclonal cryoglobulin and complement abnormalities. A patient with lymphosarcoma and cold urticaria showed evidence of complement activation by the classical pathway with low levels of the early complement components, normal levels of late acting components, normal functioning of the alternate pathway and reduction of the C1-inhibitor level. The serum contained an IgG1 monoclonal cryoglobulin responsible for the complement activation. In vitro tests demonstrated a high capacity of the serum to activate C1.


[Morphologic and virologic studies of the fetus and placenta in neorickettsial abortion in cattle]. A total of 19 fetuses and 10 placentas were studied. Four fetuses and one placenta harboured neorickettsiae, and the remaining fetuses and placentae originated from cows in the serum of which there were complement-fixing antibodies. These ranged within 1:8-1:64. The gross lesions of the fetuses consisted in the presence of edema with enlargement of the liver. The changes were more characteristic histologically. The liver, kidney, heart, adrenals, and occasionally the lung and spleen had foci of histiocytes, lymphoid and plasmatic cells, and fibroblasts, sometimes with the presence of sporadic leukcoytes. The presence of such cell elements agglomerated in foci fairly often  built up formations of granulomatous character. The focal processes prevailed, however, there were diffuse reactions too. Histologically, there were in the placenta diffuse edemas, hyperemia, single hemorrhages, and multiple necrotic foci. A correlation was established between the serologic, virologic, and morphologic changes which made more feasible the diagnosis in such abortions.


Lack of effect of hyperglycaemia on apomorphine induced growth hormone release in normal man. Six healthy adult males were studied to evaluate the effect of apomorphine on growth hormone (GH) secretion under normoglycaemic and hyperglycaemic conditions. Both under normoglycaemia and hyperglycaemia all subjects responded to the subcutaneous injection of 0.75 mg apomorphine hydrochloride with a marked increase in plasma GH concentration reaching a maximum after 30-60 min. In control studies no significant changes in plasma GH were observed following the injection of physiological saline. As apomorphine is considered a selective dopamine receptor stimulating agent, the results support the view that GH release in man can be modulated through a dopaminergic mechanism. The finding that the plasma GH rise after the administration of apomorphine is not suppressible by glucose indicates that apomorphine activates dopaminergic receptors localized distally in the hypothalamus or in the anterior pituitary. Amorphine in low dosage may be used clinically to test the capacity of the pituitary to release GH in man, at least in special cases.


Pituitary hormones in women with chronic renal failure: the effect of chronic intermittent haemo- and peritoneal dialysis. Measurements of plasma prolactin (hPr), growth hormone (HGH), thyrotrophin (TSH), luteinizing (LH)--and follicle stimulating hormone (FSH) were performed in 20 women with chronic renal failure on regular dialysis. There was no significant difference in any of the hormone levels before and after the dialysis and no significant influence of the type of dialysis (haemodialysis and peritoneal dialysis) or the time of dialysis. Higher levels of plasma prolactin was found in the women on peritoneal dialysis than in the haemodialyzed women presumably due to the medical treatment. In the peritoneally dialyzed group four women had irregular menstruations and normal gonadotrophic levels, but elevated hPr and it is suggested that this finding is similar to that seen in the amenorrhoeagalactorrhoea syndrome, where hPr presumably in some way have antigonadotrophic actions at the gonadal level.


Critical analysis of methods for estimating production rates of FSH. The urinary excretion method and the constant infusion technique were used to estimate hFSH production rates (PR) in three normal men (aged 25-40 years). Both studies were also done in a hypophysectomized nine year old boy. The PR of hFSH in the urinary excretion studies ranged from 20.0 to 45.7 IU/24 h, whereas the constant infusion studies yielded PR'S OF 68.7 to 107.8 IU/24 h. Possible reasons for the discrepancy of the results obtained by the two methods are discussed. In the hypophysectomized patient, the metabolic clearance rate (MCR) of infused hFSH was much lower (4.3 ml/min) than in the normal adults (7.8 to 12.0 ml/min) and was not affected by the dose of hFSH given.