[Metabolic degradation of clonidine (author's transl)]. From the urine of dogs treated with 14C-clonidine (Catapres) 6 radioactive substances were isolated and their chemical structures identified. The presence of unchanged clonidine, p-hydroxy-clonidine, and dichlorophenylguanidine was confirmed and three new metabolites were detected: 1-(2,6-dichloro-4-hydroxyphenyl)-guanidine; 2-[(2,6-dichlorophenyl)-imino-a1-imidazolidine-4-one; 2-[2,6-dichloro-4-hydroxyphenyl)-imino]-imidazolidine-4-one. The splitting of the imidazolidine ring and the hydroxylation of the phenyl ring are the two principal routes of metabolism. A comparison of the metabolic patterns in the urines of dog, rat, and man showed that the 6 identified compounds were eliminated by all three specieis, the relative amounts, hoever, were different. Man eliminated clonidine mainly in the unchanged form; the dog metabolized the compound most readily of the 3 species investigated.


Influence of 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride on cardio-inhibitory vagal fibres. Neural activity of cardio-inhibitory vagal fibres was recorded in anaesthetized cats. The discharges increased when the blood pressure rose after injection of an alpha-adrenergic substance such a norepinephrine or 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride (St 91). After transection of the afferent baroreceptor nerves neither norepinephrine nor St 91 influenced neural activity. These findings show that the increase in neural activity is of reflex origin. An influence of St 91 on central parasympathetic structures could not be demonstrated.


[Amikacin and kanamycin. Comparative experimental studies on nephrotoxicity]. The nephrotoxicity of amikacin and kanamycin was investigated in 110 female albino Wistar rats. The drugs were administered i.m. in different dosages (2.5; 5; 10; 20; 100 and 500 mg/kg/day; dosage interval: 12 h) over a period of 5 days. The excretion of tubular cells and urinary enzymes (MDH, LDH and GOT) was assessed before, during and after administration of the antibioitcs. In addition, the concentration of serum urea was analysed and the kidneys were investigated histologically. These investigations show that both the aminoglycosides are tubulotoxic, in higher dosages glomerulotoxic, too. The toxic threshold doses were found to be within the range of human therapeutic dosages: amikacin: 10 mg/kg/day, kanamycin: 5 mg/kg/day.


Derivatives of methyl vinyl sulfone. Distribution and elimination of methyl (2,2-diphenyl)-vinyl sulfone labelled with 14carbon in mice. The investigation of methyl (2,2-diphenyl)-vinyl sulfone (14C-MDVS) administered i.p. in mice shows that this product appears rapidly in the general circularoty system. The blood concentration of MDVS reaches a maximum 1 h after injection. Part of the MDVS is bound to the plasma proteins. Infrared spectrometry analysis of radioactive products eliminated by the urine confirms that the product is not split, but also reveals the presence of hydroxyl and carbonyl groups in the metabolic conversion products.


Positive inotropic and blood pressure lowering activity of a diterpene derivative isolated from Coleus forskohli: Forskolin. Forskolin is a diterpene derivative isolated from the Indian plant Coleus forskohli. Forskolin has positive inotropic action on the isolated guinea pig heart, on the isolated left atrium of the guinea pig heart and on the dog and cat heart in situ. It increases the heart rate. The positive inotropic effect on the increase of heart rate are not blocked by beta-blockers. On reserpinized dogs the actions on the heart could also be seen. With high doses the action potential of the guinea pig papillary muscle is shortened. The positive inotropic effect could be differentiated from the effects of theophylline, cardiac glycosides and veratrine. Forskolin lowers the blood pressure in dogs and cats and also in spontaneously hypertensive and renal hypertensive rats.


Biological properties and clinical application of propolis. IX. Experimental observation on the influence of ethanol extract of propolis (EEP) on dental pulp regeneration. The use of ethanol extract of propolis (EEP) on injured dental pulp results in the stimulation of regenerative processes. A reduction of disorders of the circulatory system is observed, inflammatory and degenerative processes are also reduced.


Biological properties and clinical application of propolis. X. Preliminary pharmacological evaluation of ethanol extract of propolis (EEP). A study consisting of an examination of the acute toxicity of ethanol extract of propolis (EEP) in mice, its effect on spontaneous movement in mice and rats, its analgesic properties and its influence on body temperature in mice was conducted. Also examined was the activity of EEP on animals under the influence of narcotics and spontaneous movement under the influence of amphetamine, its effects on blood pressure and respiration in rats. The results of these examinations indicate that EEP injected i.p. has a weak general effect on the experimental animals.


[Determination of enzyme kinetic parameters and differentiation between various mechanisms by means of a non-linear least squares method]. The effect produced by an inhibitor on an enzyme is characterized by the underlying mechanism and the molar inhibition coefficients Ki and Ki', respectively. The commonly used graphical estimation methods according to Lineweaver-Burk, Dixon and Cornish-Bowden do not always yield a differentiation between various possible mechanisms. According to our experience, a non-linear least-squares procedure allows a unique identification of the mechanism even in cases that are not at all, or not uniquely, solvable by graphical methods. The major advantages of this procedures and the used FORTRAN program are: 1. Fitting of the model equation itself-and not of a reciprocal conditional form-simultaneously to all measurements; 2. confidence limits for the parameter estimates; 3. residual plots to judge the goodness of fit; 4. parallel calculations and comparison of various mechanisms using the same set of data; 5. addition of further mechanisms as FORTRAN-subroutines.


Stimulatory effect of histone on glutathione reductase of human erythrocytes. Glutathione reductase of hemolyzates, as well as intact erythrocytes from normal individuals can be activated by the addition of human leukocyte nuclear histones and histone subfractions f1 and f3. Intact erythrocytes incubated with histone show also in their hemolyzates a high glutathione reductase activity as compared with such not treated with histone cells. The degree of stimulation of glutathione reductase by histones is comparable to that caused by flavin adenosine diphosphate (FAD). Histones  and FAD show a competitive stimulatory effect on glutathione reductase activity. ATP shows an inhibitory effect on glutathione reductase activity, which can be reversed by addition of histone.


[Blood level values of rectally applied theophylline and its derivative proxyphylline and diprophylline in aqueous enema (author's transl)]. Serum levels of theophylline and two of its oxypropylic derivatives were determined in repetitive blood samples after instillation of a mixture of the three substances by means of an aqueous enema. From the time course of serum levels a rapid onset of bronchodilation and rather a long-lasting bronchodilatory effect of about 8 h may be expected. Side effects are rare. The pharmacological characteristics of the three compounds are discussed.


[On the metabolism of antipyrine (phenazone) in man (author's transl)]. The metabolism of antipyrine (phenazone) was studied by means of C14-antipyrine labelled at C-3. Besides the metabolites already known two conjugates were isolated and characterized by their mass spectra. The occurrence of 2-hydroxymethyl-3-methyl-1-phenyl-3-pyrazolin-5-one and 3,4-dihydroxy-2,3-dimethyl-1-phenyl-pyrazolidin-5-one could not be confirmed, although 95% of the radioactivity administered was recovered.


[Pharmacokinetic studies on fluoro-alpha-acetyl-digoxin (author's transl)]. Pharmacokinetic studies with a new cardiac glycoside 3H-fluoro-alpha-acetyldigoxin were carried out in humans. The absorption of the drug is 91%. The half-life of tritium label in plasma was 25 h i.v. and 35 h p.o. 73% of the administered radioactivity were excreted after i.v. and 52% after oral administration within 84 h. More than 60% of the radioactivity in the urine could be extracted with chloroform. This fraction corresponded mainly to 3H-fluorodigoxin in the thin-layger chromatogram. Protein binding was 27% using therapeutic concentrations.


Arrest patterns of circulating lymphosarcoma cells in tumour-bearing mice as modified by previously injected cell suspensions. The effects were determined of an initial i.v. injection of 0.2 ml suspensions of 125IUdR-labelled lymphosarcoma cells on the early arrest patterns of a second injection of cancer cells into tumour-bearing mice. The results indicate that interactions between the first injection and the host markedly affected the arrest pattern of the second dose in the lungs, but not the livers, of tumour-bearing animals. These observations are explained on the basis of the injected fluid volumes, which are considerable in mice, in relation to their total blood volumes of approximately 2 ml.


Biological effects of chrysolite after SO2 sorption. iii. effects on the biochemical components of alveolar washing. The short-term effects of chrysotile asbestos before and after SO2 sorption are studied in the rabbit after intratracheal injection of low doses of these pollutants. Chrysotile, as well as SO2-chrysotile, induces an increase in the unsaturated fatty acid content of lung surfactant, which is similar to that observed in the respiratory distress syndrome of the newborn, and an increase in the protein level of pulmonary washings which may be explained by an increase of the permeability of the blood-air barrier. These soluble proteins can interact with the surfacant and thus decrease its tensio-active properites.


Early results of closed partial menisectomy. Thirty patients underwent partial meniscectomy through two puncture incisions by a closed technique under arthroscopic control. "Bucket-handle" fragments were removed from 17 knees, and flaps or tags from the remainder. The mean stay in hospital after operation was 1.3 days and the mean time for return to working fitness was 10.5 days. There were no serious complications. Further study of the long-term results of this technique is needed.


Facilities and diagnostic criteria in sexually transmitted disease clinics in England and Wales. A study was conducted to collect information from consultants about the facilities and diagnostic criteria used in clinics for sexually transmitted diseases in England and Wales. Most of the information was obtained by personal interview with a response rate of 92%. Half the clinics were open for 10 hours or less a week, the mean length of time for all clinics was 14 1/2 hours a week. Eighty per cent of clinics had a full or part-time contact-tracing service. All the clinics had microscopical and serological services and almost all (99%) had cultural facilities. The policy concerning the most efficient use of these facilities is discussed.


Default patterns of patients attending clinics for sexually transmitted diseases. The influence of gender, propaganda, and treatment methods was studied in relation to default behaviour of patients with sexually transmitted diseases. The overall default rate of men and women was similar, but a larger proportion of men defaulted after the initial visit, while the biggest fall-out in women was after the second attendance at the clinic. The institution of a propaganda campaign was followed by a reduction in defaulting. The statistical significance of this is open to question, however: moreover the observed improvement in default rate was not maintained once the propaganda had been relaxed. Men treated for non-gonococcal urethritis by a regimen which included one injection a week for three weeks showed a highly significantly lower default rate compared with those who received tablets alone.


Oncostatic effects of Alangium vitiense extracts (ICIG-EORTC 1131, 1186 and 1207) on lymphoid murine tumors. A total alkaloid and two purified alkaloid extracts of Alangium vitiense were found to be oncostatic for L1210 leukemia; the total alkaloid exerted a noticeable activity, and the purified extracts exerted a borderline activity. These two purified extracts are noticeably oncostatic for two other lymphoid neoplasias in mice, P388 leukemia and Gardner lymphosarcoma. These compounds are not active on Warner myelomonocytic leukemia WEH13 or on B16 melanoma.


Plasma insulin disappearance curve after intravenous insulin injection in human hyperthyroidism. The disappearance curves of plasma insulin after intravenous injection of unlabelled pork insulin was studied in nine young female hyperthyroid subjects with Graves' disease and eleven young female normal subjects, who served as controls. Comparison of the curves by analysis of variance did not reveal statistical differences between them (F obtained = 2.8, F F 0.05 = 4.41), implying that there was no significant differences in the transference of injected insulin from plasma to the extra-vascular space between hyper- and euthyroid subjects. The results may suggest that the metabolism of insulin is not appreciably affected in hyperthyroidism.


Chemical determination of iodinated compounds in human thyroid. As a tool with which to detect iodinated compounds in human thyroid specimens, we have reevaluated a nonincineration technique which has so far been employed in the determination of thyroxine-iodine in peripheral blood. The catalytic action of iodoamino acids in the Ce-As reaction was enhanced by a small amount of Cl2. On the contrary, a large amount of Cl2 inhibited the reaction unexpectedly. Among iodide, iodotyrosine and iodothyronine, iodide was the most effective catalyst in the Ce-As reaction and iodothyronine was the least effective one. Protein seemed to inhibit this reaction of thyroglobulin. But the result of iodine content in thyroglobulin by this technique agreed well with that by incineration when measured 127I was corrected by percent activity of dializable part of the total activity of 131I-thyroglobulin with the same protein concentration, after the NaClO treatment. The results of human thyroid specimens were as follows: the thyroglobulin content of five normal subjects was 8.0 +/- 1.5% of wet thyroid weight. That of Hashimoto's disease was significantly decreased which seemed compatible with the decrease in iodine content of thyroglobulin, whereas thyroglobulin content of Graves disease treated with 1-methyl, 2-mercaptoimidazole followed by a large dose of iodide was well preserved in spite of a lower degree of iodination of thyroglobulin. As for the distribution of iodoamino acids-iodine in normal thyroid, T4 was 20.5 +/- 0.7%. This technique ultimately looks promising as a tool with which to study intrathyroidal iodine metabolism in human.


Effect of pulsed low-power ultrasound on growing tissues. II. Malignant tissues. Pulsed ultrasound at 2.25 MHz was delivered by a transducer having an average power output of 1.5 mW to a transplantable mouse lymphosarcoma for 5 min. The transplantability of the tumor was reduced. No change in mitotic index as a result of insonation was noted.


Bile flow and biliary excretion rate of some organic anions in phenobarbital-pretreated rats. Bile flow and the biliary excretion of indocyanine green, bromcresol green, eosine, bromsulphthalein-glutathione conjugate (BSP-GSH), amaranth and iodoxamic acid were investigated in control and phenobarbital-pretreated rats (75 mg/kg i.p. daily for 5 days). The bile flow was increased by phenobarbital from an average of 50.6 to 77.7 microliter/kg/min. Depending on the dose, the biliary excretion rate of bromcresol green was increased by 48-496% and that of eosine by 30-149%. After phenobarbital pretreatment the excretion of BSP-GSH was also enhanced by 34-52%, that of amaranth by 37-53% and that of iodoxamic acid by 40-56%. However, the biliary excretion of indocyanine green remained unchanged. There was no parallelism between the increase in bile flow and biliary excretion of the drugs.


Characterization of temperature-sensitive, fertilization-defective mutants of the nematode caenorhabditis elegans. The isolation and characterization of three Caenorhabditis elegans temperature-sensitive mutants that are defective at fertilization are described. All three are alleles of the gene fer-1. At the restrictive temperature of 25 degrees, mutant hermaphrodites make sperm and oocytes in normal numbers. No oocytes are fertilized, although they pass through the spermatheca and uterus normally. The oocytes can be fertilized by sperm transferred by wild-type males, indicating that the mutant defect is in the sperm. The temperature-sensitive period for the mutants coincides with spermatogenesis. Sperm made by mutants at 25 degrees cannot be distinguished from wild-type sperm by light microscopy. The sperm do contact oocytes in mutant hermaphrodites, but do not fertilize. Mutant sperm appear to be nonmotile. Mutant males are also steril when grown at 25 degrees. They trnasfer normal numbers of sperm to hermaphrodites at mating, but these sperm fail to migrate to the spermatheca and are infertile. The phenotype of these mutants is consistent with a primary defect in sperm motility, but the cause of this defect is not known.


A natural heterohaemagglutinin in Xenopus laevis serum. In most adult Xenopus laevis the serum contains a 'natural' factor capable of lysing the erythrocytes from a wide variety of amniote species. The factor has no effect on the erythrocytes of another amphibian, Ambystoma mexicanum, nor will serum from one animal lyse red cells from another Xenopus individual. No lysing factor was present in the serum of larval (tadpole) Xenopus. Heating of Xenopus serum to 56 degrees for 30 min, absorption of the serum with zymosan or inulin, or removal of calcium and magnesium ions results in loss of lytic activity, although haemagglutinating activity remains, suggesting that the factor can fix complement. The factor elutes from a gel chromatography column in the 19S peak, and is inactivated by thiol reduction and subsequent alkylation. These findings, coupled with immunoabsorption studies suggest that the haemagglutinin is an immunoglobulin of the IgM class. The significance of this suggestion is discussed in the light of previous reports of 'natural' heterohaemagglutinins in other species.


Ultrastructure of rabbit semilunar cartilages. A light and transmission electron microscopical study of 6 to 8 months old rabbit semilunar cartilages has shown that the cells in this tissue resemble chondrocytes more than fibroblasts. The prominent organelles in these cells were rough endoplasmic reticulum and the Golgi complex. An unusual finding was the occurrence of filamentous material in Golgi sacs and vesicles, and collagen fibrils within smooth membrane-bound tubular structures, apparently within the cells. Collagen fibrils forming fibres, fibre bundles and lamellae constituted the major component of the menisci. Protein-polysaccharide particles and associated fine filaments were found in the interfibrillary matrix and in the sparse territorial matrix adjacent to the chondrocytes. Numerous immature elastic fibrils, and rare mature elastic fibres with an electorn-lucent amorphous core, were also found in the general matrix amongst the collagen fibrils.


Urinary tract infection in young women, with special reference to Staphylococcus saprophyticus. Acute urinary tract infections in young women attending a clinic for sexually transmitted diseases were caused by the same bacteria, in the same proportions, as those that caused infections in women students. Staphylococcus saprophyticus biotype 3 (formerly called Micrococcus subgroup 3) was the commonest organism after coliform bacilli and caused about 30% of the infections. It was uncommon in women over 25 years of age and rarely caused asymptomatic bacteriuria in pregnancy. Most infections, irrespective of the causative organism, started soon after sexual intercourse, but neither the staphylococci nor the other organisms were associated with promiscuity, as judged by numbers of sexual partners or the incidence of sexually transmitted diseases. There was no evidence that the staphylococci were sexually transmitted. The reasons for the virulence of Staph. saprophyticus and its predilection for the urinary tract of young women remain unknown.


Experimental forms of infection and serological analysis of the antigenic structure of Rickettsia canada. Experimental forms of Rickettsia canada infection were characterized and serological analysis of the antigenic structure of R. canada was carried out. According to its pathogenicity for experimental animals, R. canada can be characterized as a poorly virulent species of rickettsiae, similar to R. prowazekii (for guinea pigs). The complement-fixing, haemagglutinating and agglutinating antigens of R. canada are fairly similar to those of the typhus group rickettsiae. The region of antigenic activity common to or identical in R. canada and the typhus group rickettsiae, is larger in R. canada than in the typhus group rickettsiae. R. canada has common antigens with Proteus OX19. R. canada has active toxic substances similar to those of R. prowazekii which, however, are detectable only with sera of Brill's disease convalescents. The position of R. canada in the taxonomy of rickettsiae is discussed.


Spectrum of complications in the use of intrathecal fluorescein. The authors describe a case in which 0.5 cc of 5% fluorescein diluted in 10 cc of cerebrospinal fluid (CSF) was injected at the L4-5 level for evaluation of nasal CSF leakage. Within minutes, tone increased in lower extremities accompanied by knee and ankle clonus and subjective numbness up to the waist. Non-preserved saline irrigation of the lumbar CSF was administered until it became clear, and the patient's head was elevated to retard the developing symptomatology. Although a transient temperature elevation was observed with negative CSF cultures, all signs and symptoms cleared within 48 hours. In a survey of the members of the Americal Association of Neurological Surgeons regarding frequency of use and complications stemming from intrathecal fluorescein, the response rate was 58.3% (1111) of the 1907 members, of which 6.8% (76) had used intrathecal fluorescein, and among those, 25% (19 of the 76) had observed complications involving lower extremity weakness, numbness, generalized seizure activity, opisthotonos, and cranial nerve deficit. No complications were permanent. The authors recommend caution if intrathecal fluorescein must be used. Means should be available to clear the CSF of the agent and elevate the head if complications arise.


Demonstration of Ga-67 localization in human placenta. Gallium-67 uptake was noted in the mid-pelvic uterine area of a 19-week-pregnant female. Lateral and oblique Ga-67 scans revealed an anterior location of radioactivity that correlated with the position of the placenta as determined by ultrasonic technique.


Equilibrium penetration of monolayers IV: dipalmitoyllecithin-centrimonium bromide system. Equilibrium surface pressure-area isotherms of dipalmitoyllecithin monolayers were measured on substrates containing various concentrations of the surfactant, cetrimonium (hexadecyltrimethylammonium) bromide. From these isotherms, the saturation adsorptions of surfactant for various surface lecithin concentrations were calculated. Plotting of these adsorptions against the inverse of the area per lecithin molecule, as required for the "accessible area" theory, revealed two linear segments, corresponding to penetrating at high and at low monolayer areas. At both high and low areas, the adsorption into the accessible areas of the surface was similar to adsorption at a monolayer-free surface. The effective cross-sectional area of the monolayer molecule in the low area region was equal to the collapse area; in the high area region, it was equal to an area corresponding to the co-area, as calculated from the Amagat equation. The change in cross-sectional area corresponded to the transition in the monolayer from a liquid condensed state to a liquid expanded state.


The effect of zinc ions on fertilization of mouse ova in vitro. The fertilization rate of mouse gametes in a Krebs-Ringer bicarbonate medium was 60%. The rate fell to 0% when 250 micron-ZnCl2 was added, but MgCl2, CaCl2, MnCl2, FeCl2, and CuCl2 (each at 250 micron) had no effect. The inhibitory effect of Zn2+ was not evident if the spermatozoa or eggs were preincubated with Zn2+ or if previously capacitated spermatozoa were used. The Zn2+ is thought to act by interference with capacitation.


Comparison of the antitumor activity and toxicity of 2,4-diamino-5-(1-adamantyl)-6-methylpyrimidine and 2,4-diamino-5-(1-adamantyl)-6-ethylpyrimidine. The effects of two new compounds, 2,4-diamino-5-(1-adamantyl)-6-methylpyrimidine (DAMP) and 2,4-diamino-5-(1-adamantyl)-6-ethylpyrimidine (DAEP), on the growth of Walker carcinoma 256 were studied. In Sprague-Dawley rats, both compounds inhibited the growth of the Walker tumor, which is naturally resistant to methotrexate. Murphy-Sturm lymphosarcoma, which is extremely sensitive to methotrexate, was not inhibited by DAMP. In contrast, 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) inhibited the growth of the Murphy-Sturm and Walker tumors. The toxicity of DAMP and DAEP was charaxterized by convulsions followed by death; DDMP did not show such toxicity at median lethal doses. DAEP and DAMP reversibly reduced the number of polymorphonuclear leukocytes in the peripheral blood of rats, and DAMP also decreased the lymphocytes and platelets; DDMP markedly reduced all these cellular elements. Consistently, bone marrow was also markedly depressed by DDMP.


Development of intestinal host defense mechanisms and the passive protective role of human milk. In this review of development of host defense mechanisms of the gastrointestinal tract, I have attempted to develop the concept of a mucosal barrier to the uptake of intestinal antigens and microorganisms. Alterations in development of immunologic defense and non-immunologic defenses results in an increased vulnerability for clinical disease in the newborn (premature) infant. The passive role of human milk in promoting intestinal maturation and protecting the newborn gut from pathologic penetration of macromolecules is discussed. It was predicted that many, as yet undiscovered factors, will be reported in future years to further underscore the importance of human milk in perinatal host defense. Immediate and delayed disease states resulting from an altered defense were considered.


Distribution and pharmacokinetics of methotrexate in localized chemotherapy of solid Gardner's lymphosarcoma. Pharmacokinetics and organe distribution of Methotrexate (MTX) in Gardner lymphosarcoma bearing C3H mice was investigated following two ways of drug administration: 1. intraperitoneal injection, 2. intratumoral implantation of 2-hydroxyethylmethacrylate gel with sorbed Methotrexate (localized chemotherapy). The highest level of MTX in blood appeared 2 hours after intrperitoneal injection but 7 hr after localized intratumorous application. Following intraperitoneal application the drug level in tumor reached its maximum two hours after injection; after 7 hr the drug could not be detected any longer. The localized chemotherapy led to six times higher concentration of the drug in the tumors as compared with the intraperitoneal application. This high level persisted for 17 hr and decreased moderately for 48 hr. MTX was accumulated in liver after both modes of administration with a half life 6.1 hr after intraperitoneal injection and 12.4 hr after the localized chemotherpay, respectively.


Relationship between lymphocyte emigration and vascular endothelium in chronic inflammation. Small blood vessels within areas of chronic inflammation which contain large numbers of lymphocytes develop unusually thick walls. Combined histological and electron microscope study shows that the thickening is due to hypertrophy of endothelial cells which come to resemble the endothelium of post-capillary venules in lymphoid tissue. Vessels of this type have been found in experimental granulomas induced by injection of Freund's adjuvant or killed tubercle bacilli and in human biopsy material from cases of rheumatoid arthritis and Hashimoto's disease of the thyroid. Comparison with the developing Peyer's patch in young rats shows that the unusual vessels in granulomas are very similar in endothelial cell size, pattern of distribution, extent of lymphocyte migration and degree of carbon leakage to post-capillary venules of the immature Peyer's patch. Study of the time at which lymphocytes appear in large numbers within the granuloma or developing Peyer's patch and the time at which thickened vessels are first seen suggest tha the endothelial changes are a consequence and not a cause of lymphocyte emigration. The stimulus to endothelial hyperthrophy appears to be massive sustained migration of lymphocytes, but the functional significance of this change in vascular structure is not clear.


The right paratracheal stripe in children. The width of the right paratracheal stripe (RPS) has been established in normal adults but not in normal children. The thymus and great vessels are relatively larger in children than in adults and could obscure or widen the RPS. We found that obscuration does occur and, therefore, the RPS is less often measurable in children than in adults. Widening by the thymus and great vessels, however, does not occur. The width of the RPS in normal children, 0.5 to 3.0 mm, is slightly less than in adults. From this study of normal children and our subsequent experience with pediatric patients, we conclude that in a child an RPS 4 mm or wider is reliable evidence of disease affecting the trachea, mediastinum, or pleura.


Effects of asphyxia on renal function in the newborn piglet. This investigation was undertaken to determine the nature of acute alterations in renal function following the production of hypoxemia, hypercarbia, and acidosis in newborn piglets 6-96 hr of age. After completion of the surgical procedure piglets were allowed to recover from the effects of anesthesia. When respiratory dead space was increased arterial oxygen tension decreased whereas arterial carbon dioxide tension and hydrogen ion concentration increased. There was little change in glomerular filtration rate. Total renal blood flow decreased and renal vascular resistance increased significantly (504 +/- 78 mm Hg/liter/mm/m2 to 1422 +/- 504). There was no change in distribution of intrarenal blood flow. Sodium excretion and urinary flow rate demonstrated significant parallel increases following the increase in dead space. Plasma renin concentration increased from 67 to 110 ng/ml.


Pediatrics manpower requirements.

Pediatrics manpower requirements. Assessment and projection of manpower requirements are difficult and compelx undertakings for which no single methodology has proven to be entirely satisfactory. A frequently used approach to estimation of manpower requirements is the number of physicians needed per population. A numerical approach alone is inadequate for it fails to take into account the types and quality of services to be delivered. There are many factors which affect manpower estimates, several of which are not quantifiable. Factors unique to pediatrics which must be considered include the changing nature of health needs of the population in the age range from 0 to 21 years; the changes in the practice of pediatrics; the increasing emphasis on the importance of preventive health care and health maintenance; and the impact of scientific advances on the demand for services. A most important variable is the national level of cohort fertility. Fluctuations in this rate significantly affect the numbers of children and adolescents requiring care. It is concluded that there will not be an excess of pediatricians in 1980 and 1990. Indeed, it is questionable whether the health needs of the pediatric population can be adequately met in those years.


[Sisomicine in the lumbar and ventricular cerebrospinal fluid. Concentration after intramuscular or intrathecal injection. Study in 14 subjects-therapeutic implications (author's transl)]. Following intramuscular injection sisomicine, in common with other aminosides, shows poor intrathecal diffusion (less than 10% of serum levels) even during the initial phase of purulent meningitis. Following the intraspinal or intraventricular injection of 0.5 mg/kg, high levels are obtained which persist up to 48th hour. This dose is very well tolerated and no accumulation phenomena were demonstrated after repeated injections. In cases of meningitis due to organisms resistant to diffusible antibiotics, sisomicine sulphate may be used by lumbar intraspinal or sometimes intraventricular injection in severe forms, in a dose of 0.5 mg/kg every 48 hours (or even 24 hours). In combination with systemic treatment. The duration of treatment cannot be precisely defined.


[Immunoblastic lymphosarcomas. Clinicopathological aspects and course. Retrospective analysis of a series of 50 patients (author's transl)]. The immunoblastosarcoma (IB) was preceeded by another pathological state in almost one third of patients. The clinical picture was often very typical, with large inflammatory node involvement. In one third of cases, the initial site of the tumor was not nodal, but in Waldeyer's ring or a non-lymphoid organ. Analysis of topographic extension indicates a weak propensity to dissemination. The tissues which are the more frequent site of secondary invasion were the lung parenchyma and the subcutaneous tissue. The course was rapid, almost always fatal. Only a combination of radiotherapy and chemotherapy would seem capable of eradicating the tumour. On the basis of all these characteristics, the IB has a special place alongside other non-Hodgkin lymphomas and they may be individualised histologically. These cases are in general in agreement with the little data published in the literature.


[Cervical myelography using metrizamide via a lateral approach at C1-C2 (author's transl)]. Metrizamide is a new hydrosoluble contrast medium of an entirely original conception which for first time makes it possible to explore the whole cord and its spaces. The technique of latero-cervical puncture between C1 and C2 was used in 45 cases of cervical cord compression, cervico-brachial neuralgia or brachial plexus paralysis. This technique of myelography has proved to be simple and reliable. It has a number of advantages: it is far more rapid, less painful and offers good visualisation of the nerve roots as compared with air myelography; unlike myelography with iodine-based oils, it is not necessary to remove the contrast medium after the examination since Metrizamide is spontaneously resorbable. Tolerance in general is remarkably good.


Techniques for locating, filing, and retrieving scientific information. Guidelines for improving the effectiveness and efficiency of conducting a search of scientific literature are presented. Initial leads can be gained by contacting a local expert or consulting a textbook. An impression of advances being made in a particular field can be gained efficiently by scanning weekly issues of Current Contents, containing the tables of contents of most scientific journals. Recent review articles on most topics can usually be found listed in the Index Medicus. With at least one significant reference dealing with a specific topic of interest, the Science Citation Index may be used to identify articles published during a particular indexing period which cited the article as a reference. Practical guidelines are also presented for establishing a simple but comprehensive personal system for filing and retrieving on demand reprints, pamphlets, and notes.


Pulmonary processes of mature-appearing lymphocytes: pseudolymphoma, well-differentiated lymphocytic lymphoma, and lymphocytic interstitial pneumonitis. Patients with pseudolymphoma, well-differentiated lymphocytic lymphoma, and lymphocytic interstitial pneumonitis were studied. Diagnoses were confirmed by recently developed immunochemical staining techniques. Radiographic findings in pseudolymphoma were different from those in well-differentiated lymphocytic lymphoma, and clinical findings in lymphocytic interstitial pneumonitis were different from those in the other two types of lesions. The interstitial infiltrate of lymphocytic interstitial pneumonitis had two patterns: basilar with an alveolar component and diffuse with associated honeycombing. Pseudolymphoma and lymphocytic interstitial pneumonitis are being polyclonal inflammatory processes without malignant potential. Well-differentiated lymphocytic lymphoma, a monoclonal neoplasm, often has an indolent course.


[Transperitoneal anterior approach to the neoplastic kidney]. The authors present 51 cases of malignant renal tumours approached by the transperitoneal anterior route. The authors preferred a bilateral subcostal incision sectioning the insertions of both abdominals, that was prolonged in the para-rectal region on the right or on the left, according to case, into the vicinity of the femural arcade. In this group of 51 cases 8 explorations of the inferior cava were performed and in one case total resection of the abdominal cava was carried out. In 4 of the patients nephrectomy was associated with splenectomy (2 cases), with colecystectomy and with right duodeno-hemicolectomy (one case each).


[Treatment of supramalleolar open fractures by means of centro-medullary osteosynthesis of the fibula]. The study is concerned with 11 cases of open supra-malleolar fractures involving both bones. The tibial fracture was of the comminutive type, with a large number of small fragments allowing an exteriorization of the proximal end or telescoping of the ends with consecutive loss of the axis. Due to a difficult synthesis of the tibial bone synthesis of the peroneum with a thick rod or with a brooch was performed, recovering the length of the lever and allowing to de-telescope the tibial focus, to recover the normal length and a corresponding axis. Since in all the treated cases consolidation was achieved over a duration of 5 months, the advantage is stressed, of the procedure which, solving indirectly the fracture, protects the tibial focus, already poorly irrigated and susceptible to pseudarthrosis in thi;s type of location.


[Value of manometry in establishing the developmental stage of portal hypertension and the effectiveness of therapeutic portacaval shunt]. A total of 105 patients have been studied, operated for portal hypertension, that underwent porto-manometric investigations by various methods, before and during surgery. The study was aimed at establishing indications that can be provided by portal manometry on the evolutive stage of portal hypertension. Correlations have been established between ascitic decompensation, the frequency of superior digestive hemorrhages and the portal pressure. The efficiency of the post-systemic derivation was evaluated manometrically, depending on the type of the anastomosis. Conclusions are presented, on the particular value of the manometric investigation for the correct choice of the porto-caval shunt.


[The flexible metallic intramedullary nail (Mechanical model and theoretical analysis)]. An ideal mechanical model is proposed for the system which includes the fractured femur and the flexible rod. Developing through calculus the consequences of hypotheses which define the model, the rigidity and the resistance of the system are evaluated. The theoretical considerations and the numerical results of the analysis indicate the superiority of the non-parallel assembly of the rods in the case of high diaphysary fractures.


[Current problems in the treatment of thoracic hydatid cysts]. The authors present the experience of the Clinic for Thoracic Surgery of Bucharest, based on a total of 1206 cases of patients operated for hydatic cysts. An original classification is presented, of human hydatidosis, the indications of surgical treatment are stressed, namely the evacuation of the hydatic membrane with the peri-cystic tissue, even in cases of evacuated and suppuratec cysts--the authors objecting to the pulmonary resection in cases of hydatic cysts. The authors have performed simultaneous bilateral interventions, associated or not with phrenotomy, in bilateral and hepatic localizations. In the paper is also presented a new procedure (introduced by Prof. C. Coman) for the total extirpation of the hydatic membrane, a simple procedure which practically prevents effraction of the cyst. On the other hand the results confirm the efficiency of the procedure, very good results being obtained in 98,8% of the cases.


[Evaluation of therapeutic measures in toxicoseptic states]. Based on observations made in 112 cases of toxico-septic conditions that had developed in surgical and obstetrical conjunctures, the authors propose a unified codification of the major therapeutical means (etiologic therapy, general, non-specific and specific therapy, adapted for functions and organs). The removal, or surgical draining of the septic focus is the most efficient therapy of toxicoseptic conditions of surgical or obstetrical origin. Compared to this method all the other therapeutical methods are secondary or adjuvant. The authors have acquired a vast experience in the use of a device for peritoneal washing-draining in cases with toxico-septic syndrome of surgical and obstetrical origin. General, non-specific therapeutic measures for quantitative and qualitative maintenance of the internal environment of the organism are achieved with relatively large amounts of non-colloidal crystalloid isotonic solutions, administered over the entire duration of the toxico-septic condition. The importance of the specific therapy is stressed, adapted for functions and organs, stressing amost particularly the therapeutical measures in which the authors have acquired extensive experience.


[Postoperative intestinal infarction].

[Postoperative intestinal infarction]. A total of 39 cases are analized, of post-operative intestinal infarction, that occured exclusively in patients with cardiovascular diseases. The clinical signs appeared early in most of the cases (85,4% in the first 72 hours; 48,4% in the first 24 hours) and the manifestations were typical in 42,4% and non-significant in 35% of the cases. Since none of the cases benefited from a successful therapy the authors suggest that stress should be laid on prophylactic measures (correct re-equillibration).


[A new experimental procedure of intraamniotic application of substances in multiparous experimental animals (author's transl)]. In order to proof the distribution and metabolizing of various substances experimental operation models in animals were developed. The placental transfer was examined in guinea pigs and rabbits; while metabolism was studied in the Göttinger miniature pig. The presented model enables us to examine the following compartments: maternal organism, placenta, amniotic fluid and fetus.


The relationship of fatty acid composition and surface activity of lung extracts. Male weanling rats were fed fat-free diets supplemented with 4% (w/w) safflower oil (control) or 4% tripalmitin (essential fatty acid (EFA) deficient) for 14 weeks. Whereas the amount of lecithin in lung lavage material remained unchanged, lung lavage lecithin from EFA-deficient rats contained significantly less palmitic acid (61.4 +/- 2.0% vs. 77.4 +/- 5.8%, P less than 0.01) than that from controls. Surface tension vs. area hysteresis loops were obtained for total lipid extracts (TLE) of lung lavage fluid, intra- and extra-cellular lipoprotein fractions (IBI and IBE) and lipid extracts of those lipoprotein fractions (LBI and LBE). A significant increase in minimal surface tension (gammamin) was found for all samples obtained from EFA-deficient rats as compared to controls. Refeeding of diets containing safflower oil for 7-14 days reversed these changes. Air pressure-volume curves on degassed, excised lungs indicated that greater pressure is required to maintain a given lung volume in EFA-deficient rats. These results support the hypothesis that the fatty acid composition of pulmonary surfactant lecithins is a major determinant of the surface activity of lung extracts.


A model for the study of the physical behaviour of the lung-surfactant film in vitro. A model of the alveolar air-fluid boundary was developed for a future study of the influence of several gases and gas mixtures on the surfactant film of the lung. Since the surface behaviour of the film material changed after denaturation, we had to use it in its native state. It was collected as foam during lung lavage and applied upon a hypophase of concentrated lavage fluid. This combination showed a constant physical behaviour during repeated compression and expansion of its surface. After the excess of applied material had left the surface there was hardly any change of gammamin and gammamax or of the shape of the area versus surface-tension curve (A-gamma curve) during several hours. Mean values of gammamin and gammamax were 5.5 +/- 2.0 and 55.0 +/- 2.0 dyne/cm respectively. The mean value of the hysteresis area was 847 +/- 82 dyne cm. Its shape was similar in all experiments. The stability of this model makes it useful for the intended investigations, but also seems to offer useful data for calculations in relation to the actual behaviour of lung alveolar surfactant in vivo.


[Mycotic aneurysm of superior mesenteric artery (author's transl)]. Reference is made to a case of mycotic aneurysm of the superior mesenteric artery caused by bacterial endocarditis with streptococcus feacalis combined with reversible neurologic complications. On account of improvement in the treatment a careful radiological examination is very important with exact account of the size and localisation of the aneurysm. Our patient was successfully treated with aneurysmectomia and reconstruction of the vessel by transplantation of a vein.


[Clinical use of prostaglandins in obstetrics and gynecology]. The use of prostaglandins in obstetrics and gynecology is reviewed in the light of present knowledge. The important uses, induction of abortion and induction of labor at term, are discussed. The different forms of prostaglandin and the side effects are briefly described.


Enhancement of fibrinolysis in rabbits exposed to low and moderate levels of carbon monoxide inhibited by epsilon amino caproic acid. The first (control) group of rabbits breathed ambient air whereas the second was exposed to low level carbon monoxide (CO, 50 ppm by volume) for 24 hr continuously for 8 weeks. The third group was exposed to 300 ppm CO for 4 weeks. The fourth group was exposed to 300 ppm CO for the same period of time as the third group but in addition they were also given epsilon amino caproic acid (EACA) orally, and the results compared to Group III. Per cent oxyhemoglobin (HbO2), per cent hemoglobin (Hb) and per cent carboxyhemoglobin (HbCO) were monitored in all groups. Tests of fibrinolysis were monitored and showed acceleration of the whole blood clot lysis and euglobulin lysis times (ELT). A fibrin plate test confirmed the increased lysis and serum fibrin and/or fibrinogen degradation products (FDP) were elevated in the CO exposed animals. No changes were observed in the same tests in the rabbits exposed to ambient air. The fourth group of animals receiving EACA showed inhibition of lysis and decrease in serum FDP. Alpha-1-antitrypsin and alpha-2-macroglobulin assays in all groups showed no change. Microscopic examination of the large vessels in these test groups showed endothelial damage which indicates a possible source for a plasminogen activator release, or lead to action of Hageman factor and activated plasma plasminogen proactivator.


A rapid turbidimetric determination of fibrinogen degradation products (FDP). A rapid and simple turbidimetric determination of fibrinogen degradation products is described. This method is based on the increase of the turbidity due to the formation of precipitating antigen-antibody complexes after addition of rabbit antihuman fibrinogen antiserum to human serum. The increase in turbidity correlates very well with results obtained with the haemagglutination inhibition technique and has the advantage of a more objective quantitation. The reproducibility appears to be quite good. The turbidimetric method is independent of the colour of serum samples.


Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases. The medical records of 118 cases who met laboratory criteria of DIC were studied. The most frequent etiologies were: Generalized infection (39.8%), trauma (16.9%), malignancy (6.8%) and surgical cases (6.8%). The main clinical manifestations which appeared to be related solely to DIC were (in a decreasing order of frequency): Bleeding (64.4%), renal dysfunction (24.6%), liver dysfunction (18.6%), respiratory dysfunction (16.1%), shock (14.4%), thromboembolic phenonmena (6.8%) and central nervous system involvement (1.7%). In 26 patients none of these manifestations were observed. In patients with infection, liver and renal dysfunction were frequent and respiratory dysfunction rare, whereas in trauma cases, liver and renal dysfunctions were rare and respiratory dysfunction frequent. This variability indicates that the clinical manifestations are affected not only by the process of intravascular coagulation but also by the underlying clinical disorders. The most impaired coagulation tests were prothrombin time, partial thromboplastin time, platelet count and thrombin time. The degree of abnormality of these coagulation tests was found to be related to the extensiveness of organ involvement. The mortality (overall 54.7%) increased independently with age, with the number of clinical manifestations and with the degree of abnormality of the above-mentioned four most impaired coagulation tests. In addition, older patients were more likely to have an increased number of clinical manifestations and more impaired coagulation tests. Mortality was similar in the various etiologies except for trauma patients in whom it was lower (30%).


Contribution of platelets to the cardiovascular effects of ADP in the rat. The contribution of platelets to the cardiovascular effects of ADP was investigated in rats in different experimental conditions. Following rapid i.v. bolus injections of ADP (from 0.001 to 0.03 mg/kg b.w.) only a dose-related fall in blood pressure could be detected. Increasing the dose of ADP (up to 1 mg/kg b.w.), platelet fall and changes in cardiac rhythm (bradycardia, A. V. blocks and ectopic beats) became evident. All these phenomena were rapidly reversed. Inhibition of platelet aggregation by a pyrimido-pyrimidine compound (SH 869) or thrombocytopenia induced by Busulfan or antiplatelet antiserum did not significantly protect the animals from the cardiovascular effects of ADP. The fall in blood pressure, however, was reduced. Adenosine, at aquimolar concentrations, caused ECG changes similar to those induced by ADP with no platelet aggregation and a less pronounced blood pressure fall. These results suggest that most of the cardiovascular modifications induced by rapid injection of ADP are largely independent of platelets. Platelets appeared to play a more important role when ADP was given for a longer period of time. A slow i.v. infusion of ADP (6 mg/kg b.w. for 10 min) was accompanied by platelet fall, cardiovascular collapse and ECG alterations typical of myocardial ischaemia. All these effects persisted throughout the ADP infusion but disappeared soon after its termination. They were almost completely inhibited in rats given SH 869 or made thrombocytopenic. In conclusion, platelets seem to contribute to the cardiovascular effects of ADP only in certain experimental conditions. In others, the nucleotide's effects seen more important.


Evaluation of platelet tests for measurement of cell integrity. Various tests were evaluated for their capacity to differentiate between platelet suspensions with different degrees of cell damage. Those suspensions were prepared by simultaneous isolation of platelets from the same platelet-rich plasma (PRP) using the following procedures: 1. centrifugation at 4 degrees C with EDTA 2. gel filtration in Tangen's buffer 3. gel filtration in Ca2+-free Tyrode's soltuion 4. gel filtration in Ca2+-free Tyrode followed by dehydration against polyethylene glycol 20,000 and 5. albumin density gradient centrifugation. In these suspensions and in the original PRP the following parameters were studied: 1. morphology; 2. aggregability upon ADP addition; 3. platelet factor 3 availability; 4. uptake of 14C-serotonin and 3H-adenine; 5. metabolism of 3H-adenine and adenylate energy charge; 6. endogenous total ATP, ADP and serotonin and 7. lactate dehydrogenase (LDH) activity. Quantitation of pseudopod formation in the light or electron microscope and log dose response studies for ADP-induced aggregation proved to be the most sensitive and reproducible of the tests studied. Additional information could be obtained from measurement of the 3H-label in the ATP and hypoxanthine-inosine fractions and calculation of the adenylate energy charge. Determination of platelet factor 3 availability or uptake studies of 14C-serotonin and 3H-adenine were less suitable for discriminating between cell suspensions. Data for total ATP and serotonin concentrations and LDH activity differed between the cell suspensions but instead of detecting various degrees of cell damage they reflected alterations in platelet population caused by the isolation procedures.


Effect of 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141) on rabbit platelet aggregation in vitro and rat platelet retention. Effect of 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141) on rabbit platelet aggregation in vitro and rat platelet retention investigated. In the in vitro study, KC-6141 inhibited ADP-induced aggregation by 27% at 5 X 10(-4)M, being more active than dipyridamole but much less than adenosine. Inhibition of arachidonic acid- and collagen-induced aggregation by KC-6141 was more effective than that of ADP-induced one and its ED50 was 2.1 X 10(-5) and 8 X 10(-5)M, respectively. KC-6141 was 10 and 4 times more potent than aspirin in arachiodonic acid- and collagen-induced aggregation, respectively. The dose-response curve of KC-6141 was parallel to that of aspirin, suggesting it is an aspirin-like compound. In the platelet retenion study, a method for determining platelet retintion in rats was devised so that platelet retention can be measured with a volume of blood as small as possible. By use of the method, effects of KC-6141, aspirin and dipyridamole were compared. When deministered intraperitoneally at 100 mg/kg, KC-6141 indicated 54.8% inhibition of platelet retention, whereas aspirin and dipyridamole showed only 23.5 and 5.2% inhibition, respectively. On the oral administration at 200 mg/kg KC-6141 inhibited by 60.8% and its ED50 was 125 mg/kg. The activity lasted over 32 hr. The above results demonstrated that KC-6141 is a compound with more potent action on the platelet aggregation, as well as on the platelet retention than aspirin and dipyridamole-a known antithrombotic drug.


Immunochemical detection of the Thomsen-Friedenreich antigen (T-antigen) on platelet plasma membranes. Platelet plasma membranes were found to possess the disaccharide beta-D-galactosyl (1-3)-N-acetyl-D-galactosamine which was measured by gas chromatography after release by alkaline borohyride treatment and desialylation. Immunological evidence using the specific lectins from Arachis hypogoea and Agaricus bisporus and an anti-T serum confirmed the presence of this disaccharide, the immunodominant group of the Thomsen-Friedenreich antigen (T-antigen). This receptor was only found after prior neuraminidase treatment indicating that it is normally a cryptic antigen, i.e. masked by sialic acid in the native membrane. Evidence for a second receptor with terminal N-acetylgalactosamine was obtained using the lectin from Helix pomatia. The binding of myxovirus and the lectins from Phaseolus vulgaris (PHA) and Canavalia ensiformis (Con A) to platelet membrane was also demonstrated. The implication of the T-antigen in elimination of the platelets and its role in the haemolytic-uraemic syndrome is discussed.


On the preparation of bovine alpha-thrombin. An improved method for the preparation of bovine alpha-thrombin is described. The procedure involves that activation of partially purified prothrombin with tissue thromboplastin followed by chromatography on Sulfopropyl-Sephadex C-50. The purified enzyme is homogeneous on polyacrylamide discontinuous gel electrophoresis and has a specific activity toward fibrinogen of 2.200-2,700 N.I.H. U/mg. Its stability on storage in liquid media is dependent on both ionic strength and temperature. Increasing ionic strength and decreasing temperature result in optimal stability. The denaturation of alpha-thrombin by guanidine hydrochloride was found to be a partially reversible process with the renatured species possessing properties similar to "aged" thrombin. In addition, the catalytic properties of alpha-thrombin covalently attached to agarose gel beads were also examined. The activity of the immobilized enzyme toward fibrinogen was affected to a much greater extent than was the hydrolysis of low molecular weight, synthetic substrates.


Ultrastructural changes of the tissue thromboplastin after intravenous injection in rabbits. Attempts were made to demonstrate ultrastructural changes of the tissue thromboplastin after intravenous injection, as a model experiment on the pulmonary microthrombi formation induced by the tissue thromboplastin circulating from venous return. Concentrically arranged membrane structures of the injected thromboplastin disappeared in extremely short time after the injection of the thromboplastin in rabbits. The long sheet membrane of the injected thromboplastin was frequently seen as adhered to the vascular endothelium or to the surface of blood corpuscles. Furthermore, fibrin fibres were formed in contact with the long sheet membrane of the thromboplastin. Membrane structures were not found anywhere in the control rabbits.


Factor XI (PTA) deficiency in an English-American kindred. 2 sisters of English-American descent had a mild bleeding syndrome due to marked deficiency (less than 1% activity) of factor XI. This defect was transmitted in an autosomal recessive manner. Although factor XI deficiency was previously thought to occur largely, if not exclusively in Jews, extensive review of geneologic records and analysis of family names failed to disclose Jewish ancestry. These findings, together with the existence of several definite and presumed consanguineous English-American ancestors, the fact that family members had resided in a restricted geographic area for many generations, and analysis of English and Jewish immigration patterns lead to the conclusion that this defect is not likely to be of Jewish derivation. Should this mutation have occurred in the distant past it is conceivable that the gene pool for this defect is substantial, particularly in certain areas in New England.


Spontaneous platelet aggregation in cerebrovascular disease. 50 patients from a group of 130 patients with transient ischaemic attacks or cerebral infarction were found to demonstrate in vitro spontaneous platelet aggregation (SPA) while 80 normal subjects tested never showed this phenomenon. The following additional findings point towards a possible platelet abnormality: 1. Platelets from 10 patients with SPA when isolated and resuspended in normal plasma still demonstrated SPA while isolated normal platelets resuspended in patient's plasma did not. 2. Platelets demonstrating SPA showed an increased aggregation tendency upon incubation with ADP while normal platelets developed the expected refractory state. SPA was found to be dependant upon the presence of divalent cations and could further be inhibited by phentolamine and adenosine. Aspirin effectively abolished SPA in 50 patients and relieved the clinical symptoms of patients with recurrent complaints of transient blindness and paraesthesia.


Catabolism of fibrinogen in pregnant rabbits before and after delivery. 16 non-pregnant female and 19 pregnant rabbits were injected with purified rabbit 125I-fibrinogen in order to study the catabolism of fibrinogen before and after delivery. The half-life time (T 1/2) of the clottable 125I-radioactivity in pregnant rabbits during the last third of gestation was 27.3 +/- 5.3 hr in comparison to 54.4 +/- 3.7 hr in non-pregnant rabbits. After delivery, T 1/2 returned to normal values of 47.9 +/- 10.9 hr. The fractional catabolic rate (FCR) of the clotabble 125I-radioactivity was 67.1% X d-1 +/- 8.6 before and 41.6% X d-1 after delivery whereas FCR in non-pregnant rabbits amounted to 44.7% X d-1 +/- 4.8. These figures demonstrate a pronounced increase in fibrinogen catabolism during the last third of gestation in pregnant rabbits and a normalization immediately after delivery. Although in pregnant rabbits the elimination of fibrinogen from the circulating blood was pronouncedly increased, the plasma fibrinogen concentration did not change. Only after delivery did the fibrinogen concentration increase when the fibrinogen catabolism had already normalized.


Studies of fibrinogen metabolism in healthy and hypertensive female subjects with the use of autologous I-125-fibrinogen. 10 healthy female subjects and 15 female patients with essential hypertension were studied with respect to fibrinogen metabolism in a steady state. Autologous I-125-labeled fibrinogen (I-125-fibrinogen) was used as a tracer. Comparison of the results showed that plasma volume, t1/2 of plasma I-125-fibrinogen and fractional catabolic rate (j3p) of plasma fibrinogen (x) were not appreciably different in both groups of subjects, but plasma fibrinogen concentration, x and catabolic flux of x (j3px) (synthesis rate) were significantly higher in hypertensive subjects, whereas extravascular fibrinogen (y) and fractional transcapillary transferrate (j1) of x were significantly decreased in the patients. Further analyses of the data in both groups showed that there were significant correlations between diastolic blood pressure (P) and j1 with a regression equation of 41 = e-0.0285P, between x and j1 with a regression equation of x = 226e-0.939j 1 and between y and j1 with a regression equation of y = 12.6e0.624j 1. These results indicate that the observed decrease of j1 triggered the transition from normal to pathological steady state and is responsible for the altered metabolism and distribution of fibrinogen in hypertensive subjects.


Effect of orthostatic changes on urokinase excretion. The effects of orthostatic changes on the excretion of urokinase were studied in healthy normal volunteers. Urokinase excretion rose (average +69%) significantly (p less than .005) while urine volume fell (average-59%) significantly (p less than .001) after the subjects had been standing. There was no difference between men and women nor was there an apparent diurnal variation in urokinase excretion of recumbent subjects. A relationship between urokinase excretion and sympathetic nervous system activity is suggested.


Effect of 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141), an anti-aggregating compound, on experimental thrombosis in rats. In ordder to evaluate 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141) as a possible antithrombotic compound, a simple and reproducible method for experimental thrombosis in rats was devised. A silken thread was inserted in the extracorporeal shunt between the carotid artery and the jugular vein. 15 min after the circulation of blood, wet weight of thrombus which developed on the thread was measured to determine the degree and rate of thrombus formation. Equalization of average body weight of rats for each group provided good reproducibility. Microscopic examination demonstrated that the thrombus was primarily composed of platelets. By use of the technique, the activities of KC-6141 and two known inhbitors, aspirin and dipyridamole, were determined. Of the three compounds, KC-6141 was the most potent inhibitor for the thrombosis. Its ED50 was 60 mg/kg when given orally and the compound was activite for about 40 hr. Aspirin was about twice as less active than KC-6141 and dipyridamole showed no effect on the thrombosis. The ranking order of potency against the experimental thrombosis for the three compounds was the same as that for inhibition of platelet aggregation in vitro and platelet retention in rats, as reported previously by us. Therefore the method seems to be associated with platelet aggregation and retention. The above result suggests that KC-6141 is of value as antithrombotic drug in vivo.


Blood coagulation and fibrinolysis in haemorrhagic stroke. Studies of 11 patients with haemorrhagic stroke revealed no significant change in kaolin cephalin clotting time, prothrombin time, thrombin time, PF 3 availability, platelet count and factor V and VIII during the first week. Plasma fibrinogen was significantly increased while factors VII + X were decreased (borderline significance). Prolongation of plasma recalcification time and decrease in heparin tolerance reached borderline significance. There was moderate, but significant, increase in serum antithrombin activity and plasma (euglobulin fraction) fibrinolytic activity.


The value of phenformin and ethyloestrenol in the prevention of deep venous thrombosis in patients undergoing surgery. The effect of phenformin and ethyloestrenol on the incidence of post-operative deep venous thrombosis was studied in 314 surgical patients in a double-blind randomised trial. Although the laboratory tests suggested that the regime produced an increase in activators of the fibrinolytic system, the drugs used did not lower the incidence of post-operative deep venous thrombosis. Possible explanations of this paradox are advanced.


Purification of a fibrinolysis inhibitor in serum from post-traumatic patients. A fibrinolysis inhibitor was purified in serum from post-traumatic patients by the use of flat bed electrofocusing of serum desalted by gel chromatography followed by affinity chromatography on a column of matrix-linked plasminogen. Disc gel electrophoresis yielded one protein band. The inhibitor protein was also found in normal serum, but in a lower concentration.


An epidemic of venereal infection in thoroughbreds. The clinical pattern, bacteriological investigation and subsequent treatment of a serious outbreak of venereal disease in stud farms on both sides of the Irish Sea is described. The consistency with which Bacillus proteus was isolated from infected mares and stallions was remarkable. Prompt treatment with ampicillin, to which the organism was sensitive in vitro, eradicated the disease. No local treatment was applied.


[Microflora in milk powder and baby food in powder form (author's transl)]. After a discussion of the microbiological standards for milk powder and powdered baby food in various countries, the results of the microbiological analyses of some 1500 samples of these foodstuffs were presented. It emerged that the microflora of these products consists mainly of lactobacteria (they are not demonstrable with all culture methods), micrococci and bacilli: the latter are those with the greatest importance with respect to food hygiene. In addition to these Clostridia and moulds are also found in the samples; very occasionally enterobacteria are also found. No pathogenic germs were detected. With respect to the proposals for standards it was found that the latest Hungarian standards proposals are acceptable provided that the methods of analysis (culturing after Polonyi) are retained also for the proposals discussed.


Pyridoxine treatment of galactorrhoea-amenorrhoea syndromes. The effect of pyridoxine (B6) on galactorrhoea, amenorrhoea, and the galactorrhoea-amenorrhoea syndrome was studied in 22 patients. No consistent change in serum prolactin concentration and no resumption of ovulation were seen during 3 months B6 therapy. Inappropriate lactation ceased in 3 of 10 patients with galactorrhoea alone, and menses were restored in 2 of 9 patients with the galactorrhoea-amenorrhoea syndrome while on B6 therapy. Our results suggest that B6 is not generally effective in  the treatment of galactorrhoea-amenorrhoea syndromes.


Cerebral hemorrhage from a mycotic aneurysm developing during appropriate antibiotic therapy. A patient with bacterial endocarditis had headaches, cerebrospinal fluid pleocytosis and normal cerebral angiograms. Fifteen days later, while on appropriate antibiotic therapy, he developed an intracerebral hematoma due to a mycotic aneurysm. Mycotic aneurysm is an infrequent but serious complication of bacterial endocarditis. An aneurysm should be considered whenever a patient with bacterial endocarditis has neurologic symptoms even when the patient is receiving antibiotics.


Thyroid hormone formation in ectopic thyroid gland. A case study. Several steps of thyroid hormogenesis were studied on a subhyoid ectopic thyroid tissue in a case of compensated hypothyroidism with simultaneous sublingual and subhyoid ectopic thyroid. The patient, a 19-year-old girl, had normal values for serum T4, T3U and T3, and an elevated serum TSH level. The thyroidal 131I uptake was elevated both at 3 h and 24 h after oral 131I intake. No significant discharge of radioiodine was observed after perchlorate load. On the thyroid biopsy specimen, peroxidase activity was shown to be normal by both assays of guaiacol oxidizing and iodinating activity. Thyroglobulin was 19S and was normally iodinated in vitro with peroxidase. Iodine content of thyroglobulin was within the normal range. The mean percentage distribution of 131I administered 7 days prior to the biopsy showed no significant difference from the normal pattern. From these studies, no specific defects in thyroid hormogenesis could be detected in this case. It is suggested that abnormalities in thyroid function in this case are mainly due to insufficient functioning mass in the ectopic thyroid.


Effect of antithyroid treatment on calcium-phosphorus metabolism in hyperthyroidism. I: Chemical quantities in serum and urine. The effect of antithyroid treatment on the disturbed calcium-phosphorus metabolism in hyperthyroidism was studied in 16 patients. Elevated serum concentrations and urinary excretions of calcium and phosphorus were almost normalized 4 weeks after the start of medical treatment. Serum immunoreactive parathyroid hormone was decreased in the hyperthyroid state and became normal after medical treatment. Serum alkaline phosphatase levels were elevated throughout the study with an increase to a maximum peak after 8 weeks of antithyroid treatment. Urinary hydroxyproline excretion was initially markedly increased and fell rapidly during therapy. The observed changes suggest decreased bone resorption and increased bone formation with deposition of bone mineral after antithyroid treatment. Alterations in the serum albumin concentration during the investigation period influenced the total serum calcium concentration. Using albumin adjusted serum calcium values no hypocalcaemia was found during medical treatment or after a subsequent subtotal thyroidectomy.


Effect of antithyroid treatment on calcium-phosphorus metabolism in hyperthyroidism. II: Bone histomorphometry. Histomorphometric analysis of iliac crest biopsies was performed after tetracycline double-labelling in 22 hyperthyroid patients before and after medical antithyroid treatment for an average period of 4 months. The initially increased cortical porosity was normalized during treatment whereas the amount of trabecular bone was unchanged. The osteoclastic resorption in cortical bone decreased but was still elevated. The osteocytic osteolysis remained slightly increased. In trabecular bone, however, the bone turn-over decreased to a subnormal level following treatment and the surfaces were inactive in bone resorption and bone formation. An increase was observed in the amount, extent and width of osteoid seams due to an increase in the lifespan of bone forming sites and a prolongation of the maturity period of osteoid. The observed increased deposition of cortical bone after antithyroid treatment may explain the positive calcium balance in this period.


Adrenal hypertrophy produced by 17alpha-esterified glucocorticoids in rat foetus. Glucocorticoids were injected sc into rat foetuses through the uterine wall on day 19 of intrauterine development; two days later the foetuses were removed and their adrenal glands were weighed. Some betamethasone derivatives produced marked adrenal hypertrophy in the foetuses. Structural characteristics of the effective compounds were 17alpha-esterification and 16beta-methylation. 9alpha-Halogenation and 21-esterification of glucocorticoids were not essential for producing the hypertrophy. Propionic acid at the C-17 position was more effective than valeric and acetic acids in producing the hypertrophy. The effect of betamethasone 17, 21-dipropionate was dose-responsive and prevented by simultaneous administration of betamethasone 21-disodium phosphate. Results obtained with decapitated or encephalectomized foetuses suggested that the hypertrophy produced was not due to a direct action of the glucocorticoids on the adrenal gland, but mediated by the hypothalamo-pituitary system.


The time course change after castration in short-loop negative feedback control of LH by HCG in women. The time course of change in the suppressive effect of human chorionic gonadotrophin (HCG) on luteinizing hormone (LH) and/or LH-beta following castration was studied by a specific LH-beta radioimmunoassay. At 14-50 days after castration 8 women were given 10 000 IU of HCG in a single intramuscular injection (group 1), 5 women were given 2000 IU of HCG in the same way (group 2), and 5 were injected with saline as controls (group 5). In addition, 5 women 6-15 months (group 3) and 7 women 3-8 years (group 4) after castration were given 10 000 IU of HCG. The serum concentrations of HCG in groups 1, 2, 3 and 4 reached peak levels of 209.4, 44.1, 210.6 and 238.6 uU/ml, respectively, 4 h after the HCG injection. The serum LH concentration in group 1 was reduced significantly (P less than 0.01) by HCG administration, but the reductions in the LH levels in groups 2, 3 and 4 after HCG injection were not significantly different from that of the controls. These findings suggest that the threshold of the short-loop negative feedback control of LH in women changes with time after castration.


Primary intracranial HCG-producing germinoma in a boy with congenital adrenal hyperplasia. A primary intracranial HCG-producing tumour was studied in an 8 year old boy with congenital adrenal hyperplasia. The case provided a unique opportunity to study the sequential changes in serum and urinary androgens and HCG as measured by radioreceptor assay for HCG and by radioimmunoassay for HCG using antisera raised against the hormone specific for the beta subunit of HCG. Plasma concentrations of HCG, measured by the radioreceptor assay, closely correlated with the biologic activity of his tumour, as measured by serum testosterone concentration. This case demonstrates that precocious puberty in any child, including one with a known androgen disorder such as congenital adrenal hyperplasia, warrants through investigation.


Effects of cycloheximide on the ultrastructure of the zona fasciculata of the young rat adrenal. The ultrasturctural changes induced in the cells of the young rat adrenal zona fasciculata by cycloheximide are studied. Thirty minutes after administration of doses producing inhibition of protein synthesis (1.5 and 4.5 mg/kg body weight) there was a significant increase in the relative volume of the nucleolus, as shown by stereologic methods, which was accompanied by extensive perinucleolar chromatin caps. In the cytoplasm, membranous whorls were observed in several organelles and the background cytoplasm, but the volume fractions of the organelles were not significantly altered. Nucleolar changes were interpreted as suggesting that the inhibition of cytoplasmic protein synthesis may be accompanied by an enhanced formation of nucleolar proteins.


Use of HPLC to determine the effect of 17 beta-hydroxy-7 alpha-methylandrost-5-en-3-one (RMI 12,936) on production of progesterone by rat ovarian homogenate. A new high presure liquid chromatography (HPLC) method for the determination of progesterone in the presence of other delta 43-ketosteroids is described. Using this method it is shown that the rate of production of progesterone from pregn-5-ene-3,20-dione by rat ovarioan homogenate is initally rapid but falls to zero within 10 min. Experiments indicate that the inhibition is due to the progesterone formed. Inclusion of RMI 12,936 with the pregn-5-ene-3,20-dione substrate results in a lower final level of progesterone and continuous production of 7 alpha-methyltestosterone. The reduction in the levels of progesterone in presence of RMI 12,936 corresponds closely to the reduction in plasma progesterone in vivo folowing administration of RMI 12,936 described previously.


Detection of chorionic gonadotrophin like activity in infertile cycles with a short luteal phase. Three of 24 infertile women with a short luteal phase transiently showed chorionic gonadotrophin (HCG) like immunoreactivity in serum as measured by the HCG-beta subunit radioimmunoassay. The plasma progesterone concentration was elevated above the lower normal postovulatory level in 2 of these women who also had elevated basal body temperature at the time HCG was detected. Positive HCG reaction coincided with the pre-ovulatory surge of luteinizing hormone (LH) in one patient, but in 2 other cases the LH concentration was low suggesting absence of LH interference. Our results suggest that some infertile women may conceive during their cycles with a short luteal phase and maintain pregnancy until HCG becomes detectable.


HCS-HCG regulation in cultured placenta. Tissue culture has been used to study the action of different substrates on the secretion of HCG and HCS in human placental explants. The following compounds have been studied: prostaglandins E2 and F2alpha, adrenaline and noradrenaline, oestriol and progesterone, glucose concentration. The investigators first measured the normal secretion of three term placentas and 2 months placentas. The activity of the compounds tested is expressed in per cent of the normal values. The investigators have checked that the cultivated cells were always viable by measuring the oxygen consumption during all the experiments. PG E2 and F2alpha are without action on term placentas. Adrenaline and noradrenaline reduce significantly the secretion HCS by full term placentas and have no action on HCG secretion. Oestriol always stimulates HCS secretion by full term placentas and 2 months old placentas, whereas progesterone stimulates young placentas and inhibits full term placentas. Both steroids have no action on HCG secretion. Glucose is essential for HCS secretion by placentas but high values of glucose in the medium signficantly reduce the HCS secretion by full term placentas.


Hypothalmic-pituitary adrenal responsiveness to dexamethasone-insulin tolerance test in acromegalic patients before and during treatment with bromocriptine. Insulin tolerance tests were carried out in 10 acromegalic patients after 1 mg dexamethasone had been given the previous evening (DEX-ITT). Nine patients showed a rise in plasma 11-OHCS and four patients showed a rise in plasma growth hormone (GH) levels. These responses were unaltered after treatment with bromocriptine 10 mg daily for two months. Basal plasma GH levels fell in 6 of the patients and the mean plasma GH levels of the 10 patients during an oral glucose tolerance test (OGTT) fell from 63.2 +/- 25.5 ng/ml before treatment to 53.0 +/- 27.1 ng/ml (mean +/- sem; p less than 0.05). These data fail to confirm a previous report of abnormal hypothalmic-pituitary-adrenal suppressibility during a DEX-ITT in acromegalic patients. They also indicate that bromcriptine does not alter the responses of plasma 11-OHCS and plasma GH to the DEX-ITT despite lowering plasma GH levels.


Fat cell size and lipid content of subcutaneous tissue in congenital generalized lipodystrophy. Fat cell size and lipid composition of subcutaneous tissue from 3 patients with congenital generalized lipodystrophy have been measured before and after treatment with either pimozide, fenfluramine or hypophysectomy. The fat cell volume before treatment ranged between 9.8 x 10(4) and 17.7 x 10(4) micron 3, compared to 9.0 x 10(4) and 85.3 x 10(4) micron 3 in 15 controls. The amount of lipids was only 1/10 to 1/50 of normal, triglycerides being the most heavily reduced lipid component. Neither the fat cell size nor the lipid content were affected by treatment with hypophysectomy, pimozide or fenfluramine.


Histamine stimulates prolactin release in norman men. Histamine stimulates prolactin (PRL) and growth hormone (GH) release in the experimental animal. In order to evaluate the possible effect of histamine on these hormones in man, in our study, 9 normal volunteers underwent an intravenous histamine infusion (200 microgram in 15 min). Five of them also underwent an intravenous histidine infusion (200 microgram). Histamine induced a significant PRL release in 7 subjects, the maximum level reached being 36.2 +/- 12.09 ng/ml, while GH levels were not affected. Histidine was ineffective on both PRL and GH levels. It is known that histamine, administered peripherally, does not cross the blood brain barrier. This fact suggests that, in man, histamine stimulates PRL release by acting directly on the pituitary. In addition, since stressful situations may elicit both PRL and GH release, the fact that the latter was not affected by histamine, suggests that a mere stress-effect is not responsible for the PRL release observed in our subjects.


Re-examination of human calcitonin radioimmunoassay. Evaluations of human immunoreactive calcitonin (IRCT) assay have been extensively reviewed. Labelled hormone was re-purified on carboxymethyl-cellulose in order to isolate a fraction containing mainly monoiodinated calcitonin, which was found to be very stable. Two antisera with different immunochemical characteristics were used for incubation studies, one of which was incubated with unextracted and extracted plasma samples. The sensitivity of the assays was 60 pg/ml plasma. However, marked differences were observed in the results obtained by the three methods depending on the importance of the inhibitory effect of plasma on the binding of the tracer to antibodies. However, the absolute plasma IRCT level could not be related to the presence of calcitonin M, except in one case. Further studies are needed in order to ascertain the origin and the significance of the immunoreactive material which was detected in normal plasma by one antiserum.


Thyroxine: studies concerning its intrinsic physiological activity. The importance of the monodeiodination of T4 to T3 in the physiological action of T4 was explored by assessing the role of T4 in maintaining prophylthiouracil (PTU)-treated rats during exposure to 4 degrees C. (PTU inhibits both thyroid hormone biosynthesis and T4 to T3 conversion in peripheral tissues.) Firstly, the effects of cold exposure on the metabolism of T4 in control and PTU-treated rats equilibrated with [125I]T4 (2 microgram/100 g b. w./day) were determined. PTU was administered in the food (2 mg/g food). In control rats, no significant changes in T4 metabolism occurred during 3 days at 4 degrees C. Urinary 125I was greatly decreased in PTU-treated rats. Exposure of these rats to cold resulted in some increase but values were still 50% below normal. Secondly, four groups of rats were exposed to cold: control; PTU-treated; T4-treated; PTU + T4-treated. Control and T4-treated rats survived. PTU-treated rats died unless T4 was administered. Radioimmunoassay of T4 and T3 indicated significant concentrations of T3 in sera of rats from all but the PTU + T4 group. These results suggest that T4 permits survival in the cold-exposed PTU-treated rat without being converted to T3 and thus they support the concept that T4 has intrinsic biological activity.


Mammary gland prolactin receptor and pituitary prolactin secretion in lactating mice with different lactational performance. SHN female mice, a high mammary tumour strain, are superior to SLN, a low mammary tumour strain, in lactational performance. Mammary gland prolactin receptor and pituitary prolactin secretion during lactation were compared between these strains. The binding activity, the number of receptor sites per mg tissue and the association constant were measured by the in vitro incubation of mammary gland slices with 125I-labelled bovine prolactin, and the pituitary and plasma levels of prolactin were assayed by homologous radioimmunoassay. There was only a slight difference between strains in any of the parameters for prolactin receptor and for prolactin secretion on either day 4 or day 9 of the first lactation. Almost all the correlation coefficients between each parameter for prolactin receptor and the pituitary or plasma level of prolactin were not statistically significant. These findings suggest that any parameter for prolactin examined in this study is not always directly indicative of lactational performance and further show that the individual variation in the pituitary prolactin secretion during lactation is not so great as to alter the prolactin receptor.


Nitrogen retention of young men who consumed selection patterns of essential amino acids at a constant nitrogen intake. Six patterns of essential amino acids were devised to represent different sources or combinations of protein based on a daily intake of 6.0 g of nitrogen from these sources. In each diet, cereals furnished 70% and a specially designed amino acid mixture 30% of the total nitrogen. Nitrogen retention of young men who consumed amino acids equivalent to combinations of rice and soy or egg and potato did not differ from the pattern of egg, and these patterns were superior to a combination of rice and wheat; egg also was superior to corn plus beans and wheat plus milk. Relative amounts and proportions of essential amino acids could be modified without depressing nitrogen retention until one amino acid became limiting or the pattern became imbalanced. Therefore, more than one pattern of amino acids should be recognized as useful for adult human subjects; both minimal and total amounts of essential amino acids need to be considered.


Poor predictability of lactose malabsorption from clinical symptoms for Chilean populations. Clinical symptoms and lactose malabsorption may occur in persons intolerant to lactose. To predict malabsorption from symptoms and age, the authors used simple regression, multiple regression, and discrimant analysis on data from 436 Chileans. All individual r2 values from simple regression were less than 0.05. For the best stepwise multiple regression program,  R2 was only 0.09, indicating that 91% of the variability in malabsorption was "unexplained" by the five best predictor variables. Because of so much unexplained variability, the authors could detect (using multiple regression) only 56 of 90 (62%) malabsorbers and only 14 of 38 (37%) absorbers. In conclusion, for their Chilean populations the authors poorly predicted malabsorption from symptoms.


Oversimplification of diet: coronary heart disease relationships and exaggerated diet recommendations. The data relating diet to coronary heart disease, when critically examined, clearly show that there is a normal spectrum of blood serum values, and that normal persons do not develop pathological levels upon the ingestion of eggs and other cholesterol-containing the ingestion of large amounts of cholesterol-containing foods. Average data obtained from mixed populations of normal and pathological blood lipid values should not be used to advise the normal majority of that population. The harmful effects of such policy are outlined. The data demonstrating the concept that the risk of coronary heart disease is a function of serum lipids at any level is no longer valid are reviewed. The data of the National Cooperative Pooling Project of the American Heart Association are used to show that up to 250 mg/dl there is no relationship between serum cholesterol concentration and risk.


Thyroid cancer: diagnosis and management based on a review of 142 cases. Review of 142 patients with thyroid cancer diagnosed and treated in a community hospital from 1958 through 1972 suggests that total thyroidectomy and radical neck dissection are unwarranted in the treatment of papillary carcinoma. Radioactive iodine scanning and needle biopsy are also shown to be unreliable indexes of malignancy. An operation approach to the management of specific thyroid cancers is presented.


[Production and antitumor properties of carminazone]. Karminazon (13-benzoylhydrazon) was prepared by condensation of karminomycin with benzoylhydrazine. In its intravenous use in the treatment of mice with lymphosarcoma L10-1 karminazon was less toxic and had lower antitumor activity than karminomycin. Karminazon had a lower selective antitumor activity with respect to lymphosarcoma than karminomycin.


Mycotic aneurysm of the ascending aorta following coronary revascularization. A large mycotic aneurysm of the ascending aorta that appeared two years, three months after triple coronary revascularization is described. Hypothermia and total circulatory arrest were used in excising the aneurysm, and sterilization of the mediastinum was achieved with systemic and local antibiotic therapy. Follow-up at eight months showed a satisfactory postoperative course and no recurrence of mediastinal infection.


Graves' hyperthyroidism. Spontaneous occurrence after autoimmune hypothyroidism with persistent infiltrative ophthalmopathy. The clinical course of a 39-year-old woman who exhibited uncommon features of autoimmune thyroid disease was followed. The patient's thyroid status changed from hypothyroid to hyperthyroid spontaneously. She also had severe infiltrative ophthalmopathy when she was hypothyroid. The unusual sequence of her condition raises some speculation about the pathogenesis of autoimmune hyperthyroidism and ophthalmopathy. The study also indicates that treatment of hypothyroidism may occasionally not be lifelong.


T4-thyrotoxicosis.

T4-thyrotoxicosis. A 41-year-old man had thyrotoxicosis, diffuse goiter, exophthalmos, high titer of antithyroglobulin antibodies but undetectable long-acting thyroid stimulator. Initially, he had both elevated serum thyroxine (T4) and reverse triiodothyronine (rT3) levels, but normal serum triiodothyronine (T3) and free triiodothyronine (FT3) levels and 24-hour radioactive iodine uptake. Observations prior to radioactive iodine therapy uptake. Observations prior to radioactive iodine therapy showed a persistently normal T3 level in spite of development of atrial fibrillation. Iodine excess was not present, nor were any drugs or systemic illnesses that cause preferential monodeiodination of T4 to rT3 instead of T3. The data support the concept that (1) thyroxine is not just a prohormone for triiodothyronine but is metabolically active itself; (2) Graves' disease can be a cause of T4-thyrotoxicosis. We conclude that a normal serum T3 level does not rule out thyrotoxicosis.


Incidence of malignant neoplasms of all types of patients with Graves' disease. The incidence of malignancy among patients with Graves' disease who were residents of one Minnesota county was examined in 342 patients between 1935 and 1967. During 4,736 person-years of observation, 32 malignancies were diagnosed; 24 cases were expected and the difference is not significant. Four cases of breast carcinoma were found vs five expected. Other tumor sites were cervix (five), uterus (two), rectosigmoid colon (three), stomach (two), larynx (two), and lung (two). There were three cases of leukemia, and in nine other sites one cancer each was recorded. There was a slightly higher than expected incidence of malignancy in patients who had received 131I therapy; this finding requires further study in a larger patient population. Among patients who received thyroid hormone, the observed incidence of breast cancer was not significantly different from the expected incidence in our population.


Cytotoxic effect of fatty acids in vitro on Ehrlich exudative carcinoma cells and normal exudative cells (leukocytes). A mixture of pure fatty acids isolated hydrolytically from linseed oil in the form of water-soluble salts with ethanolamine were examined for cytotoxicity for Ehrlich carcinoma and normal exudative cells. Cytotoxicity of the mixture was similar to that of salts of oleic and linolenic acids. On the other hand, the mixture of fatty acids and oleic acids was more toxic for normal exudative cells than linolenic acid.


Mammary and other tumors as a response to radiation and multiple stresses. Parabiosis of paired NEDH rats and subsequent irradiation of one produced multiple stresses, particularly altered hormonal milieu. Benign mammary tumors developed in 8.6% of the control pairs, 12.7% of the shielded partners, and 19.7% of the irradiated rats. Mammary cancers developed in 5% of control pairs, 14.2% of the shielded partners, and 11.9% of the irradiated rats. With increased amounts of prolactin, the rate was 50% in shielded partner, 10% in the irradiated rats. Mesenchymal sarcoma develop at the anastomosis in parabiont rats. Their incidence rate in single controls is 3.1%, in parabiont control pairs 12.5%, in pairs with one partner irradiated 16.6%, and with both irradiated 23.1%. The incidence rate in other parts was increased threefold over controls in the irradiated partners. Radiation appears to be the dominant factor in both mammary and anastomotic tumors.


Acinous cell carcinoma of the larynx.

Acinous cell carcinoma of the larynx. Adenocarcinomas of the larynx are an unusual type of lesion that arise in the minor salivary glands. An acinous cell carcinoma that arose in a supraglottic minor salivary gland closely resembled an oncocytic adenocarcinoma on light microscopy; but on electron microscopy, the neoplasm clearly was serous in origin. Contrary to the behavior of most acinous cell carcinomas, but similar to the majority of laryngeal adenocarcinomas, the neoplasm herein discussed was extremely aggressive and developed widespread metastases, which led to the patient's death.


Parathyroid adenoma in submucosa of esophagus. We recently excised and examined a parathyroid adenoma that was located in the submucosa of the esophagus. It was discovered when an elevated calcium level was found on a screening chemistry profile. Subsequently, the patient was found to have renal stones. At operation two other small parathyroid glands were identified. A fourth one was not found. Following removal of the adenoma, the patient's calcium level returned to normal and has remained normal for several months.


Hirschsprung's disease: an appraisal of histochemically demonstrated acetylcholinesterase activity in suction rectal biopsy specimens as an aid to diagnosis. Suction rectal biopsy specimens, from a series of 168 infants and children with constipation and other gastrointestinal problems, were stained with a sensitive acetylcholinesterase method, and the results were compared with routine histology, radiology, anorectal manometry, and the final diagnosis. In all cases of Hirschsprung's disease, there was an increase in numbers and sizes of cholinergic nerves in the lamina propria and muscularis mucosae. No false-positive or false-negative results were found. The test was found to be more reliable and consistent than other methods available.


Congenital cystic adenomatoid malformation of the lung. Ultrastructural study of a congenital cystic adenomatoid malformation of the lung revealed a persistence of type 2 pneumocytes lining the alveolar and gland-like spaces. The larger cystic areas were lined by normal bronchiolar-type epithelium and were surrounded by a few smooth muscle cells. The interstitium contained undifferentiated mesenchymal cells. No cartilage or bronchial glands were present. These features suggest that this lesion is developmental in nature, with a failure of maturation resulting from an insult occurring early in embryonic life, prior to the onset of cartilaginous differentiation within the lungs.


Condition of rat testes after prolonged ethanol consumption. Rats were maintained 16 weeks on a well-balanced, semisynthetic, solid diet supplemented with ethanol, which comprised 35% of total calories. A control group was pair-fed the same basic diet with sucrose replacing ethanol isocalorically. On light microscopy, the ethanol-fed rats showed appreciable fatty changes in the liver, while the controls did not. There were no differences in testicular morphology between ethanol-fed and control rats, both of which appeared to be normal. The present findings support the view that ethanol is directly toxic to the liver, but under the present experimental conditions, not directly toxic to the testes.


Ultrastructural localization of calcium in calcifying tendinitis. To determine the site of mineralization in calcifying tendinitis, we studied the ultrastructure of tendon fragments that were obtained during surgical interventions on ten patients with that condition. We found that calcification was occurring extracellularly and essentially in areas where the tendon had undergone cartilaginous transformation. Calcific crystals were present in matrix-vesicle-like structures that were seen either singly among collagen fibers or in aggregates. When they were in aggregates, the calcifying vesicles tended to fuse with each other. Thus, the process of mineralization in calcifying tendinitis resembled those calcifying conditions that have already been described in man and animals, both normal and pathological, in which the apatite crystals are initially localized in matrix vesicles.