[Community psychological principles as the basis for the setting up and the organisation of a psycho-social counselling service at a vocational re-training centre (author's transl)].

In community psychology the individuum-centred medical model of disease, which, as a rule, determines the psychological and psychotherapeutic work has superseded socio-psychological concepts and approaches. The authors describe the basic requirements for a psychosocial counselling service at a vocational retraining centre which is guided by community psychological ideas and principles. The article reviews the manifold problems of the rehabilitees, the comprehensive services and the efficiency of the intervention strategies recorded over a two-year period. Furthermore, the authors discuss their experiences with preventive measures in connection with both early detection and prevention of problems. Through its adjustment to the concept of community psychology the responsibilities of psychological and psychotherapeutic services within an institution obtain a considerably higher differentiated structure, and at the same time, meet the demands more adequatedly.


[Emancipatory rehabilitation in logopedics (author's transl)].

The authors tries to answer the question whether logopedical rehabilitation in its present form meets the requirements of its object, i.e., the speech impaired individual as seen from the perspective of prevention or reduction of his social and vocational disadvantages resulting from the language disorder. Against the background of society's "deficiency -- classification-attitude" towards the speech impaired, logopedical rehabilitation should enhance more intensively the emancipation of the speech deviant individual. The study of the practical realization of this requirement demonstrates that logopedics -- still considerably influenced by medical conceptual models -- which is understandable both historically and socially, has not made steps towards emancipatory rehabilitation. Prospects and approaches towards emancipatory rehabilitation resulting in an improvement of the speech disorder are demonstrated.


[Emancipatory rehabilitation in logopedics -- comments from the medico-rehabilitative viewpoint (author's transl)].

In the Federal Republic of Germany speech disturbances, as sub-group of communication disorders, are treated by two professional groups: a) free practising logopedists who chose their team themselves as well as logopedists who are working in a clinic team and b) "Sprachheilpädagogen" (speech therapists) working at special education facilities. Irrespective of the age of the patient, treatment by logopedists is paid by the health insurance funds; special education therapy is paid by the financially responsible school agencies. The basis of the disease is not a deviation but a disturbance of the central nervous system which can be determined by medical, phoniatric-neurological diagnostic means.


Relaxant action of histamine on rabbit trachea: possible existence of third histamine receptor subtype.

The carbachol contracted rabbit trachea relaxes to isoproterenol, PGE1, E2, histamine and bradykinin. Histamine-induced relaxations were resistant to mepyramine (an H1-antagonist), burimamide, cimetidine, metiamide (H2-antagonists), propranolol (a beta-adrenoceptor blocker), indomethacin (a potent inhibitor of prostaglandin synthesis), trasylol (an inhibitor of kallikreins), aminophylline (a purinergic receptor blocker) and dibenzyline (a "D"-tryptamine receptor antagonist). The evidence achieved with these pharmacological agents appears to suggest that the chemical mediator responsible for the relaxant response to histamine is unlikely to be: catecholamines, prostaglandins, 5-HT, adenosine or ATP or kinins. The existence of H2-(iso or H3) histamine receptor subtype in rabbit trachea is postulated.


Pharmacological characterization of the rabbit lung strip.

Isolated rabbit lung parenchymal strips contracted to epinephrine (E), norepinephrine (NE), phenylephrine (PE), histamine, carbachol, PGF2alpha, bradykinin and 5-HT. Lung strips which were maximally contracted to histamine, carbachol and PGF2alpha, relaxed to isoproterenol, salbutamol, terbutaline and PGE1 however, they exhibited superimposed contractions to E, NE and PE. Atropine and mepyramine selectively antagonized contractions to carbachol and histamine respectively, without modifying contractions to the sympathomimetic agents. Phenotolamine antagonized responses to E, NE and PE. The results of this investigation suggest the presence of alpha- and beta-adrenergic and H1-histamine receptors in the rabbit lung strip.


The interaction of enkephalins with substance P on vascular smooth muscle.

Interactions between SP and the enkephalins have bben reported in the CNS, and the possibility of a more peripheral site of interaction has now been investigated. SP (10(-6) - 10(-4) g/ml) induced dose-related contractions of the rabbit isolated aorta, which were resistant to alpha-adrenoceptor blockade (phentolamine, 5 x 10(-6) g/ml). Neither met- nor leu-enkephalin had any intrinsic action on the aorta, but met-enkephalin at 5 x 10(-6) g/ml significantly inhibited responses to SP but not to NE. Morphine (5 x 10(-6) g/ml) potentiated responses to NE, but had no significant effect on responses to SP. It is apparent that SP and met-enkephalin act on a common receptor on vascular smooth muscle, that met-enkephalin has no intrinsic action on this receptor, and that the receptor is morphine-insensitive.


Phenotyping of South African black tuberculosis patients for inactivation of isoniazid.

Studies of isoniazid inactivation rates in black tuberculosis patients from South Africa and Birmingham, Alabama, showed a higher frequency of fast inactivation than those of North American Caucasian patients. After an oral test dose of 10 mg/kg isoniazid the percentage of fast inactivators in black patients of South Africa and Alabama was close to 60% while in North American white participants (Canadian and Birmingham Caucasians), the frequency of fast inactivation was approximately 40%.


Plasma nicotine pharmacokinetics in dogs after intravenous administration: determination by radioimmunoassay.

Nicotine plasma levels in dogs were examined by radioimmunoassay after intravenous administration of S-nicotine at the dosage of 100 microgram/kg. After a rapid decline of nicotine level in plasma immediately following the injection, retention of the level was observed until 30 min. From that point the plasma level decreased monoexponentially. A biological half life (t 1/2, beta) of 0.61 hr we observed in dogs was similar to that in man and one half of that in rats. Total body clearance (TBC) and apparent volume of distribution (Vd, beta) in dogs were about 1/5 of that in rats. The results suggested that nicotine does not distribute in dogs as readily as in rats. Similarity in a biological half life of nicotine in dogs and humans suggested that the dog may be a better experimental model than the rate in the investigation of pharmacokinetic parameters for nicotine.


Measurement of naphthoxylactic and naphtoxyacetic acid in human plasma following propranolol administration.

A method for the quantitative determination of naphthoxylactic acid and naphthoxyacetic acid, two acidic metabolites of propranolol, in human plasma is described. Preliminary data from hypertensive patients receiving chronic propranolol therapy and from normal volunteers who took a single 80 mg oral propranolol dose revealed that naphthoxylactic acid plasma levels were 4 to 20 times that of propranolol whereas naphthoxyacetic acid levels were equivalent to or less than the plasma concentrations of propranolol.


On the regulation of antipyrine and oxazepam metabolism in man.

The metabolism of antipyrine and oxazepam has been measured in twelve healthy subjects. Antipyrine, an analgesic and antipyretic drug, is extensively metabolized by oxidation at various sites and oxazepam, a benzodiazepine, is almost exclusively metabolized by conjugation with glucuronic acid. Comparing the plasma clearance rates and the plasma half lives of the two drugs, correlation coefficients of r = 0.766 (P less than 0.01) and r = 0.966 (P less than 0.01) have been obtained. The data suggests that in man the processes of oxidation and glucuronidation are linked by a common control which regulates the metabolic rates of the two reactions.


Induction of NADH-dependent aldehyde reductase by successive administration of barbiturates in rat brain.

The effect of long-term administration of phenobarbital (PB) or barbital for five weeks on brain aldehyde reductase (A1R) and aldehyde dehydrogenase (A1DH) activities in the rat was studied. Mitochondrial (m)-A1DH and NADH-dependent A1R activities were significantly increased over control values after five-week treatment with PB or barbital, while no significant alteration of supernatant (s)-A1DH and NADPH-dependent A1R activities was observed under the same condition. Increase in m-A1DH activity by the treatment with barbiturates was recovered to the control level, however, increased activity of NADH-dependent A1R was maintained even after the cessation of the treatment. In groups of rats pretreated with barbiturates for five weeks, no animals were induced to sleep after intracerebroventricular injection of PB, and this finding strongly suggests the decrease in sensitivity of rats to barbiturates.


Effects of cannabinoids on L1210 murine leukemia. III. Inhibition of respiration.

The present study was undertaken in an attempt to establish whether or not some of the many biochemical effects of cannabinoids could be explained by inhibition of energy generation. Of particular interest was the relationship of inhibition of DNA synthesis in L1210 murine leukemia cells by certain cannabinoids to possible effects on respiration. In studies using these cells, delta9-tetrahydrocannabinol (delta9-THC) and delta8-tetrahydrocannabinol (delta8-THC) were inactive when tested both in vitro and in vivo. Since these cannabinoids have previously been shown to be inhibitors of DNA synthesis in L1210 cells, there is no necessary relationship between inhibition of the two processes.


Studies on the relationship between ST-segment elevations and extent of infarction following coronary artery occlusion in dogs.

Epicardial ST-segment alterations were determined 15 min. following acute ligation of the left anterior descending coronary artery in dogs, and the extent of the left ventricular wall infarcted at each mapping site was determined 24 hours later. A close correlation was observed between the ST-segment elevation and the percent of left ventricular wall infarcted (r = .891; P less than .001) at the same mapping site. A significant portion of the left ventricular wall remained viable at sites with less than 8 mV elevation; however, the chance of transmural infarction became high at sites with elevations greater than 10 mV. It may be that sites with less than 10 mV elevation in the epicardial ST-segment elevation are ischemic areas where pharmacologic interventions designed to limit infarct size have the greatest change of success.


Use of structure-activity relationships to estimate antiallergic activity of 4-hydroxy 3-nitro coumarins.

The antiallergic activity of a series of 4-hydroxy 3-nitro coumarins was studied using Hansch equations and CNDO/2 calculations. Following these calculations a new compound was synthetised which presents an interesting activity.


Anticonvulsant, analgesic and monoamine oxidase inhibitory properties of newer 4-hydroxy-4-phenylpiperidinocarbamides.

Fourteen 1-[N-acetyl(4-hydroxy-4-phenyl-piperidino)]-3-aryl carbamides were synthesized, characterized and evaluated for their anticonvulsant, analgesic and monoamine oxidase inhibitory properties. All carbamides (100 mg/kg, i.p.) provided 20--60% protection against pentylenetetrazol-induced seizures in mice. The analgesic activity possessed by these carbamides, with the exception of two compounds, was reflected by their ability to provide 17--67% protection against tail pinch response in mice. All carbamides (1 mM) inhibited (5--90%) in vitro activity of rat brain monoamine oxidase. The low toxicity of these carbamides was reflected by their higher approximate LD50 values which ranged from 500 - greater than 1000 mg/kg.


Synthesis and biological activity evaluation of some quinolines.

Synthesis of some quinolines having the thiosemicarbazide and nitrostyryl moieties is described. 8-nitroquinoline-4-acraldehyde undergoes Vilsmeier reaction with dimethylacetamide to afford the respective pentadiene amide. Screening of the synthesized quinolines for bactericidal and mollusicidal activities is reported.


Synthesis and biological activity of some quinoline acrylamides.

Synthesis of some quinoline acrylamides is described. The NMR spectra of some representatives are discussed. Screening of the synthesized compounds for molluscicidal and bactericidal activity is commented.


Myocardial enzyme activities in congestive cardiomyopathy.

A number of enzyme activities concerned with various catabolic pathways have been measured in biopsy specimens of the left ventricle in patients with congestive cardiomyopathy and compared with those in patients undergoing surgery for valvar or congenital heart disease. The myopathic patients showed a diminution in glycolytic capacity, in hexokinase activity and in the capacity to transfer reducing equivalents across the mitochondrial membrane.


Fatty acid changes in the hepatic endoplasmic reticulum during pregnancy in the rat.

In the rat, pregnancy caused a significant reduction of total hepatic and microsomal phospholipid content mainly manifesting in phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine fractions. Fatty acid content of the liver and microsomes was also reduced. The major components involved in this change were palmitic, stearic, oleic, linoleic and arachidonic acids. The level of docosahexaenoic acid was raised; the other acyl components remained unaltered. All these chnages were reversible; both hepatic and microsomal phospholipids and fatty acids returned to the non-pregnany level 2--3 weeks after delivery.


Effect of exercise stress upon the acute toxicity of adriamycin in mice.

The effect of an acute exercise stress upon the acute toxicity of adriamycin was tested. Mice were forced to swim for 30 min following 18 or 23 mg/kg ip of adriamycin. Survival was checked daily for 30 days. The exercise stress did not appear to increase the toxicity of adriamycin in these animals.


Augmentation of hemagglutination-inhibition (HI) antibodies in gilts of breeding age by large dosages of human A/New Jersey/76 influenza vaccine.

Fifteen gilts of breeding age were studied. Four received three 4 ml.  doses three weeks apart of an experimental killed swine influenza vaccine containing A/Swine/ill/65 antigen, four received three ml. doses three weeks apart of a human influenza vaccine containing A/New Jersey/76 antigen and three received two doses of human influenza vaccine followed by a 3 ml. third dose of experimental swine influenza vaccine. All except one vaccinate responded to two doses of vaccine by the time of the third dose of vaccine. HI titers were highest four weeks after the third dose of vaccine. Geometric mean titers were highest in animals receiving human influenza vaccine containing A/New Jersey/76. Titer profiles dropped markedly by 60 days after the third vaccination.


Effect of an essential fatty acid deficient diet on dimethylnitrosamine demethylation and derangement of liver polyribosomes induced by this drug.

Cytochrome P-450 content and dimethylnitrosamine demethylase activity were determined in the liver of male rats fed a polyunsaturated fatty acid deficient diet. The damaging activity of dimethylnitrosamine (DMN) on liver polyribosomes of control and treated rats was estimated. The reduction of DMN demethylase activity did not protect against polysome derangement due to DMN. These data are consistent with the hypothesis that metabolic pathways, other than the P-450 dependent one, are involved in the DMN bioactivation.


Inability of imipramine to protect against type A or type B monoamine oxidase inhibition by pargyline.

Imipramine (30 mg/kg i.p.) did not antagonize the inhibition of either type A or type B MAO by pargyline in brain, heart or liver of rats. Occupancy of active sites on mitochondrial MAO by imipramine probably does not occur at doses of imipramine adequate to inhibit monoamine uptake.


Behavioral and biochemical effects of para-methoxyphenylethylamine.

p-methoxyphenlethylamine (p-MPEA) induces the "serotonin syndrome" in mice which consists of lateral head weaving, Straub tail, hindlimb abduction, tremor, hyperactivity, reciprocal fore-paw treading, salivation and piloerection. These p-MPEA-induced behavioral signs were partially prevented by pretreatment with serotonin (5HT) uptake blockers (fluoxetine, chlorimipramine, Org 6582) and 5HT receptor blockers (methiothepin, methysergide, cinnanserin) but not by two depletors of brain 5HT (p-chlorophenylalanine, reserpine). p-MPEA selectively released 5HT and inhibited 5HT uptake from mouse whole brain synaptosomes. The concentrations of both 5HT and 5-hydroxyindoleacetic acid (5HIAA) in whole mouse brain were increased at 1 and 2 hours after injection of p-MPEA (50 mg/kg). The effect of p-MPEA on displacement of specific tritiated 5HT binding to membranes from mouse brain was considerably less than that of p-chlorophenylethylamine (p-CPEA), p-methoxytryptamine (pMT) and quipazine. Thus p-MPEA may induce the "serotonin syndrome" predominantly by releasing 5HT from presynaptic nerve terminals.


Depressive action of clonidine on guinea pig and rabbit atrial pairs.

The effects of clonidine, a compound used clinically as a centrally active antihypertensive, were studied on isolated, spontaneously beating atria of rabbit and guinea pig. In rabbit atria clonidine induces a marked depression of spontaneous chronotropic activity which was not altered by pretreatment with atropine, and not completely reversed by washing. In guinea pig atria, clonidine alone induces a very small increase in rate. A significant decrease in rate however is unmasked when tissues are pretreated with metiamide (H2-antagonist). Since both rabbit and guinea pig atria contain histamine receptors the lack of a positive chronotropic response in rabbit atria suggests that clonidine has no direct H2-receptor activity. The small positive response obtained with guinea pig atria which can be blocked by metiamide suggests that clonidine can act indirectly by releasing endogenous histamine stores from this tissue. Clonidines direct action appears to be a significant depression of both rabbit and guinea pig atrial chronotropic activity.


Stereoselective oral bioavailability of (+/-)-propranolol in the dog. A GC-MS study using a stable isotope technique.

The disposition of (+)- and (-)-propranolol and their glucuronic acid conjugates, (+)-POG and (-)-POG, in plasma was determined in 5 dogs following single 160 mg oral doses of stable isotope labeled racemic propranolol. Each animal received one dose of the racemate with the (+)-isomer labeled with two deuteriums and one dose with the (-)-isomer labeled. The isomers were separated and measured by gas chromatography-mass spectrometry. No stable isotope effect was detected. The area under the plasma concentration - time curve (AUC) for (-)-propranolol was only 54 +/- 10 per cent (mean +/- SD; n = 10) of the AUC for (+)-propranolol. The AUC of (-)-POG exceeded the AUC of (+)-POG by 4.02 +/- 1.22 times (mean +/- SD: n = 10). The time to peak plasma concentration (3.9-4.3 hr) and the half-life (1.6-1.9 hr) were identical for both isomers of propranolol as well as of POG. These results demonstrate a significantly lower oral bioavailability of (-)- as compared to (+)-propranolol in the dog, which appears to be associated with stereoselective presystemic glucuronidation of (-)-propranolol.


Inhibitory effect of quinidine on catecholamine release from adrenal medulla.

Quinidine was found to inhibit catecholamine release from the medulla of perfused adrenal glands induced by carbamylcholine. It also inhibited the release of catecholamine from adrenomedullary granules induced by ATP-Mg++.


Saliva, urine and plasma analysis of dyphylline via HPLC.

Improved assay methods for determination of dyphylline levels in plasma, saliva, and urine utilizing high pressure liquid chromatography have been developed. Detection of levels as low as 25 ng/ml from 0.5 ml plasma and 50 ng/ml from 0.5 ml saliva were possible. Both procedures utilized the same extraction process. A separate extraction process was used for dyphylline analysis in urine due to the presence of interferring substances occurring with previous methods. The method was applied to samples of one subjects plasma, saliva and urine after administration of dyphylline.


Rapid determination of serum theophylline levels using the MPLC short column concept.

Many procedures are currently available demonstrating the feasibility of the analysis of serum theophylline concentrations by high performance, high pressure liquid chromatography utilizing chromatographic columns which can only be described by the term "expensive" in terms of column life and cost. We have developed and evaluated a rapid "medium pressure, medium performance" liquid chromatographic (MPLC) method for theophylline in serum utilizing a chromatographic column that costs up to 1/3 the cost of current HPLC columns. Less than 0.2 ml of serum is required for each determination, yet the sensitivity of the method is easily less than 1 mg/liter. The method involves liquid extractive isolation, chromatography on a micro column (4.6mm x 10cm) of RP-18 and provides adequate selectivity, accuracy and precision for routine and non-routine (neonatal) theophylline determinations. We have found no endogenous or exogenous interferences. Reproducibility for the microscale method is controlled through the use of hydroxypropyl theophylline as an internal standard.


Purification of rabbit antispermine antiserum by affinity chromatography.

Immunoglobulins G were isolated from a crude rabbit antispermine antiserum using a protein A-Sepharose CL-4B column. Affinity chromatography coupling spermine to the Sepharose matrix was employed for separation of antispermine antibodies from these immunoglobulins. Four fractions of antispermine antibodies were isolated by stepwise elution with solutions at pH range from 4 to 1. Binding constants were determined and cross-reactivity with other polyamines was tested for each fraction of antibodies. Highly specific antispermine antibodies were found in fraction IV.


The fate of intratracheally instilled 3H-styrene oxide in the isolated perfused rat lungs.

The metabolism and covalent binding of intratracheally instilled 7-3H-styrene oxide in the isolated perfused lungs of control and cigarette smoke-exposed rats were investigated. After intratracheal instillation of 100 nmoles of 7-3H-styrene oxide the lungs were perfused for 16 min and the nonrecirculating perfusate was collected in two fractions: 0--8 min and 8--16 min. About 40 percent of the instilled dose was in the 0--8 min perfusion medium, mainly in the form of unmetabolized styrene oxide. However, the radioactivity in the 8--16 min perfusion medium and lung tissue itself was mainly in the form of water soluble metabolites, probably glutathione conjugates. The amount of styrene glycol was very small. Exposure of rat to cigarette smoke had no effect on the metabolism of styrene oxide or on the amount of covalent binding to the protein and nucleic acid fractions of the perfused lungs.


Long-term estrogenization in mammals. I. Histopathology of kidney, bladder, adrenals, and gonads; polydipsia; body weight; and serum levels of corticosterone and testosterone in estrogenized Marsh mice.

Single, sublethal, long-acting doses of estrone or estradiol cypionate produced the following histologic, behavioral, and blood chemistry effects in Marsh mice: (a) Bladder pathology developed following estrogen-induced polydipsia but was not consistently associated with kidney damage. (b) This polydipsia was more intense (a maximum of 250% over control intake) when the housing was in metal cages with floor screens than in plastic cages with bedding. Water intake of control mice was unaffected by housing changes. (c) Comparing litter-mate 2.5-month-old males and females, body weight loss following estrogen administration was transient with the females. With males, initial weight losses as compared with weight gains in the controls were demonstrated over a 20-week period. (d) Estrogenization markedly increased corticosterone and decreased testosterone serum levels with a significant negative correlation for these levels in the estrogenized mice. A significant positive correlation was also observed between testosterone levels and testis weights in the estrogenized mice.


Effects of pesticides on human leukocyte functions.

Aroclor 1254 and twelve pesticides of different chemical classes were tested for their in vitro effects on lymphocyte mitogenic responses to PHA, rosette formation with sheep red blood cells (E-rosette) and neutrophil chemotaxis. By using a diluted whole blood culture, butoxide at 10 micrometers inhibit lymphocyte mitogenic response to PHA by 26%. Inhibition by other pesticides were less than 20% (5--20(). Higher degrees of inhibition were observed if the lymphocytes were pretreated with pesticides in the absence of serum: pp-DDT inhibited by 73% trithion by 50% and benzylthiocyanate by 30%. E-rosette formation was less inhibited by these pesticides except DDT, which inhibited the E-rosette formation by 50% at 10(-4)M. Only methyl parathion was found to have some inhibitory effects on neutrophil chemotaxis. These results indicate that insecticides may have direct effects on the leukocyte function and that the presence of serum may alter the interaction of insecticides and leukocyte membranes.


Effect of furosemide on canine splenic arterial blood flow.

Furosemide has been reported to cause pathological changes in the intestines as a consequence of the decrease in splanchnic blood flow that it produces. In view of the pancreatic toxicities of this diuretic, it was of interest to examine the effect of the agent on blood flow to this organ. An electromagnetic flow probe, was placed around the splenic artery, a vessel which supplies a major fraction of pancreatic blood flow. Within 60 min after furosemide (1 mg/kg, iv) administration, splenic blood flow (SBF) decreased by 20% and the decrease paralleled the drug-induced diuresis. When the diuresis was prevented, the agent failed to affect SBF. Thus, furosemide causes a reduction in SBF, which appears to involve a mechanism dependent upon the volume reduction produced by the drug-induced diuresis.


A histochemical technique for evaluation of progesterone receptors in breast cancer.

A histochemical method for the detection and localization of progesterone receptors in human breast cancer has been developed employing a fluorescein labeled conjugate of bovine serum albumin linked to a progestin as the binding hormone. Considerable tumor cell receptor heterogeneity was apparent and nuclear binding was frequently noted. The results of the new assay correlated with those obtained by dextran-coated charcoal assay in 91 per cent of specimens.


Hepatic RNA synthesis in rats treated with ethylene thiourea.

The ability of ethylene thiourea (ETU) to inhibit RNA synthesis in rat liver was investigated. This compound, a possibly carcinogenic metabolite to the ethylene-bis-dithiocarbamate fungicides, was administered to rats by intraperitoneal injection, by nasogastric tube and in the diet, and rates of RNA synthesis were determined. By contrast with the carcinogens thioacetamide and acetylaminofluorene, high doses of ETU administered by any of these routes failed to inhibit the synthesis of nuclear or cytoplasmic RNA. In this respect ETU appears to differ from most hepatocarcinogens in its effect on cellular metabolism.


Distribution of [3H]prednisolone entrapped in lipid layer of liposome after intramuscular administration in rats.

Positivery charged, sonicated liposome entrapping [3H]prednisolone was administered into the rats hip muscle to examine its absorption and distribution in comparison with that of the administration of free [3H]prednisolone. Plasma concentration of prednisolone in liposome-entrapped form showed high concentration for a long period of time, the values being 8 times after 30 min and 24 times after 24 hr compared to the free form. The concentration of liposome-entrapped form in liver, kidney and spleen was 4-10 times, and in lung and pancreas was 8-10 times higher than that of free form after 30 min and 24 hr. But, in adrenal, after 30 min and 1 hr, liposome-entrapped form were lower than that of free form, the former remained longer in the tissue, and the concentration maintained the high level after 24 hr, being about 28 times higher than that of free form. Even in the duodenum and large intestine, absorption of the liposome-entrapped form was very active and remained in the tissue for a long period of time. These facts suggested the possibility of using a small dose in intramuscular administration but allowing the steroid to remain in the tissues for a long period of time.


The effect of harmine and other monoamine oxidase inhibitors on N-acetyltransferase activity.

Prior studies indicate that the monoamine oxidase inhibitors (MAOI) harmine and iproniazide inhibit N-acetyltransferase activity from liver. In this report we have demonstrated that harmine and harmaline are potent inhibitors of N-acetyltransferase, purified from hamster and rat liver. However, other MAOI such as deprenyl, clorgyline, methysergide, cyproheptadine, phenelzine, pargyline, methyltryptamine and tranylcypromine have either no effect, or only trivial effects on N-acetyltransferase. There is no correlation between a compound's properties as an MAO and N-acetyltransferase inhibitor. One must consider the inhibitory effect of harmine and harmaline on both MAO and N-acetyltransferase when evaluating the effects of these compounds on physiological processes.


Changes in serotonin turnover and the brain sensitivity to barbiturates by disulfiram treatment in rats.

The influence of intraperitoneal administration of disulfiram on the serotonin (5HT) turnover and the brain sensitivity to barbiturates were investigated in rats. Treatment of the animals with 200 mg/kg disulfiram resulted in the prolongation of duration of barbiturate-induced hypnosis. This indication and increment of the brain sensitivity to barbiturates after disulfiram treatment. Under the identical condition, disulfiram caused both the reduction of turnover of 5HT and the elevation of 5HT levels, although this effect was less potent than that of phenobarbital. Furthermore, simultaneous administration of disulfiram and phenobarbital resulted in the severe retardation of 5HT metabolism. These results strongly suggest that disulfiram potentiates the hypnotic action of barbiturates by altering 5HT metabolism in rat brain.


Comparative aspects of nuclear proteins and nuclear composition of cultivated embryonic, neonatal and neoplastic rat brain cells of glial origin.

Differences in nuclear composition and variations in the types of acid soluble nuclear proteins were identified when cultivated neoplastic and nontransformed rat brain cells were compared. HeLa S-3 cells were used as a biological reference in these studies. The nuclei of anaplastic glioma cells were found to contain more total nuclear protein and greater amounts of nuclear RNA, than the nuclei of nontransformed embryonic and neonatal rat brain cells. Densitometer profiles of samples developed by polyacrylamide gel electrophoresis indicated that all three major histone classes were present in the nuclei of the four different cell types examined. Each type of cell was grown in the presence of 3H-lysine or 3H-lysine plus 14C-arginine to further characterize both the histones and the acid soluble nonhistone proteins. Neoplastic and nontransformed cells contained similar quantities of histones H4, H3, H2A and H2B. In contrast, transformed cells were found to contain two dominant subspecies of lysine rich H1 histone, while only one histone H1 subcomponent was extracted from the nuclei of the embryonic and neonatal rat brain cells. Nuclei isolated from HeLa cells and anaplastic glioma cells also contained increased varieties and larger quantities of acid soluble nonhistone nuclear proteins.


Suppression of cellular immune response in chemically sympathectomized mice.

Delayed-type hypersensitivity to methylated bovine serum albumin (MBSA), as induced by 6-hydroxydopamine (6-OHDA) was studied in chemically sympathectomized mice. Footpad reaction at 48 h after challenge injection of MBSA was suppressed with doses ranging from 10--300 mg/kg. 6-OHDA was neither cytotoxic to peritoneal macrophages nor was the function of immunoglobulin mediated phagocytosis suppressed. Thus, the suppression of delayed-type hypersensitivity may be attributed to interference with T-cell function.


The biphasic nature and temperature dependence of the activation of human plasminogen by urokinase. A simple urokinase assay based on this phenomenon.

Activation of plasminogen is a biphasic process, the first phase is temperature independent, the second phase is not. The first phase of activation is completed immediately when urokinase (UK) is combined with plasminogen. At 4 degrees C the fibrinolytic activity generated in the first phase is directly proportional to the concentration of UK used for activation. This linear relationship permits the construction of a standard curve for the quantitative measurement of UK in samples with unknown concentrations of UK. The second, slower phase of activation follows the first only at higher temperatures (e.g. 28 degrees C), is limited by the plasminogen concentration, and is completed within 30 minutes of incubations. Activation of plasminogen by streptokinase under the same conditions follows a different pattern.


Evaluation of various isoniazid slow releasing matrix preparations for intermittent chemotherapy of tuberculosis.

The blood level achieved with 15 mg/kg ordinary isoniazid (INH) was compared with that obtained with INH slow releasing Matrix preparation. Three brands of INH Matrix preparation were compared namely: the product of ICN Canada Ltd, utilized by Laboratory Centre for Disease Control, the preparation of Smith and Nephew, Britain employed by the Tuberculosis unit of the British Medical Research Council and Tebesium, the product of Hefa-Frenon Arzneimittel, Germany studied by the Tuberculosis Unit of South African Medical Research Council. The results of this study showed that pharmacogenetic principle have to be taken into account, it is not possible to produce INH slow releasing Matrix preparate equally applicable for slow and fast acetylators of INH.


Time and level of perinatal lead exposure for development of norepinephrine cardiotoxicity.

Neonatal lead exposure produces an enhanced susceptibility of the adult rat heart to the arrhythmogenic effects of norepinephrine. The present study examines the relationship of time and level of exposure to the extent of cardiac abnormality produced. The results indicate that the level of lead exposure required to produce norepinephrine cardiotoxicity without overt growth retardation is quite narrow, and lead must be present during the first ten days of life to cause these effects on the heart. A critical concentration of lead achieved during the early time period after birth appears necessary for the production of this cardiac abnormality, suggesting that lead interferes with neonatal cardiac and/or autonomic development.


Additional induction of microsomal cytochrome(s) P 450 in mouse liver by consecutive application of cadmium chloride and phenobarbital.

Mice were treated intraperitoneally over 20 days with 0,30; 0,10 and 0,03 mg Cd+2/kg.day. Subsequent induction of microsomal metabolism by 50 mg phenobarbital/kg.day over 5 days revealed increased microsomal cytochrome P 450 content in Cd+2-pretreated animals as compared to animals treated only with phenobarbital. The microsomal cadmium content of animals having received cadmium plus phenobarbital was about 5 times higher than that of animals treated with cadmium alone. The only enzyme activity found to be changed by cadmium in induced microsomes was ethylmorphine-N-deethylation. In phenobarbital-free animals no microsomal changes by cadmium could be detected.


Drug metabolism in diabetic isolated perfused rat liver.

The demethylation of aminopyrine was decreased while the demethylation of p-chloro-N-methylaniline was increased in both alloxan and streptozotocin diabetic isolated perfused male rat livers. Since similar effects of diabetes were observed with traditional microsomal preparations, these observations indicate that the effects of diabetes on drug metabolism observed in isolated microsomal preparations from male rat are an accurate reflection of conditions in the intact organ. These results also clearly indicate that diabetes in the male rat affects at least two different rate-limiting steps in the hepatic drug metabolism process.


Hydrolysis of 11-palmitoyloxy-delta 9-tetrahydrocannabinol to 11-hydroxy-delta 9-tetrahydrocannabinol by cholesterol esterase and a lipase.

11-Palmitoyloxy-delta 9-tetrahydrocannabinol (11-palm-delta 9-THC) has been identified in the rat in our laboratory as a long-retained metabolite of delta 9-tetrahydrocannabinol (delta 9-THC), the active component of marihuana (Leighty, 1973). Although it is not known as yet if 11-palm-delta 9-THC is itself psychoactive it could be hydrolyzed to active 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-delta 9-THC). Our in vitro studies show that cholesterol esterase and a lipase can hydrolyze 11-palm-delta 9-THC to 11-OH-delta 9-THC.


Identification of benzhydrol as a urinary metabolite of diphenylmethane in the rat.

Liquid-liquid extraction and preparative thin-layer chromatography were used to isolate 30 micromoles of benzhydrol from the beta-glucuronidase treated 24 hour urine of rats administered 5.3 mmoles of diphenylmethane. The benzhydrol was identified by its melting point, elemental analysis, infrared, nuclear magnetic resonance, and mass spectra.


Coenzyme Q10 or alpha-tocopherol reduce the acute toxicity of anthramycin in mice.

Pretreatment for 4 days with 10 mg/kg coenzyme Q10 (CoQ) or 1 day with 85U alpha-tocopherol (Vit E) produced equal reduction in the acute toxicity of 0.5 mg/kg anthramycin (ANTH). Twenty-seven days after ANTH, 40 percent of control mice survived, those pretreated with CoQ or Vit E displayed 73 and 80 percent survival. A 17.5 mg/kg dose of adriamycin (ADR) produced a percent survival-time curve resembling that produced by 0.5 mg/kg ANTH. At this dose of ADR, however, the protection afforded by CoQ and Vit E was minimal and not statistically significant (p less than 0.05). CoQ or Vit E may be of value at reducing the toxicity of anticancer agents other than the anthracyclines.


Gas liquid chromatographic studies of [1-14C] palmitate uptake by the perfused guinea-pig heart.

In addition to the uptake of palmitate by the isolated perfused guinea-pig heart, there was a substantial release of longer chain fatty acids into the perfusate amounting to about 50% of the uptake of palmitate. Both the uptake of palmitate and the release of other fatty acids was diminished in the presence of 95% N2. The specific activity of myocardial palmitate was increased under 95% N2. No significant difference in the distribution of radioactivity between the different myocardial fatty acids occurred between 95% O2 and 95% N2.


Cannabinoid inhibition of rat luteal cell progesterone synthesis.

Progesterone production by isolated rat luteal cells was inhibited by exposure to various cannabinoids in concentrations from 3.0--16.0 microM. The available evidence points to the cleavage of cholesterol esters as the site of inhibition.


[Cholecystitis and cholelithiasis induced by lincomycin. Microscopic and ultrastructural studies].

Gallbladder of 30 golden hamsters was evaluated after a seven days course of lincomycin (60 mg/kg/day). Fifteen animals injected with an equivalent volume of saline and 15 animals non injected at all, were used as controls. Weight, sex, age, and food were similar in all groups. Eight hamsters (23%) treated with lincomycin formed pigmented gallstones.


[Prevention of post appendectomy incision abscess with the use of polyvinilpyrrolidone iodine (prospective study)].

365 appendicectomy cases performed from 1972 to 1976 were studied prospectively. In 135 control cases the wound was not lavaged. In 102 cases the wound was lavaged with normal saline solution. En 108 cases the wound was lavaged with PVP-I. Wound abscess formation rate in the first group was 28.8%, in the second group was 21.35% and in the third group was 18.5%. Patients operated after 1974 and treated with PVP-I showed a 4.2% abscess formation. Morbility and mortality in appendicitis are best reduced if early diagnosis and surgical treatment are backed by a faultless technic.


[Esophageal manometry in patients with sliding hiatal hernia].

This presents the method to be followed for the valuation of the gastro-esophagic function in patients with sliding hiatal hernia, twenty-one patients with this diagnosis were studied through X-Rays. Besides gastric and esophagic endoscopy, a complete clinical examinations was made to compare the information obtained from the studies, with the direct measurement of the contractions of the esophagus and the lower sphincter through conventional manometric methods. The relationship between the simptoms and the clinical procedures done in the patients were observed as was the usefulness of esophagic manometry to detect not only the direct pressure of the gastro-esophagic sphincter, but also to determine the concurrent motor changes that can occur in patients which show hiatal hernia. The benefit of this studies to decide the therapeutic handling, specially surgical, is discussed.


[Amylase test in the diagnosis of acute pancreatitis].

The determination of serum and urinary amylase are methods used in the diagnosis of acute pancreatitis, however there are many abdominal problems that can cause hyperamylasemia, in the absence of pancreatic disease, for this reason in 1969 Levitt and col. signaled the possible advantages of amylase/creatinine clearence ratio, in the clinical diagnosis of acute pancreatitis. This test was used in cases with acute pancreatitis, as in other diseases, in correlation with levels in normal subjects, with the objective of evaluating its clinica utility, in relation to the formentioned paragraph. Results concluded that the amylase/creatinine ratio is not of greater diagnostic utility than the determination of urinary amylase, in acute pancreatitis.


[Eosinophilic gastritis].

Two case studies of eosinophilic gastritis studied by the Pathology Department of the Hospital Central de San Luis Potosi are presented. Based on these cases, the clinical pathological forms of the entity are analized together with the classification and etiopathology, from which it is considered a late allergic or hipersensitive reaction to foreign proteins. Therefore, it is essentially different from the neoplastic, histiocitic, eosinophilic granuloma of the bone.


[Percutaneus cholangiography with the Chiba needle. Results in 220 studies].

The authors employed this new technique of thin needle percutaneous cholangiography in 220 patients with the following results: 99.3% (146/147) success with previous biliary tract dilatation and 79.4% (53/73) success in patients with normal caliber bile ducts. The overall result of 92.7% (204/228) emphasizes that radiological opacification is the best way to study the icteric patient. Only 1.8% of patients with serious complications is less than in other instrumentation methods. By not requiring specialized equipment and being accessible in the majority of hospitals, study cost is reduced. In conclusion, this new technique of percutaneous cholangiography is preferable for accessibility, efficacy, cost and risk in the study of the icteric patient.


[Sensitivity to chemotherapeutic agents of bacteria isolated from generalized infections].

A study carried out on 206 bacteriemia infections showed that: the following bacterial flora was implicated in the etiology of bacteremia infections: Staphylococcus aureus in 28.6% of cases, Staphylococcus albus in 20.4% Enterobacteriaceae in 25.7% and Pseudomonas in 3.8%; an increase existed in the number of generalized infections caused by opportunists belonging to the Enterobacteriaceae family and Pseudomonas genus. Similarly, an increase in the resistance to the recently introduced antibiotics, Septrin and Gentamycin, was noted. These observation require antibiotic lebel control and, if it is necessary the association of two or more antibiotics in severe infections.


[Incidence and duration of blood HBs antigen in convalescents after type B viral hepatitis].

The presence of HBs Ag was determined by contraelectrophoresis in 500 convalescents after hepatitis B, at the moment of discharge and after 1--3 and 6 months. Antigen carriage is prolonged in hepatitis B, 51% of the convalescents being positive on discharge and 10% remaining persistent carriers. This was more frequent in males, young adults and those who had suffered from mild, prolonged forms of the disease. As only 42% of the patients became negative within the first 20 days of hospitalization it became necessary to prolong their stay in hospital and to follow up the patients subsequently in an out-patient unit.


[Spontaneous internal biliary fistula. Review of the literature].

The literature concerning internal biliary fistula is reviewed. Its frequency in autopsy ranges from 0.4 to 5%, and in biliary tract operations from 0.4 to 7%. A general approach has to be established in order to obtain a diagnosis, and an individually oriented treatment provided. Emphasis is placed on certain measures of treatment and complications. The most severe complications are cholangitis (7.5%) and gall stone ileus (2% to 6%).


[Acarids of pathological significance in urine].

The present paper reports on 7 cases of primary infections, pyelonephritis and pyelocystitis, in which acrids were found in the urine during acute attacks. The cases were detected in the clinical laboratory of a county Hospital. All the 7 patients, ranging in age from 6 to 60 years, exhibited characteristic symptoms of pyelonephritis and pyelocystitis. Numerous acarids were found in the urinary sediment and, in some cases, also their eggs. Some of the acarids were motile, others were encrusted with salts. A female acarid was detected while laying eggs. In 6 patients the acardis were found in the urine only at the first examination and disappeared following the of urinary infection; in the seventh case they were detected at three consecutive examinations performed at 3--6 days interval.


[Sensitivity to antibiotics and chemotherapeutic agents in some strains of Salmonella typhi isolated in Romania during the period 1974-1976].

Investigations were carried out on 781 S. typhi strains isolated from patients and carriers. Testing of the sensitivity to chemotherapeutical agents by diffusiometry and the incorporation technique led to the detection of four resistant strains: 1 strain isolated by coproculture from a carrier since 1958, resistant to A, K, N, Ca and Cf and 3 strains isolated by coproculture, biliculture and uroculture from a carrier since 1974, resistant to A and Ca. The R factors of these strains were transferred in their totality. The resistant strains did not manifest any particular pathogenicity for the laboratory animal, and their immunogenic potential was below that of the current typhoid vaccine. None of the 781S typhi were resistant to Cmx, C, G, T, Co and Po. Consequently, in Romania Chloramphenicol may be used in continuation in the treatment of typhoid fever, and Cotrimoxazol, Gentamycin, Tetracyclin and Ampicillin are and remain reserve substitutes. The possible unexpected appearance of resistant S. typhi strains demand, however, further control of the sensitivity to chemotherapeutics of all the isolated strains.


[The value of sonography in evaluation of unilateral nonvisualized kidney (author's transl)].

In a comparative study with 35 patients, sonography, angiography and radiorenograms are investigated on their validity for evaluation of nonvisualized kidneys. In our group of patients, angiography showed an accuracy quota of 97% (34/35) and sonography showed an accuracy quota of 88% (31/35). In 12 patients, the radiorenograms unequivocally show functional loss with the nephrectomy type. Sonography should be used first as a simple noninvasive procedure. It is independent of the remaining renal function and indicates the size of the organ. For hydronephrosis sonography cannot clarify the cause of the urinary stasis in some cases; for this purpose, further examinations are indicated (retrograde pyelography, antegrade pyelography).


[Radiological diagnosis of the ösophagus with special attention to the ösophagogastric transition of the gastro-ösophageal reflux, reflux ösophagitis, hiatal hernias and ösophageal stenoses (author's transl)].

The inferior high-pressure zone acts like a functional sphincter. This is formed in the absence of a muscle correlate, via a regional predominance of the sphincter tone caused by inhibition of activity of the longitudinal muscles through the membrane phreno-oesophagea in the region of the vestibulum gastro-oesophageale. Pressure variations in the vestibulum caused by respiration, are governed by a "rein mechanism". Swallowing produces a brief reflectory breakdown of the inferior high-pressure zone in the longitudinal muscles of the ösophagus via myogenic ventricular stimulus condution. Gastro-ösophageal reflux can be regularly identified by means of suitable x-ray examination technique. Since, however, it is not possible to arrive at a quantitative and qualitative assessment of the reflux via roentgenology, the aim of radiological examination in case of clinical suspicion of reflux is to determine a) the factors favouring reflux, ie hiatal hernia, gastric and duodenal ulcer, stenosis of the pylorus, etc, b) the sequelae of a pathological reflux, eg reflux stenosis, reflux ulcer, brachyösophagus etc, as well as c) to assess the self-cleaning function of the ösophagus. It is possible to definitely identify hiatal hernia by radiology with a well-aimed examination technique, through the intrathoracal displacement of parts of the stomach, of Schatzki's ring, and the superhiatal displacement of the entire vestibulum gastro-oesophageale. It is also regularly possible to identify by serial radiography an organic ösophagus stenosis, using large quantities of barium swallow, although pathogenetic interpretation of the x-ray film may be difficulat. Functional stenosis can be defined by pharmacoradiography and manometry. In clinically suspected reflux ösophagitis, endoscopy and histology will supply more conclusive findings in respect of mucosal assessment than x-ray examination.


[Diagnosis of subpulmonary effusion in children (author's transl)].

If an elevation of the right or left base of the lung is found on a chest x-ray film, differential diagnosis will have to consider the follwoing possibilities: 1. Elevation of the diaphragm, 2. Subpulmonary effusion and 3. Hernia of abdominal organs through the diaphragm. Suspicion of a subpulmonary effusion is prompted by the following x-ray findings: 1. Flattening of the costophrenic angle and elevation of the base of the lung. 2. Increased distance between "magenblase" (stomach bubble) and base of the lung. 3. Elevation of the lower margins of the lung, the apex being in the region of the lateral hemithorax. 4. Translucency of the margins of the diaphragm below the elevated base of the lung. 5. Absence of vascular shadoes behind the diaphragm on a wellexposed x-ray film. If one or several of these symptoms is seen, proof should be obtained by provoking issuing of the effusion by placing the patient in supine position or in lateral position on the affected side, and by trying to achieve visualization of the resulting condition.


[Diagnosis of combined malformation of lung and pulmonary vessels (author's transl)].

Diagnosis of combined malformation of lung and pulmonary vessels are presented in a case of one lobe lung on the right (Agenesis of two lobes and hypoplasia of the presenting lobe). The importance of radioisotope methods in diagnosis of lung hypoplasia is stressed. Pathogenesis and period of teratogenic termination is discussed.


[Hypertrophy of Hoffa's fat pad - an arthrographic diagnosis? (author's transl)].

The wide spectrum of conditions, ranging from normal variants over early posttraumatic swelling to Hoffa's classical syndrome with hypertrophy of the fat pad can be demonstrated in double-contrast arthrography with high reliability, demonstrated after review of 1566 arthrographies in comparison with results of surgery and histology. Following post-mortem studies in 50 knee joints statements are made about normal size and shape, physiological variants and pathological enlargement of Hoffa's fat pad in arthrography. Since post-traumatic changes of menisci, cartilage and Hoffa body often cannot be differentiated by clinical examination, double-contrast arthrography should be performed routinely before surgery, since this technique provides the surgeon with a maximum of preoperative information about the internal structures of the knee joint and may modify the planned surgical procedure considerably.


[On the technique of examination in ERCP, EPT with stone extraction and PTC from the radiologist's viewpoint (author's transl)].

Based on the empirical data of more than 2500 examinations we report on the technique of the endoscopic retrograde cholangio- and pancreaticography (ERCP), the endoscopic papillotomy (EPT) with calculus extraction and also the percutaneus transhepatic cholangiography (PTC) from the radiologic point of view. The essential tasks of the radiologist are the clarifying of the position of the probe, the quick diagnosis and the making of valid x-ray photographs. For this purpose the knowledge about an optimal technique of examination is the prerequisite. By this the experienced radiologist is an important partner of the gastroenterologist. He helps to avoid complications for the patient.


[CT scanning in cystic liver changes (author's transl)].

Computer tomography is outstandingly suitable for detecting cystic processes in the liver. The genesis of such cysts can vary widely, so that there are bound to be differences in the clinical relevance of the findings. This is discussed on the basis of 20 case histories of cystic changes of the liver observed during one and a half years. For the purpose of discussion of the value of CT scanning, comparisons with sonographic and angiographic examinations were carried out.


[Angiographic examinations in hypertension. Vascular morphology, flow rate and kidney size (author's transl)].

1. The paper reports on examinations relating to vascular morphology, flow rate and kidney size in patients suffering from arterial hypertension. 2. The results and findings differ clearly from those of the total group of patients and a control group of healthy volunteers. 3. The results and observations are discussed. 4. Renal angiography can give more information than commonly assumed. Hence it should be employed more frequently than before for the purpose of clarifying diagnosis in patients with arterial hypertension.


[Cinefluorographic studies in children with previous esophageal atresia repair (author's transl)].

Seven children with previous esophageal Atresia repair underwent cinefluorographic studies of the swalling act. They all showed disordered motor function in the esophageal segment below the Anastomosis with segmental contractions and lack of primary Peristalsis. Nevertheless we found organized propulsive waves below the Anastomosis too, which leaded to an esophageal emptying also in the supine position.


[Roentgen examination after oesophageal surgery (author's transl)].

Sutureinsufficiency has to be sought postoperatively. Later, tumors, passage disturbances and reflux must be looked for. Antirefluxsurgery with fundoplication may lead to a roentgenmorphology with tumoraspect. After transoesophageal sclerosis of varices passage disturbances and perforations may be seen. After perforations by endoscopic procedures the oesophageal roentgen examination with water-soluble substances completes the clinical surveillance.


[Spontaneous Ahlbäck's knee joint osteonecrosis].

Among the group of genuine osteonecroses there ranks the spontaneous osteonecrosis of the knee described for the first time by Ahlbäck, Bauer and Bohne in 1968. Characteristic of it is a subchondral defect on the medial condylus of the femur, which may occur in old persons, chiefly women. Supported by six illustrative cases in own patients clinical experience, radiology, diagnosis and differential diagnosis are presented and discussed.


[X-ray diagnosis of retropatellar diseases (author's transl)].

The article reports on a comprehensive, stepwise diagnosis in diseases of the knee joints. This includes a description of the indication, the technique of taking x-ray films, and x-ray findings, as well as arthrography of the femoropatellar joint in retropatellar diseases such as chondropathia patellae, osteochondrosis dissecans, traumas of the knee joints and arthrosis deformans.


Serum and pituitary prolactin variations under the influence of pyridoxine and pimozide in the male rat.

Prolactin was measured in the serum and hypophyses of the male rat after six days of i.p. administration of pyridoxine 5 mg (group B6), after a single dose of pimozide 2.5 mg/kg body (group PMZ), six days of pyridoxine and one dose of pimozide (group B6- PMZ) and a single dose of tartaric acid (controls). Both pyridoxine and pimozide increased the serum prolactin: 59.06 +/- 16.23 ng/ml and 68.45 +/- 10.78 ng/ml respectively (X +/- DS) by comparison to controls: 33.12 +/- 11.16 ng/ml, their effect being cumulative (83.75 +/- 13.86 ng/ml). However, the effect of pyridoxine and pimozide at the central level is different, pyridoxine producing an increase of the pituitary concentration of prolactin, while pimozide depleted the stored prolactin. Hypothetical mechanisms of pyridoxine action at the pituitary level are discussed.


Decrease of testosterone, cholesterol and ascorbic acid in the rat testis after administration of pineal polypeptides.

Administration of 2 ml/day/animal, of melatonin-free pineal extract to the rat for three days induced a significant decrease in the testicular tissue concentration of testosterone, cholesterol and ascorbic acid. A dose of 1 microgram melatonin/day/animal given for 3 days did not alter these biochemical elements implied in testicular steroidogenesis.


Changes in the bioelectric activity of the lateral septal nucleus, dorsal hippocampus and medial habenular nucleus after administration of the pineal peptide extract "crinofizin".

New Zealand rabbits with pairs of electrodes implanted chronically in the RFM, dorsal hippocampus, LSN and HM were tasted for electroencephalographic changes in the dorsal hippocampus, lateral septal nucleus and medial habenular nuclei in response to electric stimulation of the mesencephalic reticular formation and after slow i.v. and i.m. injection with the pineal peptidic extract "Crinofizin". Stimulation of RFM with a rectangular current of variable tension (1.5--4 volts) induced synusoidal waves on the EEG of the dorsal hippocampus, LSN and HM with a frequency of 4 to over 8 c/s persisting throughout the electric stimulation. Intramuscular administration of 10 ml pineal extract in doses of 2 ml every 48 hrs led to changes in the EEG traces in that the mean frequency of the synusoidal waves decreased from 3.8 c/s to 1.4 c/s whereas the mean amplitude of the waves was almost threefold the mean amplitude of the background traces.


Transsexualism; new observations.

Ten cases of transsexualism have been studied. All the patients present gonadal lesions, modifications of the morphotype and small hormonologic anomalies. It is supposed that the gonadal lesions are frequently associated with this psycho-behavioural disorder. Thus transsexualism may be considered a trouble of the whole process of post gonadal sexualization.


Reactivity to calcitonin after ovariectomy.

The hypocalcemic response to calcitonin injected in female rats disappeared after their castration. The substitution treatment with estrogens does no allow reestablishment of the hypocalcemic effect obtained in intact animals, a fact that lays stress on the role of the whole ovarian secretion in maintaining a normal response to calcitonin. The response of castrated animals to calcitonin calls attention to the conditional role of estrogens in validating the osteoprotecting effect of calcitonin.


Variations of catecholamines in mixed shock. Therapeutic implications. Experimental and clinical investigations.

The variations of catecholamines, cortisol and aldosterone in mixed shock (traumatic, hemorrhagic and septic) were studied experimentally and clinically. In the stage of collapse adrenaline decreased by 81.4% and noradrenaline by 62.6% as compared with the preoperative values. These decreases were found to be directly proportional to the decrease of arterial blood pressure, pulse amplitude and diuresis as well as to the slowing down or even stop of microcirculation. The value of plasma cortisol increased in the stage of collapse by 98.3% and that of aldosterone by 66.27% as compared with the preoperative values. Treatment with a pharmacodynamic sympatheticolytic-vasopressor-adrenocortical mixture is recommanded when the blood pressure remains below 50--60 mm Hg for 1--2 hrs and when the treatment for the correction of hypovolemia with fluids and sympatheticolytics has failed. Clinically, this treatment gave good results in 34 of the 58 cases studied (58.6%).


Effect of normal human serum on the binding of specific antibodies and platelet-unrelated immune complexes to human platelets.

Radiolabelled staphylococcal protein A was used to quantitate the binding of IgG on stored human platelets from human sera containing specific antibodies reactive with platelets and rabbit serum containing immune complexes (IC). Normal human serum (NHS) inhibited the binding of IC onto platelets and to various extents also the binding of specific antibodies. The attachment of inhibitors to platelets seemed to be reversible. The considerable difference in the inhibitory capacities of IgG-deficient sera and monomeric IgG indicates that IgG is the major inhibitory component of NHS. The binding of IgG from NHS onto platelets evidently hampers the detection of weak platelet antibodies even with the most sensitive tests. Purified Clq, known to modify the reactions of IC with fresh platelets did not alter the binding of IC onto stored platelets. A monoclonal, antiglobulin-active rheumatoid factor of IgM class displayed only moderate inhibition. Therefore, the application of RF or Clq for the differentiation of the binding induced by IC or antibodies is not useful in this assay system. The heterogeneity of immunologic receptors of platelets provides an explanation of the inhibitory inefficiency of Clq.


Detection of Fc receptor-bearing lymphocytes by using IgG-coated latex particles.

Latex particles coated with human IgG can be used to detect lymphocytes capable of binding to the Fc portion of IgG. Optimal conditions are described. The method is as sensitive as techniques using antibody-coated erythrocytes, is easy to perform, and has good reproducibility. A small proportion of T cells and the majority of B cells can be shown to carry receptors for Fc (IgG).


Clonotype patterns of antibodies released by single lymph nodes.

Experimental primary, secondary and tertiary stimulation with streptococcal vaccine of isolated lymph nodes in vivo in the sheep model induces largely persistence of anti-group polysaccharide antibody clonotype patterns with the rare occurrence of additional clonotypes demonstrable after secondary stimulation persisting during the tertiary stimulus. It is not clear whether these additional clonotypes are the products of mutants or whether they pre-existed and were demonstrable only after a secondary stimulus, because of threshold concentrations required for identification. Further, isolated contralateral popliteal and prescapular lymph nodes of individual sheep share completely overlapping clonotype patterns during experimental primary anti-polysaccharide antibody responses indicating an identical repertoire of specific clonotypes under this condition of responsiveness.


Degradation of thymidine to thymine by rheumatoid arthritis synovial tissue eluate.

A study was made of the effect of rheumatoid synovial tissue eluate on phytohaemagglutinin (PHA) stimulation of peripheral blood lymphocytes. It was found that rheumatoid synovial tissue eluate caused marked inhibition of 3H-thymidine incorporation by lymphocytes stimulated with PHA. Synovial tissue from traumatic joints had no effect. The inhibitor was a heat-sensitive and nondialysable substance. The inhibitory effect of PHA stimulation was diminished by thymine. In thin-layer chromatography it showed the capacity to convert thymidine to thymine. Because thymine is not incorporated by DNA-synthesizing cells, this report explains why negative results are obtained when lymphocytes are stimulated by rheumatoid synovial tissue using 3H-thymidine incorporation as an indicator of lymphocyte activation.


Hearing impairment in meningococcal meningitis.

Hearing affection as a sequel of meningococcal meningitis and its relation to age, sex, severity and duration of disease was studied in Cairo, Egypt during the period December 1966--December 1973. The total incidence of impaired hearing in the 775 cases was 5.8%. This incidence was higher in the younger age groups, females, severe cases of meningitis and in patients who received specific therapy shortly after the onset of signs and symptoms of the disease. The aetiology of hearing impairment in meningitis was reviewed.


Cefamandole nafate: an evaluation of antibacterial activity, serum levels, clinical effect, and incidence of side reactions in 58 patients.

35 males and 23 females with skin and soft tissue infection, lower respiratory tract infection, urinary tract infection or septicemia with known etiology were treated with cefamandole nafate. The patients were to a large extent (30%) alcoholics and/or drug abusers. Cefamandole was given intravenously as 4 daily doses of 1 g in 52 cases and of 2 g in 6 cases for 8 to 16 (mean 10) days. The effect was considered to be good in 40 patients (70%). Adverse reactions, mostly slight and transient, were seen in 22 patients (38%). Peak serum levels varied from 26 to 82 (mean 50) micrograms/ml after 1 g doses and from 68 to 100 micrograms/ml after 2 g. Previous statements of a better in vitro activity of cefamandole than of older cephalosporins against some gram-negative bacilli were corroborated.


Tetracyclines and host defense mechanisms: interference with leukocyte chemotaxis.

The influence of 2 etracycline preparations, lymecycline and doxycycline, on leukocyte chemotaxis, was investigated in vitro and in vivo. Doxycycline in high concentrations caused a severe depression of both spontaneous and induced migration, an effect which was more pronounced than that caused by similar concentration of lymecycline. Corresponding results were obtained both in experiments on healthy volunteers given recommended dosages of the antibiotics, and in patients treated with doxycycline for postoperative infections.


Clindamycin excretion in the pancreatic fluid of dogs.

Clindamycin phosphate in dosage of 15 mg/kg was administered intravenously to dogs. Serum and pancreatic juice clindamycin concentrations were assayed. Pancreatic juice clindamycin concentrations varied between 1.32--5.5 micrograms/ml. Clindamycin was still detectable in the pancreatic juice 4 1/2 h after its administration. Clindamycin, in combination with other antimicrobials, may be potentially effective in the prophylaxis and therapy of some of the infectious complications associated with pancreatitis.


Treatment of experimental Naegleria meningoencephalitis with a combination of amphotericin B and rifamycin.

The treatment of primary amoebic meningoencephalitis was examined using a mouse model. Rifamycin by itself was ineffective. However, a synergistic effect was observed when used in combination with amphotericin B. This finding may prove useful in the treatment of patients with primary amoebic meningoencephalitis, for which satisfactory treatment is currently unavailable.


Risk of infection among seafarers: a prospective seroepidemiological survey of the crew of a passenger cruiser.

Serial blood specimens for various serological examinations were taken from the crew of a passenger ship which sailed on winter cruises. The study covered 3 successive seasons totalling about 150 years of observation. The figures on the rates of infection were compared with data available from the general population. The study revealed no clear evidence of an increased infection risk among the crew.


The prevalence of toxoplasma antibodies among 11,736 pregnant women in Norway.

A serologic screening for toxoplasma antibodies by dye test (DT) and IgG indirect fluorescent antibody test (IgG-IFAT) has been carried out among 10729 pregnant women in the Oslo area and 1 007 pregnant women from the county of Møre and Romsdal situated on the west coast of Norway. The frequency of toxoplasma antibodies was found to be higher in women living in rural areas and a higher prevalence was observed among women living in the western districts of Oslo than among women from the eastern districts of the city. The mean frequency of DT antibodies was found to be 12.5% in the Oslo area and 13.3% in Møre and Romsdal, whereas the yearly incidence of acquired infections in the two areas was found to be 5 and 2.3%, respectively. The predicted incidence of congenital toxoplasmosis in the Oslo area, and presumably also in the whole country, would represent 2% of all pregnancies. No serologic differences were found when women with prior histories of either sporadic or habitual abortions were compared to a total group of multigravidae among the Oslo women.


Passive--active immunization in a neonate treated with repeated doses of high-titred hepatitis B immune globulin.

A newborn infant, born to a HBsAg-positive drug addict with HBeAg and DNA-polymerase activity in serum, was treated with repeated very high doses of hepatitis B immune globulin (HBIg). The mother turned HBsAg-negative about 8 months after deliver and the HBIg prophylaxis was then discontinued. A check-up of the infant about a year later revealed normal liver function tests but significantly increased levels of antibodies against HBcAg and HBsAg indicating a post subclinical hepatitis B infection, apparently without harm to the infant.


Recurrent pneumonia and encephalitis due to Mycoplasma pneumoniae.

Recurrent Mycoplasma pneumoniae encephalitis in a young man is reported. The patient appeared not to be immunodeficient and despite the presence of a focal inflammatory brain lesion with a predominance of polymorphonuclear cells no direct evidence of inent in M. pneumoniae respiratory tract infection still is unknown the case strongly indicates that certain individuals are somehow predisposed to such complications. The case also illustrates that CNS complications may occur even during a mild mycoplasma respiratory tract infection and that the radiological findings can mimic cerebral haemorrhage or abscess necessitating neurosurgical exploration.


Prophylaxis of neurosurgical infections by improved preoperative disinfection of the scalp.

The heads of neurosurgical patients were subject to 2 scrubbings with hexachlorophene detergent, performed in the ward prior to operation. After this single change of routines the frequency of wound infections after craniotomy dropped 4-fold, from 2% to 0.5%. The result indicates that the scalp of the patient is the major source of the staphylococci that cause neurosurgical infections.


Measles virus specific precipitins in sera from patients with chronic active hepatitis.

Measles virus specific antibodies in sera from 29 patients with chronic active hepatitis have been examined using standard serological tests and immunoelectrophoretic techniques. Significantly raised CF antibody titres against measles virus antigen were demonstrated in 50% of the sera. The major immunoprecipitate obtained by immunoelectrophoresis was shown to contain aggregates of measles virus nucleocapsids. Antibodies against the haemagglutinin antigen of the virus envelope were also raised and were demonstrated by line immunoelectrophoresis.


Evaluations of dangerousness.

The Supreme Court decided in O'Connor v. Donaldson that mentally ill people who were not dangerous and who could survive safely in the community could not be kept in a mental hospital against their will. In 1976, a project evaluated the legality of the commitments of 107 patients in a State mental hospital. The review was conducted by three panels, each composed of a law student, a resident psychiatrist, and a social worker. Evaluations of a patient's dangerousness were made on the basis of information from the patient's hospital records, an interview with the patient's primary therapist at the hospital, and interviews with the patient. Analysis of project recommendations revealed that commitment decisions were more related to the clinical outlook of the evaluators than to the patient's behavior.


Environment and inheritance: opposing forces?

High risk of schizophrenia requires high genetic predisposition to develop schizophrenia, plus an environmental trigger. A schizophrenic family environment is commonly believed to represent this trigger. The hypothesis is presented here that, on the contrary, a high predisposition to schizophrenia in significant others protects against overt illness. The trigger may be the predominance around the index individual of significant others with low predisposition to develop schizophrenia.


Rejecting the patient: preliminary validation of a self-report scale.

The authors describe an easily administered scale being developed to assess the rejecting feelings of family respondents toward former mental patients who return to live with their families. Based upon a sample of 133 discharged mental patients and family members, the scale demonstrates a moderately high reliability (alpha = .78) and test-retest correlation (r = .72). Data are presented for evaluating the construct validity of the scale.


The mental hospital revisited: a proposal.

Mental hospital treatment stresses an overcaring, humanistic approach that tends to foster a passive role dependence of patients on institutions and people. The author proposes a treatment concept of an "active, self-participatory involvement" by patients. This approach allows patients to experience an active role by participation in various tasks and assumption of responsibilities in running the ward. Staff gradually delegates decision-making processes, implementation of plans, and even a certain administrative authority to patients.


Taximetric strategies applied to psychiatric classification.

This article discusses limitations inherent in using unilevel behavioral descriptors as the basis for the construction of psychiatric classifications. As an alternative we consider the advantages of the polythetic classification strategy as suggested by Sokal and Sneath (1963) in their description of a "numerical taxonomic" approach. They argue for the development of naturally occurring, empirically defined classes rather than categories based on single domains of behaviors such as psychiatric symptoms. Typically the research into a topic such as schizophrenia starts with a behaviorally defined class of individuals who show schizophrenic symptoms, contrasted with a nonschizophrenic control group. These groups are then tested for aberrations in other systems of functioning (blood, neurophysiological, hormonal, attentional functioning, and the like). The approach offered here requires a classificatory strategy that treats data from all levels of functioning as equivalent in forming the classes of individuals rather than as secondary to the defining symptomatic attributes. Particular emphasis is given to the choice of measures with sufficiently broad and sensitive features to find natural classes. A set of standards is given for the selection of a test battery that might be used in a polythetic approach to the investigation of schizophrenia. Finally, the utility and limits of statistical clustering techniques for handling multilevel data banks are discussed.


Longitudinal social competence and adult psychiatric symptoms at first hospitalization.

Patterns of psychiatric symptoms of 141 patients at first hospital admission were correlated with social competence, as measured in childhood from school records and in adulthood by the Index of Social Competence, which is based on hospital records. Results confirmed the hypothesis that low social competence is associated with the more disintegrative symptoms of withdrawal, thought disorder, and antisocial acting out, but this conclusion held only when the measure of social competence was based upon adult premorbid behavior. A longitudinal perspective on social competence did not improve upon the symptomatic discrimination based on adult cross-sectional assessment alone, except that a cluster of schizoid symptoms (apathy, flat affect, hallucinations, resentfulness, and verbal hostility) was significantly associated with a longitudinal measure of social competence, though not with either cross-sectional measure by itself. Positive symptoms (delusions, hallucinations, and other florid processes) appeared not to be part of a longstanding, longitudinal process, but the negative symptoms included in the withdrawal cluster showed some association with childhood behavior.


Natural healing processes of the mind: I. Acute schizophrenic disorganization.

It is proposed that there are three fundamental adaptive systems that have developed in the course of evolution. One of these, learning, is the only one that is widely recognized. The other two consist of regulation of the energetic aspect of stimulation, and integration of the data of experience into an organized conceptual system. Corresponding to each of the three basic adaptive systems are three basic types of disorder, namely maladaptive learning, which is by far the most common source of behavioral problems; overstimulation, as in the traumatic neurosis; and collapse of the individual's conceptual integrative system, as in acute schizophrenic disorganization. Just as relearning is a natural adaptive process for correcting problems produced by learning, there are inherent processes for correcting the disorders produced by overstimulation and by a maladaptive integrative system. The present article is concerned with the natural process for correcting a poorly organized conceptual system. A second article (Epstein 1978) will be devoted to the natural process of coping with the energic aspects of stimulation. An acute disorganizational state can provide an opportunity for a new and more effective conceptual system to develop. As a desperate remedy, it is often unsuccessful. Nevertheless, an orderly process can be discerned in such states that can enhance the likelihood that new, and dissociated old, material will be assimilated into a new organization. If all goes well, the new organization will be more resilient than the old one; it will be better able to accomplish the functions of an implicit theory of reality, which are to integrate the data of experience, to maintain a favorable pleasure-pain balance, and to maintain self-esteem.


Language, reality, and schizophrenia.

In a series of articles, D.V. Forrest (1965, 1969, 1973, 1976) has attacked the contention of many cognitive psychologists that schizophrenic behavior is best signified by deviations in language and aberrancies of thought. Forrest maintains that although schizophrenics do indeed diverge from conventional standards of language and thought, such divergence is not unusual or disordered; that the schizophrenic's world is intentionally coded and is not in any way nonsensical or entropic. In defense of his position, Forrest makes three claims: (1) that all language is inherently metaphorical; (2) that the activities of the schizophrenic are akin to those of the artist; and (3) that reality is nominal and indeterminate (therefore no description of "schizophrenia" has ontological status or refers specifically to a psychopathological type). It will be the purpose of this report to show that the above claims cannot be upheld, that overwhelming difficulties pervade Forrest's position, and that said difficulties arise from a misunderstanding of language.


Early mobilization of patients with unstable fractures of the thoracic and lumbar spine. A 2-year follow-up study.

During the acute immobilization period 18 patients, with unstable fractures of the spine together with, in most cases, a spinal cord lesion, caudally of T2, were tilted in bed or on a tilting table. Twelve of these patients began the tilting already in the second week after the injury and reached +30 degrees on the 15th day, +50 degrees on the 37th day and +90 degrees on the 65th day following the injury. All patients were kept under observation at regular intervals up to 2 years. A comparison between similar patient groups, treated strictly conservatively, and the present patient groups did not show any differences either in respect to deformities in the spinal column, expected reduction in the spreading of the spinal cord lesions or in the subjective symptoms of the patients. In the hope of reducing the complications induced by protracted immobilization, the authors recommend that patients with unstable fractures of the spinal column, caudally of T2, with or without spinal cord lesion, begin a specified tilting program already in the second week following the injury.


Circulatory strain in everyday life of paraplegics.

Circulatory strain encountered in everyday life was low, taxing 15-24% of HRR. Similar results (Th8-Th12) was estimated from their heart rates (fH) recorded continuously by portable tape recorders for up to 48 h. The degree of strain was expressed in per cent of the individual's heart rate reserve (HRR), i.e. of the span between resting and maximal fH. The average strain of everyday life was low, taxing 15-24% of HRR. Similar results were obtained in a rehabilitated patient (subj. 5, Th12) at the hospital. fH higher than 50% of HRR which could be expected to have a training effect on the circulatory system was recoreded only when ambulating with crutches, driving wheelchair uphill, playing basketball, or during specific training (arm cranking in subj. 6 (Th2) who attended a post-rehabilitation course). The results confirm that daily life activities with no additional training are not intense enough to maintain the circulatory and physical fitness of rehabilitated paraplegics.


Force-velocity relationships in the human quadriceps muscles.

Isokinetic contraction were performed with the knee extensor muscles in 15 young male soccer players. The measurements were obtained by a modified isokinetic device (Orthotron). In the range of motion the angular velocity was constant from 90 degrees to 20 degrees of knee flexion. The angular velocity could be varied from 30 to 360 degrees/s. The overall variation of the pre-set speed and the peak torque, as estimated from duplicate trials through the whole velocity range, averaged 4% and 5%, respectively. The peak torque decreased linearly with increasing angular velocity in a semilogarithmic scale. An estimate of the peak torque-velocity relationship in an experimental subject was obtained from the slope and the fibre composition in the lateral portion of the quandriceps muscle in this group of subjects especially trained in fast movements. It was concluded that the present applied isokinetic device gives the opportunities to measure force-velocity characteristics in the intact quadriceps muscle of man.


[Surgery of bronchial neoplasms].

Surgical resection is the most efficient therapy for lung cancer. Preoperative investigation should determine histology, local invasion and distant dissemination. Tumor-host relation (immunocompetence and tumor burden) is essential for long-term results. Relatively crude anatomical staging does not take biological parameters into account, and any case with lympho-glandular involvement (N1) should not be considered as stage I carcinoma. 520 cases treated by pulmonary resection are reviewed and common denominators for long-term survivors determined. Stage I epidermoid carcinoma treated by lobectomy or left pneumonectomy with a short history (survey cases) are the ideal candidates for surgical resection. The importance of early diagnosis by routine screening is stressed.


[Socioeconomic aspects of lung cancer].

The socio-economic aspects of lung cancer are briefly considered, first, with regard to the causes conditioning its occurrence and clinical progress. Tobacco smoking, occupational exposure and air pollution are (in decreasing order of importance) the main determinants of lung cancer occurrence, which differs as between social classes. Social class also appears to be related to clinical progress of the disease. The economic consequences of lung cancer may be tentatively estimated, for a country like Switzerland, at 40 million Swiss francs per year, a sum which can be greatly reduced if a sustained collective effort at prevention is implemented.


[Bronchial cytology--value of various methods for the diagnosis of primary lung neoplasms. A computation of the materials sent in to the cytological laboratory of the Institute of Pathology, Kantonspital, St. Gallen].

During the period 1973-1977 some 6100 sputum cytologies from 3000 patients were performed. All patients had suspected primary bronchogenic carcinoma. Sputum cytology was diagnostic in 547 patients (18%). A synopsis of all patients with proven lung cancer and at least one primary sputum cytology shows that this method was diagnostic in 80%. Fiberoptic bronchoscopy with its associated procedures (biopsies, brushings, washings) was the most frequently performed endoscopic method at our Department of Medicine. Fiberbronchoscopy used in combination with cytologic brushings was diagnostic in 83% of the proven cancers. Formerly, bronchial washings and bronchial secretions were obtained by means of rigid bronchoscope. This material yielded the lowest percentage (51%) of all cytological methods used at the Cantonal Hospital. The indications for use of the different diagnostic methods mentioned above and important factors which yield a high percentage of positive cytologies are discussed.


Application of tumor marker analysis to patients with lung cancer.

Measurement of Clq-BA and CEA levels in patients with lung cancer may provide additional information about their clinical status discriminating between disease free patients and those with residual disease. Post-operative determination of Clq-BA and CEA levels may assist in defining patients which have poor prognosis. Preliminary evidence suggests that Clq-BA measurement may provide additional prognostic information in a small group of patients with normal CEA values. Finally, the presence of elevated Clq-BA in tumor bearing patients is of fundamental importance in the biology of cancer as it suggests that there are some tumor associated antigens which provoke the production of antibody in the host with the resultant formation of circulating immune complexes. The definition of the nature of the antigen in these immune complexes awaits further study.


[Presurgical determination of lung function in patients with bronchogenic carcinoma].

90 out of 202 lung cancer patients hospitalized for preoperative investigations were scheduled for radical surgery. 15 patients were not operated on because of insufficient lung function data. The operation was performed in 75 patients. The complication rate was 11% and mortality 8%. 7 out of 8 patients who subsequently developed severe complications had fulfilled the criteria for lung resection only after intensive antibronchitic treatment. Nearly all the survivors showed the predicted preoperative minimal lung function values after the operation. The limit of 1000 ml for postoperative FEV1 is justified, since patients with these or larger functional reserves nearly all had a favourable early and late postoperative course, and also because lung function values continuously deteriorate in chronic obstructive lung disease.


[Bronchoscopic diagnosis by means of rigid or flexible optics].

In order to expand the diagnostic potentialities of bronchoscopy and decrease its risk to the patient, the author has combined rigid-tube endoscopy with the flexible fibroscopy over the last 4 years. Rigid optical systems (angulated and straight) afford far better optical quality, whereas the flexible optic oment of the lower lobe. General anesthesia through the bronchoscopy tube lowers patient stress and discomfort and, in contrast to fiberbronchoscopy alone, allows assisted breathing of the high-risk patient.


[The place of total aerodigestive upper endoscopy in oncology].

The epidemiology of upper digestive and bronchogenic carcinoma shows a large overlap between the high risk groups. Thus, a candidate for bronchogenic carcinoma is also a possible candidate for upper digestive cancer. Furthermore, the high frequency of multiple carcinoma in the upper aero-digestive tract, the esophagus and the tracheo-bronchial tree warrants a pan-endoscopic (buccal-pharyngo-esophagoscopy and laryngo-tracheo-bronchoscopy) approach to the problem. Using this type of endoscopy, 16 multiple carcinomas have so far been simultaneously discovered among 200 pan-endoscopies.


[Experiences with VP-16 in combination with cyclophosphamide or adriamycin in the anaplastic, predominantly small cell bronchogenic carcinoma].

VP 16-213, the new semisynthetic epipodophyllotoxin, was tested for activity and toxicity in two small pilot series of 24 mainly untreated patients with anaplastic, predominantly small-cell lung cancer. It was given in combination with cyclophosphamide or adriamycin. Among 10 evaluable patients receiving VP-16 + cyclophosphamide (5 orally, 5 intravenously) only 1 good partial remission and 4 partial remissions (less than 50%) were achieved. Toxicity was minimal. In 14 patients on VP-16 and adriamycin, remission was complete in 2, good partial in 5 and lesser partial in 2. The hematological toxicity of the second combination was marked. Severe granulocytopenia required reverse isolation of most patients for periods of up to 2 weeks. The response rate for VP-16 + adriamycin was better than for VP-16 + cyclophosphamide, but lower than expected. Possible explanations are given.


[Effect of 2 retinoids (vitamin A analogs) on human bronchogenic carcinoma in vivo (nu/nu mouse) and in vitro].

The antitumor effects of 2 aromatic retinoids (analogs of vitamin A) were investigated in human bronchogenic carcinomas grown in vitro and in vivo (serially transplanted in "nude" mice). In vitro, bronchogenic carcinoma cells treated with Ro 10-1670 (the free acid of an aromatic retinoid) displayed activation of the lysosomal system and increased cellular breakdown. In vivo, nu/nu-mice treated with Ro 10-9359 (the ethyl-ester of Ro 10-1670 showed inhibition of tumor growth. In the tumors, necrotic areas were intermingled with regions displaying a higher degree of keratinization as compared to those of the controls. The extracellular matrix surrounding the tumor cells of the retinoid-treated animals was increased in volume and electron density.


[Survival of operated bronchopulmonary neoplasms. Actuarial results after 5 years].

The actuarial survival of 253 primary bronchopulmonary cancer patients undergoing surgery in Geneva between 1967 and 1976 is studied. The overall post-surgical mortality was 9.88%. The overall survival after exclusion of patients without radical tumor excision was 26.6% at 5 years. The small size of the tumor, the absence of mediastinal extension and an epidermoid histology are the best survival rate factors: 43.2% of stage I patients survive at 5 years against 4.86% of stage III patients. The survival for asymptomatic tumors is 43.9% at 5 years. This suggests the importance of mass screening by radiophotography. Thus, surgery retains its central role in the treatment of this disease, whilst chemo-, radio- and immunotherapy have not yet realized their full potential.


[Pneumonitis and fibrosis after primary radiotherapy and after combined treatment with chemotherapy in bronchogenic carcinomas].

36 patients with bronchial carcinoma treated in a randomized study were investigated for late reactions of lung tissue after radiotherapy combined with chemotherapy. The onset and extent of the lesions depended on the primary therapy. In the group of patients who received primary chemotherapy the first signs of radiation pneumonitis and fibrosis were seen earlier than in the group who underwent primary radiotherapy (70 days and 120 days respectively, and 170 days and 237 days respectively). The shrinkage of the lung tissue was greater after primary chemotherapy. However, secondary pneumonia in the irradiated lung volume occurred less frequently in the group who underwent chemotherapy first.


[Postoperative prevention of recurrence with intrapleural Corynebacterium parvum in patients with stage I and II bronchial carcinomas. Ludwig lung cancer study I].

The Ludwig Lung Cancer Group was created in 1977. Participants are from Austria, Denmark, Germany, Norway, Sweden, Switzerland, and Yugoslavia. 400 patients are randomized yearly. The clinical trial I investigating the role of C. parvum intrapleurally as adjuvant therapy in operable non-small cell lung cancer patients has been closed in February 1979 with a total accrual of 475 patients. The average follow-up time for these cases is approximately 8 months. It is early to make any definitive comparisons of the treatment groups (C. parvum versus placebo). However, it is possible to identify a few high-risk patient groups. Preliminary indications are that surgical T- and N-stage, type of resection, histological type of tumor as well as degree of tumor dedifferentiation (central histology review) are prognostic factors with regard to disease-free interval and survival. In the same, the disease-free interval appears to become shorter for patients experiencing high fever after C. parvum administration. The Ludwig Lung Cancer Group offers a sharp tool for investigating the possible role of adjuvant therapies in non-small cell lung cancer and for gathering new information on the biology of the disease.


[Treatment of cirrhotic ascites].

The treatment of cirrhotic ascites is based on restriction of dietary sodium and fluid intake coupled with diuretics. Ascitic fluid must always be sampled and infection ruled out. Large abdominal paracenteses are dangerous. Most patients with ascites respond to the dietary-diuretic regimen. The clinician must be watchful for overdiuresis. Some patients need diuretics in ever-increasing doses in an attempt to increase urine flow and are at particular risk of functional renal failure. In these diuretic-resistant cases the ascitic fluid can be withdrawn, ultra-filtered and reinfused by means of suitable apparatus. In 1974, LeVeen and co-workers described a peritoneo-venous shunt system which provides more continuous treatment over many months. The morbidity and mortality of this shunt are difficult to determine from published reports. Long-term controlled studies are needed. The beneficial effect on survival of treatment of cirrhotic ascites is still questioned.


[The physiopathology of ascites].

Sodium and water retention is constant in decompensated cirrhosis with ascites and edema. Sodium retention is due to several factors. Renal hemodynamic disturbances appear first: decrease in glomerular filtration and renal plasmatic perfusion, redistribution of renal perfusion to the juxtamedullar area where the longer nephrons reabsorb more sodium. Metabolic disorders of estrogens, natriuretic hormonal factor, prostaglandins and the kallikrein-kinin system contribute to greater sodium retention. Water retention is secondary to greater sodium reabsorption and to hyperactivity of the antidiuretic hormone. Sodium and water retention, associated with portal hypertension, with reduced oncotic pressure and with dynamic lymphatic insufficiency, is responsible for the production of ascites. The latter results in a decrease in the effective plasmatic volume, with non-suppression of the renin-angiotensin system, increased aldosterone production and additional sodium retention.