[Prophylaxis of peritoneal adhesions with streptokinase and streptodornase (Varidase). An experimental study in animals (author's transl)].

Animal experiments on 40 Wistar rats show that intraperitoneal application of Varidase can reduce or prevent the formation of adhesions after intra-abdominal interventions. This effect is interpreted as the sequel to a local increase in fibrinolytic activity which leads to the accelerated breakdown of fibrinous pseudo-membranes. The healing of intestinal sutures appears not to be impaired by Varidase.


[Thoughts on the Future of Gastroenterology (author's transl)].

The rapid growth of knowledge and and the multiplicity of new diagnostic and therapeutic methods are forcing the internal medical specialty apart and compelling us to specialize. One exponent of this development is gastroenterology. With the introduction of fiberoptics, gastroenterological diagnosis was revolutionized. Endoscopic biopsy methods are dominating diagnosis, radiological examination of the digestive tract is mainly used for supplementation. Operative endoscopy with its diagnostic and therapeutic importance forces us to closer cooperation with pathologists and surgeons. The immediate objective most likely to do justice to the development is the gastroenterological department or center which permits optimal cooperation. The gastroenterologist of the future must be trained in pathological anatomy, surgery and internist gastroenterology.


[Diagnostic methods in the bulbus duodeni. Agreement and disagreement between endoscopic, roentgenological and histological examinations (author's transl)].

In a collective of 1012 patients (700 m., 312 f.), 346 (268 m., 78 f.) had pathological endoscopic findings in the bulbus. Diseases of the bulbus appeared in women about 10 years later than in men. In comparison to the endoscopic findings, roentgen findings showed disagreement in about 35% which mainly arose from contradictions in the assessment of cicatricial changes in the bulbus. False negative ulcer findings amounted to about 21%, the false positive to 19%. Endoscopic and histologically confirmed malignancies were not overlooked in a single case.


[Diagnostic Methods in the Bulbus Duodeni. Agreement and Disagreement between Endoscopic, Roentgenological and Histological Examination (author's transl)].

In a collective of 1012 patients (700 m., 312f.), 346 (268 m., 78 f.) had pathological endoscopic findings in the bulbus. Diseases of the bulbus appeared in women about 10 years later than in men. In comparison to the endoscopic findings, roentgen findings showed disagreement in about 35% which mainly arose from contradictions in the assessment of cicatricial changes in the bulbus. False negative ulcer findings amounted to about 21%, the false positive to 19%. Endoscopic and histologically confirmed malignancies were not overlooked in a single case.


[The position of gastrointestinal suture technique. Advances through mechanical suture methods (author's transl)].

At the present time various materials and methods of manually suturing the gastrointestinal tract are used in parallel. While these methods satisfy basic standards, there is scarcely any detectable difference in the results. Further development in manual suturing with reference to security from failure and reduction of the expenditure of time is unforeseeable. Adhesive methods cannot achieve any importance in the gastrointestinal tract. Presently only the fully mechanical suture methods described at the end of the sixties show promise of possible future development in the gastrointestinal tract. They are suitable for as much as 80% of plastic gastrointestinal operations, but still need statistical comparison of results.


[The effect of antacids on stress-induced lesions of the gastric mucosa in the piglet (author's transl)].

After administration of antacids, gastric stress lesions due to hemorrhagic shock appear in the pig stomach quicker and more markedly than in animals which have been similarly treated with an indifferent substance or not at all. However, once treated, the administration of antacids seems to favor the healing of mucosal lesions after the end of the stress. At the same time it was observed that after administration of antacids in hemorrhagic shock, the serum gastrin level rises and does not remain  constant, as in the control group. An attempt is made to explain the favorable effect of antacids on the genesis of hemorrhagic stress lesions in the pig's stomach through this observation.


[Tryptic enzymes in the differential diagnosis of inflammatory diseases of the colon (author's transl)].

Inflammatory diseases of the colon can be differentiated by means of their chymotrypsin A excretion in the stool. In proctosigmoiditis and a group of comparable gastroenterological cases, the mean excretion level is between 170 and 200 mug per gram of stool. The chymotrypsin A level in proctocolitis, on the other hand, is significantly higher in all stages and increases with increasing activity of the disease. This brings a further diagnostic criterion to the clinical and endoscopic differences between proctosigmoiditis and proctocolitis (colitis ulcerosa). The fundamentally different behavior in the excretion of chymotrypsin A in the stool supports the hypothesis of two diseases differing from each other.


[Results of a double blind study with segontin--digoxin in coronary heart disease. (author's transl)].

Segontin-Digoxin and digoxin were tested in a cross-over double blind trial in 30 patients with coronary heart disease and concomitant organic insufficiency in a cardiological specialist practice. As far as the coronary symptoms were concerned, treatment with Segontin-Digoxin was clearly superior to digoxin therapy alone. With regard to the elimination or improvement of signs of myocardial insufficiency, no difference could be established between the two preparations. A distinct lowering of heart rate and blood pressure, especially in hypertensives, was observed with Segontin-Digoxin therapy compared with digoxin alone.


[Results of a double blind study with Segontin-Digoxin in coronary heart disease (author's transl)].


Mutation induction by the direct treatment of Bacillus subtilis deoxyribonucleic acid.

A procedure was developed to select for specific mutations obtained by means of transformation with DNA previously exposed to potentially dangerous chemical compounds. The 70% co-transformation of hisB and trpC genes in Bacillus subtilis provided a convenient opportunity to select for new mutations. When purified DNA from wild type bacteria was treated with N(OH) acetyl aminofluorene or Hoechst dye 37 507 and used to transform a recipient bearing of a trpC2 mutaion, a high proportion of the Trp+ transformants had new hisB mutations.


The lifetime health-monitoring program. A practical approach to preventive medicine.

Current patterns of health care and its financing need to be improved by the incorporation of cost-effective and health-effective preventive measures. As a stimulus for further development, we propose a Lifetime Health-Monitoring Program that uses clinical and epidemiologic criteria to identify specific health goals and professional services appropriate for 10 different age groups. During infancy, for example, we recommend seven immunizations, tests to detect anemia, hemorrhagic diseases, phenylketonuria and developmental deficiencies, and routine prophylaxis of gonorrheal ophthalmia. In the age group 40 to 59, tests for hypertension, cervical, mammary, and gastrointestinal cancer, and control of obesity and smoking are in order. The cost of such preventive measures. which should not be prohibitive, must be covered by health-insurance programs, whether based on fee-for-service or capitation. The program suggested, by incorporating prevention into day-to-day care, should strengthen the patient-physician relation.


Purine nucleoside phosphorylase deficiency associated with selective cellular immunodeficiency.

We studied a 15-month-old girl who had normal T-cell and B-cell immunity at birth, after which a gradual decrease in T-cell immunity developed. This selective cellular immunodeficiency was inherited as an autosomal recessive trait: two older sisters had the same immunodeficiency. Adenosine deaminase activity was present in erythrocytes and lymphocytes of the patient, parents and a healthy brother. Purine nucleoside phosphorylase activity was not found in the patient's erythrocytes and lymphocytes (the parents and brother had intermediate values, indicating that the enzyme deficiency too was inherited as an autosomal recessive trait). Analysis of serum and urine from the patient and of serum from her two deceased sisters showed high levels of inosine and guanosine in addition to hypouricemia and hypouricosuria. The bone marrow was megaloblastic, and the blood hypochromic microcytic. The patient had spastic tetraparesis. Intoxication of the T lymphocytes after birth by metabolic products may explain the progressive cellular immunodeficiency.


Foundations of cost-effectiveness analysis for health and medical practices.

Limits on health-care resources mandate that resource-allocation decisions be guided by considerations of cost in relation to expected benefits. In cost-effectiveness analysis, the ratio of net health-care costs to net health benefits provides an index by which priorities may be set. Quality-of-life concerns, including both adverse and beneficial effects of therapy, may be incorporated in the calculation of health benefits as adjustments to life expectancy. The timing of future benefits and costs may be accounted for by the appropriate use of discounting. Current decisions must inevitably be based on imperfect information, but sensitivity analysis can increase the level of confidence in some decisions while suggesting areas where further research may be valuable in guiding others. Analyses should be adaptable to the needs of various health-care decision makers, including planners, administrators and providers.


UDP-glucuronyltransferase in perfused rat liver and in microsomes. Effects of CCl4 injury.

To elucidate the disparity between glucuronidation rates in vivo and UDP-glucuronyltransferase in vitro after CCl4 injury, the time course of the effects of CCl4 (0.25 ml/kg) on kinetic properties of UDP-glucuronyltransferase (l-naphthol as substrate) was examined in rat liver homogenates and microsomes. These experiments were compared with l-naphthol glucuronidation by the perfused liver which was studied at various time points after CCl4 administration. Phenobarbital-treated rats were used to enhance the hepatotoxicity of CCl4. 1. Within 24 h UDP-glucuronyltransferase activity increased 8-fold in liver homogenates and 3-fold in microsomes. During this time the allosteric activator, UDP-N-acetylglucosamine, lost its effect whereas the inhibitor UPD showed greater inhibitory properties, thus counteracting the activation. 2. l-Naphthol glucuronidation in perfused livers was significantly decreased by 24 h. Sulfate ester formation was little affected. 3. The content of UDP-glucuronic acid was not significantly altered although liver histology revealed about 45% necrotic and prenecrotic cells and an uniform fatty degeneration of hepatocytes after 24 h. The results suggest that during CCl4 injury, UDP-glucuronyltransferase is activated. At the same time the kinetic properties of the enzyme are altered in a way leading to inefficient glucuronide synthesis, when assays are carried out under conditions presumed to exist in vivo. Nevertheless the capacity to form glucuronides is retained in the acutely injured liver.


[Effect of calcium ions on channels for entrance and exit of ionic currents in the membranes of mollusk neurons].

A newly developed method of internal dialysis was applied together with the voltage clamp method to the isolated neurons of molluscs Helix pomatia and Limnea stagnalis. Effect of Ca on the Ca inward and K delayed outward currents was investigated. Removal of Ca from the external medium was equivalent to 25-35 mV hyperpolarization of the membrane. Internal Ca in concentrations up to 3.5-10-(7)M caused insignificant depression of K outward current. 5.7-10-(8)M of internal Ca completely blocked Ca inward current. Ca-chelating agents applied either internally or externally caused an appearance of Na inward current transferred through the Ca channels.


[Comparison of scintiscans and electroencephalograms in cases of suspected symptomatic epilepsy].

In 101 patients treated for epilepsy electroencephalographic and scintigraphic investigations were carried out. In 93 cases the results of EEG investigations were abnormal, in 8 normal. Scintiscanning demonstrated presence of focal pathological changes in 20 cases, in 81 cases the scans were normal. The highest proportion of concordant results was obtained in cases with focal EEG changes -- 50% while in all cases of symmetrical seizure activity in EEG the scientiscans were normal. The combination of both methods increases the possibility of early diagnosis in cases with symptomatic epilepsy.


Fetal cardiovascular responses to distress. A review.

This review is designed to provide a broad view of fetal cardiovascular response to fetal distress. The presentation focuses on data obtained from laboratories working with fetal sheep, or occasionally fetal monkeys, instead of attempting to interpret data resulting from human fetal studies. Human fetal studies are unsatisfactory for any detailed analysis other than discussions of an occasional case history because of the difficulty of identifying controls and because cardiovascular experimentation is not ethically possible.


The formation and turnover of the membranocalyx on the tegument of Schistosoma mansoni.

The multilaminate vesicles present in the tegument cytoplasm appear to fuse with side channels projecting out into the cytoplasm from the base of the surface pits. Their lamellate contents then unroll and spread out to form a trilaminate membranocalyx lining the pits and covering the tegument surface. The plant lectin concanavalin A appears to stabilize the process of vesicle fusion leading to an aggregation of multilaminate vesicles trapped in the lumen of the surface pits. The membranocalyx can be labelled with cationized ferritin. Chase incubations in normal medium indicate that by 4 h most of the label and the membranocalyx to which it is bound have been lost to the medium. This suggests that under the conditions of these experiments the membranocalyx has a half-life of 2-3 h.


The immune response of plaice (Pleuronectes platessa L) to the metacercariae of Cryptocotyle lingua and Rhipidocotyle johnstonei.

The humoral immune response of plaice to infestations of selected metacercariae was studied. Precipitating antibodies to both Cryptocotyle lingua and Rhipidocotyle johnstonei were demonstrated using agar gel diffusion techniques. Immunochemical investigations of these antibodies indicated they were macroglobulins, resembling immunoglobulin M (IgM) of mammals. The rate and magnitude of antibody production by the host was determined by the ambient temperature.


The biologic activities of cystic fibrosis serum. I. The effects of cystic fibrosis sera and calcium ionophore A 23187 on rabbit tracheal explants.

An ionophore A23187-induced increase in membrane permeability to calcium ions in culture medium produced a rabbit tracheal mucociliary response indistinguishable from that caused by cystic fibrosis (CF) sera on three different occasions. Specific chelation of calcium ions with EGTA in the basal medium Eagle (BME) media with no additive or in native CF sera abolished the mucociliary disturbances in all cases. Increased membrane permeability to calcium may be important in the production of the mucociliary response by CF serum factor(s) in the tracheal assay system.


Influence of intravenous nutrients on bilirubin transport. I. Amino acid solutions.

The effects of synthetic amino acids on bilirubin transport were investigated with competitive binding assays, peroxidase assays, isotopic studies of bilirubin uptake by red cells, and difference spectroscopy. Results indicated that amino acids had no significant effect on the distribution of bilirubin at pigment to albumin molar ratios likely to be encountered in clinical situations.


Influence of intravenous nutrients on bilirubin transport. II. Emulsified lipid solutions.

The effects of an emulsified intravenous fat preparation (Intralipid) on bilirubin transport were analyzed by cholestyramine extraction, spectrophotometric analysis, Sephadex gel filtration, peroxidase assay, bilirubin uptake by red blood cells, and by toxicity in tissue culture (L-929) cells. Intralipid is capable of binding bilirubin, but does not compete effectively with bilirubin bound to high affinity sites on albumin. The emulsified fat appears to have a higher affinity for bilirubin than for cell membranes. Red blood cells become coated with Intralipid, resulting in an increased association of bilirubin with the cell surface, but a decrease in pigment actually incorporated into the red cell membrane. In tissue culture experiments, Intralipid protected the cells from bilirubin toxicity. It is concluded that Intralipid may enhance the carrying capacity of serum for bilirubin, and thus exert a protective effect on tissues.


Influence of intravenous nutrients on bilirubin transport. III. Emulsified fat infusion.

Infusions and injections of Intralipid were administered to congenitally jaundiced rats (Gunn) in whom the total body bilirubin pool was uniformly labeled with radioactive bilirubin. These isotopic studies indicated that Intralipid treatment had no effect on the kinetics of bilirubin formation, transport, tissue distribution, and clearance. There were no significant differences between control and fat emulsion-treated animals in the total bilirubin pool, plasma bilirubin pool, biologic half-life of bilirubin, fractional turnover, and exponential decline in plasma bilirubin specific activity at steady state. Bilirubin concentrations in blood, plasma, liver, kidneys, brain, adipose tissue, and muscle were unaltered during the course of continuous infusions (up to 24 hr) of Intralipid. These results indicate that Intralipid administered in clinically applicable doses and regimens has no discernible effects on bilirubin metabolism in jaundiced rats.


Computerized axial tomography in neurologic disorders of children.

Computerized axial tomography offers major advantages over air encephalography and angiography for studies of neurologic disorders in children. The low morbidity and the ease of the procedure permit the accurate diagnosis of intracranial pathology in situations where more invasive procedures would not be undertaken. The techniques of the procedure and its uses and limitations are emphasized in a number of neurologic problems of children.


Effect of introducing novel configurational cues on a learned color discrimination in squirrel monkeys.

The study explored the effect of introducing novel cues on a learned color discrimination. 6 squirrel monkeys were initially trained to discriminate between plaques covered with green and brown construction paper. In a series of transfer tests, these color cues were then presented in 6 different patterns and varied in 4 sizes. The results indicate that some patterns will produce more disruption than others. Furthermore, reducing the size of the cues may also lead to a decrement in performance level. The outcome corresponds well with those of studies which show that contextual variables influence the acquisition of discriminative responses.


Serial adaptation to conflicting prismatic rearrangement effects in monkey and man.

Seven adult male squirrel monkeys adapted successfully to prisms displacing in equal and opposite directions. After protracted training under certain conditions, they succeeded in conserving adaptation to both prisms without benefit of readaptation trials. Results obtained with thirty-six undergraduates under similar conditions of test (although for a much shorter period) are also reported.


Do monkeys' subjective clocks run faster in red light than in blue?

When monkeys are given control of the illumination in a testing chamber, it has been found, under three conditions, that they spend less time with red light than with blue. But the results cannot easily be explained in terms of 'preference'. Rather, the results suggest that monkeys judge 'subjective time' to pass nearly twice as fast in red light as in blue.


The control of bovine leukosis in denmark, Epidemiologic and diagnostic aspects.

The Danish programme to control bovine enzootic leukosis was initiated in 1959 and intensified in 1969. The programme has resulted in a sharp decline in total and relative numbers of leukotic tumor cases in adult animals. However, total eradication of bovine leukosis has not yet been achieved, and the statistics from recent years seem to indicate that the present programme based on haematological and histological examinations will control but not eradicate the disease. An immunodiffusion test based on an internal protein (p 24) antigen has been used experimentally. This test is a valuable tool in herd diagnosis, but it is not sensitive enough for accurate single animal diagnosis.


Frequency of latent bovine leukosis in Sweden.

The enzootic bovine leukosis occurs in Sweden especially in the south-eastern part of the country. An orientating serological survey was carried out on various categories of dairy cattle predominantly from this area. Serological and haematological examinations were also carried out on beef cattle herds connected to a volontary control program for bovine leukosis.


Intestinal absorption of 65 Zinc in A46 (Adema disease) after treatment with oxychinolines.

In two calves with the genetic defect A46 (Adema disease) intestinal absorption of 65Zn was increased during a period of oral treatment with oxychinolines. Oral supplementation with zinc oxide resulted in extremely high plasma zinc concentrations and a moderate increase in 65Zn absorption.


Medical management of angina pectoris.

Nitroglycerin should be the first agent prescribed for patients with angina pectoris. When nitroglycerin is used daily, a trial with longer-acting nitrates (eg, isosorbide dinitrate) is warranted. If angina persists, use of beta-adrenergic blocking agent (propranolol) should be considered. Appropriate use of nitrates and propranolol, singly or in combination, will relieve angina pectoris due to coronary heart disease in most patients.


The sphiningolipidoses: an overview.

An outline of the pathways of catabolism of four sphingolipids to ceramide, along with structural details of a few constituents, serves as a framework for better understanding of the sphingolipidoses. The four sphingolipids are sulfatide, sphingomyelin, globoside, and ganglioside GM1. Diseases which can be incorporated into the scheme include Niemann-Pick disease, Gaucher disease, metachromatic leukodystrophy, Krabbe disease, ceramide lactoside lipidosis, Tay-Sachs disease, generalized gangliosidosis, Fabry disease, and Sandhoff disease. Fucosidosis probably also belongs with this group. GM3 (hematoside) sphingolipodystrophy involves blocks in synthetic rather than catabolic pathways.


The effects of naloxone and nalorphine during the development of morphine dependence in rhesus monkeys.

A randomized and blind experimental design was used to study the effects of naloxone and nalorphine on the development of morphine dependence in monkeys. The results suggest: (a) that significant dose-related differences existed for combined numbers of withdrawal symptoms times frequency of occurrences; (b) that naloxone and nalorphine were qualitatively similar; (c) antagonists are more effective as dependence develops; (d) naloxone is approximately 10 times more potent than nalorphine, and (e) vomiting was the only withdrawal sign with which ED50s could be calculated. Dependence on morphine still increases up to 9 months after the commonly accepted 90-day stabilization period as measured by the ED50 for vomiting for naloxone.


Performance parameters of the Hamburg 4 pi whole body radioactivity detector.

Large 4 pi whole body counters allow the use of very low doses of radioactivity in medical research and in routine diagnosis of patients. The electronics of the 4 pi whole body counter in Hamburg (HAMCO) have recently been updated. The detector contains 1360 I of liquid organic scintillator. Experiments combined with extensive computer simulations yielded quantitative information for whole body counters and comparable systems, (1) about physical parameters such as detection efficiency, energy resolution and background count rates which are important for practical performance, and (2) concerning the optical properties of the large volume scintillation counters employed here; these are of interest for the construction of future detectors of related types.


An evaluation of the local effects of triamcinolone acetonide on normal soft tissues in monkey digits.

The lack of quantitative information on the observed effects after subcutaneous injections of triamcinolone prompted a double blind, prospective study of the drug's effects. The results demonstrate that there are gross losses in the subcutaneous fat. No significant quantitative differences were observed in the collagen content (microscopic or biochemical) in these monkey digits.


Pharmacological and biochemical studies with three metabolites of nomifensine.

Three major metabolites (M1, M2, M3) of nomifensine (8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenyl-isoquinoline) are formed by hydroxylation and methoxylation of the phenyl ring. They were compared with nomifensine 1. in various psychopharmacological tests in vivo, carried out in mice after oral or i.p. treatment and 2. in neurochemical in vitro studies, measuring inhibition of noradrenaline (NA), dopamine (DA), and serotonin (5-HT) uptake in rat brain synaptosomes. M1 (4'-hydroxy-nomifensine) was the most active metabolite, while M2 and M3 had little or no effect in pharmacological tests. M1 reversed reserpine hypothermia in doses greater than 2.5 mg/kg, antagonized tetrabenazine catalepsy (ED50 68 mg/kg) and reversed oxotremorine hypothermia (ED50 33 mg/kg). In these tests nomifensine was also active, being about 3-10 times more potent than M1. In contrast to nomifensine M1 had also serotoninergic activity, potentiating both phenelzine-induced twitching (ED50 11 mg/kg) and the anticonvulsant effect of 5-hydroxytryptophan. Moreover, M1 prolonged the hexobarbital sleeping time in doses greater than 10 mg/kg, prevented nicotine-induced convulsions (ED50 58 mg/kg) and reduced the oxotremorine tremor (ED50 59 mg/kg). The LD50 of M1 was 1100 mg/kg orally. In vitro M1 was equipotent with nomifensine in inhibiting DA uptake (IC50 1.5 x 10(-7) M) and twice as active in inhibiting NA uptake (IC50 1.1 x 10(-8) M). In contrast to nomifensine M1 was also a potent inhibitor of 5-HT uptake (IC50 3.3 x 10(-7) M). M2 and M3 were less active than M1 in all experiments.


Individual differences in average evoked responses to d- and l-amphetamine with and without lithium carbonate in depressed patients.

Visual average evoked responses (AERs) to four intensities of light were studied in hospitalized depressed patients receiving placebo, d-amphetamine, l-amphetamine, lithium and d- and l-amphetamine combined with lithium. For the assessment of the subjective effects of the drugs, the patients completed a 34-item mood and behavior self-rating scale. AER responses to repeated doses of the amphetamines were consistent within the same individual but varied greatly between different individuals. For the patient group considered as a whole, only minor AER changes occurred in response to either d- or l-amphetamine; nonetheless, these minor changes were attenuated by lithium co-administration. There were indications, however, that AER baseline measures could be used as predictors of change in self-rating due to both d- and l-amphetamine, as patients who had larger AER amplitudes on baseline also tended to have larger increases in activation ratings and reductions in depression ratings. The amount of increase in AER amplitude or amplitude/intensity slope seen with amphetamine was also significantly correlated with the amount of increase in activation or euphoria ratings with amphetamine administration. These effects were most prominent in the same P100 component that we have previously found to differentiate bipolar and unipolar depressed patient groups.


A comparative study of the behavioural responses induced by chronic administration of methamphetamine and amphetamine in mice.

The behavioural effects induced in mice by the chronic administration of (+)-methamphetamine (MA) and (+)-amphetamine (A) at three dosages were studied under identical research conditions. The results indicated that MA exerted greater central excitation than A. At the dosage 0.64 mg/kg quiescence was decreased and activity increased more by MA than A. Hyperactivity induced at the 2.5 mg/kg dosage was sustained over a longer time period with MA. Frenzied self-tearing emerged with repeated drug administration at the 10 mg/kg dose in more MA-treated than A-treated animals.


Is tolerance to delta-9-THC cellular or metabolic? The subcellular distribution of delta-9-tetrahydrocannabinol and its metabolites in brains of tolerant and non-tolerant rats.

Rats were injected intraperitoneally once every 12 h with 10 mg/kg delta-9-THC and the time course of the depressant effect was determined after one and nine injections. The motor activity of naive rats was maximally depressed between 1 and 4 h and returned to control levels 8 h after treatment. After nine injections, the maximum intensity of the depressant effect was not different from that after one injection but had completely disappeared at an earlier time point (4 h p.i.) indicating the development of tolerance to the duration of effect on motor activity. The subcellular distribution studies in brains of tolerant and non-tolerant rats indicated that an accelerated shift in the concentrations of delta-9-THC and 11-OH-delta-9-THC towards highly polar metabolites in the brains, rather than an increased elimination of these cannabinoids or decreased sensitivity of the brain may be responsible for the development of tolerance to delta-9-THC.


Effect of foot-shock intensity on amount of memory retrieval in rats by emotionally important stimuli in a drug-dependent learning escape design.

Drug-dependent learning (lack of transfer between drug states) was demonstrated and disrupted in an escape learning, forced choice T-maze task. A drug-dependent learning (DDL) group was trained to escape foot shock (0.65 mA) while in a drug (chlordiazepoxide hydrochloride) state. These rats subsequently responded randomly on non-shock test trials in the non-drug state, but continued to respond significantly (P less than 0.02) above random level when in the training drug state. Four transfer groups were also trained in the Drug state, but with a 1 kHz auditory tone simultaneously paired with foot shock. Each Transfer group received a different (0.10, 0.65, 3.5, and 4.5 mA) foot shock intensity during training. The auditory tone continued to be sounded during testing with no foot shock, and percentage correct turns, first-trial correct turns, and latency scores were significantly (P less than 0.01) different from the DDL group's performance. The results were interpreted as demonstrating that an emotionally-important auditory stimulus could initiate a memory retrieval process that could overcome a physiological state. This memory retrival process was not modified by wide variations in foot shock intensity.


Seizure activity in photosensitive baboons following antidepressant drugs and the role of serotoninergic mechanisms.

Laboratroy and clinical evidence indicates that tricyclic antidepressants lower seizure threshold and in high doses may induce generalised seizures. In baboons with photosensitive epilepsy (Papio papio) the effects of 2 tricyclic antidepressants (imipramine and chlorimipramine) and of maprotiline and Nomi fensine have been studied (i.v. dose range 1-20 mg/kg. Imipramine, chlorimipramine and maprotiline (10 mg/kg i.v.) lowered seizure threshold to a comparable extent, whereas Nomifensine (10 mg/kg i.v-) did not enhance myoclinic responses to photic stimulation. Generalised seizures were seen 15-30 min after imipramine or chlorimipramine (20 mg/kg), and these two drugs showed no difference in their epileptogenicity. Administration of 5-hydroxytryptophan (25 mg/kg i.v.) 90 min before chlorimipramine or imipramine (10 mg/kg) completely blocked the usual augmentation of photically-induced epileptic responses. It is concluded that enhancement of serotoninergic activity following blockade of 5-HT re-uptake within the brain is unlikely to be responsible for enhanced myoclonic responses and epileptogenic seizures seen after tricyclic antidepressants. Nomifensine is significantly less epileptogenic than imipramine or chlorimipramine.


Effects of prior experience and 'functional disturbance' on acute and chronic tolerance to methylphenidate.

The degree of habituation or adaptation an animal has experienced prior to the administration of methylphenidate was found to be more crucial in determining the animal's response to the drug than chronic drug administration alone. Rats allowed to adapt in a Y-maze for 24 days showed less methylphenidate-induced activity than animals receiving chronic administration of saline or methylphenidate but no adaptation, when animals were injected with the drug and tested in the Y-maze on Day 25. Animals also were shown to develop tolerance to the methylphenidate-induced activity.


Behavioral comparisons of R-2-amino-1-(2,5-dimethoxy-4-methylphenyl) butane (BL-3912A) with R-DOM and S-amphetamine.

The behavioral effects of R-2-amino-1-(2,5-dimethoxy-4-methylphenyl) butane or BL-3912A were compared with those of S-Amphetamine and R-DOM. BL-3912A facilitated acquisition of shuttle box responding by rats without increasing noncontingent intertrial (ITI) activity, while S-Amphetamine increased both avoidance and ITI responding. R-DOM had a biphasic effect on avoidance responding, increasing it at low doses and disrupting at higher doses. At doses that facilitated shuttle box responding, BL-3912A had no effect on unacclimated motor activity of rats nor on the rate of continuous avoidance responding by rats. S-Amphetamine increased the frequency of both motor activity and operant avoidance responding, while R-DOM decreased motor activity and increased operant avoidance responding. By facilitating avoidance behavior without increasing othermeasures of psychomotor activity, BL-3912A represents a unique psychopharmacological agent clearly different from R-DOM and S-Amphetamine.


The effects of chronic administration and withdrawal of (+)-amphetamine on seizure threshold and endogenous catecholamine concentrations and their rates of biosynthesis in mice.

The i.v. pentylenetetrazol seizure threshold was increased by 2.5 mg/kg and decreased by 15 mg/kg of a single (+)-amphetamine dose. After 7 consecutive days of amphetamine administration, tolerance developed to the decrease but not to the increase in seizure threshold. At 12--48 h after the last dose of 2.5 mg/kg seizure threshold was decreased, and at 36--48 h after the last dose of 15 mg/kg seizure threshold was increased. After acute and chronic administration of (+)-amphetamine (2.5 mg/kg) endogenous concentrations of whole brain dopamine (DA) were increased and returned to normal levels during the withdrawal period (12--48 h); endogenous norepinephrine (NE) levels were unchanged by acute and chronic drug treatment and during withdrawal. The rates of DA and NE synthesis were increased by chronic amphetamine administration at 24--48 h after drug withdrawal. An acute dose of (+)-amphetamine (15 mg/kg) decreased endogenous levels of DA and NE; normal levels of DA were detected with chronic drug treatment and during withdrawal, with NE remaining slightly depressed. The rates of synthesis of DA and NE were increased by acute and chronic amphetamine treatment and returned to normal 24--48 h after withdrawal. The rebound reversal in seizure threshold after (+)-amphetamine withdrawal suggests an abstinence syndrome that may be interpreted as evidence for the development of physical dependence to (+)-amphetamine after chronic drug administration.


Lack of effect of tricyclic antidepressants on serum prolactin levels.

A previous report indicated that the tricyclic antidepressants imipramine and amitriptyline markedly increased plasma prolactin levels in man. We found no increases after acute or chronic treatment with either drug in usual clinical doses. The results indicate that blockade of serotonin reuptake does not affect basal prolactin levels in man.


Intracranial reward after Lilly 110140 (fluoxetine HCl): evidence for an inhibitory role for serotonin.

The 5-hydroxytryptamine (5-HT, serotonin) specific presynaptic reuptake inhibitor Lilly 110140 (fluoxetine hydroxhloride) was injected systemically in rats trained to bar-press for rewarding stimulation to the caudal portion of the medial forebrain bundle. Rates of self stimulation were reduced in proportion to drug dosage, and these reductions were partially reversible by methysergide. These findings are consistent with previous reports suggesting an inhibitory role for 5-HT in self stimulation.


Barbiturate dependence in mice: effects of continuous vs. discontinuous drug administration.

Three groups of DBA/2J mice were continuously exposed for 3, 6 or 9 days to a milled diet containing phenobarbital. Two additional groups were given a discontinuous drug administration schedule with either one or two 24 h drug-free periods interpolated among the 6 or 9 days of phenobarbital consumption, respectively. The discontinuous schedule of drug administration significantly attenuated the development of physical dependence as determined by the severity of withdrawal symptoms. Functional tolerance development was also attenuated in a manner that closely paralleled the effects on physical dependence development. The 5 group means showed a perfect rank order correlation between functional tolerance and physical dependence development.


Changes in drug-induced stereotyped behavior after 6-OHDA lesions in noradrenaline neurons.

Drug-induced stereotyped behaviors are often assessed by rating scales where the eventual appearance of sniffing, licking, and biting are rated as increasing intensity of dopaminergic stimulation. A 6-OHDA induced bilateral lesion (4 X 3-8 mug/4 mul 6-OHDA) in the ascending noradrenaline neurons, lateral to the medial raphe nucleus, of 180 g Wistar rats, affecting selectively noradrenaline and not dopamine or 5-hydroxytryptamine neurons, caused a change in the d-amphetamine sulphate (5-3 mg/kg s.c.) and phenethylamine hydrochloride (40 mg/kg) induced stereotyped sniffing behavior to the performance of discontinuous or continuous licking behavior; biting/gnawing was rarely induced. The site of the lesion and the partial antagonism of 6-OHDA by the uptake inhibitor protriptyline indicate a noradrenergic influence on the behavioral expression of the dopaminergically mediated stereotyped behavior.


Interaction between yohimbine alkaloids and amphetamine in mice.

The toxicity (LD50) of the isomers yohimbine, beta-yohimbine, and corynanthine was determined in mice. The LD50 of amphetamine in the presence of a constant dose of a yohimbine isomer and that of the isomer in the presence of a constant dose of amphetamine were determined in aggregated mice. Isobolograms were constructed from these data and used to evaluate the interaction of the yohimbine alkaloids and amphetamine. Beta-yohimbine was found to be approximately twice as toxic as yohimbine and corynanthine about one fifth as toxic. There was a mutual potentiation between the toxicities of yohimbine and amphetamine. Potentiation of the toxicity of amphetamine occurred with beta-yohimbine but the effect was not as marked as with yohimbine. In contrast, corynanthine antagonized the toxicity of amphetamine. The interaction between yohimbine and amphetamine is unlikely to be due to noradrenergic mechanisms but could conceivably involve serotonergic or dopaminergic mechanisms.


Enhancement of propoxyphene-induced analgesia by doxepin.

The activity of the centrally acting analgesic, propoxyphene, either alone or combined with the tricyclic antidepressant, doxepin, has been studied. Doses of doxepin, in themselves lacking any analgesic effect, remarkably enhanced the analgesic activity of propoxyphene, either by the oral or intraperitoneal route. On the other hand, oral toxicity data prove that doxepin does not alter significantly propoxyphene acute toxicity.


Angiographic abnormalities in partial Budd-Chiari syndrome.

Partial Budd-Chiari syndrome was produced in 8 monkeys by obstructing 2 or 3 lobar hepatic veins with a rapidly polymerizing plastic. Hepatic angiography done 1-3 months later revealed crowded tortuous arteries and a dense hepatogram in the lobe with venous occlusion. Unobstructed lobes were hypertrophied. Retrograde injection of persistently patent hepatic veins demonstrated a "spiderweb" collateral system. Retrograde venography to demonstrate this pathognomonic plexus is the procedure of choice when partial Budd-Chiari syndrome is suspected.


Internal auditory canal enlargement in neurofibromatosis without acoustic neuroma.

Acoustic neuroma has always been reported to accompany neurofibromatosis in patients with enlargement of the internal auditory canal. The authors describe a case in which the internal auditory canal was enlarged but there was no tumor. This may represent a normal variant or a manifestation of the bony dysplasia of neurofibromatosis.


Radiation therapy for exophthalmos: report of seven cases.

Five of 7 cases of exophthalmos showed improvement within three months with 2,000 rads of 6 MeV radiation. A new technique of X-ray beam localization employing a direct measurement 12 mm posterior to the anterior extent of the cornea was used and found more accurate than using a fixed point (external canthus). All cases should be treated bilaterally. Retreatment after radiation failure is not recommended. There were no complications. Improvement is usually rapid as orbital irradiation, not including the pituitary, causes rapid destruction of the massive collection of lymphocytes and a reduction in the bulky mass and edema of the orbit.


Luteolytic action of 15-keto prostaglandin F2alpha in the rhesus monkey.

The naturally-occurring metabolite of prostaglandin F2alpha, 15-keto prostaglandin F2alpha (15-keto PGF2alpha), elicited rapid and sustained declines in serum progesterone concentrations when administered to rhesus monkeys beginning on day 22 of normal menstrual cycles. Evidence for luteolysis of a more convincing nature was obtained in studies where a single dose of 15-keto PGF2alpha was given on day 20 of ovulatory menstrual cycles in which intramuscular injections of hCG were also given on days 18-20; serum progesterone concentrations fell precipitously in monkeys within 24 hours following intramuscular administration of 15-keto PGF2alpha. However, corpus luteum function was impaired in only 4 of 11 early pregnant monkeys when 15-keto PGF2alpha was administered on days 30 and 31 from the last menses, a time when the ovary is essential for the maintenance of pregnancy. Gestation failed in 2 additional monkeys 32 and 60 days after treatment with 15-keto PGF2alpha, but progressed in an apparently normal manner in the remaining 5 animals. Two pregnant monkeys treated with 15-keto PGF2alpha on day 42 from the last menstrual period, a time when the ovary is no longer required for gestation, continued their pregnancies uneventfully. Corpus luteum function was not impaired in 9 control monkeys which received injections of vehicle or hCG at appropriate times during the menstrual cycle or pregnancy.


Improved port film quality with six megavolt linear accelerator.

This article introduces a new technique for accurate verification of therapy treatment sites with radiographs. It can be used not only on most linear accelerators, but also on cobalt treatment units, with slight variation in exposure technique. It can eliminate the poor image detail presently seen and accepted at various therapy instiutions with a new method of quality control.


Rat liver post-microsomal D-T diaphorase: activation of the enzymes by two carcinogens.

The effects of two carcinogens (N-acetylaminofluorene and 7, 12-dimethylbenz(a)anthracene) on the rat liver soluble D-T diaphorase are reported in this communication. The activity of the enzyme is increased in 24 hours by both compounds tested in this study.


A potent antinociceptive cannabinoid which lacks opiate substitution properties in monkeys.

(-)-9-Nor-9beta-hydroxy-hexahydrocannabinol[(-)-9-nor-9beta-OH-HHC] produced hypotension and bradycardia in anesthetized dogs, was a potent antinociceptive agent in the mouse tail-flick and p-phenylquinone abdominal-stretching tests, but did not reverse the effects of morphine withdrawal in dependent monkeys.


Experimental hepatic injury: the sequential changes in drug metabolizing enzyme activities after administration of acetaminophen.

Experimental hepatic necrosis was induced in phenobarbital pretreated rats by means of the intraperitoneal administration of an acetaminophen-dimethyl sulfixide (DMSO) mixture. Cytochrome P-450 content and the specific activities of aminopyrine demethylase, aniline hydroxylase and bilirubin glucuronyl transferase diminished over the three-day study period, as compared with control animals. The reductions, however, were generally modest; not uniform for all the enzymes assayed; and correlated poorly with histologic necrosis and standard liver function tests. It is concluded that in acute liver disease changes in the hepatic in vitro drug metabolizing enzyme capacity may not be closely related to cellular necrosis, per se, and the degree of change in enzyme activities will vary from one enzyme system to another. These findings may explain, in part, the often inconsistent alterations in the disposition and elimination of drugs described in associated liver disease.


An evaluation of indirect immunofluorescence in the serological diagnosis of Nosema cuniculi infection.

An indirect immunofluorescence test for serum antibodies to Nosema cuniculi was evaluated in rabbits by comparison with established histopathological methods of diagnosis. Cell-culture isolation procedures and immunofluorescence and histological techniques designed to detect the parasite in urine or tissues were used to confirm the diagnosis. The serological diagnosis showed excellent correlation with presence of brain lesions characteristic of nosematosis, and N cuniculi were detected in 63 per cent of seropositive rabbits but in no seronegatives. Serum cross-reactivity tests between N cuniculi and Toxoplasma gondii showed that these two protozoa are antigenically distinct. The technique offers a simple, sensitive and reliable procedure for diagnosis of nosematosis in a living animal.


A material balance study of polychlorinated biphenyls in Lake Michigan.

This paper integrates the known chemical and physical properties of polychlorinated biphenyls (PCB) derived in the laboratory with a mathematical model describing their behavior in Lake Michigan. The conclusion that emerges is that the observed levels of PCB both in Lake Michigan and the fish biomass are consistent with these laboratory measurements. In addition, it is concluded that it will take several years for this ecosystem to cleanse itself of the compounds even if no new input is made. The final sink for PCB is predicted to be degradation in the atmosphere, with some fraction being buried in the underlying sediments of the lake.


Lysis of human cultured lymphoblastoid cells by cell-induced activation of the properdin pathway.

Human cultured lymphoblastoid cells incubated in normal human serum activate the properdin complement pathway without antibody. However, only cells bearing C3b immune adherence receptors bind components of the properdin complement pathway and undergo lysis. A similar surveillance mechanism may exist in man to limit growth of malignant B cells bearing C3b immune adherence receptors.


Angiogenesis: a marker for neoplastic transformation of mammary papillary hyperplasia.

Mouse mammary papillomas elicit new formation of vessels when transplanted onto the rabbit iris. This angiogenic capacity is a property of carcinomas but not of the resting mammary gland. In mouse papillary hyperplasias, however, this property appears much earlier than any morphological or clinical sign of carcinoma. A test for angiogenic capacity may reveal a step in the progression toward clinical malignancy and thus could be used to screen for neoplastic potential of hyperplastic epithelium in biopsy tissues.


Effect of bacterial products on inflammatory reactions in the dental pulp.

Culture filtrates (extracellular components) and material obtained from disintegrated cells (intracellular components) of cultured plaque bacteria were studied for their capacity to induce inflammatory reactions in the dental pulp. Class V cavities were prepared on the buccal surface of 94 teeth: 42 test and 52 control teeth in six adult monkeys. lyophilized bacterial components were sealed into the test cavities either alone or following an 8-h topical application of a solution of the same components in phosphate-buffered saline (PBS). Culture medium and PBS were applied in two sets of control cavities. A third set was restored with zinc oxide-eugenol cement. The animals were killed 32 h after the initiation of the experiment and the pulps were examined histologically. Teeth treated trophil leukocytes in the area of the pulp subjacent to the cut dentin tubules. Abscess formation was frequently found. The severe reactions which developed were independent of differences between individual animals and differences in thickness of the remaining dentin. The controls showed damage to the odontoblasts but little or no neutrophil infiltration. The findings confirm that products of bacteria applied to exposed dentin initiate inflammatory reactions in the dental pulp.


Conjugal transfer of the gonococcal penicillinase plasmid.

Certain gonococci, which heretofore have lacked a conjugal mating system, can sexually transfer a small plasmid (4.5 x 10)6) daltons) which carries the gene for beta-lactamase production. Frequencies of conjugal transfer were similar into diverse recipients (other gonococci, Neisseria flava, and Escherichia coli), which suggests that gonococci may transfer the plasmid promiscuously in nature.


Experimental palatal candidosis and saliva flow in monkeys.

Maxillary acrylic plates, inoculated with Candida albicans, were inserted for 3 weeks in 10 monkeys (Cercopithecus aethiops) (Series I), and reinserted in five of the animals 8 weeks after removal (Series II). To suppress saliva flow oxyphencyclimine was injected intramuscularly (0.125 mg/kg) thrice daily for 3 weeks in six monkeys of Series I, while four controls received no drug. In Series II the oxyphencyclimine dose was doubled in three animals, and two controls were sham-treated with sodium chloride. Mean saliva flow was reduced to 58% after 1 week and to 63% after 3 weeks with the low dose of oxyphencyclimine. The values with the high dose were 56% and 64%, respectively. After 1 week thrush had developed beneath the plates of all monkeys. The patches were more extensive and regressed slower with oxyphencyclimine. Enlarged lesions were seen with the double dose. In Series I intraepithelial invasion by hyphae was detected more frequently and longer after inoculation in the oxyphencyclimine group. Such invasion was not found in biopsies from Series II. It is likely that saliva offers some protection against yeasts colonizing the fitting size of a denture.


Sarcocystosis: a clinical outbreak in dairy calves.

Death and illness in a pen of eight yearling dairy heifers was caused by the protozoan parasite Sarcocystis. All animals had weight loss, weakness, marginal anemia, and elevated serum enzymes. Affected animals had high hemagglutinating antibody titers to Sarcocystis antigen. Affected tissues of the two animals that died demonstrated schizonits and young cysts during pathologic examination. The resident farm dog was shedding Sarcocystis sporocysts and was incriminated as the source of infection.


Angiotensin injected into the neostriatum after learning disrupts retention performance.

Angiotensin II, injected into the dorsal neostriatum of rats 5 minutes after they had learned a passive avoidance task, disrupted the retention of the task 24 hours later. Identical neostriatal injections given 22 hours after learning (2 hours before retention) were without effect on retention performance. Ventral neostriatum or posterior thalamus were ineffective sites for injection of angiotensin. Injection of thyrotropin releasing hormone or lysine-8-vasopressin into the dorsal neostriatum was ineffective. These findings indicate a possible role for endogenous angiotensin in the neostriatum on retention performance and suggest potential involvement in mnemonic processes.


Penicillin V therapy for streptococcal pharyngitis: comparison of dosage schedules.

Two dosage regimens of penicillin V were compared in 327 patients with mild to moderately severe streptococcal pharyngitis. Patients fulfilling study criteria were randomly assigned to a b.i.d. or a t.i.d. dosage schedule. Those in the b.i.d. group were given 500 mg twice daily; those in the t.i.d. group were given 250 mg three times daily. Duration of therapy was ten days for both groups. Cure was based on prompt symptomatic improvement, subsidence of clinical signs, and negative throat cultures for group A beta-hemolytic streptococci. Both dosage schedules yielded similar cure rates, indicating that with penicillin V, a b.i.d. regimen is as effective as a t.i.d. regimen in treating streptococcal pharyngitis.


Free thyroxine index or effective thyroxine ratio?

The ability of the free thyroxine index (FTI) and the effective thyroxine ratio (ETR) to distinguish abnormal from normal thyroid function is compared in a series of 422 patients; they were equally successful in detecting hyperthyroidism. In hypothyroidism, however, the ETR values of 22% were within 95% 'normal' limits compared with 7,4% of the FTI values. Other authors have shown a similar poorer sensitivity of the ETR compared with the FTI.


Rationale for seeking occult metastases in patients with bronchial carcinoma.

The usefulness of performing diagnostic staging tests on patients thought to have operable bronchial carcinoma was explored by modeling the diagnostic and therapeutic processes for patients with this disease. The availability of appropriate autopsy and survival data allowed this investigation. We analyzed the results of two diagnostic and therapeeutic strategies: a test strategy in which extensive staging tests are performed preoperatively on patients with Stage I or II disease and a no test strategy in which such examinations are not performed. Average survival times are little affected by the choice of the test or no test diagnostic strategy. The chance of an immediate postoperative death, of an unnecessary operation and of a long term cure are affected more. Within the error of measurement, financial costs for the two strategies are probably the same. This investigation is a prototype for estimating the value of diagnostic staging tests and the effects of consequent alternative methods of treatment for patients with known malignant conditions.


Teratogenicity studies on late blighted potatoes in nonhuman primates (Macaca mulatta and Saguinus labiatus).

Female rhesus monkeys and marmosets were fed a diet containing blighted potatoes (Phytophthora infestans) at a level of 10g/kg per day for at least two weeks prior to breeding and six weeks following conception in order to gain additional information on the association of blighted potatoes and the development of anencephaly and spina bifida in primate species. There was an absence of either of these neural-tube defects in 32 rhesus and 14 marmoset infants whose mothers had received a blighted potato diet. In addition there were no cranial osseous defects. There were, however, two rhesus monkey infants with internal hydrocephalus whose mothers had consumed blighted potatoes.


Teratogenic effects of retinoic acid in pigtail monkeys (Macaca nemestrina). I. General features.

Daily oral administration of 10 mg/kg retinoic acid to pregnant Macaca nemestrina monkeys on days 20 to 44 resulted in a high frequency of craniofacial and musculoskeletal malformations. Craniofacial defects including cleft palate and anomalies of the prinna were common as were ectrodactyly, kyphosis, and muscular-joint contractures. Transposition of the great vessels of the heart occurred in one animal and polycystic kidney and associated urogenital anomalies in another. Shorter treatment periods with similar or higher dosages were not teratogenic and were less fetocidal. Although only relatively long treatment courses were teratogenic, the defects that resulted were morphologically similar to those induced with retinoic acid or other vitamin A compounds in other animal orders.


Mycobacterium tuberculosis resistance to rifampicin and ethambutol: a clinical survey.

Ninety-seven cultures of Myco, tuberculosis referred to the Tuberculosis Reference Laboratory, Cardiff during 1972-73 and found to be resistant to rifampicin or ethambutol were studied. Resistance to each drug appeared equally common. Few lower grades of rifampicin resistance occurred, cultures tending to be either fully sensitive or highly resistant. Intermediate grades of ethambutol resistance, however, were common, and a majority of highly resistant cultures were preceded by cultures showing lower grades of resistance. Case-notes were obtained on 84 patients (87%) and revealed no cases of primary resistance. In the three years since first developing resistance 36% of patients died: in the majority tuberculosis was a major cause of death. Half the patients had been prescribed unsatisfactory drug regimens containing rifampicin or ethambutol by their physicians, and only a small minority were considered to have co-operated well. One-third had discharged themselves from hospital against medical advice and only 21% attended clinics regularly. These two factors probably accounted for the development of resistance in most cases.


The effect of intravenous adenosine diphosphate on the number of circulating platelets in experimental animals: inhibition by prostaglandin E1, dipyridamole, SH-869 and VK-774.

The number of circulating platelets was monitored in anaesthetized animals by a continuous flow technique, using a Technicon Autocounter. Intravenous infusions of adenosine diphosphate (ADP) produced transient, dose-dependent falls in circulating platelet numbers in rabbits, dogs, rats, pigs and squirrel monkeys. The rat was the most sensitive of the species investigated. In the rabbit, the effect of a submaximal dose of ADP was inhibited in a dose-dependent manner by intravenous infusions of prostaglandin E1 (PGE1), dipyridamole, and two derivatives of dipyridamole (SH-869 and VK-774). The dose-response curves for PGE1, SH-869 and VK-774 were approximately parallel, whereas that for dipyridamole was considerably less steep. PGE1 was the most potent inhibitor, but the duration of action was very short. Dipyridamole and SH-869 produced inhibition of long duration. The duration of action of VK-774 was intermediate. All inhibitors produced marked and often long-lasting hypotension. The fact no inhibition of ADP effects could be demonstrated with dibenzyline and hexamethonium, which also produced marked hypotension of long duration, indicated that inhibition of the ADP effect by the four antagonists studied was not due to changes in blood pressure.


Half-life of platelet factor 4 (PF-4) in plasma and platelets from macaca mulatta.

Human platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipitation from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.


[Ulcerative tracheo-esophageal fistula--a complication of longterm respiratory support (author's transl)].

A case of ulcerative tracheoesophageal fistula following long term respiratory support is described. After establishing the diagnosis of TEF, an attempt at surgical repair should be made as quickly as patient's condition permits it, ideally immediately. We suggest right side thoracotomy with the resection of the fourth rib, thereby facilitating preparation of a pedicled flap which should be interponated between trachea and esophagus after the closure of the esophagus defect by sutures has been performed.


Acute toxicity of the leaves and extracts of Dichapetalum barteri (Engl.) in mice, rabbits and goats.

Acute toxicity of the leaves and extracts of Dichapetalum barteri for mice, rabbits and goats was investigated. Consumption of 0.5 g/kg and 2.2 g/kg body weight of dried leaves was lethal to rabbits and goats, respectively, within 4 h. Plants collected in the dry season were more toxic than those collected during the wet season. Clinical signs observed were initial depression followed by restlessness, convulsions, and death. The main lesions observed were acute vasculitis and congestion of the liver, lung, kidney, spleen as well as extensive oedema and congestion of the myocardium. The water extract of the leaves was lethal to mice at 2.0 g/kg, to rabbits at 0.1 g/kg and toxic to isolated rabbit heart at 2 mg/ml of Locke's solution. Monofluoroacetate was detected in the plant material and is probably the toxic principle of D. barteri.


[Optimation of the dose geometry during irradiation of the para-aortic lymph nodes with 42 MeV photons (author's transl)].

Different irradiation techniques for therapy of para-aortic lymph nodes are compared using fixed or pendulous fields of photons with the energy 42 MeV from a 42 MeV betatron. The techniques are estimated considering the load to the radio-vulnerable contiguous organs, especially to the spinal cord and kidneys. The findings presented, being founded on measurements and on computations resulting therefrom, show that the most satisfying dose distributions are obtained by the Y-shaped three-field technique, by the combination of telecentric-excentric dorso-ventral pendulous irradiation with a ventral irradiation by fixed fields, or be means of a biaxial excentric pendulous irradiation. By examples evidence is given of the possibility of delivering a focal dose of 6000 rd or more to the tissue within a large-sized target volume, whilst the radiation load to the contiguous radiosensitive organs, i.e. spinal cord and kidneys, does not exceed the tolerance dose.


[Consideration of inhomogeneities in irradiation planning. 3. Influence of inhomogeneities on the shape of the depth dose curve in water with electronic radiation of different energies (author's transl)].

For electron beams the shift of the depth dose curve in water produced by an inhomogeneity with density rho2 and thickness d is to be calculated from Vcalc-d(rho1 -1). Because of additional energy losses by bremsstrahl production, this calculable value Vcalc has to be corrected by means of a factor K to be found experimentally. In the case of larger atomic numbers (metallic plate), and most intensely in the lower energy range from 10 to 20 MeV the loss of dosage on account of inhomogeneities is particularly high due to elastic scattering of electrons (e.g. 86% by a 4.5 mm metallic plate with 10 MeV electronic radiation).


[Electron therapy].

The limited range of electrons yields depth doses and dose distributions offering the possibility to spare the tissue situated behind the tumor and to deliver a smaller volume dose. Electrons, therefore, can produce dose distributions being more favorable than those to be obtained with X-rays. The general radiation responses to electronic treatment are feeble. Clinical experiences also have shown that electrons are doing less harm to normal tissues than do X-rays. This may be derived from more important beta-effects and lesser alpha-effects of the electronic irradiation. The normal cells have a capacity for repair following beta-lesions which surpasses that of tumor cells, and thus, the electivity of electronic irradiation will increase and the clinical results are being explained. Schumacher (Berlin) has developed an improved fractionation schedule for electrons, using higher single doses once a week. The new schedule diminishes the number of tumor cells much more effectively than the conventional scheme utilized until now, and brings about, moreover, an additional protection of normal cells. Reoxygenation of anoxic tumor cells is sponsored. The clinical results from the new schedule (4262 cases) are very good.


Diurnal variations of serum testosterone levels in intact and gonadectomized male and female rhesus monkeys.

A radioimmunoassay for serum testosterone which does not require chromatographic separation was used to measure the diurnal variations in intact and orchidecomized males and intact and ovariectomized females. The intact male rhesus monkey shows a distinctive diurnal variation in serum levels of testosterone characterized by lower values during the day and a marked increase in the early evening (1900-2200 hr). The testosterone levels remain high throughout most of the lights-off period in the intact male. In contrast to the intact male, the markedly lowered serum levels of testosterone in the orchidectomized male were higher during the day and consistently showed a nadir during the early evening (2000-2200 hr). The evening nadir of testosterone levels was 51.0% lower than the 24-hr mean whereas the maximum serum level was 46.4% higher. A similar circadian pattern of testosterone was seen in both the intact and ovariectomized females. The testosterone values were higher during the day and consistently showed a nadir during the early evening. These results suggest that the adrenal secretion of testosterone varies in a diurnal pattern characterized by an early evening nadir. This adrenal pattern is overshadowed by a much larger gonadal rhythm in the intact male.


Corpus luteum function during the early postpartum interval in lactating rhesus monkeys: in vivo and in vitro response to exogenous gonadotropin.

The response of the postpartum corpus luteum to exogenous gonadotropin was studied in 12 lactating rhesus monkeys given daily injections of either human chorionic gonadotropin (HCG, n = 6) or saline (control, n = 6) for 4 days immediately following parturition. Peripheral blood samples were collected daily. On the 5th day postpartum, luteectomy was performed progesterone production by dispersed luteal cells was examined. Whereas progesterone in the peripheral circulation of control monkeys progressively declined between days 1 and 5 postpartum, progesterone levels increased significantly (p less than 0.025) with the onset of HCG treatment and remained significantly (p less than 0.025) elevated above the controls throughout the period of HCG treatment. However, despite the daily administration of HCG, circulating progesterone levels declined (p less than 0.05) between days 3 and 5 postpartum. The weight of the corpus luteum excised from HCG-treated macaques was significantly (p less than 0.005) greater than that of the controls. Dispersed cells from corpora lutea of saline-treated monkeys produced progesterone in vitro under control conditions (nutrient medium alone) and responded to the addition of high (100 ng/ml), but not low (1 ng/ml), levels of HCG with increased steroidogenesis. Although luteal cells from HCG-treated macaques tended to produce more progesterone in vitro than cells from control monkeys, they also exhibited a 50-fold reduction in sensitivity to HCG in vitro. These data suggest that the corpus luteum of lactating postpartum rhesus monkeys exhibited steroidogenic function which was stimulated by exogenous gonadotropin. However, prolonged exposure of the corpus luteum to high levels of exogenous gonadotropin appeared to produce a state of refractoriness to additional gonadotropic stimuli.


Effect of estrogens on glucose phosphate dehydrogenase activity of liver and oviduct in the amphibian Bufo arenarum.

Glucose- 6phosphate dehydrogenase (G-6PDH) stimulation by estradiol- 17beta has been studied in oviduct and liver of Bufa arenarum. OviducalG-6PDH has been found to be stimulated by a single dose of estradiol- 17beta (100 mug/100 g body weight), the stimulation being dependent on season. Hepatic G-6PDH of females is susceptible to hormonal stimulation, without seasonal variation, while in males the enzymatic activity is not modified under the same conditions. The stimulating effect of estrogen on oviducal and hepatic G- 6PDH was inhibited by Actynomicin D. The susceptibility of G- 6PDH to estrogenic action would assure NADPH production, indispensable for the biosynthesis of lipids which are required for cell growth and for hepatic vitellogenesis.


Cholesterol side chain cleavage and aromatase activities in the corpus luteum of the pregnant rhesus monkey.

Cholesterol side-chain cleavage (CSCC) and aromatase activities were measured in luteal mitochondria and tissue pieces, respectively, from rhesus monkeys on days 22, 49, 128 and 160 of gestation. CSCC activity did not vary significantly during gestation and thus probably does not respond to chorionic gonadotropin which is elevated on day 22 of pregnancy. It is not known, however, whether CSCC can be stimulated prior to day 22 when the corpus luteum is steroidogenically more active. Both 3H-pregnenolone and 3H-progesterone were synthesized from [1,2-3/]cholesterol. Aromatase activity declined from high levels on days 22 and 49 to a nadir on day 128 of pregnancy. Utilizing either [1beta-3H]androstenedione or [1beta-3H]testosterone as substrate yielded comparable results throughout gestation.


Placental and luteal steroidogenesis in the pregnant rhesus monkey.

Progesterone, 20alpha-dihydroprogesterone, estrone and estradiol-17beta concentrations were estimated by radioimmunoassay in blood plasma from uterine, uteroovarian and femoral veins of rhesus monkeys (Macaca mulatta) on days 22, 49, 128 and 160 of gestation. Steroids were consistently more concentrated in uterine and uteroovarian that in femoral venous plasma and in many cases levels in the uteroovarian vein were also higher than those in the uterine vein indicating luteal secretion of both progestins and estrogens thoughout gestation. In some animals, however, the corpus luteum appeared quiescent. As reflected in the decline in the uterine venous progesterone/estradiol-17beta concentration ratio, a shift in steroid contribution from the uterus and its contents occurred between days 22 and 49 of gestation with progesterone declining more rapidly than estradiol-17beta. Progesterone/20alpha-dihydroprogesterone was higher in both uterine and uteroovarian than in femoral venous plasma suggesting peripheral metabolism of progesterone to 20alpha-dihydroprogesterone.


Scrub typhus: a common cause of illness in indigenous populations.

An explanation was sought for the disparity between the low reported incidence of scrub typhus and the high prevalence of antibody to Rickettsia tsutsugamushi in the rural population of Malaysia. A combination of isolation of the organism, titration of antibody by indirect immunofluorescence, and the Weil-Felix test was used to confirm infections. Scrub typhus was found to be very common, causing 23% of all febrile illnesses at one hospital. The infection was particularly prevalent in oil-palm workers, causing an estimated 400 cases annually in a population of 10,000 people living on one plantation. The clinical syndrome, whether mild or severe, was difficult to distinguish from that due to other infections. Eschars, rashes and adenopathy were uncommon. When used to examine early sera, the Weil-Felix test failed to confirm the diagnosis in most infections.20


Human behaviour and the propagation of Chagaś disease.

During 12 months, 26 households with 172 residents in São Felipe, Bahia, Brazil, entertained 74 different guests who were potentially exposed to attack by Panstrongylus megistus for an average of about 23 nights per guest per year. During the same period 52 of the residents spent an average of about two weeks a year away from home. These exchanges established contact with 79 other households in the district. These and other observations reinforce the opinion that human behaviour plays an important role in propagating Chagas' disease.


Changes in blood catecholamine levels and ultrastructure of dog adrenal medullary cells during hemorrhagic shock.

Blood catcholamine levels and ultrastructural changes in adrenal medullary cells were followed during the course of oligemic and normovolemic shock in dogs. Blood adrenaline concentration rose promptly after hemorrhage, reaching a maximum that was 10-fold greater than normal during the early period of hemorrhagic hypotension. Thereafter, adrenaline levels gradually declined until the end of the critical stage of hemorrhagic shock when the blood concentration rose to a level 8-fold that of normal. Following the critical stage, and throughout the irreversible stages of shock, adrenaline levels remained near normal. Noradrenaline, which was initially undetectable, first appeared in the impending stage of hemorrhagic hypotension and showed little change during the course of severe hemorrhagic hypotension. Ultrastructural studies demonstrated A-cell degranulation as early as 5 min after initiation of hemorrhage. Degranulation continued throughout the impending stage of hemorrhagic hypotension and was associated with an increasing number of autophagic vacuoles containing empty vesicles. At the end of the critical stage, all A cells showed complete degranulation and degenerative hydropic change. Progression to necrosis rather than arrest or reversal of hydropic change was observed after reinfusion of blood. In contrast to the marked alterations in A cells, most N cells were morphologically unchanged.


Induction of liver lysosomal enzymes during the autophagic phase following phenobarbital treatment of rat.

Phenobarbital was given to male rats as a single injection and as repetitive injections for 7 days. The effects of treatment on the lysosomal hydrolases acid phosphatase, cathepsin D, and aryl sulfatase were analyzed at different intervals ranging from 1 to 15 days after seven injections, and from 1 to 48 h after a single injection. In both cases, microsomal protein and NADPH-cytochrome c reductase were measured to ensure proper induction. After a single injection, a slight decrease in hydrolytic activities was observed. Repetitive administration of phenobarbital gave rise to a marked decrease of lysosomal enzyme activities 1 day after cessation of treatment. This decrease was followed by a continuous increase in activity up to day 3 and 4. One or 2 weeks after treatment, enzyme activities declined to control values. The increase in activity of lysosomal hydrolytic enzymes was correlated with the onset of induced autophagy of endoplasmic reticulum membranes described as occurring in liver upon cessation of phenobarbital exposure. It is concluded that phenobarbital treatment per se decreases lysosomal enzyme activities, whereas the induced autophagy following cessation of exposure is associated with enhanced levels of lysosomal hydrolases in rat liver.


Annulate lamellae in rete ovarii of juvenile rabbits.

Annulate lamellae, though few, were observed in the epithelial cells of rete ovarii of 1-month-old rabbits, but not of other-aged juvenile rabbits examined. There were little differences in the fine structural details between the rete ovarii with annulate lamellae and those without annulate lamellae. Most rete ovarii cells were undergoing atrophy. This finding suggests that annulate lamellae may be quite ordinal, transitory organelles common to virtually all cell types.


Freeze-fracture of the normal and pathological megakaryocyte lineage in chronic megakaryocytic-granulocytic myelosis.

Freeze-fracture and thin sections were performed on human bone marrow of chronic megakaryocytic-granulocytic myelosis (CMGM) to study the three-dimensional fine structure and maturation of normal and atypical megakaryocytes and thrombocytes. In the many normally maturing megakaryocytes the development of the demarcation membrane system (DMS) was best investigated by comparison of thin sections with freeze-fracture replicas. The DMS shows no connections with the Golgi apparatus or rough-surfaced endoplasmic reticulum, but originates from tubular infoldings of the plasma membrane. These infoldings are always in continuity with the extracellular space and form an intracellular membranous pool by branching and coalescing of flattened tubules from which finally the perforated cisternae of the DMS arise. Freeze-fracture of the normal thrombocytes confirms earlier findings. The abnormal giant platelets seen in CMGM display extensive areas of smooth membranes of a spongy structure consisting of dense tubules surrounded by the labyrinth of the surface-connected system. Their physiological significance in these atypical platelets remains unsolved.


Sites of sulfatation in the chondrocytes of the articular cartilage of the rabbit. A study by quantitative radioautography of high resolution.

35S sulfate uptake by the articular cartilage chondrocytes, from biopsies of rabbit, have been studied by high resolution autoradiography. The Golgi apparatus, rough endoplasmic reticulum, cytosol, cytoplasmic membrane and extracellular space were considered as cell compartments in the quantitative analysis of the autoradiograms. The results obtained show: 1) a high activity of radiosotope incorporation in the Golgi apparatus; 2) a fast rhythm of transfer of the substances labelled in the Golgi apparatus to the cell membrane; 3) significant labelling of the rough endoplasmic reticulum, throughout the experiment. It is concluded: 1) The grains observed in the rough endoplasmic reticulum show a significant radioisotope uptake on this level, and this evidence some sulfotransferase activity. 2) The high 35S sulfate uptake level which is observed in the Golgi apparatus demonstrates that the highest sulfotransferase enzyme activity is located in this cell area, thus showing that the "early" sulfation that began in the rough endoplasmic reticulum was completed by a "late" sulfation in the Golgi apparatus. It is here that complete chondromucoprotein building takes place before being excreted. 3) The high transfer level of the labelled substances from the Golgi apparatus shows that the sulfated product secretion for building the cartilage matrix takes place rapidly since a great label increase can be already observed at the beginning of the chase period in the outer surrounding area of the chondrocyte membrane.


Zinc distribution in injured myocardium. EMMA-4 examinations of dogs' hearts after coronary ligation.

Electron microscopic X-ray microanalysis and atomic absorption spectrophotometry were used to determine changes in zinc concentration after myocardial ischemic injury by coronary ligature in dogs. The zinc concentration increased in the damaged myocardium especially in specific intracellular locations identified by means of the microprobe. It was concluded that the selective zinc augmentation was related to proliferative and biosynthetic reactive processes in the myocardium.


Lipid pigment formation in cultures of chick hepatocytes. Effects of aging and of oxidizable agents.

Tissue cultures of hepatocytes were studied for the formation of lipid pigments as related to aging of the cultures and of the addition to them of: 1) colloidal iron; 2) L-ascorbic acid; and 3) tyrosine. The presence of lipid pigments was gauged by their sudanophilia after a light solvent extraction and yellow autofluorescence. It has been found that all the three agents enhanced pigmentogenesis. It has been concluded that both pro-oxidants and antioxidants may enhance lipid pigment formation: the first by enhancing lipid oxidation, the second by enhancing copolymerization which terminates the oxidative chain.


Pathological changes of human sural nerves in Minamato disease (methylmercury poisoning). Light and electron microscopic studies.

Biopsy of the sural nerve was performed on six patients with relatively mild Minamata disease of 10-year or longer duration. All of the six patients presented characteristic pathologic changes. Light microscopy disclosed the formation of irregularly shaped myelin sheaths and fine axons, an increase in them, which is suggestive of incomplete regeneration, cicatrization following the loss of nerve fibers, increase in Schwann's nuclei, and formation of Büngner's bands. Electron microscopy revealed incomplete myelinated fibers and ultrafine unmyelinated fibers associated with incomplete regeneration, formation of regeneration units, and collagen increase. The laminar encapsulation with the processes of Schwann's cells were often observed in ultrafine fibers. In view of the fact that small quantities of mercury-contaminated fishes are still being caught in the Minamata district, myelin degeneration, glycogen deposits and appearance of dense bodies in axons, and vesiculation and fragmentation of endoplasmic reticulum were observed as degenerative changes due to the effects of mercury accumulation.


Esterase activity in the guinea pig thyroid under normal and pathological conditions (vitamin A deficiency) with special regard to cyst-like structures.

By use of different activators and inhibitors, TOCP(tri-o-cresyl phosphate), PCMB (parachloromercury benzoate), NiCl2, Pb(NO3)2, HgCl2, Hg(NO3)2, eserine and sodium taurocholate, it is shown that the esterase in the cyst cells and in group I cells of the guinea pig thyroid probably are A-esterase isoenzymes. The activity in the majority of cyst cells is considerably stronger than in the other thyroid epithelial cells, and it is resistant to Hg inactivation. Neither esterase type nor intensity of the reaction product is altered in group I-II or cyst cells during vitamin A-deficiency. When a normal diet is given, the esterase in all thyroid epithelial cells is very sensitive to sodium taurocholate, while in cyst cells it is rather resistant to this inhibitor at vitamin-A-deficiency.


Aurintricarboxylic acid (ATA) and DNA synthesis. I. Inhibition of DNA synthesis by ATA in Go cells stimulated to proliferate.

Aurintricarboxylic acid (ATA) at a concentration which produces 40% inhibition of protein synthesis, inhibits completely isoproterenol-stimulated DNA synthesis in mouse parotid glands. The drug was found to interfere with some essential changes occurring during the prereplicative phase of IPR-stimulated DNA synthesis. It inhibits the increase in ribosonal protein synthesis that takes place by 2 h after stimulation. The peak of ribosonal RNA that occurs 8 h after isoproterenol was also abolished by ATA. Since the drug completely inhibits isoproterenol-stimulated DNA synthesis, these results suggest that the control of ribosome production may be involved in cell growth activation. In view of the finding that ATA first inerferes with the binding of adenylate-rich RNA to polysomes, it was suggested that the drug may act by preferentially inhibiting that fraction of protein synthesis dependent on the newly transcribed messenger RNA.


Aurintricarboxylic acid (ATA) and DNA synthesis. II. Effect of ATA on structure and function of the crypts of the small intestine.

ATA affects only slightly DNA synthesis of continuously replicating cells. A single injection of the drug reduces the incorporation of (3H)-thymidine into DNA of crypt cells to only 62% of the control. The effect on DNA synthesis is preceded by a slight inhibition of protein synthesis, and by a partial decrease in the number of dividing cells. On the contrary, the incorporation of (3H)-uridine into RNA was enhanced. Electron microscopic studies revealed no cytologic abnormalities in ATA-treated animals. In view of the fact that ATA at the same concentration inhibits DNA synthesis of growth stimulated cells to 100% (Novi, 1976), it was suggested that the drug may become an useful tool in inducing a preferential inhibition of growth stimulation.


Influence of L-thyroxine upon enzymatic activity in the renal tubular epithelium of the rat under normal conditions and mercury-induced lesions. II. Histochemical studies of lactate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, unspecific esterase, and glucose-6-phosphate dehydrogenase.

Mercury-induced renal tubular lesions in the rat present histochemically with a decrease of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G-6-PD), and unspecific esterase (UE), but with an increase of lactate dehydrogenase (LDH), indicating a drop of energy supply as well as a switch from oxidative to glycolytic energy production. L-thyroxine has the same effect on SDH, G-6-PD, and LDH, but an inverse effect on MDH and UE, pointing to stimulation of gluconeogenesis. However, administration of L-thyroxine to animals which have been submitted to sublimate intoxication even further decreases the MDH and UE activity while raising or partly restoring the activity of LDH, SDH, and G-6-PD. This observation is interpreted as an attempt of the damaged epithelial cell, as the gluconeogenesis ceases, to gain relatively more energy supply for the benefit of the vitally indispensable tubular Na+ reabsorption.


[Comparison of the nuclear alterations induced by actinomysin D and alpha-amantine in hapatocytes of the rat (author's transl)].

Comparing the morphological effects of actinomycin D and alpha amanitine on the rat liver, it can be seen that the nuclear alterations caused by actinomycin (=segregation of the nucleolus and condensation of all the chromatin) occur simultaneously. After treatment with amanitine, the lesions appear in two steps. First of all one sees condensation of only the extranucleolar chromatin and fragmentation of the nucleolus. These two phenomena are related to each other not only chronogically but also causetively. In our opinion the shrinkage of the extranucleolar parts of chromosones results in the individual nucleolus-organizers being removed into different quarters of the nucleoplasm. The fragments themselves must not be altered structurally and functionally, as Kedinger and Simard (1974) have already shown. We always observed changes of the nucleolar fragments 30-90 min after the fragmentation. These changes consisted of the condensation of the intranucleolar chromatin, and the segregation and degranulation of the nucleolus, in the same manner found directly after the actinomycin-poisoning in the whole nucleolus. The delay of the lesions observed on the dispersed nucleolar fragments indicates that is a consequence of the amanitine-poisoning -- probably the result of the disturbed protein synthesis and the inactivation of a hypothetical extranucleolar regulatorgene, which controls nucleolar function.


Assembly site of cyanophage LPP-2-SPI in Plectonema boryanum.

Electron microscope studies of infection by the temperature cyanophage SPI show two possible assembly sites within the host Plectonema boryanum: the nucleoplasm and a phage-created space, the "virogenic stroma". Induced prophages appear to develop preferentially in the nucleoplasm.


[Parenteral hyperalimentation (author's transl)].

Intravenous hyperalimentation allows complete nutrition and anabolism in patients who cannot be fed by the oral route. However, several complications have been reported, e.g. septicaemia and hyperglycaemina. In 51 intensive-care patients receiving hyperalimentation, 18% were found to be hyperglycaemic in spite of insulin administration. Hyperglycaemia was frequently associated with stress. In 8 patients undergoing major surgery, which was chosen as a stress model, decreased insulin and increased glucagon, growth hormone and cortisone levels were observed. These findings could explain stress-induced glucose intolerance. In a further experiment, 8 intensive-care patients were given alternative intravenous feedings with either 600g of a mixture of glucose, fructose and xylitol in a ration of 1:2:1 or 600g glucose per day. During both regimens insulin administration was required in 4 patients, but the insulin dosage was lower with the mixture. Plasma glucose during glucose infusion was 205+/-25mg/100ml(M+/-SEM) and the sum of plasma glucose, fructose and xylitol during infusion of the mixture was 176+/-33mg/100ml, the difference being of borderline significance (p less than 0.05). The advantages and disadvantages of infusable substrates are summarized on the basis of the available literature and it is concluded that, in general, glucose is preferable. However, if hyperglycaemia is difficult to control, partial replacement of glucose by glucose substitutes or fat emulsions may be advantageous. A routine infusion programme for central venous feeding is suggested. Causes and prevention of side-effects are reviewed. In many patients receiving central venous nutrition less hazardous and less expensive methods could be used such as nasogastric tube feeding, elemental diet or peripheral venous nutrition.


[Diabetic coma: incidence of infections and mortality (author's transl)].

An analysis of 752 cases of severe diabetic coma during the period 1931 to 1973 showed that infections were present in one or more organs in 58% of the cases. The incidence of infections showed an increase from 53% (1931 to 1940 to 57% (1961 to 1970), with a further rise to 61%(1971 to 1973). A decrease in pulmonary infections from 40% to 17% and a distinct increase in urogenitial tract infections from 6% to 20% and in multiple infective complications from 3% to 7% were the most striking findings. The incidence of infections in other organs (abdominal, dermatological, laryngological and miscellaneous) remained virtually constant over the individual decades. Mortality was altogether higher in patients with infections (30% versus 20% in patients without infections). The highest mortality (35%) was recorded in the period 1951 to 1960; THE latest figure was 29%(1971 to 1973). Antibiotics are presumeably responsible for the decrease in the initially high mortality rate of 41% to 50% in urogenitial tract infections to 23% for the decade 1961-1970, with a further drop to 18% in the most recent period (1971 to 1973). Similarly, with multiple infections the mortality of 100% up till 1950 decreased to a recent figure of 63%, partly on account of the introduction of intensive care therapy during the past years. In abdominal infections there was also a  distinct decrease in mortality form 43% to 14%, whilst in pulmonary infections the mortality remained at about the same level (24% to 28%).


[Light and electron microscope studies on two types of giant schizonts (globidial schizonts) in the small intestine of sheep (author's transl)].

The jujunum of sheep was investigated for globidial schizont infection. Two types of giant schizonts, which had a maximum diameter of about 500 mum, were observed. Each type was found to contain morphologically different parasites. In type 1 the parasites were hook-shaped with a length of about 15-18 mum. Often they had an additional tight lacing at the apcial pole. The merozoites of the second type were spindle-shaped, measuring only 9-12 mum in length. Both types of parasites had 22 subpellicular microtubles beneath their pellicle. The parasites observed here differed clearly from those of globidial schizonts from the abomasum as well as from those of sarcosporidian cysts of the same host. In light microscopy the globidial schizonts from the jejunum of sheep seemed to be covered by a thin, mono-layered wall. By means of electron microscopy, it was shown, that this layer is identical with the host-cell cytoplasm enclosing utricle-like a giant, membrane-bound parasitophorus vacuole, which in both types of schizonts was closely filled with parasites and an enclosing ground substance. The host cell of the second type of schizonts had always numerous microvilli at the outer surface. The inner surface of the host cell formed numerous intravacuolar tubules of about 50 nm in diameter and with a considerable length. The cytoplasm of the host cells appeared always very condensed. Summarizing it was shown that the globidial schizonts from the jejunum differed clearly from those in the abomasum as well as from the sarcosporidian cysts. Thus it can be stated that more species than supposed up to now form giant schizonts within the digestive system of sheep causing the lesions of high economical importance.


Identification of some Japanese leptospiral strains as serotypes copenhageni and icterohaemorrhagiae by preciptin-absorption test in gel.

Nine strains of Leptospira belonging to the Icterohaemorrhagiae serogroups isolated in Japan were identified by the precipitin-absorption test in gel. The results of the precipitin-absorption test matched closely with those of the agglutinin-absorption test. Two strains were identified as serotype copenhageni and 7 were serotype icterohaemorrhagiae. Strain Shibaura, which was thought to belong to serotype icterohaemorrhagiae and used in many laboratories in Japan, was corrected as belonging to serotype copenhageni.


[Biological properties and ultrastructure of brucellae during L-transformation and reversion].

There was shown a difference in the biological properties and the ultrastructure of two strains of brucellae, spheroplasts obtained from them under the action of penicillin, L-form and revertants obtained from the L-form. Spheroplasts formation was characterized by a change of brucellae into R-form and some virulence reduction. The cells had an outer and a cytoplasmic membranes, and usually lost their capacity to binary division. L-forms were obtained during the 9th and the 35th passage on a medium with penicillin; their formation was accompanied by the change in serological properties of the culture and significant reduction of the virulence; the cells were characterized by a marked polymorphism and the capacity to budding; they had 2 membranes on the cell surface and an intensively developed system of intracytoplasmic membranes. The revertants formed on the medium without penicillin during the 16th-30th passage or spontaneously on the medium with penicillin. They differed from the initial strains of brucella culture by a marked increase in penicillin-resistance, by the changes in serological properties, and also by polymorphism of cells, capable, however, of binary division.


[Rheoencephalographic method of of analyzing several risk factors for cerebrovascular disease (epidemiologic study)].

For the first time in mass studied of populations the author applied a REG method for the assessment of different risk factors in cerebrovascular disorders. REG changes were studied in 1446 individuals (males from 40-59 years and females from 50-59 years) living in 2 districts of Moscow in relation to the influence of age, sex, arterial hypertension, smoking, excessive weight and hypercholesterolemia. A certain specificity of changes depending upon the acting factors was established. The highest REG changes were connected with advent of age, arterial hypertension and smoking. The achieved results make it possible to recommend REG for use in epidemiological studies. This method may also facilitate a detection of pathological changes in the brain due to the action of unfavourable factors.


[Pathogenetic mechanisms of tick-borne encephalitis].

The main cause of progressive forms of tickborne encephalitis is a prolonged persistence of certain viral strains in the brain. Although there are no virals with a selective capability to lead only to an acute or chronic encephalitis, nevertheless in the epidemiological process there is a selection of virals capable of bringing on chronic forms of the disease. In cases of an incapacity of immunological factors bor a defence during the initial phase of the infectious process there may be prerequisites to a fixation of the virals in the brain and a chronic development of the neuroinfections. It is necessary to differentiate active neuroinfectious processes due to persistent virals and postencephalitic reparative-dystrophical syndromes. This permits to avoid a hyperdiagnosis and more reasonably select therapeutical measures in the evaluation of their effectivity.


Influence of anti-rheumatic drugs on human lymphocytes in vitro.

Influence of anti-rheumatic drugs on human lymphocytes, especially T and B cell membranes, was studies with D-penicillamine, aurothiomalate, dexamethasone, cyclophosphamide, mitomycin C and aspirin. Peripheral blood obtained from five healthy individuals and lymphocytes were separated by centrifugation with Lymphoprep. The separated lymphocytes were adjusted to 5 X 10(6)/ml in PBS. The suspension of lymphocytes was mixed with equal volume of each concentration of the above drugs. After suspensions, we investigated the percentages of T -and B-cells, compared to control. The results are as follows: 1. Drugs which act only on the T cell membrane: D-penicillamine, aurothiomalate. 2. Drug which acts only on B cell membrane: dexamethasone. 3. Drugs which act on both T- and B-cell membrane: mitomycin C, cyclophosphamide and aspirin.