[Action of KCN on intact and refractory thrombocytes]. The effect of low KCN concentrations (5-10(4) M) on the ADP-induced aggregation of intact and refractory rabbit platelets was studied. KCN did not change the aggregation of the intact platelets, but stimulated that of the refractory platelets. The effect of the inhibitor stimulating the aggregation was not connected with the release of additional amounts of ADP. A different sensitivity of the aggregation capacity of the intact and refractory cells to the partial inhibition of metabolism was discussed in terms of the suggested earlier "calcium" model of autoregulation of platelet aggregation.


[Interaction of reversible inhibitors with the catalytic centers and allosteric sites of cholinesterases]. The kinetics of inhibition of the human red blood cell cholinesterase with galanthamine tacrine and oxazyl (ambenonium) and the effect of these drugs on chick, mouse, cat and rat blood plasma enzyme activity was studied. Galanthamine proved to bind with acetylcholinesterase in the anionic areas of the catalytic centres, oxazyl interacted in the area of the allosteric anionic site, and tacrin interacted with the hydrophobic areas of the enzyme.


[Accelerin (factor V), the catobolic product of fibrinogen ]. The authors describe a method of obtaining a highly active and well purified human Ac-globulin (factor Y) preparation. Factor Y proved to be a part of the fibrinogen molecule--its intermediate transformation product under the effect of thrombin or some other enzyme analogous by its action.


[Effect of exogenous DNA on the content and biosynthesis of endogenous DNA in rat bone marrow]. The influence of exogenous DNA on the content of endogenous DNA and the rate of biosynthesis was studied in rat bone marrow. After the injection of highly-polymerized homologous DNA to intact rats the content of rat DNA per 1 gm of the bone marrow decreased within the first 3 days (the most marked fall occurred in 3 days--by 36%), and returned to the normal by the 6th day. The rate of DNA biosynthesis in rat bone marrow increased in 18 hours (doublled in comparison with control), remained elevated within 6 days (by 58%) and approached the normal level from 1 to 3 days after the DNA injection.


[Study of rat erythrocyte superoxide dismutase activity during a toxic regimen of interrupted hyperbaric oxygenation]. Development of toxic manifestations in rats under conditions of hyperoxia was accompanied by a significant lowering of the rat erythrocyte superoxide dismutase activity. The incubation of control rats hemolysate with hydrogen peroxide (10(-3)M) or with kumole peroxide (1.6 10(-4)M) also led to pronounced fall of the initial erythrocyte superoxide dismutase activity. As supposed, the lowering of the erythrocyte superoxide dismutase activity under hyperoxia could be due to the formation of peroxidation products.


[Physicochemical properties of the human lymphocyte mitogenic factor induced by phytohemagglutinin]. Some physical and chemical properties of the mitogenic factor (MF) produced in vitro by PHA-stimulated human lymphocytes were investigated. Treatment of the culture medium with proteases proved to decrease the MF activity sharply. The MF was found to have an elution pattern in Sephadex and Bio-gel gels similar to proteins with the molecular weight of 20 000--30 000 daltons (peak--25 000). In experiments with the MF fractionation by disc-electrophoresis on 5% polyacylamide gel the MF formed a few discrete peaks in the fractions corresponding to the mobility of alpha1- and alpha2-globulins and transferrin. In isoelectric focusing the MF formed 3 fractions in the pH range of 4.5--8.3. Functional heterogeneity of the MF is suggested.


[Role of clasmatosis of the phagocytes in immunogenesis]. With the aid of cytological and cytochemical studies it was shown that clasmatosis of phagocytes (micro- and macrophages) was primarily characteristic of active phagocytising cells, and not of dying cells as considered formerly. Experiements were conducted on guinea pigs in the course of vaccinal and infectious processes in brucellosis. As noted, clasmatosis of phagocytes known in intact animals was considerably enhanced during vaccinal and infectious processes. Pieces of cytoplasm separating from phagocytes were full of acid phosphatase, brucella antigen; fragments of macrophage cytoplasm in addition contained RNA. There are reasons to suppose that with the aid of clasmocytosis of phagocytes became intensified and the antigenic information spread rapidly in the animal organism.


[Cytotoxicity of sera against brain and spinal cord antigens in relation to lymphocytes of varying origin]. Rabbit sera against antigens prepared from the brain and the spinal cord antigens were investigated in a cytotoxic test with mouse and guinea pig lymphocytes. None of the sera exerted a cytotoxic effect on the bone marrow lymphocytes. The sera against mouse brain and spinal cord and guinea pig brain and myelin isolated from it exerted the greatest cytotoxic activity; the cytotoxicity was maximum against the thymocytes, less pronounced against the lymph node lymphocytes, and least--against the spleen cells. The cytotoxicity of the sera against the bovine spinal cord homogenate, myelin and the basic protein isolated from it was the minimal and equal with lymphocytes from any of the three mentioned sources. The serum against the encephalitogenic polypeptide 2c was practically devoid of the cytotoxic activity. The encephalitogenic activity of the 2c fraction was greater than that of the myelin and basic protein from the bovine spinal cord. Experiment of antibrain serum absorption suggested that the brain cortex contained a cross-reacting antigen. The subcutaneous injection of a relatively high dose (224 x 10(6)) of thymocytes in the complete Freund's adjuvant failed to induce the development of allergic encephalomyelitis in guinea pigs.


[Effect of bilateral destruction of the structures of the medial hypothalamus on the course of anaphylactic shock]. Anaphylactic shock induced in rabbits by the preliminary injury of various areas of the medial hypothalamus coursed more severly than in control. Irrespective of the localization of the foci of injury a more pronounced hypotensive reaction and a slower compensatory elevation of the blood pressure occurred in response to the administration of the  reactive dose of the antigen. The severity of anaphylactic shock depended on the time lapse from the moment of hypothalamic injury to the moment of administration of the reactive dose of the antigen.


[Cortisol metabolic intensity in the liver of guinea pigs in allergic processes of the immediate and delayed types]. The intensity of cortisol metabolism was studied under conditions of perfusion of the liver in situ by solutions containing cortisol in different concentrations; in this case metabolism coursed chiefly in the direction of cortisone formation. With the increase of cortisol concentration in the inflowing perusate there was also a rise in the intensity of its metabolism in the hepatic tissue. In anaphylactic alteration of hepatic tissue the intensity of cortisol transformation into cortisone decreased, this pointing to disturbances of cortisol oxidation. Experimental allergic encephalomyelitis is also acccompanied by a reduction in the intensity of cortisol metabolism.


[Kinetics of cell populations in the compartment of maturing, non-dividing neutrophils of rat bone marrow]. The kinetics of cell movement through the compartment of maturing, nondividing neutrophils of the Wistar rat bone marrow was studied by autoradiography using H3-thymidine. There were transit and reserved neutrophil populations in each cell compartment. The transit periods of the maturing nondividing cells, the mean time of cell renewal in the subcompartments of metamyelocytes, the band and the sementonuclear neutrophils were determined with consideration to the reserved cell population.


[Experimental sensitization with an extract of Dermatophagoides pteronyssinus ticks]. Immunogenic properties of Dermatophagoides pteronyssinus ticks were studied in subcutaneous injection of the antigen to guinea pigs and rabbits. Marked changes in the immunological reactivity of the animal organism were revealed; these changes were accompanied by production of agglutinating, sensitizing the mast cells and precipitating (in rabbits) antibodies, and by the development of hypersensitivity of the immediate and delayed type.


[Cytological analysis of the intact and regenerating liver of different strains of rats]. Comparative cytological studies were conducted on control and regenerating liver of two strains (August and Cotton) of rats, 2/3 of the liver was resected; 5 or 6 animals were sacrificed at each of the following postoperative periods: in 30 hours, 3, 8, 42 and 120 days. The number of binuclear cells, the size of mononuclear hepatocytes and their nuclei, the mitotic activity, and ploidity of hepatocytes were determined. The intact and regenerating liver of the August rats differed from the intact and regenerating liver of the Cotton rats by a number of cytological indices, excluding the mitotic activity. A conclusion was drawn that the observed interstrain differences in the cytological indices providing regeneration of the liver after resection in the August and Cotton rats depended on the genotype of the given strain.


[Study of the specificity of the estradiol-binding system in the uteri of guinea pigs]. The authors analyzed the affinity of the steroids belonging to the estran series to the estradiol-binding system of the guinea pig uteri. The presence of free hydroxyl groups in positions 3 (phenol) and 17beta and their interorientation proved to determine the interaction with the recptor system of the guinea pig uterus. The data obtained indicated that the biological activity of the steroids was  determined by the peculiarities of their structural interaction with the receptor systems of the uteri.


[Proliferation of the myoctes of the left atrium and ventricle after different kinds of myocardial injuries in adult rats]. Myocardial infarction of the left ventricle was induced in adult rats weighing 120-160 g by ligation of the left coronary artery at various levels: in the area of the auricle, of the first  third of the left ventricle, and in the middle of it. The left auricle was injured in the other experimental series: the ligature was applied to its anterior wall or to the auricular appendage. Sham-operated animals served as control; only pericardium was  removed in them. The left half of the heart was examined on the 5th postoperative day. Mitosis of myocytes was found in the auricle or in the auricular appendage of the animals in those experimental series in which these sections of the heart were injured directly and had a thickened epicardium (in 35 of 49 cases); mitotic index varied from 0.9 to 10%. No mitoses were found in the myocytes of the auricle and the auricular appendage after ligation of the coronary artery in the middle of the ventricle. Mitoses in the myocytes of the ventricle were rare (in 7 of 49 cases) and were located far from the site of infarction, in the subepicardial region; mitotic index here varied from 1 to 2%.


Lassa fever (arenaviruses) as a public health problem. Two "new" virus infections, Marburg and Lassa fever, now constitute diseases of public health importance in several countries of Africa, especially West Africa. Lassa fever has an insidious onset, is initially difficult to diagnose, has "nonspecific" clinical symptoms which have been confused with yellow fever and typhoid, shows evidence of persistent infection, is tremendously contagious, has a high mortality rate, and in particular exhibits unusual nosocomial propensity. It has also been shown to be the cause of premature births and spontaneous abortions in pregnant women. The virus is transmitted by the respiratory route and by direct contact with contaminated materials. Persistent complement-fixing antibodies have been demonstrated in patients recovered from the disease. The causative agent, a member of the arenavirus group, is known to be enzootic in rodents, especially Mastomys natalensis.


Computer simulation of leukemia therapy: combined pharmacokinetics, intracellular enzyme kinetics, and cell kinetics of the treatment of L1210 leukemia by cytosine arabinoside. An integrated mathematic computer-based model of the pharmacokinetics, intracellular enzyme kinetics, and cell kinetics of the treatment of L1210 leukemia by cytosine arabinoside (ara-C) is described. The compartment model of Bischoff and Dedrick is extended to the intracellular level by inclusion of equations describing the phosphorylation, dephosphorylation, and deamination of ara-C with enzymatic feedback control. The activities of kinase, deaminase, and phosphatase are explicitly included in the models and are estimated from relevant data. Cell proliferation is described by a continuous-flow mathematic model in which cellular maturation and cell-to-cell variability in maturation rates are key variables. Cell proliferation is related to intracellular biochemistry through mathematic expressions which relate cell lethality and progression delay to the time course of intracellular ara-CTP. In vitro and in vivo experiments performed in a number of laboratories are compared by simulation. The most sensitive parameters in dose-response and cell-survival simulations are deoxycytidine kinase activity, ara-CTP half-life, renal clearance of ara-C, and cell-kinetic parameters for proliferation and cell killing. Progression delay is vital to the realistic simulation of divided-dose schedules. By comparative simulation we have identified areas of uncertainty which can be classified by a few additional measurements. The applications of simulations combining pharmacokinetic, biochemical, and cell-kinetic data in vitro and in vivo are discussed, exploring consistency among different measurements, and relating experimental protocols to clinical treatment.


Size dependence of the response of Lewis lung tumors to BCNU. The survival of Lewis lung tumor cells has been studied after a single ip dose of BCNU. In dissectible subcutaneous and intramuscular tumors and artificial lung metastases survival was measured by colony formation in soft agar and in vivo in the lung. The long-term control of small lung nodules by single doses of BCNU was studied and cell-survival estimates were inferred. The results demonstrate that the cytotoxic action of BCNU shows a strong dependence upon tumor size.


Effects of surgery on the cell kinetics of residual tumor. Noncurative excision of a primary sc Lewis lung tumor performed on Day 7 or later results in an increase in the thymidine index and growth rate with minimal changes in the cell cycle parameters of the lung metastases. The stimulation of the lung nodules is accompanied by a small but consistent decrease in median lifespan. Sham surgery performed on Day 3 or later also results in a decrease in median lifespan and an increase in the thymidine index of the undisturbed primary tumor. Artifical metastases (10(6) cells iv) are inhibited by the presence of a second (sc) implant and the median lifespan of the doubly implanted mice exceeds that of mice bearing iv implants only. In mice bearing widely metastasized Lewis lung carcinoma, surgery alone may have a detrimental effect on life expectancy, but the residual tumor foci, stimulated to more rapid growth, should be appropriate targets for adjuvant chemotherapy.


Effects of tumor bearing on the dynamics of host hemopoietic cells. Hemopoietic status of the host is an important consideration in any cancer chemotherapy protocol. This paper examines several aspects of the response of the host lymphomyeloid system to tumors transplanted elsewhere: (a) characteristics of host leukocytes migrating into the tumor; (b) leukocyte dynamics in the marrow and the spleen; and (c) dynamics of hemopoietic stem cells. Repeated prelabeling of mice with 3HTdR prior to Ehrlich ascites tumor (EAT) transplantation indicated a large-scale, selective migration and/or retention of newly formed lymphocytes and monocytes within the tumor. Similar observations were also made in sc transplants of strain-specific TA-3(St) tumor. Bone marrow was found to be a major source of these mononuclear cells since their accumulation was suppressed by a prior irradiation of host marrow. Labeling with 125I-antimouse IgM, with or without prior incubation of cells with anti-theta serum, revealed that, within the 7-day-old EAT, about a third of the small lymphocytes were maturing B cells having readily detectable surface IgM, about a third were T cells expressing theta antigen, and the rest had neither marker, possible including very immature B cells. A high incidence of last cell category was also found in subcutaneous TA-3(St) tumors. Ip transplantation of 10(6) EAT cells into CBA/HT6 or TA-3(St) cells into A/J mice caused a transient decline in femoral marrow leukocyte level (affecting lymphocytes most) followed by a recovery and an overshoot. In contrast, there was a steady rise in splenic weight or cellularity mostly accountable for by lymphocytes. This was partly due to local lymphoid proliferation and partly due to extraneous migration. Parabiosis of CBA with T6 chromosome-bearing CBA/HT6 mice revealed that a large proportion of cells dividing in the spleen of the CBA host after tumor transplantation had migrated recently from blood. Using partial marrow chimeras (repopulated with T6 chromosome-bearing marrow cells), bone marrow was identified as their major source. Furthermore, host spleens showed an increased incidence of small lymphocytes bearing no detectable surface-IgM nor theta antigen (possibly inclusive of immature B cells), and a low incidence of T cells. Tumor transplantation produced a rapid and substantial decline in the pleuripotent stem cell (CFU-S) content of the femoral marrow followed by a recovery. The converse was true for the CFU content of the spleen, and in addition, there was an initial rise in the blood CFU level, suggesting an early CFU traffic from marrow to spleen. A qualitatively similar pattern was also noted for stem cells committed to granulocyte or macrophage development as evaluated from in vitro colony assays. An early rise in splenic CFU level was also elicited by injecting sonicated tumor cells or their plasma membrane fractions, thus possibly indicating an antigen-driven effect. A high level of colony-stimulating activity (for in vitro colony growth) was found in the tumor fluid...


Evidence for recruitment and synchronization in leukemia and solid tumors. In malignant cell populations which are sensitive to drug therapy it does not seem necessary to potentiate treatment with perturbation of the proliferative characteristics. However, in some relatively drug-resistant populations significant advantages can be obtained by recruiting resting cells into the drug-sensitive cell cycle. Further studies of growth-regulatory mechanisms for malignant cell populations may help a great deal in designing better methods of recruiting the resting cells back into active cell division. Synchronization of the dividing cells in a specificially drug-sensitive phase of the cell cycle is another method of potentiating chemotherapeutic effectiveness in relatively drug-resistant cell populations. The biochemical changes induced by sequential drug administration may be equally important in sensitizing the malignant cell to subsequent drug administration.


Synchronization with phase-specific agents in leukemia and correlation with clinical response to chemotherapy. Mitotic indices, labeling indices (LI), and tritiated thymidine incorporation into DNA of marrow cells were conducted in patients with leukemia to determine if correlations existed between kinetic measurements, clinical features, and response to chemotherapy. Higher proliferative activity was observed in chronic granulocytic leukemia (CGL) and blastic phase of CGL than in acute leukemia. In acute myelogenous leukemia there was no correlation with various clinical features studied. Those patients demonstrating greater than 60% reduction in circulating leukemia cells within 7 days had a higher initial LI than those with less than 60% reduction. Cytosine arabinoside, methotrexate, and hydroxyurea were investigated to determine their synchronizing capability; cytosine arabinoside and methotrexate were superior to hydroxyurea. In a cycle-sensitive schedule specifically designed to synchronize cells, responses occurred more frequently in patients who increased thier LI 48 hours after priming doses of cytosine arabinoside. In an intensive-chemotherapy schedule which produced more remissions than the cycle-sensitive schedule, there was no relationship between initial kinetic measurements and response. Kinetic values increased as patients achieved remissions.


Role of radioautographic studies in clinical investigative oncology and chemotherapy. Three clinical areas are identified in which radioautographic studies may be of practical usefulness. First, human tumors can be classified according to the predominant pattern of DNA synthesis in the slowly proliferating cell fraction. This classification scheme groups carcinoma of the breast and ovary together, melanoma and carcinoma of the lung together, and places acute adult leukemia in a separate class. If there are correlations between kinetic characteristics and drug response behavior, this classification scheme may simplify the clinical study of new drugs and drug combinations. Second, changes in the labeling index (LI) and/or cell labeling intensity may serve as useful guides in drug scheduling. There are circumstances where changes in cell labeling intensity may be more reliable than changes in the LI. Third, cell morphology, population kinetics, and clinical course may all be correlated in certain human tumors, particularly the lymphomas. Supporting evidence in Sézary's syndrome is presented.


Comparison of cell proliferation kinetics in human and experimental tumors: response to irradiation. Available data on the parameters of cell kinetics in human solid tumors were reviewed. The mean duration of the cell cycle is 2 days; for G1 it is 1 day, for S it is 18 hours, and for G2 it is 6 hours. G1 has the greatest variability from tumor to tumor. The cell cycle and its phases are shorter in animal tumors but the relative durations and variabilities are similar. The labeling index (LI) and the growth fraction vary widely among human tumors, but they are correlated with the histologic type of the tumor. There is a correlation between the mean doubling time and the mean LI of the various histologic types of tumors. Cell loss is considerable in all human tumors, but it is more important in tumors with a high LI. Metastases and recurrence appear to have shorter doubling and cell cycle times than the primary tumor. There seems to be in patients with metastases a correlation between the survival and the growth rate of the metastases. There does not seem to be any correlation between the LI and the probability of dissemination. The depression of LI after irradiation is more important in human tumors than in experimental tumors and varies widely among human tumors. After irradiation, the depopulation seems more important in tumors with a high LI. The histologic groups of tumors with a high mean LI are on the average more radiosensitive and more sensitive to drugs.


Combined effect of cytosine arabinoside and thiopurines. Dose and time survival for leukemic colony-forming units (LCFU) and normal hematopoietic colony-forming units (NCFU) were obtained after the administration of either 6-mercaptopurine (6-MP) or 6-thioguanine (TG). Survival decreased to a plateau level with increasing doses as expected with phase-specific agents. Time survival curves demonstrated increased killing of LCFU after administration of 2 mg of 6-MP/mouse or 0.1 mg of TG/mouse reaching a minimum by 3-8 hours with repopulation therafter. Cytosine arabinoside (Ara-C) (1 mg/mouse) was combined with each agent, and the effects of sequence and interval were examined in terms of LCFU and NCFU survival. When Ara-C and either thiopurine were administered together, fractional survival was less than additive. However, as the interval was increased for either sequence and for both combinations, survival decreased to synergistic levels. Variation in dose of Ara-C and TG showed an inhibitory effect to be dependent upon the Ara-C dose. A correlation between results from the colony assay for for LCFU and survival of treated tumor-bearing mice was demonstrated for Ara-C plus TG. The results of these experiments are interpreted in terms of the proliferation kinetics of L1210 and the cellular effects of the agents; their clinical implications are discussed.


[The problem of death in current medicine]. The actual question of the determination of the time of death and the transplantation of organs have made the phenomenon of death in a special way important nowadays and have opened a new area of tasks, especially for the subject of neuropsychiatry. A reflection and discussion of the problem of death can only be possible in the context of actual historical and sociocultural developments. Regarding a fundamental reflection of the phenomenon of death in medicine and a physician's work, the author names especially the philosophical, theological, sociological, and psychological aspects of death.


Special technics in renovascular surgery. Apart from the critical selection of patients, surgical results in renovascular surgery depend mainly on technical problems. To overcome most frequent technical handicaps, such as a deep abdominal cavity, intervening structures, additional distal stenoses and limited ischemic tolerance time, several technical principles may be recommended. An anterior transperitoneal approach usually ensures an optimal exposure. The 'one-field repair' and the 'partial ex situ repair', include the advantage of excellent exposure and a superficial operating field. Particularly in cases of renal artery stenosis of the fibromuscular type, the routinely performed distal 'run-off control' by mechanical dilatation of the arterial branches, allows a high degree security. As in other fields of surgery, renovascular interventions should be directed to the principle of technical simplicity. Following this surgical concept there is only limited indication for the use of 'total ex situ repair' with heterotopic kidney replantation. We feel that this major time-consuming procedure has only a very small place in renovascular surgery, but a very real place in the correction of intrarenal lesions.


Results of medical and surgical treatment in renovascular hypertension. Long-term results and choice of antihypertensive drugs. 107 patients have been operated upon for atherosclerotic or fibromuscular renal artery stenosis from January 1, 1962 through December 31, 1973. At the time of last follow-up, or at 1 year 67% of patients with atherosclerotic renal artery stenosis, and 79% of patients with fibromuscular renal artery disease were considered to be improved. More recently 50 patients have been treated by surgery (24 patients) or with antihypertensive drugs. 70% (17 of 24) surgically treated patients and 61% (16 of 26) medically treated patients were improved after an average of approximately 1.5 years follow-up.


Renin, renin substrate and angiotensin II concentration in renal venous blood. In 22 hypertensive patients with unilateral renal artery stenosis (RAS) and in 8 patients with unilateral or bilateral renal or renal arterial disease, plasma renin activity (PRA), renin substrate (PRS), and angiotensin II (AT II) concentrations were measured in both renal veins and in a peripheral vein 1-2 h after stimulation of renin secretion by injection of frusemide. In patients with elevated PRA in venous blood from a kidney with RAS, AT II was either also elevated, lower than or equal to PRA in peripheral blood, while the contralateral kidney almost invariably extracted AT II. In the 8 patients with variable renal diseases, the concordance between PRA and AT II measurements was better. Results suggest that AT II measurements in renal venous blood are less useful in assessing the functional significance of a RAS than those of PRA. Since PRS is not different in venous plasma of the diseased and the normal kidney, PRA measurements can be regarded as proportional to plasma renin concentration in this condition.


Relevant diagnostic procedures in renovascular hypertension. The validity of invasive preoperative diagnostic procedures in patients with unilateral renovascular hypertension was assessed. A significant lowering of blood pressure following reconstructive surgery can be predicted if following stimulation with Dihydralazine the renal-venous renin ratio of the involved to the noninvolved kidney is at least 2.0. Furthermore, it is of importance to determine the renal perfusion rate in the contralateral non-stenotic kidney which should be within normal limits. If these two criteria are met then in the majority of cases surgical intervention in unilateral hypertension is meaningful.


Measurement of plasma renin concentration and angiotensin II in peripheral and renal venous plasma in the management of renovascular hypertension. Athough in general, measurement of renal vein renin appears to give a good prediction as to the subsequent response to surgery, its main value lies in its ability to reflect changes in renal plasma flow; true changes in renin secretion rate being much more difficult to detect. Although it is a little early to say how much information can be derived from saralasin infusions, caution must be exercised in necessarily assuming that the test accurately reflects subsequent surgical response.


Angiographic aspects of renovascular hypertension. Angiography is the most important diagnostic procedure for evaluation of renovascular hypertension. Technique and limits of this method as well as possible ways of improving its diagnostic value are discussed. The pathogenetic significance of a renal artery stenosis in hypertension and the prognosis for a vascular surgical intervention is discussed in the light of bilateral renin determination and the 138 Xe method of measuring intrarenal hemodynamics.


Extracorporeal renal surgery for renovascular hypertension. Nine cases of renovascular hypertension caused either by lesions in the distal part of the renal artery or by proximal renal atery stenosis where local reconstruction was considered dangerous were treated by extracorporeal reconstructive surgery and autotransplantation. The kidney were removed, cooled and preserved by simple hypothermia during workbench reconstruction on a separate side table. After reconstruction the kidneys were reimplanted to the groin. One kidney was lost due to infection and bleeding. All patients were preoperatively severely hypertensive. Blood pressure was normalized in all cases but one with a homotransplanted kidney which also was undergoing chronic rejection. The method is simple and safe and offers new possibilities to treat lesions in the kidney which previously were impossible or very risky to treat surgically. It is a safe alternative to conventional methods in case of anatomical structures making local reconstruction difficult.


Polyploidization in rat liver: the role of binucleate cells. Liver cells were isolated from rats undergoing active formation of tetraploid cells and prelabelled in their DNA with 14C thymidine. Autoradiography of the isolated cells showed that binucleate diploid cells, a major component of the parenchymal cell population at this time, are also active in DNA synthesis. These cells probably pass through mitosis and generate mononucleate tetraploid cells, the dominant cell type of mature rat liver, since the frequency of binucleate tetraploid cells is very low at this stage in rat liver development. The biological significance of liver polyploidy is discussed and it is suggested that this lies in enhanced resistance to mutagenesis.


Transcriptional and post-transcriptional control of rRNA synthesis in human liver cells cultured in presence of L-triiodothyronine. The synthesis of rRNA in cultured human liver cells grown in the presence of L-triiodothyronine (1.6 x 10(-5)M) was measured by means of polyacrylamide gel electrophoresis using a double labelling technique. The rate of accumulation of rRNA in the cytoplasm as well as the turnover of rRNA in ribosomes remained unchanged in comparison to control cells regardless of growth stage or cell population density. L-triiodothyronine, however, induced an increased synthesis of rpreRNA when added in the early growth phase of sparse cultures. This induction was time dependent and occurred temporarily, but it was never followed by a similar accumulation of mature rRNA. Therefore, in this system two control mechanisms counteracting each other were effective: the increased rpreRNA synthesis indicates a transcriptional control, and the wastage of odd rpreRNA, however, a post-transcriptional control.


Shape changes and reduced calcium level in the surface membrane region of human platelets exposed to manganese in vitro. The effect of exogenous manganese ions upon human platelets in vitro has been studied. Morphological changes reported include the loss of discoid shape, increase in filopodia and close apposition of platelet surfaces. Electron microscope X-ray microanalysis of thin-sectioned material revealed a significant decrease in the bound calcium levels of the surface membrane as a result of manganese treatment. Analysis of whole platelet homogenates using atomic absorption spectrophotometry indicated that the total internal platelet calcium content had increased significantly. It is suggested that manganese induces the observed changes by displacing calcium from the regulatory system of an actomyosin-like protein complex at the periphery of the platelet.


Endoscopy in experimental urology using an argon-laser beam. For the first time cystoscopic argon and neodymium-YAG laser irradiation of the bladder wall using a flexible quartz fiber light guide (as described by Nath) was studied morphologically and histologically. It was seen that it is possible to control the depth of tissue removal without the risk of perforation of the bladder wall. Therefore endoscopic surgery of bladder tumors by laser radiation seems to be possible. Hydronephrosis could not be observed even after direct laser irradiation of the orifices.


[Intestinal placement of Miller-Abbott-tubes under endoscopic guidance (author's transl)]. Based on experiences with 9 treatments in 7 cases of intestinal obstruction, the technique of endoscopic transgastric guidance of Miller-Abbott-tubes is reported. On our service, the above mentioned method was applied in the treatment of intestinal obstruction observed in cases of advanced malignant lesions as well as in patients with intestinal obstruction in the early postoperative period. Apparative aids and technical guidelines are accentuated. The method requires a team consisting of at least one physician and three assistents with clearly defined competence. Success also depends on the selection of material used. Special problems arise in the treatment of patients following partial gastrectomy. Routine X-rays are important in order to control the course of treatment and to documentate the result. The inclusion of endoscopic aids resulted in successful intestinal intubation in all cases treated. The utilization of recommended guidelines seemingly rules out technical failure in the attempt of placing the tube in the desired anatomic position.


Colonoscopic perforation: its emergency treatment. One of the accepted complications of colonoscopy is perforation. This is known to occur in greater frequency in patients having undergone previous pelvic or colonic surgery, as well as patients suffering from diverticulosis. A case is presented of colonic perforation during diagnostic examination in an area of adhesions secondary to pelvic surgery. Immediately after the perforation, the patient entered into vascular collapse and respiratory distress, with a distended abdomen. The introduction of a large bore intravenous catheter into the abdominal cavity with the release of the pneumoperitoneum resulted in an instantaneous return of vital signs and the patient subsequently underwent surgery and recovered. It is felt that this method of emergency treatment can be life-saving in a patient perforating during colonoscopy.


The endoscopic demonstration of coeliac disease. The first part of the duodenum has been studied endoscopically in treated and untreated coeliac patients. Biopsies taken from the duodenal cap during endoscopic examination, show villous atrophy similar to that found in the distal duodenum and jejunum. Using the indigocarmine scattering method, severe atrophy of the mucosal surface can be demonstrated throughout the duodenal cap, in vivo, in untreated coeliac disease.


Technique, indication and evidence of sinuscopy. It is reported on experiences made with endoscopy of the maxillary sinus by means of three different angular optics according to Hopkins (0 degree, 30 degrees, 70 degrees). A sinuscopy is indicated in order to obtain an early diagnosis of malignant tumour growth; it is decisive as to an operation of the maxillary sinus to be carried out; it clarifies clinically uncertain maxillary sinus findings. In addition to the usual investigation methods, the sinuscopy allows a direct local diagnosis. Moreover, diagnostic and therapeutic operations may be carried out by means of a biopsy forceps.


Results of diagnostic pelviscopy in cases of chronic recurrent pelvic disease. During the last two years we have performed diagnostic pelviscopy in 90 patients suffering from a syndrome of chronic repeated pelvic disease. In 44 patients extragenital endometriosis was diagnosed as the causing factor. In 15 cases we found wide-spread adhesions in the region of the lower pelvis after preceeding laparotomies. Only in 12 patients pelvic-alterations caused by chronic inflammatory processes of the adnexa with peritubal adhesions were discovered. As these results show extragenital endometriosis represents in far more cases as generally believed the cause of gynecological pains. We want to give special emphasis to the diagnosis and treatment of this disease.


Removal of foreign bodies from subsegmental bronchi with the fiberbronchoscope. Though the fiberbronchoscope has been designed for diagnostic purposes, it can be used, as well, for the removal of small foreign bodies from segmental and subsegmental bronchi; In this paper we report two cases in which we successfully removed from subsegmental bronchi a pulp-canal reamer and a melon seed. This fact proves that in some of these cases we can avoid thoracotomies.


A new device for endoscopic foreign body extraction. A yoghurt-spoon with a long handle which could not be removed initially from the stomach during several sessions was finally successfully extracted by a new simple device.


A new self-twisting polypectomy snare.

A new self-twisting polypectomy snare. In contrast to the hitherto available polypectomy snares the newly designed snare for endoscopic polypectomy offers the following advantages: when the tip of the endoscope is directed towards the polyp the snare turns automatically into a position parallel to the polyp-bearing bowel wall. "Combusting ulcers" are avoided, a homogenous circular flow of electric current is guaranteed.


Transgastroscopic ultrasonography.

Transgastroscopic ultrasonography. A newly designed ultrasonography probe is presented which can be advanced through the instrumentation channel of an operative endoscope (TGF-Olympus). The A-scan allows the differentiation between solid and cystic masses in the upper abdomen leading to gastric impression. Guided puncture of pancreatic pseudocysts is based on a solid diagnosis and can be performed from the gastric lumen thus avoiding the development of pancreato-cutaneous fistulas.


Oesophagus bezoar diagnosed and removed endoscopically. The authors describe the rare case of bezoar in the oesophagus. Their patient was sent to their Clinics with a diagnosed oesophageal tumor. The exact diagnosis was established by endoscopical examination. The bezoar was removed by endoscope, therefore, an operation was not necessary.


Double pylorus and esophageal achalasia. 29 cases of double pylorus have been reported so far. It is thought that in 85% of the cases it has been due to a fistulous gastro-duodenal ulcer and the remaining 15% would be of a congenital origin. In the case we have reported the double pylorus is believed to be a congenital anomaly associated with a mega-esophagus of similar etiology.


A case of common bile duct ascariasis diagnosed by duodenoscopy. A case of common bile duct ascariasis diagnosed by duodenoscopy is presented. At the admission, the patient, cholecystectomized for gallstones 13 years before, had been complaining of epigastric pain associated with post-prandial and nocturnal vomiting. Physical examination showed only slight tenderness in the epigastrium. Laboratory findings were within normal limits, with the exception of a moderate leukocytosis. Intravenous cholangiography showed the lack of visualization of the terminal common bile duct, but the flow of contrast medium was normal. Duodenoscopy, carried out without a specific clinical suspicion, revealed an ascaris lumbricoides inserted in the common bile duct and partially protruding from the papilla Vateri. The patient was treated by piperazine, intravenous fluids, antibiotics and a choleretic compound. After 24 hours an ascaris 33 cm long was excreted in the faeces and the patient became symptom-free. Some pathophysiological, clinical and epidemiological aspects of biliary ascariasis are discussed.


Hypogammaglobulinemia with lymphoid nodular hyperplasia of the small bowel: endoscopic diagnosis of one case. A 37-year-old man suffering from abdominal pain and diarrhea, was hospitalized because of abdominal discomfort. Gastroduodenal series showed multiple duodenal filling defects. Gastroduodenoscopic examination revealed numerous nodular lesions in the duodenum and biopsy specimen demonstrated nodular lymphoid hyperplasia. The serum immunoelectrophoretic pattern showed a virtual absence of IgA and IgM and a very decreased level of IgG. To our knowledge, it is the first case of hypogammaglobulinaemia with nodular hyperplasia of the small bowel, diagnosed by endoscopy and forceps biopsy.


Measurement of some potentially hazardous materials in the atmosphere of rubber factories. Two separate topics of work are outlined: methods for the measurement of chlorinated monomers in PVC and polychloroprene, and also methods for the measurement of these materials in factory air. Typical results which have been obtained in supplies of raw materials, in finished products, and in the working atmosphere at manufacturing operations are given. The second topic concerns the measurement of benzo[a]pyrene in the atmosphere of a tire manufacturing plant. This material is present in trace quantities in the mineral oils and carbon blacks used by the industry. The atmospheric concentrations present at various processes in this plant were measured on a daily basis over a period of two years, and the results obtained compared with results taken concurrently from an outside air station. It is shown that no significant quantities of benzo[a]pyrene are produced by tire manufacturing operations.


Quantitative analysis of styrene monomer in polystyrene and foods including some preliminary studies of the uptake and pharmacodynamics of the monomer in rats. A variety of food containers, drinking cups and cutlery, fabricated from polystyrene (PS) or polystyrene-related plastic, were analyzed for their styrene monomer content. Samples of yogurt, packaged in PS cups, were similarly analyzed and the leaching of styrene monomer from PS containers by some food simulants was also determined. Blood level studies with rats, dosed with styrene monomer by various routes, illustrated uptake phenomena that were dependent on the dose and route of administration and were also affected by the vehicle used to convey the styrene monomer.


Chronic diseases in the rubber industry. An overview is presented of epidemiologic studies of chronic diseases in the rubber industry. Analyses of the mortality experience during the period 1964-1972 of workers age 40-64 and retirees age 65-84 of two large rubber and tire manufacturing companies consistently disclosed excesses of deaths attributed to leukemia and lymphosarcoma, and for cancers of the stomach, large intestine, and prostate. The relation of site-specific malignancies to work histories and grouped occupational titles as surrogate measures of work-related exposures to possible carcinogens is described. There was no evidence of company-wide, sizable, consistent excess for the other major chronic diseases causes of death. Although a total cohort deficit in the mortality rate for lung cancer was found, there was a history of increased frequency of exposure to certain work areas among lung cancer decedents. Morbidity studies, including analysis of disability retirements, and ad hoc questionnaire and health testing surveys, disclosed excesses of chronic pulmonary diseases. There was evidence of an interactive effect in the association of work and smoking histories with pulmonary disability retirement.


Hepatic and extrahepatic metabolism of 14C-styrene oxide. With 8-(14)C-styrene oxide as substrate, specific glutathione S-transferase and epoxide hydrase activities were determined in subcellular fractions of liver, lungs, kidney, and intestinal mucosa from rabbit, rat, and guinea pig. Liver had the highest enzyme activities in each species. Rat and guinea pig had higher glutathione S-transferase activity in both liver and kidney than rabbit. Rat testis also had appreciable glutathione S-transferase activity. The perinatal development of epoxide hydrase and glutathione S-transferase was followed in liver and several extrahepatic tissues of fetal and neonatal guinea pigs and rabbits. The rates at which enzyme activities reached adult levels in the extrahepatic tissues differed from the liver in both species. Epoxide hydrase and glutathione S-transferases developed at different rates in each organ, demonstrating that the relative importance of these two detoxifying pathways for styrene oxide may shift before and after birth. The effects of pretreating male and female rats with phenobarbital (PB), 1,2,3,4-dibenzanthracene (DBA), pregnenolone-16alpha-carbonitrile (PCN), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic and extrahepatic epoxide hydrase and glutathione S-transferase activities toward styrene oxide were determined. PB increased both enzyme activities in liver of both sexes. PCN induced only glutathione S-transferase activity in female liver. Extrahepatic epoxide hydrase and glutathione S-transferase activities were unaffected except that TCDD doubled female renal epoxide hydrase activity and PB increased intestinal epoxide hydrase activity in both sexes. Styrene oxide biotransformation was studied in isolated, perfused rat liver and rabbit lung preparations. Conjugation with glutathione was a major metabolic pathway although significant amounts of diol were also formed in each instance. In rat liver, 27-40% of the administered styrene oxide was excreted via the bile mainly as S-(1-phenyl-2-hydroxyethyl)glutathione.


Dose-dependent fate of vinyl chloride and its possible relationship to oncogenicity in rats. Studies on the fate of 14C-labeled vinyl chloride (VC) following oral administration and inhalation exposure in rats demonstrated that the disposition of VC in the body is a function of the dose. More importantly, from the data available, it appears that a correlation exists between doses of VC which cause tumors and those that saturate metabolic or detoxifying pathways. Additional studies characterized the depression of liver non-protein sulfhydryl content (primarily GSH) with the duration and concentration of exposure to VC. The results of these investigations indicate that statistical projections utilizing data collected from rats exposed to high doses of VC are invalid for predicting the hazard of low level exposure, because such projections violate a priori assumption that the dynamics governing the fate of VC in the body are unaltered.


Demographic variation in cancer in relation to industrial and environmental influence. Mortality data (183,064 deaths in a 30-year period, 1940-1969) by sex and three ethnic groups (white excluding Spanish-surnamed, nonwhite, and Spanish-surnamed) in 15 regions within the city (Houston), grouped around the air pollution sample collection stations have been analyzed. Valid contrast studies were possible in only one region within the city for all three groups and in six regions for white excluding Spanish-surnamed and nonwhite. There is evidence that the environmental factors of exposure over time to air and industrial pollutants in Houston has had a demonstrable effect in increasing regional mortality from cancer of the respiratory tract as well as from all other diseases and conditions of the respiratory tract and heart disease. This study points out the need for mutually sustained collaboration of effort of the scientific and industrial communities to redirect their attention and research efforts to the exploration of the carcinogenic potential of the microchemical environment.


Mortality and cancer morbidity in a group of Swedish VCM and PCV production workers. The cohort of workers employed in a Swedish vinyl chloride/poly(vinyl chloride) plant since its start in the early 1940's has been followed for mortality and cancer morbidity patterns. Only 21 of the 771 persons could not be traced. Difficulties in establishing exposure levels at different work areas in the past makes an evaluation of dose-effect relationships impossible. A four- to fivefold excess of pancreas/liver tumors was found, including two cases later classified as angiosarcomas of the liver. The number of brain tumors and suicide do not deviate significantly from expected. Cardiovascular and cerebrovascular diseases, on the other hand, differ significantly from the expected. The discrepancies between previous reports on VCM/PVC workers and this report are discussed. The possible etiology of the cardiovascular deaths is also discussed.


Clinical studies of styrene workers: initial findings. Styrene monomer is a high volume chemical used chiefly in production of polystyrene. A clinical survey of 493 production workers was undertaken at the oldest and largest monomer production, polymerization, and extrusion facility in the U.S. Relative exposure durations and levels were obtained from occupational histories. Significant differences between the high and low exposure groups were found with regard to history of acute prenarcotic symptoms, acute lower respiratory symptoms, prevalence of FEV 1/FV less than 75 per cent, and elevated GCTP. Other liver function tests, chest x-ray, FVC less than 80 per cent, and hematological parameters showed no distinct pattern. A concomitant mortality study has been mounted and is in progress.


Malignant tumors of the liver and lungs in an area with a PVC industry. The incidence of malignant tumors of the lung and bronchus and of cytologically confirmed primary malignant tumor of the liver was analyzed for a 4-yr period in a city with several factories, including a PVC industry. Prior to the study two cases of angio-sarcoma of the liver were diagnosed in workers employed in PVC production. The total incidence of analyzed tumors was only slightly higher than predicted. The tumors of the liver recorded did not show any dependence on place of work or residence. During the period of observation, malignant tumors of the bronchus (lung) were not recorded in the PVC industry. Their rate in the area in which the PVC industry is situated was approximately the same as that for the entire city area. The study does not indicate that the occurrence of malignant tumors other than angiosarcoma is associated with exposure to vinyl chloride.


Health hazards in the production and processing of some fibers, resins, and plastics in Bulgaria. Results of the toxicological studies of working conditions, general and professional morbidity, and complex examinations carried out on workers engaged in the production of polyamides, polyacrylonitrile fibers, polyester fibers and poly (vinyl chloride) resin, urea-formaldehyde glue, glass fibre materials and polyurethane resins are given. An extremely high occupational hazard for workers in the production of poly (vinyl chloride) resin and porous materials from polyurethane resins and urea-formaldehyde glue has been established. Cases of vinyl chloride disease, poisoning from formaldehyde, isocyanates, and styrene were noted. Prophylactic measures were taken in Bulgaria to lessen the occupational hazard in the productions as set forth included limitation of the work day to 6 hr, free food, additional bonus and leave, and annual physical examinations of workers.


Recent progress in safety evaluation studies on plasticizers and plastics and their controlled use in Japan. Recent experimental studies in Japan on the evaluation of potential health hazards from phthalate esters used in manufacturing poly (vinyl chloride) as well as several plastics for medical devices and for food containers and packages were introduced. Development of pulmonary granuloma formation after intravenous injection of diethylhexyl phthalate was assumed to be dependent on the particle size of the phthalate in vehicle used. Dietary administration of large amount of diethylhexyl phthalate and dibutyl phthalate produced renal cysts in mothers and in descendants in reproduction studies in mice. Cytotoxicity and mutagenicity of the phthalates and several plastics and resins were also examined by in vivo and in vitro studies. Hematological parameters examined in rabbits after repeated intravenous injection of diethylhexyl phthalate and after implantation of plastics in aorta for 3--6 months did not show any significant change. A slow decrease of radioactivity was observed in adipose tissue of rats following oral administration of 14C-labeled diethylhexyl phthalate. tthe administrative action on phthalates by the Japanese Ministry of Health and Welfare is briefly reviewed.


Problems and perspective in epidemiological study of occupational health hazards in the rubber industry. An epidemiological analysis of the problems in the study of companies engaged in the manufacture of rubber products in different countries and in different time periods is given. Selected findings on cancer of gallbladder and biliary system, cancer of the lung, and tumors of the central nervous system among rubber workers are presented.


Studies on the metabolism of vinyl chloride. Vinyl chloride (VCM) is not carcinogenic by itself, it is bioactivated to the highly reactive alkylating oxirane chloroethylene oxide. Further metabolism, apparently, leads via an interaction of the primary alkylating metabolites with glutathion to S-(2-carboxy-methyl)-cysteine and thiodiacetic acid which are eliminated with the urine. Up to now, it has not been ascertained whether the oxirane alone is the essential carcinogenic factor or whether other metabolites are also involved in carcinogenicity. Likewise, it is still unknown whether the metabolites excreted in the urine might be used as biological criteria for exposure to VCM, because these metabolites probably can originate from a series of substances other than VCM. This problem could stimulate investigations on the possible carcinogenic activity of these substances.


Consumer hazards of plastics.

Consumer hazards of plastics. The modern consumer is exposed to a wide variety of plastic and rubber products in his day to day life: at home, work, school, shopping, recreation and play, and transport. A large variety of toxic sequellae have resulted from untoward exposures by many different routes: oral, dermal, inhalation, and parenteral. Toxic change may result from the plastic itself, migration of unbound components and additives, chemical decomposition or toxic pyrolysis products. The type of damage may involve acute poisoning, chronic organ damage, reproductive disorders, and carcinogenic, mutagenic and teratogenic episodes. Typical examples for all routes are cited along with the activites of Canadian regulatory agencies to reduce both the incidence and severity of plastic-induced disease.


Diffusion of residual monomer in polymer resins. A simplified mathematical model which made use of Fick's laws of diffusion written in spherical coordinates was developed to describe the rate of diffusion of residual monomers from polymer resins. The properties of the monomer-polymer system which influenced the amount of monomer remaining in the polymer as a function of time were the diffusivity and solubility of the monomer in the polymer, and the particle size of the polymer resin. This model was used to analyze literature data on the diffusion of residual vinyl chloride monomer in polyvinyl chloride resins made by the suspension process. It was concluded that particle size of the resin was a significant parameter which should be taken advantage of in process equipment designed to remove residual monomer from PVC resins. The diffusivity of the monomer in the polymer was a function of the solubility of the monomer in the polymer. Monomer solubility can be determined from Henry's law. It was suggested that this model could be adapted to describe diffusion of monomers from any monomer-polymer system, and would be a useful approach to modeling the transport of nonreactive chemical additives from plastics.


Recent achievements and research initiated in the Swedish plastics and rubber industry. The improvement in exposure conditions in the Swedish vinyl chloride producing industry is reported. The article comments on the technology and control methods by which the vinyl chloride concentration has been lowered to less than 1 ppm vinyl chloride. Two epidemiological retrospective cohort studies are presently under way on workers in PVC-utilizing industries and in the rubber industry.


Criteria for the health evaluation of polymeric materials building. Various polymer-based synthetic materials have become increasingly ubiquitous in manufactured materials in the U.S.S.R. These release various chemical compounds to the ambient air. The maximum permissible concentrations that have been established for various hazardous chemicals in ambient air must be adjusted to account for the conditions of apartment life. Studies have been conducted to determine exactly what compounds are released and at what rate. Toxicological studies and studies of various physical and chemical properties are required to determine the health effects of these chemicals at concentrations at which they are expected to occur in apartments. More research has to be carried out in this field to further expand our knowledge, and we must beware of any introduction of new polymeric materials without first studying their contribution to possible detrimental health effects.


Occupational disease in the rubber industry. We have studied mortality patterns in a large cohort of rubber workers. We have examined workers exposed to curing fumes, processing dusts, and industrial talc and have begun to evaluate exposures of these workers in detail. Gastrointestinal (especially stomach) cancer appears in excess in processing workers. Lung cancer is excessive in curing workers. Leukemia is increased generally. All three groups studied for respiratory disease have an increase in disease prevalence which is related to intensity and duration of exposure. Since both an increase in stomach cancer and respiratory disease is seen in processing workers, exposures in this area must be controlled. Since both lung cancer and chronic respiratory disease is excessive in curing rooms, this exposure must be controlled. The leukemia risk is probably related to solvents. Whether this is all explainable by past benzene exposure is unknown. Further studies are planned to refine our knowledge concerning these risks so that occupational disease in the rubber industry can be prevented.


Neurotoxicity and behavioral effects of thiram in rats. Eight of 24 female rats fed 66.9 mg/kg-day of thiram developed neurotoxicity. The neurotoxic effects were characterized by ataxia and paralysis of the hind legs. There were demyelination, degeneration of the axis cylinders, and presence of macrophages in the nerve bundle of the sciatic nerve. Degeneration in the ventral horn of the lower lumbar region of the spinal cord was evidenced by chromatolysis of motorneurons, pyknosis, and satellitosis. During a second experiment, 4 of 24 females fed 65.8 mg/kg--day also developed ataxia and paralysis. An additional 9 females showed clasping of the hind feet when picked up by the tail. Nerve conduction could not be measured for one severely ataxic rat and the electromyogram indicated a loss of motor unit function. Histopathology of this rat, along with the others, suggests the peripheral nerve as the primary site of the lesion. Thiram also caused behavioral changes in apparently normal rats. The walking pattern of the hind legs was altered with decreases in stride width and the angle between contralateral steps. These rats required significantly more shock-motivations and cleared a lower height in a jump/climb ability test. An open-field study indicated that thiram caused hyperactivity in the nonataxic rats of both sexes. Three of 24 rats fed 95.8 mg/kg-day of ferbam also developed ataxia or paralysis.


Health aspects of the curing of synthetic rubbers. A commonly used tread rubber formulation was cured in the laboratory under conditions simulating vulcanization in the Bag-O-Matic press. Volatile emissions were collected on charcoal and analyzed by combined GC-mass spectrometry. The compounds identified were either contaminants present in the raw material or reaction products. Some of these compounds were also identified in charcoal tube samples collected in the atmosphere of the industrial operations. Estimates based on the loss of weight of rubber during curing were used to predict airborne concentrations and compared to the concentrations actually found. The literature of the toxicity of raw materials and effluents was reviewed, and no acute or chronic toxicological effects would be anticipated. Information concerning potential carcinogenicity was not available and could not be evaluated.


Priorities in the investigation of human health hazards in the plastics and synthetic rubber industries. Experiences in the past decade provide guidance in selecting priorities for investigation of health hazards in chemical industries. Pride of place should be given to the experience of large industrial populations, in part simply because large numbers of people are at risk and in part because such studies are more likely to give reliable answers. This recommendation has further strength when there is community exposure as well. Parenthetically, large populations provide opportunity to study multiple factor interaction; without this, toxic potential of a single agent may be obscured. Second, investigations should be mounted when there is reason for suspicion, as with particular chemical configurations, observed organ toxicity, animal carcinogenicity, unusual clinical experience ("signal" tumors). It may be added that when agents have already been used several decades, evaluation of human experience with them is now in order, if only to document absence of toxicity. The same recommendations hold for planned introduction of new agents or widened distribution of existing ones, until we have better information concerning validity of "pretesting" programs. Major advances have been made in epidemiological methods for these investigations. These now allow us to successfully focus on small defined groups as well as to manage large populations.


Chemistry and toxicity of flame retardants for plastics. An overview of commercially used flame retardants is give. The most used flame retardants are illustrated and the seven major markets, which use 96% of all flame-retarded polymers, are described. Annual flame retardant growth rate for each major market is also projected. Toxicity data are reviewed on only those compositions that are considered commercially significant today. This includes 18 compounds or families of compounds and four inherently flame-retarded polymers. Toxicological studies of flame retardants for most synthetic materials are of recent origin and only a few of the compounds have been evaluated in any great detail. Considerable toxicological problems may exist in the manufacturing of some flame retardants, their by-products, and possible decomposition products.


Toxicity of combustion products from burning polymers: development and evaluation of methods. Laboratory and room-scale experiments were conducted with natural and synthetic polymers: cotton, paper, wood, wool, acetate, acrylic, nylon, and urethane. Smoke and off-gases from single materials were generated in a dual-compartment 110-liter exposure chamber. Multicomponent, composite fuel loads were burned within a 100 m(3) facility subdivided into rooms. In chamber experiments, mortality depended on the amount of material burned, i.e., fuel consumption (FC). Conventional dose (FC)/mortality curves were obtained, and the amount of fuel required to produce 50% mortality (FC(50)) was calculated. With simple flame ignition, cotton was the only material that produced smoke concentrations lethal to rats; FC(50) values for cotton ranged from 2 g to 9 g, depending on the configuration of the cotton sample burned. When supplemental conductive heat was added to flame ignition, the following FC(50) values were obtained; nylon, 7 g; acrylic, 8 g; newsprint, 9 g; cotton, 10 g; and wood, 11 g. Mortality resulting from any given material depended upon the specific conditions employed for its thermal decomposition. Toxicity of off-gasses from pyrolysis of phosphorus-containing trimethylol propane-polyurethane foams was markedly decreased by addition of a flame ignition source. Further studies are needed to determine the possible relevance of single-material laboratory scale smoke toxicity experiments. Room-scale burns were conducted to assess the relative contributions of single materials to toxicity of smoke produced by a multicomponent self-perpetuating fire. Preliminary results suggest that this approach permits a realistic evaluation of the contribution of single materials to the toxicity of smoke from residential fires.


An exploration of the dynamics of the overlapping worlds of work and family. The relationship between the working lives and family lives of people in our society is a concern to both families and corporations. This article describes a research project that yielded theoretical statements about the interactions between organization life and family life for members of large corporations; grounded theory methodology and a systems theory approach were used. Data were obtained in a large multinational corporation from managers and their families who were undergoing three different kinds of organizational stress: international transfer, extensive travel, and job change to facilitator of personal and organizational change. The findings give reason for viewing organization and family as interacting systems and for considering the uniqueness of each individual's response to stressful events. They also indicate that an individual's feeling of influence over stressful events at the organization-family boundaries are significant for both organizational and family effectiveness.


Isolation and biochemical properties of toxic tryptic peptides of ricinotoxin from Ricinus communis seeds. Tryptic hydrolysis conditions of ricinotoxin were studied in order to produce not only digestion of this glycoprotein but also still toxic tryptic peptides. No hydrolysis was obtained without prior denaturation. The best conditions of denaturation were obtained with 0.2 M guanidine hydrochloride and, to a lower extent, by heat treatment at 90 degrees C during 6 minutes. The hydrolysates were fractionated on Sephadex G100 column. In each case highly toxic peptide fractions were obtained which showed, like native ricinotoxin, a strong inhibitory action on the in vitro protein synthesis ina cell-free eukaryotic system but were without any action on a prokaryotic cell-free system.


Individuation: from fusion to dialogue.

Individuation: from fusion to dialogue. Growing interest in concepts of fusion and individuation within a number of different theoretical systems of psychotherapy suggests an emerging shift in perspective in the conceptualization of psychopathology and psychotherapy. This shift may represent a first step in the integration of individual and relational dynamic theories. A theoretical framework for the exploration of processes of fusion and individuation is presented, with suggested applications for the study of problems experienced by adult couples. The process of individuation from fusion to dialogue is outlined in the description of four modes of relationship. In this context, the paper suggests ways in which a variety of problematic relational patterns seen in couples may be viewed as reflecting the partners' struggles to move from fusion to dialogue.


[Absorption of diethylstilbestrol (DES) by plants. Dangers of using manure of animals treated with DES]. Diethylstilboestrol, an anabolist used per os or in sub-cutaneous implants in a number of countries, but not in France, on animals of the  bovine species, is absorbed by plants when spread on alfafa cultures. As this product is eliminated to a great extent through the fecal matter, its presence in fertilisers constitutes a danger to the environment, in view of its toxicity, whether direct or transmitted. This is a further reason for its use to be banned.


[Effects in the guinea pig of an aerosol with a tributylitin oxide base]. The authors report a toxicological study of bis (tributyltin oxide) (TBTO) given by inhalation (oily aerosol) to 105 Hartley albino guinea pigs. Doses vary from 1 mg to 0.1 mg of TBTO per liter of aerosol. Death occurs for doses of 0.2 mg per le more resistant than the male ones. The intoxication is marked by a period of ocular and nasal irritation followed by a short remission time, then death occurs after asphyxic convulsions. With doses less than 0.2 mg per liter of aerosol, we observe only an irritation without mortality after one hour intoxication. Seven days later the animals are alive. Because of its liposulibility, TBTO is present in the whole body, particularly in liver, kidney, lung, brain and heart. Histological study does not reveal any peculiar lesion of the examinated organs. Especially there is no specific alteration of the respiratory system. The merely observed trouble is a diffuse congestion.


Family therapy in treatment of the deaf: a case report. Deaf patients with psychological problems have developmental handicaps and clinical characteristics that reduce the effectiveness of traditional modes of psychotherapy. Attempts have been made to utilize individual and group therapy, but family therapy has been largely overlooked as a method of alleviating problems of the deaf. Clinical and research writings provide us with rich insights into the family dynamics of the deaf. These data suggest to the authors that the problems of deaf individuals are largely related to family problems, and therefore merit a family orientation as the focus for treatment. This paper describes an attempt to apply family therapy with a range of deaf patients over a period of two years. From a review of their work, the authors conclude that family therapy can be effective, particularly in the treatment of deaf adolescents and children.


Experimenting with family treatment approaches to alcoholism, 1950-1975: a review. The attention given family therapy approaches to alcoholism has been disproportionately low in relation to the magnitude of alcohol abuse as a clinical problem and its acknowledged impact on family life. Although the literature to date is limited and most studies should be characterized as pilot in nature, preliminary results have enthusiastically endorsed family therapy approaches to alcoholism. This critical review assesses the existing experimental and clinical literature of the pase 25 years. It also offers potential explanations for the reluctance of family therapists to engage this problem more actively.


[Toxicologic evaluation of irradiated corn starch by long term experimentation with rats]. Maize starch pasteurized by irradiation was fed to OFA rats (Sprague Dawley derived) in an uncooked form (irradiated at 300 krad.) and in a cooked form (irradiated at 300 and 600 krad.) at dietary level of 62%. A six month toxicity trial was performed with uncooked starch and a 24 month trial with cooked starch. At the same time a reproduction study was conducted, over 3 generations with 2 litters per generation, using both uncooked and cooked irradiated starch. The parent generation (Fo) was randomly selected from animals in the feeding study and after the production of the F1a and F1b generations they were returned to that study. Control groups corresponding to each form of starch were established. They were fed the same diet except that the starch was not irradiated. The results of the various investigations conducted during the study (behavior, growth, mortality, haematology, serum biochemistry, histopathology) did not reveal any toxicological effect due to treatment, nor any effect on reproduction. No significant differences were shown between treated and control group.


A method for co-therapy for schizophrenic families. This paper describes a model of treatment for families in which one child has been given the diagnosis of schizophrenia. Male and female therapists adopt structured roles that are used as a paradigm for exploring family patterns. The paradigm employs a three-generational hypothesis that defines schizophrenia as a lifelong, restricting mode of relating, involving the primary family triad, that makes the child vulnerable to repeated psychotic episodes. Therapy is directed at the difficulties of autonomous development within the family by focusing on differentiating the relationship between nuclear and extended family members, expecially defining and strengthening generational and sexual boundaries. The second focus of therapy is on the resolution of issues of separation and loss, with attention to unresolved mourning in the family of origin and the concomitant stress in giving up the infantile relationship with the index child in the nuclear family. Stages of therapy will be described including: (a) initiation of therapy, (b) breaking of fusion, (c) repair of alienation, and (d) solidifying the marital alliance and generational boundaries. Case illustrations will be included.


[Acute ethylene glycol poisoning].

[Acute ethylene glycol poisoning]. During last 7 years, 13 cases of acute ethylene glycol poisoning have been observed with 4 fatal outbreaks. All cases--except one--were accidental. Six patients had drunk a mixture of antifreeze in water as they were lost in a desert. A patient who had taken 970 ml of ethylene glycol survived. In one case, death was due to irreversible brain damage; two other fatalities occurred from cardiorespiratory distress. CNS involvement was noticed in 8 cases and acute renal failure-constantly controlled-occurred in 9 patients. Post mortem examination has shown bi-refringent calcium oxalate crystals in both kidney and brain. Specific treatment with ethanol has been performed in 3 cases with ingestion of large amounts of toxic who were seen before definitive renal lesions have occurred. Emphasis is placed in symptomatic treatment including gastric lavage, extrarenal epuration and conservative management.


Family of origin as a therapeutic resource for adults in marital and family therapy: you can and should go home again. This paper presents a general method of involving adults who are in marital and family therapy in sessions with their family of origin, offering a clinical application of the author's depth theoretical orientation. The method is based on the thesis that current marital and family difficulties are elaborations of relationship problems of the spouses in their original families. If adults are able to go back to deal directly with past and present issues with their families or origin, an opportunity exists for reconstructive changes to come about in their present family. This present work is compared with Bowen's methods. Procedures are outlined for preparing for these sessions and for overcoming resistances. Typical courses these sessions tend to take are described, and some preliminary results are presented. Several case histories are presented, and theoretical and clinical implications of this method are discussed.


The product of the consensus Rorschach in families of male schizophrenics. A consensus Rorschach was given to the families of 36 male schizophrenics, 13 psychiatrically hospitalized nonschizophrenic controls, and 38 normal controls with the goal of discriminating the families of schizophrenics from the other two groups of families. After the family agreed on a response, each member was asked to write the response on a separate sheet of paper. This study focused on these written responses, the product of the interaction, rather than on the process of reaching agreement. A system was developed to score the responses based on the degree of shared meaning achieved by the family. Adequate interscorer reliability was obtained. The scores significantly differentiated the three groups. More families of schizophrenics had low scores indicating lack of shared meaning than families of hospitalized and normal controls. In the normal control group, more upper-class families had high scores than lower-class families, wheras in the schizophrenic group there was a trend in the opposite direction.


Problems in measuring the success of family therapy in a common clinical setting: impasse and solutions. Families treated in conjoint therapy in the outpatient clinic of a general community hospital for about a year and other families that refused further contact with the same clinic after no more than two interviews were followed up about four and a half years later. The main difference found was that the treated group reported more new symptoms. The complexities of interpreting the data obtained are used as a basis for discussing problems that confront, and may deter, clinics attempting to evaluate their clinical work by means of controlled, nonfactorial or related designs. Process or correlational studies are suggested as an alternate choice.


The incest taboo and family structure.

The incest taboo and family structure. The evolutionary advantage of outbreeding has influenced the family structure and the mating, attachment, and dominance behaviors of all animals. Nature has selected for those species that have evolved family structures with detachment and dominance patterns that create a relatively intact incest barrier. Man inherits from his animal forebears the biological imperative of an incest barrier but brings to it his special complexity of psychology and symbolization--incest barrier becomes incest taboo. We present a discussion of human patterns of speparation-individuation and Oedipal conflict and relate this to the detachment and dominance behaviors of animals. This is an interface between psychoanalysis, family theory, and ethology. In addition, we pursue in detail the asymmetrical operation of the incest taboo within the family: that it is stronger for mother-son than for father-daughter than for brother-sister.


Balance theory: possible consequences of number of family members. This paper outlines one theoretical issue involved in considering the relationships that may exist in a family. The usual approach is to treat the family as a whole, made up of n members. The main issue here is the effects of the numerical size of the family and the many possible total and sub-total relationships that may exist within family constellations. Family structure and function is multivariate, but the focus here is the numberical factor.


An effect of change in patient status on marital interaction. In the treatment of couples and families, even more so than of individuals, therapists invariably are forced to face the problem of assessment of change in the marital or family "system." The purpose of the present study was to investigate changes in marital interaction for a special population, that is, in which one member of each married pair had been, but was no longer, a hospitalized psychiatric patient. The primary question we addressed was whether changes in marital interaction could be amply detected and whether these changes could be attributed to the particular role shift that had occurred in one spouse--from "patient" to "nonpatient." Utilizing a technique called Interaction Testing, which the senior authors devised in 1960, we found that such alterations in marital interaction do indeed arise when one member of the couple moves out of a patient role and that our instrument is useful in elucidating the nature of such effects. In addition, it can be expected that a study of this kind will be of theoretical and methodological value in dealing with the general issues of problem-solving interaction in couples and families. The clinical aspect of the study may also be expected to stimulate useful thinking regarding family theapy in hospital settings, patient management, and aftercare.


Family photographs: in treatment and training. The universal appeal of nostalgia and reminiscence makes photographs a natural instrument for studying the impact of the past upon the present. This paper explores photography as a medium for facilitating reminiscence to discover individual roles, interpersonal relationships, and family dynamics. A method is described for using family photographs in treatment and training of clinicians at a Family Therapy Clinic.


The dynamics of owning and disowning: psychoanalytic and family perspectives. The dynamics of owning and disowning one's inner life have both intrapsychic and transactional or interpersonal dimensions. Freud opened new vistas on our inner world using psycoanalysis as a tool. Although not unaware of the effects of family members upon each other, Freud's rejection of the seduction theory of neurosis in 1897 fatefully influenced the future course of psychoanalysis, placing the primary focus on intrapsychic relations. Until today, it has remained the task-perhaps the principal one--of psychoanalytic theorists to do justice to the interpersonal and family realm that Freud neglected, without sacrificing the enormous insights we owe to Freud. Three conditions for successful inner ownership are described: a capacity for self-object differentiation; tolerance of ambivalence; and a sense of physical integrity, of having a cohesive, nuclear ego. The pathology of inner ownership is related to a pathology of interpersonal ownership as transacted on the family level. One form of such relational pathology--parental overowning, as revealed primarily in families with schizophrenic members--is discussed, with a case example.


Lack of acknowledgment in the family Rorschachs of families with a child at risk for schizophrenia. Lack of acknowledgment, a characteristic of the direct interactions of families of schizophrenics, was found also to characterize the Family Rorschach interactions of families whose disturbed, non-psychotic adolescents were assessed at high risk for schizophrenia on the basis of parental communication deviance. The same high-risk families had unbalanced interaction patterns as reflected in three measures of family structure.


The family-school interview: an eco-structural approach. This paper describes the family-school interview, and intervention with a child, family, and school, taking into account the dynamics of each system in that ecological context and the structural interrelationships of these systems relative to the problem presented by the child.


Family systems model in organizational consultation: vignettes of consultation to a day-care center. "Bowen Theory," 1adapted to organizational dynamics, is presented as a framework for understanding the dysfunctional behavior of individuals in the context of a particular organization.


"Enmeshment" and "fusion".

"Enmeshment" and "fusion". The paper examines two related concepts utilized by two different schools of family therapy. Any family seen to be "enmeshed" is also seen as "fused," and vice versa. The difference in the level of focus, on the "system containing the individuals" (structural) or the "individual in the system" (fusion), determines the difference in therapeutic approach of these two schools.


Case studies in the family treatment of drug abuse. This article, with case illustrations, attempts to demonstrate that drug-abuse behavior can be understood more clearly in the light of family loyalties and unresolved family crises than from the perspective that drug abusers are social deviates.1 Drug abuse is viewed as symptomatic, as a signal that both drug abuser and his or her family are having difficulty in getting past a particular stage in the natural unfolding life cycle of a family. Treatment of drug abuse is seen primarily as helping the family to become "unstuck," thereby freeing the individual's and family's energy for the task of self-development and growth rather than expending it to maintain rigid patterns of interaction in an attempt to prevent change.


Observations on two natural amnesias.

Observations on two natural amnesias. The role of interpersonal sequences in determining amnesias has not been as explored as the role of intrapsychic conflict. This paper examines two natural amnesias, emphasizing their function as part of the process of sequencing phenomena.


Temporal patterning in the family.

Temporal patterning in the family. The authors propose that time be considered as a variable in family process. Previous theory and research on human temporal patterning and experience are reviewed, and empirical generalizations from an initial pilot study concerned with marital and family members' orientation to "morningness" and "nightness" are presented. Further implications from this work-in-progress are delineated.


A typology of family social environments. A sample of 100 families measured on ten dimensions of their social environments was subjected to cluster analysis to develop an empirically based taxonomy of families. Six distinctive clusters of families were indentified: Expression-Oriented, Structure-Oriented, Independence-Oriented, Achievement-Oriented, Moral/Religious-Oriented and Conflict-Oriented. The clusters showed systematic differences in background characteristics such as size, ethnic minority composition, drinking patterns, and family disturbance and incongruence. Some evidence that certain clusters of families are composed of different sub-clusters was presented. An empirically derived taxonomy of the social environments of families may help to understand how different family environments are linked to different family outcomes.


Designed experience: a multiple, goal-directed training program in family therapy. A family-therapy training program, one of three main branches of the "Boston model," is described in detail. Salient features of the program include planned integration of a multiplicity of experiential and cognitive learning modes; grounding in a unified, theoretical framework that is neither eclectic nor limited to a single school of thought; focus on nonpathological process in families; and systematic structuring in terms of specific, articulated, training objectives. The goal-directed design process by which training units are developed is explained.


Depression and marital interaction.

Depression and marital interaction. A family-systems model of depression is presented and discussed. In this model, the intrapsychic concept of cognitive schema and the interpersonal concepts of social stimulation and social reingorcement are integrated within a systems-theory perspective. The effects of positive and negative feedback are delineated, and a concept of depression-triggering and depression-maintaining feedback loops is described. A clinical illustration is utilized to exemplify the theoretical model.


An integrated treatment program for psychogenic pain. The family characteristics associated with the presence of recurrent abdominal pain are identified. The involvement on the pediatrician and the effects of this involvement on the patient, family, and perpetuation of the symptoms are described. A successful therapeutic program combining behavior modification and family therapy is elaborated. Changes in the structure and functioning of the family are vital to the outcome of therapy and the prevention of recurrence of symptoms.


Social networks, support, and coping: an exploratory study. This paper reports a study that investigated the areas of stress, support, and coping, using the structural model of the social network. The social network model is borrowed from sociology and anthropology and is used to describe and quantify not only an individual's immediate family but also all of those with whom the individual has regular contact. By comparing the networks of a sample of "normal" and schizophrenic males, it was possible to identify differences in their relationships to their social networks, in the make-up of the networks themselves, and in the coping styles and recent histories of the subjects. The results suggest, first, that the network model can be used to investigate the larger social system with which individuals interact and, second, that it may be a valuable approach to the expansion of family research.


The consultation-demonstration interview. In recent years the consultation-demonstration interview, in which a family is interviewed before a workshop, has become increasingly prevalent. While this method of presenting the therapist's style of interviewing can be an exciting and valuable learning experience, it can also lead to a sense of boredom and disappointment. In some instances, the experience can be traumatic, especially for the family and the guest therapist. Common pitfalls in the organization and planning of the interview are explored, and a number of specific recommendations are made for attempting to maximize the potential in this interview process. Written to both the planner and the leader of the workshop in family therapy, this paper is based on the author's personal experience.


The use of teaching stories in conjoint family therapy. Two general factors have been singled out as being held in common by all types of psychotherapy: an educational, rational factor (often called "content") and a factor operative in the relationship between the therapist and his patient (often called "process"). In the field of family therapy, the non-educational aspects of intervention are sometimes presented in the form of "therapeutic, paradoxical communications" (Haley, Bateson, Jackson, Weakland) or the 'therapy of the absurd" (Whitaker, Malone). In the present paper, I wish to present a form of therapeutic communication, the teaching story, that embodies a unique mixture of both the educational and the paradox, or absurd.


"Nonlabeled" family interaction: prelimiary report on a prospective study. This paper is a preliminary report on the first year of a two-year exploratory, prospective study of psychiatrically "nonlabeled" families. The project studies families from a nonpathology-oriented point of view. It focuses primarily on whole-family interaction as it progresses through time. Because of limited funds, only two families are being studied in this exploratory phase. Nevertheless, the work touches on many issues of a general nature that may be of interest of other researchers. Each family has been interviewed once a month for the past year. The paper outlines: procedural matters, including selection criteria and recruitment; data collection, including interviews, rating scales, and "clinical" discussions; processing of data; preliminary findings, including quantitative and qualitative aspects; and problem areas, including methodological and ethical aspects.


[Effect of lithium chloride on bioelectric activity of the cortex and various subcortical structures of rabbit brain]. In a dose of 100 mg/kg and with intravenous administration to rabbits lithium chloride produces a depressing influence on the spontaneous bioelectric activity of the cerebral cortex and its subcortical formations, which extends from the cortex to subcortical structures. The compound brings down the electric excitability of the hippocampus, caudate nucleus, tonsils, reticular formation of the mesensephalic segment and of the thalamus, while in a dose of 300 mg/kg it increases the excitability of the motor cortex. No correlation between the lithium chloride induced electroencephalographic changes in the cerebral structures, on the one hand, and the content therein of biogenic amines and accumulation of lithium ions, on the other, was revealed.


[Inhibition of the activity of human serum cholinesterase by aminoalkyl benzenesulfonyl fluorides]. Aminoalkyl benzenesulfonyl fluorides, like organophosphates, act as irreversible inhibitors of serine proteinases by splitting off hydrogen fluoride to form an enzyme-inhibitor complex, stable in the physiological pH region. Several of these compounds are characterized by a higher rate of inhibition when trypsin is used and the second order rate constants are compared with those of organophosphates. On the other hand, upon inhibition of human serum cholinesterase by DFP and 4-nitrophenyl diethyl phosphate, some orders of magnitude higher than that of benzenesul fonyl fluorydes are observed. As shown by an oral toxicity study in mice similar differences exist with respect to LD50 values.


[Relationship between chemical structure and anti-arrhythmic effect of ethmosine analogs]. The relationship between the chemical structure and antiarrhthmic action in the series of 10-actlaminopropionyl phenothiazine derivatives with different urethan groups in the second position of the phenothiazine cycle (methy, ethyl and isobutyl) was studied. Subject to investigation were also aetmozine isomers containing ethyl-carbaminate in the first, third and fourth position, as well as compounds containing aminopropionyl residues in the tenth and trifluoromethyl group or bromine in the second position. The available data indicated that the antiarrhythmic action of 10-acylamino-derivatives of phenothiazine depends not only on the structure of the side chain and substitution of hydrogen in the second position of the phenothiazine nucleus, but also upon the position of the urethan group in the phenothiazine cycle. Moving ethyl-carbaminate to the first, third and fourth positions results in the fall of the anti-arrhythmic action. The absence of any relation between the length of the urethan radical and the effect produced by the substance was also shown. By substituting the methyl or isobutyl radicals for the ethyl one the antiarrthythmic action of the substances declines.


[Effect of phenobarbital, morphine and ethanol on the physico-chemical properties of erythrocyte membranes]. The effect of narcotics--phenobarbital, morphine and ethanol on the hemolysis of erythrocytes in a hypotonic solution was studied. The narcotics under study are shown to influence the stability of the erythrocytes membranes. Behind the mechanism of stabilization apparrently lies the action of the said substances on the critical hemolytic volume of the cells. A common nature of some mechanisms underlying the action of phenobarbital, morphine and ethanol on the erythrocytes membranes is suggested.


[Elimination of products of fluoracizine by the gastrointestinal tract in animals of different species]. A study on elimination of phthoracizine metabolites with feces of different animal species evidenced that bulk of its transformation products with an intact side-chain was contained in the feces of rats. In the feces of mice they are found in much smaller amount, while in rabbits they are practically untracable. The phthoracizine transformation products devoid of the side-chain are demonstrable both in rats and in other animal species either as traces or not definable at all. These phenomena are, apparently, to be attributed to a different ability of eliminating the phthoracizine biotransformation products with bile by different animal species, which, among other factors. is determined by the molecular weight of individual metabolites.


[Effect of no-shpa, halidor, dibazol and euphylline on the fibrinogen content and fibrinolytic activity of blood]. With a single intravenous administration to albino rats of both sexes of nospanum and halidor in a dose of 2 mg/kg and dibazol--in 1 mg/kg produce activation of fibrinolysis, while euphylline in a dose of 12 mg/kg has no effect on this process. A protracted introduction by the subcuataneous route of halidor and nospanum in a dose of 10 mg/kg, of dibazol--in 5 mg/kg and of euphylline intramuscularly in a dose of 24 mg/kg depresses in animals the activity of the proteolytic process. It was found that in vitro nospanum, halidor and dibazol accelerate fibrinolysis, whereas the presence of euphylline in the blood plasma deccelerates this process.


[Effect of lithium chloride on kidney function in rats]. Test staged on rats have brought evidence that lithium chloride acts damagingly on all parts of the nephron, inhibiting, first of all, the processes of filtration and then of secretion and reabsorption. Polyuria arising under the effect of lithium is caused by reduced reabsorption of water in the tubules and anuria--by depression of the glomerular filtration.


[Local-anesthetic activity of l-aminoacetyl-2, 3-dihydroindole derivatives]. 1-(N-piperidine-acetyl)-2,3-dihydroindoles display high activity in infiltration and conduction anestheia, exceeding that of trimecaine. N-alkylaminoacetyl-indolines are moderately active, while N-morpholine and N-indolylacetyl-indolines are practically inactive when employed in the given types of local anesthesia. All the N-substituted aminoacetyl-indolines are little active in terminal anesthesia.