Carotid-cavernous fistula: a complication of maxillofacial trauma.

Fistulas of the internal carotid-cavernous sinus are an unusual arteriovenous malformation. Two types exist: (1) spontaneous fistulas and (2) traumatic fistulas. This paper deals with the traumatic variety which is seen more commonly in men as a direct result of severe maxillofacial injury. Recent anatomic studies are correlated with the physical findings associated with carotid-cavernous fistula, ie, headache, chemosis, exophthalmos, pulsatile bruit, and multiple cranial nerve paralyses. A case report illustrates these findings. The differential diagnosis which varies from tumors, to cavernous sinus thrombosis, to intraorbital aneurysm is discussed. The role of angiography in diagnosis is described. Present management consists of intracranial ligation of the internal carotid artery with use of a muscle embolus to occlude the fistula and selective ligation of the cervical carotid.


Hypercholesterolaemia in primary cancer of the liver.

Hepatic synthesis of cholesterol in higher animals is normally markedly suppressed by dietary cholesterol. This feedback regulation has been shown to be absent in all experimental hepatomas studied, and also in the only 2 humans with primary hepatocellular cancer (PHC) who have been investigated. Another patient who presented with hypercholesterolaemia is described in whom cholesterogenesis in the tumour was not suppressed by cholesterol feeding. In order to determine the frequency with which hypercholesterolaemia occurs in PHC, serum cholesterol levels were measured in 132 Black patients with this tumour. Raised levels were found in 14 of the patients (11%). In only 2 of these was hypercholesterolaemia associated with obstructive jaundice.


The potential for carcinoma existing synchronously on a microscopic level within the second breast.

In the present study, 23 of 314 patients presented with asymptomatic lesions in the second breast, comparing favorably with the incidence of asymptomatic carcinomas of the second breast reported in other series. The type of biopys used appears important, most surgeons advocating resection of a segment of breast ranging from 20 to 30 per cent of the quadrant being sampled. It appears that treatment of carcinoma of the second breast is essentially curative when the lesion is not noted clinically. Adequate treatment of the second breast lesion appears to reduce the at risk group within the second breast. It is usually stated that 10 per cent of patients will have a second carcinoma of the breast develop. In this study, metachronous lesions developed in six of 291 patients. Considering that these tumors all recurred in the outer quadrant of the remaining breast, the possibility arises that it may be more productive to do all biopsies in the tail of the second breast rather than to perform the so-called mirror image biopsy that was used in the present study. Results from this and other studies do appear to indicate that the utilization of a mirror image biopsy or outer quadrant biopsy is an effective way to detect and treat occult malignant tumors as well as the earliest forms of premalignant disease.


[The incidence of lymphosarcoma (leukaemia) and feline leukaemia virus (FeLV) in cats in the Netherlands (author's transl)].

Seven different groups of cats were examined to study the incidence and distribution of feline leukaemia virus (FeLV) in the Netherlands. The indirect fluorescent antibody (IFA) technique was used to detect FeLV antigen. Of the cats with lymphosarcoma (leukaemia), 73.2 per cent and of those with infectious peritonitis, 32.4 per cent were found to be positive for FeLV antigen. Of the sixty-six cats with other tumours, only one, a cat with carcinoma of the mammary gland; was positive for FeLV antigen. Of 557 cats with various lesions, forty-two (7.5 percent) were positive for FeLV antigen. The IFA-test was found to be a useful adjunct in establishing the correct diagnosis. Of all stud cats which had been in contact with FeLV-positive cats, 24.7 percent were positive for FeLV antigen, wheras all those which had not been in contact with these cats, were negative. There was a marked difference between the proportions of FeLV-positive cats in the groups of clinically normal cats which had (20.6 per cent) and which had not (0.4 per cent) been in contact with FeLV-positive cats. Follow-up studies showed that 67.8 percent of the clinically normal, FeLV-positive cats had died from or been sacrificed because of FeLV-associated diseases within twenty months.


[Pathological anatomy of the malformation of the lung (author's transl)].

With short sidelights to embryology a survey of clinically important malformations of the airways, respiratory tissue, and vessels is given and their differential diagnosis with similiar acquired lesions discussed.


The effect of agents which modulate levels of the cyclic nucleotides on human lymphotoxin secretion and activity in vitro.

The ability of concanavalin-A (Con-A) to activate lymphocytes to secrete human lymphotoxin (LT) was tested in the presence of agents known to modify the intracellular levels of cyclic nucleotides (cAMP and cGMP). Lymphocytes were treated with these agents at different stages of activation: (1) during the first encounter with mitogens, and (2) after they had been fully activated and were restimulated. Two agents, Dibutyryl cAMP and theophylline, dramatically inhibit the amount of LT secreted during both "primary" and "secondary" activation by Con-A. In contrast; DL-isoproterenol had a weak effect during primary activation, but greatly reduced the level of LT secreted during secondary activation. Agents which affect the intracellular level of cGMP were also tested. Imidazole had no effect on LT secretion by either primary or secondary Con-A activated cells. In contrast, carbamyl choline greatly reduced LT secretion to a level comparable to Dibutyryl cAMP and theophylline. All agents tested protected, to some degree, the sensitive alpha-L cell against LT-induced destruction in vitro. Agents which affect the levels of cyclic nucleotides affect both the effectiveness of the aggressor cell and the sensitivity of the target cells in vitro.


[Ultrastructure of the cytoplasm of the lower holotrichous infusorian Tracheloraphis prenanti].

The ciliature of T. prenanti Dragesco 1960 (forma oligocineta Raikov et Kovaleva, 1968) consists of 14-18 ventral and lateral longitudinal kineties with paired kinetosomes, carrying either two cilia or one cilium per kinetosome pair (in the latter case, the nonciliated kinetosome is always the posterior one). The ectoplasmic fibrillar system belongs to the postciliary type. A pair of kinetosomes shares a common basal plate. The anterior kinetosome gives rise to a short ribbon of transverse microtubules, the posterior one, to a poorly developed kinetodesmal filament and to a strong ribbon of postciliary microtubules. The latter proceeds backwards along 8 to 12 kinetosome pairs, being incorporated into a laminated postciliodesma which accompanies each kinety on its right side. Rows of Golgi elements, sending secretory vesicles and channels towards the body surface, exist beneath the kinetosome bases. Each kinety is accompanied on its left by a microfibrillar myoneme, surrounded by perimyary vesicles and underlain by a row of mitochondria. The median part of the dorsal surface is nonciliated; the cytoplasm here is rich of membrane systems, contains peripheral, electron-dense, extrusible inclusions and sometimes also bacteria. The electron-dense inclusions develop in the endoplasm, in close contact with mitochondria. The endoplasm contains also large microfibrillar spheres of unknown nature.


[Electron microscopic study of intracellular digestion in intestinal cells of the ixodid tick Hyalomma asiaticum. I. Formation of primary and secondary lysosomes].

The formation of primary and secondary lysosomes in digestive cells of midgut of the tick H. asiaticum was investigated using ultracytochemical methods for acid phosphatase. This enzyme is synthesized in the rough endoplasmic reticulum cisternae to be concentrated in the Golgi complex. Vesicles 0.1-0.15 mum in diameter filled with the enzyme are propagated from the distal Golgi cisternae which are primary lysosomes. Secondary lysosomes are produced in result of fusion of primary lysosomes with heterophagosomes that appear during endocytosis. Another type of structures responsible for transport of lysosomal enzymes into heterophagosomes is represented by dense bodies 0.3-0.5 mum in size. These are rich in acid phosphatase being different stages of heterophagolysosomes and telolysosomes.


[Morphological and cytochemical characteristics of human cells transformed and made malignant by Rous and polyoma viruses].

In cells of human embryo skin--muscle tissue transformed by the Rouse sarcoma virus (23rd cell line) and polyoma virus (P-2 cell line), the mitotic activity was 48 0/00 for 23rd line, 51 0/00 for P-2 line as against 28 0/00 in the control cells. The transformed cells possessed greater amounts of RNA and DNA and protein--bound SH-groups, different forms of glycogen deposits, as well as higher acid phosphatase enzyme activities; there was practically no difference in acid mucopolysaccharide content or NAD-H2-diaphorase and succinate dehydrogenase activities.


[Bovine enzootic leukemia and study of c-type particles in a cow with acute lymphatic leukemia and in cattle of the same herd with persistent lymphocytosis].

A case of acute lymphatic leukemia in a 7-month-pregnant Italian Friesian cow, aged about 6 years and belonging to a small dairy herd of 11 cows is described. Hematologic, histopatologic and ultrastructural examinations were performed, the ultrastructural studies were confined to the lymphnodes, thymus and buffy-coat cultures from peripheral blood. The remaining animals were subjected to hematologic examination and electron microscopy examination of buffy-coat cultures from peripheral blood. C-type particles were found in phytohemagglutinin (PHA)-treated and untreated buffy-coat cultures from the leukemic cow and from the animals with persistent lymphocytosis. C-type particles were also found in milk samples from 3 cows with persistent lymphocytosis.


[Multivariate analysis of aminoacyl-tRNA synthetase activities of liver and hepatomas (author's transl)].

Data on the aminoacyl-tRNA synthetase activities in normal liver and in three transplantable rat hepatomas, viz Yoshida's AH 130 and Morris's 5123C and 7793, were studied by means of factor analysis, a powerful technique of multivariate analysis particularly suitable foridentifying factors which theoretically may account for the pattern of interrelations between several variables. The analysis has been performed on 51 patterns of enzyme activities, covering 17 out of the 20 aminoacyl-tRNA synthetases; 80% on average of the total variability of the 17 enzyme activities may be accounted for by the first 4 factors extracted. The enzymes seem to fall into different groups, depending on their relationship with the factors thus identified. The results suggest that enzymes belonging to the same group share a common control mechanism, and are independent of the enzymes belonging to different groups, both in normal liver and in hepatomas.


[The ultrastructure of mixed mammary gland tumours in bitches. III. The early stages of the myoepithelial proliferation (author's transl)].

The early stages of myoepithelial proliferation in 14 mixed canine mammary tumours were studied by light- and electron microscopy. Two different early stages can be distinguished: 1. Proliferations inside the basal lamina with partial maintenance of the organoid pattern. 2. Proliferations with a break through the basal lamina and transposition of tumour cells into the surrounding connective tissue. The intracytoplasmic fibrillae of myoepithelial tumour cells are striped periodically and thicker than those of normal myothelia. It is suggested that the amorphous as well as the fibrous intercellular substance in the early stages is derived from the described myoepithelial tumour cells.


[Use of cross-absorbed sera in neutralization tests with viral titration by the cytopathogenic effect].

A new method for intratypic antigenic differentiation of poliovirus strains has been developed. The method is based on the use of cross-absorbed sera in neutralization tests where virus is titrated by the cytopathic effect. Qualitative differences between the antigenic structure of vaccine and "wild" strains as well as between some "wild" strains of the same serologic type have been found. The method may be used in practical laboratories.


[Results of examining wild monkeys for the presence of smallpox antibodies and smallpox group viruses].

The results of examinations of sera, blood and organs of different species of monkeys from some Asian and African countries for the presence of antibody to smallpox and viruses of the smallpox group. Significant titers of smallpox antibodies (antihemagglutinins virus-neutralizing and, in some cases, precipitating antibody) were found in a considerable number of monkeys shot near foci with human cases (Equatorial province of Zair Republic). In the same monkeys kidney tissues yielded 3 isolates of smallpox virus group two of which were indistinguishable in the laboratory tests from variola virus. On the basis of these data it is concluded that smallpox viruses circulate among wildlife monkeys in some areas of Equatorial Africa. Further studies along these lines are necessary.


Ocular complications in renal transplant recipients.

Twenty-five patients were examined for ocular complaints following renal transplantation. Besides the expected complications of posterior subcapsular cataract and cytomegalovirus retinitis, other findings-such as focal depigmentation of the retinal pigment epithelium, a lack of hypertensive retinopathy, elevated intraocular tensions, microaneurysms, preretinal wrinkling, serous detachments of the retina, hemorrhages and exudates-were observed.A laboratory clue to the onset of cytomegalovirus retinitis was a rapid rise in cytomegalovirus (CMV) antibody titer and a positive CMV plaque count in tissue culture.


[Morphological manifestations of the intracellular toxic effect of microorganisms of the ornithosis-lymphogranuloma-trachoma group].

Interactions of the causative agents of meningopneumonia and ovine abortion with pulmonary macrophages in experimental infection in white mice were studied by histological, immunofluorescent and electron microscopic methods. The causative agent of meningopneumonia did not multiply in colonies and caused toxic lesions in the cells and formed cytoplasmic oxiphilic inclusion bodies. Being the product of cell degeneration, these oxiphilic inclusion bodies were conducive to long-term survival of the cell and slow release from them of elementary bodies of meningopneumonia agent. The agent of ovine abortion multiplied in colonies without toxic affection of the cells or formation of oxiphilic inclusion bodies. It is suggested that oxiphilic inclusion bodies represent morphological manifestation of the intracellular toxic effect of rickettsial and ornithosis-like agents possessing dissociated (non-colonial) mode of multiplication.


[Damaging effect of 2 simian viruses on mammalian cell chromosomes].

A green monkey myxovirus (SV5) causes chromosome breaks in embryonal diploid fibroblasts of man, cotton rats, striped hairy-footed hamster, and in cells of one heteroploid line of newborn lamb kidney. Adenovirus SV15 is mutagenic for all cultures under study (diploid strains of human and cotton rat embryo fibroblasts and three continuous kidney cell lines from newborn lambs). The mutagenic activity of these viruses may be manifested without their undergoing a complete cycle of replication.


[Characteristics of experimental para-influenza in Syrian hamsters infected by different routes].

The pathomorphological and virological study of peculiar features of parainfluenza infection caused by intranasal, aerosol and oral administration of the virus was carried out. The most marked lesions in the respiratory tract were observed in hamsters infected by the intranasal route, whereas with other routes of infection the intensity of lesions was minimal. Such differences in the pathomorphological manifestations of the process are most probably due to uneven distribution of the virus in the respiratory organs and to peculiar features of the immunological response of the animals.


Serologic studies of acute respiratory infections in military personnel.

The advantages, disadvantages, and uses of serological epidemiology are discussed in relation to acute respiratory infections in military personnel.  The prevalence of antibody reflects both current and past experience with respiratory agents and is a measure of susceptinility.  Incidence data calculated by testing two serial serum samples, on entry and discharge from the service, has indicated high influenza and mycoplasma pneumoniae rates in South American recruits and low rates of adenovirus and parainfluenza infections.  Serologic analysis of reinfection rates showed high protection against influenza infections at HI antibody levels of over 1:40, against adenovirus infections at neutralizing titers of 1:5, and against M. pneumoniae infections at TRI antibody levels over 1:8.  Antibody responses persisting at least 7 mo following immunization were demonstrated in 70% of 428 vaccinated young adults for A2 antigen and 20% for influenza B antigen.  No relation of ABO blood groups to respiratory infection was found.  The lack of myxovirus infections in four Polaris submarines is presented.


[Dermatoglyphics in children with embryonic tumors (author's transl)].

Dermatoglyphics were analyzed in 60 children with embryonic tumors.  In comparison with normal children, several differences were found.  Thus, the embryonal origin of the different tumors is underlined and the hypothesis of embryonic tumors as malformations is sustained.  These tumors seem to be the clinically most important manifestation of a much more comprehensive malformation syndrome, which is not yet known in all its details.


Electron microscopic and electron histochemical studies on embryonal rhabdomyosarcoma of the orbit.

A small number of differentiated tumor cells could be found besides a great number of undifferentiated ones. Abnormal dense granules were found in the nuclei of undifferentiated tumor cells, not in differentiated ones. Non-specific filaments were seen in the cytoplasm of undifferentiated tumor cells. Differentiated tumor cells demonstrated various stages of myofibrillar structures such as A, I, and Z bands, many glycogen granules, mitochondria and a basement membrane. Polyglucose particles synthesized from glycose-1-phosphate by phosphorylase activity were located in the cytoplasmic matrix of undifferentiated and differentiated tumor cells and in the karyolymph of undifferentiated tumor cells. Polyglucose partices increased in number according to the degree of differentiation of tumor cells.


The use of fluorescent probes for studying the interaction of proteins with black lipid membranes.

The number of 1-anilino-8-naphthalene sulphonate (ANS) molecules bound to black phosphatidylcholine (PC) and phosphatidylinositol (PI)-membranes was calculated. The fluorescences change of membrane bound ANS was measured after the additon of positively charged proteins to the same side as ANS. Cytochrome c caused a fluorescence decrease, lysozyme and protamine an increase. These effects were completely reversible in the case of cytochrome c and lysozyme and only partly reversible in the case of protamine by increasing the ionic strength. The fluorescence polarization of membrane bound ANS was not significantly changed by protein addition. The results are discussed with respect to the binding of proteins to black lipid membranes and the use of ANS as a probe compared with other fluorescent probes.


Ultrastructure of acinar cells of submaxillary gland after treatment with ACTH and cortisone.

The applied hormones cause changes in the ultrastructure of acinar cells, and the changes caused by each of them are different. The effect of ACTH on these cells is more distinct and the nature of the changes permits the suggestion that ACTH acts mainly on secretory activity (increase). The changes caused by treatment with cortisone cannot be interpreted unequivocally.


[Studies on the influence of the host system on the result of the neutralization of monodispersed and untreated foot- and mouth disease virus (author's transl)].

Monodispersed foot- and mouth disease virus was obtained by filtration through membranes having a porosity only twice the diameter of the virus. This monodispersed virus was neutralized by immune sera in the same manner as not treated virus. This was shown by the inactivation curve comparing the amount of virus used for the test (calculated as ID50) with the neutralization titre (ND50) or comparing  the reduction of infectivity (also calculated as ID50) with the dilution factor of the antiserum. When the virus was assayed by counting the plaque forming units, the monodispersed virus needed more antiserum to be neutralized than a not treated virus suspension. The same mixtures of virus and antiserum were inoculated into different host systems. Using suckling mice there was observed only about 1% of the infectivity measured in primary calf kidney cells. Primary calf kidney cells showed only a tenth of the infectivity seen in BHK-21 cells. The difference between the results in mice and calf kidney cells has been found to be caused by the existence of infectious virus in the mice, which does not cause illness or death in the presence of antibodies. Comparing the same size of cell sheet there is more virus absorbed by BHK-cells in the presence of antibodies than by calf kidney cells. The different results obtained in different hosts for the same virus antibody mixtures are discussed with respect to the detection of small amounts of antibodies and to the limits for the comparison of neutralization titres.


Influence of Bordetella pertussis and bacterial endotoxins on the immunological reactivity of germfree mice.

As compared to specifically pathogen-free NMRI mice, in principle, the immunological reactivity of germfree mice of the same strain and age was not found to be reduced. This is documented by the cellular kinetics of the primary immune responses, evoked by the intraperitoneal (i.p.) injection of either a "saturated" dose of 4 times 10(8) sheep erythrocytes (SE) or the simultaneous injection of 4 times 10(8) SE and 3 times 10(9) killed Bordetella pertussis organisms (PO). Thereby, adjuvancy of PO was not found to be reduced in germfree mice. The only difference consisted in the demonstration of significantly reduced numbers of both direct and indirect plaque-forming spleen cells (PFC) on the 4th day after primary antigenic stimulation. This is suggested to be due to a lack of sufficient training of the immunological apparatus of germfree mice. Both in germfree and conventional mice significant splenomegaly, blood leukocytosis as well as increase in the numbers of pre-existing "background" PFC became detectable following a single i.p. injection of 3 times 10(9) PO without SE. Similarly, the injection of endotoxin from Serratia marcescens produced a moderate increase in the numbers of "background" PFC. From the data presented it is suggested that strict gnotobiotic conditions do not cause noteworthy deficiency in immunological competence.


The significance of serum progesterone and serum unconjugated oestradiol-17beta in unaborted hydatidiform mole.

Both serum progesterone and serum unconjugated oestradiol-17beta (Oe2) were measured by competitive protein binding assay and radioimmunoassay respectively in 42 cases of unaborted hydatidiform mole. Serum human chorionic gonadotrophin (HCG) was measured by a haemagglutination-inhibition technique. In 26 cases of intact molar pregnancies without theca lutein cysts (TLC), serum progesterone ranged from 18.0 to 289.0 ng/ml with a mean +/- standard error of the mean (SEM) of 65.9 +/- 13.1 ng/ml; serum Oe2 ranged from 4.0 to 37.0 ng/ml with a mean +/- SEM of 17.9 +/- 1.9 ng/ml; serum HCG ranged from 60 to 1920 IU/ml with a mean +/- SEM of 531.5 +/- 105.7 IU/ml. In contrast, 16 cases of intact molar pregnancies with TLC had serum progesterone ranging from 34.1 to 288.0 ng/ml with a mean +/- SEM of 134.1 +/- 2.4 ng/ml; serum Oe2 ranging from 1.7 to 76.3 ng/ml with a mean +/- SEM of 31.5 +/- 5.3 ng/ml; serum HCG ranging from 320 to 2560 IU/ml with a mean +/- SEM 1400 +/- 196.2 ng/ml. The differences between the mean of these three hormones in hydatidiform mole with and without TLC were significant (progesterone: P less than 0.005; Oe2: P less than 0,0125; HCG: P less than 0.005). There was a significant correlation between serum HCG and serum Oe2 (coefficient of correlation r = +0.3565, P less than 0.0125) and between serum Oe2 and serum progesterone (r = +0.3787, P less than 0.0125). There was no significant difference in the mean levels of serum progesterone, Oe2 and HCG in hydatidiform mole with and without subsequent malignant sequelae. The mean ratios of Oe2/progesterone were essentially similar in moles with and without TLC and with and without malignant sequelae. The significance of these findings are discussed.


Pentose shunt, phosphoribosylpyrophosphate generation and purine-phosphoribosyltransferases in erythrocytes of patients with polycythemia vera.

Erythrocytes of patients with polycythemia vera exhibited increased activity of oxidative pentose shunt, accelerated generation of phosphoribosylpyrophosphate, increased incorporation of 14C-adenine into nucleotides, and increased activity and thermostability of adenine-phosphoribosyltransferase.  These abnormalities are attributed to age dependency of the pathways concerned and presence in polycythemia vera of an erythrocyte population younger than normal.


Parallel tubular structures in lymphocytes.  II. Correlation with cellular immunity and cytomegalovirus and Epstein-Barr virus antibodies in Hodgkin's disease.

The increased incidence of parallel tubular structures in lymphocytes of patients with Hodgkin's disease was investigated for a correlation with either impairment of cellular immunity (measured by DNCB-skin test and PHA-induced lymphocyte stimulation in vitro) or an increase of antibodies against cytomegalovirus or Epstein-Barr virus. No correlations were found. Statistical analysis revealed antibody titers especially in the group of patients with high percentages of lymphocytes containing the tubular inclusions. This probably reflects only the connection  between these findings and the progression of the disease. The nature and function of the parallel tubular structures have to be investigated further. In Hodgkin's disease they may have significance for the understanding of an alteration in lymphocyte function and morphology.


Cyclic changes in the uterine phosphatases of Suncus murinus sindensis Anderson, the Indian common house shrew.

Cyclic changes in the phosphatases were studied histochemically in the uterine complex of the female Suncus. Alkaline phosphatase activity showed constant and predictable changes in the various phases of the cycle with the maximum activity during metaestrus. Acid phosphatase and ATPase activities also showed constant changes with moderate activity during diestrus and proestrus but with maximal activities during estrus and metaestrus. No proper localization of the enzyme is discernible in the case of G-1-Pase and G-6-Pase.


Histochemical localization of enzyme activity in the kidneys of male marmosets (Callithrix jacchus and Callithrix penicillata).

The distribution of several hydrolases and oxidoreductases was studied in the renal parenchyma of adult male marmosets (Callithrix jacchus and Callithrix penicillata). The oxidative enzymes showed a high reactivity in the proximal and distal tubules, whereas the hydrolases reacted strongly in the proximal tubules but only weakly or not at all in the thick limb of Henle's loop, distal tubules and collecting ducts. The NAD-dependent enzymes (except alpha-GPDH) showed a stronger reactivity in the proximal tubules, while the NADP-dependent ones were more reactive in the thick limb of Henle's loop and distal convoluted tubules. Two groups of interstitial cells were found in the medulla. A first group inside the outer medulla, showing cells rich in acid phosphatase and nonspecific esterases and a second group, close to the papilla, reactive to a certain number of oxidative enzymes. A different reactivity in cells of the distal convoluted tubules, thick limb of Henle's loops and collecting ducts (dark cells) was seen in the case of some enzymes like nonspecific esterase, alpha-GPDH and SDH.


Unusual infections of the nervous system in malignant lymphomas.

Infection of the nervous system by toxoplasma, cytomegalovirus and varicella-zoster virus is described in three adult patients with malignant lymphoma. Morphologic identification of these organisms in otherwise nonspecific lesions is emphasized. Since such intercurrent infections are not usually diagnosed clinically in debiliated patients, their recognition at autopsy is important, particularly in view of the wide spread distribution of these organisms in normal population.


[Primary and secondary glioblastoma. Distinction by glutamate dehydrogenase activity].

The study by bistochemical method of some dehydrogenases in 74 glioblastoma multiforma permits to distinguish several metabolic groups. But if particular attention is payed to the activity of glutamate dehydrogenase, it is noted to be observed only in the small, dedifferentiated cells when the survival postoperative time was more than twelve months. As it is known that an operated glioblastoma does not survive more than one year, except if it is a secondary glioblastoma, it is concluded that the existence of this enzyme in those little cells permits to distinguish secondary from primitive glioblastoma.


[Necrotizing herpetic encephalitis. Electro-clinical and pathological studies on two infantile cases (author's transl)].

The electroclinical and pathological features of two infantile cases of acute necrotizing herpetic encephalitis are reported. The distribution of the lesions has been compared with those observed in fourteen other cases including four with EEG records. Various electroencephalographic features have been recorded including repetitive slow spikes and periodic stereotyped paroxysmal discharges. The pathological data are interpreted to attempt unravelling the physiopathology of the EEG features.


[Recent medical research on yoga and states of concentration].

Traditional oriental thinking attracts the growing scientific interest of occidental practitioners. Dr. Pierre Etévenon, head of the Department of Neuro-Psycho-Pharmacology at the French Institute for Health and Medical Research (INSERM), held several conversations and scientific exchanges with the author, and kindly provided copies of some of his works. They are at the basis of the present paper. M. A. Descamps (Paris) found that asanas--yoga postures-- are generators of dynamic action when there is an extension of the spinal column, whilst they lead to quiet states when there is a flexion of it. Claeys and Gones (Belgium) proved that overall global relaxation, as well as differential relaxation were far more effective and deep when obtained by yogis than those attempted by University students majoring in Physical Education. Lonsdorfer and Nussbaum (France) studied several parameters concerning hatha-yoga and concluded that it provides a regular functioning of the main bodily functions fostering thus a psycho-physical balance. Wallace and Benson (U.S.A.) proved that transcendental meditation increases aerobic metabolism, counteracting anaerobic metabolism which is related to mental distress. Etévenon (Paris) investigated neurophysiological effects of yoga in connection to ancient Indian concepts (Upanishads) on sleeping, meditation and degree of consciousness. Dr. Etévenon has studied the phylogenetic evolution of waking-sleeping cycles, focusing on phylogenetic and ontongenetic appearances of REM cycles (activated sleep). A correlation has been made with EEG studies during states of concentration (yoga, transcendental meditation, Zen). These states have been found to be specific brain activities, and different from deep sleep, in spite of certain similarities in the EEG. Several hypothesis are set forth to explain brain activities underlying sites of concentration. The possibilities of developing a conscious mastering of dreams are also under research, and special attention is paid to the works of Saint Denys (1867), and hindu tradition. This paper discusses also the psychological, therapeutic and anthropological implications of recent discoveries in the field.


The diagnostic value of hypothalamic-pituitary-adrenocortical function tests in patients with Cushing's syndrome.

The following examinations, including the estimation of urinary neutral steroid metabolites, plasma cortisol, the percentage of unbound-cortisol, cortisol production rate, plasma adrenocorticotrophin (ACTH), dexamethasone suppression test, ACTH stimulation test, metopirone test, lysine-vasopressin (LVP) test and insulin tolerance test, were conducted in 16 patients with Cushing's syndrome for the presence of hypercoticism and for identifying the cause of this syndrome. Of these tests, the measurements of plasma cortisol late in the day and single dose dexamethasone suppression test were most useful for the diagnosis of hypercorticism because of their reliability and simplicity. Urinary 17-KGS, THF/THE ratio, cortisol production rate and low dose dexamethasone suppression test were also useful, whereas insulin test and LVP test were less valuable for this purpose. For the identification of the causes of this syndrome, lysine vasopressin test and metopirone test were most reliable, and plasma ACTH was also useful for this purpose, whereas insulin test and ACTH stimulation test were less valuable.


Preparation of single cell suspensions from hepatoma cells in culture.

Fundamental examination was carried out on the liberation of single cells from hepatoma cells in culture. dRLa-74 cells derived from rat hepatoma, which hardly disperse as single cell suspensions with several proteolytic enzymes or EDTA alone, dispersed with a high yield of single cells by the combination of trypsin and EDTA. HUH-6 cells derived from human hepatoblastoma also showed similar results. The degree of cell dissociation by the combination was dependent on the incubation temperature or pH.


Undifferentiated patterns of key glycolytic and gluconeogenic enzymes in epithelial cell lines derived from rat liver.

Established epithelial cell lines derived from livers of 7-day (B, B-R, B-3-4-7, J-C-1, J-C-13, J-5-2-1, E-C-4 and E-C-7) and adult (AL-2, AL-3, AL-4, AL-5 and AL-6) rats were analyzed for hexokinase (HK), pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glucose 6-phosphatase (G6Pase) and fructose 1,6-diphosphatase (FDPase). None of the cell lines showed appreciable activities of adult type liver enzymes (HK Type IVs (glucokinase), PK Type L, G6Pase and FDPase). On the contrary, the activities of fetal type liver enzymes (HK Types I and II, PK Type M2 and G6PD) increased markedly as compared with dispersed cells or tissues of adult liver. 6PGD gave minimum changes in activity, and the 6PGD/G6PD ratio decreased consistently. HK Type III was found only in J-C-13, AL-5 and AL-6, while HK Type IVf (high Km) was present in all the cell lines examined. Possible explanations for the undifferentiated patterns of carbohydrate-metabolizing enzymes in the established cell lines, which have several evidence of hepatocyte origin, are presented.


Response of cat cerebellar vermis induced by sound. II. The role of the mossy and climbing fibers in acoustic transmission to the cerebellar cortex and influence of stimuli parameters.

Experiments were performed on cats under Chloralose or Nembutal anesthesia. The parameters of the acoustic click stimuli were found to have a strong influence on the responses registered from both the surface of the cerebellar vermis lobuli V up VII as well as from single units. It was shown that a stimulus frequency rate not greater than 1/2 s should be used, since higher frequencies caused strong attenuation of the response. The type of anesthesia did not change the latencies of reactions of both evoked potentials and single units. However, decreasing the strength of the click resulted in increased response latencies, in the case of single unit reactions. A very strong influence of weak visual stimuli on units was also observed. It is suggested that mossy fibers are the most important fibers in the transmission of acoustic information to the cerebellar cortex.


Encephalomyocarditis (EMC) virus infection of the femoral vein of newborn mice.

The EMC virus was found to infect and injure the femoral veins of newborn mice. EMC viral crystals were found in the advential fibroblasts of these veins. In view of the extensive damage observed in the extremely small amount of tissue examined electron microscopically, the extent of the viral phlebitis must have been considerable. The relationship of these findings to the pathogenesis of thrombophlebitis in man provokes interesting speculations.


Incorporation of the dietary trans fatty acid (C18:1) into the serum lipids, the serum lipoproteins and adipose tissue.

Two diets, identical except for differences in trans and cis fatty acids, were fed to rabbits in order to evaluate the effects of dietary trans fatty acids on the fatty acid composition of serum lipids, lipoproteins and adipose tissue. The animals were first starved to deplete adipose tissue stores and then were red a diet containing 15% of the calories as C18:1 trans fatty acid (elaidic acid). A second group received a diet containing an equivalent amount of C18:1 cis fatty acid (oleic acid). A third group of animals, the control group, was fed only the baseline low fat rabbit chow. Dietary trans fatty acid was incorporated into all serum lipid and lipoprotein fractions and into the adipose tissue. In the serum the triglycerides contained the greatest amount of trans fatty acid followed by the phospholipids with cholesterol esters containing the least. The trans fatty acids of the phospholipids and cholesterol esters were distributed equally among the lipoprotein fractions, but the triglycerides of high density lipoproteins contained less trans fatty acids than did the triglycerides of other lipoproteins. Adipose tissue developed a high content of C18:1 trans fatty acid (21.7%), apparently at the expense of C18:1 cis fatty acid. In addition to the incorporation of C18:1 trans fatty acid, the content of other fatty acids, including C18:2 and the total of C18:1 cis and trans, was influenced by the substitution of dietary trans for cis fatty acids. The serum phospholipids of the trans-fed rabbits contained more C18:2 than the phospholipids of the cis-fed rabbits. The serum cholesterol esters of the trans-fed rabbits contained more C18:2 and a smaller total of C18:1 (cis puls trans) than the cholesterol esters of the cis-fed rabbits. These differences indicated that C18:1 trans fatty acid was not necessarily the metabolic equivalent of 18:1 cis fatty acid. These results suggested that dietary trans fatty acids which are contained in hydrogenated margarines, shortenings and oils of the human diet are readily incorporated into the lipids of the body including membranous structures such as lipoproteins.


Hepatocellular carcinoma and intermediate alpha1-antitrypsin deficiency (MZ phenotype).

A case history of a 16-year-old boy with hepatocellular carcinoma and an intermediate deficiency of alpha1-antitrypsin (MZ phenotype) is presented. Previous reports have suggested that hepatocellular carcinoma may be associated with the Z variant of antitrypsin and either a severe or intermediate antitrypsin deficiency. The present case is unusual because of the rather high level of the serum trypsin inhibitory capacity for an MZ heterozygote (1.633 units), which may be due to involvement of the liver by the tumor or to a recent partial hepatectomy. PAS-positive antitrypsin globules were seen in the primary tumor and in nodules metastatic to the mesentery, as well as in nonneoplastic portions of the liver. Hepatocellular carcinoma is another disease state that may occur preferentially in individuals with either severe or intermediate deficiencies of alpha1-antitrypsin.


Ex-hospital clients evaluate their aftercare experiences.

Seventy-two previously hospitalized clients of an inner-city community clinic, assigned to three treatment groups - medication-only, medication plus individual therapy, and medication plus therapy plus group experiences - evaluated their respective aftercare programs by responding to five questions. As compared with the others, medication-only clients were less inclined to see either the clinic or the medication as preventing rehospitalization, were alone in reporting that the clinic was responsible for preventing rehospitalization to the extent that the medication was effective, and responded to the question of rehospitalization by emphasizing worsening symptoms. Others emphasized therapy failure. Clients agreed with the professionals - aftercare should not be medication alone.


Nosocomial and maternally acquired herpesvirus hominis infections. A report of four fatal cases in neonates.

Four fatal cases of neonatal herpes simplex infection occurred during a two-month period in the perinatal intensive care unit of a hospital. Virus isolation or serologic studies, or both, implicated herpesvirus hominis type 2 in all four cases. Three of the infants developed symptoms in the first week of life and were probably infected in utero or at delivery. The fourth infant did not develop signs of illness until age 6 weeks, an interval much longer than that expected with disease acquired at birth. An epidemiologic investigation indicated that the most likely source of this fourth infant's herpes infection was by indirect contact with one of the other three infected neonates. Nosocomial spread of herpes simplex virus within a hospital nursery, although uncommon, may pose an added risk to the newborn infant if nursery techniques among infants are compromised.


Hypoglycemia in hypopituitary children.

Fifty-two children with growth hormone (GH) deficiency were examined for factors that might influence development of hypoglycemia. Symptomatic and asymptomatic hypoglycemia occurred with equal frequency in children with isolated GH and multiple anterior pituitary deficiencies. Of 52 children, nine (17%) had symptomatic hypoglycemia and 14 (27%) had asymptomatic hypoglycemia. Symptomatic hypoglycemia was more frequent in children who were both young (less than 4 years of age) and lean (elevated height age/weight age [HA/WA] ratio). With HGH therapy, these children had decreases in HA/WA ratios and improvement in carbohydrate homeostasis. Insulin responses to oral glucose and intravenous arginine administration were substantially lowered in children with symptomatic hypoglycemia, A deficiency of gluconeogenic substrate or impairment of amino acid mobilization may be a factor in the development of hypoglycemia in hypopituitarism similar to that postulated for  ketotic hypoglycemia.


Primary aldosteronism. A study in contrasts.

Two patient with primary aldosteronism, one with a solitary adrenal adenoma and the other with bilateral nodular hyperplasia, are described. Both patients showed the classic features of primary aldosteronism in electrolyte and hormone patterns, but there were important differences in the biochemistry of their excised adrenal tissue. In addition, the injection of plasma from the patient with bilateral adrenal hyperplasia into the sheep's transplanted adrenal gland elicited a definite aldosterone secretory response, but there was no aldosterone response to the injection of plasma from the patient with a solitary adrenal adenoma. The findings support the hypothesis that an extra-adrenal stimulus may contribute to the pathogenesis of bilateral adrenal hyperplasia.


Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis.

The level of serum angiotensin-converting enzyme (ACE) was elevated in 15 of 17 patients with active sarcoidosis. Serum ACE was studied to determine the effect of chronic lung disease upon the blood level of an enzyme believed to originate from the lungs. The assay was performed in approximately 200 control subjects and 200 patients with chronic lung disease using hippuryl-L-histidyl-L-leucine as substrate. Enzyme activity greater in male control subjects than in female subjects of comparable age and greater in children than in adults. Serum ACE was significantly reduced in patients with chronic obstructive lung disease, lung cancer, tuberculosis and cystic fibrosis, as compared to control subjects, and was even lower in those receiving corticosteroids. Of greatest interest, however, was that levels in patients with active sarcoidosis not receiving steroids were greater than 2 standard deviations above the mean for the adult control subjects (greater than 11.6 units) whereas levels in patients with sarcoidosis receiving steroids and in those with resolved disease were normal. A survey of subjects with other granulomatous diseases failed to reveal any other condition that was significantly associated with a similar elevation of serum ACE levels. Elevation of ACE levels in sarcoidosis appears to be associated with the active disease process and  does not appear to be a familial inherited enzyme abnormality. An assay of serum ACE is a useful tool for regulating therapy in sarcoidosis and for confirming the diagnosis, since it readily distinguishes these patients from others with tuberculosis, lung cancer or lymphoma.


Immunology of sarcoidosis.

The cardinal immunologic changes in sarcoidosis consist of depression of delayed-type hypersensitivity, hyperreactive circulating antibody responses and the Kveim-Siltzbach skin test phenomenon. Depression of delayed-type hypersensitivity is demonstrated by skin tests using tuberculin, mumps, pertussis, trichophytin, oidiomycin, dinitrochlorobenzene and Californian keyhole limpet hemocyanin. The cultured lymphocytes from patients with depression of delayed-type hypersensitivity react poorly to phytohemagglutinin, and there is a close correlation between anergy of lymphocytes in culture and by cutaneous anergy. In vivo cutaneous anergy mirrors in vitro cellular hyporeactivity. Other technics used to expose immunologic defects in peripheral lymphocytes of patients with sarcoidosis include tests of T and B cell function, rosetie formation and migration inhibition. Whereas there is cutaneous anergy and impaired cellular immunity in patients with sarcoidosis, the reverse holds for circulating factors. There are increased circulating immunoglobulin levels, increased circulating antibody levels to Epstein-Barr, herpes simplex, rubella, measles and parainfluenza viruses, increase antibody response to mismatched blood and occasional false-positive Wassermann reactions, but there is no increase in circulating autoan tibodies. There is no evidence that patients with sarcoidosis belong predominantly to any particular histocompatibility locus. Worldwide figures for the Kveim-Siltzbach skin test are presented. They provide evidence of its specificity in various international series. The causes of nonspecific reactions are discussed.


Hereditary cataracts in deer mice (Peromyscus maniculatus).

A new type of hereditary cataract was predicted in the deer mouse (Peromyscus maniculatus) by the presence of syndactyly of the hind feet. Early morphologic changes were found in the equatorial cells that differentiated into new lens fibers. Later swelling at the anterior and posterior poles of these cells produced lens opacities. Anterior and posterior subcapsular cataracts progressed to a hypermature shrunken lens.


A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration.

A 23-year-old man had slow psychomotor development at 6 months of age and developed intermittent corneal clouding at about 18 months. He developed a truncal ataxia and hypotonia of the limbs combined with spasticity and active deep reflexes that did not progress. His skeleton and facies were normal. Between 1 and 13 years of age, he developed severe optic atrophy, absence of retinal blood vessels, and an extinguished electroretinogram. Biochemical analysis of cultured fibroblasts indicated no lysosomal hydrolase deficiency; cellular metachromasia was absent and there was no mucopolysaccharidoses. Ultrastructural studies indicated single-membrane-limited vacuoles containing lamellated membranes and a polymorphous substance in tissue-cultured cells and conjunctiva.


The influence of prostaglandin endoperoxides on platelet ultrastructure.

Prostaglandin endoperoxides produced during aggregation of blood platelets are potent promoters of platelet aggregation and the release reaction. The present investigation has studied the effects of prostaglandin endoperoxides produced by platelet microsomes after incubation with arachidonic acid on the ultrastructure of platelets. Prostaglandin endoperoxides caused platelet pseudopod formation and internal transformation associated with a contractile wave within the platelet. The contractile process was similar to that seen following incubation of platelets with collagen or thrombin but was more complete than that seen with 25 muM ADP. Platelet aggregation was more prominent in unstirred samples incubated with the prostaglandin endoperoxides than in samples similarly incubated with 25 muM ADP. Dilatation of the open canalicular system was not a prominent feature except at 45 minutes after addition of the endoperoxides to the platelets, when the platelets appeared to be in a recovery phase. We conclude that the endoperoxides promote platelet stickiness and platelet aggregation by directly or indirectly stimulating the platelet contractile system.


The course and nature of acinar cell death following pancreatic ligation in the guinea pig.

The course and nature of acinar cell death (ACD) following pancreatic ligation in the guinea pig was studied as a possible model for human disease. Ultrastructural studies after various periods of ligation suggested a biphasic pattern of ACD. Early phase ACD involved only a small portion of acinar cells and occurred within a few hours of ligation. It was preceded by swelling and vesiculation of the rough endoplasmic reticulum. Morphometric measurements disclosed celular swelling at this time, and NaCl equilibration studies demonstrated a change in cellular osmoregulation. Late phase ACD, characterized by cellular wasting and autophagic vacuole formation, became prominent several days after ligation. Marked increases in lysosomal enzyme activities were found in tissue homogenates at this time, and acid phosphatase electron histochemistry localized the majority of this increased activity to lysosomes and autophagic vacuoles within the acinar cells. The etiology and nature of both phases of ACD are discussed.


Production of ferritin by rat hepatoma cells in vitro. Demonstration of protein subunits and ferritin by immunofluorescence.

Using precipitating antibodies to ACI rat liver ferritin and to sodium-dodecyl-sulfate-dissociated protein subunits of ACI rat liver ferritin, we have demonstrated the presence of ferritin-positive sites and subunit-positive sites in situ in several rat hepatoma cell lines by immunofluorescence. Hepatoma cells from three transplantable rat hepatomas (Reuber H-139, Reuber H-35, and Morris 5123) were explanted and propagated. Rabbit antibodies specific for either protein subunits of ferritin or ferritin were prepared by affinity chromatography or by dissociation of antibody-antigen complexes with 0.1 M acetic acid followed by differential ultracentrifugation. Explants of Reuber H-139, Reuber H-35, and Morris 5123 hepatoma cells, grown either in ordinary McCoy's 5a medium or in such medium enriched with iron (0.002% Fe), gave positive immunofluorescence for subunits as well as ferritin. Exposure of a clonal strain of Morris 5123 hepatoma cells to iron-enriched culture medium for varying lengths of time of up to 24 hours resulted in progressive increase in the quantity of ferritin-specific immunofluorescent cytoplasmic material, which was at first present diffusely, and later in clumps. By contrast, during the initial 24-hour period, subunit-specific immunofluorescence remained at relatively low intensity, with diffuse distribution through the cytoplasma. Our findings indicate a) the presence, in the cytoplasm, of the three kinds of hepatoma cells, of unassembled or only partly assembled subunits of fragments of subunits as well as of ferritin, and b) rapid assembly of the protein subunits into apoferritin and ferritin after administration of iron, so that the concentration of subunits in the cytoplasm was not significantly increased.


Quantitative study on the effect of an ACTH-producing pituitary tumor on the ultrastructure of the mouse adrenal gland.

The ultrastructure of the adrenal cortex was studied by quantitative stereologic techniques in LAF1 mice bearing a transplantable, ACTH-secreting pituitary tumor (AtT). The tumor stimulated a significant increase in volume and surface area of smooth endoplasmic reticulum and mitochondrial membranes in all three zones of the adrenal cortex. Concomitantly, plasma corticosterone was increased significantly in tumor-bearing animals. The AtT was an adenoma of the chromophobe type. Continuity of the nuclear membrane with the rough endoplasmic reticulum was readily observed in tumor parenchymal cells.


The lead line in bone---a lesion apparently due to chondroclastic indigestion.

The metaphyseal line of increased radiodensity which occurs in lead poisoning was studied in children and young monkeys with lead encephalopathy and in guinea pigs. The histologic lesion consists of impaired resorption of calcified metaphyseal cartilage, depressed bone deposition on cartilaginous surfaces, and the accumulation of numerous multinucleate giant cells, some containing lead inclusions. By electron microscopy, the giant cells appear to be osteoclasts and chondroclasts containing large amounts of mineralized cartilage matrix. We interpret the lead line to be the result of a lead-induced inability of cartilage-resorbing cells to degrade mineralized matrix, with a resultant impairment of metaphyseal cartilage resorption. The radiodensity of the lead line would thus be due to persistent mineralized metaphyseal cartilage and not to a primary osseous change. Some observations on lead inclusions in these cells suggest that the fibrillar component forms before the amorphous part.


Coronary artery cyclic AMP content during adrenergic receptor stimulation.

The purpose of this study was to test the hypothesis that the mechanical response of coronary smooth muscle following adrenergic receptor stimulation was mediated by changes in cyclic AMP content. Dibutyryl cyclic AMP caused relaxation of coronary artery strips. Aminophyline caused relaxation and a 254% elevation of cyclic AMP content (P less than 0.005). Phenylephrine caused contraction but no significant change in cyclic AMP content (P greater than 0.4). Epinephrine alone caused contraction and a 99% elevation of cyclic AMP content (P less than 0.001). The alpha blocker, phentolamine, reversed the mechanicaal response to epinephrine, but it did not significantly (P greater than 0.15) reduce the effect of epinephrine on cyclic AMP content. Propranolol enhanced the contractile response to epinephrine and attenuated the epinephrine-induced increase in cyclic AMP content. These results suggest that the contraction of coronary arteries associated with alpha-receptor stimulation is not mediated by changes in cyclic AMP content; however, relaxation associated with beta-receptor stimulation may be mediated by an increase in cyclic AMP content.


Estimation of cyclic AMP turnover in normal and methylprednisolone-treated dogs: effect of catecholamines.

The turnover rate of plasma cAMP was measured in unanesthetized normal and methylprednisolone (MP)-treated dogs with [8-3H]cAMP. Determination of specific activity was based on saturation of the specific binding protein, thus bypassing the need to know the plasma level of cAMP. In normal dogs the infusion of epinephrine increased plasma glucose by 33% and both the plasma level and rate of appearance (Ra) of cAMP 2.5-fold. Treatment with MP decreased the concentration as well as the turnover rate of cAMP by about 50%. It greatly potentiated not only the hyperglycemic effect (4-fold) of epinephrine but also the rise of plasma cAMP (8.5-fold) and that of Ra (6.8-fold). Norepinephrine infusion increased cAMP only by 50%. This effect was not potentiated by MP treatment and not altered by Na nicotinate. There was a linear correlation between plasma cAMP concentration and the rate of disappearance (Rd) of cAMP. It is concluded that: a) the increase of hepatic glycogenolysis is accompanied by a rise of cAMP output, whereas that of lipolysis is not; b) glucocorticoid treatment affects cAMP turnover; and c) the plasma level of cAMP is controlled by Ra, whereas Rd is the result of the mass-action effect of the concentration.


Hypercholesterolemia of total starvation: its mechanism via tissue mobilization of cholesterol.

After the establishment of a relatively linear decay curve for plasma [4-14C]cholesterol, rabbits were starved for 26-32 days. The plasma cholesterol concentration increased 400% during starvation. Concurrently, the plasma triglyceride level declined by 50%. While the plasma cholesterol was rising, the cholesterol specific radioactivity of the plasma remained unchanged in starved animals, but in control animals the plasma cholesterol specific radioactivity declined substantially. The cholesterol content of the liver and adipose tissue increased with starvation. The cholesterol specific radioactivities relative to plasma for adipose tissue were lower in the starved animals versus controls. These results support the hypothesis that cholesterol stored in the lipid droplet of the adipose tissue cell is released into plasma and is the chief source of the hypercholesterolemia observed during complete caloric starvation. Cholesterol metabolism in the starved animal can be depicted as a virtually closed system in both the input from biosynthesis and diet being low or zero and the output likewise being close to zero.


Hepatoma associated with anabolic steroid therapy.

A patient with Fanconi's anemia who developed a hepatoma after 50 months of therapy with anabolic steroids is reported. The lesion presented as a cold focal defect on a Tc99m sulfur colloid scintigram, but was avascular on dynamic scintigraphy. Both the unusual avascularity of the hepatoma, and its association with anabolic steriod therapy are discussed.


[Electron microscopic investigations of vitreous collagen after treating the vitreous with liquefying substances (author's transl)].

By electron microscopic studies collagenase, hyaluronidase, HCl, ascorbic acid, and iron ions have been found to attack the collagen fibers of bovine vitreous. Because of the possible role of ascorbic acid in collagen synthesis and the ability of ascorbic acid to degrade hyaluronic acid and collagen we suggest that the ascorbic acid of the vitreous essentially participates in construction and metabolism of the vitreous body.


On the function of sleep.

It is proposed that sleep serves the function of maintaining immobility in animals at times when immobility is an optimum behavioural survival strategem. Sleep is of great evolutionary age and is always carefully tailored to the life-style of each animal; abundant in some species and absent from others. The survival advantages conferred on an animal by the power of sleep to schedule behaviour effectively may justify its existence and persistence in the evolution of species.


Mammary cancer in the dog: a study of 120 cases.

Of the 120 cases of mammary cancer occurring in 117 female dogs (15 spayed), 2 male dogs, and 1 dog of undetermined sex, 107 (nearly 90%) were observed in dogs 8 to 15 years old. Mammary tumors occurred in nearly 14% of 875 female dogs with neoplasms. Nearly 60% of 128 neoplasms were located in the 4th and 5th mammary glands. Of the 128 cancers in these 120 dogs, 85 were classified as duct carcinoma, 38 as lobular carcinoma, 3 as malignant mixed tumor, and 2 as duct and lobular carcinomas. Most duct carcinomas originated in the epithelial cells of ducts at all levels, and a few arose in previously benign duct papillomas. The lobular carcinomas arose in alveoli and developed into progressively larger lobules. A negative factor in the development of mammary cancer is ovariectomy before or shortly after the first estrous cycle in the dog and before the age of 40 in women. In both dog and man, aging is a positive factor in the development of mammary cancer. In women, other positive factors are nulliparity and inheritance; e.g., a high rate of breast cancer in close female relatives of Jewish extraction. An epidemiologic study of breast cancer in man and dog in high-risk countries(e.g., United States) and low-risk countries (e.g., Japan) is indicated.


The chemotaxis of selected cell types to connective tissue degradation products.

Because rheumatoid inflammation is associated with the presence of large numbers of leukocytes in joint effusions, the question of whether enzymatic splitting of collagen and fibrin can lead to generation of chemotactic factors was investigated. Fibrinogen was purified from the plasma of four different species, and the homogeneity of the preparations was established by physicochemical and immunologic techniques. Fibrin was prepared and then lysed with plasmin to obtain fibrin degradation products (FDP). Similarly, purified collagenase was used to lyse collagen in vitro, and the chemotactic activity of the reaction mixtures was analyzed. The experiments presented indicate that fibrinogen, fibrin, and plasmin do not possess any intrinsic chemotactic activity. However, when fibrin was split by plasmin, FDP of human, bovine, sheep, and equine origin all proved to be strong leukotactic agents for polymorphonuclear leukocytes (PMN). Purified collagenase per se was found to be a cell type-specific chemotactic agent for PMN. Not only were collagen degradation products not chemotactic, but they also inhibited the leukotactic activity of the purified collagenase. Furthermore, this inhibition of the chemotactic activity of collagenase was independent of its enzymatic activity. The results presented suggest that there is a direct correlation between the process of fibrinolysis and the chemotactic attraction of leukocytes and between the presence of collagenase and leukotaxis. This system may serve as a model to explain the mechanisms by which cells accumulate in inflamed joints.


Prostaglandins in the rheumatic diseases.

The prostaglandins may participate in the pathogenesis of the inflammatory rheumatic diseases by acting as mediators of inflammation and in promoting bone resorption. Levels of PGB (presumed to arise from PGE) in synovial fluids are elevated in the majority of a group of patients with inflammatory rheumatic diseases, as compared to similar patients treated with aspirin and indomethacin and patients with osteoarthritis. Rheumatoid synovium produces large amounts of PGE2 in organ culture. In addition, fibroblast cell lines derived from rheumatoid synovia synthesize more PGE and more cAMP than do cells from normal synovia or skin. The media from rheumatoid synovial organ cultures contain large quantities of bone-resorbing activity toward mouse calvaria in vitro. The bone resorption can be accounted for by PGE2 produced by the synovia, because the activity and PG synthesis are inhibited by more than 90% by incubation of the tissue with indomethacin, because it is quantitatively extractable into ether, and because it bears a relationship to the concentrations of PGE2 present, as measured by radioimmunoassay.


[Mechanism of hyocorticosteronemia action of Strongyloides ratti in the rat].

In order to explain the hypocorticosteronemia which establishes itself in rats with Strongyloides ratti parasites, we are proceeding with a functional exploration of the hypothalamo-hypophyso-corticosurrenal axis in experimentally infested rodents. The adreno-cortico-tropic-hormone test (A.C.T.H.), stress to ether and the Lysin-8-Vasopressin and Metopirone tests lead to concordant results: -- the hypothalamo-pituitary-corticosurrenal present a functional integrity which allows it to react normally to direct stimulation or to feed-back; -- the deficiency seems to relate to the hypothalamic secretion of the cortico-releasing factor; -- the cause would stem from an inhibition of the nervous mechanism which regulates this neurosecretion.


Detection of agents that alter the bacterial cell surface.

Proteus mirabilis is not killed by polymyxin B, normal serum, or sodium deoxycholate. Exposure to polymyxin B renders the cells susceptible to killing by the latter two agents. The data suggest that this synergism is due to polymyxin B-induced surface changes. The results point out an inadequacy of existing methods of screening for antibiotics; they fail to detect agents which, while showing no in vitro effect on growth, may alter a resistant organism so that it becomes more susceptible to other antimicrobials or host defense mechanisms. A method is described which can be used to detect such cell surface-modifying agents.


Non-myogenic tumors involving skeletal muscle. A survey with special reference to alveolar soft part sarcoma.

Skeletal muscle is remarkably free of neoplasms despite its great body mass. Metastatic tumors to skeletal muscle are distinctly uncommon. Primary myogenous tumors (defined as those whose cytoplasm contains myofibrils) are infrequent, compared to primary lesions of supporting stroma and vascular origin. Almost all non-myogenic tumors of striated muscle occur also in other areas of the body and many represent extension from contiguous structures. The distinctive non-myogenic tumor which occurs exclusively in skeletal muscle, alveolar soft part sarcoma, has ultrastrucutral features of a secretory lesion with distinctive membrane bound crystalloids which may be lipid in nature. The ultrastructural features of alveolar soft part sarcoma do not support a myogenous derivation.


Activity of gentamicin, tobramycin, polymyxin B, and colistimethate in mouse protection tests with Pseudomonas aeruginosa.

Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.


Diagnostic value of cytologic specimens obtained from children with cancer.

The practical value of cytologic examination in the clinical management of children with cancer was determined by analyzing 2,363 cytologic specimens collected during a two year period. The specimens included cerebrospinal fluid, pleural and peritoneal effusions, urine and tracheal aspirates from 347 children with cancer. Malignant tumor cells were detected in 266 specimens obtained from 106 children with the following malignant neoplasms: leukemia 44/133, malignant lymphoma 13/64, soft tissue sarcoma 13/48, neuroblastoma 13/26, Wilms' tumor 4/18, malignant teratoma 4/13, osteogenic sarcoma 7/11, Ewing's sarcoma 2/10, brain tumor 5/6 and retinoblastoma 1/1. No malignant cells were detected in fluids from 18 patients with other tumors. The malignant cells were identified most ofter in spinal fluid, pleural and peritoneal effusions. Cytologic examination appears to be of value in the clinical management of children with cancer.


Action of polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella typhimurium and Escherichia coli B.

Though the primary action of the cationic antibiotic polymyxin B is against the membrane of susceptible bacteria, severe morphological changes are detected in the cytoplasm. Using fluorescence microscopy and a mono-N-dansyl-polymyxin B derivative, we could demonstrate aggregations of the antibiotic with cellular material, possibly nucleic acids and/or ribosomes. These aggregations were only produced by minimum inhibitory or higher concentrations of the antibiotic as shown with Salmonella and Escherichia strains differing in their polymyxin susceptibility. The outer membrane of Salmonella typhimurium revealed characteristic blebs when treated with polymyxin B. This was investigated by the gentle methods of spray-freezing and freeze-etching. The obtained electron micrographs suggest that the polymyxin-induced blebs are projections of the outer monolayer of the outer membrane. A possible mechanism of penetration of polymyxin B through the cell envelope of gram-negative bacteria is presented.


Removal of enteroviruses from sewage by bench-scale rotary-tube trickling filters.

The efficacy of a rotary-tube type of trickling filter for removing coxsackievirus A9, poliovirus 1, and echovirus 12 suspended in raw settled sewage was investigated. At filtration rates equivalent to about 10 MGD (million gallons per day)/acre (ca. 3,785 m3/day per acre), the filters removed 95% of the poliovirus, 83% of echovirus 12, and 94% of coxsackievirus A9. Coliform, fecal streptococci, biochemical oxygen demand, and chemical oxygen demand removals were remarkably similar, averaging 94, 92, 93, and 95%, respectively. At filtration rates equivalent to about 23 MGD/acre, 59% of the poliovirus, 63% of the echovirus 23, and 81% of the coxsackievirus A9 were removed. Coliform, fecal streptococci, biochemical oxygen demand, and chemical oxygen demand removals at this filtration rate were 68, 75, 72, and 56%, respectively. Viruses were assumed to be adsorbed to the biological slime growing in the filters, but attempts to disassociate the viruses from the slime were unsuccessful, indicating that the slime-virus complex is very stable or that the viruses were somehow inactivated. The data indicate that coliform and fecal streptococci reductions in this type sewage treatment process can be used as an index of virus reduction. Disinfection, however, must be used to ensure a virus-free final effluent.


Microbiological hazards of household toilets: droplet production and the fate of residual organisms.

Large numbers of bacteria and viruses when seeded into household toilets were shown to remain in the bowl after flushing, and even continual flushing could not remove a persistent fraction. This was found to be due to the adsorption of the organsims to the porcelain surfaces of the bowl, with gradual elution occuring after each flush. Droplets produced by flushing toilets were found to harbor both bacteria and viruses which had been seeded. The detection of bacteria and firuses falling out onto surfaces in bathrooms after flushing indicated that they remain airborne long enough to settle on surfaces throughout the bathroom. Thus, there is a possibility that a person may acquire an infection from an aerosol produced by a toilet.


Survival of human enteric and other sewage microorganisms under simulated deep-sea conditions.

The survival of pure cultures of Escherichia coli, Streptococcus faecalis, Clostridium perfringens, and Vibrio parahaemolyticus under simulated deep-sea conditions of low temperature (4 C), seawater, and hydrostatic pressures ranging from 1 to 1,000 atm was determined over a period exceeding 300 h. The viability of E. coli and total aerobic bacteria in seawater-diluted raw sewage subjected to these deep-sea conditions was also measured. There was a greater survival of both E. coli and S. faecalis at 250 and 500 atm than at 1 atm at 4 C. S. faecalis was quite insensitive to 1,000 atm, whereas with E. coli there was a 10-fold die-off per 50-h exposure to 1,000 atm. In contrast, V. parahaemolyticus and C. perfringens were quite sensitive to pressures exceeding 250 atm, and with both of these species there was a total loss of viability of approximately 10(8) cells per ml within 100 h at 1,000 arm and within 200 h at 500 atm. The viability of the naturally occurring fecal coliforms in sewage exposed to moderate pressures at 4 C was found to be similar to the survival patterns demonstrated with pure cultures of E. coli. The total numbers of aerobic bacteria in these sewage samples, however, stabilized at 500 and 1,000 atm after 100 h, and at 1 and 250 atm there was significant growth of sewage-associated bacteria, which apparently utilized the organic compounds in the seawater-diluted sewage samples. A preliminary classification of some of these bacteria indicated that approximately 90% (160 isolates) of the organisms that survived over a 400-h exposure to 500 and 1,000 atm were Arthrobacter/Corynebacterium species, and the representative organisms capable of growing at 1 and 250 atm in seawater at 4 C were gram-positive cellulose digesters and an unidentified gram-negative coccus. The significance of these results with respect to the contamination of the deep ocean with human pathogens and the possibility of sewage-associated microorganisms growing and competing with indigenous marine microbial flora in situ is discussed.


Inhibition of Clostridium botulinum by strains of Clostridium perfringens isolated from soil.

Thirty-one soil samples were examined for the presence of organisms capable of inhibiting growth and toxin production of strains of Clostridium botulinum type A. Such organisms were found in eight samples of soil. Inhibiting strains of C. perfringens were found in five samples, of C. sporogenes in three and of Bacillus cereus in three. Three of the C. perfringens strains produced an inhibitor effective on all 11 strains of C. botulinum type A against which they were tested, seven of eight proteolytic type B strains, one nonproteolytic type B strain, five of nine type E strains and all seven type F strains, whether proteolytic or nonproteolytic. They did not inhibit any of 26 type C strains, 6 type D strains, 4 type E strains, or 24 C. sporogenes strains. In mixed culture, an inhibitor strain of C. perfringens repressed growth and toxin production by a C. botulinum type A strain even though it was outnumbered by the latter about 40 times. It also repressed growth and toxin production of C. botulinum in mixed culture of soils in which this latter organism naturally occurred when cooked meat medium but not when trypticase medium was used.


Nitrosyl-hemoglobin formation in the blood of animals exposed to nitric oxide.

Animals were exposed to nitric oxide (NO) in order to study its biological effect. First a method was developed to exclude nitrogen dioxide formed during exposure of NO. Nitrosyl-hemoglobin (NOHb) in the blood of mice, rats, and rabbits exposed to NO was determined by electron spin resonance spectrometry at -100C. The content of NOHb in the blood of the mouse reached the maximum (0.13% of the total hemoglobin) 20 minutes after the exposure was begun and thereafter a state of equilibrium was maintained. The NOHv level decreased to one half in several minutes after the mouse was removed to a filtered air environment. Dose-response relationship was observed between gas concentrations and the maximum NOHb level.


Evaluation of craniofacial surgery in the treatment of facial deformities.

Surgical access to the cranial, orbital, and facial areas, as developed by Tessier, has produced not only definitive repair of previously uncorrectable congenital deformities such as orbital hypertelorism and facial stenosis (e.g., Crouzon's, Apert's syndromes) but also has improved markedly the treatment of traumatic and neoplastic defects. The surgical approach allows complete dissection of facial soft tisses including the orbits from the underlying bones followed by corrective osteotomies and fixation. Mobilization of the frontal lobes through a frontal bone flap exposure may be required. The ramifications of this latest intrusion by surgeons into a previously inviolate anatomic area have involved neurosurgeons, ophthalmologists, anesthesiologists, and dental and psycho-social disciplines. The disciplines of genetics and embryology are being influenced by this new field of surgery, much as the study of immunology was influenced by transplantation surgery two decades ago. This report analyzes a 10 year experience with over 100 patients with emphasis on patient selection by disease, age, intellectual status, morbidity, complications, and the psycho-social reactions of patient and family. Procedures initially planned to correct dental and aesthetic defects are proving beneficial for other functions including hearing, taste and smell, articulation and tongue movement, respiratory function, vision, and possibly bone growth. The development of self image, a normal process always in operation, is also strikingly altered. These operations may last as long as 14 to 16 hours. We have had no deaths or postoperative blindness. One postoperative cerebrospinal fluid leak was successfully repaired. Three partial losses of bone grafts and four instances of late cellulitis have occurred. Prevention of infection seems related to avoidance of dead spaces and primary closure of all mucosal, dural, conjunctival and skin surfaces.


The prediction of hormonal dependency of mammary cancer.

The estrogen receptor protein (estrophilin) was determined in specimens from 359 primary breast cancers and from metastatic tumors of 214 patients. Ninety-eight patients were eventually treated by some form of endocrine therapy: 82 patients were treated by ablative therapy, and 16 by hormonal additive treatment. The records of 81 of the 98 patients whose tumors were characterized for estrogen receptor content and who had received some type of endocrine therapy were reviewed by a peer review group that assessed the objective data for these patients regarding objective remission or failure to treatment. A positive estrophilin determination was defined as receptor content greater than 250 fmole per gram of tumor for premenopausal females and greater than 750 fmole per gram of tumor for postmenopausal and previously castrated patients. Estrogen receptor determinations may be made from tumor specimens as small as 200 mg. Sixty-nine patients underwent some form of ablative therapy. Twenty-seven of these patients were found to have significant receptor determinations. Of those patients in whom a definite determination was made of their post-treatment response, roughly two-thirds experienced objective remissions. None of the 42 patients with negative estrogen receptor determination experienced an objective remission to ablative endocrine therapy. Only one of 6 patients with negative determinations benefited from additive hormonal therapy; 4 of 6 patients with positive determinations benefited from additive therapy. Not all women with receptor containing mammary cancer will respond favorably to endocrine therapy, but those patients whose tumors lack a critical amount of estrophilin have little chance of benefit from either endocrine ablation or hormone administration. The estrogen receptor content of the primary tumor indicates the hormonal dependency of the tumor and may be used to predict the response to endocrine treatment when recurrent disease appears.


Effect of thymectomy on zoxazolamine paralysis and metabolism in untreated and (PCN) pregnenolone-16alpha-carbonitril- or ACTH-pretreated rats.

The effect of thymectomy on zoxazolamine paralysis and metabolism was investigated in young female untreated and PCN- or ACTH-pretreated rats. Thymectomy performed at least 24 hr before injection of zoxazolamine significantly prolonges paralysis time. Pretreatment with PCN (an inducer of hepatic microsomal enzymes) or ACTH (known to alter protein binding and excretion of zoxazolamine) shortened paralysis in thymectomized animals; but only in comparison to thymus ablated controls. The surgical intervention seemed to decrease the metabolism of zoxazolamine in the 9,000g supernatant fraction of the liver.


Effect of methadone on the male reproductive system.

Daily injections (s.c.) of methadone HCL (5, 10 or 20 mg/kg) for 5 or 10 days caused significant regression (p less than or equal to 0.05) in the weights of sex accessory organs and testes in mature mice. Similar treatment regimens led to significant elevations in the levels of cyclic adenosine monophosphate (cAMP) in the prostate gland (P less than or equal to 0.05). Daily injuctions of morphine sulfate (10, 20 or 40 mg/kg) likewise caused significant increases in cAMP levels in the prostate gland (P less than or equal to 0.05). When either of these drugs were incubated in vitro with prostate glands obtained from normal mice, the cAMP levels were also observed to be elevated (P less than or equal to 0.05). The results reveal that so-called analgesic drugs can exert deleterious actions upon male reproductive tissues in the mouse.


Further studies on the effect of cyclic nucleotides on testis DNA synthesis.

The inhibitory effect of dibutyryl cyclic AMP (dbcAPM) on in vitro rat testis DNA synthesis appears to be relatively specific in nature. Of 7 organs studied, only testis and kidney in vitro DNA synthesis was significantly affected. In addition, another cyclic nucleotide, dibutyryl cyclic GMP (by dbc AMP), had no effect on in vitro testis DNA synthesis. This was true whether testis tissue was mature or immature. Similarly, by dbcAMP had no significant effect on in vitro testicular protein or RNA synthesis. The inhibition of in vitro testicular DNA synthesis by dbcAMP occurs while 3H-cAMP is accumulating in testis tissue.  dbcGMP was found to have no antagonistic effect towards the inhibitory effect of dbcAMP on in vitro testis DNA synthesis.


[Antibodies in patients with cervicouterine carcinoma].

Cervical smears and serum samples were obtained from 28 ABO compatible patients with carcinoma of the cervix (CaCx) in O to IV clinical stages. Serum IgG antibodies against autologous CaCx cells were detected by immunofluorescence reactions in 24/24 patients with carcinoma of the cervix in I to IV clinical stages. These antibodies also reacted against alogeneic CaCx cells 53/54. Negative reactions were obtained n 4/4 cases of carcinoma of the cervix in stage O, and in control group, 10 normal persons and in 33 neoplastic sera from patients with other malignancies. Hence, detection of serum antibodies against CaCx cells could be an additional tool for CaCx detection.


[Neonatal lactic acidosis and hypoglycemia due to a congenital hepatic fructose-1,6-diphosphatase deficiency].

Famialial defect of hepatic fructose-1,6-diphosphatase. Diagnosis was suspected in a male newborn since a brother was also concerned by the disease. The disease may be therefore diagnosed early, when the onset is neonatal. In the neonatal distress syndromes due to hereditery disorders of metabolism, a semiologic field may be isolated in which symptoms begin after an interval of short duration with hypoglycemia, hepatomegaly, lactic acidosis and ketosis ("enlarged liver hypoglycemia"). This possibility leads first to a symptomatic treatment of hypoglycemia and acidoketosis, then to the feeding with human milk and simple functional tests for the diagnostic approach.


Activity of some enzymes which synthesize and metabolize catecholamines in the brain and peripheral organs in developing rats.

Activities of monoamine oxidase (MAO), DOPA-decarboxylase (DD), phenoletha-nolamine-N-methyltransferase (PNMT) and phosphodiesterase (PDE) were studied in the brain and its parts, heart, kidneys, adrenals and liver in developing rats. In vitro, the action of nialamid on MAO activity in the liver, RO-4-4602 on DD activity in the liver, and D(-) INPEA on PNMT activity in the adrenals was investigated. The influence of 6-hydroxydopamine (6-OHDA), 200 mg/kg i. p., on MAO activity in the liver of developing rats was also studied. Irregular changes in activities of examined enzymes during development were observed. 6-OHDA, nialamid and RO-4-4602 inhibited enzyme activities in young rats more strongly than in adult animals.


Action of biogenic amines injected intracerebrally on duration of hexobarbital-induced sleep in rats.

The influence of intracerebrally injected biogenic amines and cyclic AMP dibutyrate on duration of sleep induced with hexobarbital (50 mg/kg i.v.) in rats was studied. Duration of sleep was markedly prolonged by adrenaline, noradrenaline, dopamine, 5-hydroxydopamine and acetylcholine. Cyclic AMP dibutyrate injected 30 minutes before hexobarbital shortened time of sleep. The role of biogenic amines in hexobarbital-induced sleep is discussed.


[Cytomegaly and central nervous system abnormalities. Report of 2 cases associated with agenesia of the corpus callosum and cystic encephalopathy].

Two cases of cytomegaly of the central nervous system of infants, disclosing typical viral inclusions in the brain tissues, associated with agenesia of the corpus callosum and cystic symmetrical post-infarction encephalopathy are reported. It is suggested that the callosal defect was caused by cystic degeneration occuring within the lamina reuniens and the prematurely fused sulcus medianus, in early intrauterine life. The possibility of cytomegalic etiology of the malformation is discussed. However the occurrence of viral disease in a previous abnormal brain cannot be discarded. The cystic symmetrical encephalopathy is explained through a redistribution (shunting) of the cerebral blood flow, brought about by the existence of a peculiar mechanism which he calls - priority blood supplying system. This proposed system probably acts independently of the cerebral blood flow autoregulatory mechanisms in emergency states, shunting the blood to the vitaly more important homeostatic neurovegetative centers. This mechanism, in spite of its actual effectiveness, if prolonged, may be deleterious to the excluded territories and produce irreversible damages. The morphologic expression of these damages are the multiple symmetrical brain infarctions. Following occasional survival, the tissue debris of the destroyed structures in the involved areas, are slowly and progressively removed by reabsorption and replaced by unusual symmetrical cavitations.


Adrenoleukodystrophy. A clinical and pathological study of 17 cases.

Adrenoleukodystrophy was diagnosed pathologically in 17 male patients. The diagnosis was suggested by clinical and laboratory signs of primary adrenal failure and by neurological signs referable to the degeneration of white matter. Neurological findings usually predominated over clinical stigmata of adrenal failure. Adrenal biopsy has proved to be the most reliable diagnostic test, while brain biopsy has often been misleading. The histological picture of the brain lesion differs substantially from that of the adrenal, but the presence of similar ultrastructural cytoplasmic inclusions suggests a common metabolic disorder. Morphological analysis of the cerebral lesion indicates that the destruction may spread in a caudal-rostral direction. The intense inflammatory cell response occurs within the demyelinated areas, behing the area of active myelin breakdown, and appears to be a secondary feature of white matter degeneration.


APO low density lipoprotein localization. Intracranial and extracranial atherosclerotic lesions from human normolipoproteinemics and hyperlipoproteinemics.

APO low density lipoprotein (apoB), the major protein in plasma low (LDL) and very low (VLDL) density lipoproteins, was localized in extracranial and intracranial arteries from normolipoproteinemics and hyperlipoproteinemics to determine if apoB extensiveness and localization varied with plasma lipoprotein profile. Specimens of carotid bifureation, internal carotid, basilar, and middle cerebral arteries from 23 subjects with normal lipoprotein levels, four with elevated LDL (type II), and 13 with elevated VLDL (type IV) values were studied with the employment of immunofluorescence techniques. Although the apoB localization pattern was identical in each group, extensiveness of positive localization was greatest in lesions from type II cases and the same in lesions from type IV and normolipoproteinemics. This suggests that sites of apoB retention are dependent on the chemical and structural changes in atherosclerotic arteries, whereas extensiveness correlates with the apoB concentration gradient between plasma and tissue.


Reye's syndrome and cerebellar intracytoplasmic inclusion bodies.

A patient with Reye syndrome had intracytoplasmic inclusion bodies in Purkinje cells. Electron microscopical examination demonstrated the inclusions to contain internal particles, but these were not identifiable as known virions. Results of viral studies were normal.


Acute SSPE.

Two patients had acute fulminanting encephalitis and the typical pathological changes of subacute slcerosing panencephalitis (SSPE). It is suggested that SSPE should be considered in the differential diagnosis of acute viral encephalitis.


Synovial sarcoma of the laryngopharynx.

Synovial sarcoma of the laryngopharynx is an extremely rare neoplasm. To date, only two such cases have been reported. We describe two additional patients in whom this lesion occurred as a primary neoplasm of the laryngopharynx. Hoarseness, upper respiratory distress, and dysphagia characterize the original complaints in laryngopharyngeal synovial sarcoma. The difficulties that may be encountered in histologic diagnosis are emphasized. Our findings suggest that an aggressive surgical approach is indicated. Adjuvant therapy with irradiation and the chemotherapeutic agent, doxorubicin (Adriamycin), may contribute to better survival rates.


Davis-1961 revisited. Signal transmission in the cochlear hair cell-nerve junction.

In 1961, Hallowell Davis proposed the occurrence of the following general sequence of interrelated events in sense organs, in response to specific sensory inputs: (1) the generation of receptor potentials in the sensory cells; (2) chemical transmission across the synapses between hair cells and afferent dendrites; and (3) the triggering of postsynaptic generator potentials capable of eliciting the actual nerve action potentials. Although at the time of his writing there was no evidence for this hypothesis in the auditory organ, there is now good support for the occurrence of all three events and for their general importance in the sensory transduction process.


Epstein-Barr virus associated with episodes of recurrent tonsillitis.

A group of patients with a history of recurrent tonsillitis were observed during an acute episode to determine the cause of the infection. The microbial pathogen that was consistently implicated was the Epstein-Barr virus. Seventeen (65%) of 26 patients exhibited a substantial seroconversion to the early antigen of Epstein-Barr-virus-infected lymphoblastoid cells (P3HR-1). We conclude that there is a high incidence of tonsillitis associated with the Epstein-Barr virus. The propensity of the virus for the palatine tonsils, a rich source of B cells, in suggested. Furthermore, the value of monitoring early antigen titers to confirm the nature of the infection is apparent, bearing relevance to future studies of this virus.


Temporal bone findings in cryptococcal meningitis.

A 19-year-old woman with cryptococcal meningitis died as a result of her disease, in spite of both intravenous and intraventricular administration of amphotericin B. Gross and microscopic examinations revealed multiple cysts containing Cryptococcus neoformans within the central nervous system. Studies of the temporal bones revealed both neural and end organ destruction with the presence of Cryptococcus when stained by Gomori methenamine silver nitrate method. We present the results of audiometric and vestibular examinations. The case history depicts a progressive neurological involvement by Cryptococcus.


Pulmonary interstitial fibrosis from paraquat in the hamster.

The effects of paraquat in hamsters were evaluated to find a rodent model of interstitial pulmonary disease free from spontaneous infection. Because the repeated doses necessary to produce chronic lung injury suggested hypersensitivity mechanisms, concurrently administered Freund adjuvant and adenocorticotrophic hormone (ACTH) were tested separately. Effects were measured by mortality, change in body weight, and morphometric estimate of lung injury. Findings were as follows: (1) only repeated doses in a very narrow range produced chronic interstitial injury; (2) ACTH clearly protected animals from the general systemic and pulmonary effects of paraquat; and (3) adjuvant specifically protected against the pulmonary injury alone. There was no evidence of immunologic contribution to paraquat injury.


The effects of additives on the thermal behaviour of gypsum-bonded casting investments. Part I.

In the formulation of gypsum-bonded casting investments, small amounts of certain modifiers are sometimes added to increase the investment's thermal expansion. In the present investigation, a systematic study has been made of the effects on thermal expansion of adding boric acid and sodium chloride to the investment powder, and glycerol to the mixing water. The combination of 0.2 per cent of sodium chloride in the powder, and 10 per cent of glycerol in the mixing water, appears to offer most promise in the formulation of an investment with a high thermal expansion.


The sterilization of gutta-percha points.

The traditional methods employed for the sterilization of gutta-percha points are unsatisfactory. The use of propylene oxide for this purpose is described and experimental evidence is advanced to support this use.


Urinary cyclic AMP in diagnosis and management of hypercalcaemia: studies of patients without primary hyperparathyroidism.

Urinary adenosine -3' ,5' - cyclic monophosphate was measured in 14 patients with hypercalcaemia not caused by primary hyperparathyroidism. Increased levels were found in patients with malignant disease without bone metastases and believed to be examples of paraendocrine syndrome. Decreased levels were found in patients with metastatic carcinoma involving bone, and in patients with multiple myeloma, lymphoma and immobilisation after fracture. Results obtained during treatment for hypercalaemia are described in three patients. In two hypercalcaemic patients (one with hyperthyroidism and one with breast cancer with bone metastases) normal levels were found. This measurement is a useful substitute for assay of serum parathyroid hormone and is of value in the diagnosis of hypercalcaemia, in monitoring effects of treatment and in revealing underlying mechanisms.


Urinary excretion of cyclic AMP in primary hyperparathyroidism.

Urinary adenosine 3' 5' - cyclic monophosphate (cyclic AMP) was assessed by a competitive protein binding method in 19 patients with primary hyperparathyroidism (PHPT) and in 15 control subjects. The mean value of 6.6 +/- S.E. 0-64 muM per 24 hours for the patients with PHPT was higher (P less than 0-001) than the mean control value of 3-2 +/- 0-24 muM per 24 hours. In all hypercalcaemic patients without renal insufficiency, urinary cyclic AMP excretion was more than 4 muM per 24 hours and decreased in the 15 patients investigated after parathyroidectomy. In a normocalcaemic hyperparathyroid patient and in three hyperparathyroid patients with renal insufficiency, urinary cyclic AMP was less than 4 muM per 24 hours.


Type V hyperlipoproteinaemia re-visted: findings in a sydney population.

The clinical and biochemical features of eleven patients with Type V hyperlipoproteinaemia have been reviewed.  All patients were male, and there was a high incidence in the group of obesity, vascular disease, acute abdominal pain, gout, diabetes mellitus and alcoholism.  Plasma cholesterol concentrations ranged from 212 to 1512 mg/100ml and triglycerides from 708 to 7670 mg/100 ml.  Lipaemia was associated with significant hyponatraemia, and also interfered with the determination of plasma glucose and serum amylase.  Chylomicronaemia and hyperprebetalipoproteinaemia were accompanied by reduction in the pools of beta and alpha lipoproteins.  All lipoprotein classes were relatively depleted of cholesterol compared to triglyceride.  There was a variable pattern of treatment response.  In some patients alcohol withdrawal produced a rapid improvement in plasma lipids.  In diabetes mellitus there were two types of response: a rapid one in chronic insulin deficiency, and secondly, a more gradual one in mild diabetes associated with hyperinsulinaemia.  In other patients there was a rapid response to carbohydrate-calorie restriction but the respective contributions of each of the steps remained unclear.