[Generalized monkeypox in orally infected rabbits and white mice].

In the past 5 years 17 human cases of monkeypox with 4 deaths were reported in African countries. The source and the mechanism of transmission of the infection are unknown. One of the possible modes of human infection could be through monkey meat used for food. The paper presents the results of the study of susceptibility of 4 species of laboratory animals to monkeypox virus given orally. Adult rabbits, guinea pigs, and hamsters were found to be resistant. Ten-day-old rabbits and 8-, 10- and 12-day-old mice developed generalized infection with eruptions and high lethality. The infection was transmitted to uninfected rabbits of the same litter, apparently by air-borne droplet mode. The obtained model of generalized monkeypox infection after per os administration of the virus and the fact of air-borne droplet transmission of infection may serve as indirect evidence of the possibility of transmission of the infection by this mode in nature.


[Nature of membrane cellular antigens induced by avian leukosis-sarcoma viruses].

Using the immunofluorescent procedure and cross adsorption tests it was established that the common membrane cellular antigen coded for by avian sarcoma-leukemia virus genome could be found not only in Rous tumours of different animal classes but also in normal chick embryo cells after their propagation in vitro. The nature and function of the discovered antigen are discussed.


[Cancer chemotherapy of inoperable bronchial carcinomas (author's transl)].

The nowadays' therapeutic results in bronchogenic cancer are rather poor. However, chemotherapy-promises some improvements in remission rates and survival. These results are achievable as well as by mono and by polychemotherapy. The current clinical studies are aimed at optimal application regimes of the drugs beeing at hand. Cyclophosphamide, Methotrexate and Adriamycin are the most effective drugs for montherapy. Alkylants and Methotrexate are especially effective in the oat cell carcinomas. Many cases seem to be more benefited by polychemotherapy than by monotherapy. However, a randomized clinical trial is presented which shows that a montherapy with Adriamycin gave the same results as polychemotherapy. In the case of bronchogenic carcinoma a simultaneously given polychemotherapy is more effective than a sequentially given one. Novel approaches aiming at further improvement of therapeutic results should more consider individual tumour-biological parameters of the tumour-host relationships and possbilities of pharmacological influences upon hemostasis, tumour vascularisation and immunological defense system.


[Study of tissue culture herpes vaccine].

Features of propagation of 4 herpes simplex virus strains and their biological properties in the course of passages in chick embryo fibroblast cultures were studied. Investigations of experimental formalin-inactivated polyvaccine in animals and in trials in volunteers, patients with relapsing herpes, established its safety and sufficient effectiveness.


[Cell-culture-tests (oncobiograms) in 105 bronchial carcinomas (author's transl)].

Thirty-six oncobiograms (cell culture tests) of bronchial carcinomas are reported. One hundred forty-eight single tests showed a predominant cytostatic sensibility of the different squamous cell carcinomas and alluded to a special effectiveness of the alkylating chemotherapeutical agents, so that the oncobiogram may be able at the same time to support the polychemotherapy to day discussed and realized in all special branches.


[Difficulties with diagnosis of intrathoracic neurogenic tumors (author's transl)].

58 patients have been operated for neurogenic tumors of the mediastinum. Diagnostic problems are discussed. Some rare cases are presented: a neurofibroma of the n. vagus with mediastinal localization, a cavernous hemangioma, a leiomyoma and a fibrosarcoma; all of these imitating typical neurogenic tumors. The patient with the fibrosarcoma had several operations for recurrence of the histologically benign neurofibroma and died 4 years later of generalized fibrosarcoma. Because of this possible histological error all seemingly benign neurogenic tumors should be removed early.


[Biologic factors and malignancy in mediastinal neoplasms (author's transl)].

The clinical and histological diagnosis of mediastinal tumors has to be completed with an appreciation of the biological relationship between the tumor and its host. This is most important for neurogenic and thymic tumors. Successful removal is sometimes possible even after a long time of observation. Auxillary use of radiation and cystostatics is recommended.


[The reaction of the secretory elements of the mucosa of the upper respiratory tract from physiological and pathophysiological aspects (author's transl)].

The main function of the secretory elements of the mucosa of the upper respiratory tract - endoepithelial beaker cells and complex glands, exoepithelially situated - is surface defense. From this point of view ciliary system and secretion form a functional unit. Disorders of the synergism of the components may irreversible change the structure of the mucosa as demonstrated e.g. by the chronic forms of inflammation, when the limits of compensation are exceeded. The interrelation between epithelium and lamina propria are explained on the basis of histochemical evidence from normal and pathological mucosa of the upper respiratory tract. The metabolic processes between the vascular system and the cells form the basis of the normal as well as pathological secretion of the mucosa.


[Early IgM decrease in the serum of carcinoma patients with paraneoplastic skin manifestations].

The authors describe two patients suffering from cancer accompanied with paraneoplastic skin disorders (bullous pemphigoid, dermatomyositis). Before the diagnosis of stomach cancer was obtained by X-ray examination, the IgM-level was found lower than in normal persons. The value of the IgM-estimation in the serum seems to be high in the diagnosis of tumours. Other causes of the decreased IgM-level than tumours and paraneoplastic disorders of the skin were not found.


[Results of treatment with the Herpes simplex antigen Lupidon H, resp. Lupidon G].

The results of treatment with LUPIDON achieved by 215 dermatologists with reference to a total number of 1059 cases are reported taking into account the controlled evaluation of questionnaires. Due to the considerable number of patients and physicians involved in this clinical investigation the presuppositions for objectiveness in respect of statistical evaluation were especially favourable. The results of treatment with LUPIDON--LUPIDON H and LUPIDON G proved to be of equal effectiveness--can be denoted as very positive because of the good or very good effects that could be observed in more than 80% of all the cases concerned. Such a therapeutically favourable result refers primarily to Herpes labialis, Herpes genitalis and Herpes eruptions infesting trunk and head; other types of herpes disease, for example Herpes glutealis or stomatitis aphthosa were only improved to about 60%. The compatability of LUPIDON was striking. The rate of side-effects was at 3%. Moreover, other series of data are given with the intention to inform about criteria such as: Frequency of localisations with regard to Herpes simplex diseases; distribution according to sex of patients being suffering from Herpes labialis and Herpes genitalis; distribution according to age; duration of Herpes simplex before starting a treatment with LUPIDON; accompanying skin diseases.


[Moebius' syndrome and Poland's anomaly (author's transl)].

The syndrome of Moebius and Poland's anomaly have some features in common. The malformations of the limbs-especially those of the fingers (brady-, syn-, symbrachydactyly)-are identical in both disorders. Hypoplasia of the m. pectoralis major, characteristic for Poland's anomaly, may accompany Moebius' syndrome and cerebral nerve pareses may be associated with Poland's anomaly, thus distinction between the two disorders may be impossible. Both disorders affect the embryo at the same gestational age and the causative factor is unknown in either of them. Simultaneous evaluation of findings observed in patients suffering of either condition should be performed to elucidate pathogenesis and aetiology.


Spectrometric and biological data of 1, N6-ethenoadenosine 3', 5'-cyclic monophosphate.

Spectroscopic properties of 1, N6-ethenoadenosine cyclic 3', 5'-monophosphate were studied and compared with cyclic adenosine 3', 5'-monophosphate. Date of nuclear magnetic resonance-, mass-, ultraviolet-, and fluorescence spectroscopy were given. Additionally biochemical activity was tested in protein kinase system of beef adrenals. No significant biological difference between cyclic adenosine 3', 5'-monophosphate and its fluorescent analog has been found.


Mixed monomolecular films of chlorophyll and cytochromes.

Mixed monomolecular films of cytochrome (Cyt) and chlorophyll (Chl) were spread at a nitrogen-water interface. A large interaction is observed between reduced Cyt f and Chl a in a mixed film. Oxidized Cyt f and Chl a in a mixed film show little evidence for interaction. Mixed monomolecular films of Chl a with either reduced or oxidized Cyt c appears to result in denaturation of the protein at the surface. A light reaction is observed only in mixed films of reduced Cy f and Chl a.


[On the determination of coffeine in soft drinks and coffeine-containing food preparations (author's transl)].

The recently proposed spectroscopical determination of coffeine in soft drinks after filtration of polyamide leads to higher coffeine values than originally present, due to substances absorbed by the UV light. Therefore a method is proposed for identification and quantitative determination of coffeine in soft drinks and in methanol extracts of coffeine-containing foods by column chromatography on silical gel.


[Light and electron microscopie examination of a case of primary liver carcinoma in an infant (author's transl)].

The course of an infantial liver carcinoma is reported. Two liver biopsies and autopsy material were studied by light- and electron microscope. The histological findings and the clinical data are discussed. The first biopsy taken from the liver showed glycogen storage within the hepatic cells. It is suggested that this phenomenon is consistent with the preblastomatous stage of the liver cells. This fact is supported also by experimental way. The detection of this glycogen storage could be used as an early sign of the liver cancer in childhood, and might stress an early surgical intervention.


[Medical evaluation and rehabilitation following intensive therapy of malignomas in the female genitalia and breast].

The selective therapy of malignant tumours of the female genital tract has led to the abandonment of radical procedures in the treatment of early stages of carcinomas. The histological diagnosis, including tumour localisation, tumour grading, applied therapy, early and late complications are criterion to be taken into consideration in laying down the degree of infirmity. In the light of functional gynaecology, principles for such patients care are laid down, taking into account the time of disablement as well as problems of rehabilitation, not only for patients with malignant tumours of the female genitals but for those with mammary tumours as well.


[Effects of estrogenic hormones on blood lipids].

The authors have followed the effects of application of the deposit estradiolbenzoat on the blood lipides level of women at the beginning of menopause and women with arteriosclerosis. They have registered a moderate drop of the concentration of cholesterol, beta-lipoproteins, and slight changes of the non-esterified fatty acids level. Women using contraceptive hormonal mixtures were found with higher level of cholesterol in the blood serum than those being watched. The application of a single dose of androgen did not have any substantial effects on the blood lipides level.


[In vitro studies of the antiviral activity of enzymatically oxidized o-diphenolic compounds against herpes simplex virus type 1 and 2 (author's transl)].

Oxidation of the o-diphenolic compounds, catechol, protocatechuic acid, caffeic acid, and chlorogenic acid by o-diphenol oxidase (EC 1.10.3.1) resulted in compounds with antiviral activity against herpes simplex virus types 1 and 2. In the system HSV-1/rabbit kidney primary cells, a 90 per cent plaque reduction was obtained by the oxidation product from 1 mug caffeic acid, 9 mug catechol, 13 mug chlorogenic acid, or 20 mug protocatechuic acid (per ml), respectively. In comparision to the basic compounds or those oxidized in the presence of bovine serum albumin, the inhibitory effect of oxidized o-diphenolic compounds free from albumin was higher. From the basic o-diphenolic compounds, only catechol and caffeic acid showed remarkable antiviral activities in the system investigated. Although there have not experiments on the mechanism of action yet been the compounds are supposed to act during the earliest phases of the HSV-multiplication, because o-diphenolic compounds had been found to be present in the virus-cell system only 90 minutes after infection. In this respect the substances were similar to those of humic acids which also inhibit the adsorption phase of herpes simplex virus. There were no essential differences between herpes simplex virus type 1 and type 2 in respect of their sensitivity to enzymatically oxidized o-diphenolic compounds.


[About the influence of beta-toxin of Clostridium perfringens (type C) on the motorics of intestine segments (in vitro). I. Communication].

The Beta-Toxin of Clostridium perfringens (Type C) was introduced intra lumen to jejunum and ileum segments of rabbits, then examined by pharmacologic method (in vitro). The Beta-Toxin showed a paralysing activity on the motorics of the intestine which fact may be in relation to the paralysing activity of this toxin in dysenteria in piglets.


Drug controlled of Cushing's syndrome. Combined aminoglutethimide and metyrapone therapy.

Eighteen patients with Cushing's syndrome (16 pituitary-dependent Cushing's disease, 1 ectopic ACTH syndrome, 1 primary adrenal adenoma) were given a combination of aminoglutethimide and metyrapone, with the object of controlling cortisol overproduction using less toxic doses than would be required with each drug alone. A preliminary trial of this combination using doses of aminoglutethimide of 1 g or more a day was assessed over 2 weeks. Control of cortisol overproduction and clinical improvement was achieved but side effects led to withdrawal of the drugs in 6 out of the 12 patients. A lower dose trial of this combination over 2 weeks, using 750 mg/day of aminoglutethimide also controlled cortisol overproduction and side effects led to drug withdrawal in only 2 out of 6 patients. Four of these patients were successfully controlled with even lower doses (500-750 mg/day of aminoglutethimide) for longer periods (26 days-1 year). This low regimen which consists of aminoglutethimide 500-750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b.d. and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as a long-term treatment of milder cases.


Evidence for the adrenal source of androgens in precocious adrenarche.

In order to determine the source of androgens in precocious adrenarche, serum androgens were determined in 8 girls with precocious adrenarche and 5 agonadal children in adrenarche under conditions of adrenal and gonadal stimulation and suppression. All androgens increased with ACTH stimulation in both groups. Stimulability of serum androgens in girls with precocious adrenarche with ACTH was more consistent than in 13 prepubertal children. Human chorionic gonadotrophin administration increased serum delta4-androstenedione, testosterone and dihydrotestosterone in the girls with precocious adrenarche but not in the agonadal children, demonstrating the failure of HCG to stimulate adrenals. Dexamethasone suppression decreased levels of all androgens in both groups, whereas Norlutin or Ovral produced variable changes. These studies support the adrenal origin of androgens in precocious adrenarche and the lack of ovarian contributions in this condition.


Ovarian biochemical competence following gonadotrophic deprivation from birth.

Normal ovarian morphogenesis is impaired by the absence of gonadotrophic hormones from birth. In the present study, the following question was asked: Does gonadotrophic deprivation also affect ovarian biochemical competence? Newborn mice were treated daily with an antiserum neutralizing endogenous circulating gonadotrophins. At the age of 14 days, ovaries from these mice and control littermates were incubated in the presence and absence of gonadotrophic preparations; cAMP and lactic acid levels were then measured in tissue and incubation medium. Ovaries from anti-gonadotrophin treated and control mice had the same basal levels, per mg tissue, of cAMP and lactic acid. Moreover, the levels increased to approximately the same extent following in vitro gonadotrophic stimulation: an increase in cAMP of 8-10-fold (using a preparation with an hLH:hFSH ratio of 1:1) or 2 1/2-fold (using a preparation with an hLH:hFSH ratio of 1:5), and about a 2-fold increase in lactic acid (using oLH). The acute effect of gonadotrophins on ovarian glycolysis, reported up till now only in the rat ovary, is the first such demonstration in mice. The results also indicate that despite impaired morphogenesis, the enzymatic systems necessary for ovarian glycolysis (as measured by lactic acid production) and cAMP formation can develop without gonadotrophic participation. Furthermore, ovarian capacity to respond to hormonal stimulation is acquired post-natally, as shown by refractoriness to gonadotrophic stimulation during the first week of life. Finally, post-natal gonadotrophic exposure does not seem an essential requirement, at least as measured by the above parameters, for acquiring ovarian competence to respond to hormonal stimulation.


Herpesvirus in bladder cancer.

A case of squamous cell carcinoma of the urinary bladder in which herpesvirus virions could be identified by electron microscopy is presented. The value of cytology in the recognition of the typical intranuclear inclusions which led to the initiation of further studies is emphasized. Recent evidence concerning the relationship between herpesviruses and human cancer is briefly reviewed. Although previous reports have emphasized the association of HSV and uterine cervical carcinoma, other combinations, especially with neoplasms of squamous cell type, have been reported. The accumulation of additional cases in which viruses can be demonstrated in cancers will help to define their role in human neoplasia.


The response of the immature rat ovary to gonadotrophins: acute changes in cyclic AMP, progesteron, testosteron, androstenedione and oestradiol after treatment with PMS or FSH + LH.

Radioimmunoassays were used to measure changes in progesterone, testosterone, androstenedione, oestradiol, gonadotrophin and ovarian cyclic AMP in immature female rats during the first 24 h after exposure to slowly (PMS) or rapidly (FSH + LH) disappearing gonadotrophins. Cyclic AMP was increased 30 min after injection of either kind of gonadotrophin but it had returned to control level within 4 h. Serum and ovarian testosterone and androstenedione also increased to a peak at 30 min but decreased to base line by the 4th h. Multiple injections of FSH + LH maintained an elevated serum testosterone level but they had little effect upon the secretion of androstenedione. Serum and ovarian progesterone increased quickly after treatment with gonadotrophin. With PMS the peak in the serum was reached at 8 h, it remained high for 4 h and then fell precipitously between the 12th and 16th h. FSH + LH produced a prompt increase in serum progesterone but the level could be maintained only by repeated doses given every 4 h. Oestradiol was not increased in the serum or the ovot produce an increase in oestrogen but a transient increase was found with 3 doses; 4 doses kept an elevated level of oestradiol for 12 h. These results indicate that the aromatizing system of the immature rat ovary is relatively inactive and that continual stimulation by gonadotrophin for about 10-12 h is necessary to bring about increased function. In contrast, the mechanisms for the synthesis and secretion of progesterone and androgens are vary active and can be immediately stimulated by exposure to gonadotrophins.


Alpha 1-antitrypsin phenotypes in cirrhosis and hepatoma.

The phenotypic distribution of alpha-1-antitrypsin variants has been studied in 101 patients with cirrhosis and in 50 with cirrhosis plus hepatoma. 504 healthy Greeks served as controls. The ZZ and MZ phenotypes were found only once in the group of cirrhosis. The very low PiZ gene frequency suggests that the association of PiZ gene with cirrhosis is fortuitous. The FM phenotype has been observed in 14% of patients with hepatoma arised on cirrhosis and this incidence differed significantly between the two groups of patients and the controls. It is possible that cirrhotic patients phenotypically FM develop for as yet unknown reasons hepatoma in high percentage.


[Histochemical and histological studies on the vagina of pigs with in various phases of the estrus cycle (author's transl)].

During estrus (1st day) the vaginal epithelium is highly proliferated; its thickness amounts up to 20 cell layers and even more. During metestrus (3rd day) the epithelium measures 12 to 15 layers due to degeneration and desquamation. During diestrus a further decrease in height is noticed. During late diestrus (16th day) the epithelium reaches its minimal height with 3 to 5 layers. The stratum superficiale consists during this phase of tall columnar cells. Starting from day 18 proliferation begins again. During all phases of the genital cycle the presence of infiltrated leucocytes is highest during middle and late diestrus. Leucocytes are easily recognized by their strong reaction for alkaline phosphatase whereas the epithelium proper remains negative. Mucification in the porcine vaginal epithelium is but moderate. Mucous substances occupy from from proestrus to early diestrus the intercellular gaps in the adluminal half of the epithelium. During middle and late diestrus mucous substances are localized in the supranuclear region of the superficial columnar cells. Histochemical tests for enzymes of oxidative pathways give relatively uniform and weak results during the entire cycle. Fluctuations of epithelial esterase activity may be correlated with phases of proliferation and differentiation.


[Effect of phenobarbital stimulation on morphological and cytoenzymatic changes in the liver of benzene intoxicated rats (author's transl)].

The experiments were carried out on male Wistar-Rats. They were divided into 2 groups. The rats of the control groups were treated to Phenobarbital intraperitoneally for 3 consecutive days. The animals of the experimental group were additionaly injected with Benzen intraperitoneally on the 4th day of experiment. It has been found that Phenobarbital brought about the formation of 2 types of bright and dark cells in the liver. The action of Phenobarbital is carried on by Benzene. The authors discuss morphological and functional evaluation of bright and dark cells from the point of view of stimulating action of Phenobarbital as well as the course of Benzene biotransformation in liver cells.


Parkinson's disease: distribution of Lewy bodies and monoamine neuron system.

A systematic study of the central and peripheral nervous systems in 3 cases of Parkinson's disease has demonstrated that Lewy bodies are present in 27 nuclei. Of these 20 nuclei (12 pigmented and 8 unpigmented) are involved in 2 or all 3 cases. It is noticed that the distribution of Lewy bodies in Parkinson's disease described here corresponds surprisingly well to that of monoamine (dopamine, noradrenaline and serotonin) cell bodies demonstrated in rats by the histochemical fluorescence method. This correlation is similar to that of Alzheimer's neurofibillary changes in postencephalitic Parkinsonism as described by Ishii. Inasmuch as these viewpoints are also in agreement with preciously reported biochemical data on Parkinsonism, it is suggested that Parkinsonism (idiopathic and postencephalitic) should represent a system degeneration of monoamine neuron systems.


Retinal lipidosis in albino rats treated with chlorphentermine and with tricyclic antidepressants.

Retinal pigment epithelium is known to be engaged in continuous phagocytosis and digestion of old discs of visual cell outer segments, which have a high phospholipid content. The present ultrastructural study was focused mainly on the effects, upon pigment epithelium, of several drugs that are thought to interfere with the enzymatic degradation of phospholipids. Albino rats received high oral doses of chlorphentermine, iprindole, 1-chloroamitriptyline, imipramine, or clomipramine. After treatment for several weeks the pigment epithelial cells were doubled in height due to deposition of excessive amounts of abnormal cytoplasmic inclusions which had a crystalloid substructure. Such inclusions which are known from previous studies to be associated with drug-induced phospholipid storage are suggested to contain nondigestible phospholipids, which in pigment epithelium originate mainly from phagocytosed outer segment discs. The alterations were reversible by withdrawal of the drugs. The functional implications of the epithelial alterations remain to be elucidated. Additional examination of the neuroretina revealed numerous abnormal inclusions, mainly of multilamellated structure. Ganglion cells were affected most. The neuroretinal alterations were reminiscent of those described in human cases of inherited lipidoses.


Inclusion bodies in brain cell cultures from Creutzfeldt-Jakob disease.

Brain cell cultures were established from 20 patients with various forms of dementia and studied for evidence of virus induced alterations. Changes were detected in the cultured cells from 1 patient (L.C.) with the clinical and pathological diagnosis of Creutzfeldt-Jakob disease. These changes were present in the early passages of the brain tissue and were not seen in the cultures from the other cases.


Primary angle-closure glaucoma. Oculometry, epidemiology, and genetics in a high risk population.

The ocular dimensions in patients suffering from primary angle-closure glaucoma (a.c.g.) have been studied in several clinical series, chiefly in Caucasians. The epidemiology and aetiology of a.c.g. are less well known although genetic factors seem to be involved. Eskimos have recently been shown to constitute a high risk population with respect to a.c.g. Consequently, a series of oculometric, epidemiologic, and genetic studies among Greenland Eskimos was undertaken. Besides the immediate purpose, prevention of blindness in this population, the survey had important general aspects and the following main results were obtained: 1a) Ocular dimensions, as well as clinical symptoms, in Eskimo a.c.g. patients correspond closely to those of a.c.g. reports from other ethnic groups and 1b) ocular dimensions of the anterior segment in the general Eskimo population deviate conspicuously towards the low level characteristic of all samples of a.c.g. patients. 2) A.c.g. prevalence rates were estimated at 1.6% in males and 5.1% in females of the general population aged 40 years or more. The epidemiology of a.c.g. seems to reflect closely the variations of axial anterior chamber depth (ACD) according to race (Eskimo, Caucasian), sex and age. Empirical a.c.g. risk estimates, depending on the ACD value, were obtained in elderly females. 3) A relatively shallow chamber was found in 1st and 2nd degree relatives of a.c.g. patients, in close agreement with an earlier study in Caucasians (Törnquist 1953). However, also in the general Eskimo population a pronounced familial resemblance with respect to ACD and corneal diameter was found. Thus the family studies indicate that the size of the anterior chamber shows a mainly genetic determination, which probably constitutes the genetic basis of a.c.g. as well. With this background a hypothesis is discussed, which interprets the small anterior chambers in Eskimos as a result of genetic adaptation to arctic environment. Corneal protection may have been the significant advantage and the a.c.g. load in elderly persons a relatively less important cost.


Synovial sarcoma: a case report.

The case described, of a 40-year-old woman with a 26-year history of a chronic, non-specific knee disorder, is a rather typical example of synovial sarcoma, according to the information given by other authors over the past three to four decades. The diagnostic difficulties and failures are clearly illustrated. It must be emphasized that severe, obscure joint symptoms such as our patient presented over the many years before death should have led to a proper surgical exploration of the knee. Furthermore, it should be unnecessary to stress the importance of performing a histological examination whenever excising abnormal tissue.


Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia.

A deficiency of extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase has been demonstrated in a boy with severe, persistent neonatal hypoglycaemia. Hepatic glucose-6-phosphatase, fructose-1.6-diphosphatase and pyruvate carboxylase were normal. The total activity of phosphoenolpyruvate carboxykinase was also normal, but the enzyme showed an abnormal subcellular distribution, virtually no activity being detected in the extramitochondrial fraction of a liver homogenate. The boy died at the age of 2 years 10 months. Autopsy revealed severe cerebral atrophy, atrophy of the optic nerve, and fatty infiltration of liver and kidney.


GH, ACTH, LH and FSH behaviour in the first seven days of life.

--43 neonates, born vaginally after spontaneous labor between the 38th and the 42nd week of pregnancy, were examined. GH and ACTH levels were assayed in 14 newborn infants. LH and FSH were determined in the remaining 29 patients (16 boys and 13 girls). Samples were collected from all infants for the assay of the above mentioned hormones at the 2nd, 6th, 12th and 24th hour of life, then every day for 7 consecutive days. During the whole first week of life plasma GH gave values that were significantly higher than those found in subjects over four years of age. The highest mean value of plasma ACTH was found at the 2nd hour of life (162.2 +/- 34.1 pg/ml). Then, there is a significant fall in the hormone level beginning with the 12th hour (p less than 0.01). Minimum level was reached on the 7th day. Plasma hCG-LH presents its maximum mean value at the 2nd hour, both in boys and girls (48.5 +/- 16.2 and 33.0 +/- 24.9 mU/ML, respectively). after this, plasma hCG-LH decreases progressively. No significant differences between the two sexes were found. Even though the mean values of plasma FSH do not change significantly during the whole test period, they do demonstrate a sex difference (significantly higher values in the females) from the fifth day afterwards.


Neonatal hypertriglyceridemia: a new index of antepartum-intrapartum fetal stress?

The 95th percentile value of cord serum triglyceride concentration in 82 consecutively live born infants was found to be 0.79 mmol/l. This level was arbitrarily used to define neonatal hypertriglyceridemia. A comparison between 78 normotriglyceridemic and 61 hypertriglyceridemic newborn infants showed a significant association between elevated cord serum triglyceride concentration and insufficiency of the placenta, fetal bradycardia, meconium-stained amniotic fluid and one-minute Apgar score less than or equal to 7. A significantly (p less than 0.001) greater number of infants with one or several of these four factors, indicating antepartum and/or intrapartum fetal stress were found to be hypertriglyceridemic at birth. This finding suggests that estimation of cord serum triglyceride which is easy and inexpensive might be of value for a more complete evaluation of the newborn infant, and can serve as a supplement to the Apgar Score system.


Congenital hyperparathyroidism and vitamin D deficiency secondary to maternal hypoparathyroidism.

A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 mulEq/ml (Normal: less than 50 mulEq/ml). A very low plasma 25-OH-D concentration (less than 4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remained high 3 weeks before (210 mulEq/ml) were found to be normal one week after this vitamin D load (37 mulEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.


Acute facial palsy. Some clinical and virological observations.

A prospective clinical and virological study on 44 patients with acute, peripheral facial paralysis was carried out in consecutive cases during one year. In 9 cases varicella-zoster infections were serologically established. In 5 additional patients an associated varicella-zoster, or herpes simplex, infection was possible. Of the 9 confirmed cases, 6 were clinically diagnosed as zoster oticus, whereas on clinical grounds, 3 were regarded as Bell's palsy. No evidence was obtained of associated enterovirus, mumps, measles, cytomegalovirus, tick-borne encephalitis virus, para-influenza virus, mononucleosis or Mycoplasma pneumoniae infection.


Ceroid-like histiocytic granuloma of gall-bladder --a previously undescribed lesion--.

In the present study, 13 cases of a peculiar gall-bladder granuloma characterized by marked proliferation of ceroid-filled brown histiocytes were pathomorphologically, histochemically and ultrastructurally examined to define the pathologic features of such a lesion previously undescribed in the literature. The lesion grossly showed a granulomatous appearance of yellow brown to dark brown color developing in the wall of gall-bladder. Histologically, there was proliferation of histiocytes containing abundant brown pigment granules in their cytoplasm. The pigment granules proved to have staining characteristics closely resembling those of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic osmiophilic inclusions of heterogenous materials. With regard to the pathogenesis of this granuloma, it may be suggested that lipid components of bile juice, particularly unsaturated fatty acids and phospholipids, play an important role as a source of ceroidogenesis in the proliferating histiocytes.


An ultrastructural and histochemical study on bone lesions of Hand-Schüller-Christian disease.

A correlated light microscopical, histochemical and ultrastructural study was made on bone lesions repeatedly biopsied from three patients with Hand-Schüller-Christian disease. The histiocytic cells proliferating in the early lesions had a markedly indented nucleus and contained in their cytoplasm varying numbers of Langerhans cell granules and round or irregular-shaped lipid droplets. Histochemically, the lipid droplets were verified to the lipo-protein rich in fatty acids. Such histiocytic cells differ from highly phagocytic histiocytes or macrophages because of indistinct phagocytotic activity, and are regarded as a metabolic type of histiocytes. The late lesions were mostly dominated by a xanthogranulomatous tissue chiefly comprised of xanthoma cells and collagen fibers. The xanthoma cells were usually filled with numerous lipid vacuoles which were histochemically proved to mainly contain cholesterol. Almost all the xanthoma cells were closely attached to collagen fibers and often had well-developed rough endoplasmic reticula. Ultrastructurally, it is suggested that the xanthoma cells are originated from fibroblasts or fibrocytes. As an important factor to induce proliferation and xanthoma cell transformation of fibroblasts in the late phase, the presence of such a lipoprotein produced in the histiocytic cells of the early phase is emphasized.


Release of adenosine-like material from isolated perfused dog adipose tissue following sympathetic nerve stimulation and its inhibition by adrenergic alpha-receptor blockade.

Following the intraarterial infusion of 3H-adenine to isolated perfused canine subcutaneous adipose tissue, its adenine nucleotides are labelled. A continuous release of radioactivity, comprised of non-nucleotide material, was observed. The rate of this release was markedly enhanced by sympathetic nerve stimulation. The major components of the enhanced release appeared to be inosine and adenosine. Adrenergic alpha-receptor blockade (phentolamine or Hydergin) abolished the enhanced nucleoside release, while glycerol release was enhanced. The release of radioactivity was decreased during mechanical blood flow reduction and enhanced afterwards. However, the magnitude of this enhancement of release after clamp was much less than following nerve stimulation. The results suggest that adenosine or a closely related compound is released from canine subcutaneous adipose tissue by sympathetic nerve stimulation and that the release is related to adrenergic alpha-receptor stimulation. Since adenosine is a potent inhibitor of catecholamine induced lipolysis in this tissue the possibility of a regulatory role must be considered.


Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. III. Effects from supraspinal pathways.

Supraspinal effects were investigated in interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as Ia inhibitory interneurones). It was revealed that volleys in the vestibulospinal tract may evoke mono- and disynaptic EPSPs in interneurones monosynaptically excited from extensor muscles, i.e. extensor coupled Ia inhibitory interneurones. Flexor coupled interneurones instead received disynaptic inhibition. Volleys in the rubrospinal tract evoked a dominating polysynaptic excitation, usually mixed with inhibition, in flexor as well as extensor coupled interneurones. Disynaptic rubrospinal EPSPs and IPSPs were also revealed. The pyramidal tract also gives rise to a dominating polysynaptic excitation, usually mixed with inhibition, in flexor as well as extensor coupled Ia inhibitory interneurones. Rubrospinal and pyramidal volleys were shown to facilitate transmission in various segmental reflex pathways to the Ia inhibitory interneurones. A detailed comparison reveals a striking parallelism of segmental and supraspinal effects on alpha-motoneurones and Ia inhibitory interneurones connected to the same muscles. This considerably strengthens the hypothesis of an "alpha-gamma-linkage in the reciprocal inhibition".


Effect of strength training on enzyme activities and fibre characteristics in human skeletal muscle.

Progressive strength training was performed 3 times a week for 8 weeks by 14 male students (19-31 yrs.). The training program consisted mainly of dynamic exercises for the leg extensors with maximal or close to maximal loads. The training caused significant improvements in dynamic and isometric strength. One repetition maximum in squats increased with 67%, Sargent jump with 22%, and maximal voluntary isometric contraction (MVC) with 13%, respectively. Body weight and leg muscle circumferences remained unchanged after training, whereas total body potassium, lean body mass and calculated total muscle mass increased, suggesting a change in body composition with training. Muscle biopsies were obtained from vastus lateralis for fibre analyses and determination of enzyme activities. There were no changes in muscle fibre composition or fibre area with training. The activities of Mg2+ stimulated ATPase, creatine phosphokinase and phosphofructokinase remained unchanged, whereas myokinase activity was increased after training from (1.41 to 1.52 moles x 10(-4) x g-1 x min-1, p less than 0.05). After training significant correlations (p less than 0.01) were demonstrated between Mg2+ stimulated ATPase activity and % fast twitch fibres (% FT) (r = 0.67), as well as between myokinase activity and % FT (r = 0.86).


Mitochondrial cytochrome concentrations in rat heart and liver as a consequence of different hypoxic periods.

Rat heart and liver cytochrome concentrations were determined after three hypoxic conditions (atmospheric pressure 50.5 kPa, 40.8 kPa and 38.0 kPa) lasting one week and two weeks. The heart showed clear hypertrophy which was 38% in most severe hypoxia (38 kPa, 2 weeks). A small decline in the liver weight to body weight ratio was observed, this decrease being 21% in the most severe case. During the hypoxic periods the mitochondrial cytochrome concentration decreased. This phenomenon was more obvious when the degree of hypoxia was increased and more pronounced after 2 weeks than one week. The heart and liver showed quite similar patterns in this respect. In most severe hypoxia the decreases in the liver were 29% for cytochrome aa3, 30% for cytochrome b, 20% for cytochrome c and 15% for cytochrome c1, with the concentrations expressed on mitochondrial protein basis. The corresponding values in the heart were 31%, 43%, 28%, and 22%. It can be concluded that in mammals the mitochondrial cytochrome content probably varies according to the amount of oxygen available.


Mechanical and metabolic effects of beta-receptor stimulators, the C-terminal octapeptide of cholecystokinin, and prostaglandin E2 on the isolated, depolarized sphincter of Oddi.

Similar to their actions on normally polarized, isolated sphincter of Oddi, the beta-receptor stimulators isoprenaline and tebutaline, and prostaglandin E2 produced relaxation of the depolarized preparation. The relaxation was accompained by an increase in the intracellular content of cyclic AMP. In contrast to its relaxing effect on normally polarized sphincter preparations, the C-terminal octapeptide of cholecystokinin (C8-CCK) contracted or had no effect on the depolarized sphincter. There was no change or a small decrease in the content of cyclic AMP in the muscle. It is suggested that the relaxing effects of beta-receptor stimulators and prostaglandin E2 on isolated sphinceter of Oddi, and the simultaneous increase in cyclic AMP-content are mediated processes independent of the electrical acitivty of the membrane. However, C8-CCK mediated relaxation and increase in cyclic AMP is dependent on the membrane potential.


Effects of emulsified iodo-lipids. A toxicologic investigation in the rabbit.

Two different iodized oil emulsion have been intravascularly injected into rabbits, one with a particle size of 15 mum or more and one with a size of about 1 mum. The effects of the emulsions have been evaluated on the brain, the heart, the kidney, the liver and the circulation. The reactions to the small particle emulsion was minor, especially if administered slowly. The injection site was of critical importance. The safest place for injection was the superior mesenteric artery. If supplied directly to the brain or the heart the emulsions were often deleterious, particularly the coarse one.


Whole-body autoradiography of 99Tcm-labelled pyrophosphate and related compounds in young rats.

The distribution of 99Tcm-labelled pyrophosphate in young rats was analysed by wholebody autoradiography and compared with those observed for 99Tcm-pertechnetate, 32P-labelled pyrophosphate and 85Sr-chloride. 99Tcm-labelled pyrophosphate was rapidly accumulated in bone and dentine and was similar to 32P-labelled pyrophosphate and 85Sr-chloride. The uptake of these substances in developing enamel was rather low in contrast to 99Tcm-pertechnetate, which had no affinity for bone.


Electron microscopy of Rous sarcoma virus genome RNA and its heat-dissociated subunits.

Native and heat-treated RNAs from the purified Schmidt-Ruppin strain of Rous sarcoma virus (RSV) were fractionated by sucrose density gradients in the presence of ribonuclease inhibitor diethyl-pyrocarbonate and observed by electron microscopy. The structure of native 60-70S RNA was classified into two forms: tanglefolded type and linear type. In the tangle-folded type double stranded portions were observed in several sites. A high frequency of 60-70S RNA were 1.0 mum and 3-3.5 mum in length. Molecules with length about 9mum were of the tangle-folded type while molecules shorter than 6 mum were of the linear form. The structure of heat-treated RNA(30-40S) was linear with the most frequent length being 1-1.5 mum. These results indicate that native 60-70S RNA is folded with the total molecular length being in the order of 6 to 9 mum. Molecules about 3mum long are likely to be the main subunits of 60-70S RNA, and they are fragmented further into smaller subunits of about 1 mum length.


Avian myeloblastosis virus-induced lymphosarcoma producing erythroblastic leucosis in chicks.

Acute myeloblastosis and several forms of tumor, including one case of lymphosarcoma occurred when avian myeloblastosis virus (BAI-A strain) was inoculated into newly hatched chicks (SPF). The homogenate of lymphosarcoma inoculated intraperitoneally into other newly hatched chicks induced a high incidence of erythroblastic leucosis. Electron microscopy did not reveal the presence of C-type virus particles in the tumor tissue. The relationship between avian myeloblastosis virus, lymphosarcoma and erythroblastic leucosis is discussed.


The effect of antilipolytic agents on cyclic AMP, free fatty acid and total catecholamine concentrations in plasma.

Plasma concentrations of adenosine 3':5' cyclic monophosphate (cyclic AMP) and free fatty acids have been measured in 15 patients with acute myocardial infarction and in 6 dogs given infusions of isoprenaline. Plasma total catecholamines were also estimated in the patients. Inhibition of adipose tissue lipolysis with a nicotinic acid analogue did not decrease plasma cyclic AMP concentrations, either in the patients or when elevated in the dogs, thus suggesting that this tissue is not a major source of the nucleotide in plasma.


Production of 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-14beta-ol-17-ones and 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-17alpha-ol-14-ones by microbial enzymes.

For the purpose of producing hydroxy-keto-seco-steroids in which hydroxyl group is attached to a carbon atom having the R-configuration, numerous biochemically active microorganisms were tested without any success. The hydroxysteroid oxidoreductase enzymes of the investigated bacterial, yeast and fungal strains were suitable only for the production of 17beta-ol-14-one and 14alpha-ol-17-one derivatives. The required compounds were prepared by combinations of enzymatic reactions with chemical reduction. (i) By hydroxysteroid oxidoreductase of Saccharomyces uvarum and Saccharomyces drosophilarum, 17beta-ol-14-one and 14alpha-ol-17-one derivatives of 14,17-dione, respectively, were obtained. (ii) The above compounds were acetylated then reduced by sodium borohydride. (iii) 14beta,17beta-diol-17-acetate and 14alpha,17alpha-diol-14-acetate were dehydrogenated by dehydroxysteroid oxidoreductase of Nocardia sp. and Mycobacterum sp., respectively, in the presence of steroid esterase. The reaction mixture contained either 14beta-ol-17-one or 17alpha-ol-14-one derivatives, since oxidation by hydroxysteroid oxidoreductase was limited to the hydroxyl group attached to a carbon atom having the S-configuration.


17Beta-hydroxysteroid dehydrogenase activity in Streptomyces hydrogenans.

Streptomyces hydrogenans converts 17beta-hydroxyandrost-4-ene-3-one (testosterone) to androst-4-ene-3,17-dione (androstenedione) in good yields. Time-dependence of the conversion, steroid uptake and release have been studied in vivo. Steroid analysis was done by thin-layer chromatography and recrystallization to constant specific radioactivity. After sonification of the cells the postulated 17beta-hydroxysteroid dehydrogenase activity was recovered in the 105 000 g supernatant. The enzyme was enriched by gel filtration on Sephadex G-200. It required NAD+ as cofactor. Its activity could be studied photometrically, because there are no further testosterone-netabolites. If S. hydrogenans was cultured in the presence of testosterone, estradiol or 5alphaH-dihydrotestosterone, the activity of 17beta-hydroxysteroid dehydrogenase increased.


Apo-lipoprotein localization in human atherosclerotic arteries.

A study documenting the localization in human arteries of apoproteins from human plasma high density (HDL, low density (LDL), and very low density (VLDL) lipoproteins was undertaken in light of their possible roles in the pathogenesis and regression of the atherosclerotic process in man. Apo A-I from HDL, apo B from LDL, apo C-III from VLDL were all localized by immunohistochemical techniques to generally the same areas of athersclerotic lesions. These consisted of certain bands of collagen and elastic fibers in fatty streaks and fibrous plaques, and extracellular pools of neutral lipid in fibrous plaques. Apoproteins were also occasionally present in areas of diffuse intimal thickening in coronary arteries. Extensiveness and frequency of appearance of apo B in atherosclerotic lesions was greatest in type II hyperlipoproteinemics, thus correlating with the plasma apo B levels. Employing an immuno-peroxidase procedure, apo B was localized ultrastructurally in atherosclerotic lesions to the outer surface of spheres ranging in diameter between 250 and 700 A. These spheres, localized predominantly in lipid cores and between collagen bands, were also seen in negatively-stained preparations of arterial extracts which also reacted positively against anti-apo B, SUGGESTING THAT THE SPHERES MAY REPRESENT NATIVE LDL and VLDL. The superimposed localization of apo A-I, apo B, and apo C-III in atherosclerotic lesions suggests that a specific interaction exists between certain lesion components and these apoproteins.


Rabbits as a model for the study of hyperlipoproteinemia and atherosclerosis.

Lipoproteins of normal and cholesteremic plasma were compared in New Zealand White (hyperresponder) and Dutch Belt (hyporesponder) rabbits. Three major differences were observed between the strains: (1) New Zealand White rabbits developed much higher plasma levels of very low, intermediate, and low density lipoproteins after cholesterol feeding; (2) Dutch Belt rabbits, normal and cholesteremic, had higher ratios of the more dense high density lipoproteins HDL3 (d 1.125-1.20 g/ml) to the less dense HDL2 (d 1.081-1.125 g/ml); (3) cholesteremic Dutch Belt rabbits had higher plasma levels of the more dense HDL3 subfraction than did cholesteremic New Zealand White rabbits. Cholesteremic very low density lipoproteins of both strains are large particles of beta electrophoretic mobility that are rich in cholesteryl esters and an arginine-rich apolipoprotein(s). The intermediate and low density lipoprotein fractions were similarly altered in composition, although the proportion of arginine-rich protein to total protein was ledd than in the very low density fraction. Although the high density lipoproteins were greatly decreased in concentration in cholesteremic plasma, no major changes in their apolipoproteins were seen in either strain of rabbits. The major high density apolipoprotein of rabbits occurs in two electrophoretically separable forms and is similar to human apo A-I. Six minor apolipoproteins were isolated from the high density lipoproteins; some of these occur also in other density fractions.


Turnover and aortic uptake of very low density lipoproteins (VLDL) from hypercholesteremic rabbits as a model for testing antiatherosclerotic compounds.

VLDL from hypercholesteremic (HC) rabbits display features which are suggestive of inherent atherogenicity. The lipid composition, compared to that of control VLDL, shows an enrichment of cholesterol esters, which have a very high 18:1/18:2 ratio in their fatty acids, and an increased sphingomyelin content, with decreased PC/Sph ratio. This lipid composition is very similar to that of the atherosclerotic plaqua. Apoprotein peptides of HC VLDL show a predominance of arg-rich proteins, similar to human conditions (Type III hyperlipoproteinemia and hypothyroidism) characterized by early and severe atherosclerosis. Turnover of 125I-labelled HC VLDL is significantly slower than that of control VLDL, both when the lipoprotein is injected into the donor animals and into controls. Conversion of HC VLDL into lipoproteins of higher density is also very small, as compared to control VLDL. Uptake of radioactivity into the aortic wall after injection is about doubled, as compared to control VLDL, when HC rabbits receive HC VLDL. This experimental model suggests that structural modifications of the HC VLDL make them poorly metabolizable, and possible more akin to the recently described arterial lipoprotein complexing factor (ALCF). Metformin was selected as the test compound, because it has been shown to decrease aortic and liver lipid accumulation in cholesterol fed rabbits, while only slightly affecting plasma cholesterol levels. VLDL from rabbits fed cholesterol and metformin (HC+Met), while still enriched in cholesterol esters, have a higher protein content, less sphingomyelin and more phosphatidylethanolamine and phosphatidylinositol than HC VLDL, while fatty acid composition of cholesterol esters does not differ. Turnover of HC+Met VLDL is extremely rapid, with a t1/2 even shorter than that of control VLDL.


High volume screening procedures for hypobetalipoproteinemic activity in rats.

We describe high volume screening tests for hypobetalipoproteinemic agents in which compounds are administered orally to cholesterol-cholic acid fed (hypercholesterolemic( or normally fed weanling rats for 4 days. In these tests total serum cholesterol levels and heparin precipitating lipoproteins (HPL) are determined by automated analyses interfaced with a computer which eliminates all manual data reduction and provides necessary reports. The hypercholesterolemic rat test detects compounds which specifically reduce HPL (beta and pre beta lipoproteins) causing a decrease in the HPL: cholesterol ratio. Such activity is called hypobetalipoproteinemia. This activity is exhibited by bicyclo (2.2.2)-octyloxyaniline (U-26328) but not by any of the familiar hypocholesterolemic agents including clofibrats, lifibrats, nicotinic acid, probucol, triparanol, lentysine, D-throxine or the estrogens estrone and diethylstilbestrol.


Biological activity of a hypobetalipoproteinemic agent.

A new -ind of pharmacologic activity called hypobetalipoproteinemia is described. Iperationally the activity consists of a marked reduction of heparin precipitating lipoproteins (beta and/or pre-beta electrophoretic mobility) in hypercholesterolemic animals with a simultaneous decrease in the heparin precipitating lipoprotein: cholesterol ratio. As determined by ultracentrifugal fractionation of the lipoproteins from hypercholesterolemic rat serum, this activity consists of both a reduction in heparin precipitating lipoproteins and an increase high density lipoproteins that are not precipitated by heparin. Changes in composition were also induced in both lipoprotein fractions. The greatest changes were observed for free and esterified cholesterol, which were markedly reduced in the heparin precipitating lipoproteins and concomitantly increased in the high density lipoproteins. The hypobetalipoproteinemic agent exhibiting this activity is 1-[p-(1'-adamantyloxy) phenyl]-piperidine (U-41792). This agent is active in hypercholesterolemic rats, mice, quail, and pigeons.


Nonisotopic method for estimating cholesterogenesis in the rat.

Influence of several compounds on sterol production was determined from serum desmosterol (D) levels in rats treated with U-18666A:3beta-(2-diethylaminoethoxy) androst-5-en-17-one HCl. U-18666A blocks biosynthesis of cholesterol (C) by inhibiting conversion from D to C. Diets containing C (2%), the bile acid sequestrant colestipol HCl (1%), clofibrate (0.2%), combination of colestipol HCl and clofibrate, or basal diet were fed to normal or U-18666A (3 mg/kg/d) mald rats for 2 weeks. In normal rats, C feeding increased serum C levels (39%), colestipol HC l had no significant effect, while clofibrate or the combination with colestipated rats, C feeding reduced D concentration (30 to 13 mg/dl) indicating inhibition of synthesis via negative feedback system. Colestipol HCl increased D level (33%) and reduced C (60%) indicating increased synthesis; results are compatible with an agent capable of binding bile acids in the rat which can compensate for loss of these acids by increasing sterol synthesis. Compared to control, clofibrate reduced serum C (33%) and D (43%); in combination with colestipol HCl it inhibited the increased synthesis caused by the latter. Clofibrate appears to be an inhibitor of C biosynthesis. Also, tests with other compounds make it apparent that the U-18666A-treated rat model system can be useful in evaluating cholesterogenesis.


Inbred mice and their hypbrids as an animal model for atherosclerosis research.

1. The inbred strain of mouse is a relatively inexpensive and easily controlled animal that produces consistent results within each of the P1, P2, F1, F2, B1 and B2 generations. 2. The mother and father exert an equal influence on the development of fatty deposits in the aortic sinus wall and on serum total cholesterol levels. 3. Different strains of inbred mice react to the high-fat, high-cholesterol diet in different ways. 4. The control mice of the CBA/J (P2) strain had significantly lower values of serum total cholesterol and size of the largest lesion at some weeks than the control mice of the C57BR/cdJ and F1, F2, B1 and B2 generations. 5. The experiments indicate a multifactorial (polygenic) system of inheritance.


The nonhuman primates as models for studying human atherosclerosis: studies on the chimpanzee, the baboon and the rhesus macacus.

There is no dearth of experimental techniques for producing the hyperlipoproteinemia resulting in atherosclerotic complications and for myocardial infarction in the non human primates. Most of the recent experiments which have given information of great value have been studied with relatively expensive animals for a long period of time up to 6-7 years. It is evident that no animal model perfectly duplicates the human disease or satisfies all desirable requirements. The chimpanzees, representatives of the New World monkeys, have circulating plasma lipoproteins identical to man in composition as well as in function. The results reported above indicate that the compositional changes of chimpanzee plasma lipoproteins in response to dietary changes reflect the appearance of type II and type IV hyperlipoproteinemia similar to the human disease. Moreover, there are more indications about the existence of genotype II a in the chimpanzee, and also on the influence of stress on the plasma lipids, so that the developed intimal lesions similar to the human pathology are in this sense multifactorially influenced. From a phylogenetic point of view the chimpanzee is closer to man than any other non human primate. Furthermore, the chimpanzee lipoproteins are useful models for understanding the relationship between function and structure of the plasma lipoproteins in health and disease. Baboon and rhesus monkeys show similar results, but more differences to the human lipoproteins in health and disease were observed. At present it appears that the most useful models of human atherosclerosis are those induced in the non human primates, especially in the chimpanzee.


The influence of some dietary factors and/or treadmill exercise on rat and chicken tissue lipids and serum lipoproteins.

Four different experiments, one with cockerels and three with rats, are described which relate to the effect of dietary factors and/or exercise on serum and liver lipids as well as on serum lipoproteins. Several classes of lipoproteins were isolated by preparative ultracentrifugation, and their purity assessed by gel electrophoresis. The lipid composition and protein content of serum lipoproteins and tissue were also determined. Dietary cholesterol produced an enormous increase (200 fold) in serum very low density lipoproteins in cockerels. This lipoprotein was apparently of very large particle size because it failed to penetrate the spacer gel during disc electrophoresis. In rats fed a cholesterol-supplemented diet, the increase in very low and low density lipoproteins was relatively insignificant in comparison with the cockerels. However, in both species, the liver was overloaded with cholesterol. Further, the serum high density lipoproteins, HDL2 were greatly diminished in both species as a result of cholesterol ingestion for 7 weeks. As a possible explanation for these related observations, it was proposed that HDL2 was utilized in the formation of cellular membranes by cholesterol-burdened, hyperplastic livers. A very high level of dietary corn oil (40% by weight) caused drastic changes in rat liver lipid levels and in serum lipoprotein profiles. Specifically, liver cholesterol and triglycerides were increased about 200% over normal. In another experiment, tissue lipids and serum lipoprotein levels were determined in treadmill-exercised rats and in sedentary controls. Two levels (4 and 40%) of a fat mixture (1:1, hydrogenated coconut oil: corn oil) were used in this study. The serum cholesterol was unchanged in the 4 groups, while the serum triglycerides were reduced in exercised rats given 4% but not 40% fat as compared to respective controls. Rats fed 40% fat and exercised had near normal levels of liver lipids which was in sharp contrast to their sedentary controls. The low denstiy lipoproteins were surprisingly higher in exercised rats given high fat than in sedentary controls. It was suggested that the direct synthesis of these lipoproteins by the liver may be necessitated under unusual conditions. In conclusion, considering the central role of liver in lipid and lipoprotein metabolism greater attention should be focused on this organ in future experiments on the control of hyperlipoproteinemia.


Mechanism of inhibition of cholesterol uptake by the arterial wall.

Experiments have been described dealing with lipid synthesis and cholesterol uptake in perfused human and pig coronary arteries, rabbit aortas, and with the inhibitory effect of 7-ketocholesterol on cholesterol uptake in these preparations and in rabbits in vivo. Human and pig coronary arteries failed to synthesize cholesterol in vitro. 7-ketocholesterol inhibited cholesterol uptake in human coronary arteries and aortas of pigs and rabbits in vitro and by rabbit aortas in vivo. The inhibitory effect in vivo could only be shown after repeated i.v. injections of 7-ketocholesterol after solubilizing the steroid with bile sale (Na-glycocholate). Although 7-ketocholesterol was absorbed from the G.I. tract, gastric feeding of the bile salt steroid complex was ineffective, probably because of inadequate blood levels of 7-ketocholesterol achieved. The metabolic fate of 7-ketocholesterol and the nature of its effect on cholesterol are discussed. It is not likely that inhibition of HMG-CoA reductase is responsible for the inhibition of cholesterol uptake. The possibility was discussed that both cholesterol and 7-ketocholesterol actively compete for identical and specific binding sites or that an increase in 7-ketocholesterol in plasma leads to an increase in intracellular concentrations of this steroid thus inhibiting cholesterol transfer across the cell membrane. However definite conclusions on the nature of inhibition must await further experimentation.


Lipoprotein uptake and degradation by cultured human arterial smooth muscle cells.

The multipotential smooth muscle cell (SMC) is the predominant cell in intima and media of large arteries, proliferating eraly in the development of atheroma to become the lipid-laden foam cell. Thomogeneous cultures of human SMA have now been successfully grown from explants of normal pieces of artery obtained during surgery. In contrast to previous results with rat SMC, human SMC preferentially bind and take up large, lipid-rich lipoproteins (I125 labeled low density and very low denstiy lipoproteins) (LDL and VLDL), in comparison to smaller, high density lipoproteins (HDL). This species selectivity appears to be related to differences both in cells and in lipoproteins. Specific binding of lipoproteins by SMC, analyzed by release of radioactive protein from the cell surfaces by trypsin, accounted for approximately hal of the protein radioactivity associated with the cell layer during the first few hours of incubation. Specific binding appears to be related to the presence of apoprotein B on the lipoproteins. Lipoproteins progressively accumulate within cells as a function of incubation time. Lipoprotein degradation, assessed by appearance of TCA soluble, non-iodide radioactivity in the incubation medium, increased rapidly after an initial delay of 2 to 4 hours. Cells grown under hypoxic (5% O2) conditions instead of the usual room air showed impaired degradation of lipoproteins. These results suggest that there are receptors on arterial SMC, highly specific for different lipoproteins (as shown for skin fibroblasts). This tissue culture system may be useful for assessment of the effects of a variety of hormones, metabolites, and drugs on the handling of lipoproteins by arterial smooth muscle cells.


Phylogenetic variability of serum lipids and lipoproteins in non-human primates fed diets with different contents of dietary cholesterol.

The response of serum lipids and lipoproteins to different levels of dietary cholesterol (0.05% to 1.5% w/w) was measured in six nonhuman primate species. Relative response of serum cholesterol in different species, measured in terms of response, index, varied with dietary cholesterol concentration. The overall response for the different diets allowed ranking of the species as follows: Squirrel is greater than green is greater then spider is approximately thesus is approximately patas is greater than chimpanzee The serum cholesterol response was reflected not only in an increase in beta + pre-beta-lipoprotein cholesterol but also in alpha-lipoprotein cholesterol, with significant differences among species in the amount of cholesterol transported in the lipoprotein classes.


Femoral neck fractures in elderly women: a prospective study.

Fifty female patients admitted to the orthopaedic unit at the Royal East Sussex Hospital with a fracture of the proximal femur were followed prospectively. Forty-six of these patients had concurrent medical problems. Six patients required resettlement after recovery from their fracture, and of the twenty-six returning home, eighteen required support from social services. The function of the geriatric/orthopaedic unit is reviewed and it is suggested that the combined unit is of value to all elderly patients with a proximal fracture of the femur.


In defense of the dust count technique.

NISOH has recommended a Standard for Occupational Exposure to crystalline silica to OSHA with documentation based on dust count studies relating to health effects. This standard dictates sampling by mass respirable method only. A dual standard as in ACGIH-TLV list should be promulgated by OSHA which includes the dust count standard.


The effects of a 20-week nutritional insult on the skeletal development of Cebus albifrons during the 1st year of life.

Using an atlas constructed from records of a group of normal monkeys in the same colony, the effects of a 20-week low-calorie or low-protein nutritional insult on skeletal development were determined. The most significantly retarded sites were the late-forming ossifications (epiphyses, sesamoids, and tuberosites). A general increase in ossification anomalies and in individual variation was evident. The similarity of these findings to studies previously reported for man indicates the utility of nonhuman primate models for the further study of nutritional deficiency.


Immunosuppressive effect of intra-lymphatic irradiation.

The effect of intra-lymphatic administration of Lipiodol-l131 on the number of T and B lymphocytes, and on the in vivo response to common antigens and to DNCB, was investigated in uremic patients in the pre-transplant period. T lymphocytes have been detected by rosette formation with sheep erythrocytes (E) and B lymphocytes by rosette formation with erythrocytes sensitized with antibody and complement (EAC). After irradiation it was observed a lymphopenia due to a statistically significant decrease in the number of both T and B peripheral blood lymphocytes and a depletion of these cells in the irradiated lymph nodes. Their ability to give delayed hypersensitivity response to common antigens in vivo was lost after intralymphatic irradiation. Two patients were able to develop sensitization to DNCB and this reaction was supressed in one of them by irradiation. These effects of intralymphatic irradiation on the immune system favours further study of this method in clinical renal transplantation.


Further heterogeneity of the oral-facial-digital syndromes.

Two patients with polysyndactyly of the halluces and typical features of oral-facial-digital syndrome, type I (OFS I), are described. Previously, bilateral hallucal polysyndactyly was considered to be a distinctive feature of OFD II, Mohr syndrome. The original classification of OFD II was based on clinical similarities between the affected members of the Mohr-Claussen kindred and the two siblings described by Rimoin and Edgerton. Review of these cases deomnstrates important clinical differences, so that justification for the original classification of OFD II is questioned. Retrospectively, a small number of individuals have been considered to have had OFD II, but on review these cases appear to represent a clinically heterogeneous group of disorders.


A review of macromolecular transport and secretion at the cellular level.

This is a review of current information concerning mechanisms involved in transport and secretion of macromolecules in exocrine glands. Emphasis has been placed on information available for pancreatic acinar cells. The review was prompted by the availability of considerable amounts of new information developed during the past several years. Exportable proteins in the pancreatic acinar cells are synthesized on ribosomes attached to the endoplasmic reticulum. Following synthesis, nascent proteins are transported from ribosomes attached to the endoplasmic reticulum into intracisternal spaces bound by the endoplasmic reticulum. The proteins are then carried to the Golgi complex by transitional elements. Zymogen granules are formed in the Golgi complex and migrate to the cell apex. Appropriate stimulation leads to fusion of the zymogen granule membrane and apical plasmalemma followed by a break in the membrane and consequent release of the granule content into the ductules. The extact molecular events involved in the process of secretion are not known. The roles of cAMP and cGMP in pancreatic secretion are supported by indirect evidence only. The role of calcium in secretion is apparent, but further investigation is needed to delineate the exact mechanism of its action. Membrane depolarization and associated ionic fluexes seem to play a significant role.


Benign breast tumor and estrogenic hormones: a population-based retrospective study.

Histories of the usage of oral contraceptives and other estrogens were obtained from 320 women 20-49 years of age who had pathologically confirmed diagnoses of benign breast disease made at Washington County Hospital in Hagerstown, Maryland, during the period 1968 through 1972. Similar histories were obtained from 320 controls matched for race, sex, age, residence in county, and willingness to participate in a health survey. No association could be found between oral contraceptive usage and benign breast tumor. The use of other estrogens, notably diethylstilbestrol, was significantly related to the presence of benign breast disease.


Selection of cell culture systems for virus isolation.

A survey of cell culture systems for virus isolation is presented. Because there is not single cell culture system which will support the many viruses that may be encountered in clinical specimens, the characteristics and susceptibility of primary, diploid, and continuous cell cultures are reviewed. The primary cell culture system should be susceptible to infection with myxoviruses, paramyxoviruses, adenoviruses, and Coxsackie B viruses, since these are not consistently recognized in diploid cell cultures. Conversely, rhinoviruses, cytomegalovirus and varicella-zoster virus may be isolated only in diploid cell cultures. Upon consideration of expected viruses, and cell cultures available for isolation of these, one can choose a combination of a primary and a diploid cell system for virus isolation which will assure detection of most human virus groups known. The usefulness of continuous cell culture systems is generally limited to a very few specific viruses.


Sexually transmissible diseases.

There is a widespread recrudescence of venereal disease. The possible reasons for this are discussed. Each disease is then considered from the viewpoints of clinical course, diagnosis, and treatment. Treatment failures are discussed in detail, immunity is covered, and recommendations for the future conclude the presentation.


An experimental model for disseminated herpesvirus infection of the neonate.

Pregnant mice at 10 days of gestation were more susceptible to vaginal inoculation with herpesvirus, type 2, than were nonpregnant mice. This mouse model system also was used to compare delivery through a birth canal contaminated with herpesvirus, type 2, to delivery after maternal paranteral inoculation by the same virus. Approximately 26 per cent of newborn mice either died or had evidence of disseminated herpesvirus infections after delivering through a vagina inoculated with herpesvirus, whereas only 4 per cent of newborn mice died after subcutaneous inoculation of pregnant animals. Only 1 per cent of neonates delivered of subcutaneously inoculated pregnant mice had any evidence of herpesvirus infection. Pregnant mice immunized to herpesvirus, type 1, had significantly less newborn infection after delivery through a herpesvirus-inoculated birth canal when compared to nonimmunized mice.


Progesterone binding in human endometrial carcinomas.

By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3H-rone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade I, 3 out of 8 Grade II, and 2 out or 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific  progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship betweeen age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity.


Blindness caused by photoreceptor degeneration as a remote effect of cancer.

Three postmenopausal women developed photoreceptor degeneration one to four months preceding or following discovery of an anaplastic tumor. Two patients had transitory visual obscurations and bizarre visual sensations. Ring scotomas progressed to severe visual field loss. Retinal arteries were markedly narrowed. Electroretinograms revealed almost total absence of response in one patient, and another complained of the recent onset of night blindness. In all three patients severe degeneration of the photoreceptor cells associated with melanophagic activity was shown histologically. In two patients neuropathologic examination from the retinal bipolar cells to the occipital cortex revealed no significant alterations.


Effect of aspirin and dexamethasone on intraocular pressure in primary uveitis produced by Herpes simplex virus.

The intracameral injection of New Zealand white male rabbits with type 1 herpes simplex virus produced acute anterior uveitis with biphasic elevation of the intraocular pressure (IOP). The first IOP increase occurred on day 1 and 2 and the second increase on day 8. There was no significant correlation between the IOP changes and multiplication of herpes simplex virus in the uvea and cornea, nor between the IOP changes and histopathologic alteration of the tissue. Aspirin suppressed significantly the first as well as the second IOP elevation, whereas dexamethasone suppressed significantly only the second elevation.


Optic nerve manifestations of human congenital cytomegalovirus infection.

A Latin American male and a white female infant who had a cytomegalovirus infection on the first day of life had unilateral optic nerve hypoplasia. A white male infant who had cytomegalovirus isolated at 5 weeks of age had a unilateral partial coloboma of the optic nerve. A 4-month-old black infant with cytomegalovirus infection diagnosed at 2 days of age had a unilateral complete coloboma of the optic nerve associated with microphthalmia. Optic nerve involvement was an important manifestation of this disease.


Skeletal ossification and the adolescent growth spurt.

Fourteen ossification events in the hand and wrist were studied in relation to the age of peak growth velocity in body height in fifty-two boys and thirty-six girls. The subjects were aborigines enrolled in a longitudinal growth study. Peak growth velocity and the ossification events occurred in aborigines at about the same ages as in Caucasian children. The results indicate that the ossification events can be used by the orthodontist to assess a child's growth activity. The accelerative phase of the adolescent growth spurt is accompanied by epiphyseal widths reaching diaphyseal widths in the fingers and radius and by ossification of the pisiform and hamate Stage 1. Peak growth velocity occurs at about the time of epiphyseal capping in the fingers and radius and ossification of the sesamoid and hamate Stage 2. The decelerative phase of growth is indicated by epiphyseal union in the third finger, progressively from distal to proximal phalanges, and in the radius. The value of these indicators in orthodontic practice is discussed.


Evolution of cytoplasmic fibrillar bodies induced by lead in rat and mouse kidneys.

Characteristic cytoplasmic and intranuclear fibrillar bodies were produced, within 24 hours, in epithelial cells of the proximal convoluted renal tubules of rats and mice by injecting a single dose of lead acetate either intraperitoneally (100 mug Pb/g) or into the heart (10 mug Pb/g). The frequency of cytoplasmic fibrillar bodies (CFB) rose during the first 4 days following injection of lead and diminished thereafter. Ten days after intracardiac injection of lead no CFB were found; 10 days after intraperitoneal injection, they were still present, though probably in diminished number. Disappearance of CFB may be related to autophagocytosis. Intranuclear fibrillar bodies did not disappear, perhaps because nuclei lack a lysosomal apparatus. Within the first 3 days after injection of lead, clusters or paracrystalline arrays of ferritin molecules were frequently situated in the immediate vicinity of CRB or abutted against CFB; after the third day, little or no ferritin was found near CFB. Intramuscular injection of iron-dextran complex (50 mg Fe/ml) 24 hours prior to intraperitoneal administration of lead did not increase incidence or size of ferritin clusters in the vicinity of CFB in rats. The presence of ferritin near CFB may have been an indirect consequence of inhibition, by lead, of synthesis of heme prosthetic groups.


The fine structure of intracranial neoplasms induced by the inoculation of avian sarcoma virus in neonatal and adult rats.

Groups of F-344 rats were inoculated with the Bratislava-77 strain of avian sarcoma virus (B-77 ASV) within 24 hours of birth, at 9 days of age, or between 97 and 119 days of age. Intracranial tumors developed in each age group. Multiple tumors with mixed histologic patterns developed in rats inoculated at 1 or 9 days of age. Solitary tumors with a uniform histologic pattern developed in rats inoculated as adults. On the basis of light and electron microscopic study, the majority of tumors in each age group were classified as astrocytomas and divided into either poorly differentiated, gemistocytic, pilocytic, or polymorphic varieties. The polymorphic astrocytomas were most common among neonatally inoculated rats, while the pilocytic astrocytomas were most common among rats inoculated as adults. Ultrastructural characteristics of astrocytes, including gap junctions and 7- to 9-nm filaments, were present in the majority of tumors in each age groups. Astrocytomas induced in adult rats were remarkable for the presence of extensive basement membrane alone the astrocytic cell surfaces. Intracytoplasmic virus-like particles (R particles) were common in the tumor cells. These virus-like particles are morphologically distinct from C-type B-77 ASV, and no morphologic evidence of C-type virus replication was observed in any of the tumors.


Angiotensin II binding to renal glomeruli from sodium-loaded and sodium-depleted rats.

125I-labeled angiotensin II (125I-labeled AII) and [3H]angiotensin II ([3H]AII) bind specifically to isolated rat glomeruli. Three groups of receptor sites could be defined by the KD value (7.1 +/- 0.3 X 10(-11, 3.4 +/- 0.2 X 10(-10), and 1.6 X 10(-9) M, respectively) and the number of receptor sites (11.6 +/- 1.2, 29.4 +/- 3.9, and 113.8 +/- 3.8 fmol/mg glomerular protein, respectively). Both association and dissociation constants for 125I-labeled AII were greater than those for [3H]AII, but their ratio (KD) remained unchanged. Specificity of binding to these three groups of receptor sites was demonstrated by the following: 1) inhibition of binding of labeled AII by unlabeled hormone or by antagonists; and 2) reversibility of binding, independent of either hormone or receptor degradation. Binding was increased in glomerular preparations from acutely and chronically sodium-loaded rats, compared with glomerular preparations from acutely and chronically sodium-depleted rats. This change in binding resulted from both a change in the number of receptor sites and modification of the affinity of AII for its receptors. KD was higher in preparations from sodium-depleted rats (12.9 +/- 3.3 and 14.6 +/- 3.9 X 10(-11) M in chronically and acutely depleted rats, respectively) than in those from sodium-loaded rats (2.7 +/- 0.2 and 3.9 +/- 1 X 10(-11) M in chronically and acutely sodium-loaded rats, respectively). Changes in the binding of AII to its glomerular receptors could play a role in the adaptation of glomerular filtration rate to the sodium balance.


Biochemical adaptations in skeletal muscle of trained thyroidectomized rats.

The cytochrome c concentrations of the different types of skeletal muscle of trained and nontrained normal and thyroidectomized rats were measured. Animals were trained by treadmill running 1 mph, at a 15% incline, 1 h/day, 5 days/wk for at least 12 wk. This training program induced an expected 50% increase in cytochrome c in the high-oxidative fast-twitch red (FTR) and slow-twitch red (STR) fibers and only a 25% increase in the low-oxidative fast-twitch white (FTW) fibers of the normal rats. This same training program caused a greater increase (100%) in the FTR and STR fibers of the thyroidectomized runners and a dramatic 243% increase in the FTW fiber. Even though the thyroidectomy procedure caused a reduction in oxidative capacity of all types of skeletal muscle fibers to about one-half normal, the absolute increase in cytochrome c in the muscles of the trained thyroidectomized animals was essentially the same or greater than that of the normal trained animals. These results indicate that the adaptive response to training of an increased oxidative capacity in skeletal muscle occurs in the absence of normal thyroid function. They also suggest that the exercise bouts of the thyroidectomized animals were performed with a relatively greater involvement of the FTW muscle fibers.


Adenosine relaxation of isolated vascular smooth muscle.

Adenosine relaxed hog carotid media strips contracted with norepinephrine (NE) and potassium (K+). Adenosine (3 X 10(-6)M) was more effective in relaxing the NE contractures than those produced by K+. In both cases, adenosine's efficacy decreased with increasing concentrations of the stimulating agent. A high adenosine concentration (1 X 10(-3)M) was necessary to elicit relaxation of completely depolarized (124 mM K+) media strips and equimolar concentrations of aminophylline caused greater relaxation than did adenosine. Adenosine inhibited the Ca2+ dose-response curves of strips stimulated with 20 mM and 30 mM K+ and its effect was dependent on the Ca2+ concentration. Neither 1 X 10(-6)M nor 1 X 10(-4)M adenosine produced any change in the cAMP content of vascular strips. Only at high concentrations did adenosine increase the cAMP content of vascular strips, but the increase was signficantly more than that observed with the same dose of aminophylline. The present results are consistent with the possibility that adenosine relaxes vascular smooth muscle by directly altering Ca2+ permeability and/or membrane potential; they do not support a role for cAMP in the adenosine-induced relaxation of vascular smooth muscle.


Lipolytic activity of swine adipocytes.

Lipolysis in isolated swine adipocytes was stimulated by epinephrine, dibutyryl cyclic AMP, and weakly by adrenocorticotropin but not by glucagon or cyclic AMP. Theophylline, a phosphodiesterase inhibitor, stimulated lipolysis and greatly enhanced the activity of adrenocorticotropin. The epinephrine-stimulated lipolytic activity, expressed on a tissue or cell volume basis, was greatest at 25 days postpartum, whereas, expressed on a cell basis, the activity was maximal at day 80. Regardless of the mode of expression, the activity at day 150 was low. Cells from younger animals were more sensitive to epinephrine than cells from older animals.


EEG sleep changes as predictors in depression.

The authors conducted a study of 18 depressed patients to see whether EEG sleep measurements might provide a predictive tool for response to antidepressant medication. They found that although the sedative characteristics of amitriptyline did not differentiate good responders from poor responders until the third week of drug treatment, the good responders showed significant increases in REM latency, decreases in REM sleep time, decreases in REM sleep percent, and decreases in REM activity after only 2 nights of drug treatment.


Loss of colonic haustration in progressive systemic sclerosis.

Complete loss of colonic haustration was observed in six cases of progressive systemic sclerosis. Varying degrees of haustral loss or sacculation were noted in twelve others. An increase in colonic length was characteristic and, occasionally, there was slight to moderate generalized dilatation. Correlation of these findings with the microscopic appearance of the colon showed that muscular atrophy and fibrous replacement were consistent findings, varying in degree. Although the data are insufficient to permit definite conclusions, it is suggested that these changes may be responsible for colonic lengthening and loss of haustration. Attention is drawn to the importance of not confusing this appearance with other conditions, particularly chronic ulcerative colitis.


Roentgen findings in aorto-enteric fistulae.

Six cases of aorto-enteric fistulas are discussed. In three patients the aorta ruptured into the duodenum and in three there was rupture into the esophagus. Aorto-enteric fistula is usually caused by atherosclerosis, but may also be due to syphilis or tuberculosis. Following insertion of an aortic graft, fistula is usually the result of breakdown of the anastomosis. Gastrointestinal bleeding usually heralds the problem. The roentgen signs of rupture are pressure on the esophagus or intestine, bleeding into the wall or lumen, and demonstration of the fistula. The abnormal connection may not be demonstrable by aortography. These signs permit early diagnosis and subsequent possible life saving surgical correction.


Multiple benign ureteral fibrous polyps.

Two cases of benign polyps of the ureter are reported with emphasis on the uroradiological features and methods of evaluation in the diagnosis of benign mesodermal tumors of the ureter. The apparently excellent results from conservative surgery make the recognition and preoperative roentgenologic diagnosis of this entity mandatory.


Cavitating lung nodules and pneumothorax in children with metastatic Wilms' tumor.

Lung metastases evolved into large thin-walled cysts in two children with Wilms' tumor. Histologic examination of one lesion suggested that invasion of a small bronchus or bronchiole, leading to ball-valve obstruction, was responsible. One patient also experienced recurrent pneumothorax, probably on the same basis. The formation of thin-walled cysts has not previously been observed with metastatic Wilms' tumor. Pneumothorax is a rare complication of metastatic Wilms' tumor.


The spotted nephrogram of renal scleroderma.

The renal angiographic findings in our two patients with scleroderma and recent onset of hypertension included minor changes in the distal interlobar and arcuate arteries and a nephrogram displaying diffuse, spotty lucencies. Although the spotted nephrogram is occasionally seen in cases of severe nephrosclerosis, we believe that, in the absence of major arterial changes in the arcuate and distal interlobar arteries, it is virtually diagnostic of renal scleroderma.


The role of emergency excretory urography in evaluation of blunt, abdominal trauma.

In our hospital, patients seen for blunt, abdominal trauma have an "emergency" urogram. The results of our review of 209 such patients with complete urographic evaluations indicate that (1) the clinical examination, urinalysis, and plain abdominal roentgenogram do not reliably allow one to predict which patients would show urographic abnormalities and (2) the clinical management of these patients is rarely altered by the knowledge of the results of the urogram.


Arthrography in total hip prosthesis complications.

Previous reports have stressed the value of hip arthrography primarily in determining the presence of loosening of the total hip prosthesis. Although loosening is a common complication and frequently associated with infection, other complications producing a painful hip prosthesis exist and are demonstrable by arthrography. Since the etiologies of these are as diversely different as the treatment, the hip arthrogram is advocated as an integral part of the diagnostic approach to the patient with a painful hip prosthesis in order to assess the specific complication and determine the therapeutic approach.


Chiba percutaneous transhepatic cholangiography. A valuable method for visualizing the nondilated biliary tract.

Percutaneous transhepatic cholangiography with the Chiba needle has had remarkable results in cannulating small bile ducts. We have roentgenographically visualized a nondilated biliary system in the first five out of seven cases attempted. Including our series, there have been 71 successful Chiba studies in 107 nondilated or presumed normal biliary tracts with only one questionable major complication. The technique is simple to learn, particularly in comparison with endoscopic retrograde cholangiography. Since the incidence of complications is low, surgical standby should seldom be necessary. The value of the Chiba percutaneous transhepatic cholangiogram is described via four unusual case reports.


Computerized tomography (CT) in acute head trauma.

The retrospective evaluation of 100 cases of head trauma that were subjected to computerized tomography (CT) leads to the following conclusions: (1) Computerized tomography and plain skull survey, should be the first neuroradiological procedures to perform. (2) Angiography may be carried out after computerized tomography when necessary, but as proved by this series, it will be needed in a relatively small number of cases. These include patients with technically limited CT scans or those in whom the possibility of an associated vascular lesion of the cervical or intracranial vessel is clinically suspected. (3) It is essential to obtain CT scans of the best possible quality. Sedation will be required in many instances, but this is considered worth doing because a normal CT scan, without significant technical limitations, will exclude the presence of lesions requiring prompt surgical intervention. Those patients who require surgery will need general anesthesia under any circumstances. (4) There is generally a direct relationship between the severity of clinical presentation and the CT demonstration of the abnormality responsible for the clinical status. Seventy percent of the patients clinically diagnosed as contusion had positive CT scans, and for all practical purposes, 100 percent of patients having trauma more severe than our Group III (contusion) had abnormal CT scans. Likewise, the number and intensity of tissue abnormalities on CT scans increase proportionately with the severity of the clinical signs and symptons. (5) It is foreseen that, with the advent of faster computerized tomographic scanners, the usefulness of this method will increase further, owing to a reduction in the total examination time and the lessened requirement for sedation.


Individualized computer tomography of the skull with the EMI scanner using the 160 X 160 matrix.

The individualized approach to the performance of computerized tomography of the skull is described. With the use of the 160X160 matrix it is possible to look at the initial scans almost immediately after their completion. If necessary, unsatisfactory scans can be repeated, the position of the head can be changed and artifacts due to motion can be minimized or eliminated. Lesions can be revealed or enhanced with intravenously injected contrast material if desired. The individualized approach has eliminated the need to recall patients and has improved the diagnostic capability of the method.


Computed tomography of the normal and infarcted myocardium.

After intravenous administration of contrast agent, in vitro cardiac scanning showed a significant difference between the attenuation coefficients of the intracavitary blood pool and the myocardial wall, permitting clear delineation of the ventricular cavity. A substantial alteration in hematocrit permitted similar visualization of the intracavitary blood pool-myocardial wall interface. The attenuation coefficient of infarcted myocardium differed sufficiently from that of normal myocardium to render computed tomographic distinction feasible. In three hour old infarctions, the differences between normal and ischemic or infarcted tissue were enhanced by prior administration of contrast agent. These differences in attenuation coefficient indicate that a properly gated CT scanner could be utilized as a noninvasive approach to evaluating suspected or known myocardial infarction and other aspects of cardiac structure and function both in man and in experimental animals.


The value of repeat cerebral arteriography in the evaluation of trauma.

In most patients with head or neck trauma, a single angiogram is sufficient to guide therapy. For those who improve slowly or not at all, however, this is not an adequate basis for diagnosis. Angiography should be repeated after an interval of time to exclude development of a surgically correctable lesion, such as pseudoaneurysm or intracerebral or extracerebral fluid collection.


Caudal dislocation of the pons in the adult Arnold-Chiari malformation: an angiographic evaluation.

The position of the pons, determined angiographically, can be related to the clivus and sella. In adult patients with the Chiari malformation, a caudal dislocation of the pons is frequently associated with the well known anomalously low position of the cerebellar tonsils. This finding may aid in the angiographic diagnosis of the Chiari malformation.


Angiographic manifestations of bilateral Wilms' tumor.

Two cases of bilateral Wilms' tumor are presented with discussion of angiographic features. Emphasis is placed on selective angiography in addition to inferior vena cavography for complete evaluation. Because of the incidence of bilateral disease, and the highly vascular nature of the tumor, selective angiography of the contralateral side should be considered in the initial evaluation of unilateral Wilms'tumor. Evaluation of the interface between tumor and normal parenchyma is extremely important in bilateral disease, in anticipation of partial nephrectomy.