Glucocorticoid binding to adenohypophysis receptors and its physiological role. The binding characteristics of glucocorticoids to cytoplasmic and nuclear fractions of the adenohypophysis were determined and an attempt was made to correlate steroid uptake with physiological action. Binding was of high affinity and exhibited a limited number of acceptor sites for dexamethasone (Dx). It was shown that the steroid-receptor complex dissociated rapidly at 37 degree C, but was stable at low temperatures. An inverse relationship was detected between the plasma corticosterone (B) titer and the capacity of receptors to combine 3h-Dx. Shortly after stress or injection of physiological doses of B,50 to 70% of the acceptor sites were saturated. Progressive desaturation of the occupied receptors appeared to depend upon time and the plasma B concentration. Some evidence was also provided supporting a possible correlation between the extent of Dx inhibition of in vitro ACTH secretion and the degree of binding sites' occupancy. These results suggest that glucocorticoid binding to pituitary receptors may be correlated with the physiological action of the steroids on ACTH release.


Subcortical pathways involved in the mediation of andrenocortical responses following sciatic nerve stimulation. Previous experiments from this laboratory using the hypothalamic island have demonstrated that the adrenocortical discharge following sciatic nerve stimulation is mediated by neural pathways only. With the purpose of identifying the neural structures involved, this response was studied in rats with bilateral lesions in the medial forebrain bundle (MFB), mammillary peduncle (MP), fasciculus longitudinalis dorsalis (FLD), midbrain reticular formation MRF) and the medial geniculate body (GM). Lesions in the MFB, MP and MRF have inhibited the adrenocortical response following sciatic nerve stimulation. These and other data indicate that the above structures are involved in the mediation of this response and that the afferent pathway enters the mediobasal hypothalamus anteriorly.


The use of steroids in the treatment of idiopathic polyneuritis. The efficacy of steroids in the treatment of acute idiopathic polyneuritis (Guillain-Barré syndrome) continues to be uncertain. Since 1965, 38 patients with idiopathic polyneuritis have been at the University of Kentucky Medical Center, and 16 of them were entered in a prospective double blind study designed to assess the effectiveness of steroid therapy. Seriously ill patients were excluded from the study and most of them received steroids. In both the double-blind group and the entire group of patients, the time from the onset of illness to recovery was significantly less in patients treated with steroids, although steroids did not alter the initial severity of illness or the duration of hospitalization.


Glue sniffer's neuropathy.

Glue sniffer's neuropathy. Progressive sensorimotor neuropathy developed in two patients exposed to prolonged (chronic) inhalation of n-hexane (glue sniffing). Sural nerve biopsies showed loss of axons; remaining axons were either normal or showed accumulation of filaments of 90 to 100 A thick, widened nodes of Ranvier, and focal enlargements. The muscle biopsy revealed neurogenic atrophy. Intramuscular nerve twigs and end-plates, studied in one patient, showed loss of axons and nerve terminals. Unmyelinated axons also showed accululation of 60 to 100 A thick filaments. The similarities between the pathologic findings in the peripheral nerve of these patients and those with acrylamide neuropathy suggest that the n-hexane inhalation produces a dying back neuropathy.


Initiation of labor by intraamniotic cortisol instillation in prolonged human pregnancy. The fetal adrenal cortex has recently been implicated in the etiology of postmaturity on the basis of low cortisol levels found in the plasma of postmature neonates. These findings suggested that labor could be initiated in prolonged pregnancy by iatrogenic elevation of fetal plasma cortisol. In the current investigation designed to test this hypothesis, 500 mg of hydrocortisone sodium succinate, dissolved in the accompanying diluent of bacteriostatic water to form 4 ml of solution, was injected intraamniotically in 10 patients with unfavorable cervices who were 12 or more days past their expected date of confinement. Nine similar patients serving as controls received 4 ml of bacteriostatic water intraamniotically. All patients were followed with daily determinations of urinary estriol. Eight of the 10 patients who received cortisol went into labor within 120 hours of instillation, as compared with 2 of the 9 patients in the control group. Comparison of the two groups revealed a significant difference (p less than 0.01). The mean instillation-labor time for the cortisol group was 86 hours compared with 228 hours in the control group. This difference was also significant (p less than 0.001). Urinary estriol excretion declined sequentially following cortisol but not after infusion of water. These findings are consistent with the hypotheses that a) spontaneous labor in the human may be preceded by a sudden rise in fetal plasma cortisol, as in the sheep; b) the fetal pituitary-hypothalamic axis is responsive to cortisol, hence the falling estriol excretion; and c) ACTH may be the tropic hormone for the provisional zone of the fetal adrenal cortex.


Hydatidiform mole: a vascular congenital anomaly. The thesis is advanced that a critical time for development of embryonic blood vessels in the placenta is 13 to 21 days after conception, especially during days 18 to 21. Dietary requirements at this time are specific and demanding for nutritional precursors of thymidine which is an important constituent of DNA. Folic acid and histidine are specifically essential for thymidine synthesis. These are reviewed with respect to cultures and socioeconomon levels in societies where occurrence of hydatidiform mole is endemic. Specific nutritional deficiencies are discussed in relation to kinds of diets and ways of food preparation. When specific dietary requirements are lacking at a time of high need, embryo death, abnormality, and/or avascularity of trophoblastic placental villi may be the earliest pathogenic signs of hydatidiform mole.


Pulsatile gonadotropin output in menstrual dysfunction. Patterns of gonadotorpin output were studied in normal individuals and in patients with menstrual dysfunction by radioimmunoassay measurement of LH and FSH output in samples taken every 20 minutes for 6-8 hours, and following administration of synthetic luteinizing hormone releasing hormone (LRH). Follicular phase LH pulses occurred every 1-2 hours, whereas those in the luteal phase occurred less frequently and with higher amplitude. FSH output was irregular, and had no correlation with LH dynamics. In anorixia nervosa, pulsatile LH activity was minimal, and the response to LRH variable, correlating somewhat with the clinical status of the patient. Pulsatile LH activity was observed in patients with postpill and postpartum amenorrhea, and also in one individual with a probable prolactin-producing pituitary tumor. Patients with polycystic ovarian disease had obvious LH pulsatile activity, with a greater amplitude and frequency than seen in the luteal phase, and a decrease in percentage increment, suggesting some difference in the hypothalamic-pituitary control mechanisms under these conditions. The character and pattern of the LH pulsatile activity does vary with different forms of menstrual dysfunction and may be predictive of the LRH response when considered in relation to the LH baseline values. Pulsatile LH activity, analyzed in conjunction with response patterns following LRH stimulation, may reflect the degree of hypothalamic dysfunction.


Insulinoma in a pregnant woman.

Insulinoma in a pregnant woman. The case of a 37-year-old primigravida suffering from severe hypoglycemia due to insulinoma is reported. Diagnosis was established on clinical grounds by assessment of inappropriate insulin release. Laparotomy was performed by the 12th gestational week. A wide distal pancreatectomy was carried out, and histopathologic study proved the existence of multiple islet cell adenomatosis. Glycemic levels and insulin secretion returned to normal immediately after surgery. The course of pregnancy was unhampered, judged by clinical criteria and by serial estimations of human chorionic somatomammotropin levels before and after removal of the insulin-producing tumor. A normal female infant was delivered at term, and no histopatholgic changes were detected in the placenta. After 1 year, clinical and analytical evaluation of both mother and child was normal.


Ergonomics study shows effect of full-body suit on energy use. It stands to reason that a full-body protective suit has an impact on the worker's body. It has weight, it does restrict movement to an extent. It's not like wearing a sport shirt. But, how much of an impact and what kind; how much of an energy drain is it? This ergonomic study addresses itself to the energy expenditure from wearing such a suit. The study reveals that the energy requirements in workers undergoing light to moderate exercise do increase. In some cases, the increase may be marked, with the physiological work level going from light to moderate to heavy. This work-level jump isn't always detectable by monitoring pulse rate alone. It's also reflected by an increase in minute ventilation and oxygen consumption. One tentative conclusion coming from this study is the possibility of improving comfort and reducing the energy requirements of workers using such equipment by increasing the volume of air supplied to the suit.


[Oxygen consumption and cytochrome oxidase activity of muscle tissue from the limbs of axolotls following restoration of regenerative capability suppressed by x-ray irradiation]. The intensity of oxygen consumption and the activity of cytochrome oxidase have been studied in the homogenate, mitochondria and nuclei of the limb muscle tissue in axolotls after the suppression of regenerative ability by X-irradiation and its experimental restoration. Under the suppression of regenerative ability, the oxygen consumption was inhibited. The cytochrome oxidase activity in the homogenate and mitochondria decreased and in the nuclei remained at the same level or even increased as compared with the intact limb. Under the restoration of regenerative ability, the intensity of respiration of the homogenate and mitochondria increased and this increase was accompanied by the increase of the cytochrome oxidase activity. The activity of cytochrome oxidase in the nuclei did not change at the stage of blastema and sharply fell at the stage of formed limb.


[Pyridoxal phosphate and activity of pyridoxalkinase in serum of preterm and term infants (author's transl)]. Vitamin B6 nutriture was measured in 14 preterm infants (born between 30th and 35th week of gestation) by means of determination of pyridoxalphosphate and activity of pyridoxalkinase in serum on the 1st and 4th day of life. 11 term infants were included as control group. At the 1st day pyridoxalphosphate and activity of pyridoxalkinase in preterm infants were significantly decreased in comparison with the control group. 50% of preterm infants--all were delivered before the 33rd week of pregnancy--did not show any activity of pyridoxalkinase in serum. On the 4th day, vitamin B6 nutriture of preterm infants was still decreased in comparison with the control group. Measurable activity of pyridoxalkinase, however, was now found in all preterm infants. There was a positive correlation at the 1st and 4th day of life between pyridoxalphosphate and weight and activity of pyridoxalkinase and weight. According to our results pyridoxalkinase is an enzyme which depends on the gestational age of the newborn. After the 32nd week of gestation the enzyme becomes active. Moreover pyridoxalkinase is an enzyme that can be induced by formulas containing vitamin B6. We consider the administration of vitamin B6 to the preterm infant as necessary.


[Antibodies against the Epstein-Barr virus, capsid antigen in children with malignant neoplasms (author's transl)]. Sera from children were tested for antibodies to viral capsid antigens of Epstein-Barr virus. The method applied was the indirect immunofluorescence test. 25 sera from healthy donors were titrated as controls. In 14 patients with acute lymphocytic leukemia we found low levels, a tiny little girl with chronic myelocytic leukemia (?) AND THREE CHILDREN.WITH LYMPHOPROLIFERATIVE DISORDERS SHOWed highly increased serological reactivities. Investigated children with other kinds of tumours did not serologically differ significantly from the control group. Further investigations should clarify the role of this infectious agent.


Control of glycolysis in skeletal muscle from fetal rhesus monkeys. In our studies of metabolic control mechanisms in skeletal muscle from rhesus fetus we have determined the tissue levels of the metabolic intermediates and cofactors of the glycolytic pathway and have calculated the mass-action ratios for each reaction. Skeletal muscle from rhesus fetuses (Macaca mulatta), 90-155 days of gestational age, and from adult rhesus monkeys was used in these experiments. The apparent equilibrium constants for hexokinase and phosphofructokinase (PFK) in these tissues were over 1,000 times larger than the mass-action ratios at all ages studied; the corresponding values for pyruvate kinase were more than 800 times different. The data suggest that these three enzymes are rate-limiting for fetal skeletal muscle as early as 54% of gestation. The next step was to study some of the numerous factors that modify these non-equilibrium reactions. Increasing the ATP concentration had a marked effect on the PFK activity of both fetal and adult muscle, first increasing and then inhibiting enzyme activity. At maximum PFK activity, the amount of fructose-6-PO4(F6P) phosphorylated per mg of protein was 2-3 times greater in the two fetal than in the adult series. At a concentration of 0.3 mM, citrate decreased PFK activity of the 100-day fetal muscle; a further decrease occurred at 1.2 mM citrate. At a citrate level of 0.3 mM. the addition of inorganic phosphate (Pi) or cyclic AMP returned PFK activity to the uninhibited levels (pH 7.0). Relief of ATP inhibition of F6P phosphorylation with Pi and cyclic AMP was also observed at pH 7.0 in extracts of 100-day fetal skeletal muscle.


Neonatal diagnosis of familial type II hyperlipoproteinemia. Cord serum prebeta-beta-lipoprotein concentration was measured in a radial immunodiffusion assay in 303 randomly selected, full-term infants whose parental phenotypes were unknown. Six infants had elevated concentrations, that is above a cut-off limit of 197 mg/100 ml (97.5th percentile). Three of these infants suffered from classic type II hyperlipoproteinemia, and this diagnosis was confirmed by family studies at follow-up. The three other infants and their parents were shown to be normolipemic at follow-up. The elevated cord serum prebeta-beta-lipoprotein in these three infants could be explained by highly elevated cord serum triglyceride and/or cholesterol. The 297 infants with normal cord serum prebeta-beta-lipoprotein and their parents were all shown to be normalipemic at follow-up. It is concluded that the measurement of prebeta-beta-lipoportein in cord serum allows the identification of children with familial type II hyperlipoproteinemia, if infants with transient neonatal hypertriglyceridemia and hypercholesterolemia are excluded.


Serum 25-hydroxyvitamin D in infantile rickets. In small children with nutritional vitamin D deficiency, the serum concentration of 25-hydroxyvitamin D (25-OH-D), the major circulating metabolite of vitamin D, was correlated with the stage of clinical disease. It was low (16 to 20 ng/ml) but within the normal range in the earliest (hypocalcemic) stage of the deficiency syndrome and decreased (less than 15 ng/ml) in the more advanced stages. In patients with familial hypophosphatemia (X-linked dominant), mean serum 25-OH-D concentration was the same as in age-matched normal controls. Evidence is presented that endogenous parathyroid hormone may have a role in the depletion of serum 25-OH0D in deficiency states.


Color and form perception on the Rorschach as a function of eye color. Recent research had demonstrated that dark-eyed individuals are more reactive than light-eyed people. The present paper investigated one area of reactivity, ease of emotional arousal. The hypothesis that dark-eyed male subjects (n equals 40) would show greater ease of arousal than light-eyed male subjects (n equals 40) was tested using color and form responses on the Rorschach as dependent measures. The predicted interaction was significant; light-eyed subjects gave relatively more form responses, but dark-eyed subjects gave relatively more color responses. Implications for future research and application were discussed.


[Bone scintigraphy with 99mTc-pyrophosphate: pharmokinetics of the substance and clinical experiences with the scintigraphy]. Kinetics and clinical studies of bone scintiscanning with 99mTc-pyrophosphate in 92 patients with certified diagnosis allowed the following conclusions: 1. After i.v. injection 99mTc-pyrophosphate is distributed in 3 compartments, from which it is cleared with biological half-lives of 32.7 minutes, 5.1 hours and 22.54 hours respectively. The relative size of these compartments is 1 : 3 : 6. After application of the substance, an initially high renal excretion with a consecutive exponential drop can be observed. The optimal period for scintigraphic studies seems therefore to be from 3-6 hrs, as at this time there is still an adequate activity in bone structures, while the low background activity yields a good contrast on scintiscans. 2. The clinical results of bone scintigraphy with 99mTc-pyrophosphate with 88.6% correct diagnoses can be considered as "very good". This feature can partly be attributed to an improved correlation of radiographic and scintigraphic images by the use of a specially designed, combined radiographic-photoscanning detector system. 3. Preliminary results concerning the quantitative uptake of 99mTc-pyrophosphate in fractures of the extremities suggest, that the quantitative analyses of the registered data can provide valuable prognostic information in traumatic, inflammatory and neoplastic bone lesions.


Duplication of single stranded DNA catalyzed by calf thymus DNA polymerase alpha. Purified calf thymus DNA polymerase alpha is inactive with native DNA as template and shows little activity with denatured DNA. DNA synthesis with denatured DNA as template is greatly stimulated by the addition of a nuclease which initially copurifies with DNA polymerase but is separated from the polymerase on DEAE-cellulose chromatography. A limit digest of nuclease treated native DNA which is then denatured is replicated 80-95%; extensive replication is also obtained with native DNA partially degraded by pancreatic DNase and then denatured. The product of the reaction with calf thymus nuclease-treated DNA as template is double-stranded DNA with a hairpin (looped back) structure.


Specific spin-labeling of transfer ribonucleic acid molecules. The spin labels anhydride (ASL), bromoacetamide (BSL) and carbodiimide (CSL) were used to label selectively tRNAGlu, tRNA fMet and tRNAPhe from E. coli. The preparation and characterization of the sites of labeling of eight new spin-labeled tRNAs are described. The sites of labeling are: s2U using ASL, BSL and CLS and tRNAGlu; s4U using ASL and BSL on tRNAfMet and tRNAPhe; U-37 with CSL on tRNfMet; U-33 with CSL on tRNAPhe. The rare base X at position 47 of tRNAPhe has been acylated with a spin-labeled N-hydroxysuccinimide (HSL). The 3'end of unfractionated tRNA molecules has been chemically modified to a morpholino spin-labeled analogue (MSL). Their respective e.s.r. spectra are reported and discussed.


A spin label study of the thermal unfolding of secondary and tertiary structure in E. colic transfer RNAs. The molecular mechanism of thermal unfolding of E. coli tRNAGlu, tRNAfMet and tRNAPhe (in 0.02M Tris-HC1, pH 7.5. 10 MM Mg C12) has been examined by the spin-labeling technique. The rate of tumbling of the spin label has been measured as a function of temperature for ten different selectively spin-labeled tRNAs. Only spin labels at position s4U-8 were able to probe the tertiary structure. Evidences are presented which support the hypothesis that the thermal denaturation of the three species of tRNAs studied is sequential. The unfolding process occurs in three discrete stages. The first step (30 degrees-32 degrees) could either be assigned to a localized reorganization of the cold-denatured structure or to a "transient" melting, followed by the simultaneous disruption of the tertiary structure and part of the hU helix. This transition is observed even in the absence of magnesium. The second step (50 degrees-54 degrees) involves the melting of the anticodon and miniloop regions. The last step occurs above 65 degrees where the t psi c and amino acid acceptor stems, forming one continuous double helix, melt. A simple dynamic model is considered for tRNA function in protein biosynthesis.


Specific oligoribonucleotide synthesis using primer-independent polynucleotide phosphorylase. Oligoribonucleotides of a predetermined base sequence beginning with adenylyl-3', 5'-adenosine at the 5' end have been synthesized in yields varying between 13% and 42%. The synthesis was carried out using primer-independent polynucleotide phosphorylase from E. coli in the presence of high concentrations of primer and of sodium chloride.


The autonomic nervous system in alcoholic and diabetic neuropathy. Tests of autonomic function were performed on 10 controls, 16 subjects with diabetic neuropathy and 12 subjects with alcoholic neuropathy. Abnormal sweating occurred in 10/10 alcoholics (100%) and 10/10 diabetics (100%) who were examined. An abnormal Valsalva ratio was present in 7/11 (64%) of diabetics and only 2/9 (22%) of alcoholics. Denervation hypersensitivity to phenylephrine occurred in 2/8 (25%) of diabetics and was absent in alcoholics. A quantitative assessment of baroreceptor function was made. In diabetics there was a reduced resting heart period, heart period range and mean gain, whilst these parameters were essentially normal in alcoholics.


Autonomic disturbances produced by lung cancer: a report of two unusual cases. Two cases of malignant infiltration of nerve are presented in whom a major feature was excessive spontaneous sweat secretion. The possible mechanisms for the production of this unusual symptom are discussed.


Purification and buoyant density of infectious bovine rhinotracheitis virus. A purification scheme for infectious bovine rhinotracheitis virus utilizing rate-zonal centrifugation in a 10-40% potassium tartrate gradient was described. The density of IBRV in the potassium tartrate gradient was found to be 1.22 g/cm3. Electron microscopic examination of purified virus preparations revealed homogeneous populations of enveloped virions with minute projections on the envelope surface.


The involvement of cyclic-3',5'-AMP in the release of hormones from the anterior pituitary in vitro. DBcAMP significantly increased the release of GH but not of LH, FSH, TSH, or PRL, except in the presence of hypothalamic extract when it augmented the release of LH, FSH, and GH, reversed the inhibition of PRL, but did not further influence TSH release. Theophylline increased release of GH and PRL while inducing increased tissue content of cAMP without consistently increasing the release of TSH, LH, or FSH. Hypothalamic extractor K+-stimulated hormone rel-ase was consistently and significantly potentiated by theophylline. Neither hypothalamic extract, increased [K+], or synthetic TRH and LRH were able to raise tissue content of cAMP while producing their expected effects on hormone release. Cholera enterotoxin produced a highly significant increase in tissue content of the cyclic nucleotide but increased the release of GH only, and not that of LH, FSH, TSH, or PRL. DBcAMP was able to lower the threshold concentration of K+ required to stimulate release of GH, LH, and FSH and also to augment K+-stimulated release to the higher levels induced by the hypothalamic releasing hormones. It did not augment K+-induced release of TSH.


Effects of LH-RH on isolated pituitary gonadotropic cells. Rat anterior pituitary glands were dissociated with Pronase and the cells were separated by velocity sedimentation at unit gravity. After 30 min of incubation of the enriched gonadotropic cells with LH-RH, there was a significant increase in LH and FSH in the incubation medium. LH-RH (100 ng/ml) and 10(-3) M cAMP both caused significant increases in LH in the incubation medium after 24 hr of incubation.


Effects of hypothalamic-releasing hormones on LH, FSH, and prolactin in pituitary monolayer cultures. Four-day-old pituitary monolayer cultures were incubated with various hypothalamic releasing hormones. Rat hypothalamic extract stimulated the release of LH, FSH, and PRL by these cultures in a dose-related fashion. Synthetic LH-RH stimulated the release of LH and FSH but not of PRL. Synthetic TRH increased the release of PRL but had no effect on LH or FSH. At 10(-8) M, somatostatin did not affect any of the three adenohypophyseal hormones. Incubation with DBcAMP or theophylline also stimulated PRL release without any detectable effect on LH and FSH release. These data suggest the involvement of cyclic AMP--adenylate cyclase system in the mechanism of PRL release, but their involvement in gonadotropin release requires further studies.


Influence of dietary Ca, Mg, and P on cyclic-AMP excretion and kidney calcification in the rat. A series of five experiments was conducted with young male albino rats to investigate effects of various levels of dietary Ca, P and Mg on urinary cAMP excretion and kidney calcification. Urinary cAMP excretion was shown to be directly correlated with injected parathyroid (PT) hormone dose level and to be inversely associated with dietary Ca intake. Thus, cAMP excretion may be presumed to reflect PT activity in the young rat. Magnesium deficiency tended to reduce cAMP excretion, while P excess did not affect it. Each treatment induced kidney calcification. Calcium deficiency increased cAMP excretion irrespective of Mg status, although nephrocalcinosis appeared only in the Mg-deficient animals. These data support the view that nephrocalcinosis of dietary origin in the rat is not mediated by increased PT activity.


Macrophage migration inhibition and lymphocyte stimulation with mammary tumor virus associated antigens in Balb/c mice. Lymphocytes of MTV-negative Balb/c mice are sensitive to one or more antigens of MTV as determined by blastogenic transformation and migration inhibition assays. The lymphocytes from MTV-positive Balb/cfC3H mice are nonresponsive in these assays but become responsive after the mice have been implanted with MTV-positive tumors. The latter findings imply that there may be either a state of tolerance to MTV antigens which is broken by the tumor transplant or that the responses are directed towards antigens to which the host is not tolerant. The cause of the sensitivity of lymphocytes from MTV-negative Balb/c mice to MTV antigens has not been determined but two possible explanations are discussed: horizontal transmission and derepression of genetic information for viral antigen.


Prolyl hydroxylase activity in normal and diseased human liver. Prolyl hydroxylase activity was determined in liver biopsy samples obtained from 10 patients. The liver prolyl hydroxylase values in patients with active hepatitis distribute into two numerical populations based on the extent of elevation over control. The first of these groups includes those with enzyme levels elevated approximately 2.5-fold over normal. Included in this group are patients with active (but nonagrressive) hepatitis and patients where advanced portal fibrosis is already established. The second group where prolyl hydroxylase is elevated approximately nine-fold is comprised of two patients with advanced clinical symptoms of active alcoholic hepatitis with evidence of aggressive cirrhosis but with only early minimal evidence of existing fibrosis.


Rabbits as a source of antisera against SV40 virus-induced cell surface antigens. Rabbits immunized with SV40 virus-transformed rabbit cells yielded antisera highly reactive in a mixed-hemadsorption assay against SV40-transformed hamster, mouse, and rabbit cells. Such antisera may prove of value in studies requiring large amounts of antibody angainst SV40-induced cell surface antigens.


Different lipolytic effects of theophylline and dibutyryl cyclic AMP in vivo and in vitro. Both dcAMP and theophylline are known to promote lipolysis in vitro by increasing intracellular cAMP. Although theophylline stimulates FFA mobilization in vivo as well, a report of low circulating FFA levels in the rat given dcAMP suggested that dcAMP may inhibit lipolysis in the intact animal. To explore this possibility, a comparison of the in vitro and in vivo lipolytic effects of theophylline and dcAMP was made in the young dog. Circulating glycerol and FFA levels rose following the administration of theophylline. While glycerol and FFA fell slightly in puppies given dcAMP, only the FFA change was significant. Epinephrine infusions given alone produced sustained elevations of glycerol and FFA. When theophylline was given in conjunction with ongoing epinephrine infusions, plasma glycerol and FFA levels remained high. On the other hand, epinephrine-stimulated lipolysis was markedly inhibited by dcAMP, as shown by pronounced falls of glycerol and FFA from the elevated levels found with epinephrine alone. In vitro studies involving fragments of puppy adipose tissue reveal that epinephrine, theophylline, and dcAMP promoted glycerol release. In contrast to the in vivo observations, lipolysis was also stimulated by combinations of both epinephrine and theophylline as well as by epinephrine and dcAMP. Thus, theophylline stimulates lipolysis in vitro and in vivo in the puppy. In contrast, dcAMP stimulates lipolysis in vitro but inhibits this action in the intact animal. This important difference in the two pharmacologic agents suggests the need for caution when using them in in vivo studies involving the action of cAMP.


Progesterone binding in rabbit oviduct and uterus. Progesterone binding of high affinity with a dissociation constant of 10(-9) M was identified in cytosol of rabbit oviduct and uterus. Macromolecules with sedimentation coefficients of 7-8 S and 4-5 S were present. Progesterone receptor concentration was two to fivefold lower in the oviduct when compared with the uterus. The receptor concentration declined steadily from 3 hr until 144 hr after mating in the uterus; however, the decline in oviductal receptor was not significant until the sixth day of pregnancy. Progesterone receptor concentration in rabbit oviduct and uterus in estrus and early pregnancy was greater than estradiol receptor levels.


Deoxycytidine kinase from rabbit kidney cells infected with herpes simplex virus type 1 or 2. When rabbit kidney cells were infected with herpes simplex virus type 1 (strain Seibert) or herpes simplex virus type 2 (strain 316D), deoxycytidine kinase (CdR kinase) activity, assayed at 38 degrees, increased 5- to 15-fold relative to controls. The CdR kinase activity induced by type 2 virus was more thermolabile than the enzyme activity induced by type 1 virus. When CdR kinase activity was assayed at various temperatures between 0.5 and 38 degrees, maximum activity for type 1 enzyme was obtained at 16 degrees while maximum activities for host and type 2 enzymes were obtained at 38 degrees. Both type 1 and type 2 induced CdR kinase activities eluted at the same positions as deoxythymidine kinase activities on a Sephadex G-100 column. The estimated mol wt for HSV-1 (Seibert) and HSV-2 (316D) induced CdR kinases are 67,000 and 60,000, respectively.


Modification of renal tumorigenic effect of streptozotocin by nicotinamide: spontaneous reversibility of streptozotocin diabetes. The renal oncogenic activity of streptozotocin in male Holtzman rats was significantly decreased by nicotinamide. Adenomas of the kidney were noted in 77% (21/28) of the animals treated with single iv dose of the streptozotocin, 50 mg/kg, while only 18% (5/28) of animals given nicotinamide ip, 350 mg/kg, 10 min before and 180 min after the same dose of streptozotocin had demonstrable renal tumors. Moreover, the renal adenomas induced by streptozotocin alone occurred sooner and were generally larger when compared with those in the animals treated with the nicotinamide-streptozotocin combination. The 50 mg/kg dose of streptozotocin was diabetogenic in all rats, but the diabetic state was not permanent. Spontaneous recovery from the diabetes was first noted after 8 and 10 months of followup, and after 16 months none of the surviving rats were diabetic.


Induction of SMON-type virus form avian infectious laryngotracheitis virus. SMON-type virus which shows different host range was induced from ILT virus under unsuitable culture conditions for the growth of the parental ILT virus, such as cultivation in CAM of 12-day-old eggs or cultivation in CHK cells at 32 degrees. Furthermore, it was induced from ILT virus by mutagenesis by either BrdU or NG in CHK cell cultures.


Characterization of a triglyceride hydrolase secreted by canine liver maintained in vitro. These studies demonstrate that canine liver synthesizes a TGH activated by C-I but not by C-II. This TGH has properties similar to lipoprotein lipase C-I isolated from postheparin plasma of human subjects, but differs from a previously reported liver triglyceride-lipase or protamine insensitive-lipase in its sensitivity to NaCl and protamine sulfate, as well as in its requirement for a serum cofactor, C-I. These data suggest the possiblity that, in dogs, liver is a source of plasma LPLC-I.


Growth characteristics of bovine herpesvirus 1 (infectious bovine rhinotracheitis) in human diploid cell strain WI-38. IBR virus was found to replicate in WI-38 cells. At a high input multiplicity the virus yield was comparable to that obtained in bovine cells, but comparable degree of CPE took longer to achieve. At a low input multiplicity of IBR virus, such as may be encountered in virus contaminated bovine serum, virus yield was only about 1% of that in bovine cells, with 50% of the cells showing CPE, followed by cell regrowth. Infectious virus was not recoverable from the regrown cells by 5 weeks after initial infection, and these regrown cells were susceptible to reinfection with IBR virus. Aging of WI-38 cells in cultures for as little as 1 week reduced IBR virus yield to 90% less than the yield from the same lot of cells inoculated 7 days earlier.


A model of the mechanisms of memory.

A model of the mechanisms of memory. The neuronal information is formed by 2 waves: electronic and ionic, which enter the neuron at the level of the excited synapses. The neurofilaments lead to the transmission of the electronic wave, while the microtubules direct the ionic wave. Arriving at the level of the nuclear membrane, the electronic wave of excitation enters the system DNA-histones, which works as a computer. The electronic wave is retransmited to a bundle of neurofilaments, then it is carried to a certain collateral of the axon. In its movement, the electronic wave guides the ionic wave toward certain synapses, so that the specific connections between the input and the output signals are assured.


Lateral-volar finger flap for the treatment of burn syndactyly. To completely open the web space in burn syndactyly and provide tissue that is pliable and elastic, we describe a flap from the lateral and volar surfaces of an adjacent finger which will completely cover the opened defect. The results of this procedure in 24 web spaces are reported.


Disruption of healed scars in scurvy -- the result of a disequilibrium in collagen metabolism. Old scars break open in scorbutic patients because (1) the rate of collagen degradation is greater in an old scar than it is in normal skin, and (2) the rate of collagen synthesis is diminished throughout the body in ascorbate deficiency.


[Action of alpha-methyl-dopa on waking-sleep cycles in two inbred strains of mice, C57BR and C57BL/6 (author's transl)]. The effects of alpha-methyl-Dopa at several dose levels on waking-sleep cycle of 175 mice from two inbred strains (C57BR and C57BL/6) have been studied. The results showed that each dose (25, 50, 100, 200 and 400 mg/kg), of alpha-methyl-Dopa completely suppresses paradoxical sleep (PS), after a period of sedation. Duration of PS inhibition varied as a function of dose, time of injection, and strain of mice. Using a multiple injection schedule of one injection per day for 5 consecutive days, there was suppression of nocturnal PS followed at the 4th day by rebound during day light hours.


Excitation-mediating and inhibition-mediating dopamine-receptors: a new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data. A great number of earlier reported experimental data dealing with the role of dopamine in dopamine-loaded structures within the mammalian brain have raised questions concerning the concept of dopamine as an inhibitory agent acting on one type of receptor. A critical review of the anatomical, histochemical, electrophysiological, pharmacological and functional studies reveals that the dopamine-loaded structures are marked by an internal differentiation at various levels. It is attempted to demonstrate that this is due to a heterogeneous distribution of two distinct types of dopamine-receptors, each characterized by their own properties: DAe and DAi-receptors. Furthermore, the experimental and clinical implications are discussed in view of the hypothesis that balance between both types of receptors is essential for normal psychomotor functioning.


A syndrome of widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness (the Singleton-Merten syndrome). Two patients with clinical and radiological features similar to those of Singleton and Merten's patients are described. These patients exhibit features of a unique clinical syndrome of unknown etiology: generalized muscular weakness with secondary hip and foot deformities, progressive calcification of the thoracic aorta beginning in childhood, calcific aortic stenosis leading to heart failure, dysplasia of the teeth, poor physical development, osteoporosis, expanded medullary cavities of the metacarpal and metatarsal bones, and chronic psoriaform skin lesions.


The arthropathy of hemochromatosis.

The arthropathy of hemochromatosis. Five cases of hemochromatosis arthropathy are presented and the distinctive radiological features of the disease are described. Although the condition is typically degenerative, showing subchondral cyst formation, sclerosis, and thinning of cartilage, its distribution is characteristic. Selective degenerative changes of the second and third metacarpophalangeal joints are striking, particularly in the hands, while abnormalities in the intercarpal joints are variable and the interphalangeal joints are spared. Chondrocalcinosis involving both fibrous and hyaline cartilage is frequently seen as well, particularly in the large joints. The calcification is due to deposition of calcium pyrophosphate crystals, perhaps resulting from iron inhibition of pyrophosphatase.


Diffuse cavernous hemangioma of the colon in the Klippel-Trenaunay syndrome. Large, infiltrative cavernous hemangiomas of the distal colon were present in 3 children with the Klippel-Trenaunay syndrome, 2 of whom are the subject of this report. The lesion is manifested clinically as intermittent rectal bleeding starting in the first 5 years of life. The radiographic features include (a) varicose lesions in the wall of the rectosigmoid, ranging from a network of distended submucosal veins to nodular defects, (b) narrowing of the rectum by the surrounding extramural portion of the hemangioma, and (c) phleboliths within the lesion. Inferior mesenteric angiography and sigmoidoscopy are useful for preoperative confirmation. The occurrence of visceral hemangiomas in the Klippel-Trenaunay syndrome and its relevant diagnostic and therapeutic implications are discussed.


The effect of non-steroid anti-inflammatory drugs, dibutyryl cyclic 3',5'-adenosine monophosphate and phosphodiesterase inhibitors on platelet aggregation and the platelet release reaction in normal and essential fatty acid deficient rats. A comparison was made of the action of three classes of substances with platelet aggregation inhibiting effect in normal and essential fatty acid deficient rats. In the latter group, the effect of indomethacin was considerably reduced, whereas the difference was smaller with aspirin. Dibutyryl cyclic AMP had the same inhibiting effect in both groups. Of the phosphodiesterase inhibitors tested, dipyridamole was inactive, whereas the inhibiting effects of caffeine and papaverine are slightly reduced in the deficient animals. The same differences between the two groups were seen in the magnitude of the release reaction after 14C-serotonin labelling. These data support the idea that the non-steroid anti-inflammatory drugs act by inhibiting the formation of an aggregation-inducing substance from arachidonic acid.


[Morphological and enzymatic studies of the supratumoral distended colonic loop in colorectal cancers (therapeutic aspects)]. The authors carried out experimental and clinical studies in an attempt to explain the causes leading to anastomotic dehiscences, a major complication of exeresis surgery of the left colon and of the rectum. In this view they have performed in dogs incomplete stenoses at the level of the sigmoid and also made parallel studies of the morphological and histochemical changes occuring in the supra-stenosis colon wall, with those of the supra-tumoral colon wall found in human colo-rectal carcinomas, in the "sub-occlusion" stage. Histological alterations are presented, characterized by marked edema in all the layers of the wall, leading to evidently hampered colon vascularization. From the enzymological viewpoint there was noted an intensive phosphatasic and ATP-ase reaction in all the layers of the colon wall. These studies led to the conclusion that it is necessary to evaluate the degree and the duration of the supra-tumoral colic distension before a decision is taken to carry out primary colectomy or rectal resection (single-step procedure), and not to avoid the practice of a seriated intervention when necessary. The reversibility of the lesions noted by the authors allows for the possibility to perform a resection after the colic wall to be anastomosed has returned to an almost normal condition, thus avoiding the dehiscence of the sutures.


Fatty acid oxidation by ischemic myocardium. Ischemia markedly depresses fatty acid oxidation and increases fatty acyl-CoA and fatty acylcarnitine levels in the isolated heart during palmitate oxidation. Evidence suggests that the major defect is impaired beta-oxidation due to decreased electron transport rather than to diminished fatty acyl uptake, activation, or intramitochondrial transfer. Important metabolic effects may include decreased mitochondrial adenine nucleotide translocation and altered carnitine-palmity-l-CoA transferase activity.


Dependence of myocardial redox systems on the concentration of exogenous substrate. Isolated rat hearts were perfused according to Langendorff at a range of perfusion pressures and the variations of intracellular oxygenation were studied under these conditions by optical methods. The oxygen consumption was directly related to left ventricular performance in all cases examined, the relationship being independent of both the substrate used (glucose, beta-OH-butyrate) and its concentration (2.5, 5.0, 10.0 mM). The changes in the respiratory rate were accompanied by modifications of the redox state of mitochondrial enzyme systems (reduced nicotinamide adenine dinucleotide (NADH), cytochromes) in presence of low concentration (2.5 mM) of substrate. At higher substrate concentrations (5.0, 10.0 mM), however, no change in the redox state of cytochromes and only inconsistent fluctuations of that of NADH were observed. These results suggest that the generally accepted relationship between the rate of electron transport and the degree of reduction of respiratory coenzymes exists only under special conditions (low substrate concentration). Other factors, such as the size of the pool of hydrogen available, should be considered. Furthermore, this work specifies the optimal experimental conditions for the study of mitochondrial respiratory transitions (low substrate) in the intact myocardium by means of direct optical techniques.


Opposing regulatory influences of cyclic guanosine monophosphate and cyclic adenosine monophosphate in the control of cardiac muscle contraction. The effects of acetylcholine chloride (ACh) and isoproterenol (Iso) on myocardial levels of guanosine 3', 5'-monophosphate (cyclic GMP) and adenosine 3', 5'-monophosphate (cyclic AMP) and on force of contraction were studied in elelctrically driven isolated rabbit atria. Incubation of atria with Tyrode's solution containing ACh (5 x 10(-7) M) produced significant decreases in contractile force that were associated with significant elevations in atrial cyclic GMP levels. Atrial levels of cyclic AMP were significantly lowered at 15 sec after the addition of ACh but were only slightly lowered at earlier time intervals. The effects of acetylcholine on force of contraction and on cyclic nucleotide levels were prevented with atropine (1 x 10(-7) M). The addition of Iso (1 x 10(-7)-M) to isolated atria produced significant increases in contractile force that were associated with significant elevations in effects of Iso on force of contraction and on cyclic nucleotide levels were prevented with practolol (1 x 10(-5) M). The increases in atrial cyclic GMP and cyclic AMP levels following addition of ACh and Iso, respectively, precede the changes in contractile force. These data support our hypothesis that cyclic AMP and cyclic GMP exert oppositional effects on cardiac contrctility.


Alterations in myocardial and plasma cyclic adenosine monophosphate in experimental myocardial ischemia. Alterations in myocardial and plasma cyclic adenosine monophosphate (cyclic AMP) levels were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic AMP levels increased markedly after thoracotomy but returned to control levels 2 hr later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham occlusion. Localized coronary occlusion tended to increase plasma cAMP levels in anesthetized animals and also in concious dogs. The present study suggests that adrenergically mediated changes in tissue and plasma cyclic AMP content are early manifestations of both generalized and local myocardial ischemia and tend to reflect the magnitude of the insult.


Regulation of myocardial energy metabolism. Closed aorta working hearts perfused with 1 mM pyruvate were subjected to a 4-fold increase in work load by raising the left atrial filling pressure. Citric acid cycle flux, pyruvate uptake, and oxygen consumption rose 3-fold when cardiac output was increased. In the first 40 sec after the transition tissue glutamate and citrate fell by 22 and 45%, respectively, and there were reciprocal decreases in malate and aspartate. The ratio of creatine phosphate/creatine declined by 50% within 30 sec, with a corresponding increase in inorganic phosphate, but the fall in the ATP/ADP ratio was only 10%. During the first 10 sec the surface fluorescence from cardiac pyridine nucleotides fell by 30% and this change was synchronous with a sharp decline in the calculated adenine nucleotide phosphate potential. This suggests that heart mitochondrial respiration is controlled by the cytosolic phosphate potential, and that a state 4 to state 3 transition occurs when cardiac output is increased. Apparent disequilbrium of creatine phosphokinase can be explained by the compartmentation of most of the cardiac ADP within the mitochondria. Citric acid cycle flux was coordinated by activational interactions at citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, but a transient imbalance between the individual cycle steps leads to a sharp peak of lactate production shortly after the work transition.


Lysosomes of cardiac and skeletal muscle: resolution by zonal centrifugation. The application of zonal centrifugation to the analysis of homogenates of cardiac and skeletal muscle permits selection of fractions that are enriched in markers for lysosomes, sarcolemma, sarcoplasmic reticulum, and mitochondria. The method of disruption of normal and pathological tissue alters significantly the distribution of total protein and peaks of enzymatic activity on the gradient. Total activities of cathepsin, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and para-nitrophenylphosphatase are distributed at different concentrations of sucrose on the gradient. Beta-Glucuronidase appears to "mark" the sarcoplasmic reticulum, as well as lysosomes, of skeletal muscle, para-Nitrophenylphosphatase, a common marker of acid phosphatase of lysosomes, is enriched in those fractions of cardiac muscle containing the highest specific activity of ouabain-inhibited Na-K-ATPase. Thus, these two enzymes appear to have a localization in at least two separate organelles. On the other hand, these results may indicate the isolation of several "populations" of lysosomes that are associated constantly with distribution peaks of other organelles. In any event, attempts to correlate changes in structure of organelles of normal and pathological specimens of tissue with functional impairment, e.g., Ca2+ uptake, activity of Na-K-ATPase, etc., must include consideration of dual localization of enzymatic markers or cross contamination by populations of other organelles.


Vinyl chloride-induced deactivation of cytochrome P-450 and other components of the liver mixed function oxidase system: an in vivo study. Liver microsomal enzyme activities were measured 24 hr after a 6 hr exposure to 5% vinyl chloride in male rats pretreated with phenobarbital, Aroclor 1254 or the control vehicle. Liver injury as indicated by serum transaminase elevations after vinyl chloride, was found only in phenobarbital and Aroclor 1254 animals while cytochrome P-450 contents and oxidative N-demethylation of aminoantipyrine and ethylmorphine were markedly decreased in all groups. Glucose-6-phosphatase, cytochrome b5 and NADPH and NADH cytochrome P-450 reductase were scarcely affected. This selective enzymatic deactivation is consistent with a cytochrome P-450 centered activation of vinyl chloride to a reactive electrophile.


Effect of cadmium chloride on the rat testicular soluble selenoenzyme, glutathione peroxidase. Thirty-six hours after male rats were injected with 25 mumoles cadmium chloride/ml/kg of body weight they exhibited decreased plasma and testicular glutathione (GSH) peroxidase activity, testicular atrophy and necrosis, and increased testicular thiobarbituric acid-reactive products. Seven days after injection, only the plasma GSH peroxidase activity returned to normal. The decrease in testicular GSH peroxidase activity was not reversible by dialysis against buffer or by the addition of selenium as buffered selenomethionine. In vitro inhibition of testicular GSH peroxidase activity occurred at 0.3 mM cadmium. All in vivo effects were prevented by a prior injection of 25 mumoles sodium selenite/ml/kg of body weight. Testicular GSH peroxidase may be the direct or indirect target of cadmium-induced testicular damage, and this damage results in lipid peroxidation.


Cholesterol and beta-lipoprotein on lipid inclusions and lysosomal and mitochondrial permeability of cultured heart muscle and endothelioid cells. Cultured rat heart endothelioid cells were used to study the effect of beta-lipoprotein and cholesterol on the production and persistence of cellular lipid inclusions. Both heart endothelioid and muscle cells were used to study the effects of beta-lipoprotein with and without cholesterol or cholesterol esters on lysosomal or mitochondrial lability. Beta lipoprotein enhanced the production and maintanence of lipid inclusions. In the concentration employed (20mg%) it alone produced no effect after 72 hours on lysosomal or mitochondrial lability but with cholesterol, cholesterol stearate, cholesterol oleate or cholesterol linoleate (5mg%) there was a trend toward labilization.


[Effects of parenteral infusion of glycerol on glycerol kinase and adenosintriphosphate in rat kidneys (author's transl)]. Effects of intravenous glycerol infusions on glycerol kinase and adenosintriphosphate in rat kidneys. Intravenous infusions of glycerol with rates near and above the average maximal turnover capacity (0,74 g.kg-1.h-1) cause alterations of the kidneys such as weight increase, decrease of protein content and activity of glycerol kinase with excretion of this enzyme in the urine. At infusion rates of 0,6 g.kg-1.h-1 and more a decrease of the ATP-content of the kidneys is observed. Effects on the liver are not consistent and only demonstrable at infusion rates above the maximal turnover rate of glycerol. The results are discussed with regard to osmotic nephrosis. The appearance of glycerol kinase in the urine is discussed as an early symptom of kidney damage.


[The influence of propranolol, practolol and theophylline on the plasma renin activity (author's transl)]. The stimulating effect of theophylline on the plasma renin activity (PRA) under beta-receptor blockade by propranolol or practolol was investigated in 27 patients with essential hypertension of degree I-II. After propranolol and also practolol PRA decreased about thirty per cent of the basal value, increased however by the factor of 2 to 3 after application of theophylline, in spite of the blockade of the beta-receptors indicated by a slight decrease of systolic blood pressure and heart rate. The effect of propranolol and practolol on the basal PRA was not different. Our results show the possibility, to stimulate renin secretion despite blockade of beta receptors by propranolol or practolol, respectively.


Gastric mucosal blood flow and pepsin secretion in dogs--stimulation by 13-nle-motilin. In response to graded doses of intravenous 13-norleucine-motilin (13-nle-motilin)--a synthetic analogue of motilin and biologically equivalent to the natural polypeptide-, gastric mucosal blood flow (GMBF) in canine vagally denervated fundic pouches was studied using the aminopyrine clearance technique. As 13-nle-motilin did not exert any detectable effect on gastric secretion of hydrogen ions, intraluminal instillation of 160 mM HCl was used to provide a pH gradient allowing aminopyrine to move into the pouch lumen. With increasing doses of 13-nle-motilin, GMBF increased to 148% of control values; pepsin secretion  - due to augmented pepsin concentration - rose concomitantly. Enhanced pepsin secretion was not accompanied by an increase in cyclic 3',5'-adenosine monophosphate secretion.


A rare case of megaloblastic anaemia caused by disturbances in the plasma cobalamin binding proteins in a patient with hepatocellular carcinoma. A patient with hepatocellular carcinoma, megaloblastic anaemia and increased concentration of serum cobalamin is described. Plasma TC I was increased to 10,000 times the normal concentration, thus explaining the increased concentration of serum cobalamin and a false Schilling test. The increase in plasma TC I in concurrence with undetectable amounts of plasma TC II was a likely explanation for the anaemia. The electron microscopic picture of the hepatocellular carcinoma was in accordance with TC I being produced by the tumour cells.


Search for uro-genital tract infections in patients with symptoms of prostatitis. Studies on aerobic and strictly anaerobic bacteria, mycoplasmas, fungi, trichomonads and viruses. Seventy-nine patients with symptoms of nonacute prostatitis and 20 healthy volunteers were examined for uro-genital tract infection with bacteria, mycoplasmas, fungi, trichomonads and viruses. No differences in the results of the bacterial cultures were found between the patients and the controls. In only a few cases were established urinary tract pathogens found, but in no instance were these findings reproducible in later specimens. The cultures of the expressed prostatic fluids and the samples of semen gave no information of the occurrence of bacteria over and above that obtainable from examination of the urethral specimens. Significant bacteriuria was not found in any of the patients. Though Neisseria gonorrhoeae could not be isolated from any of the subjects, immunofluorescent studies revealed such organisms in seminal fluid in 8% of the patients. Nine of the patients had 1 to 3 years been considered successfully treated for gonorrhoea. Five of these nine patients were still found to harbour gonococci, as judged from the immunofluorescent studies. Corynebacterium vaginale was recovered in an equally low frequency (5%) from the patients and the volunteers. There was no significant difference in the incidence of T-mycoplasmas between the patients (46%) and the controls (35%), while Mycoplasma hominis was only found in the patients (10%). Trichomonas vaginalis could not be detected in wet smears of expressed prostatic fluid in any of the subjects, but could be cultured from one such specimen. Metacycline treatment (performed according the double blind cross-over technique) was studied for effects on the bacterial flora. In about 10% of the patients, an earlier not observed relative dominance of gram-negative rods was found on the cultures made after the therapy. Candida albicans was only isolated from the patients. It was found more often after (24%) than before the (15%) treatment. Complement-fixing antibodies to N. gonorrhoeae, cytomegalovirus and Chlamydia were found in 10, 19, and 33% of the patients, respectively. The corresponding figures for the healthy males were 0, 20 and 5%.


[Hyperlipoproteinemia in liver diseases]. Disorders of liver function frequently lead to raised plasma lipid values. The methods for analyzing plasma lipids and lipoproteins developed in recent years have yielded a great deal of data. This information provides new insights into the interrelationships of these disorders and are furthermore important in differential diagnosis of jaundice. An abnormal lipoprotein (LP-X) has been isolated from the plasma of patients with intra- or extrahepatic cholestasis, and a simple and sensitive method of demonstrating this lipoprotein has subsequently been developed. This parameter is today the surest clinico-chemical test for excluding or demonstrating cholestasis, triglyceride-rich lipoproteins accumulate in the plasma due to lack of lipase. This leads to hypertriglyceridemia. The disappearance of pre-beta and alpha-lipoprotein bands in agarose gel electrophoresis, which is a most frequent sign of severe liver damage (irrespective of its origin) is probably caused by a defective lipoprotein A. The capacity of lipoprotein A to bind certain lipid fractions is reduced or abolished. By no means all the mechanisms leading to structural changes in plasma lipoproteins and hyperlipoproteinemia in disorders of liver function are known at present. However, new findings emphasize the central role played by the liver in synthesis and degradation of plasma lipoproteins.


[The after-care of tumor patients in radiotherapy]. A report is presented on the organization and goals of consultative outpatient follow-up of patients with irradiated tumors by the radiotherapeutic oncologist in a radiation therapy clinic. Organization involves a close working relationship with the referring physician and routine patient checkups at regular intervals after radiation therapy. The goals of the follow-up program include detection and treatment of irradiation-induced early and late alterations of normal tissue, assessment of therapeutic results, early recognition of recurrences, metastases and/or additional tumors and initiation of therapy of these. For these reasons standardized follow-up examinations are required. These must be adapted to the type of tumor and supplemented with the usually expensive and time-consuming tumor workup only where there is suspicion of tumor progression or if problems of differential diagnosis arise.


[The diagnosis of liver metastases and primary hepatomas by means of scintigraphy, laparoscopy and laparotomy]. To evaluate the presence or absence of hepatic metastases or primary hepatoma 106 patients were examined by liver scintigram as well as laparoscopy or laparotomy. A definite diagnosis was established in all patients by histology, autopsy or observation of clinical course for at least one year. Only scintigrams resulted in false positive diagnosis (in 5%). False negative diagnoses were obtained in 29% of laparoscopies and in 36% of scintigrams when evaluated routinely with knowledge of the clinical findings and laboratory examinations. Analysis of the same scintigrams by an experienced examiner without knowledge of the clinical findings lowered the proportion of false negative scintigrams to 12%. In 5 patients with liver metastases or hepatoma coexisting in liver cirrhosis or advanced chronic liver congestion, both methods of examination gave false negative results.


[Proceedings: Clinical presentations in nephrology]. Four clinical cases are presented: (a) cured systemic lupus erythematosus, fracture of the odontoid process of the axis; (b) renovascular stenosis following renal transplant; dissecting aneurysm of aorta, consolidated for the last 3 years; (c) rejection glomerulonephritis following renal transplant; (d) unusual complications in a patient of intermittent hemodialysis for the last 8 years.


[The current state of masculine contraception]. The present state of male contraception is reviewed with reference to pharmacological methods only. Since spermatogenesis is the result of a long chain of endocrine mechanisms starting in the hypothalamus, any review of contraceptive techniques must follow these physiological links. Spermatogenesis itself involves different stages and each of them can be a target for pharmacological compounds. Although no drug is currently available that offers all the necessary guarantees required of a contraceptive, interesting interconnections have nevertheless emerged. In consequence there are grounds for moderate optimism as to the availability of a male contraceptive in the coming years.


Behaviorally evoked hippocampal theta waves: a cholinergic response. Forced running in a treadmill results in the instantaneous appearance of a synchronous electroencephalographic pattern in the dorsal hippocampus of the rat. A similar bioelectric response in the absence of movement is induced by physostigmine. Both responses are blocked with scopolamine. Lesions of the medial septal nucleus abolish hippocampal theta waves induced by forced running or physostigmine.


Glycerol phosphate shuttle in virus-transformed cells in culture. The glycerol phosphate shuttle is shown not only to be present and functional in virus-transformed cells, but its level is higher than in normal cells in culture. The increased aerobic glycolysis that has been demonstrated for these cells after transformation, therefore, is not due to an impairment of hydrogen transfer pathways.


Estrogen receptor in the mammalian liver. The cytosol from livers of adult female mammals contains [3H]estradiol-binding proteins that can translocate to the nucleus and attach to chromatin. In comparison to the prepubescent rat, adults have higher estrogen binding in the liver and greater increases in plasma renin substrate after administration of estrogen. The protein in the liver which binds estrogen may be an estrogen receptor involved in modulating hepatic synthesis of selective plasma proteins.


Photoreceptor-bipolar cell transmission in the perfused retina eyecup of the mudpuppy. The hypothesis that a synaptic transmitter is released by photoreceptors in the dark is supported by experiments in which cobalt was used as a synaptic blocking agent, while intracellular recordings of receptors and neurons that are directly postsynaptic to receptors were maintained. In the dark the depolarizing bipolars are hyperpolarized, whereas the hyperpolarizing bipolars are depolarized.


Angiotensin-converting enzyme: vascular endothelial localization. Fluorescein-labeled antibody to rabbit pulmonary angiotensin-converting enzyme localized in the vascular endothelium of rabbit lung, liver, adrenal cortex, pancreas, kidney, and spleen. Epithelial cells of the renal proximal tubules were the only parenchymal cells among the organs studied that demonstrated immunoreactivity.


[Bronchopulmonary aspergilloma in children and bronchogenic cyst. A new case]. The authors report a new case of aspergilloma developing in an intra-pulmonary bronchogenic cyst in a girl aged 10 years. A cure was obtained after surgical excision. The possibility of serious complications, such as hemoptysis, abscess formation and spread of the aspergillus, has two consequences; the first is the utility of regular supervision of any intra-pulmonary air cavity and, eventually, surgical removal. The second is the necessity of operation as soon as the diagnosis of aspergilloma has been made.


[Malignant lymphopathy and breast cancer (apropos of 3 cases)]. Two cases of Hodgkin's disease were associated with a breast tumor after a remission of seven years. Conversely, another patient was affected by a mammary adenocarcinoma prior to the onset of an overt acute lymphoblastic leukemia in the same delay. These three observations focussed our attention upon the development of secondary neoplasias and the possible relationship between both types of disorders. In a period with extensive research on cancer etiology, it seemed interesting to discuss the role of several factors: genetic, therapeutic and/or immunological ones.


[Prostaglandins and reproduction].

[Prostaglandins and reproduction]. The prostaglandins probably play an important role in the physiology of reproduction. In women as in men, they intervene at several levels. At the level of the ovary, the prostaglandins E may be modulators of the action of gonadostimulin on ovarian hormonogenesis, in close relationship with cyclic AMP and, furthermore, represent an important biochemical intermediate stage in the mechanism of ovulation. F2 prostaglandin, F2 alpha, on the other hand, represents in numerous animals, but not in women, a luteolytic factor of uterine origin. At the level of the hypothalamopituitary axis, E prostaglandins may modulate hypothalamic neuro-secretion and to a lesser degree, the liberation of pituitary stimulins, and thus intervene in gonadotropic function. At the level of the female genital tract, prostaglandins may influence uterine and tubal motility. It is perhaps by this latter effect that the very large quantities of seminal prostaglandin influence the process of fertilisation.


[Granulopoiesis and its regulation].

[Granulopoiesis and its regulation]. The neutrophil granulocytes are derived, in the present state of our knowledge, from a hemocytoblast identical with that of the other blood cells, defined by its power to form in vivo clones of multiple composition, defining their characteristic of totipotential undifferentiated cell. The way in which the clone-forming cell evolves in vivo towards granulopoiesis, depends on a genetic factor, phenomena of derepression and an extrinsic factor, the origin of which is probably cellular. Differentiation of the hemocytoblast leads to a cell, the destiny of which is then fixed, which may then form clones in vitro in semi-solid medium (clone-forming cell in vitro or CFC). This cell is definitely a true entity. A humoral factor of macrophage origin intervenes to ensure granulopoiesis in vivo (clone-stimulating factor CSF3. The phenomena which regulate this granulopoiesis then cause to intervene various biochemical forms of this clone-stimulating factor and an inhibitor, the reality of which is not yet definitely demonstrated in vivo. Laboratory animals and cell culture of human normal and leukemic granular cells now supplies experimental models which permit studies of the granular differentiation of the hemocytoblast completed by kinetic studies in vivo to make rapid progress, especially in our knowledge of the human leukemic process.


[Kinetics of polynuclear cells].

[Kinetics of polynuclear cells]. Polymorphonuclear leukocytosis and granulopenia in infectious diseases have been studied for several years, either by intravascular kinetics of the polymorphs labelled previously in vitro, or by isotopic labelling in vivo and autoradiography of the bone marrow, using medullary kinetic study of granulopoiesis. Polymorpho-nuclear leukocytosis is usually due to an increased production and a relative mobilisation of reserves. Leukopenia may be due to various mechanisms, but there does not seem to be any qualitative disorder of circulating polymorphonuclear leukocytes with corpuscular hyperdestruction nor any abnormalities of multiplication of the bone marrow nor of maturation. On the other hand, one frequently finds abnormalities of distribution between the marginal and circulating compartments, increased extracorpuscular destruction, reduction in production due to reduction in absolute number or differentiation of the granulopoietic parent cells.


[Leukocytosis and polynucleosis in infectious disease]. During bacterial infections, the intensity of the polymorphonuclear leukocytosis depends on the bacterium but also on the mechanism and extent of the infection. Polymorphonuclear leukocytosis is greater during pyogenic and anaerobic infections. It is due to deep suppuration, septicemia of thrombophlebitic origin, acute endocarditis, purulent meningitis and pneumonia. The increase in the number of polymorphonuclear cells is, on the other hand, less marked in sub-acute bacterial endocarditis. Apart from bacterial infections, a polymorphonuclear leukocytosis is common in inflammatory disease, such as tissue necrosis and several malignant diseases. It may also be due to drug allergy.


[Granulopenia of infectious origin].

[Granulopenia of infectious origin]. Among the various infectious and parasitic disease liable to produce granulopenia, the authors selected certain diseases which represented their personal experience. Classically, leukopenia may occur during typhoid fever, but was not present in all of the series of 114 adults they observed with this disease. It only occurs after antibiotic treatment (Thiamphenicol in the majority of cases). During acute brucellosis (188 cases studied) granulopenia was constant. It occurs early and is lasting. It reappears during septicemic relapse. Leukopenia is corrected during treatment by tetracycline antibiotics. Neutropenia during disease is frequent but usually labile. This characteristic explains why there was no granulopenia in 90 cases of mumps and 64 cases of chickenpox. Finally, during Kala Azar, 8 cases confirmed certain already well known data: the considerable reduction in granulocytes but also anemia and thrombocytopenia.


[Infections in agranulocytosis and their treatment]. A quantitative deficiency in polymorpho-nuclear leukocytes, due to aplastic anemia, exposes to infection. The risk is all the greater when the neutropenia is more marked and more lasting. The infections have a different distribution from that commonly observed in normal subjects. There is little inflammatory reaction, no pus formation and bacterial multiplication invades the parenchyma and may create necrosis due to arteriolar obstruction. The prognosis is very bad. For example, pulmonary infections in acute leukemia of adults, have a mortality greater than 75%. Antibiotic treatment and leukocyte transfusions give disappointing results. The prevention of infections has permitted spectacular progress. Nevertheless, the long-term prognosis is not linked to the infection itself, but to the sub-jacent disease responsible for the agranulocytosis. The infections become cured in transient toxic aplasia and in leukemia where chemotherapy permits one to obtain a remission. The infections remain fatal whatever the treatment used if the medullary aplasia is not curable.


[Massive ascites in pancreatitis. Review apropos of 10 personal cases]. Massive ascites is are complication, but not exceptional, in pancreatitis. In a series of ten personal cases and a review of one hundred cases in the world literature, the authors attempt to define the main pathological and clinical characteristics of this disease and the best treatment. Ascites may follow abdominal trauma, involving the pancreas, sometimes it occurs during known chronic pancreatitis, often it is the first sign of pancreatic disease, whether acute or chronic. High levels of pancreatic enzymes in the ascitic fluid are the main factor in diagnosis of pancreatic ascites. The mechanism of formation of the ascites is loss of pancreatic fluid into the peritoneal cavity owing to a breach in the pancreas, the presence of enzyme-rich fluid, causing secondarily "chemical" peritonitis. Paracentesis abdominis or drainage of the fluid during exploratory laparotomy, permits one to obtain in certain cases, a cure of the ascites, but surgical drainage by an anastomosis between the pancreatic cyst and the digestive tract (pancreatico-digestive anastomosis), has the advantage of ensuring treatment of the ascites and of the responsible pancreatic disease.


[Evaluation of the involvement of the spleen in Hodgkin's disease]. In the light of personal data and 60 cases in the literature, the authors attempt to evaluate the risk of splenic involvement during Hodgkin's disease. Neither clinical examination nor scintiscanning of the spleen, permit one with sufficient security to recognise splenic involvement. Study of the context reveals, on the contrary, that the following factors contribute to the splenic risk: --Signs of evolutivity: their presence implies splenic involvement in 63% of cases; --the histological type of the frequency of the splenic involvement increases from type 1 (38%) to type 4 (61%); --the distribution of the lymph nodes above the diaphragm, the spleen is involved in 66% of forms with cervical and mediastinal and axillary lymph node involvement, 56% in forms with cervical and axillary nodes alone and 24% in forms with cervical and mediastinal nodes alone; --the data obtained by lymphography, as 89% of patients with lumboaortic gland involvement, also had invasion of the spleen. There may be errors of interpretation of lymphography, depending on the series, of from 6 to 25%. Thus, assessment of the risk of splenic involvement in Hodgkin's disease is carried out less on the splenic signs themselves, than on the clinical, laboratory, histological and radiological context.


[Detection of anti-DNA antibodies by electroimmunodiffusion. Comparison of the results with the study of antinuclear factors by immunofluorescence]. The detection of anti-DNA antibodies was carried out by the electroimmunodiffusion method. The results were compared to those of the immunofluorescent method for anti-nuclear factors. Positive results were obtained with the electroimmunodiffusion method in 86% of the lupus erythematosus cases, 77% of the sero-positive rhumatoid polyarthritis cases and 67% of the scleroderma cases. They are comparable to those obtained by other methods. The electroimmunodiffusion method allowed in 3 out of 54 sera to defect anti-DNA antibodies although no anti-nuclear factor was found.


[Unilateral renal atrophy].

[Unilateral renal atrophy]. The authors report 45 cases of unilateral renal atrophy. The circumstances of discovery are related to the urological symptoms: pain, hematuria, pyuria. On the other hand, hypertension is rarely the reason for consultation. Women are more affected than men. Intravenous urography, retrograde cystography and arteriography are essential examinations to collect information concerning the etiology. Dynamic scintiscanning with measurement of the percentage of isotope fixed on the kidneys, has the advantage of permitting comparative evaluation of renal function on each side. In our study, obstruction of the urinary tract was more frequent than parenchymatous disease favoured by infection. Vascular abnormalities were rare. The etiological enquiry remained, however, negative in one third of cases. Surgical operation was necessary when a urological abnormality was the cause of persistence of severe symptoms. On the other hand, removal of the atrophic kidney does not seem to us advisable when decided simply to relieve hypertension. The latter point is particularly discussed.


[Effect of rest on the course of viral hepatitis]. Discussions having lately raised the importance of rest in the treatment of viral hepatitis the authors report some studies made on the subject. They take into account 3 personal unpublished statistics analyzing the role of effort at 3 different stages -- in the acute phase, during convalescence and as an eventual factor producing aggravation. Although their results appear to be in contradiction with those found in American studies the authors show that the importance of rest in the initial phase is unanimously recognized and that there is no statistical evidence that such a prescription should be given up before the normalization of the main biological parameters. Furthermore though it is statistically proved that a certain activity between the 30th and 60th day does not affect the later course of the disease yet there is no element which allows to authorize the patient to resume his normal professionnal activity before the 60th day. Finally the lack of controlled studies does not allow any precise determination of the impact of effort in the determinism of an eventual aggravation. However according to the authors' experience physical tiredness can legitimately be suspected to have produced this aggravation in 47.06 % of cases of a secondarily aggravated hepatitis.


[Orthostatic hypotension in the aged. Systematic exploration in 400 persons]. The authors study the adaptation of the blood pressure to changes in posture in 400 people, and studied the world literature on the subject. They found that postural hypotension in the elderly is quite different from that in young adults. A full study is difficult and the response to changes in posture are inconstant, this it is only possible to take into consideration changes in systolic blood pressure, and one should not neglect falls in blood pressure of low amplitude. This definition, once accepted, postural hypotension in the elderly is a frequent phenomenon which gives complex symptoms owing to the intrication of vascular disturbances and lesions of the central nervous system. Among the numerous permanent or occasional causes, more particularly those due to drugs, the role of hypovolemia seems to be of importance in orthostatic hypotension and should be sought as a routine.


[Alpha 1 antitrypsin deficiency and liver diseases]. Alpha-1 antitrypsin is mainly responsible for the inhibitory power with regard to serum of numerous enzymes, in particular, trypsin. Alpha-1 antitrypsin deficiency is linked to pulmonary and hepatic disease. The special characteristic constantly found during liver disease, associated with alpha-1 antitrypsin deficiency, is the existence of intra-cytoplasmic globules within the hepatocytes due to accumulation of alpha-1 antitrypsin. This latter enzyme differs chemically from serum alpha-1 antitrypsin.


[Practical significance of HL-A groups in rheumatology]. Since 1972, several relations have been demonstrated between some HL-A antigens and some articular diseases. The W27 antigen frequency is highly increased in ankylosing spondylitis (88%) and in Reiter disease (78%) compared with controls (5%). In peripheral forms of psoriatic rheumatism, the W17 and HL-A13 antigens are more fréquent (24% and 15%) than in healthy subjects (4% and 5%). In central forms of psoriatic rheumatism, there is a relation with W27 (48%) and still, we do not know if this association concerns only spondylitis or also sacro-ileitis. The HL-A typing may be useful for the diagnosis of some rheumatic diseases, when they present atypical appearances. W27 possesses a considerable value for the diagnosis of ankylosing spondylitis. The relation between W27 and ankylosing spondylitis is clearly stronger than that between Waaler-Rose reaction and rheumatoid arthritis.


[Intrahepatic cholestasis].

[Intrahepatic cholestasis]. Intrahepatic cholestasis has become a very important aspect of liver disease. The author, in the light of electron microscopy and the theory of filtration-reabsorption of bile secretion proposes that the disease may be explained by obstructions situated at various levels of the inter-cellular spaces of the liver. This obstruction is functional at first, but is maintained by a duodeno-hepatic inhibitory reflex, the existence of which has been demonstrated by the author. In the light of facts and documents presented here, one may see that from Monneret until now, various authors have come very close to the true mechanism of this type of jaundice, each discovering some aspect of the truth.


[Extensive bony condensation of the vertebrae in intervertebral disc degeneration. (Study of 25 cases)]. The authors report 25 cases of extensive bony condensation of the vertebrae due to degeneration of the intervertebral discs, giving on lateral XRay a dome-shaped or helmet-shaped appearance. 19 cases occurred in women. Two-thirds of the patients were aged between 35 and 55 years, with an average of 45 years. The lesions were lumbar in 21 patients. They affected in 20 cases two adjacent vertebrae. All the clinical, radiological, pathological and discographic findings, together with the course, confirmed the degenerative origin of these bony condensations, the pathogenesis of which is still not perfectly understood.


[Idiopathic hemochromatosis and primary cancer of the liver]. In 74 patients admitted to hospital for primary hemochromatosis, the authors observed in 5 cases, the development of primary carcinoma of the liver. The frequency of this complication was definitely greater than in alcoholic or post-hepatitic cirrhosis, whether one considers patients in hospital or on autopsy. The best signs of malignant change are alterations in the surface of the liver and the development of hemorrhagic ascites. Using modern methods of clinical investigation, it is possible to make the diagnosis during the patient's life. Laparoscopy, permitting biopsy under direct vision, is the best investigation but it is not always possible. A search for alpha 1 foeto-protein was positive in one third of cases and the demonstration by hepatic arteriography of characteristic vascular abnormalities and, perhaps in future, information supplied by ultra-sonic echography, usually permit one to make the diagnosis. The course was fatal within a few months, and it seems that metastases and vascular spread are less frequent than in carcinoma developing on cirrhosis due to other causes.


[Study of the incidence of complement-fixing antibodies against the cytomegalovirus in 339 subjects]. The authors studied complement-fixing anticytomegalovirus antibodies in a population of 339 subjects, divided up into 8 groups, from birth to 60 years. The adult group consisted of blood donors. At birth, the new-born acquired temporary passive immunity from their mothers ; then they became actively immunised over the course of several years. The increase in the number of immunised subjects was greater during infancy and adolescence, passing from 6 % to 28.1 %, than during adult age (45.1 to 52.9 %). A very important difference of 17 %) definitely separated the age groups of adolescents and young adults. 47.4 % of blood donors have complement fixing anticytomegalo-virus antibodies.


[Prognostic value of bone and marrow lesions in primary myeloid splenomegaly]. The diagnosis of myelofibrosis depends on three fundamental criteria. Myeloid metaplasia of the liver and spleen, absence of Philadelphia chromosome and a variable degree of myelofibrosis. It is thus necessary to have available bone and marrow biopsies to make the diagnosis. The analysis of elementary lesions, together with their grouping, was at the origin of various pathological classifications, including those of Hickling and Jacquillat, Chom and Ripault. The latter, adopted by most authors, distinguishes three histological types, depending on the degree of myelofibrosis and bony sclerosis. They are usually considered as successive stages of the disease.


[IgD myeloma. Apropos of a case].

[IgD myeloma. Apropos of a case]. The authors report the case of a 72 year old man admitted to hospital for thoracic pain, who was found to have an Igd myeloma of lambda type. The diagnosis, suspected, in view of anemia, raised sedimentation rate and abnormal electrophoresis of serum proteins, was confirmed by marrow examination after sternal aspiration and by the use of a specific anti-serum during immuno-electrophoresis and on Ouchteriony medium. There were radiological lesions of diffuse, decalcifying myelomatous type. The course was characterised by : 1) a constant tendency to anemia, then preterminal thrombocytopenia, whereas the leukopenia remained moderate. 2) The secondary onset of Bence-Jones proteinuria and mild albuminuria with the aggravation of pre-existing renal failure. 3) Repeated attacks of infection and the intermittent onset of mental confusion, the etiology of which was not clear. Death occurred ten months later. No autopsy was carried out. In the light of this case, the authors review the world literature and the special characteristics of IgD myeloma.


[Hemorrhagic gastritis caused by localised intravascular coagulation during the course of cryptogenic inflammatory cirrhosis]. The authors report here a case of antral hemorrhagic gastritis without ulceration nor erosion, but with intravascular coagulation within the chorionic layer, which had a prolonged course in a patient with non-alcoholic cirrhosis, and which continued in spite of surgical cure of portal hypertension. The authors discuss various theories which might explain this hemorrhage and the development of localised intravascular coagulation, together with its relationship with the cirrhosis.


[Sex hormones and calcitonin secretion]. The increase in serum calcitonin during pregnoncy raises the problem of the role of oestrogens in the secretion of calcitonin. The authors show that oestrogen causes, in castrated rats, an increase in calcitonin activity as measured in the plasma by a biological method. This effect of injected oestrogen does not occur if the castrated animal is also submitted to thyroidectomy. The effects of progesterone studied on a small number of cases, seem to be less marked. This report shows that oestrogens have a synergistic effect with calcitonin in the maintenance of calcium within the bone. This is of importance during pregnancy and after the menopause.


[Our experience with the radioimmunoassay of insulin: Its practical value. Apropos of 140 cases]. What is the interest of insulin determinations in diabetics? The interest is considerable, scientifically, particularly in obese patients with hyperinsulinism. In practice, in intermediate cases of diabetes, it may help in deciding whether or not to administer insulin. The authors studied insulin secretion in various varieties of diabetes and its role in the onset of vascular complications. Low insulin secretion seems to favour the development and frequency of the latter.


[Diagnosis of human active or latent human brucellosis by lymphocyte transformation. Inhibition of leukocyte migration and passive hemagglutination. Possible interference between brucellosis and some mental disorders]. Passive hemagglutination tests (H.T.), involving the coating of a soluble B. abortus antigen onto sheep red blood cells through chromium chloride, were always negative in non-brucellic subjects. Positive H.T., even at low titers (1:50), were associated with positive specific lymphoblastic (T.T.L.) and inhibition of leucocyte migration (I.M.L.) tests in 13 patients. These 3 tests were negative in 17 control brucellosis-free individuals. Positive H.T. confirmed a clinical diagnosis of brucellosis in 27 patients with dubious or negative responses to classical tests. Low positive (1:50, 1:100) H.T. may correspond to Brucella primary-infection or to a quiescent chronic infection, and higher titers to clinically active brucellosis. There is a correlation between cellular immunity tests (T.T.L., I.M.L.) and passive hemagglutination test. Furthermore, 39/88 women hospitalized in psychiatric wards were positive to H.T., and 6 of them were also highly positive to complement fixation and tube agglutination tests. Three T.T.L. and I.M.L., performed on samples from 3 H.T. (1:50) positive patients, were positive. These 30 patients were classified as depression or severe anorexia.


[Periodic hemodialysis. Application of new theories and technics to shortening the dialysis sessions]. Many attempts are now being made to reduce the time of dialysis in chronic uremia. The method developed by Funck-Brentano, Man and Sausse, which includes the use of a highly permeable membrane and precise control of ultrafiltration, is theoretically logical. It was easily applied to 22 unselected patients, treated nine hours weekly for two to eight months. Of course, the follow-up is insufficient. The dosage of products permitting the digestive elimination of phosphorus and potassium must be revised, but the improvement in physical and psychological tolerance of treatment is such that a return to long duration dialysis can no longer be considered possible.


[Cardiovascular manifestations of pancreatitis. Apropos of 4 cases]. The authors report four cases of cardiovascular signs in pancreatitis in patients aged between 31 and 42 years. They then consider the main aspects observed. T-wave disorders, pericarditis, myocardial infarction and coronary heart disease and arterio-pancreatic syndrome. They consider the points in common between myocardial infarction and acute pancreatitis and then review the various pathogenic theories proposed.


[Posterior fossa syndrome terminating the course of histiocytosis X. Study of lesions of the central nervous system. Association with polyvinylpyrrolidone thesaurismosis]. The authors report the pathological and clinical findings in a case of histiocytosis X in a child. A rapidly progressive neurological syndrome of brain stem damage, occurred 5 years after the onset. Blockage of the 3rd ventricle led to surgical exploration of the posterior fossa. Lesions of the brain stem and cerebellum, in addition to the granuloma of the hypothalamus, are described. The neurological symptoms in histiocytosis X often suggest a space-occupying lesion but usually occur in the later prolonged forms in the adult. Association of thesaurismosis due to P.V.P., of therapeutic origin, produced numerous clinical skin and joint signs.


[Recurrent acute pericarditis and corticoid dependence. Apropos of 10 cases]. The authors report ten cases of acute recurrent pericarditis observed over a period of 5 years and emphasize the frequency of these relapses involving 15 to 20% of cases of acute pericarditis. Usually, no cause is found and, althrough an immunological mechanism has been suggested, there is no common test which may confirm or disprove this theory. The risk of ultimate constrictive pericarditis is minimal and this risk is thus not taken into consideration in deciding on treatment. On the other hand, the undesirable effects of corticosteroids which favour relapses, seem to be demonstrated. The use of corticosteroids in cases of acute pericarditis should thus be exceptional and one should prefer non-steroid anti-inflammatory drugs. Immunosuppressors and pericardectomy should be reserved for the rare forms where the disease progresses and relapses continue after cortisone has been stopped.


[Pancytopenic form of acute tuberculosis]. The authors report two cases of febrile pancytopenia of tuberculous origin. In both cases specific antibiotic treatment led to disappearance of the clinical and blood signs. These cases, together with 65 others, found in the world literature were then analysed. In most cases (54), death occurred owing to lack of early diagnosis and treatment, whilst in 14 cases, cure was obtained when the treatment was not started to late. The authors emphasize the necessity of liver biopsy to make the diagnosis of tuberculosis in any case of unexplained pancytopenia with fever.


[Several methodologic aspects of chronic bronchitis surveys]. The frequency of chronic bronchitis and the late and irreversible character of the respiratory invalidity thus caused, led to recognition at an early stage when the disease is usually neglected by the patient. In the choice of examinations designed to select pathological cases, it is important to take into consideration a few elementary notions of methodology. 1 - Precise definition of objectives. 2 - Drawing up a questionnaire and evaluation of its performance. 3 - The place, execution and interpretation of morphological and functional investigations, are the main points developed from personal investigations and similar investigations carried out in other countries. Quality controls of these main methods of analysis of the disease under study are necessary for reliable numerical evaluation. The principles drawn up should be borne in mind at a time when epidemiology is occupying a basic position in bioclinical research and numerous attempts have been made to carry out investigations from which one should obtain the maximum information.


[Thrombopenic purpura revealing Hodgkin's disease]. The authors report a case of Hodgkin's disease at the subdiaphragmatic II B b stage with cell type III, revealed by thrombopenic purpura. Laparotomy and splenectomy confirmed the invasion of the spleen whereas there was no clinical splenomegaly and splenic radio-isotope scan was normal. The course is at present favourable, the purpura has been treated by corticotherapy then splenectomy, and the disease has been brought under control by classical treatment (cobalt radiotherapy and chemotherapy). The authors then discuss eight other cases in the world literature. Splenectomy is of dual interest for the assessment of Hodgkin's disease, on the one hand, and for the treatment of thrombopenic purpura on the other hand.


[Acute transformation in 45 cases of chronic myeloid leukemia]. After a chronic phase, the average duration of which in this series was 38 months, the acute phase of myeloid leukemia was very short, not exceeding 7 months. The clinical signs which suggest an acute exacerbation are, in order of importance, increase in the volume of the spleen, changes in general health, fever. The blood signs, which are often found later than the clinical signs, are increased white cell count, anemia and marrow leukoblastosis higher than 20%. The laboratory criteria of acute exacerbation are of lesser importance. Chemotherapy gives very poor results at this stage.


[Water-electrolyte re-equilibration in chronic interstitial nephritis]. In chronic interstitial nephritis there is a salt-losing syndrome. The reduction in the number of nephrons provides an experimental model for a study of the effects of a sodium load on the kidney. Partial restoral of renal function follows administration of sodium chloride and permits one to consider the main mechanisms of the regulation of sodium balance.


[Actinomycosis. Apropos 4 cases with thoracic and abdominal localization]. Actinomycosis is a rare disease and may be discovered at operation. It may produce numberous thoracic or abdominal signs; the diagnosis is very difficult and requires histological examination.


[Association of Behçet's disease and pelvispondylitis in a subject without HLA W 27 antigen]. The authors report a new case of Behcet's disease in association with ankylosing spondylitis. A study of the HLA system in this patient, showed the presence of an HLA 5 (Behcet's disease) and the absence of HLA W 27 (ankylosing spondylitis). The authors recall the frequency of HLA W 27 during ankylosing spondylitis, whether primary or associated with psoriasis, or enteric disease. Desensitisation to autologous saliva proved a failure. A trial of D-Penicillamine produced no beneficial effect on the course of the mucosal ulcers and the inflammatory joints.


[Gastric and pleural localization of Waldenström's disease]. The authors report a case of Waldenstrom's disease, the first sign of which, remaining for a long time the only sign, was a pseudo-carcinomatous infiltration of the stomach. Later, the patient developed a pleural localisation. These two lesions, gastric and pleural, are known but rare. The authors recall the main signs. They emphasize the long duration of the disease when treated by chlorambucil. A pathological IgM was found, not only in the serum of this patient, but also in the jejunal fluid aspirated during small intestinal biopsy.


[Isolated rupture of the chordae tendineae of the mitral valve]. The authors report a personal case of mitral incompetence, due to rupture of the chordae tendineae and note the signs of this disease. The patient first developed pulmonary oedema with thoracic pain, a mitral systolic murmur and a presystolic gallop rhythm, which suggested the diagnosis in a patient in sinus rhythm with a normal size heart, the left atrium was expansive and there were obvious signs of pulmonary congestion. The rapidly fatal course may be explained by the large number of ruptured chordae tendineae. Autopsy showed that the mitral valve was normal in texture. Histological study of the ruptured cord, showed lesions of dense hyaline fibrosis and mucoid infiltration of the basic substance.


[Brown-Sequard syndrome and extradural spinal cord hematoma in a patient taking antivitamin K]. The authors report a new case of extra-dural hematoma of the spinal cord due to anticoagulants causing a clinical Brown-Sequard syndrome. Spontaneous recovery, which was almost complete, appears quite exceptional.