Impaired potency for feedback regulation of glomerular filtration rate in DOCA escaped rats. The present experiments were performed to study the effect of chronic extracellular volume expansion on the magnitude of tubulo-glomerular feedback responses in the rat kidney. Extracellular volume expansion was achieved by giving isotonic saline as drinking water and by injecting DOCA in a dose of 2.5 mg/kg - day. When Ringer perfusion rate through the loop of Henle was elevated in control rats (receiving only saline as drinking water) stop flow pressure (SFP) fell by an average of 0.47 +/- 0.81 mm Hg (mean +/- S.D.) and 7.93 +/- 2.85 mm Hg at the flow rate steps of 0--15 nl/min and 15--40 nl/min respectively. SN-GFR was reduced by a mean of 1.3 +/- 0.97 nl/min (0--15 nl/min) and 10.3 +/- 2.45 nl/min (15--40 nl/min). In DOCA treated rats the mean reductions of SFP were 0.98 +/- 0.9 mmHg and 2.1 +/- 1.4 mmHg and of SN-GFR 0.06 +/- 1.8 nl/min and 1.94 +/- 2.3 nl/min. Thus, significantly smaller changes of both SFP and SN-GFR were found in DOCA treated animals when flow rate was elevated from 15--40 nl/min. Net loop NaCl absorption rates did not significantly differ between control and DOCA rats. Renin activity of 5 pooled microdissected glomeruli was 15.6 +/- 17.1 ng/hr-0.1 ml in control and 2.94 +/- 2.6 ng/hr-0.1 ml in DOCA treated rats (P less than 0.01). It is possible therefore that the reduced feedback reactivity in DOCA treated rats is related to the diminished juxtaglomerular renin activity.


Ventral midbrain stimulation, blood pressure responses and their relation to the dopaminergic nigro-striatal pathways. In 40 cats systematic, electrical stimulation of ventral midbrain structures was performed. In the lightly anaesthetised animals, fixed in a stereotaxic frame, ECoG and arterial blood pressure were registrated. As a result stimulation-induced phasic blood pressure increases have been found within a distinct area including substantia nigra and ventral tegmentum. From the same region nonspecific responses in the ECoG (spindling, recruiting and desynchronisation by low and middle frequent stimulation) could be obtained. The blood pressure responses were enhanced after hemisection at the level of the posterior hypothalamus ipsilateral to the stimulation side. Drugs (Haloperidol, alpha-methyltyrosin and 6-hydroxydopamine), affecting the dopamine metabolism in different ways, abolished the stimulation-induced blood pressure responses. In agreement with previous findings it is concluded that motor and autonomic activation, elicited in ventral midbrain structures are mediated by catecholaminergic transmission.


Vitamin B12 absorption from eggs.

Vitamin B12 absorption from eggs. The assimilation of 57Co B12 from in vivo labeled eggs was much inferior to that of a comparable amount of crystalline 57Co B12. Furthermore, the absorption varied with the form in which the eggs were served. Judged by the urinary excretion test and the plasma absorption of radioactivity the average absorption from boiled and fried eggs was more than twice that from scrambled whole eggs, but less than half that absorbed from crystalline 57Co B12.


Sesquiterpene lactones. Part XIII. Cytotoxic activity of eupatolide and eupatoriopicrin on human and animal malignant cells in tissue culture in vitro. The activity was determined in tissue culture of KB, HeLa human tumor cells. RK normal animal and EAC-E4 Ehrlich ascites carcinoma cells. Eupatolide (EUP) and eupatoriopicrin (EUPP) show similar cytotoxic activity (ED50 from 0-5 to 1-3 mug/ml), dependent on the cell strain used. In plate test EUP and EUPP give inhibition zones of 18--19 mm. EUPP exerts progressively destructive influence on EAC-E4 cells in the conditions of Miyamura test. The decrease in EUPP activity was noted in aqueous (pH = 9) and acetone solutions.


Spontaneous and oxytocin induced uterine motility during the oestrous cycle in goats. Spontaneous uterine motility and reactivity to intravenously administered oxytocin were recorded through the oestrous cycle in a group of goats. Contractions during oestrus were of significantly greater amplitude than in dioestrus and both the sensitivity and degree of response to oxytocin were greater in the oestrous phase. Evidence from a previous study suggests that the depressed spontaneous and oxytocin-induced motility in dioestrus is due to the predominating influence of progesterone during this stage of the cycle.


Further studies on the adjuvant effect of an interferon inducer (BRL 5907) on Newcastle disease and avian influenza inactivated vaccines. Vaccination of fowls with inactivated Newcastle disease (ND) virus and avian influenza (AI) virus oil emulsion vaccines containing an interferon inducer (BRL 5907) produced an enhanced immunological response. The Newcastle disease vaccine containing BRL 5907 induced earlier protection to challenge than Newcastle disease vaccine by itself and also produced an increase immune response when administered to day-old maternally immune and susceptible chicks.


Comparative value of arecoline hydrobromide and bunamidine hydrochloride for the treatment of Echinococcus granulosus in dogs. A controlled trial involving 122 dogs experimentally infected with Echinococcus granulosus was carried out to compare the efficiency of arecoline hydrobromide and bunamidine hydrochloride. A single treatment with arecoline hydrobromide at a dose rate of 4 mg/kg or with bunamidine hydrochloride at 50 mg/kg gave a similar degree of efficiency against young worms. At these dose rates, worms were still present in almost half the dogs at autopsy.


The effect of nitroscanate on Echinococcus granulosus and Taenia hydatigena infections in dogs. Trials with nitroscanate carried out on 186 dogs infected with either Echinococcus granulosus or Taenia hydatigena indicated that a single treatment at a dose rate of 1000 mg/kg or two treatments at 250 mg/kg eliminated the former, but a single treatment at 64 mg/kg was sufficient to eliminate the latter. At this dosing schedule, vomiting and diarrhoea occurred, as well as a transient 'tranquillising' effect on some dogs.


A pilot study on the effect of BCG vaccination in patients with bronchial carcinoma. Eight patients with non-resectable bronchial carcinoma were treated with a combination of cyclophosphamide and BCG. No effect on survival was noted; mean survival was 11 months from the first admission to hospital.


Abdominal urethropexy: Vesicourethrolysis vs Marshall-Marchetti-Krantz procedure. In a series of 35 cases, I used a relatively uncommon but simple operation to correct urinary stress incontinence by the abdominal route. The operation is known as vesicourethrolysis and consists of dissection of the tissues in the space of Retzius. This establishes an anatomical urethrovesical angle without suturing and relieves urinary stress incontinence. The operation was first described in 1951 by Mulvaney, and although it has been done by others since, apparently with good results, the operation has never gained great popularity. Comparison of this operation with the Marshall-Marchetti-Krantz procedure shows that vesicourethrolysis yields excellent results with minimal complications. Different criteria are used to establish the indications for vesicourethrolysis versus the Marshall-Marchetti-Krantz procedure.


[Some ethological features in farm animals (author's transl)]. A number of general ethological principles are discussed in the present paper. Attention is paid to normal and ritualized behaviour of cattle and swine during mating and on aggression. The fact is stressed that external stimuli during the period of so-called imprinting may also affect the future behaviour of cattle and swine. This is of particular importance in male animals used in artificial insemination. Finally, the effect of social stress on symptoms such as cannibalism, gastric ulcers and avian hysteria is discussed.


[Fertility problems caused by infectious agents pigs in the Netherlands(author's transl)]. The concept of fertility problems is defined in the introduction and their economic importance in pig breeding are pointed out. The infectious causes of the problem are reviewed. Infections with L. tarassovi and with Aujezky's virus regularly lead to practically endemic abortions; Brucella suis and swine-plague infections do so sporadically. The SMEDI syndrom is considered. The clinical symptoms, diagnosis, epizootiology, and the therapeutical and prophylactic measures of these infections are discussed. In the case of brucellosis, attention is paid to the differential diagnosis in the serological examination. The incidence of Yersinia enterocolitica among the Dutch pig population is high. This micro-organism has antigen components in common with brucellae. In Holland the significance of infectious agents as the causes of sterility is not considered to be high.


[Anaphrodisia in gilts and sows(author's transl)]. The economy of pig breeding and rearing farms is determined mainly by the fertility of the animals. Anaphrodisia causes a considerable disturbance of the fertility. This has a direct effect on the number of litters born per sow per year and thus on the economic results. On the basis of several years of experience at the research station and the production unit of Varkensonderzoekcentrum Nieuw-Dalland the clinical symptoms in gilts and sows are described. Gilts should normally have come into oestrus at the age of about 8 months, and on a well-managed farm about 80% of the sows should come into oestrus within 10 days of weaning, provided that weaning takes place at 5 to 6 weeks. Different forms of anaphrodisia are described, based on the findings of post mortem examinations. These show that in 65-75% of the anaphrodisiac animals the ovaries were insufficiently active. In 20% of the animals that had not shown signs of oestrus, ovulation had in fact taken place. The causes of anaphrodisia must be sought in a disturbance of the hypothalamo-hypophysial ovarian system, in which genetic and health factors play an important role, besides housing and management (insluding feeding). A good keeping of records of sows is indispensable in the solving of the anaphrodisia problem on farms, and this hinges also on an analysis of the farm management and on the power of observation of the farmer. Finally, hormonal therapy is discussed, a distinction being made between breeding and rearing farms.


[Combined artificial insemination and synchronisation of oestrus in sheep (author's transl)]. A brief introduction is followed by a description of artificial insemination in sheep, based on a review of the literature. A number of experiments are then discussed, which were mainly concerned with the possibilities arising when artificial insemination and synchronisation of oestrus are combined. It is concluded that satisfactory results (70-80 per cent pregnant) may be obtained, provided a large number of live spermatozoa (500 x 10(6)) are inseminated at the right time.


[Inability to have erections in male swine (author's transl)]. There are three degrees of impotence or diminished ability to have an erection: (a) there is no erection at all; (b) erection only occurs prior to ejaculation; (c) there is a short-lived erection at the beginning of ejaculation and occasionally also during the final stage of ejaculation. There are differences of degree in erection, ranging from the absence of erection to normal erection. When abnormalities such as those referred to under (b) and (c) are observed in young male swine, the mating pattern may be restored to normal as time goes on.


An epidemiological assessment of the residual effect of DDT on Anopheles hyrcanus sensulato and A. pulcherrimus (Theobold) in the North eastern region of Afghanistan. In the irrigated zones of North-eastern region of Afghanistan malaria transmission is sustained by A. pulcherrimus and A. hyrcanus despite many years of DDT spraying. A. hyrcanus is an exophilic and exophagic mosquito, strongly resistant to DDT. A. pulcherrimus is still largely susceptible to the insecticide but seems to be deterred from entering houses when these are sprayed with DDT. Entomological and parasitological studies in an area of the province of Kunduz where DDT has not been applied for 2 consecutive years have clearly indicated that the insecticide still plays an important role in reducing malaria transmission in the area though, as expected, it cannot interrupt transmission. A deterioration of the epidemiological situation in the area can be expected if the insecticide is withdrawn. The technical problems now existing in the irrigated zones of the North-eastern region of Afghanistan cannot be solved by routine attack measures. Malaria in the area can be eradicated only with the introduction of new attack measures which are very expensive and for which, at present, the necessary funds are not available.


Quantitative determination of immunoglobulins, lysozyme, and certain electrolytes in breast milk during the entire period of lactation, during a 24-hour period, and in milk from the individual mammary gland. During a period commencing at birth and lasting for up to 27 months 193 milk samples have been collected from 29 mothers. The IgA globulin content was high immediately after birth, averaging 2.7 arb.U, decreasing to 0.3 arb.U within the first 2 to 3 weeks after birth, then remaining almost constant for the rest of the lactational period. In the case of IgG globulin, similar results were obtained, but the quantity was much smaller. IgM globulin was demonstrated in small quantities during the first 3 weeks of lactation. The lysozyme content varied considerably during the whole lactational period. Individual variations were found for all the immunoglobulins, while the concentration in the individual woman varied only slightly from day to day following in other respects the pattern described above. In 19 mothers IgA, IgG, IgM, lysozyme and electrolyte content were determined in serum and in milk from the right and the left breast on the same day. No difference in content was found between milk from the left and the right mammary gland. A positive correlation was found between the concentrations of IgA and sodium chloride in milk, between those of IgG in milk and serum, and between those of lysozyme in milk and serum. No variations were registered during the individual breast feeding, nor for the 24-hour period as a whole.


Production of gibberellin-like substances by fungi isolated from mycorrhizae of pine (Pinus silvestris/L.). Gibberellin-like substances were found to be produced by fungi isolated from mycorrhizae of pine. Among the isolates studied gibberellin-like substances producers were most numerous among the Basidiomycetes forming ectotrophic mycorrhiza and among non-sporulating fungi forming no mycorrhiza. In most strains the gibberellin-like subtances were elaborated after 10--20 days of incubation. The Rf values of the gibberellin-like compounds were different in various strains, but in most of them substances showing gibberellin activity appeared on the chromatograms run with benzene, acetic acid (10:3 v/v) at Rf 0.2--0.6.


Studies on the decomposition of lignosulfonates by the fungi Pleurotus ostreatus and Trametes pubescens. The fungi Pleurotus ostreatus and Trametes pubescens were grown in a mineral medium containing 1% of glucose and 0.9% of lignosulfonates introduced into the culture medium in the form of yeast waste liquor. Chromatography of extracts of the medium and determinations of sulphur and lignosulfonates have revealed that the fungi studied utilized the constituents of the yeast waste liquor (lignosulfonates) as carbon source. This was manifested in an increase of dry mass of the mycelium and protein as compared with the control. The constituents of the yeast waste liquor were also found to have a stimulating effect on the formation of both exo-and endoenzymes, laccase and peroxidase. This may indicate that these oxidases take part in the decomposition of lignosulfonates.


Ultrastructure of the early ovary and testis in pig embryos. Pig embryos aged 26-27 days were used for an ultrastructural study of the early ovary and testis. Sex was identified by both chromosomal analysis and gonadal histology, with consistent results. The gonads occupied their original site in the medial coelomic angles in both sexes. The female gonad was composed of three tissues: the surface epithelium, the gonadal blastema and the mesenchyme. The gonadal structure was similar to that seen earlier at the age of 24 days. At 26 days the testis had distinctly differentiated into four tissues. The new components were the testicular cords and the interstitium, both derived from the gonadal blastema. The testicular cords resembled anastomosing sheets more than cords. The ultrastructure of the tissues and their cell types are described and compared to the previous indifferent stage at the age of 24 days. The cells of the surface epithelium, of the primitive cords, of the mesenchyme, and the primordial germ cells had an ultrastructure that was similar in both sexes. The sustentacular cells of the testicular cords resembled the primitive cord cells and the spermatogonia were similar to the primordial germ cells. No Leydig cells were present yet. The process of testicular differentiation is described on the basis of the present and a previous study, and a new hypothesis, based on the vascular organization, is presented.


Dilatation of the mitral anulus. A rare cause of mitral regurgitation. To confirm or deny the thesis that mitral anular dilatation is a cause of mitral regurgitation, this anulus was measured in 102 patients, 24 of whom had normal hearts and 78 of whom had dilated left ventricles, some associated with mitral regurgitation, others not. The circumference of the mitral anulus in the 24 patients with normal hearts averaged 9 cm (range 7 to 11 cm); in 24 patients with idiopathic cardiomyopathy of the ventricular dilated type, both with (12 patients) and without (12 patients) mild to moderate regurgitation, 11 cm (range 10 to 14 cm); and in 31 patients with severe mitral regurgitation, 12 cm (range 8 to 18 cm). Among the latter 31 patients with severe mitral regurgitation, the anulus was only mildly dilated in the 15 with rheumatic disease (average 11 cm) and in the six with ruptured chordae tendinease on previously normal valves (average 10 cm); in contrast, in the 10 patients with floppy mitral valves with or without the Marfan syndrome the mitral anulus was greatly dilated (average 15.5 cm). Thus, only in patients with floppy valves with or without the Marfan syndrome or both does anular dilatation by itself appear great enough to cause mitral regurgitation. It appears, therefore, that dilatation of the mitral anulus is a rare cause of mitral regurgitation and that abnormality of the fibrous skeleton of the heart is necessary for the mitral anulus to dilate enough to cause mitral regurgitation.


Clinical criteria for psychiatric diagnosis and DSM-III. The authors identify the differences in formal inclusion and exclusion criteria used to classify patient data into diagnoses as the largest source of diagnostic unreliability in psychiatry. They describe the efforts that have been made to reduce these differences, particularly the specified criteria approach to defining diagnostic categories, which was developed for research purposes. On the basis of studies showing that the use of specified criteria increases the reliability of diagnostic judgments, they suggest that including such criteria in the next edition of APA's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) would improve the reliability and validity of routine psychiatric diagnosis.


A comprehensive approach to psychiatric diagnosis. The author discusses problems of the typological diagnostic system currently used in psychiatry, which focuses primarily on symptoms in classifying psychiatric disorders. He describes a comprehensive diagnostic system that would involve routine evaluation of five patient characteristics: symptoms, circumstances associated with symptoms, previous duration and course of illness, quality of personal relationships, and level of work function. He suggests that such a multivariable approach to psychiatric diagnosis can provide valuable information about the patient to clinicians, researchers, and other mental health workers.


Human complement C7 and C9 in fetal and newborn sera. Using specific immune sera, C7, C9, and C3 activator were detected in sera from human fetuses more than 16 weeks old and in newborn samples. Levels of C9 in cord sera ranged between 10 and 30% of those present in sera from adult subjects. The mean value of Ce activator was about half that in maternal blood. The mean level of C7 in newborns was nearly 70% of the amount in normal adults.


The influence of diabetic regulation on the diurnal variation in blood and the urinary excretion of ketone bodies. Studies in newly diagnosed diabetics. A typical diurnal variation of blood ketone bodies (acetacetate+3-hydroxybutyrate) has been found in 23 newly diagnosed, untreated diabetics regardless of diabetic type. It was characterized by high morning concentrations, followed by a fall, and later on a rise in concentration during the evening and night. Satisfactory diabetic regulation, judged from glucose measurements, did not change this diabetic pattern, which differed fundamentally from the normal diurnal variation. In the regulated state the morning concentration of ketone bodies in blood was still abnormally high in the juvenile and the non-obese maturity onset diabetics, while the concentration in the phenformin-treated diabetics had increased on each sampling time. The 24-hour urinary excretion of ketone bodies also remained abnormally high in the phenformin-treated patients.


[Identification and differentiation of lens cells in tissue culture]. The cells of S-phase labelled prior to cultivation with H3-thymidine and other neighbouring cambial cells of the lens of the pig, cattle and sheep were found to form morphologically underdifferentiated zones of growth. The zones of growth were formed in the culture from differentiating in vivo cells of the lens. The cells of these zones occasionally resembled abortively differentiated lens fibres in vivo. The growth zones of the lens cells in vitro are comparable by its growings in trauma or cataract in vivo. In lens cultures under routine conditions of cultivation there occurs disturbance of normal embryonic histogenesis and abortive differentiation of the already differentiated in vivo cells.


[Morphological changes in the thyroid gland of rats during various phases of the estral cycle]. The functional state of the thyroid gland and the concentration of thyroid hormones in the peripheral blood were studied in 20 mature female albino rats during their estral cycle. Evaluation of the thyroid functional state was made according to data of histological, morphological (the diameter of folliculi, the height of the thyroid epithelium) and histochemical analysis (determination of NAD and NADP-dehydrogenase, succinatedehydrogenase, lactate dehydrogenase, peroxydase, acid and alkaline phosphatase) as well as biochemical determination of iodine bound with protein (IBP) in the blood plasma and investigation of the ratio of the parameters in question under conditions of the sex cycle. The cyclic changes of the morphological state of the thyroid gland attended by the phases of the estral cycle were revealed. The activation of the organ was observed in proestrus and estrus which was evidenced by high levels of activity of the enzymes under study, high concentration of IBP in the blood and increased height of thyreocytes. A decreased function of the thyroid parenchyma was observed at the period of metaestrus-diestrus.


Effects of egg yolk, glycerol and the freezing rate on the viability and acrosomal structures of frozen ram spermatozoa. The influence of egg yolk, glycerol and the freezing rate on the survival of ram spermatozoa and on the structure of their acrosomes after freezing was investigated. Egg yolk was shown to be beneficial not only during chilling but also during freezing; of the levels examined, 1-5% gave the greatest protection. Although the presence of glycerol in the diluent improved the survival of spermatozoa, increasing concentrations produced significant deterioration of the acrosomes. With closely controlled linear cooling rates, no overall difference was detected in the survival of spermatozoa frozen at rates between 6 and 24 degrees C per min. However, a significant interaction between freezing rate and the inclusion of glycerol in the diluent showed that glycerol was less important at the highest freezing rate. A sudden cooling phase near to the freezing point following the release of the latent heat of fusion was not detrimental to spermatozoa.


The duration of the oestrous cycle of ewes affected with clover disease. Oestrous cycles in ewes affected with clover disease were compared with those for control animals at two locations. Significantly fewer diseased ewes were observed in oestrus. There was a significant increase in variability of oestrous cycle duration in the diseased ewes at one location. Some of the cycle irregularities could be related to gross lesions in the internal genitalia. Despite these findings, there was no association between oestrous cycle abnormalities and previous fertility records, suggesting that they are of little consequence to the infertility of clover disease under field conditions.


Association of xanthine oxidase with the bovine milk-fat-globule membrane. Nature of the enzyme-membrane association. 1. Xanthine oxidase (EC 1.2.3.2) was found to represent more than 8% of the intrinsic protein of the bovine milk-fat-globule membranes. 2. Less than 25% of the xanthine oxidase activity of the fat-globule membrane was solubilized with 0.1 M-sodium pyrophosphate buffer or 2M-NaCl. Of the particulate activity remaining 56% was solubilized with Triton X-100. 3. The xanthine oxidase activity solubilized with buffer, 2M-NaCl or Triton X-100 was not liberated as the free enzyme. Only tryptic digestion was found to release the free enzyme from the fat-globule membrane. Tryptic digestion also liberated free xanthine oxidase from those fractions solubilized by buffer or NaCl, but not from those fractions solubilized with Triton X-100 or by sonication. 4. The effect of membrane association on the catalytic properties of the enzyme could be mimicked by low pH or by the presence in the assay mixture of certain concentrations of 2-methyl-propan-2-ol, but not 1,4-dioxan, suggesting that hydrogen-bonding rather than low dielectric constant may be involved. 5. The origin of the milk-fat-globule membrane is discussed with reference to the intrinsic nature of the associated xanthine oxidase activity.


Stability of pyrimidine oligodeoxyribonucleotides released during degradation of deoxyribonucleic acid with formic acid-diphenylamine reagent. A small release of Pi from a diphenylamine-formic acid digest of DNA was detected after elimination of interpurine phosphodiester bonds was complete. Minor components in the DNA digest were identified as pyrimidine oligonucleotides which had lost one terminal phosphate. Isolated pyrimidine tracts released Pi on  redigestion with the formic acid-diphenylamine reagent in amounts that increased with the number of nucleotides in the oligonucleotide taken. The oligonucleotides were also partially degraded by the formic acid-diphenylamine reagent and the degradation (2-3% of phosphodiester bonds between consecutive nucleotides) was almost independent of chain length. The cleavage was random with no preference for a phosphodiester bond flanked by particular nucleosides. This minor lack of specificity in the formic acid-diphenylamine-catalysed degradation of DNA can, however, account for the low recoveries of long pyrimidine tracts previously reported. Any analysis of pyrimidine tracts in a DNA molecule should make some correction for this small degree of degradation if exact assignments of the numbers of pyrimidine tracts are to be made.


The amino acid sequence of a carbohydrate-containing fragment of hen ovotransferrin. 1. Hen ovotransferrin was treated with CNBr and fractionated by gel filtration. 2. After further treatment by reduction and carboxymethylation a carbohydrate-containing fragment of molecular weight 11990 was obtained (fragment BCd). 3. The amino acid sequence of this fragment was determined. It consists of a single chain of 94 residues. 4. The structure of a tryptic glycopeptide derived from whole ovotransferrin permitted a further eight residues to be assigned at the N-terminus of fragment BCd. 5. Heterogeneity was found at two positions. 6. Further evidence has been deposited as Supplementary Publication SUP 50045 (19 pages) at the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms indicated in Biochem. J. (1975), 145, 5.


Acyl intermediates in penicillopepsin-catalysed reactions and a discussion of the mechanism of action of pepsins. Penicillopepsin catalyses transpeptidation reactions involving the transfer of the N-terminal amino acids of suitable substrates via covalent acyl intermediates to acceptor peptides, usually the substrate. The major products obtained when Phe-Tyr-Thr-Pro-Lys-Ala and Met-Leu-Gly were used as substrates were Phe-Phe and Met-Met respectively. With Met-Leu-Gly the tetrapeptide Met-Met-Leu-Gly was observed as probable intermediate. Co-incubation of Leu-Tyr-Leu and Phe-Tyr-Thr-Pro-Lys-Ala led to the formation of Leu-Phe and Phe-Leu as well as Leu-Leu and Phe-Phe. No reaction was observed with tripeptides in which the first or second amino acid is glycine. It appears that two amino aicds with large hydrophobic residues are needed for the transpeptidation reaction. Nucleophilic compounds other than peptides, such as hydroxylamine, aliphatic alcohols and dinitrophenylhydrazine, were not acceptors for the acyl group. Leucine, phenylalanine and leucine methyl ester also had no effect on the reaction. The transpeptidation reaction proceeded readily at pH 3.6 and 4.7. At pH 6.0 the reaction was slow and at pH 1.9 little or no transpeptidation was observed. Porcine pepsin catalyses similar transpeptidation reactions. Sequence studies show that porcine pepsin and penicillopepsin are homologous. The present study also suggests that they have a very similar mechanism. Evidence available at this time indicates that the mechanism of these enzymes is complex and may be modulated by secondary substrate-enzyme interactions. A hypothesis is presented which proposes that pepsin-catalysed reactions proceed via different covalent intermediates (amino-intermediates or acylintermediates) depending on the nature of the substrate. The possibility that some reactions do not involve covalent intermediates is also discussed.


Glucose- and phlorrhizin-protected thiol groups in pig intestinal brush-border membranes. Purified brush borders, prepared fro newborn pig intestine, were incubated in the presence of 203Hg-labelled p-chloromercuribenzenesulphonic acid and the membrane proteins later separated by polyacrylamide-gel electrophoresis. The presence of either D-glucose or phlorrhizin, during a preliminary incubation in non-radioactive p-chloromercuribenzenesulphonic acid, increased the subsequent binding of the 203Hg-labelled compound to a protein of molecular weight 31500. This increase appeared to be specific for the low-molecular-weight protein, provided that the concentration of protecting agent used corresponded to that used to produce a biological response in the intact tissue. These results are discussed in relation to the known properties of other presumptive sugar carriers isolated from different membranes.


The presence of a high-molecular-weight (guanine-plus-cytosine)-rich segment at the 3' end of rabbit 28S ribosomal ribonucleic acid. The 3' hydroxyl end of 28S L-rRNA (major RNA species of the larger subribosomal particle) was labelled by coupling its 2-hydroxy-3-naphthoic acid hydrazine with diazotized [3H]aniline. The RNA was hydrolysed partially with ribonuclease T1 and fractionated on Sephadex G-200. The results show that a highly structured segment with 78% G+C content and a number-average molecular weight of at least 1.0x10(5)-1.8x10(5) is located at the 3' hydroxyl end of the 28S rRNA molecule.


The effect of Tuftsin on the nitrous blue tetrazolium reduction of normal human polymorphonuclear leukocytes. The influence of Tuftsin, the synthetic phagocytosis-stimulating tetrapeptide (L-threonyl-L-lysyl-L-prolyl-L-arginine), on the nitrous blue tetrazolium (NBT) reduction by human polymorphonuclear leukocytes was investigated. It was found that this substance increases the NBT reduction by approximately as much as endotoxin. Other tetrapeptides do not share this property. When Tuftsin analogs are added to the cell suspension and incubated, they prevent the action of both Tuftsin and endotoxin but not of methylene blue. When washed of the analogs, the cells regain the property to be activated by both Tuftsin and endotoxin. It appears that methylene blue on one hand and Tuftsin and endotoxin on the other hand have different sites for their actions. We suggest that whereas methylene blue diffuses into the cell and acts directly upon the hexosemonophosphate shunt activation, Tuftsin and endotoxin appear to act on the cell membrane binding to specific receptors. By treating the cells with Tuftsin analogs, we probably block these receptors.


Acute fatty liver of pregnancy. Complication by disseminated intravascular coagulation. A 31-year-old white woman had idiopathic acute fatty liver of pregnancy. Shortly after admission to the hospital, it became apparent that she was also suffering from disseminated intravascular coagulation. This was treated with heparin sodium, resulting in cessation of overt bleeding and laboratory evidence of moderate abatement of her coagulation abnormalities. Nevertheless, both patient and fetus died. This case report reemphasizes the need for recognition and therapy for the nonhepatic complications of this syndrome.


Chloramphenicol-resistant Salmonella typhi in Saigon. Chloramphenicol-resistant Salmonella typhi was detected in Saigon in September 1971. Subsequently, 163 strains of S typhi were isolated, 46 percent of which were resistant to choramphenicol by the agar-disk method. Sixty-two strains were studied by the broth-dilution method; 37 percent had minimal inhibitory concentrations for chloramphenicol greater than 250mug/ml, but all strains were susceptible to 0.4mug/ml of ampicillin and to a disk of a combination of trimethoprim and sulfamethoxazole (Bactrim). Persons infected with chloramphenicol-resistant strains of S typhi responded poorly to chloramphenicol alone, but ampicillin or the combination drug was effective.


Disseminated intravascular coagulation and head trauma. Two case studies. Disseminated intravascular coagulation (DIC) developed in two patients following head trauma. Brain parenchyma and highly vascular connective tissue of the choroid plexus and meninges are important pools of systemic coagulation components. This is an important consideration in the treatment of head injury.


The bizarre stiff hip. Possible idiopathic chondrolysis. Idiopathic chondrolysis of the hip is characterized by pain and limp in adolescence, with progressive loss of articular cartilage space and stiffness of the hip. In our five cases, the best results were obtained in those patients immobilized in a position of function. Those cases in which range-of-motion exercises were carried out resulted in ankylosis in a position of excessive flexion.


Adjuvant therapy of cancer via the cellular immune mechanism or fibrin by induced fibrinolysis and oral anticoagulants. The value of the oral anticoagulant warfarin sodium and fibrinolytic agents is discussed in relation to cancer surgery. A controlled trial of 128 patients showed that in a variety of recurrent cases the addition of warfarin to chemotherapy doubled the 2-year survival rate. The best results were obtained in postmenopausal patients with breast cancer. Warfarin depresses cellular immune responses which might militate against its use for cases undergoing "curative" surgery. Instead, induction of fibrinolysis by streptokinase or Brinase is suggested, because it increases the activity of the cellular immune mechanism. The results to date of an ongoing controlled randomized trial of streptokinase with surgery of tumors of the large bowel are presented, showing that the trends are in favor of streptokinase therapy; however, insufficient time has elapsed to make it, as yet, statistically significant. The action of streptokinase-induced plasmin and Brinase on lymphocytes is described.


RNA polymerase isolated from bovine lymphosarcoma by sequential low- and high-salt extraction. Bovine lymphosarcoma tissue has been extracted with low- and high-salt buffers [0.05 M Tris-C1 plus or minus 0.3 M (NH4) 2S04]. Diethylaminoethyl-Sephadex chromatography of both the high-salt and low-salt extracts yields RNA polymerases I and II, although low-salt extraction releases only one-third as much activity. Extraction by high salt of the residue from the low-salt extract, followed by diethylaminoethyl-Sephadex chromatography, yields additional enzyme activity with properties of Form II. Purification of the low-salt extract by protamine precipitation, elution with sodium succinate, and phosphocellulose chromatography yields a preparation of RNA polymerase (RNAP) with hybrid properties, combining the salt optimum of Form I, diethylaminoethyl-Sephadex elution pattern of form II, and alpha-amanitin sensitivity of Form III. RNAP. transcribes native D,A and chromatin efficiently. More RNAPL is recovered from lymphosarcoma tissue than from calf thymus.


Infiltrative retinopathy in systemic lymphoma. A 48-year-old woman with a diffuse well-differentiated lymphocytic lymphoma developed an unusually extensive bilateral infilfrative retinopathy during a period of quiescence of her systemic illness. Although radiation therapy to each orbit initially induced clearing of the infiltration and significant improvement in visual acuity, late visual acuity loss due to retinal and optic nerve changes ensued.


Early changes in lungs of rats exposed to 70 per cent O2. Sixty-six respiratory disease-free rats, divided into four groups, were exposed to 70% O2 for 1.5, 4, 7, and 10 days and compared with 31 littermates exposed to room air for equal times. Lung surfactant was separated from macrophages and potential serum protein contamination by differential centrifugation of endobronchial washings. In the O2-exposed rats, developing lung edema was demonstrated by decreased dried/fresh lung weight ratio and increased alveolar protein content at 7 and 10 days. At 7 days, lung compliance slope and hysteresis loop area decreased, while critical opening pressure increased. Ultrastructurally, the only abnormality seen was an irregular widening of the alveolar capillary basement membrane on day 10. Alveolar lecithin content decreased slightly during the 10 days exposure, but remained highly saturated, whereas whole lung lecithin content increased. These results suggest that the initial mechanical and morphological alterations in rats exposed to 70% O2 are related to lung edema and are not dependent upon lung surfactant alterations.


Methods of burn treatment. Comparison by probit analysis. No one method of burn treatment has been shown to give results clearly superior to any other, although results of therapy in units using different methods do vary significantly. Probit analysis can be used to see whether or not a burn unit meets the standard of care of representative units.


HL-A antigens and sacroiliitis.

HL-A antigens and sacroiliitis. The histocompatibility antigen W27 has been found to have a high incidence in ankylosing spondylitis (96%), Reiter syndrome (74%), and other forms of arthritis that may involve the axial skeleton. In patients with Reiter syndrome, there was no correlation between the presence of W27 antigen and the extent or duration of the symptoms. Sacroiliitis was predominantly found in those patients with W27 antigen in all the axial arthropathies. Tissue-typing techniques may be of value in detecting early or atypical disease.


Pentazocine-induced fibrous myopathy.

Pentazocine-induced fibrous myopathy. Fibrous myopathy was found in three patients who had taken pentazocine intramuscularly for years. Fibrotic induration in the quadriceps and deltoid muscles, the considerable limitation of motion due to the fibrotic muscle contracture, and the minimal weakness of involved muscles are the most characteristic findings in this condition. Results of animal experiments support the close relationship between myopathy and pentazocine. This serious complication emphasizes more judicious use of pentazocine


Influenza type B-related encephalopathy. The 1971 outbreak of Reye syndrome in Chicago. Between Jan 15 and March 15, 1971, forty-eight grade-school patients living in western Chicago were hospitalized with an encephalopathic illness. Fourteen of these children had illnesses compatible with Reye syndrome (encephalpathy with liver impairment). Most of the children showed evidence of central nervous system (CNS) dysfunction within ten days after onset of a febrile upper respiratory tract illness. Seizures developed in 11 of the 48 patients (including 4 of the 14 with Reye syndrome). Eight of the encephalopathic patients, including 6 of the 14 with Reye syndrome, died. Two children without Reye syndrome had abnormalities of liver enzymes coincident with cerebrospinal fluid pleocytosis. Sixteen of the 24 patients tested had titer rises in serum against influenza type B only; influenza type B was isolated from throat cultures of 2 patients. This, the seventh report of CNS complications (Reye syndrome) associated with influenza type B, suggests that surveillance for neurologic sequelae should become part of the epidemiologic evaluation of influenza epidemics.


Intracranial pressure in Reye syndrome. Monitoring and control. Two patients who became comatose with Reye syndrome had continuous monitoring of intracranial pressure and blood pressure. Respirations were controlled, and mannitol and urea were administered to control elevated intracranial pressure. Continuous intracranial pressure monitoring proved to be a valuable adjunct to therapy for Reye syndrome.


Potassium chloride preparations and fecal blood loss. A parallel study with a 10 percent solution and a non-enteric-coated waxy-matrix tablet. Concentrated potassium chloride produces ulceration of the gastrointestinal mucosa. Dilute solutions are frequently not acceptable to the patient. A tablet containing potassium chloride crystals suspended in a waxy matrix has been developed to avoid these drawbacks. We measured fecal blood loss by a radioactive chromium technique on 20 subjects during five days while they were given potassium chloride, 40mEq/day; ten subjects took a 10% solution; the others the waxy-matrix tablet. Fecal blood loss did not differ significantly between these groups. Mean fecal blood losses in both groups were slightly increased during the potassium chloride administration but never exceeded acceptable normal limits.


Insoluble particulate antigen(s) in cell-mediated immunity of autoimmune thyroid disease. Cell-mediated immunity (CMI) in patients with Grave's disease, chronic thyroiditis, and primary hypothyroidism was observed by assay of lymphocyte-mediated cytotoxicity (LMC) and leukocyte migration inhibition (LMC). Lymphocyte responsivity to phytohemagglutinin (PHA) is normal in these disease. In the LMC assay, lymphocytes of patients in each category responded to the antigens of thyroid homogenates, but not purified human thyroglobulin. Cytotoxicity is least in Graves disease and most obvious in primary hypothyroidism. In the LMI assay, patients lymphocytes responded to thyroid microsomal--mitochondrial antigens, but not to thyroid cell sap. Lymphocytes of Graves disease patients also responded to liver microsomal mitochondrial antigens. The particulate antigens lost activity when solubilized by ultrasonication or KCL extraction. There is no correlation between the PHA responsivity of lymphocytes and thyroid function, or between CMI and serum antithyroid antibodies or thyroid size. Treated and untreated patients had similar evidence of CMI. These data indicate that function of thymus-derived lymphocyte in vitro is not disturbed in autommune thyroid disease and that CMI against thyroid antigens can be demonstrated by assay of LMC and LMI. Insoluble particulate antigens appear more important than soluble antigens in CMI. LMC, resumably induced by soluble cytotoxic factor, "lymphotoxin," may play an important role in the progress of the autoimmune thyroid disease to hypothyroidism.


[Macronucleolar transformation of a leukemic lymphosarcoma. Clinical morphologic and molecular biologic parameters]. In a case with leukemic lymphosarcomatosis huge nucleoli developed at a final stage refractory to chemotherapy. The lymphosarcoma cells were characterized before and after their macronucleolar transformation by cell fractionation and by biochemical characterization of their nuclear 45S RNA fraction after high specific labelling with 32P-orthophosphate. The analyses provided evidence for a marked increase in nucleolar 45S RNA production. Processing of preribosomal RNA did not seem to be blocked. The biochemical alterations are discussed especially with respect to a possible significance of biological changes during the development of drug resistance against cytostatic agents.


Bovine leukosis. IV. Trypanosomiasis, lymphocytosis and DNA synthesis. The possible influence of natural trypanosome infection on lymphocytosis and DNA synthesizing lymphocyte counts in peripheral blood was determined on 220 cows from two leukosis herds and 25 cows from leukosis free control herd. Trypanosome incidences were determined during summers of 1969 and 1970 by inoculating whole blood onto blood agar slants and incubating at room temperature. Incidence of trypanosomiasis in cattle was found to be variable, possibly due to factors affecting the primary isolation of Trypanosoma theileri. A small trypanosome resembling Trypanosoma uniforme was found occasionally as a concomitant infection with T. theileri. Trypanosomiasis occurred with equal frequency in the animals of the leukosis and the control herds. No correlations were noted between trypanosomiasis, lymphocytosis and DNA synthesizing lymphocytes in peripheral circulation.


Splenectomy for hematologic depression in lymphocytic lymphoma and leukemia. Fifty patients with lymphocytic lymphoma and chronic lymphocytic leukemia underwent splenectomy for various combinations of anemia, thrombocytopenia, and leukopenia. All of these patients had advanced lymphoproliferative disease, and most had infiltration of bone marrow by neoplastic cells. Good response in all hematologic parameters was obtained in 27 of 48 evaluable patients. An additional 13 patients responded in one or two parameters; there were only 8 complete failures. The over-all surgical mortality was 8%. The median duration of response was 4 months, and the mean, 7 months. Increased tolerance to further antitumor therapy and a decreased transfusion requirement were seen among responding patients. Those patients with anemia who had evidence of shortened erythrocyte survival and splenic sequestration of 51Cr-labelled erythrocytes uniformly responded with rises in hemoglobin. However, half of the patients with negative splenic sequestration also showed improvement of anemia. Preoperative diagnostic studies failed to predict favorable responses of patients with thrombocytopenia or leukopenia. The classical criteria for the diagnosis of hypersplenism are not applicable in many cases of neoplastic lymphoproliferative disease; splenectomy could have been considered "contraindicated" in most of the patients in this series. We conclude that splenectomy is worth undertaking in patients with lymphoproliferative disease complicated by hematologic depression regardless of marrow findings or the results of other diagnostic studies.


The destruction of type 2 pneumocytes by airborne influenza PR8-A virus; its effect on surfactant and lecithin content of the pneumonic lesions of mice. Influenzal pneumonia has been studied in mice subjected to sublethal doses of airborne PR8-A influenza virus. Electron microscopy revealed that the virus propagated in and at the same time destroyed the ciliated and nonciliated bronchial cells and the types 1 and 2 alveolar pneumocytes. The regenerating bronchial membranes were metaplastic and grew peripherally into the surrounding alveolar ducts and alveoli to form epithelial nodules which caused obstruction and collapse of the involved lobes. The development of the lung lesions was correlated with phospholipid (lecithin) levels in consolidated and unconsolidated infected and normal lungs. As the lungs became more and more consolidated, there was a corresponding and significant decrease in the amount of phospholipid (dipalmitoyl lecithin) compared to the amount of normal or unconsolidated infected tissue. The destruction of the type 2 pneumocytes by the influenza virus and their failure to regenerate is considered to be the reason for the low phospholipid levels in the involved lobes, and thus an important cause of post-influenzal collapse in mice. The above adds additional evidence to the view that the type 2 pneumocytes are a major source of surfactant in mammalian lungs.


Major fatty acids and proximate composition of dairy products. Data are reported on the major fatty acids and moisture, protein, fat, lactose, and ash content of several important dairy products, including major cheeses, presently available to the consumer. Samples of milk products, cheeses, wheys produced in processing, and the original milks from which the products were made were obtained from dairy processing plants. Samples of cheeses were also obtained from retail markets in six geographic areas of the United States. Nonfat fluid whole milk contained amounts of protein, lactose, and ash similar to those found in fluid whole milk. The fatty acid distribution of milk fat was not appreciably altered by the processing employed for this study. Protein and fat values were quite constant among samples of each cheese. No lactose was detected in the ripened cheeses. Mean fatty acid patterns for the different cheeses were not appreciably different from each other. The butyric acid (4:0) in the cheeses showed the greatest sample variation. The cheeses did not contain appreciably different proportions of polyunsaturated fatty acids. Procedures for converting data on fatty acid methyl ester to fatty acids (free acids or triglycerides) as weight percentages of the food are presented.


Pathophysiology of chronic communicating hydrocephalus in dogs (Canis familiaris). Experimental studies. A model designed to produce chronic communicating hydrocephalus in dogs has been developed in our laboratory. The animals tolerate the procedure well and the yield of animals with communicating hydrocephalus is high. Serial cisternograms show ventricular entry first with "clearing" and later with "stasis". CSF pressures are initially increased, but when the ventricles become enlarged the pressure falls into the normal range. Grossly there is generalized ventricular enlargement and, on histological studies, the ependyma is flattened and denuded. Periventricular edema occurs in the white matter. Autoradiographs show transependymal movement of protein. CSF production appears to be normal despite obstruction to flow of CSF to areas where resorption is greatest. Diversionary shunting probably produces relief of many of the neurological symptoms by providing an efficient pathway for the removal of CSF and thus by lessening edema and ventricular enlargement. A more appropriate treatment would appear to be a noninvasive method of decreasing CSF production. Only when the basic pathophysiological alterations of CSF production and absorption are understood will this be possible. We believe that this animal model affords us the opportunity of studying these mechanisms.


Experimental meconium aspiration: Effects of glucocorticoid treatment. An animal model of meconium aspiration was developed to determine the efficacy of glucocorticoids in its treatment. Rabbit pups were made to aspirate either meconium or saline prior to the onset of respiration. Cortisol was administered in a random, blind fashion. Slight decrease in respiratory rate and less severe histopathologic changes in the lungs were seen in corticosteroid-treated animals. Survival was significantly decreased, without definite cause, in the glucocorticoid-treated animals whether or not they had aspirated meconium. Because of this decreased survival and the relatively insignificant improvement in clinical course and histopathology found with glucocorticoid treatment, we cannot recommend cortisol for the treatment of meconium aspiration.


Blast injury of the chest. A review of the problem and its treatment. Primary blast injury of the chest is a potentially lethal entity. Immersion blast is even more damaging than that incurred out of water. Illustrative cases of a group of patients injured by an underwater explosion are presented. The pathogenesis, clinical manifestations and diagnosis of the entity are described. Complications include arterial occlusion by air emboli, affecting the central nervous system and heart, and respiratory insufficiency and failure. Conventional management of respiratory failure with intermittent positive pressure breathing may further aggravate the air embolism. An attempt to circumvent this conflict with the aid of the membrane oxygenator and hyperbaric facilities is discussed. It is suggested that expeditious compression with oxygen in a one-man chamber might be the most favorable emergency measure, to be followed later by more extensive and definitive treatment in a major hospital equipped for such contingencies.


Embryonic antigens shared between chemically induced lymphosarcomas and fibrosarcomas of the mouse. An antiserum obtained by the immunization of C57BL/HeDp mice with a pool of C3HF/Dp 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced fibrosarcomas exerted a specific cytotoxic activity in vitro on C57BL/HeDp chemically induced lymphosarcomas. Conversely, C57BL/HeDp spleen cells sensitized against C3Hf/Dp chemically induced lymphosarcomas or embryo cells were cytotoxic for plated cells of syngeneic DMBA-induced fibrosarcomas. Absorption studies with antiembryo and antilymphoma antisera showed that embryonic antigens were shared between lymphosarcomas and fibrosarcomas and that all serologically defined antigens present on lymphoma cells, including virus-related antigens, were also on fibrosarcoma cells.


Renovascular occlusive disease. Results of operative treatment. The blood pressure response to operative treatment in 502 patients with renal artery stenosis and coexisting hypertension was as follows: 51% cured, 15% improved, and 34% failure. The operative mortality was 5.9%. Patients with unilateral fibromuscular disease had a favorable blood pressure response (79.8%) more frequently than the patients with unilateral atherosclerosis (63.4%). In patients with bilateral stenosis, a favorable result occurred in 56%. The anatomic failure rate due to thrombosis of arterial reconstructions, as well as the operative mortality, varied considerably between institutions. If preoperative diagnostic studies demonstrated significant functional disparity between kidneys, and if the operation was anatomically successful, then approximately 80% of these patients were benefited by surgical intervention.


Food-borne hepatitis A in a general hospital. Epidemiologic study of an outbreak attributed to sandwiches. In November and December 1973, an outbreak of food-borne hepatitis A occurred in a busy general hospital. Epidemiologic investigation implicated cafeteria-made sandwiches. Eventually, 44 clinical and 22 subclinical cases of hepatitis were diagnosed among hospital employees. In addition, at least seven persons in the community became ill with hepatitis after eating in the hospital cafeteria; hospital patients were not, in general, affected. Two cafeteria workers were potentially implicated in the spread of hepatitis; both would have had subclinical hepatitis during the probable transmission period. It was recommended that food-handlers with icteric hepatitis remain out of work for at least two to three weeks after the onset of jaundice, while food-handlers with subclinical hepatitis remain out of work for at least two to three weeks after the peak of enzyme level elevation.


Radionuclide imaging in intrascrotal lesions. Twenty-three patients with a variety of intrascrotal lesions were studied by means of imaging after the intravenous injection of sodium pertechnetate Tc 99m. The features of the radionuclide image correlated well with the clinical course or findings at surgical exploration or both. The conditions in which this technique was helpful in diagnosis included testicular torsion, acute inflammatory lesions, abscess, and hematoma.


Allopurinol and gouty hyperuricemia. Efficacy of a single daily dose. The effect of daily administration of a single 300-mg tablet of allopurinol on serum urate levels was compared with the effect of divided doses of the drug (100 mg three times a day) in an open-labeled crossover trial of 20 patients with hyperuricemia and gout. Under both regimens of treatment there was a prompt fall in serum urate levels, and analysis of variance indicated no significant difference between the two modes of administration of allopurinol. Nor was there any significant difference in the minimum serum levels of oxypurinol. On the basis of this short-term study, the use of a single 300-mg tablet of allopurinol per day appears to be an effective means of lowering the elevated serum urate levels of individuals with gouty hyperuricemia and compares favorably with the results obtained by allopurinol in divided doses.


Operative morbidity and mortality in renovascular disease. There were 104 major complications (13.1%) and 34 deaths (5.9%) among 502 patients with evidence of renovascular disease who underwent 577 operative procedures. The operative mortality rate in patients with atherosclerotic renovascular disease was 9.3% vs 3.4% with fibromuscular hyperplasia. Important determinants of renovascular operative mortality are (1) cause of disease, (2) presence of coronary artery disease, (3) presence of bilateral renal functional impairment, (4) the complexity of the renal operative procedure, and (5) concurrent extrarenal surgery.


Immunotherapy in bee-sting anaphylaxis. Use of honeybee venom. After nine months of immunotherapy with commercially prepared wholebody bee extract, a beekeeper's wife experienced anaphylaxis after a controlled bee-sting challenge. High risk of future bee stings prompted a decision to attempt desensitization with honeybee venom. This was extracted from the bee into Coca solution and administered parenterally in increasing daily doses until an equivalent of one venom sac was given per day. This maintenance dosage was continued for a month. Anaphylaxis did not occur after another bee-sting challenge. Therapy has been maintained with venom. With this treatment, there has been an increase in the level of IgG-blocking antibody and a fall in IgE titer to bee venom (radioallergosorbent test [RAST]).


Pseudomembranous colitis. Association with antibiotics and therapy with cholestyramine. Two patients with diarrhea and pseudomembranous colitis associated with lincomycin hydrochloride monohydrate and clindamycin phosphate therapy were treated with cholestyramine resin, with prompt remission of symptoms.


Lead in pet foods and processed organ meats. A human problem? The finding that canned pet foods contain considerable amounts of lead is important, since it had been alleged that some of these products are used for human consumption. The lead content of canned dog and cat food ranged from 0.9 to 7 ppm, and ingestion of 170 gm (6 oz) could provide up to 0.95 mg of this toxic element. The lead probably comes from organ meats used in the manufacture of pet foods. The lead content of liverwurst ranged from 1.6 to 7.6 ppm.


Further reflections on cervical discography. Ten years ago in THE JOURNAL, I-1 presented evidence that cervical discography was without diagnostic value and was prompting overdiagnosis and serving as an excuse for unnecessary surgical treatment. Evidence has accumulated to uphold this view, and, in my opinion, unless some modification of method and interpretation of the test is forthcoming, it should be abolished.


The diagnosis of pheochromocytoma. Overnight excretion of catecholamine metabolites. The diurnal variation of urinary vanillylmandelic acid (VMA) and metanephrine-normetanephrine levels was studied in six patients with phechromocytoma and 32 patients with essential hypertension. Despite variable degrees of day-night differences, urinary excretion of VMA and metanephrines, per unit of time or per gram of urinary creatinine, was invariably higher in patients with pheochromocytoma than in controls whether the collection was 7 AM through 7 PM or 7 PM through 7 AM. Thus, shorter study periods are sufficient to exclude the presence of a chromaffinoma in most patients with hypertension.


Muscial hallucinations in deafness.

Muscial hallucinations in deafness. Formed auditory hallucinations associated with acquired deafness have seldom been reported in the English literature. In the past year we have had the unusual opportunity of examining two deaf patients whose complaint when first seen was that of hearing music.


Evaluation of an anti-infective combination. Trimethoprim-sulfamethoxazole (Bactrim, Septra). Trimethoprim and sulfamethoxazole, combined in a synthetic anti-infective preparation, act  synergistically to inhibit the growth of certain microorganisms. This  combination is effective orally in acute and chronic urinary tract infections. It also has been used successfully to treat other infectious conditions, including bacterial upper respiratory tract infections, ear infections, skin and soft-tissue infections, septicemias, acute and subacute bacterial endocarditis, enteric fever, brucellosis, prostatitis, and gonorrhea. It is well tolerated by most patients.


The Dalkon Shield controversy. Structural and bacteriological studies of IUD tails. The recent report of 209 cases of septic spontaneous abortion and 11 maternal deaths in the United States in women using the Dalkon Shield intrauterine device (IUD) raised the question about a possible causal relationship between the IUD and pelvic sepsis. It is essential to determine whether or not this sipsis is unique to the Dalkon Shield or generic to all types of IUDs. Our studies permit the conclusion that the tail of the Dalkon Shield is structurally and functionally different from the tails of the four other IUDs tested. The unique characteristics of the Dalkon tail theoretically could provide a mechanism whereby pathogenic bacteria from the vagina enter the uterine cavity and cause sepsis.


Oral contraceptives and stroke in young women. Associated risk factors. Oral contraceptive use alone, in the absence of smoking, hypertension, or migraine, significantly increases the risk of stroke. Regardless of use or nonuse of these agents, hypertension is a risk factor for development of either thrombotic or hemorrhagic stroke. Regular cigarette smoking and a history of symptoms indicative of migraine also increase the likelihood of one or the other type of stroke, but more information is needed before a definite relationship can be established between these clinical factors and cerebrovascular disease.


Gastrointestinal illness on passenger cruise ships. Medical logs of 2,445 cruises taken by 38 vessels over a 20-month period beginning Jan 1, 1972, were reviewed. On 92% of the cruises, the recorded incidence of gastrointestinal illness was 1% or less; on 2% of cruises, it was 5% or greater. The actual incidence of gastrointestinal illness determined by a questionnaire survey of passengers sailing on nine cruises was found to be at least four times as high as that recorded in the medical logs. Although the cause of the illnesses was not known, there was evidence that transmission took place aboard ship. A survey of food-handling practices and water systems aboard selected ships demonstrated a significant potential for transmission of foodborne and waterborne disease.


Controlled study of the cytotoxic food test. The cytotoxic food test was not found to be an accurate method for diagnosing atopic reactions to foods. Claims that the test correlated with other untoward reactions to foods (eg, headache, diarrhea, fatigue) could not be corroborated. The test itself is time-consuming, dependent on subjective interpretation, and inconsistent in results when repetitive runs are performed on the same patient.


Oral contraceptives, serum folate, and hematologic status. Previous reports have suggested deleterious effects on folate balance in users of contraceptives. A study of folate in 526 women attending a family-planning clinic demonstrated, both with the Lactobacillus casei assay and with a new radioassay, that the mean serum folate level for women taking oral contraceptives was not significantly lower than that for women in a control group. There was no correlation between serum folate level and length of time oral contraceptives were taken. Also, there was no macrocytosis or hypersegmentation of polymorphonuclear leukocytes and no case of macrocytic anemia in the 280 users of oral contraceptive agents. Probably, oral contraceptive agents do not cause folate deficiency anemia in otherwise normal subjects.


Pulmonary sling. Case report and collective review. The eighteenth survivor of correction of an anomalous left pulmonary artery arising from the right pulmonary artery is reported. This is the first case in which postoperative angiography demonstrated patency of the left pulmonary artery. The onset of symptoms in infancy, predominance of expiratory rather than inspiratory stridor, anterior indentation of the esophagus, and lethal progression of symptoms during the first year of life are peculiar to this anomaly. Operation through a left thoracotomy is advocated, with division of the proximal left pulmonary artery and implantation into the main pulmonary artery posterior to the phrenic nerve. Previously reported cases are collectively reviewed.


Malignancy and the benign lymphoepithelial lesion. The benign lymphoepithelial lesion of salivary glands is now considered the histological hallmark of a variety of clinical and pathological disorders affecting salivary tissues. Malignancy arising in the lesion is uncommon, but may take origin in either the epithelial or lymphoreticular components. Lymphomas and pseudolymphomas associated with salivary gland lymphoepithelial lesions have been predominately extra-salivary and strongly correlated with Sjögren's syndrome. Epithelial malignancy has not been associated with autoimmunity and with few exceptions has been of the anaplastic type. This report presents two patients with intra-salivary lymphomas arising in a benign lymphoepithelial lesion of salivary glands and a patient with anaplastic carcinoma arising in the epithelial islands of the lesion. The fourth patient manifested pseudolymphomatous lymphoreticular hyperplasia in lung and submandibular gland and illustrates the possible multiple organ involvement that may occur in patients with benign lymphoepithelial lesion, even without clinical evidence of concommitant autoimmune disorders.


[Pulmonary surfactants].

[Pulmonary surfactants]. Reference is made to classic studies pointing to the existence of lung surfactants in the alveolar lining layer and more recent investigations of their chemical nature. Attention is also given to work on biochemical and lung elasticity modifications caused by the employment of various drugs.


Further characterization of some heterophile agglutinins reacting with alkali-labile carbohydrate chains of human erythrocyte glycoproteins. The nature of the receptor sites for several agglutinins is characterized by hemagglutination inhibition assays. The inhibitory activity of human erythrocytes glycoproteins, from which sialic acid, sialic acid and galactose or alkali-labile oligosaccharides have been removed, is compared to the inhibitory effect of compounds with known structure. It is shown that the lectin from Arachis hypogea and anti-T bind to alkali-labile galactosyl-residues. Agglutinins from Bauhinia purpurea and variegata (non- or N-specific), Maclura aurantiaca, Iberis amara, sempervirens, umbellata hybrida and umbellata nana (M- or nonspecific), Moluccella laevis (A- plus N-specific), Helix pomatia, Helix aspersa, Helix lucorum and Caucasotachea atrolabiata interact with alkali-labile N-acetylgalactosamine. The results obtained with the anti-A agglutinins from various snails suggest that human erythrocyte glycoproteins contain, besides the alkali-labile tetrasaccharide, a peptide-linked sialyl-N-acetyl-galactosaminyl-residue. The investigations do not allow a precise definition of the receptor sites for the lectins having M- or N-specificity.


Effects of LH and HCG on the metabolism of the prepubertal rat ovary: stimulation of amino acid transport, protein synthesis, and glycolysis. It has earlier been reported from this laboratory that FSH can stimulate amino acid uptake, protein synthesis and glycolysis in the isolated prepubertal rat ovary. In the present investigation to the effects of LH and HCG were studied. The hormones were injected to prepubertal female rats, and the ovaries were extirpated for incubation in Krebs bicarbonate buffer 120 min later. Injected of 1 mu g/100g body weight of a bovine LH preparation (NIH-LH-B8) produced a significant increase in the in vitro uptake of (14C) alpha-amino-isobutyric acid (14C)AIB) and (3H)leucine as well as of the incorporation of radioactivity into the ovarian protein. Higher doses (10 and 100 mu g) of NIH-LH-B8 gave only minor futher increases. Lactic acid production during the incubation period was also measured as a determination of the rate of glycolysis. Lactic acid production was stimulated by the LH injections with a clear dose-response between 0.1 and 10 mu g/100 g body weight. The effects of LH were also investigated with shorter intervals between the injection of the hormone and the extirpation of the ovaries. While lactic acid production was maximally stimulated at a time interval of 30 min (the shortest time interval studied), 60 min was necessary for the stimulation of amino acid uptake and amino acid incorporation into protein. Injections of HCG mimicked the effects of LH on all parameters studied.


Glucose tolerance in newborn infants of healthy mothers: its relationship to the mothers' insulin response to glucose infusion. It has earlier been postulated that a low insulin response to a glucose infusion is characteristic for the prediabetic individual (Cerasi & Luft 1967c). There is also evidence that some infants of individuals with low insulin response might have a carbohydrate metabolism that is in some respects similar to that of newborn infants to diabetic mothers (Edström et al. 1974). In the present study 15 infants to low insulin responders (ILR) and 22 infants to high insulin responders (IHR) were subjected to an intravenous glucose load (IVGTT) at 2-24 h age. A significant difference in glucose tolerance was found between the groups, the mean k-value for the ILR being 1.39 plus or minus 0.41 and that for the IHR 1.05 plus or minus 0.09 (P smaller than 0.05). No mothers were found to have a gestational diabetes (with the possible exception of one low insulin responders) but during late pregnancy the mean k-value at IVGTT in the low responders decreased from non-pregnant values (the mean difference being 0.41 plus or minus 0.20, P smaller 0.025) while the high responders did not show a corresponding decrease (mean difference 0.12 plus or minus 0.25, P greater than 0.05). No other differences between the groups of infants that could influence the k-value could be found apart from the mothers being low or high insulin responders. Our findings show that a low insulin response in the mothers might effect the glucose tolerance of the foetus even in the absence of continuous maternal hyperglycaemia in late pregnancy.


Dose-dependent effects of ethinyloestradiol, diethylstilboestrol and oestradiol on the metabolism of 4-androstene-3,17-dione in rat liver microsomes. The effects of administration of ethinyloestradiol (EtE2), 0.1, 0.5 or 1 mu g per day, diethylstilboestrol, 5, 100 or 500 mu g per day, and oestradiol, 1 or 100 mu g per day for 12 days on the hepatic microsomal metabolism of 4-(4-14C)androstene-3,17-dione were studied in castrated male and female rats. When rats were given EtE2 in daily doses of 0.1 and 0.5 mu g, the activities of the 3 alpha- and 17 beta-hydroxysteroid oxidoreducatses increased in both male and female rats. A similar tendency was noted for the 5 alpha-reductase in female rats. On the other hand, the activities of the 3 beta-hydroxysteroid oxidoreductase and 7 alpha-hydroxylase enzyme systems were suppressed in both male and female rats already after administration of 0.1 mu g of EtE2. Diethylstilboestrol, administered in doses of 100 and 500 mu g, and oestradiol, given in a dose of 100 mu g, suppressed the microsomal enzyme activities whereas the lower doses of 5 mu g of diethylstilboestrol and 1 mu g of oestradiol were without effects. The results indicate that oestrogenic compounds given in doses higher than the physiological one have a suppressing effect on microsomal steroid metabolizing enzyme activities. Ethinyloestradiol has a stimulating effect on certain microsomal enzyme activities and an inhibiting effect on others when administered in an amount of 0.5 mu g-kg-1 per day. The findings are discussed in relation to recent reports on impaired drug metabolism in women taking contraceptives.


Urinary excretion of free cortisol in impaired renal function. Total cortisol and free, non protein-bound coritsol in plasma and urinary excretion of unconjugated free cortisol were measured during iv infusion of cortisol at varying dose rates in eight patients with impaired renal function. The results showed that free urinary cortisol decreased with decreased glomerular filtration rate (GFR), also compared to free cortisol level in plasma. An increase in free cortisol in plasma had no influence on GFR. It is concluded that determination of free urinary cortisol, otherwise useful in diagnosing Cushing's syndrome, may be of less value in patients with impaired renal function.


The in vivo metabolism of cortisol and corticosterone by the macaque monkey (Macaca fascicularis). (4-14C) Cortisol was administered intramuscularly to one adult female macaque monkey, MF3 (Macaca fascicularis). To adult female macaque monkey, MF4, (4-14C)corticosterone was administered intramuscularly. Urine samples were collected and the metabolites excreted identified using gas chromatography, radio-gas chromatography and gas chromatography-mass spectrometry. The principal metabolites of cortisol were identified as glucuronide conjugates of 11-oxygenated-17-oxosteroids. The excretion of tetrahydrocortisol and tetrahydrocortisone relative to the other corticosteroid metabolites was low compared with that of man. Two compounds, 3 beta-cortol and 3 beta-cortolone not normally present in human urine were identified in the urine from this species. The prinicpal metabolites of corticosterone were glucuronide conjugates of hexahydroCompound A and hexahydrocorticosterone. Two unidentified radioactive compounds were also present.


Correlation between somatomedin A in serum and body height development in healthy children and children with certain growth disturbances. The somatomedin A level in serum was determined in a series of 66 children in whom longitudinal data on body height growth and dental development were available. The series comprised normal children as well as children with some different types of growth disturbances. A high correlation was found between the somatomedin A level and the age at a certain stage of the dental maturity (r equals to minus 0.67) and between the somatomedrin A level and the growth rate at this age (r equals to 0.67). The different groups of patients ranging from pituitary dwarfs to unusually tall children demonstrated a continuous gradient in the correlation between the level of somatomedin A and the different variables of the somatic development.


Effects of general anaesthesia and severity of surgical stress on serum LH and testosterone in males. Significantly decreased levels of serum testosterone from the pre-anaesthesia level were found during and up to 7 days following major surgery under general anaesthesia (nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride) in 18 male patients. On the other hand in the same patients, the serum lutenizing hormone (LH) increased significantly from the pre-anaesthesia level 30 min and 1 h after the beginning of anaesthesia. A slight increase in LH level was also noted on the 7th post-operative day. The determinations of serum testosterone and LH in fiberoptic bronchoscopy under the same general anaesthesia as that used in surgery or local anaesthesia in 26 male patients, revealed that the change in the serum LH during and following surgery seemed to be mainly induced by the general anaesthesia and that the rate of decrease in the serum testosterone may be related to the severity of surgical stress including the anaesthesia. The rate of increase in serum testosterone following the injection of gonadotrophin in 20 males on the 6th post-operative day was similar to that in 10 pre-operative males. The effects of pulmonary lobectomy on serum testosterone and urinary steroids were also studied in 6 males under adrenal suppression with dexamethasone. On the 6th post-operative day, the urinary aetiocholanolone plus androsterone and serum testosterone were found to be half the level of those on the pre-operative day, while the urinary 5beta-pregnane-3alpha, 17alpha, 20alpha-triol remained unchanged. These observations in human are not inconsistent with the report of Tcholakian and Eik-Nes (1971) in dogs namely that a shift in androgen biosynthetic pathway is present in the testis under surgical stress.


On the modulating effects of ovaries on neonatal androgen programming of rat liver enzymes. The metabolism of 4-[4-14C]androstene-3,17-dione in rat liver microsomal and cytosol fractions was investigated in adult female rats treated with 1.45 mumole of testosterone propionate at birth. The effects of ovariectomy at 14 and 43 days of age on neonatal testosterone imprinting of enzyme levels were studied. Animals spayed 14 days after birth showed a typical masculinized hepatic enzyme activity pattern with a decreased level of the 5alpha-reductase activity and increased level of 5beta-reductase, 16alpha-hydroxylase and 17alpha- and 3beta-hydroxysteroid reductase levels. The pattern was essentially the same in testosterone propionate-treated rats spayed 43 days after birth - with the exception of a feminized 5alpha-reductase activity - whereas a completely feminized ("de-imprinted") pattern of enzyme activities was found in the rats with intact ovaries at the time of death. It is concluded that de-imprinting action of ovaries is mainly of a reversible nature.


Corticosteroids in nocturnal blood plasma of cows in the field related to stage of lactation and plasma acetoacetate. Two materials of nocturnal blood plasma samples, each representing more than 100 cows unselected with respect to health condition, showed acetoacetate variations within a wide range, overlapping with the range for animals with clinical ketosis. Within each of the two materials a statistically significant (P smaller than 0.001) negative correlation (r equal to minus 0.30) was obtained between plasma corticosteroids and log acetoacetate. The lowest corticosteroid and the highest acetoacetate averages were obtained for animals which were within the first month of the lactation cycle. With increasing time post-partum the two components varied inversely, a maximum in corticosteroids coinciding with a minimum in acetoacetate in cows which had calved 2 1/2 to 3 months before the date of sampling. At this stage the mean plasma sugar was about 10 per cent higher than in early lactation. The corticosteroid ranges for different levels of acetoacetate overlapped extensively. Still cows with acetoacetate smaller than or equal to 0.6 mg/100 ml gave significantly higher corticosteroid averages than the rest of the material. But in animals exceeding the 0.6 mg limit no relationship was found between the severity of the ketonaemia and the steroid level. Thus, no difference was obtained between cows with clinical ketosis and animals which were moderately ketonaemic. Some change in adrenal function may be associated with the development of ketonaemic conditions in cows. But no proof has been provided of a direct adrenal involvement in the transformation of a case of subclinical ketosis to the clinical stage.


Androgenic properties and adrenal depressant activity of megestrol acetate observed in castrated male rats. Megestrol acetate (17alpha-acetoxy-6-dehydro-6-methylprogesterone), a synthetic steroid with high progestational activity, is used in oral contraceptives but also in the treatment of prostatic diseases in man. To investigate whether megestrol acetate has any androgenic properties the growth of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles was studied morphologically in castrated rats treated with megestrol acetate and in non-treated castrated rats. The effect of megestrol acetate on the body weight, the levator ani muscle and the adrenals was also studied. Megestrol acetate was administered in daily doses of 0.02 mg, 0.2 mg, 2.0 mg or 20.0 mg for a period of 21 days. Megestrol acetate in the two higher doses retarded growth and gave a low weight for the levator ani muscle at autopsy indicating an anti-anabolic or catabolic action of megestrol acetate in high doses. Megestrol acetate in daily doses of 0.2, 2.0 and 20.0 mg caused an involution of the adrenal glands. After the two higher doses the weight of the adrenals amounted to only about a third of that of the untreated rats. Megestrol acetate in the lower doses had no demonstrable effect on the growth of the accessory reproductive glands. After the two higher doses of megestrol acetate some growth of the dorsal part of the dorsolateral prostate and of the coagulating glands was observed. Only the seminal vesicles exhibited complete morphological criteria of an androgenic stimulation and then only after the largest dose of megestrol acetate. The investigation shows that megesterol acetate has weak androgenic properties which are apparent at a dose per kg body weight approximately 200 times greater than that used in the treatment of prostatic diseases in man.


Ovarian function during treatment with lynoestrenol 0.5 mg daily. Twenty-four women, all with normal ovulatory menstrual periods, were studied during in total 64 cycles on lynoestrenol 0.5 mg daily and during 11 control cycles. The 24-hour urines were collected for assay of total oestrogens on the 21st, 22nd and 23rd days of viz. the 1st, 4th, 6th and 12th cycles and for pregnanediol on the 22nd and 23rd days of the same cycles. Oestrogen excretion was at the same level during treatment and control cycles. All the control cycles and 9 and 14 % respectively of the treatment cycles were ovulatory judging by the plasma progesterone and the pregnanediol excretion. On the basis of the latter parameter there was a certain luteal activity during 36 % of the treatment cycles. In all cycles but one, however, the plasma progesterone and the pregnanediol excretion were lower than during the control cycles. It must be assumed, therefore, that lynoestrenol in a dose of 0.5 mg daily inhibits the ovulation or function of the corpora lutea in practically all cases.


Ovulation inhibition with human chorionic gonadotrophin. Eight women with regular menstrual cycles were treated daily during 9 cycles with HCG (Human Chorionic Gonadotrophin) 3000 or 5000 IU daily for a period of 4-7 days. This treatment was started between the 1st and the 6th day after the onset of menstruation. Control of the treatment cycles was performed by basal body temperature, pregnanediol serial estimations, endometrial biopsies and in addition in 5 treatment cycles by radio-immunological assay of estradiol-17 beta (Oe2), progesterone, LH and FSH from the serum at intervals of 1 to 3 days. In 6 of these cycles where treatment started on the 4th day or later, ovulation was inhibited (2 cycles) or postponed (4 cycles) to the 24th-46th day. In these 6 treatment cycles the progesterone and pregnanediol increase during HCG treatment was poor or absent. The typical Oe2 increase of the normal menstrual cycle was impaired. In the 3 remaining cycles where treatment was started on the 1st, 2nd and 4th day, we observed during HCG treatment increases in Oe2 and progesterone serum values similar to that found during corpus luteum activity, and menstruation from a secretory endometrium between the 13th-19th day of the cycle. The histologically examined ovaries of one woman who was treated with HCG from the 2nd to the 6th day of the cycle showed distinct luteinization of the theca interna of all tertiary follicles and a beginning degeneration of the granulosa. These findings give support to the hypothesis that the luteinization of the theca interna leads to degeneration of the tertiary follicles thereby causing ovulation inhibition or postponent of ovulation.


Effect of indomethacin, an inhibitor of prostaglandin biosynthesis on the length of pseudopregnancy in rats and hamsters. Pseudopregnancy (PSP) in rats was significantly lengthened after subcutaneous administration of 0.2-1.0 mg indomethacin/day, starting on day 5 of PSP. Injections of 1 mg indomethacin on days 5 and 6 or days 7 and 8, as well as a single injection of 2 mg indomethacin on day 6, also produced a significant increase of the duration of PSP. In hamsters, doses of 300-500 mug indomethacin per day starting on day 5 of PSP did not alter the length of PSP, but a significant prolongation varying from 11 to more than 30 days was observed after a treatment with 1 mg of indomethacin daily. It was further observed that the ovaries of hamsters autopsied on day 31 of PSP were very small and the uteri resembled those of ovariectomized animals. It is concluded that indomethacin lengthens pseudopregnancy in both rats and hamsters and that the latter species showed a more variable response. It seems that chronic administration of indomethacin in hamsters caused a long-lasting suppression of ovarian hormone production.


Influence of progesterone in the mitochondrial size in the uterine glands of the rat mouse, hamster, and guinea-pig. The administration of progesterone produced giant mitochondria in the gland cells of the rat uterus but not in those of the mouse, hamster, and guinea-pig uteri. Chloramphenicol did not impede the appearance of the giant mitochondria. The implication of the differential response of the mitochondria is not yet known.


Effect of long-term testosterone oenanthate administration on male reproductive function: clinical evaluation, serum FSH, LH, testosterone, and seminal fluid analyses in normal men. The effect of long-term testosterone administration on male reproductive function has been investigated in seven healthy young men age 20 to 27 years. Testosterone oenanthate (TOe) was administered in doses of 250 mg per week for 21 weeks. No toxic side-effects were observed. Libido, sexual potency, frequency of sexual intercourse and body hair development generally remained unaffected, but there was a reversible mean weight gain of 3.6 kg during TOe administration. Seminal fluid parameters and radioimmunoassayable serum FSH, LH, testosterone, and androstenedione levels were monitored before, during, and after TOe administration. The serum testosterone rose approximately by a factor of two, while the serum FSH and LH were rapidly suppressed after the initiation of the TOe therapy. The mean sperm concentration fell to values below three million spermatozoa per ml, and changes in sperm motility, the percentage of normal sperm morphology, and seminal fructose concentrations generally paralleled those of the mean sperm concentrations. In contrast, the mean seminal fluid volume and serum androstenedione levels did not change significantly during TOe administration. The mean sperm concentration showed a marked recovery 13 to 16 weeks after TOe withdrawal, but sperm counts remained below pre-treatment levels in three out of seven subjects 25 to 28 weeks after discontinuation of TOe.


5alpha-androstenone in peripheral plasma of pigs, diurnal variation in boars, effects of intravenous HCG administration and castration. 5alpha-Androstenone2) has been measured in pig peripheral plasma by radioimmunoassay (RIA). In 73 mature boars values ranging from 1.2 ng to 54.1 ng per ml plasma with a mean value of 18.3 ng/ml and SD equal to 15.9 were found. In female pigs and castrated male pigs the mean concentrations were 2.3 ng/ml (n equal to 18) and 1.1 ng/ml (n equal to 19) with SD equal to 0.8 and SD equal to 0.3 respectively. Clear-cut diurnal variations in the concentration of 5alpha-androstenone in plasma samples from boars were not observed. Intravenous injection of HCG in boars caused an abrupt rise in the 5alpha-androstenone level reaching a maximum in 90 min. Twenty-eight hours after the injection a second peak of plasma 5alpha-androstenone was observed. Following castration of boars the level of 5alpha-androstenone in peripheral plasma fell within 4 days, to levels found in female pigs.


Hemiagenesis of the thyroid gland.

Hemiagenesis of the thyroid gland. Three patients with hemiagenesis of the typhoid gland are described. One was clinically euthyroid, whereas the other two were more unusual in that one had coincident Graves' disease with thyrotoxicosis, and one had primary myxodema. In all three cases diagnosis of hemiagenesis was established by the administration of thyroid-stimulating hormone (TSH). The literature on hemiagenetic thyroid glands with and without associated thyroid disease is reviewed. Although the anomaly is uncommon, awareness and recogniton of its existence may clarify an otherwise puzzling clinical thyroid evaluation, and thus possible avert an unnecessary surgical procedure.


A prospective evaluation of the lecithin/sphingomyelin ratio and the rapid surfactant test in relation to fetal pulmonary maturity. Fetal lung maturity was correlated to the results of amniatic fluid analysis in 578 samples obtained over a 2 1/2 year interval. Lecithin/sphingomyelin (L/S) ratios obtained by planimetric and densitometric methods were compared to the rapid surfactant test (RST). Both the planimetric L/S ratio (P L/S) and the densitometric L/S ratio (D L/S) correlated positively in a highly significant fashion with the RST. Both RST and D L/S were reliable in predicting fetal lung maturity (99 to 100 per cent, respectively). The RST was the most reliable test for fetal lung immaturity (69 per cent). Therefore, this series indicates that the RST could be used as a primary method with the D L/S being useful as an additional indicator of fetal maturity when the RST was intermediate, or the sample contaminated with blood and/or meconium.


IgA associated lymphoplasmacytic tumor involving the conjunctiva, eyelid, and orbit. A 65-year-old white man had an unusual disseminated lymphoid tumor that first appeared in the subconjunctival tissues of the right eye. The tumor later appeared in the skin, lymph nodes, and left upper eyelid and orbit. A monoclonal serum IgA spike was present although the urine did not contain Bence Jones proteins. The cells of the tumor appeared to be plasmacytoid lymphocytes. Prominent intranuclear inclusions, or Dutcher bodies, were present. Throughtout the 11-year history, the patient has been treated only with local excision and radiation.


Orbital radiation for the ocular changes of Gravess' disease. We reviewed the records of 37 patients who received orbital radiation for ocular changes of Graves' disease. Signs of orbital congestion improved in many patients. Proptosis extraocular muscle involvement, and corneal involvement were not appreciably altered. The best response was found in patients with optic nerve involvement. Radiation therapy is recommended as an initial therapeutic attack for the optic neuropathy of Graves' disease.


Bilateral trephine bone marrow biopsies in lymphoma and other neoplastic diseases. We have evaluated the usefulness of bilateral rather than unilateral posterior iliac spine trephine biopsies in searching for lymphoma and other neoplastic diseases in the bone marrow. Two hundred and eighty-two patients with these diseases were studied. Tumor was found on only one side in 22% of patients with non-Hodgkin's malignant lymphoma, in 43% of patients with Hodgkin's disease, and in 36% of patients with other neoplastic processes. Thus, the second biopsy yields an additional 11% to 22% of positive biopsies. We conclude that bilateral trephine bone marrow biopsies should be routinely performed when searching for tumor in the bone marrow.


Clinical manifestations of splenic abscess. Two patients with splenic abscess were successfully treated. In one patient, Streptococcus viridans, possibly arising in a dental abscess, led to inflammatory left upper quadrant signs. An exploratory laparotomy was performed, and the spleen, being found enlarged, was removed. The other patient showed no peritoneal signs. Laparotomy was done for pyrexia of unknown origin, and the removal of a normal-sized spleen was elected on the suspicion of lymphosarcoma. The spleen was abscessed, apparently because of old infarcts. A high index of suspicion is important in diagnosis, and selective angiography, not used in these two patients, is recommended.


Effects of long-term exposures to 100% oxygen at selected simulated altitudes on the pulmonary surfactant in mice. The purpose of this investigation was to evaluate the effects on pulmonary surfactant in mice after long-duration exposure to 100% oxygen at various partial pressures equivalent to 842 mb (632) mmHg) or less. Six-month-old female CBA mice, weighing 25-35 g, were exposed to the pure oxygen environment. The effect on pulmonary surfactant was evaluated in two groups of 16 experimental animals and compared with control groups which were maintained in a similar environmentally controlled chamber at sea level conditions. Group I was exposed to pure oxygen at 842 mb (632 mmHg), a level known to be toxic and lethal. Group II was initially exposed for 60 d to pure oxygen at 420 mb (315 mmHg), a level not expected to be lethal, and the oxygen partial pressure gradually increased in steps over a 150-d period until an oxygen partial pressure at 842 mb (632 mmHg) was reached. In Group I, 12 out of 16 mice died of respiratory distress within 7 d. One died on the 10th day and three survived to complete 15 d of exposure but were euthanized because of severe despiratory distress. Mice in Group II which were exposed to pregressively increasing oxygen partial pressures survived. Pulmonary surfactant was obtained by saline lavage of the lungs. Chloroform/methanol extracted samples from oxygen-exposed mice in Group I displayed lower surfactant activity than Group II or controls. In fact, surfactant activity of mice dying in respiratory distress after 7 d was markedly lower than that of all other animals. Mice in Group II exhibited significantly lower(p less than 0.05) surfactant activity than controls, X = 34.71 and 38.58 respectively. This lower surfactant activity was consistent for Group II throughout the 150-d exposure except at the 90-d and 150-d exposures. The findings of this investigation support preceding studies which contend that the lung is the most vulnerable target for oxygen toxicity at altitude. It appears that an adaptive process involving both quantitative and qualitative changes in the pulmonary surfactant enabled animals in Group II to survive the progressively increasing ocygen partial pressures in an environment where survival would not normally be possible.


Increased susceptibility to pulmonary oxygen toxicity after cholesterol biosynthesis inhibition. AY-9944, a cholesterol biosynthesis inhibitor, reduces adrenal corticosteroid production and may accelerate pulmonary surfactant production. Divided into four experimental groups were 130 male 100-g, 5-week-old Wistar-Lewis rats. Group 1 received no injections. Group 2 received 0.5 ml N NaCl ip qd times 21 d, and Group 3 received 1.5 mg AY-9944 in 0.5 ml N NaCl ip qd times 21 d. Group 4 animals received 5.0 mg hydrocortisone phosphate in 0.5 ml N NaCl sc qd times 7 d. All injections were done prior to exposing the animals to 98-99 plus % oxygen at 1 atmospheric pressure (OAP) for varying lengths of time. AY-9944 treatment resulted in a significant (p smaller than 0.05) reduction in body growth by Day 7 when compared to saline-injected litter-mates. By Day 21 this difference was highly significant (p equals 0.00002). Lungs from AY-9944 treated rats were heavier than the lungs from the other groups. Surprisingly, there were no differences in lung deflation compliance or area of pressure-volume loop hysteresis between groups before expsoure to O2. Exposure to OAP caused significant increases in lung weights and lung weight/body weight ratios by 48 h in all groups. Lung dry/wet weight ratios decreased in all groups initially but returned to non-OAP levels at 72 h. Lung compliance had decreased significantly from non-OAP levels 56 h in the normal (p equals 0.018), AY-9944 (p equals 0.045) and hydrocortisone (p equals 0.002) groups and after 72 h in the saline group (p equals 0.0015). AY-9944-treated rats had the highest mortality rate from OAP. By 72 h OAP, 40.0% of the normal, 42.9% of the hydrocortisone, 50.0% of the saline, and 100% of the AY-9944 animals were dead. Our study suggests that the effect of AY-9944 on lung lipid metabolism is more detrimental in OAP-exposed rats than the expected benefit of AY-9944's simultaneous reduction in adrenal cortical activity.