Comparative contributions of dietary protein quality and quantity to growth during gestation, lactation and postweaning in the rat.

The growth promotion by feeding purified diets containing 25%, 12% or 7% of either casein or wheat gluten (W.G.) and the supplementation value of adding cystine to the low casein diets, and lysine or lysine plus threonine to the wheat gluten diets ascertained in rats by comparing the weight achieved at birth, after 3 weeks suckling or 4 weeks postweaning. Birth weight was depressed by 30% with 7% casein; by 20% with 7% W.G.; by 15% with 25% W.G. compared to controls and there was no change when lysine alone was added to 7% W.G. Addition of lysine plus threonine to 7% W.G., lysine to 25% W.G. and cystine to 7% casein increased birth weight. The weight gain of dams reflected birth weight of pups in most cases. Weaning weight was depressed by 60% with either 12% casein or 12% W.G., and by 40% with 25% W.G. compared to controls. Addition of cystine to 12% casein and lysine to 25% W.G. increased the weaning weight slightly. Addition of lysine, lysine plus threonine or lysine plus glutamic acid (G.A.) to 12% W.G. had no effect on weaning weight. Maternal weight loss was decreased by amino acid supplementation of the diet. Four-week postweaning body weight was equal to the control when cystine was added to 12% casein and lysine was added to 25% W.G. Addition of lysine to 12% W.G. improved the growth rate, and addition of lysine plus threonine further improved the growth rate. Food intake was not decreased by protein deficiency during gestation. Food intake was significantly lowered by protein deficiency during both lactation and postweaning, however, supplementation of amino acid partially restored food intake to normal levels.


Metabolic responses to prolonged fasting and subsequent refeeding in the pig.

Metabolic responses associated with prolonged fasting and subsequent refeeding of pigs were investigated. Fasting for 14 or 28 days produced significant increases in serum levels of alanine, aspartic and glutamic acid in the three branched-chain amino acids. Glycine, serine and lysine levels were elevated after 28 days of fasting while the levels of histidine, methionine, threonine and phenylalanine were reduced. Fasting markedly stimulated hepatic and renal gluconeogenesis and the activity of the urea cycle enzymes. Fatty acid synthesis and glucose oxidation were virtually abolished in hepatic and adipose tissue in pigs subjected to a 14- or 28-day fast. After the first day of refeeding, the levels of amino acids returned to the control values. The activity of the hepatic urea cycle enzymes, fructose-1,6-diphosphatase and phosphoenolpyruvate carboxykinase remained elevated after the first day of refeeding but returned to the control levels thereafter. The activity of hepatic glucose-6-phosphate dehydrogenase, malic dehydrogenase and acetyl CoA carboxylase were slightly enhanced in pigs refed for 4 and 8 days. The activity of these enzymes in adipose tissue was enhanced 8 days after refeeding. Hepatic synthesis of fatty acids from glucose was slightly stimulated in refed pigs on days 4 and 8 but returned to control values on day 16. Refeeding did not enhance glucose incorporation into fatty acids in adipose tissue above the values observed in fed controls.


Diurnal periodicity of uridine uptake by Hymenolepis diminuta.

A diurnal pattern in the uptake of uridine was displayed by the rat cestode Hymenolepis diminuta. No periodicity in the uptake of uracil was observed over a 48-hr period. A high level of uridine uptake occurred at 6 PM. when 10-day-old worms were in a posterior location in the intestine of rats maintained on a 6 PM.-6 AM. dark cycle-feeding regime, while low levels of uptake were correlated with an anteriad location at 6 AM. The lowest levels of uridine uptake were recorded at noon. Coincubation with thymine caused a stimulation of uridine uptake at midnight, 6 AM., and noon when uridine's transport rate in the absence of thymine was low. Stimulation was not demonstrable when uridine's transport rate was at its highest at 6 PM. Preincubation with uridine did not alter the diurnal uridine uptake pattern. This diurnal phenomenon is an important consideration essential to future studies on transport in parasitic and other organisms.


A model for the kinetics of distribution of actinomycin-D in the beagle dog.

A pharmacokinetic model is presented for the distribution of actinomycin-D in the beagle dog. A simple, flow-limited model provides good simulations of the data at doses of 0.6 mg/m2 (0.03 mg/kg) and 2.7 mg/m2 (0.135 mg/kg) for most normal tissues. This implies that uptake of actinomycin-D in vivo is limited by tissue blood flow rate rather than by cell permeability. However, uptake by the testes is restricted by a blood-testis barrier, and a linear membrane-limited model is required to simulate the testis data. Linear binding of actinomycin-D to tissue is suggested by the fact that tissue concentrations are proportional to dose at least up to the lethal dose in dogs. The binding is also rapid and reversible as indicated by the tissue concentration curves which are parallel to the time course of the declining plasma curves.


A comparison of the effects of naloxone upon body weight loss and suppression of fixed-ratio operant behavior in morphine-dependent rats.

Rats were trained to press a lever (respond) under a fixed-ratio 20 schedule for food presentation. Administration of 10 or 25 mg of naloxone (NX) per kg i.p. to drug-naive rats supressed responding whereas 1 mg of NX per kg was without effect. However, administration of 0.25 mg of NX per kg to rats which had received 10 or 15 mg of morphine sulfate per kg 48 hours previously induced small, but statistically reliable, decrements in responding. Rats implanted with one pellet containing 75 mg of morphine base displayed tolerance to the depressant effects of the morphine pellet within 2 days after implantation. A systematic study of the effects of naloxone given to morphine tolerant-dependent rats revealed good concordance between the amount of weight lost and the severity of behavioral disruption, within the same subject, after administration of the antagonist. Although 0.03 mg of NX per kg given 3 to 6 days after pellet implantation significantly suppressed responding, 0.1 mg of NX per kg was required to produce a significant reduction in body weight. Semiweekly injections of 1 mg of NX per kg continued to suppress responding up to 4 weeks after implantation of a single morphine pellet. The body weight changes were significant only up to 3 weeks after implantation. The data suggest that disruption of fixed-ratio responding is a sensitive indicator of antagonist-precipitated morphine withdrawal.


Responses of intradental nerves to electrical and thermal stimulation of teeth in dogs.

1. Experiments were carried out to investigate the mechanism whereby thermal stimul excite nerves to produce pain from teeth. 2. Recordings have been made from single fibres dissected from the inferior dental nerve in dogs during thermal stimulation of the lower canine tooth. 3. In preliminary experiments, no units were found with thresholds close to the thresholds for pain in man (45 and 27 degrees C) and subsequently test stimuli of 55 degrees C, applied for up to 15 sec, and 0-5 degrees C were used. 4. Of 117 fibres tested, forty-three responded to cooling but not to heating and nine responded to heating but not to cooling. 5. By applying thermal stimuli direct to the saphenous nerve in cats, it was shown that these responses might have been due to direct excitation of nerves and not to stimulation of specialized receptors. 6. Some units responded to electrical stimulation of the tooth pulp with a latency which decreased abruptly at a critical intensity as the stimulus was increased above threshold. Evidence was obtained which suggested that this was due to branching of the fibres.


[Splenic arterial aneurysm rupturing into the splenic vein. A rare cause of acute fortal hypertension in the post-partum period (author's transl)].

Following the sudden onset of a clinical syndrome of acute portal hypertension in a young woman in the course of childbirth, angiography revealed a voluminous aneurysm of the splenic artery rupture into the splenic vein. Surgical treatment was successful. The authors review the main characteristics of splenic arterio-venous fistulae and discuss the physiopathological problems of portal hypertension associated with such lesions.


Secretion and reabsorption of uterine luminal fluid in rats.

Treatment of ovariectomized rats with oestradiol-17beta and progesterone demonstrated that oestradiol-17beta causes secretion of sodium, potassium and water into the lumen of the uterine horn and that progesterone causes reabsorption of these substances.


Sexual behavior and plasma androgen concentrations in the male eider duck (Somateria mollissima).

Eider ducks showed clear tidal and seasonal cycles of display when involved in pair-formation behaviour. Plasma androgen (testosterone and dihydrotestosterone) concentrations did not follow similar tidal  cycles but there was a 4-fold increase of androgen in spring when rates of display increased 2-fold. There was no difference in androgen levels in blood samples taken from paired birds before and after coitus. Androgens therefore appear to be essential for the expression of sexual behaviour, but there is no apparent quantitative correlation between overt sexual activity and androgen concentrations.


The effects of inhibitors of energy metabolism on the growth of one-cell rabbit ova to blastocysts in vitro.

Fertilized 1-cell rabbit ova were cultured in the presence of three oxidative phosphorylation inhibitors (cyanide, 2,4-dinitrophenol and oligomycin), two tricarboxylic acid (TCA) cycle inhibitors (malonate and fluoroacetate) and one glycolytic inhibitor (2-deoxyglucose). All three oxidative phosphorylation inhibitors killed ova at the 1-cell stage and the damage caused by each was similar. Malonate was non-toxic at all concentrations whereas some concentrations of fluoroacetate stopped growth at the 1-cell stage. This toxic effect could, in some circumstances, be reversed by the presence of acetate but not of glucose. 2-Deoxyglucose blocked only the transition from morula to blastocyst, and this was prevented by the addition of glucose to the medium; pyruvate, ribose, glycerol, and L-alpha-glycerol phosphate were ineffective. An active oxidative phosphorylation system and tricarboxylic cycle appear to be present and essential in the rabbit embryo from the 1-cell stage, but glycolysis may not be essential until blastocyst formation.


The relationship between sexual and aggressive behaviour, and pituitary and testicular activity during the seasonal sexual cycle of rams, and the influence of photoperiod.

Six adult Soay rams were housed under artificial lighting conditions with alternating 16-week periods of long (16 h light: 8 h darkness) and short days (8L:16D) During long days the rams were reproductively quiescent: the abrupt change from long to short days induced a specific succession of responses in the reproductive system. Plasma LH and FSH levels began to increase after 2-4 weeks, followed almost immediately by a rise in plasma testosterone levels accompanied by growth of the testes. Testicular activity continued to increase during short days and the greatly elevated androgen levels apparent after 5-10 weeks caused changes in the peripheral target organs, including growth of the epididymides, development of the sexual flush on the exposed ventral skin and heightened genital sensitivity. High testosterone levels were also associated with an increase in aggressive (scored by a mechanical device) and sexual (incidence of Flehmen) behavior which was at peak about 1 month after the start of the peak androgen levels. The change to long days was associated with a decrease in plasma gonadotrophin levels within 2 weeks followed by a progressive decline in all reproductive parameters measured. Implantation of a low dose of testosterone (200 mg) during the period of reproductive quiescence induced the development of the sexual flush and an increase in genital tactile sensitivity, although behaviour was not significantly affected. The annual changes in reproductive physiology and behaviour of 12 Soay rams living under natural lighting conditions were recorded for comparison with the experimental situation. The nadir of the sexual cycle was in the spring and early summer, and the sequence of events culminating in the mating season in the autumn was similar to that induced experimentally.


The separation of lipoproteins from egg yolk and their effect on the motility and integrity of bovine spermatozoa.

Lipoproteins were separated by centrifugation and column chromatography and included in citrate-based semen diluents. One lipoprotein fraction was particularly effective in preventing injury to bovine spermatozoa during dilution and freezing and thawing when assessed using motility and release of hyaluronidase as criteria of cell damage. Radioactive labelling of egg-yolk lipids demonstrated that egg-yolk components remained associated with spermatozoa even after extensive washing to remove diluent. The patterns of labelling of lipids extracte from the washed spermatozoa did not indicate that particular lipids became associated with spermatozoa. Increases in the specific radioactivity of lipid extracts from washed spermatozoa lent support to the contention that lipoproteins become firmly bound to the cells.


The sexual behaviour of prenatally androgenized ewes observed in the field.

Pregnant ewes were implanted with 1 g testosterone between Days 30-80, 50-100, 70-120 or 90-140 of gestation. Treatments which began on Days 30, 50 or 70 resulted in the birth of androgenized females which failed to show regular oestrous cycles in adult life, but which exhibited patterns of male-like behaviour. This was most marked in the Day 50-100 and 70-120 groups, whereas complete masculinization of the external genitalia was confined to the Day 30-80 group. Animals in the Day 90-140 group had regular oestrous cycles although they showed slight enhancement of masculine behaviour compared to the control ewes. These results demonstrate that androgenization involves both a suppression of female behavioural patterns, and the development of male patterns; these are not mutually exclusive.


Assessment of relative fertility of males (cockerels and boars) by competitive mating.

When hens were inseminated with an equal number of spermatozoa from one of 3 Leghorn (L) and one of 3 Columbian (C) cocks in the 9 possible L and C combination, a hierarchy of fertility was established based on the proportion of chicks sired by each cock. A similar hierarchy was established for 3 Duroc (D) and 3 Yorkshire (Y) boars by mating gilts in rapid succession to one D and one Y boar. A second hierarchy of fertility was established by inseminating hens with 40 x 10(6) spermatozoa from only one cock or by mating gilts to only one of the boars. The hierarchies for the cocks and boars were essentially the same for each method. Minor discrepancies were observed for males which appeared to be nearly equally fertile when used alone or in combination with another male. After homospermic insemination, the hierarchy of cocks was identical whether the ranking was based on the percentage of eggs fertilized or on hatchability of fertilized eggs. Similarly, the boars ranked highest in fertility by double mating had higher conception rates, higher embryonic survival rates and larger litter sizes when used alone. Heterospermic insemination and double mating appear to be more efficient and sensitive than methods of estimating fertility which depend on homospermic insemination of high or low numbers of spermatozoa, single matings or the examination of various characteristics of semen. The method of heterospermic insemination or double mating offers a simple and effective method of assessing the relative fertility of males.


Plasma progesterone and LH concentrations in ewes after injection of an analogue of prostaglandin F-2alpha.

Plasma progesterone and LH concentrations were monitored throughout a natural oestrous cycle in 12 Clun Forest ewes and compared to those following treatment with a single i.m. injection of 100 microng ICI 80,996, an analogoue of prostaglandin F-2alpha, given during the luteal phase of the cycle. After injection of the analogue there was a high degree of synchrony in the return of oestrus (440 +/- 1-9 h; mean +/- S.E.M.) and the timing of the LH peak (48-5 +/- 2-0 h) from injection. There were no significant differences in the plasma progesterone concentrations or in the height and duration of the preovulatory LH peak between control and treatment cycles. The technique offers the possibility of controlled ovulation in the ewe.


Nitrones. 7. alpha-Quinoxalinyl-N-substituted nitrone 1,4-dioxides.

A series of alpha-quinoxalinyl-N-substitute nitrone 1,4-dioxides has been synthesize and evaluated as antibacterial and antiprotozoal agents. Structure-activity relationships are discussed. Of the compounds tested, alpha-(3-methyl-2-quinoxalinyl)-N-methylnitrone 1,4-dioxide (2) was the most active agent in vivo against the gram-negative and the gram-positive organisms.


Tetramisole analogues as inhibitors of alkaline phosphatase, an enzyme involved in the resistance of neoplastic cells to 6-thiopurines.

A series of tetramisole derivatives was synthesized and tested for inhibitory activity against alkaline phosphatase which was partially purified from a murine ascitic neoplasm resistant to 6-thiopurines (Sarcoma 180/TG). These agents included derivatives substituted with halogens, CH3, or NO2 groups at either the meta or para position of the phenyl ring of tetramisole and 2,3-dehydrotetramisole. The phenyl ring of tetramisole and 2,3-dehydrotetramisole was also replaced by a naphthyl ring, and the phenyl ring of 2,3-dehydrotetramisole was substituted by a thienyl ring system. The presence of both the thiazolidine and dihydroimidazole rings of tetramisole was found to be essential for enzyme inhibitory activity. Substitution of a naphthyl for the phenyl group and dehydrogenation at the 2,3 position of the thiazolidine ring were found to significantly enhance inhibitory activity for alkaline phosphatase. Tests employing (S)-(-)-6-(4-bromophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole oxalate in combination with 6-thioguanine demonstrated that the inhibitor of alkaline phosphatase was capable of increasing the toxicity of 6-thioguanine to Sarcoma 180/TG cells in tissue culture.


4-Halovinyl- and 4-ethynyl-4-deformylpyridoxal derivatives and related analogues as potentially irreversible antagonists of vitamin B6.

Analogues of pyridoxal bearing alpha- and beta-chlorovinyl, beta-bromovinyl, butadienyl, acetyl, and 1-butenyl groups in place of the formyl group have been synthesized by subjecting 3,alpha5-di-O-benzylpyridoxal to appropriate Wittig or Grignard reactions. Similar methods yielded one-carbon homologues of pyridoxal and pyridoxol. Synthesis of the 4-ethynyl analogue of pyridoxal was achieved by dehalogenating blocked beta-halovinyl derivatives. The substituted vinyl and the ethynyl analogues were found to be active as inhibitors of mouse mammary adenocarcinoma cells grown in cell culture at an ID50 of 10(-5)-10(-6) M. The inhibitory activity of the 4-ethynyl analogue could be partially reversed by pyridoxal. This analogue was found to inhibit pyridoxal phosphokinase, and its 5'-phosphate was likewise found to be a potent noncompetitive inhibitor of pyridoxine-P oxidase.


Production of carcinoembryonic antigen by human prostate epithelial cells in vitro.

The medium from all 16 human prostate epithelial cell cultures tested contained elevated levels of carcinoembryonic antigen (CEA) or CEA-like substance; 11 of 16 had greater than 20 ng CEA/ml. In contrast, medium from cultures of other human tissues (prostate fibroblasts, genitourinary tumors, melanoma, and nontumor tissue), as well as media controls, contained less than 1 ng CEA/ml. Results indicated that CEA determination may provide a way to identify human prostatic epithelium in culture.


Oncogenicity of a nude mouse cell line transformed by a human papovavirus.

Primary cultures of NIH nude mouse (nu/nu) kidney cells were transformed with a human papovavirus (MMV). The transformed cell line expressed T-antigen, and MMV DNA was found to be associated with the cell DNA. When NIH nu/nu mice were inoculated with the transformed cells, they developed tumors at the injection site but failed to generate detectable levels of T-antibody. A control group of nu/+ littermates rejected the tumor inoculum but mounted an antibody response to T-antigen. It was proposed that nude mouse cells may be a suitable system to test oncogenicity of in vitro transformed cells.


Reversal by vitamin A analogues (retinoids) of hyperplasia induced by N-methyl-N'-nitro-N-nitrosoguanidine in mouse prostate organ cultures.

The antihyperplastic activity of beta-retinoic acid (RA) and nine synthetic analogues (retinoids) was examined in organ cultures of mouse prostate made hyperplastic by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After 8 or 10 days, when most explants developed hyperplasia, the carcinogen was withdrawn and explants were incubated in control medium and medium containing different concentrations of a retinoid. The antimitotic activity of retinoids was compared with that of RA. Different retinoids produced variable degrees of mitotic inhibition in the hyperplastic prostate epithelium. The methylketo cyclopentenyl and 1-methoxyethyl cyclopentenyl analogues of RA were at least 50-fold more active than RA in reversing MNNG-induced hyperplasia. The trimethylmethoxyphenyl analogue of RA and retinyl methyl ether were significantly more active than RA. Three analogues, N-acetyiretinylamine, retinal acetyl hydrazone, and retinal oxime, were as active as RA. The chlorotrimethylphenyl analogue showed less activity than RA, and alpha-retinyl acetate was completely devoid of mitotic inhibitory activity.


Lipids of rabies virus and BHK-21 cell membranes.

The lipid composition of highly purified Flury strain of rabies virus (HEP) propagated in BHK-21 cells in a chemically defined medium was observed to be 6.7% neutral lipids, 15.8% phospholipids, and 1.5% glycolipids. In the virion, phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin were the most abundant phospholipids, accounting for 90% of the total, and the molar ratio of cholesterol to phospholipid was 0.48. Uninfected BHK-21 cell membranes were obtained by nitrogen cavitation techniques and separated by density gradient centrifugation, and the membranes were assayed for purity using 5'-nucleotidase, cytochrome oxidase, and reduced nicotinamide adenine dinucleotide phosphate diaphorase activities. Lipids of the plasma membrane were enriched in cholesterol, phosphatidylcholine, and phosphatidylethanolamine. In contrast, membranes of the endoplasmic reticulum were enriched in phosphatidylcholine, but contained smaller amounts of phosphatidylethanolamine and sphingomyelin. Comparison of the fatty acyl chains of virus and membranes from uninfected cells revealed the virion to have the lowest ratio of C18:1 to C18:0 (1.771), compared with values of about 3.0 for the plasma membrane and endoplasmic reticulum. Total polyenoic fatty acids were enriched in the plasma membrane, whereas the virus contained higher amounts of total saturates than either of the two membrane preparations. Analysis of the polar and neutral lipid fractions as well as the acyl chain analysis suggests the virion has a lipid composition that is intermiediate to that of the plasma membrane and endoplasmic reticulum and is consistent with the view that numerous viral particles are synthesized de novo by not utilizing a preexisting membrane template. From the ratio of cholesterol to phospholipid of 0.48, we calculated that 1.92 X 10(5) molecules of lipid would cover 4.14 X 10(4) nm2 in the form of a bilayer. Considerations of the molecular dimensions of the rabies envelope (total surface area, 5 X 10(4) nm2) as a bilayer suggest that some penetration of lipids by envelope proteins (M and G) is necessary.


[A report on ocusert (author's transl)].

The fourth communication on the Ocular Therapeutic System Ocusert (Alza Corp., Palo Alto/Calif.; Federal Republic of Germany: Chemie Grünenthal, Stolberg) deals with experiences of a 24 months follow-up study as well as with the results of an omission test. From the diurnal curves carried out over 24 months, and the regression curves the conclusion can be drawn that the continuous application of pilocarpine has not led either to clinically recognisable changes in morphological structures or to a noticeable decreasing sensitivity to the drug so far. The omission test performed with placebo units shows the effect of intraocular pressure reduction remains reversible.


[The immunological characterization and isoelectric focusing of water-soluble proteins in the lens related to aging (author's transl)].

Immunelectrophoresis, antigen/antibody crossed electrophoresis and isoelectric focusing are applied to characterize lens crystallins. Using isoelectric focusing alpha-, beta- and gamma-crystallins are determined in bovine lens nucleus and equator. The data obtained are compared with those of rat and human lenses. In these three species a disappearance of specific beta- and gamma-crystallin components is observed depending on age. Further, the presence of crystallins is demonstrated in cornea and vitreous body.


[Immunoblastic lymphadenopathy--malignant neoplasia or hyperimmune reaction? (author's transl)].

Six patients have been observed which exhibited the features of the so called immunoblastic lymphadenopathy. The histological and clinical findings allow to distinguish the disease from both the malignant lymphomas and other forms of benign pseudolymphomas. The most important clinical features are severe general symptoms, generalised lymphadenopathy, hepatosplenomegaly, skin rash and a variety of abnormal reactions in the B-cell system such as hypergammaglobulinaemia, a transient positive Coombs test and the appearance of plasma cells in the peripheral blood. Evidence for a neoplastic nature of the disease is lacking. Nevertheless, the course of the disease may be progressive and fatal, but spontaneous remissions and subsequent relapses have also been essential part of the therapeutic strategy. Immunosupressants such as corticosteroids may have a positive effect in cases with immunological complications.


Effects of Aspiculuris tetraptera dn Syphacia obvelata on exploratory behavior of an inbred mouse strain.

Sixty C57BL/6 male mice were treated with an anthelmintic for 2 weeks to free them of pinworms. They were then divided into six groups. Two groups were infected with Aspiculuris tetraptera, two groups with Syphacia obvelata, and two groups were left uninfected as controls. At intervals of 2 and 4 weeks after infection, the mice were tested for exploratory activity in a barriered field apparatus. Following the second test, each mouse was necropsied to determine presence of nematodes and to estimate worm burdens. Statistical analysis showed significant depression of exploratory activity in mice harboring S obvelata. No significant depression was found in those harboring A tetraptera.


Heat dissipation biorhythms of laboratory animals.

Body heat dissipation rates were determined in greyhound and beagle dogs, the rabbit, and the rat. Each group of animals was confined in standard cages in a controlled environment room maintained under conditions of 24 degrees C, 50% relative humidity, and fixed ventilation rats. Food and water were available ad libitum. Heat dissipation rates were determined for each group and normalized to an individual animal basis. The ratio of actual heat dissipation to standard metabolic rate, the metabolic heat ratio, was 2.01+/-0.18 for the greyhound, 1.98+/-0.03 for the beagle, 2.66+/-0.20 for the rabbit, and 1.95+/-0.13 for the rat. For each species, the ratio displayed a 24-hour cyclic pattern in which four contiguous maximum values differed significantly from four contiguous minimum values. The ratios of maximum values to minimum values were between 1.54 and 1.75.


Morbidity and mortality in a closed foxhound breeding colony.

A 3-year mortality and morbidity survey was conducted in a research foxhound breeding colony. Its purpose was to identify specific problem areas for further study and rectification. Three-hundred and thirty-nine litters (2,872 puppies) were whelped. Seventeen percent (17.4%) of the puppies died before weaning and 4.0% died between weaning and 30 weeks of age. Major puppy losses (55.6% of the total mortality) occurred during the 1st week after birth. The majority of deaths during this period was attributable to stillbirth, immaturity or runting, trauma and congenital abnormalities. The predominant causes of death thereafter were pneumonia, malnutrition, and gastrointestinal disease. The most frequent causes of morbidity among puppies were respiratory disease, anorexia and dehydration, skin disorders, and gastrointestinal disease. These entities were most commonly observed during the 2 weeks before and after weaning at 6 weeks of age. Clinical disease problems among breeding stock were few and were easily resolved. Fighting and infections of the skin and ear canals constituted 75.5% of the cases observed.


Nursery rearing of infant monkeys (Macaca fascicularis) for toxicity studies.

At birth, nine infant male cynomolgus monkeys (Macaca fascicularis) weighed an average of 402 g and 16 infant female cynomolgus monkeys weighed an average of 362 g. Both female and male infants last 15-20 g by the fourth day after birth. Female and male infants showed a growth rate of approximately 4 and 5 g body wt/day, respectively, from 4 to 150 days of age. Caloric intake increased from approximately 140 cal/gkg body weight/day in both females and males on the first day after birth to peak values of 325 and 290 cal/kg body weight/day in females and males, respectively, and subsequently declined to about 200 cal/kg/day in males and 250 cal/kg/day for females. Total calories consumed per day increased from 53 cal/day in females and 68 cal/day in males to approximately 200 cal/day after 60 days of age in both females and males. Erythrocyte counts, packed cell volume, and hemoglobin values decreased from birth to 2 weeks of age, then stabilized. An increase in lymphocyte count, with a concomitant decrease in mature neutrophils, was observed from birth to 6 weeks of age. "Temper fits" and certain aggressive behavioral signs were observed as early as 3-4 days after birth, and infants began to develop social orders as early as the 30-40th day. Behavioral abnormalities frequently seen in infants reared in isolation were not observed.


CO2 laser as a clinical tool in otolaryngology.

The CO2 laser has been used in a variety of lesions for two and one half years in areas other than the larynx. These lesions include viral papillomas, leukoplakias and erosive lichen planus in various otolaryngological sites. Laser therapy is compared with other modalities of treatment for similar lesions and the advantages and disadvantages of this type treatment is evaluated.


The nonpolar egg wax lipids of the cattle tick, Boophilus microplus (canestrini).

About 40% of the lipids of the egg wax of Boophilus microplus are nonpolar and comprise hydrocarbons (10%) and wax esters (90%). The hydrocarbon fraction is 87% unbranched alkanes, the major components being n-nonadecane (10.8%), n-eicosane (12.1%), and n-heneicosane (9.8%). This fraction also contains 2,4,6-cholestatriene (4.6%). The majority of the acids are branched (77%) the major components being 12-methyl-tetradecanoic (16.3%) and branched hexadecanoic acids (28%). The major alcohols are n26:0 (20.4%), n28:0 (47.3%) and n36:0 (18.2%). A steroid possibly 2,4,6-cholestatrien-25-ol (5.6%), is also present.


Serum prolactin levels in normal women and in women with disorders of menstruation.

The mean (+/-SD) serum prolactin (PRL) level of 78 normal premenopausal women was 10-6+/-3-0 ng/ml, and this was significantly different from that of post-menopausal women (8-2+/-4-0 ng/ml) and women taking combined oral contraceptive preparations (12-2+/-4-0 ng/ml). No significant differences were found between follicular and luteal phase PRL levels. Serum PRL levels higher than the ranges given above were found in 31 of 87 patients with secondary amenorrhoea and two of 41 patients with oligomenorrhoea. Nine of the 33 patients with hyperprolactinaemia did not have galactorrhoea. Only two of the patients with hyperprolactinaemia had pituitary tumours evident on skull X-ray films. Serum PRL levels were of value in predicting the likely success in achieving ovulation with clomiphene citrate or CB-154; clomiphene citrate was less likely to be successful in the presence of hyperprolactinaemia, whereas the reverse applied for treatment with CB-154.


The changing clinical presentation of coeliac disease in adults.

A diagnosis of coeliac disease was confirmed in 57 patients referred to a gastroenterology clinic over a 5 1/2-year period. Although diarrhoea was present in two-thirds of the patients, this was the major symptom leading to referral in less than half of them. When present, diarrhoea was usually intermittent and frequently not typical of steatorrhoea. Symptoms were of less than six months' duration in half the patients, but a review of the past and family history strongly indicated the possibility of coeliac disease in 39 of the 57 patients. A high spontaneous abortion rate during pregnancy was noted. The frequent absence of the classical features of malabsorption, diarrhoea with typical steatorrhoea and chronic debility was noted. All screening tests for malabsorption were found to be unreliable and their routine use was rarely justified. A random serum folate and carotene assay proved as valuable as more expensive and troublesome tests. It is stressed that in any case in which there is a clinical suspicion of this diagnosis, a small intestinal biopsy should be undertaken.


Malformations in infants of very low birth weight.

The incidence of lethal, serious and trivial malformations was determined in a consecutive series of 675 infants who weightd 1500 g or less (very low birth weight infants). All patients were born in one maternity hospital. Most of the 169 survivors were followed until at least five years of age. Of these children, 15 had a trivial malformation that either disappeared spontaneously or was corrected surgically. A further five children have a significant or serious residual defect. There were 506 perinatal and infant deaths and 51 of the babies who died had malformations confirmed at necropsy. In 30 of these, death was inevitable. There were 10 seriously malformed infants for whom survival was possible, but in six cases, the diagnosis was obvious at birth. The patients were treated between 1966 and 1970 when techniques of intensive care were evolving. Consequently, some of the infants who died would have survived with the treatment now available. Amongst the perinatal deaths in this report, only 2.0% had a serious malformation compatible with survival.


5'-Terminal structure and mRNA stability.

Reovirus mRNAs with 5'terminal m7GpppGm or GpppG are more stable than mRNA containing unblocked ppG 5'-ends when injected into Xenopus laevis oocytes or incubated in cell-free protein synthesising extracts of wheat germ and mouse L cells. The greater stability of mRNA with blocked 5' termini is not dependent upon translation but seems to result from protection against 5'-exonucleolytic degradation.


[Dimer-X in the intracranial subarachnoid space - electrocorticographic study (author's transl)].

As a sequel to our first report, we are now presenting the results of the ECoG examination of the rats in about 15 min. after injecting Dimer-X into their cisternae magnae. The injection of 28% iodine Dimer-X into the cisterna magna causes the multiple bursts of spikes, but the occurrence is less frequent when the low concentration of Dimer-X are injected. The ECoGs show occurence of a few spikes with the premedication of Valium or Decadron, and very few spikes are seen on the ECoG, when Valium and Decadron are given as a premedication. From these results as seen on ECoG, we conclude that during Dimer-X ventriculography lw concentration of Dimer-X should be used with premedication of Valium and Decadron.


[Clinical study on penetration of antibiotics into cerebrospinal fluid (second report),-Study on intravenous administration of sodium cephalothin with mannitol solution (author's transl)].

Penetration of Sodium Cephalothin (CET) into CSF follwing intravenous administration was studied in 23 patients with intracranial diseases excluding inflammation and severe subarachnoid hemorrhage. 1) After intravenous injection of 2 g of CET, ventricular CSF was obtained in 4 cases. All these 4 cases showed CET concentration in CSF to be below 0.1 mcg/ml. 2) After intravenous injection of 2 g of CET, lumbar CSF was obtained in 6 cases. In two cases out of these 6 cases, CET concentration in CSF was higher than 0.7 mcg/ml. 3) In 13 cases 2 g of CET with 200ml of 20% Mannitol was injected intravenously and lumbar CSF was examined. CET concentrations in CSF between 0.7 mcg/ml and 6.0 mcg/ml were observed in 9 cases of this group. 4) According to the results it is strongly suggested that the administration of Monnitol and CET is very effective for penetration of CET into CSF.


[A case of hypertensive intracerebral hemorrhage associated with cerebral arteriovenous malformation and aneurysm (author's transl)].

A 45-year-old man suddenly developed right hemiparesis and aphasia during work and lost conciousness next day, when he was admitted to us. Lumbar puncture showed bloody C.S.F. with the initial pressure of 220 mm H2O. Physical examination revealed hypertension and arteriosclerosis. Cerebral angiogram revealed an arteriovenous malformation in the left frontoparietal-parasagittal region and a saccular aneurysm at the left internal carotid-posterior communicating artery junction. In addition, the existence of putaminal hematoma was suspected on account of the displacement of the left anterior cerebral artery and the left lenticulostriate arteries. On the fourth day after admission his consciousness returned and the right hemiparesis gradually improved. One month later the disappearance of the displacement of the anterior cerebral artery was demonstrated by cerebral angiogram. A frontoparietal craniotomy was done and no hematoma was found around the arteriovenous malformation and the basis of the aneurysm did not adhere to the temporal lobe. Taking these findings into consideration, it is presumed that the hematoma in putaminal region was due to neither arteriovenous malformation nor aneurysm but was a hypertensive intracerebral hemorrhage.


[Dural arteriovenous malformation in posterior fossa treated with artificial embolization using a liquid silicon rubber, phycon (author's transl)].

Many cases of dural arteriovenous malformation have been reported recently. However, the surgical treatment for these diseases has not been established yet. We propose a new method of treatment on this peculiar vascular diseases, that is one of the artificial embolizations; A catheter is inserted into feeding artery, from which liquid silicon rubber, Phycon, is injected. The rubber is hardened in the vascular net-work. It can not pass into drainer because of its viscosity. Therefore the malformation never develope again. We tried this new method on 46-year-old woman, who suffered from subarachnoidal bleeding, tinnitus and headache. The left common carotid and vertebral angiography revealed dural arteriovenous malformation in posterior fossa (Fig. 1); the feeding arteries of which were middle meningeal arteries, occipital artery, and tentorial artery, etc; the drainers were transverse and sigmoid sinuses. We treated for this case with above-mentioned method; The liquid plastic of 1 - 2 ml injected into each of the main feeding arteries, namely two middle meningeal arteries and occipital artery. Postoperative angiograms revealed this technic was convenient and sufficient for the treatment of dural arteriovenous malformations (Fig. 7).


[Calcified epidural hematoma-report of a case incidentally found 16 years after head injury (author's transl)].

A calcified epidural hydroma, or old hematoma, was incidentally found in the left parietal region of a 55-year-old man presenting status epilepticus due to uremia after a lapse of 16 years following head injury. The hydroma (10x7x1.2 cm) was extirpated operatirelly. There was an extensive calcificantion in the wall, and the outer wall showed bone-like metaplasia and hemosiderin deposit. No skull fracture was discernible. The dura and the brain surface neighboring the hydroma were gloslsly normal. The patient eventually died of uremia.


[Subdural hematoma after cerebrospinal fluid shunt for hydrocephalus following subarachnoid hemorrhage-report of two cases (author's transl)].

Post-shunt subdural hematoma was found in two patients with hydrocephalus due to subarachnoid hemorrhage. The first case was a 46-year-old man with two episodes of subarachnoid hemorrhage from anterior communicating aneurysm. Two weeks after neck-clipping for the aneurysm, a ventriculo-peritoneal shunt with Pudenz's system was performed since hydrocephalus with moderately increased pressure had been found. He did well for one month, then soon after mild head injury, disorientation and right hemiparesis developed. Cerebral angiogram revealed avascular space in the left parietotemporal region. After the ligation of the shunt tube, subdural hematoma was removed. The symptoms improved in two weeks. The second case was a 62-year-old man with an aneurysm at the trifurcation of the right middle cerebral artery. One month after successful clipping of the aneurysm, he received a ventriculoperitoneal shunt with Pudenz's system for normal pressur hydrocephalus. One and a half years after the operations he hit his head against the ground during his convulsive seizure. Since then, disorientation, urinary incontinence and gait disturbance appeared. After cerebral angiogram, the subdural hematoma was removed and the shunt tube was ligated. He became free of these symptoms in two weeks. The cerebrospinal fluid shunt is recommended for hydrocephalus induced by subarachnoid hemorrhage, but careful follow-up is necessary since these patients might develop post-shunt subdural hematoma, especially after head trauma as shown in our cases.


[The association of intracranial meningioma with arteriovenous malformation and aneurysm (author's transl)].

A rate case was reported in which a brain tumor was also found in a patient who had an intracranial arteriovenous malformation and a cerebral aneurysm separately. A 56-year-old man was admitted with motor weakness and repeated convulsions in the left lower limb. Preoperative right and left carotid angiograms showed an arteriovenous malformation in the left parietal region and a left internal carotid artery aneurysm, but both the carotid angiograms and brain scintigrams could reveal no brain tumor. After the radical operation for these two lesions, pneumoencephalography, right serial carotid angiography and brain scintigraphy were performed, demonstrating a right parasagittal tumor. The tumor was totally removed and histological findings were fibrous meningioma.


[Incidentally-discovered aneurysm--a report of eight cases (author's transl)].

There have been only a few reports of asymptomatic aneurysm clinically treated up to the present. The authors incidentally found eight cases of intracranial aneurysm: five cases with brain tumor, one with brain abscess and the remaining three with head injury. It may be considered that the careful observation of angiograms could reveal more asymptomatic aneurysms. The ideal treatment of aneurysm should be direct operation before rupture. But it is difficult to find out them before the onset of signs and symptoms of subarachnoid hemorrhage or cranial nerve involvement. The only chance of finding asymptomatic aneurysm is brought about by paying special attention to aneurysm even in angiography for other intracranial diseases such as tumors, head injuries, vascular diseases and so on. It was thus concluded that incidentally-discovered aneurysm should be directly treated if the prognosis of the original disease is thought to be good. The authors operated on four aneurysms of three patients and operative result was excellent.


[Spinal subdural abscess-report of a case (author's transl)].

A successfully treated case with a spinal subdural abscess in the lumbar region is reported. The patient, a 58-year-old male, had been suffered from fever and pain in the back for 2 months prior to the visit to a hospital, where pus was obtained through a lumbar puncture. He was then admitted to the Neurosurgical Clinic, Gunma University Hospital on September 6, 1974. On admission, neurological examination revealed an alert patient with flaccid paraparesis, sensory disturbance in bilateral lower limbs and urinary retention. Stiffness of the neck and Lasègue's sign were observed. The body temperature was 38.7 degrees C, white blood cell count 18,900/mn3, and erythrocyte sedimentation rate 118 mn per hour. Pus was again obtained from the spinal canal through a lumbar puncture between the fourth and fifth lumbar vertebrae. Cerebrospinal fluid obtained by a cisternal puncture was colorless clear, and the cell count was 60 WBCs/mn3, protein 154 mg/dl, and glucose 90 mg/dl. Plain roentgenograms of the spine were normal. Myelography showed a block at the level of the first thoracic vertebra, being accompanied with irregular subarachnoid defects. A lumbar laminectomy was performed on September 12, and an abscess adhering to the cauda equina was totally extirpated from the subdural space. Smear of the pus contained Gram-positive bacilli, but the culture was negative. Postoperative course was uneventful, and the neurological deficits were gradually improved. Fifteen months later, the patient could walk with a stick. A review of the available literature, including the present report, lists 14 cases with spinal subdural abscesses which have been induced via hematogenous spread. The symptomotology, clinical diagnosis, treatment and prognosis are briefly discussed. It should be emphasized that early diagnosis and emergency treatment are of choice in order to obtain an excellent operative morbidity.


[Cerebral polyuric hyponatremia--discussion of a new syndrome with disturbance of electrolyte balance of central origin (author's transl)].

We have experienced with 50 cases of parasellar tumors, four cases of which had persistent thirst, polydipsia, polyuria, and reversible temporary hyponatremia secondary to hypernatriuresis. The mechanism of the syndrome in these four cases could not be explained by either that of the syndrome of hypernatremia or of the so-called SIADH. We tentatively named this syndrome as "CEREBRAL POLYURIC HYPONATREMIA" and the criteria of this syndrome as as follows: 1) persistent thirst, polydipsia polyuria, 2) reversible temporary hyponatremia secondary to hypernatriuresis, 3) exception of the following items--administration of uretic drugs, renal and adrenal dysfunction, hyperglycemia, hyperlipemia, overadministration of water, and poor administration of NaCl. The mechanism of this syndrome is presumed as follows: 1) compression by a tumor or surgical attack to the anterior hypothalamus, 2) disturbance of the mechanism of ADH secret-on, 3) extrasecretion of natriuretic factor possibly produced in the anterior hypthalamus, and 4) preservation of the thirst center.


[Simplfied technique of lumbar subarachnoid-peritoneal shunt (author's transl)].

The authors have developed a simplified technique of lumbar subarachnoid peritoneal shunt in which the spinal tube is easily introduced through a puncture needle without doing a laminectomy. Seventeen cases of communicating hydrocephalus of various orgin have been treated by this procedure. In this paper, we reported our shunting system and the technique of precedures, and discussed the clinical results and some advantages of this method. The spinal tube is a custom made Silastic tube with small side holes 2 mm apart from each other at slanting tip located within the first 1.0 cm of the end. French No. 5 tube is available for older children and for adults, and French No. 3.6 tube for infants. Total length of the tube measures 30 cm with 4 black markers at 5 cm intervals from the tip for assisting in positioning. The puncture needle is a modified Touhey needle. Two needles different in size are prepared according to the size of the tube. Outer diameter of these needles is 2.1 mn & 1.8 mn. Our operative procedures are divided into following three steps. 1) Puncture of the lumbar subarachnoid space and insertion of the spinal tube through the needle. 2) Introduction and placement of the peritoneal tube into some point of the peritoneal cavity. Concerning to this point, we have the three candidates, namely into the Douglas pouch, the suprahepatic space, and the bursa omental cavity. 3) Connection of the spinal tube and the peritoneal catheter end. We used a kind of flushing device only in some exceptional cases, and recently, we feel that it is not so necessary for this shunting. We have employed this technique in a total of 17 cases. Eleven cases of them are adults and the other 6 cases are children less than 2 years of age. Postoperative follow up period varied from 13 months to 1 month, and all the cases except two had good result, suggesting the shunt system is working well with no evidence of complications such as low pressure syndrome or radicular irritation. Some troubles occurred in two children. One was a disconnection between the spinal and the peritoneal tube, and the other was an obstruction at the peritoneal tube end. The authors believe that our L-P shunt has several advantages as listed below, 1)Procedure is very simple, in other words, there is no need of laminectomy. 2) The entire system is short. 3) No need to pass the catheter into the brain tissue. 4) Obstruction of the spinal catheter end is very unusual. 5) Alteration of communicating hydrocepalus into non communicating one by secondary obstruction of aqueduct of Sylvius is less likely with this shunting system. 6) Siphon effect might be minimal, if present. 7) As compared to V-A shunt, severe complication like septicemia will not occur in the L-P shunt. With this simple method and good material, we hope that this L-P shunt is employed more widely for the patients with communicating hydrocephalus.


[Post-shunt subdural hematoma in infants and children--analysis of eleven cases (author's transl)].

Out of 122 hydrocephalic infants and children treated by cerebrospinal fluid shunt, post-shunt subdural hematoma was found in 11 patients in total, 8 cases with non-tumorous hydrocephalus and 3 cases with brain tumors obstructing the cerebrospinal fluid pathway. In most cases the diagnosis of subdural hematoma was delayed since signs of increased intracranial pressure were absent initially. The signs of increased intracranial pressure appeared later, when the shunted venricle collapsed and could not give any more space to the growing subdural hematoma. At this stage those cases were easily misdiagnosed as shunt dysfunction. Post-shunt subdural hematoma was apparently induced by the tear of the bridging vein or leakage of the cerebrospinal fluid into the subdural space through the torn arachnoid membrane due to over-drainage of the cerebrospinal fluid, especially when the patients took the erect position. Since such a complication is not rare and difficult to be diagnosed, intensive follow-up is necessary in the post-shunt period. The precautionary measures as well as the treatment for these subdural hematoma were also discussed.


[Radiological diagnosis of the lateral ventricle tumor (author's transl)].

The radiological characteristics of intraventricular tumors were studied with special reference to differential diagnosis from paraventricular tumors by careful analysis of seven cases intraventricular tumors and five cases paraventricular tumors. As, in the radiological term, intraventricular tumors have been dividied into two groups according to their location by Bernasconi et al., seven cases intraventricular tumors reported in this paper were also divided into two groups; 1) 2 cases ependymom occupying the frontal horn and the body of lateral ventricle, 2) 4 cases meningioma and one plexus papilloma occupying the trigone and the adjucent regions. In case of tumors belonged to group 1, the filling defect showing the circumference of tumors and the associated unilateral hydrocephalus were characteristic findings on the ventriculogram, while the depression of ventricular wall was observed in paraventricular tumors. Angiographic characteristics in group 1 tumors were the splay of subependymal veins of the medial group from those of lateral group and the increased density of deep veins due to raised circulation, and these findings demonstrated in all cases of ependymoma reported here. On the other hand, in all meningiomas belonged to group 2, the hypertrophia of choridal arteries was noticed in the angiogram. Moreover, the anterior choroidal artery was shown to be divided into two branches at its plexal segments, and the tumor stain at the trigone always lied between these two branches. We named this dissociation of these two plexal branches due to tumor as "flare sing". This is considered to be specific finding for a trigone meningioma, and this "flare sing" was observed in all of our 4 cases meningioma. In two cases out of four, the inferior ventricular vein was displaced anteriorly delineating the anterior margin of the tumor. This again is considered as a sign indicating the tumor occupying the trigone and adjacent regions.


[The usefulnessof STA-MCA anastomosis in trapping vascular disorder (author's transl)].

Huge aneurysm taking place within the cavernous sinus or at the junction of the internal carotid artery with the ophthalmic artery must be treated by intra- and extracranial ligation of the internal carotid artery because of its anatomical specificity, if it is to be radically treated. Carotid-cavernous fistula which cannot be cured by embolization must also be treated by ligation of the internal carotid artery. However, if there is only a poor collateral circulation over the area distal to ligated portion, the operation surely incurs severe neurological deficit, so that trapping must be abandoned in such cases. Nevertheless, by establishing a bypass through anastomosis between the superficial temporal artery and the middle cerebral artery, the operation can be done safely. Further, even in cases of aneurysm taking place on the cerebral main vessel in which the aneurysm must be extirpated despite the presence of an important branch shooting-off from the aneurysm, or in some other cases (sphenoidal ridge meningioma, for instance) in which total extirpation of the tumor must necessarily be associated with sacrifice of the main vessel because it is involved in the brain tumor, we think that the operation can be performed rather safely through anastomosis with the vessel to be sacrificed. Some representative examples of such cases are described, and the usefulness of anastomosis between the superficial temporal artery and the middle cerebral artery in trapping of vascular disorders.


[Effect of extracranial-intracranial vascular bypass formation on experimental cerebral infarction in dogs (author's transl)].

The middle cerebral artery was occluded at its origin via subtemporal approach by microsurgical technique in 24 dogs. In 8 of these 24 dogs, end-to-side anastomosis between the maxillary artery and a branch of the middle cerebral artery (MA-MCA anastomosis) was made 4 hours after MCA occlusion. In 5 dogs, MA-MCA anastomosis was performed under microscopic control 3 weeks after MCA occlusion. Remaining 11 dogs without shunt operation were used as control animals. All the animals were clinically observed every day until sacrifice. In the control animals, common carotid angiography was performed between the 2nd and the 5th postoperative weeks. The treated animals were studied by selective external carotid angiography 2 weeks after MA-MCA anastomosis. After sacrifice, transcarotid perfusion with 10% formalin solution was carried out and the brain was carefully removed. Each brain was additionally fixed in 10% formalin, sectioned, stained and examined pathologically. Clinical evaluation in all the control animals showed mild to severe neurological deficits or death. On the other hand, the animals with patent bypass in acute stage demonstrated no neurological deficits. Gross and microscopic evaluation of the brains showed that the permanent occlusion produced a medium or large-sized infarct in the occluded MCA territory, and the patent prompt bypass usually caused no or only microscopic infarct. In the patent delayed bypass, the size of infarct seemed smaller than that in the untreated animals. No hemorrhagic infarct was found in treated animals with either prompt or delayed bypass. In general, it seemed that the animals with patent bypass fared better than untreated animals both clinically and pathologically. The experimental data suggest that reestablishment of blood flow by extra-intracranial anastomosis, particularly within 4 hours after MCA occlusion, may lead to a significant restoration of neurological function without pathological damage of the brain.


[Acute epidural hematoma with extravasation on cerebral angiogram in an infant (author's transl)].

The authors recently operated on a boy four years of age with acute epidural hematoma showing an extravasation on the cerebral angiogram. The hematoma (hematoma volume 125 ml) was evacuated 7 hours after the head injury. The postoperative course was quite uneventful, and he was discharged a month after surgery without any neurologic deficits. The authors reviewed the literature and found 4 cases of acute epidural hematoma with extravasations in infants and children. In all cases the operative results were good. The age incidence and frequency of occurence overall for acute epidural hematomas, extravasations on cerebral angiograms and their mechanism, and the length of time from injury to operation were also discussed. It should be emphasized that, for acute epidural hematoma in infants and children, the early diagnosis and early surgery are essential to save the patients.


[The tentorial meningioma fed by "marginal tentorial artery" arising from the external carotid artery--a case report and review of literature (author's transl)].

It is well known that a Bernasconi-Cassinari artery is an important finding at diagnosis of the abnormality in tentorium. Since Bernasconi and Cassinari reported the artery in 1956, many reports have been presented and showed that the artery arose from the intracavernous portion of the internal carotid artery. We presented a 54-year-old female with tentorial meningioma. In selective external carotid angiography, the artery feeding the tumor was revealed arising from the accessory meningeal artery, which came off the internal maxillary artery and passed into the carnium through the foramen ovale, and took the same course of "Bernasconi-Cassinari artery". This angiographic finding suggests that it is possible for marginal tentorial artery to arise from an external carotid arterial system. It is said in the anatomical studies, when the trunk of primitive maxillary artery which is one of maxillo-carotid anastomotic arteries in fetus regresses, "marginal tentorial artery" usually remains linked to the internal carotid artery. But, if this transition of "the artery" from the external to the internal carotid artery failed, it is easily conceived the artery results in the origin of accessory meningeal artery, a branch of the external carotid artery.


[Spinal arteriovenous malformation fed by branches of the internal iliac artery (author's transl)].

A 51-year-old male had lumbago and intermittent progressive gait disturbance for 2 years. Finally, he could not walk due to paraparesis. Neurological examination revealed flaccid paraparesis, dysuria, constipation and sensory disturbance below the L-4 dermatome. Myelogram showed serpiginous filling defects from sacral to thoracic region suggesting spinal arteriovenous malformation. Angiogram performed by conventional selective injections into the subclavian, intercostal, and lumbar arteries demonstrated no abnormal lesions but abdominal aortogram carried out at the aortic bifurcation revealed spinal arteriovenous malformation fed by branches of the right internal iliac artery. The angiographic findings may be identified at the single coiled vessel type of Doppamn's or A-V shunt type of Saito's classification. Laminectomies were performed from Th-8 to Th-9 and Th-12 to L-2. Feeder was clipped and the drainers were partially removed. No intramedulllary extension was recognized. After one month postperatively, the patient could walk with support. Postoperative angiographic control performed by selective injections into four iliac arteries disclosed no abnormal vessels. Angiographic examinations of the spinal arteriovenous malformations are usually limited to branches of the subclavian, intercostal and lumbar arteries. But at the cauda equina or conus medullaris, anterior and posterior spinal arteries are sometimes anastomosed with medullary feeders from lateral sacral or other hypogastric arteries. Therefore, it is possible that these branches of iliac arteries may feed spinal arteriovenous malformations as seen also in the cases reported by Picard, Stein and Heindel. This report emphasizes the importance of selective iliac angiogram to demonstrate spinal arteriorvenous malformations when conventional methods fail to show lesions.


Extravasation of contrast medium during spinal angiography: a case of paraplegia.

A case of spinal cord haemangioblastoma, with paraplegia resulting from intramedullary and subarachnoid extravasation during angiography, is described.


Muscle fiber hypotrophy with intact neuromuscular junctions. A study of a patient with congenital neuromuscular disease and ophthalmoplegia.

An infant born with severe but nonprogressive somatic and cranial muscle weakness including bilateral external ophthalmoplegia was studied with a motor-point muscle biopsy. There was a strinking generalized decrease in the size of muscle fibers (hypotrophy), most marked in the type I fibers. Many of the small fibers were immature, resembling myotubes. Neuromuscular junctions on severely hypotrophic fibers were normal with esterase staining and by ultrastructural criteria. Although these are unusual clinical and biopsy characteristics, this infant's condition bears a resemblance to two other congenital nonprogressive neuromuscular diseases:myotubular myopathy and congenital fiber type disproportion. In these conditions and in our patient, there is no primary degenerative process affecting nerve or muscle but, rather, an apparent lack of maturation of fetal muscle fibers, indicating a defective normal trophic interaction between nerve and muscle.


Elevated manganese levels associated with dementia and extrapyramidal signs.

In a patient with elevated manganese levels, dementia, and an extrapyramidal syndrome, brain biopsy showed numerous neuritic plaques and neurofibrillary tangles typical of Alzheimer's disease. Manganese was elevated beyond toxic levels in serum, hair, urine, feces, and brain. The possible relationship of elevated manganese levels, dementia, and the extrapyramidal syndrome warrants further studies of similar cases.


Thalamic hemorrhage: a computed tomographic-clinical correlation.

An analysis has been made of the clinical manifestations in 18 cases of hypertensive thalamic hemorrhage diagnosed by computed tomography (CT). CT scans permitted accurate determination of the site, size, and extension of the hemorrhages. A sensorimotor hemiplegia or hemiparesis was present in all cases. Diagnostic clinical features included limitation of vertical gaze, downward deviation of the eyes, and small unreactive or sluggish pupils. All hemorrhages larger than 3.3 cm in diameter were fatal.


Hyponatremia and central pontine myelinolysis.

Autopsy in a patient with severe hyponatremia showed central pontine myelinolysis. Review of our patients with central pontine myelinolysis and those described in the English literature to data disclosed that 61 percent had documented hyponatremia. While the exact mechanism involving hyponatremia and central pontine myelinolysis cannot be defined, a circumstantial relationship is apparent. The purpose of this paper is to emphasize this relationship and to suggest that the possibility of central pontine myelinolysis be considered in any patient with hyponatremia and neurologic dysfunction.


Evaluation of central nervous system vaccinia antibody synthesis in multiple sclerosis patients.

A serum/cerebrospinal fluid (CSF) ratio method was used to determine whether elevated CSF vaccinia antibody titers in some patients with multiple sclerosis are the result of central nervous system antibody synthesis or of a leak in the blood-brain barrier. Nine of 20 multiple sclerosis patients were noted to have a depressed serum/CSF vaccinia antibody ratio and a normal ratio for poliovirus-I, an agent thought not to be involved in the pathogenesis of multiple sclerosis. These data suggest central nervous system synthesis of vaccinia neutralizing antibody. Vaccinia virus antigens may play an important direct or indirect role in the pathogenesis of multiple sclerosis.


Localization of technetium-99m diphosphonate in acutely injured muscle. Relationship to muscle calcium deposition.

In rats with experimental ischemic myopathy, there was a significant correlation (r = 0.778, p less than 0.001) between muscle uptake of technetium-99m (99mTc) diphosphonate and tissue calcium concentration. In addition, the accumulation of both calcium and 99mTc-diphosphonate in acutely injured muscles was further increased in rats with vitamin D-induced hypercalcemia. Histologic studies demonstrated staining of damaged muscle fibers with alizarin red, indicating the presence of microcrystalline or ultramicrocrystalline calcium salts. Staining of muscle fibers was most intense in the outer marginal zones of individual microscopic infarcts. Our results suggest that the uptake of 99mTc-diphosphonate in acutely damaged skeletal muscle is directly related to the deposition of calcium salts within the injured muscle fibers.


Inverse cerebellum and occipital encephalocele. A dorsal fusion defect uniting the Arnold-Chiari and Dandy-Walker spectrum.

The malformation of inverse cerebellum and occipital encephalocele is situated morphologically between the Arnold-Chiari and Dandy-Walker malformations. In the three reported cases, hydrocephalus was not present, concomitant malformations of the lamina terminalis were present in two, and polymicrogyria was found in all three. The primary defect in the malformation is a complex occipital encephalocele composed of miniature hemispheres connected to the brain stem by an extension of the midbrain tectum. The cerebellar folia extend ventrally and cover the basilar artery. We propose that the encephalocele arises through the processes of overgrowth and dysraphism and thus falls into the organogenetic malformations of Yakovlev. Supporting this theory is the consistent observation of the duplicate hemispheres in the encephalocele and the hydromyelia in the examined spinal cords.


Aspartate-taurine imbalance in dominantly inherited olivopontocerebellar atrophy.

Amino acids were measured in autopsied brain from two patients who died with a dominantly inherited form of olivopontocerebellar atrophy. Neuropathologic changes found in the brain of these patients suggested a loss of cerebellar climbing fibers. The contents of aspartic acid, gamma-aminobutyric acid, and homocarnosine were reduced in the cerebellar cortex and the dentate nucleus, while taurine content was markedly elevated in the same brain regions. These findings are compatible with the possibility that aspartic acid is the excitatory synaptic transmitter of the climbing fibers and taurine is the inhibitory neurotransmitter of one or more types of interneurons in the cerebellum.


Subacute meningitis heralding a diffuse granulomatous angiitis: (Wegener's granulomatosis?).

Subacute meningitis was the first manifestation of illness in a young man with multisystem disease involving lung, kidney, eye, and central nervous system. Necrotizing granulomatous angiitis was found in tissue obtained at thoracotomy and the diagnosis of Wegener's granulomatosis was suggested. This patient had an excellent functional recovery with cyclophosphamide and prednisone.


Characteristics of life headache histories in a nonclinic population.

A detailed questionnaire concerning life history of headache and its characteristics was administered to 1,809 nonmedical volunteers. Questions dealt with severity of headache, the nature of preceding and accompanying phenomena (nausea, visual scotomata, neurologic symptoms), precipitating factors, and history of other illness. For the total sample and in the 25 to 39 age group, severe or disabling headaches were significantly more frequent in women and mild headaches were significantly more common in men. Migraine characteristics were common with mild headache. An association between hypertension and severe headache was found in women, between asthma and severe headache in men.


Myokymia and facial contracture in brain stem tuberculoma. A clinicopathologic report.

The syndrome of persistent facial myokymia and spastic facial contracture is a rare sign of pontine glioma. In none of the previously published cases has this syndrome been reported in association with a nonneoplastic lesion. A patient is described in whom facial myokymia and contracture were caused by a pontine tuberculoma.


Agarose electrophoresis of cerebrospinal fluid in multiple sclerosis. A simplified method for demonstrating cerebrospinal fluid oligoclonal immunoglobulin bands.

The gamma globulins in cerebrospinal fluid from almost all patients with multiple sclerosis migrate in agarose electrophoresis as abnormal discrete populations, so-called oligoclonal bands. Such bands have also appeared in cerebrospinal fluid from patients with other types of inflammatory pathology such as neurosyphilis, acute idiopathic polyneuropathy, and subacute sclerosing panencephalitis. The demonstration of cerebrospinal fluid oligoclonal bands may aid in the evaluation of patients with early or atypical multiple sclerosis. This report describes a simple method for demonstrating cerebrospinal fluid oligoclonal bands using readily available commercial reagents and apparatus. Oligoclonal bands were seen in cerebrospinal fluid from all patients with clinically definite multiple sclerosis, even though some had normal cerebrospinal fluid gamma globulin levels, and in most patients with presumptive multiple sclerosis or other inflammatory conditions of the nervous system. They were not seen in cerebrospinal fluid of control patients with a variety of other neurologic diseases.


Square-wave jerks: a disorder of microsaccades?

A patient with presenile dementia had instability of ocular fixation caused by small rapid horizontal eye movements (square-wave jerks). High resolution recordings of these eye movements were characteristic of microsaccades, which ordinarily occur during fixation, in all respects except amplitude. In addition, the patient showed complete absence of normal microsaccades. We suggest that microsaccades have become altered in our patient to form a clinical disorder of fixation.


Effects of immunologically induced growth hormone deficiency on myelinogenesis in developing rat cerebrum.

Chronic deficiency of growth hormone was produced in rats by injecting highly specific antibodies against rat somatotropin during the first week of postnatal life. Antisera were prepared by immunizing adult rhesus monkeys with purified rat growth hormone. The rate of body and brain growth was significantly decreased when compared with controls injected with nonimmune serum, and 50-day-old animals showed a profound and apparently specific endocrine deficiency of pituitary growth hormone as measured by bioassay. Defective cerebral maturation was evidenced by a 70 to 80 percent decrease of myelin lipids, a 65 percent reduction of deoxyribonucleic acid, and a small but significant decline in ribonucleic acid. An abnormal accumulation of undifferentiated glia was seen in the subependymal zone in association with decreased amounts of stainable myelin in subcortical white matter. The data suggest that pituitary growth hormone and/or its secondarily induced trophic factor, somatomedin B, influences the maturation of neural cells by regulating the replication of glia and the subsequent differentiation of oligodendrocytes to form myelin.


Primary position upbeat nystagmus. A clinicopathologic study.

Eye movements were studied with electro-oculography in a patient with primary position, large amplitude, upbeat nystagmus. The upbeat nystagmus increased in amplitude on upward gaze, decreased on downward gaze, and was not altered by loss of fixation. The patient could not produce smooth pursuit movements upward or to the left, but had normal saccadic and vestibular induced eye movements in all directions. At necropsy, a low grade glioma was found involving primarily the medulla and caudal pons. The inferior olives and prepositus hypoglossal nuclei were diffusely infiltrated with tumor. These results suggest (1) primary position upbeat nystagmus is due to a defect in the upward smooth pursuit system, (2) the lower brain stem at the level of the inferior olives and nucleus prepositus hypoglossi is important in the mediation of vertical pursuit, and (3) primary position upbeat nystagmus can result from damage to several nuclei and interconnecting pathways in the caudal brain stem and midline cerebellum involved in control of vertical smooth pursuit.


Malabsorption of pyridostigmine in patients with myasthenia gravis.

Four patients with myasthenia gravis were under unsatisfactory control while receiving oral pyridostigmine. In each of these patients, the serum levels of this drug were below those observed in patients with myasthenia gravis who are well controlled. The strength of each of these patients improved when the serum pyridostigmine level was increased by intravenous administration of this agent. Furthermore, the rate of disappearance of pyridostigmine from the serum following intravenous administration was the same as that for control subjects and patients under good control. This demonstrates that failure to achieve adequate serum pyridostigmine levels following oral administration is due to malabsorption rather than to increased rates of tissue uptake, degradation, or excretion of the drug.


Improvement in multiple sclerosis during prolonged induced hypothermia.

Moderate hypothermia (33 degrees C) was induced for 7 and 3 days, respectively, in two patients with multiple sclerosis. In both patients, striking improvement of clinical signs persisted throughout the period of cooling, indicating the potential for sustained reversal of the neurologic deficit. Hypothermia may aid management of severe acute exacerbations of multiple sclerosis.


Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model.

Peroxidase-conjugated alpha-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in end-plates in external intercostal muscles of four patients with myasthenia gravis, in forelimb digit extensor muscles of rats with advanced chronic experimental autoimmune myasthenia gravis, and in suitable human and rat controls. In control end-plates, the previously reported localization of acetylcholine receptor on the terminal expansions of the postsynaptic folds and, in traces, on the presynaptic membrane was confirmed. By contrast, in myasthenia gravis some postsynaptic regions bound no P-BGT; in other regions, the folds displayed only faint traces of the reaction product, or only some segments of the postsynaptic membrane showed the reaction product; finally, in some regions there was no apparent decrease in reaction product. In general, those postsynaptic regions showing the greatest decrease in P-BGT binding were also the simplest or showed the most degenerative changes, and the presynaptic staining was decreased in proportion to the decrease in the adjacent postsynaptic P-BGT binding. In the experimental animals, the abnormalities in the amount and distribution of the acetylcholine receptor were essentially like those in the more severely affected patients. Morphometric estimates of the postsynaptic acetylcholine receptor surface correlated well with the patients' clinical status and linearly with the miniature end-plate potential amplitude.


Clinical and pathologic correlates of brain stem auditory response abnormalities.

Short-latency auditory evoked responses were recorded in over 100 neurologic patients. Abnormalities of each response component were correlated with postmortem or radiologic localization of different brain stem lesions. These findings suggested that waves I-VII largely reflect activity at the following levels of the auditory pathway: acoustic nerve (I), pontomedullary junction (II), caudal pons (III), rostral pons or midbrain (IV), midbrain (V), thalamus (VI), and thalamus or auditory radiation (VII). When this information was applied prospectively to the evaluation of brain stem dysfunction, response abnormalities proved useful in detecting and localizing certain lesions not revealed by other tests. Serial recordings provided information about the evolution of brain stem lesions and their response to therapy.


Brain lesions that produce delta waves in the EEG.

Localized delta activity appears in cortex overlying a circumscribed white matter lesion. Less commonly, localized delta activity may result from a localized thalamic lesion. Unilateral diffuse delta activity appears on the side of thalamic or hypothalamic lesions. Bilateral delta activity results from bilateral lesions of the midbrain tegmentum. Localized lesions of the cerebral cortex, unilateral mesencephalic tegmental lesions, and vasogenic edema of the cerebral white matter do not produce delta activity. Marked edema of a cerebral hemisphere when no surgical decompression is provided may produce unilateral delta activity by pressure on or displacement of the brain stem or diencephalon.


Fusiform basilar artery aneurysm in a child.

A giant fusiform aneurysm of the basilar artery was present in a 10-year-old boy with a 2-year history of intermittent headaches and the acute onset of neurologic signs. Elevated sedimentation rate, cerebrospinal fluid pleocytosis, and an apparent response to corticosteroid therapy suggest a chronic inflammatory vascular process. The uniqueness of this aneurysm in a child and the possible underlying arteriopathies are discussed.


Mass casualty alert program.

The occupational health nurse has professional responsibility to be prepared to provide proper reaction if a major crisis should occur. A mass casualty alert program enables the nurse to meet that responsibility. But the nurse cannot do this all alone. There must be a comprehensive, cooperative plan which involves the entire plant. All interested groups, of course, should have individual plans. However, they should all be interrelated as a part of a totally coordinated plan. The mass casualty alert program should clearly indicate who is in charge, with alternates designating who is responsible for what. Things to remember in maintaining the program include: 1. There must be an up-to-date mass casualty alert program. 2. There must be total involvement. a. Ambulance--list should be up-to-date. b. Hospitals--list and capabilities should be up-to-date. c. Other Community Emergency Facilities--e.g., helicopter ambulance list should be up-to-date. d. Plant Management--fully informed and supportive of program. e. Communication--everyone involved should know what to do in-plant. f. Equipment and supplies should be ready at all times. There must also be disaster drills with simulated casualties. There should also be formal critiques of the drills to point out the weak points as well as the strong. This program will be very effective if planned ahead and carried out in this manner, either in a small plant with a small number of employees or a large complex with many employees, such as ours.


Prepubertal XY gonadal dysgenesis.

Two children had prepubertal XY gonadal dysgenesis. A 7-year-old girl with clitoral enlargement had a left ovarian tumor that contained a dysgerminoma; the right gonad proved to be a gonadoblastoma. The second child (a 2-year-old girl) showed poor physical development and slight virilization of the genitalia. Her bilateral dysgenetic gonads were removed at exploratory laparotomy. The occurrence of gonadal tumors in XY gonadal dysgenesis is increased. It is probably related to the hypergonadotropinism existing from childhood as well as to genetic predisposition of the cryptorchid testis in the presence of a Y chromosome. Our first patient is one of the youngest who had XY gonadal dysgenesis iwth gonadoblastoma reported. The indication of prophylactic gonadectomy in XY gonadal dysgenesis is emphasized.


Fractionation by size of casein micelles on controlled-pore glass.

Casein micelles have been separated from skim milk by chromatography on CPG-10 3000 glass beads. Fractionation of the micelles according to size has been demonstrated. Polyacrylamide gel electrophoresis of urea treated micelles reveals that different relative amounts of the major casein components occur in the various micelle fractions. No discernible dissociation of the micelles into monomeric caseins has been observed.


Effects of intrastriatal injections of atropine and methacholine on the apomorphine-induced gnawing in the rabbit.

To find out the anatomical location of the target point of cholinergic-dopaminergic equilibrium, atropine (40 microng) or methacholine (10 microng) were injected through previously implanted cannulas into various places of caudate nucleus and putamen of the rabbit, and the effect of the injections on stereotype gnawing induced by subcutaneously or intravenously administered apomorphine (1--2 mg/kg) was assessed. The intensity of gnawing was measured using a special apparatus, counting each bite. Atropine inhibited the stereotype, while metacholine potentiated it. The effects were evident with the method used, but difficult to reveal with the classical method of assessing the intensity of stereotyped behavior, based on visual observation. The results suggest that the striatum is not a target point for the cholinergic component of the cholinergic-dopaminergic equilibrium in the central nervous system.


The role of radiation therapy in the treatment of germinal cell tumors of the testis other than pure seminoma.

Between March 1944 and September 1976, 279 patients with nonseminomatous testicular tumors were treated. The 3-year NED rates for patients with Stages I, IIA, and IIB were 78.2%, 46.7%, and 17.6%, respectively. However, the results were better for patients treated with preoperative radiotherapy and lymphadenectomy with or without postoperative radiotherapy (Stage IIA: 77.5%--14/18; Stage IIB: 12.9%--3/7). Postoperative radiotherapy is not necessary for patients with negative nodes at lymphadenectomy because the periaortic failure rate is low for this group. However, when positive nodes are found, the control is improved with radiotherapy. The minimum tumor dose required when tumor is found but resected is not known. When there is gross residual tumor, a dose of 4,500-5,500 rad is required to achieve any salvage. In this series, 42.2% of patients with positive nodes at lymphadenectomy (Stages I and II) developed extranodal metastases. This group might benefit from adjunctive chemotherapy.


Hemangiosarcoma of the spleen and liver metastases: angiographic manifestations.

The arteriographic findings in two cases of hemangiosarcoma of the spleen with liver metastases are described. These are the second and third reported cases of angiographically demonstrated malignant splenic tumors of vascular origin. Despite the absence of tumor vessels, there were multiple vascular takes in the arterial through the venous phase, mimicking benign cavernous hemangioma. Multiple metastases in the liver were the only clue to malignancy. Arteriography combined with liver-spleen scintigraphy not only provides information which is valuable in the preoperative diagnosis but also aids in management of the patient.


Angiosarcoma of the superficial femoral artery with distal embolization.

Angiosarcoma of the intima is a very rare tumor. The authors report a case which involved early metastases to the periphery of the leg. Cramping pain, circumscribed clusters of cells, and gangrene appear to be characteristic and should be kept in mind, as this condition imitates occlusive arteriosclerotic disease.


Prostaglandin F2alpha specific binding in equine corpora lutea.

Preliminary studies indicate the presence of PGF2alpha specific binding sites in membrane fractions prepared from equine corpora lutea. The equilibrium binding data indicate an apparent dissociation constant of 3.2 X 10(-9)M and the concentration of binding sites of -0.1 pmoles/mg membrane protein. Competition of several natural prostaglandins for equine luteal PGF2alpha specific binding sites indicates specificity for the 9alpha-hydroxyl moiety and the 5,6-cis doublebond. Significant increases in relative binding affinities were demonstrated for PGF2alpha analogs with a phenyl ring introduced at carbons 16 or 17. Specific PGF2alpha binding was demonstrated in corpora lutea collected at known stages of the estrous cycle. There was no pattern in these values based on the stage of the cycle. While specific 3H-PGE1 binding could be demonstrated, no high affinity sites could be quantitated. 3H-PGE1 binding appeared unaffected by changes in temperature or time of incubation, whereas PGF2alpha specific binding was significantly modified by both these factors.


Effects of cadium on growth, sexual development, and metabolism in female rats.

Female rats were exposed to cadmium by multiple intramuscular injections of 250 mug CaCl2 for 54 days. Activity and haircoat were affected, sores on the sites of injection and persistent diestrus were observed in the treated rats. Morphological examination of organs revealed a smaller weight and size in reproductive organs and pituitary, but enlargement of liver, spleen, and kidney. The ratic enzymatic demethylation activity.


Adaptation of the growing lung to increased oxygen consumption. II. Morphometric analysis.

This paper is the second part of a study investigating the effect of increased O2 consumption on the lungs of growing animals. By means of injections of the drug IDPN (imino-betabeta'-dipropionitrile) hyperkinesia was permanently induced in white mice aged 3 weeks, thus increasing their Vo2 per gram body weight (= specific VO2) by 50%. 3 1/2 months later the lungs of these animals were fixed by standardized procedure, analysed by morphometric techniques and the results compared with those of control mice originating from the same litters. Whereas the specific weights (= weights per gram body weight) of various organs did not differ significantly in the two groups, the specific volume of the lungs fixed with standardized techniques was up by 23% in IDPN mice. The relative composotion of lung parenchyma was also altered: air space volume density was slightly but significantly reduced, whereas tissue and capillary volume densities were both increased by 15%. An analogous increase was detected in alveolar and capillary surface densities. These changes led to significantly higher specific capillary and tissue volumes, as well as higher specific gas exchange surface areas in DIPN mice. Therefore the morphometrically determined specific pulmonary diffusion capacity was increased by more than 40% in the IDPN-treated animals. The findings are compared with those hitherto reported, where a structural adaptation of the gas exchange apparatus to exercise or altered PO2 had been found. In view of our present knowledge of the postnatal lung growth the quantitative structural alterations found in this experiment indicate that the higher O2 requirements in IDPN mice induced an alteration in the septal morphology. This consisted in an augmentation of septal volume possibly due to a lengthening and corrugation of the intralveolar septa. This change is reflected by the increased alveolar surface area in IDPN mice and by the increase of the ratio Sa/Va estimating the air space surface complexity.


Metabolism of testosterone in the human prostate and seminal vesicles.

Tissue from the normal, hyperplastic and the cancerous human prostate as well as tissue from the human seminal vesicles are capable of metabolizing testosterone in vitro. By incubating minced tissue with 3H-testosterone for 2 hours at 37 degrees C the following radioactive metabolites were identified: testosterone (17 beta-hydroxyl-4-androsten-3-one), androstenedione (4-androstene-3,17-dione), androstanedione (5alpha-androstane-3,17-dione), 5alpha-dihydrostestosterone (17 beta-hydroxy-5alpha-androstane-3-one, DHT), 3alpha-androstanediol (5alpha-androstane-3alpha,17beta-diol), 3beta-androstanediol (5alpha-androstane-3beta-17beta-diol) and androsterone (3alpha-hydroxy-5alpha-androstane-17-one). When normal human prostatic tissue was incubated with 3H-testosterone approximately 40% of the hormone was metabolized and 30-35% of the metabolites were identified as DHT. There were apparently no differences in testosterone metabolism between the dorsal and lateral prostatic lobes. A much lower conversion of 3H-testosterone was observed in the seminal vesicles (24%). The same metabolites were formed by prostatic carcinoma tissue, although distinctive quantitative differences from the normal prostate were observed. Thus, only 23% of the testosterone was metabolized by cancerous tissue of which 15% was present as DHT. The formation of 17-keto metabolites and androstanediols in the prostatic carcinoma tissue was approximately the same as in the normal prostatic tissue. The most extensive metabolism of testosterone was found by incubation of tissue from benign nodular prostatic hyperplasia. About 65% of the testosterone was metabolized, and 40% of the metabolites were identified as DHT. Hyperplastic prostatic tissue also showed a significantly higher formation of 5alpha-androstanedoils and the other tissues examined. The high formation of DHT and 5alpha-androstanediols in benign nodular prostatic hyperplasia in comparison with normal and cancerous prostatic tissue and seminal vesicle tissue might indicate that these metabolites should be studied more closely as possible aetiological factors for prostatic hyperplasia. The very low metabolism of testosterone in prostatic carcinoma tissue should be examined further in relation to tumour differentiation and clinical effect of endocrine therapy.


[Surgical treatment of hypertropic obstructive cardiomyopathy].

The clinical picture of hypertrophic obstructive cardiomyopathy and the pathogenesis of its hemodynamic alterations are discussed. Dynamic systolic obstruction of the left ventricular outflow-tract, i.e. muscular subaortic stenosis, may or may not be accompanied by hindrance of diastolic filling of the left ventricle and vice versa. It cannot yet be assessed to what extent the reduction of compliance is caused by the pressure load in subaortic stenosis through secondary hypertrophy of the left ventricle. Study of the late course in 28 patients who had undergone surgery reveals that surgery abolishes the pressure gradient in the left ventricular outflow tract and provides year-long relief of symptoms. Complications of obstructive hypertrophic cardiomyopathy, such as mitral incompetence, may be cured by the operation. On the other hand, although progression of the cardiomyopathy is apparently slowed, it can not be abolished by surgical treatment.


Analysis of chicken ribosomal RNA genes and construction of lambda hybrids containing gene fragments.

The ribosomal RNA genes (ribosomal DNA) of chicken are present in approximately 200 copies and are cleaved into two fragments of molecular weight 5 X 10(6) and 12 to 14 X 10(6) by restriction endonuclease Eco RI. Recombinant phages have been constructed in vitro by joining the smaller fragment of ribosomal DNA and the outer arms of DNA from the vector lambdagtWES-lambdaC. In one of the recombinants, the coding strand of the cloned fragment is in the proper orientation for transcription with lambda "early" genes; in the other two the orientation is reversed, with the coding strand in the proper position for transcription with lambda "late" genes.


The role of the pineal gland in reproduction.

The present paper presents a number of results concerning the role of the pineal gland in reproduction. It has been demonstrated that the pineal polypeptides and a substance isolated by the author from children's urine and proved to have pineal extract-like actions, administered to laboratory animals induced the following effects: 1) inhibition of the exogenous HCG stimulating effect on mouse uterus, 2) decrease in excretion of the 17-KS of both testicular and adrenal origin, 3) decrease in the testis oxygen consumption in vitro, and 4) marked decrease of the serum and testicular testosterone. Melatonin, a pineal indole, studied in parallel did not alter the above biochemical indices. Pinealectomy produced in all the cases completely opposite effects. The effects obtained with the pineal polypeptides, the urinary antisteroid substance, and melatonin are discussed.


Monosodium glutamate admlinistration to the newborn reduces reproductive ability in female and male mice.

Monosodium glutamate (MSG) administered during the neonatal period (days 2 to 11) resulted in a sequence of events that were manifested in adulthood. Reproductive dysfunction was seen in both female and male animals. Females treated with MSG had fewer pregnancies and smaller litters, while males treated with MSG showed reduced fertility. The MSG-treated mice showed increased body weight and decreased pituitary, thyroid, ovary, or testis weights.


Pheromonally induced sexual maturation in females: regulation by the social environment of the male.

Social subordination, which suppresses gonadal function in juvenile and adult male house mice, also suppresses the activity of an androgen-dependent urinary pheromone that accelerates the rate of sexual maturation in juvenile females. Pheromone production may also be suppressed by the presence of pregnant or lactating females. This suggests that the social environment may influence the fertility of population females by altering urinary pheromone activity in the male.


The hormonal pattern in alcoholic disease. I. Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone.

The study included 48 male chronic alcoholics, aged 20 through 50 years, classified in two groups according to the presence (22 patients) or absence (26 patients) of clinically evident sexual disorders. The blood samples were collected the first 2-3 days after hospitalization, before any anti-alcoholic treatment. The control group included 10 adult male normal subjects. By comparison to the control group, the basal level of LH was significantly (p less than 0.01) lower in both groups of alcoholic patients while the FSH level was significantly higher (p less than 0.01) in the group with sexual disorders. The serum levels of testosterone were increased (p less than 0.05) only in the group having sexual disorders. Our data suggest that the feedback regulation of the hypophyseal LH release seems to be impaired by defects in the peripheral metabolization of testosterone.


Alcohol drinking: abnormal intake caused by tetrahydropapaveroline in brain.

Tetrahydropapaveroline (THP), a dopamine-dopaldehyde condensation product, was delivered directly into the cerebral ventricle of rats automatically every 15 minutes for 12 days. The animals were given access to both water and ethylalcohol, the latter being presented in 12 concentrations from 3 to 30 percent. Within 3 to 6 days of the start of the infusion of THP, the rats, which normally rejected alcohol, drank alcohol solutions in increasingly excessive amounts; this was accompanied by symptoms that were similar to those of withdrawal and intoxication. These results provide evidence that an abnormal metabolite in the brain may produce the addictive state caused by alcoholic beverages.


Estradiol shortens the period of hamster circadian rhythms.

Continuous administration of estradiol benzoate by means of subcutaneously implanted capsules shortened the free-running circadian period of locomotor activity of blind hamsters (Mesocricetus auratus) that had had their ovaries removed. Estradiol also advanced the phase of the wheel running of sighted female hamsters without ovaries that were entrained to a photoperiod with 12 hours of light and 12 of darkness. These results, and findings from hamsters undergoing natural estrous cycles, indicate that endogenous estradiol is involved in the regulation of circadian periodicity.


Stress-induced modulation of the immune response.

After mice were exposed to a daily auditory stressor for varying lengths of time, the responses of their splenic lymphoid cells in vitro were assessed. Both the blastogenic activity of concanavalin A or lipopolysaccharide and the ability of immune lymphocytes to lyse P815 target cells showed the same patterns of immunosuppression and enhancement.


Membrane currents examined under voltage clamp in cultured neuroblastoma cells.

Examination of ionic membrane currents in a voltage-clamped neuronal cell line derived from the mouse C1300 neuroblastoma disclosed four kinetically different components: sodium, potassium, calcium, and leakage current. The kinetics, voltage dependence, and pharmacological properties of the sodium and potassium currents qualitatively resemble those of the corresponding currents in squid giant axon and frog myelinated nerve fiber, suggesting that the molecular structures of the sodium and potassium channels in neuroblastoma are similar to those of the non-mammalian preparations.