Overview of some aspects of occurrence, formation and analysis of nitrosamines. This review principally addresses a number of aspects of the occurrence and formation of the nitrosamines, highlighting principal areas of potential concern ranging from the spectrum of nitrosatable moieties found in the environment (e.g., secondary and tertiary amines, quaternary ammonium compounds, ureas, carbamates and guanidines), specific examples of nitrosamines found in food, alcoholic beverages, feed (and their significance for carcinogenesis bioassays), air and water. The factors influencing in vitro and in vivo nitrosation and the evidence for the latter in man are also discussed. Additionally, germane areas of the analysis of nitrosamines are reviewed with a focus on the major areas of concern and requirements of extreme sensitivity and selectivity in addition to the problems of artifacts in the analytical procedures.


Heparin: an old drug with a new paradigm. Recent studies have shown that heparin is a biochemical representative of a distinct class of compounds known as linear anionic polyelectrolytes. Members of this class are mixtures of individual highly negatively charged chains that show a wide spectrum of specific reactions with biologically active proteins. Upon administration, heparin chains enter a cellular pool and effectively prevent thrombosis by increasing the electronegative potential of the vessel wall. Anticoagulant activity is an unusual feature of a few heparin chains and appears to play a minor role in many clinical uses and in physiological and pathological responses.


Antibodies to sporozoites: their frequent occurrence in individuals living in an area of hyperendemic malaria. Serum samples from 158 West Africans were tested for antibodies against sporozoites, the vector stage of the malaria parasite. Antibodies specific for Plasmodium falciparum sporozoites were detected by means of the circumsporozoite precipitation assay and indirect immunofluorescence. More than 90 percent of the serum samples from adults gave positive immunofluorescent reactions against falciparum sporozoites, whereas most of the samples from children gave low or negative reactions.


Calcium dependence of toxic cell death: a final common pathway. Primary cultures of adult rat hepatocytes were treated in the presence or absence of extracellular calcium with ten different membrane-active toxins. In all cases more than half the cells were killed in 1 to 6 hours in the presence but not in the absence of extracellular calcium. An effect of calcium on the primary mechanism of membrane injury by any of the agents cannot be implicated. Viability, as determined by trypan blue exclusion correlated well with other indices of viability such as plating efficiency and the hydrolysis of fluorescein diacetate. It is concluded that the cells are killed by processes that involve at least two steps. In each type of injury, disruption of the integrity of the plasma membrane by widely differing mechanisms is followed by a common functional consequence involving extracellular calcium, and most likely representing an influx of calcium across the damaged plasma membrane and down a steep concentration gradient. This later step represents, or at least initiates, a final common pathway for the toxic death of these cells.


Rapid killing of single neurons by irradiation of intracellularly injected dye. A simple technique for rapidly killing all or part of single neurons consists of filling the cell with Lucifer Yellow CH and irradiating all or part of it with intense blue light. Such treatment kills the irradiated part of the cell within a few minutes. Adjacent cells are not affected.


Rheumatic syndromes in endocrine disease. It is not widely appreciated that endocrine disease may present primarily as rheumatic syndromes, sometimes spectacular in onset, more commonly insidious and subtle, making their true recognition difficult. The underlying hormonal, biochemical, and metabolic events have understandable reflection in the structure and function of bone, joint, and muscle.


Pharmacology of the neonate.

Pharmacology of the neonate. Drugs need not necessarily be administered directly to the neonate, but may reach the newborn infant as a result of drug administration to the mother during gestation, at parturition, or during the course of lactation. The processes of absorption, distribution, metabolism and excretion of drugs in the neonate are discussed. Differences between the neonate and the adult in this regard are outlined. The pharmacology and pharmacokinetics of specific drugs to which the neonate may be exposed are discussed.


Rudolf Virchow and Heinrich Schliemann. An essay on the friendship of two great men. This essay briefly relates the great friendship between two great men whose origins and curricula vitae differed exceedingly, but whose common scientific interest in archaeology was to unite them closely. Virchow, a medical doctor, and Schliemann, a doctor of science, were able eventually to secure safekeeping for the Trojan treasure discovered by Schliemann, whose contributions to the culture of our Western civilization have not been surpassed. What has happened to the Trojan treasure since the occupation of Berlin is a question still unanswered.


The diabetic foot.

The diabetic foot. Modern thought regarding the pathogenesis, clinical features and management of the 'diabetic foot' is reviewed. The interplay of the triad of ischaemia, neuropathy and infection is emphasized throughout. Management is directed at maintaining or providing a pain-free, working foot.


In defence of ancient bloodletting.

In defence of ancient bloodletting. The ancients used bloodletting extensively in infectious and other diseases. When recent work on iron and bacterial infection is taken into account, it is possible to argue that bloodletting, which reduced plasma iron and transferrin saturation, might have been of value in increasing resistance to infection by bacteria or plasmodia. Galen's bloodletting methods are summarized, and their probable effect on plasma iron is considered. The ancient physicans who had no specific remedies for infection whatsoever, may well have been justified in making responsible use of bloodletting, both for the treatment and for the prophylaxis of infectious disease.


Chlamydia trachomatis-induced urethritis in female partners of men with nongonococcal urethritis. The rate of isolation of Chlamydia trachomatis from cervical and urethral specimens from 99 culture-positive female partners of men with nongonococcal urethritis who were attending a gynecological outpatient clinic was correlated with the clinical status of the women. The agent was recovered from both sites in 46 women, from the cervix only in 28, and from the urethra only in 25 women. Urethral symptoms were reported by 38 (54%) of those with positive urethral cultures, as compared with six (21%) of those with positive cervical cultures only (P less than 0.01). Significant bacteriuria was found in only three patients with urethral symptoms; two of them had negative urethral cultures for C. trachomatis. Frequencies of cervicitis, rises in titer of antibody, and geometric mean titers of immunofluorescent antibody to C. trachomatis did not differ significantly among the three groups.


A solid-phase radioimmunoassay for the detection of antibodies to Treponema pallidum. A solid-phase radioimmunoassay (RIA) procedure was developed for the detection of antibodies to Treponema pallidum. The source of antigen used was T. pallidum (Nichols strain), which was specifically bound to the solid phase by use of rabbit antibody to T. pallidum (Nichols strain). The solid-phase system for this RIA test is the well of a microtiter plate. Preliminary data suggest that the RIA procedure is sensitive and specific and might be a useful addition to the research tools and serologic tests used in the study and diagnosis of syphilis.


Comparison of ampicillin plus probenecid with amoxicillin plus probenecid for treatment of uncomplicated gonorrhea. The efficacy of 3 g of amoxicillin plus 1 g of probenecid was compared with the efficacy of 3.5 g of ampicillin plus 1 g of probenecid for the treatment of uncomplicated gonorrhea. In a clinical trial no therapeutic failure was seen among 60 patients who were treated with the former regimen. The combination of ampicillin plus probenecid resulted in two therapeutic failures (3.6%) among the 55 patients given it. It was concluded that amoxicillin plus probenecid is as effective as ampicillin plus probenecid for the treatment of uncomplicated gonorrhea.


Lung bacterial clearance following pulmonary contusion. Bacterial infections frequently,complicate pulmonary contusion and are the leading cause of death in such patients. This study evaluated the effects of pulmonary contusion alone and contusion associated with other factors on the ability to clear aerosolized bacteria from the lung. Lung bacterial clearance of Staphylococcus aureus and Klebsiella pneumoniae was studied in animals with isolated pulmonary contusion, or contusion associated with blood loss, rapid crystalloid infusion, or steroid administration. An isolated pulmonary contusion produced no impairment of the ability of the contused lung to clear either gram-negative or gram-positive organisms. The addition of acute blood loss and crystalloid infusion resulted in decreased clearance from the contused lung; steroid administration caused a marked depression in lung bacterial clearance from the noninjured lung as well. The canine model described allowed for study of regional differences in bacterial clearance. The data presented support several conclusions; (1) the contused lung is not more susceptible to bacterial infection than the normal lung: (2) acute blood loss renders the contused lung less able to clear bacteria; (3) crystalloid infusion markedly depresses lung bacterial clearance; and (4) steroids have a deleterious antibacterial effect on both contused and noncontused lungs.


Splenorrhaphy: changing concepts for the traumatized spleen. Established doctrine dictating splenectomy for the traumatized spleen has come under considerable critism since the report of fatal postsplenectomy sepsis by King and Shumacher in 1952. With expanding knowledge of immunologic and physiologic function, splenectomized persons have been proven at risk in different areas, but the most important impetus for splenic preservation has been the observation of overwhelming postsplenectomy sepsis. Several reports have confirmed this concern, with a documented increase in morbidity and death of splenectomized patients of 50 to 200 times the normal. Successful results with surgical repair of traumatized spleens have been reported, experimentally and clinically proving excellent healing capabilities. It is not uncommon to frequently find little if any active bleeding with such injuries; in fact, even significant bleeding can be controlled with splenic salvage. Several different techniques to accomplish this have been reported. These are reviewed, two new successful and previously unreported techniques are outlined in detail, and statistical information supporting the use of these techniques is presented.


Detection of the K99 antigen of Escherichia coli in calf faeces by enzyme-linked immunosorbent assay (ELISA). An enzyme-linked immunosorbent assay (ELISA) is presented for the detection of the K99 antigen of Escherichia coli in calf faeces. False-positive reactions were not observed with K99-negative strains and with several viral antigens. Only bovine coronavirus caused slight positive reactions which could be eliminated by a blocking test. As compared with the conventional procedure for the detection of the K99 antigen, ELISA seemed to be a least as sensitive and had the advantage that samples could be stored at --20 degrees C before testing. In addition many samples could be handled at the same time and the results became available quickly. By carrying out the assay as a blocking test, specific antibody against K99 in serum or colostrum could be detected and titrated.


The immune response to vasectomy and its relation to the HLA system. We examined 188 men who had undergone vasectomy up to 6 years previously and, for comparative purposes, 100 men who were about to undergo the operation. Blood specimens were available from a total of 283 men. Sperm antibody assays using immunofluorescence, microagglutination, and microimmobilization confirmed that the prevalance of several types of antibody is higher after vasectomy. Immobilizing and agglutinating antibodies appeared to be the most important. Trends in antibody prevalence according to the time after the operation were analyzed. Screening against lymphocytes and lymphoid lines showed that the anti-sperm activity of era was not related to anti-HLA or anti-Ia activity. Associations were examined between different types of sperm antibody, and between these antibodies and autoantibodies to other antigens. When antibody prevalence was studied in relation to HLA types, the HLA antigen A28 was found to be strongly associated with production of head agglutinating antibody (and immobilizing and immunofluorescent equatorial antibodies) after vasectomy. This is one of the first clear-cut examples of antibody production associated with the HLA system.


Effects of desensitization on different kinds of in vitro PPD-induced response of lymph node lymphocytes from tuberculin-sensitive guinea pigs. Guinea pigs rendered hypersensitive to tuberculin 2 to 3 weeks (early stage) or 10 to 14 weeks (late stage) after sensitization with complete Freund's adjuvant could be completely desensitized by a single or double injections of a sufficient amount of PPD (purified protein derivative). Lymph node cells from such desensitized animals 48 to 72 hr after the challenge showed a considerable reduction of the ability to produce blastogenic factor and skin reactive factor upon PPD-stimulation, whereas the macrophage migration inhibitory factor activity remained still unaffected. As regards antigen-induced 3H-thymidine incorporation in vitro, lymph node cells from animals desensitized in the late stage after sensitization showed no substantial reduction in the degree of enhanced DNA synthesis upon PPD-stimulation, although the desensitization in the early stage resulted in a significant loss of this activity. These results suggest the possibility that desensitizing challenge does not bring about a uniform and regular effect on every lymphocyte subpopulations relevant to different functions and, in addition, indicate that there are some exceptions to the compartmentalization concept of antigen-reactive lymphocytes.


Prolonged survival time of allogeneic skin grafts in host pretreated with somatic cell hybrids and prednisolone. By applying somatic cell hybrids to transplantation immunity, the prolongation of survival time of mouse skin allografts was investigated. The hybrid cells (LJ) were made by cell fusion between L cells derived from C3H/He mouse and JLS-V9 cells derived from BALB/c mouse with UV-irradiated Sendai viruses. Skin grafts from female (C3H/He . JmsX BALB/c . Slc) F1 donors were transplanted to male BALB/c . Slc. The survival of the transplant in BALB/c pretreated with the LJ cells and prednisolone showed a significant prolongation, compared with that in animals pretreated with only prednisolone or the LJ cells. The mean survival time and standard deviation of the grafts in mice injected with 1 X 10(5) LJ cells i.v. 4 days before the grafting, and subsequently treated with prednisolone 50 mg/kg i.p. 1 day before and at the time of the grafting were 17.3 +/- 2.2 days. Controls were 9.2 +/- 0.4 days. The mechanisms of prolongation of skin grafts were discussed in terms of cell-mediated immunity and humoral factors. Somatic cell hybrids are useful, not only for inducing immunological enhancement, but also for studying the function of major histocompatibility antigens in cellular immunity and can be applied to clinical organ transplantation.


[Impression taking in the edentulous mouth with special regard to closed mouth impression with simultaneous determination of the jaw relation]. In view of the increase in mean life expectancy and in the need for care in the gerostomatological sphere, more attention must be paid to such methods which optimize the construction of full dentures from the anatomico-pathological viewpoint, exert a rationalizing effect, and are likely to improve the success rate in the treatment of edentulous patients. The method of closed mouth impression and simultaneous determination of the jaw relation refers to well-proved principles of impression making, considers new findings concerning the determination of the jaw relation, incorporates modern materials and instruments, and forms the system character of clinico-technological measures.


Effects of HLA-A and B matching on success of cadaver grafts at a single center. The effect of HLA matching on the success of cadaver renal allografts was examined utilizing computerized multifactoral analysis in a large single renal transplant center. One hundred ninety-one consecutive cadaver transplant recipients (from January 1968 to August 1975) were followed from 2 1/2 to 9 years. During the period surveyed we had not utilized the tissue typing results in a prospective manner to select recipients. The data presented attest to the beneficial effect of utilizing well matched cadaver grafts. HLA matching of two or more antigens results in significantly superior 2- and 4-year patient survival and graft function compared to results for cadaver kidneys matched for zero and one HLA antigen. The results are not greatly influenced when age, sex, or time of transplant are controlled. The importance of tissue typing is particularly clear if higher doses of antilymphoblast globulin (ALG) are administered. The risk inherent in advancing recipient age is markedly reduced by better transplant matches. Graft function is also superior in the diabetic patients receiving good HLA matches, but there are too few patients to make these results statistically significant.


Cross-reactive antibodies against human cultured B cells and bovine erythrocytes in human renal transplantation sera. Sera of 58 recipients of renal allografts were studied for the presence of antibodies against cell cultures of human B lymphoid cell lines (B-LCL) and bovine erythrocytes (BRBC). Cytotoxic anti-B-LCL antibodies were found in 13% of the sera from recipients with the grafts and in 67% of the sera obtained after removal of the rejected grafts. Most of these sera also contained BRBC lysins of high titers. Absorption studies showed that the anti-B-LCL antibodies are directed against antigens shared by BRBC and that they can be absorbed with corresponding graft tissues. The specificity of BRBC lysins found in some of the transplantation sera was shown to be similar to that of Hanutziu-Deicher antibodies.


Privileged status of the subcutaneous site for skin allografts in rats. Evidence is presented that in rats the subcutaneous site can extend privilege to both major histocompatibility complex (MHC)-incompatible (FI X DA)F1 leads to FI and MHC-compatible LEW leads to FI skin allografts, approximately doubling the median survival time of similar grafts transplanted orthotopically. Unlike graft dosage, "gene" dosage was an important variable in that grafts from (FI X DA)F1 donors significantly outlived those from DA strain donors. Prior splenectomy of the hosts did not prejudice the capacity of their subcutaneous sites to extend privilege. It was found that the hemagglutinin response incited by subcutaneous grafts was significantly delayed compared with that evoked by similar grafts transplanted orthotopically or intraperitoneally. This observation, coupled with our inability to demonstrate the passage of India ink to regional lymph nodes after its injection into the dermis of established subcutaneous grafts of syngenic skin, is consistent with the concept that poor endowment of the subcutaneous milieu with both blood and lymph vessels is the principal factor underlying its hospitality to allografts.


Immune responses to organ allografts. II. Decreased B cell responses to cardiac allografts in rats pretreated with enhancing, suppressor cell, or T lymphocyte depletion protocols. Primarily vascularized LBN cardiac allografts transplanted to LEW rats are rejected 6 to 8 days after transplantation. Immunoperoxidase stains for cells producing immunoglobulin (Ig) demonstrate a proliferation of Ig-containing immunoblasts in the splenic red pulp (RP) and peripheral periarterial sheath (PAS) within 2 days after transplantation. These immunoblasts differentiate into plasma cells that triple the RP volume by the time of rejection. By 14 days, the plasma cells are replaced by mitotically active large and small lymphocytes with no demonstrable cytoplasmic Ig. Splenic Ig production is followed by a venous vasculitis in the graft and by the appearance of circulating cytotoxic antibodies 5 days after grafting. Three biological methods of prolonging cardiac graft survival were found to derange this sequence of immunological reactions at different stages. Enhancement by antigen and antibody pretreatment of the recipient elicited a premature production of Ig that subsided and was not reinitiated by cardiac transplantation. Transfer of suppression with thymocytes from enhanced cardiac recipients temporarily inhibited differentiation of splenic B cells into immunoblasts and plasma cells. T cell depletion by thymectomy, irradiation, and bone marrow reconstitution also decreased the plasma cell response, possibly by removing helper cells required to switch IgM production to IgG. These studies reemphasize the importance of Ig production in the complex interaction of immune reactions leading to acute rejection of organ transplants.


Effect of trimethoprim-sulfamethoxazole on hematological recovery after total body irradiation and autologous marrow infusion in dogs. To test the effect of the combination of trimethoprim-sulfamethoxazole (TMP-SMX) on hematological recovery after bone marrow transplantation, dogs were conditioned with 1,200 R total body irradiation and then infused with autologous marrow. Twenty dogs were given TMP-SMX at doses equivalent to 10, 20, or 40 mg TMP/kg/day beginning on the day of marrow infusion and continued until the granulocyte count reached 10(3)/mul; in addition, one-half of the dogs received methotrexate, 0.4 mg/kg on days 1, 3, 6, and 11 and then weekly until termination of the study. Granulocyte and platelet changes were compared to those of dogs given 1,200 R, autologous marrow infusion, and no TMP-SMX. Dogs given 10 and 20 mg TMP/kg/day had normal granulocyte and platelet recovery after irradiation. Dogs given 40 mg TMP/kg/day showed a significant delay in granulocyte recovery and mildly delayed platelet recovery. This suggests that TMP-SMX in prophylactic doses (5 mg TMP/kg/day) can be given safely to human patients immediately after allogeneic marrow transplantation and thus probably prevent even very early cases of Pneumocystis carinii pneumonia, and possibly bacterial infections as well.


5-Fuorouracil cardiotoxicity.

5-Fuorouracil cardiotoxicity. Two cases of 5-fluorouracil cardiotoxicity, resulting in one patient in myocardial infarction, are described. A review of the literature confirms that cardiotoxicity is a rare but genuine complication of 5-fluorouracil treatment; the cardiotoxic effect seems to range from mild angina without persistent electrocardiographic changes to severe myocardial infarction. No factors predictive of this complication were identified. The authors therefore feel it is advisable to stop 5-fluorouracil treatment when precordial pain occurs, even if the ECG (after angina) is normal, since angina can in some cases result in myocardial infarction.


[Determination of auto-antibodies against spermatozoa after vasectomy and epididymectomy by indirect immunofluorescence (author's transl)]. As a result of successful recanalization of the vas deferens, a low pregnancy rate has been observed. The formation of auto-antibodies is considered as cause. In vasectomized and epididymectomized rats, the presence of auto-antibodies against spermatozoa was proven by indirect immunofluorescence. After uni- and/or bilateral obstruction of the vasa, the formation of antibodies against spermatozoa takes place which - after 2 months - proves to be permanent for 9 months, then showing a decreased titre. An animal model is presented suitable for the study of immunological processes in unilateral gonadal diseases.


[Twenty years of urology in a children's hospital (1954--1974). Together with an epicrisis of 101 children with bilateral anomalies of the urinary passages, operated on in the first year of life (author's transl)]. This work encompasses a 20-year period, during which a urologist spent an important part of his time in a children's hospital, because of his conviction that attemps at effective treatment of urinary passage anomalies in childhood have a chance only when treatment is begun as early as possible. A report is presented on 101 children with bilateral, severe urinary passage anomalies, who were operated on in the first year of life, with the goal of early, total correction. The following experiences are of general significance: 1. The earlier the symptoms -- in 90% of cases, pyuria -- the more severe are the findings. -- 2. Males are primarily affected, here at a ratio of 7:3. As a result, pyuria in infants must be explained urologically, particularly when it occurs in males. -- This report is a plea for early, total correction and against periodic urinary drainage. Results show a 50% decrease in infections, flow disturbances, and biochemical changes, as well as a postoperative burst of growth also in 50% of cases. Cinematographic examinations show normal peristalsis even after skeletization and drastic reduction of a megaureter. The mortality was 9%, in the first year of life, 6%. Surprisingly, the result was not influenced by the presence or absence of reflux, but rather by stigmas and inferior development. Reflux had probably already played its fateful part in this severe bilateral disease, so that antireflux plastic surgery loses its prophylactic value. Compared with reports of experiences with periodic urinary drainage, our aim is to disprove the argument that, in difficult cases, total correction is dangerous: on the contrary, our results are better and coincide with the experiences of Hendren. Although Bischoff did not live to see the results of this work, in retrospect, our results bear out his pioneering concepts and ideas.


Urologic microsurgery--current perspectives: I. Vasovasostomy. Microsurgical procedures are receiving increased attention in urology, and claims of improved results of vasovasostomy performed with operating microscope have been made. This review examines the available results, sometimes conflicting, of both macro- and microsurgical methods of vasovasostomy. The weight of the data leads to the conclusion that improved results of vasovasostomy will occur with the use of the operating microscope regardless of the type of anastomosis performed because increased appreciation of the detail of the small vasal lumen is afforded by optical magnification.


Antireflux ureteroileal anastomosis: experimental technique. A technique for ureteroileal anastomosis with an antireflux extraluminal seromuscular ureteral tunnel was evaluated in 9 dogs. Evidence will be presented to show that this approach is effective in preventing reflux while preserving the integrity of the renal units.


Hemodilution -- new clothes for an anemic emperor. This review deals with the rationale for the use of hemodilution in patients not subjected to open heart surgery. The claim for an optimum of circulatory oxygen transport at 30% hematocrit has been disproved; hemodilution thus simply means acute normovolemic anemia. Accordingly, it generates a cardiovascular strain and particularly jeopardizes cerebral and myocardial oxygen supply. Potentially serious clinical side effects have been reported. Hemodilution should therefore not be carried beyong the lower normal range for the hemoglobin or hematocrit level, i.e. 12--12.5 g% or 35--36%.


Preparation of factor VIII-deficient plasma by immunoadsorption. An immunoadsorbent was prepared by coupling rabbit and human antibodies against human factor VIII to Sepharose CL-2B. The resulting insoluble antibodies completely removed factor VIII and fibrinogen from normal human citrate plasma. Other coagulation factors were satisfactorily recovered in the eluted plasma. Following addition of fibrinogen, the factor VIII-deficient plasma was used for calibration of the one-stage factor VIII assay and compared with the hemophilic plasma. Parallel straight lines were obtained in the log-log plot against VIII:C, indicating that the artificial reagent can be used as a substitute for hemophilic plasma in determination of factor VIII procoagulant activity. The immunoadsorbent can be regenerated and repeatedly used for affinity chromatography binding of factor VIII.


The occurrence of antibody markers of hepatitis B virus infection in an HBsAg-negative blood donor population. Anti HBs, anti-HBc and anti-HBe were tested in blood donors negative for HBsAg by radio- and enzyme-immunoassay. In this population 6.4% of the donors were positive for at least one type of antibody to HBV: 4.0% for anti-HBs, 2.3% for anti-HBc and 4.3% for anti-HBe. Two sera (0.2%) were exclusively positive for anti-HBc, eight sera (2.2%) were weakly positive only for anti-HBe. Further studies of the infectivity of such samples might be of interest.


The influence of ionic strength and incubation time on the sensitivity of methods using papainized red cells. The sensitivity of a combination of various papain methods with normal and low ionic strength (lis) of the serum-cell mixture for the detection of red cell antibodies was tested after varying periods of incubation of the mixture. The mixture was centrifuged before reading when the period of incubation was short. The maximum sensitivity without centrifugation was always reached after a period of 60 min. With a longer incubation the sensitivity decreased. A sensitivity that equalled the maximum sensitivity without centrifugation could be obtained after only 10 min of incubation, if it was followed by a centrifugation before reading. Lis consistently increased the sensitivity of the papain methods, especially after 45--60 min of incubation.


[Insulin metabolism and its interaction with specific cytoplasmic membrane receptors of the liver in alloxan diabetes in rats]. Biosynthesis of insulin, its degradation in liver tissue and binding with specific receptors of cytoplasmic membranes were studied in rats with alloxage diabetes and in normal state. Content of sugar was approximately 372 +/- 25 mg/100 ml of blood in animals, treated with alloxane within 5 days, as compared with 83 +/- 7 mg of sugar per 100 ml of blood in the control group; content of insulin was also decreased in blood plasma to 12.1 +/- +/- 2.0 mU/ml as compared with 49.8 +/- 3.8 mU/ml controls. In rats with alloxane diabetes biosynthesis of insulin was increased, its degradation in liver tissue was lowered and binding of insulin with specific receptors of liver c itoplasmic membranes was elevated. The decreased degradation of the hormone together with deficiency in its formation, even though the rate of its synthesis and binding with receptors were increased, served as a compensatory mechanism due to impairment of a considerable part of beta-cells on baàkground of the alloxane treatment.


HLA, DRW (IA-like) and additional surface antigens expressed on adenoid T and B lymphocytes. Pregnancy sera were found to react differently when screened simultaneously with adenoid and peripheral blood lymphocytes (PBL) obtained from the same individual. Some of the reactions were attributed to the higher sensitivity of adenoid lymphocytes to a low titer HLA or Ia antibody, while others were shown to be due to the expression of DRw (Ia-like) antigens on both T and B lymphocytes separated from adenoids. Positive reactions specific to adenoid lymphocytes, or manifested only following anti-beta2-microglobulin (a-beta2-m) treatment, suggest the presence of antigens other than HLA or Ia on the cell membrane. Unmasking of antigenic sites by the a-beta2-m capping process and rearrangement of the membrane structure may also contribute to the observed phenomena.


Role of blood transfusions and pregnancies in kidney transplantation. A retrospective study in 71 cadaver renal transplant patients showed a significantly better 2-year graft survival rate (62%) in patients who received pretransplant transfusions or who were parous than in nontransfused patients or patients who have not been pregnant (29%). The beneficial influence of blood transfusion and of pregnancy is thus confirmed. An additive effect of blood transfuion and pregnancy is suggested by the results of this study.


Evaluation of the 'Mason' (continuous-thaw-siphon) method for cryoprecipitate production. A comparison was made of the factor VIII recovery in cryoprecipitate made by the continuous-thaw-siphon technique of Mason [1], by our routine method of overnight thawing at 4 degrees C and by a fast-thaw method. The siphon method resulted in a mean recovery of 71% of the factor VIII. This is at least double the yield obtained by the routine method and could not be solely attributed to the faster processing as cryoprecipitate prepared by the fast-thaw method gave a factor VIII yield of 53%, which was significantly less than the Mason product. This product also contained increased amounts of factor VIII-related antigen and fibrinogen. Characterisation of the thaw-siphon cryoprecipitate factor VII by gel filtration, electrophoretic mobility, stability and measurement of isoagglutinin titre did not reveal any significant qualitative differences from cryoprecipitate produced by other methods.


[Principles of differential immunodiagnostics in tuberculosis and other pulmonary diseases (author's transl)]. When differential diagnostics between tuberculosis, sarcoidosis, bronchial carcinoma and non-specific pulmonary diseases is not possible with clinical and laboratory methods, diagnosis may be often put by the aid of immunological methods. Differential diagnostics, usually, has not to delimit all these diseases one from another. In most cases it is necessary to differ only between two of these diseases, tuberculosis versus sarcoidosis, tuberculosis or bronchial carcinoma, tuberculosis or non-specific lung disease. By the aid of antibody determination (against streptococci, staphylococci, and pneumococci), determination of Ig and of immunological tests patterns of values for differential diagnostics between these groups of diseases can be elaborated and are shown in this paper.


[Animal experiments on the detection of an exposure to "chemical mace" (author's transl)]. To answer the question whether a negative result of gas chromatographic blood analysis for components of chemical mace proves that no or at most only slight tear gas exposure can have occurred, animal experiments were carried out. In the blood of 10 guinea pigs, which were exposed to the contents of chemical mace for 1--6 h, the solvants 1,1,2-trichloro-1,2,2-trifluorethane (freon 113) and 1,1,1-trichloroethane could easily be detected--even 23 h after the end of exposure or after a storage of the blood samples for 18 weeks--whereas the lacrimator chloracetophenone (CN) could not be found at all. In vitro experiments showed that CN relatively quickly reacts with components of blood. Therefore, blood samples should be analyzed for CN after withdrawal as soon as possible. In case of inhalation of the contents of chemical mace, i.e., after the comparatively mildest form of CN application, most probably no traces of the lacrimator at all can pass into the blood due to the quick reaction of CN with proteins of the respiratory surface of the lung.


[A screening radioimmunoassay for 1,4-benzodiazepines in human blood, serum, and urine using anti-oxazepam-hemisuccinate-antibodies (author's transl)]. A simple and specific radioimmunoassay (RIA) was developed for the determination of oxazepam and other 1,4-benzodiazepines in human blood serum and urine (e.g., diazepam, desmethyldiazepam, chlorazepate). For serum a 1:10 dilution, for urine a 1:100 dilution is recommended. Blood and hemolyzed samples need prior extraction by Amberlite XAD-2. The antisera were raised by immunizing "White New Zealand"-rabbits with an oxazepam-3-hemisuccinate bovine serum albumin conjugate. Using 0.1 ml serum dilution the sensitivity is 0.01 mg/l per tube. Especially higher concentrations show a tendency toward underestimation. Being not limited to a single 1,4-benzodiazepine derivative, the specificity of the antisera is also suitable for a screening analysis. Compared to thin-layer chromatographic analysis of urine this assay shows improved sensitivity (0.05--0.1 mg/l in 0.1 ml of a 1:100 dilution = 1 microliter of urine). For forensic investigations, an analysis in the sequence of urine-RIA, blood/serum-RIA, blood/serum-"electron-capture"-gas-liquid chromatography (ECD-GLC) seems to be a helpful approach. Blood levels of diazepam and desmethyldiazepam determined by RIA and GLC after extraction are in satisfactory agreement.


Circadian rhythms: influences of internal and external factors on the period measured in constant conditions. The article reviews most of the data available on the period tau of freerunning circadian rhythms, measured in constant conditions. Emphasis is placed on the effects of light intensity and ambient temperature on tau, with references to influences of other external as well as internal factors. In the introduction, examples are given of spontaneous and induced variations in tau and its dependence on the experimental history. The discussion concentrates largely on results obtained from arthropods and vertebrates.


[System for cultivation of bacteria to follow up gas production (author's transl)]. The construction, workwise and handling of a system for cultivation of bacteria to follow up gas production is described.


[Standardization of measuring technique and documentation in traumatology (author's transl)]. Standardized clinical measuring methods, development of uniform measuring instruments, standardization of the measuring technique have internationally been accepted. This covers especially the measurement of length, girth, distance and joint mobility as well as their recording.


[Radiation-borne changes to vaginal and portio epithelium (author's transl)]. Radiotherapy of cervix carcinoma may cause radiation-borne reactive cell changes to epithelial cells of the vagina and portio which are sizeable but harmless. However, postradiation dysplasia with damage to the DNA and RNA is a genuine dysplasia and may be a precancerous condition. It is cytologically characterised by impairment of the nucleocytoplasmatic ratio as well as by hyperchromia and heterochromia of nuclei. Statistically secured correlation with recurrent carcinomas was established only for severe types with aneuploid DNA in the nuclei.


[Bacteriological aspects of trichomonal vaginitis (author's transl)]. An analysis was made of the vaginal flora of 25 gynaecological patients with acute trichomomal vaginitis, with the view to elucidating the bacteriological situation. Eighty-four isolates, an average of 3.4 per patient, were taken and included a wide range of aerobic and anaerobic bacteria. - Obligate anaerobic species, such as bacteriodes and peptostreptococci, with susceptibility to metronidazole were among the predominant pathogens. - The differentiated susceptibility of the most common bacteria to antibiotics may yield information useful to therapy in the case of aggravated infection.


[Applicability of ultrasonic B-scan diagnosis to localisation of intra-uterine contraceptive devices (author's transl)]. The types Dana super and Copper T intra-uterine devices (IUD) were reliably localised by ultrasonic B-scanning in 100 patients. Five dislocalisations were recorded and one erroneous interpretation in a case of uterus myomatosus. The method was found to be applicable to screening test and is recommended particularly for the following cases: clinically undetectable thread, following insertion, before removal of IUD, and in early pregnancy by the tenth gestational week.


[Recurrent Sonne dysentery morbidity caused by Shigella of varying enzymatic types]. The proportion of repeated cases of dysentery caused by Sh. sonnei does not exceed 3.59% of the total number of bacteriologically confirmed cases of this infection. The frequency of reinfection depended on the enzymatic type of the causative agent. The rarest cases of reinfection were those occurring after the primary infection with Sh. sonnei, biochemical type 2, whereas the most frequent after the primary infection with Sh. sonnei, type 3. Reinfection with heterologous Sh. sonnei was registered mostly 6-12 months after the primary infection, and with homologous Sh. sonnei after a 1 year and later.


[Evaluation of the state of the nonspecific resistance of the body in children in an organized collective]. Nonspecific body resistance was evaluated by 2 methods: the surface autoflora of the skin and the degree of autoimmune reaction were determined. An increase in the number of microorganisms in the autoflora (more than 40 colonies on the impression) and the number of cells secreting antibodies against autoerythrocytes suggested a decrease in body resistance against bacterial and viral infections (increased morbidity rate for respiratory and pyoinflammatory infections). The above methods make it possible to detect the weakest children in closed institutions and to carry out observation of such children with the implementation of the necessary prophylactic measures.


[Comparative study of modifications in the immunoperoxidase and immunofluorescent methods of detecting human tissue immunoglobulins]. The comparison of the data obtained by using different modifications of the immunoperoxidase and immunofluorescent methods for detecting immunoglobulins in intestinal tissues was made. The direct immunoperoxidase method was shown to allow the quantitative study of immunoglobulin-containing cells. The direct immunoperidase method was found to be technically simpler, but the indirect and complex peroxidase-antiperoxidase methods proved to be more sensitive.


[Blocking action of the soluble H-2 antigens and H-2 antibody isolated by various methods and mouse immune lymphocytes]. The treatment of tumour and lymphoid cells of mice with 3M KC1 solution having high ionic strength, nonionic detergent and by subsequent freeze-thawing resulted in obtaining serologically active H-2 antigen preparation capable of specifically blocking the cytotoxicity of H-2 antisera. The antigenic activity of the preparations thus obtained depended on the source from which they were isolated (spleen cells and their membrane fragments proved to be the best source), on the degree of maturity of tumor cells and the degree of purification of the preparation, as well as on the methods of solubilization. The blocking action of soluble H-2 antigens on the cytotoxicity of immune lymphocytes depended on the method used for isslating these antigens. The interaction of immune lymphocytes and H-2 antisera with soluble antigens was probably effected by different mechanisms.


[Susceptibility and sensitivity of the Siberian lemming and Middendorff's vole to leptospirae of the grippotyphosa serogroup]. Siberian lemmings and Middendorf's voles were found to be susceptible to infection caused by Leptospira of the Grippotyphosa serogroup after the intraperitoneal injection of Leptospira culture, the application of the culture or infected urine to the skin, as well as after Leptospira-carrying animals were placed together with the animals to be infected. The infectious sensitivity of these animals to Leptospira was not high: leptospiruria was observed for 1-3 weeks; in some of the voles leptospiruria was slightly pronounced, whereas other voles had a great number of Leptospira in urine. Antibodies appeared in the blood on day 5 after infection, and their titers increased till days 61-63. In no case could Leptospira be isolated from the kidneys of the animals killed on days 61-83 of the experiment.


[Seasonal problems of bacterial dysentery in the Dagestan ASSR]. During the period of 1959-1973 bacterial dysentery showed high morbidity rate in Daghestan in all seasons, this tendency existing both in urban and rural areas. The peculiarity of the monthly distribution of dysentery cases, observed all over the repulic, was the shift of the morbidity peak from August to September-October, and in some years even to November; this could be clearly observed from the analysis of the material as a whole and from the analysis of dysentery morbidity rates in rural and urban areas separately. This rise in dysentery morbidity rate in August--September might be due to the reassembling of children at various institutions after their mass return from summer resorts in the country, as well as to thhe influx of new children to crèches and kindergartens. Moreover, as the period of August--September is the bathing and fruit-harvesting season in Daghestan, a rise in morbidity rate in these months was obviously caused by the unsatisfactory level of sanitation and hygiene due to an acute deficiency of water.


[Cell-mediated and humoral immunity in HBS-Ag carriers]. The presence of HBs--Ag in the blood was established in 1.8% of practically healthy persons, in 29.7% of virus hepatitis patients and in 86.0% of serum hepatitis patients. The immunological study of clinically healthy HBs--Ag carriers revealed a statistically significant decrease in the number of T and B lymphocytes and an increased level of serum IgA, IgM and IgG in the blood. Among donors, 7.6% were found to have lymphocytes sensitized to HBs--Ag and 15.4% were found to have lymphocytes sensitized to liver antigen, while for HBs--Ag carriers these data were 62.5% and 50%, respectively.


[Cholesterol synthesis by several strains of Escherichia]. The results of the study of lipids in the media used for growing different Escherichia strains are presented. Donor plasma with carbon-labeled sodium acetate was used as culture medium. Those strains which induced an increase in cholesterol content in the medium after 48-hour incubation were considered cholesterin-synthetizing. During the growth of these strains the radioactive marker became incorporated into the lipids accumulated in the medium: phospholipids, cholesterol, fatty acids. The degree of this incorporation depended on the dose of labeled sodium acetate and the amount of the inoculated culture. Cholesterol-synthetizing activity of Escherichia is characteristic of only freshly isolated strains.


[Effectiveness of oral immunization of white mice with a complex S. typhimurium antigen]. The protective properties of hydroxylamine preparation obtained from a virulent strain of S. typhimurium were studied in experiments with natural infection after a single oral immunization. The new data obtained in these experiments suggest that the treatment of bacteria with hydroxylamine allows to produce the preparation which, when administered orally, has the immunizing dose only 20 times as great as its immunizing dose for subcutaneous administration. The action of gastric juice on hydroxylamine preparation, as well as the duration and specificity of immunity induced by the oral administration of this preparation were studied. The oral administration of some adjuvants was found to make it possible to considerably decrease the effective dose of the vaccine.


[Effects of electric stimulation and destruction of the centrum medianum of the optic thalamus in patients with akinetic forms of parkinsonism]. Results of electrostimulation and destruction of the median centre of the thalamus in 15 patients with parkinsonism and in 7 patients with uncontrollable pain are presented. Reactions of activation and inhibition in the psychoemotional, somatic and vegetosensory spheres in response to the stimulation are described. Data on bioelectrical activity changes in the cortex of the large hemispheres are presented. Special studies of the effect of the median centre destruction on the muscular tone and tremor were carried out. In the akinetic forms of parkinsonism the effect of reactivation after the median centre destruction was found to be of little clinical importance.


Effect of preoperative oral administration of oxytetracycline and neomycin on postoperative infectious complications in cases of cancer coli-recti. A prospective randomized study on the effects of Enterobiotic (oxytetracycline + neomycin) given per os to patients operated upon electively and curatively for carcinoma coli and recti is presented. 75 patients were treated and 66 were controls. A highly significant reduction of peroperative total and Gram-negative bacterial growth from the bowel was registered and a probably significant reduction of anaerobic bacterial growth. In the whole material a highly significant lower incidence of wound sepsis and intra-abdominal infectious complications occurred in the treated group, compared with the control group. This applies also to the resection material, while the difference is of probable significance in the excision group. 13 of 66 patients died, 8 of septic complications, all in the non-treated group. There was no mortality in the pretreated group. The difference between the noninfected and the infected patient groups was significant as regards the preoperative intraluminal total growth of bacteria and the growth of Gram-negative bacteria. The subsequent non-infected patients show a significantly increased number of cultures not showing any growth of bacteria. No negative side effects of Enterobiotic therapy were noted.


Thromboembolism after elective and post-traumatic hip surgery--a controlled prophylactic trial with dextran 70 and low-dose heparin. A prospective randomized controlled study has been undertaken to evaluate two different prophylactic treatments against postoperative thromboembolic complications after hip surgery. Patients with hip fracture (77) and patients undergoing elective hip arthroplasty (213) were separately randomized into one of three groups: control, dextran 70, or low-dose heparin. Deep vein thrombosis was diagnosed in both groups with the 125I-fibrinogen test and pulmonary perfusion defects in the arthroplasty group with a combination of pulmonary X-ray and perfusion scintigraphy. The frequency of thrombosis was significantly higher in untreated hip fracture patients than in untreated arthroplasty patients. In hip fracture patients both treatments significantly reduced the frequency of thrombosis. Only dextran reduced the frequency of major thrombosis and in the heparin group one fatal pulmonary embolism occurred. After elective hip surgery the overall frequency of thrombosis was not influenced by the two treatments, but with dextran 70 thigh thrombi were reduced and with low-dose heparin the frequency of bilateral thrombosis was reduced. Two patients in the control group died of pulmonary embolism, but the frequency of pulmonary perfusion defects was not influenced by the treatment. Bleeding and transfusions were the same in the three groups.


The prophylaxis of septic complications in colo-rectal surgery. A controlled trial of metronidazole and oxytetracycline. The prophylactic effect of systemic metronidazole on infectious complications following elective colo-rectal surgery was compared with the prophylactic effect of oxytetracycline. Allocation to receive metronidazole or oxytetracycline was random. A total of 137 patients were accepted for the trial, 67 receiving metronidazole and 70 oxytetracycline. The numbers of abdominal wound infections, intra-abdominal infections, fever and deaths were few in both groups, and the differences statistically insignificant. Clinically significant side effects of the antimicrobial agents were not observed. The influence of the antimicrobial agents on colonic flora was also studied. No significant difference in the effect on colonic anaerobic flora was demonstrated, whereas the aerobic flora was significantly suppressed by oxytetracycline. It is concluded that systemic metronidazole, although acting solely on the anaerobic flora, is as effective as oxytetracycline in preventing postoperative infectious complications following elective colo-rectal surgery. The prophylactic use of metronidazole is advocated.


Role of phagocytic cells in host defence in relation to trauma--a brief review. Present evidence available support a relationship between phagocytic cell function and survival from various types of trauma, e.g. burn, traumatic shock, and haemorrhage. Both polymorphonuclear phagocytes and mononuclear phagocytes (monocytes and macrophages) participating in the body's host defence are of crucial importance in preventing post-traumatic infections by microorganisms. The role of macrophages constituting the reticuloendothelial system (RES) in relation to trauma is paid special attention in this review. Deficit in a humoral opsonic glycoprotein (alpha 2 SB glycoprotein) important for reticuloendothelial phagocytosis is described in various types of traumatic injuries, and the role of RES in relation to pulmonary insufficiency is finally summarized.


Gonadotropin-release upon intravenous administration of a long-acting analogue of luteinizing hormone-releasing hormone in females with increased plasma-androgens. D-Ser-(TBU)3-EA10-LH-RH, an analogue of luteinizing hormone-releasing hormone (LH-RH) with prolonged action evokes in normal male and female subjects a qualitatively different secretory pattern of LH, as peak levels are reached between 30 and 60 min in males and between 120 and 240 min in females. Females with increased production of adrenal androgens due to congenital adrenal hyperplasia (off substitution therapy; N=8), idiopathic hirsutism (N=1) and adrenocortical carcinoma (N=2) present upon the administration of the LH-RH-analogue with a secretory pattern of LH and FSH which is qualitatively identical with that of normal female subjects, whereas the response of LH in these patients differs from that seen in normal males. Pre-treatment with dexamethasone did not induce any qualitative changes in the secretory response of LH and FSH upon the LH-RH-analogue in patients with increased endogenous production of adrenal androgens. A larger pool and/or a more pronounced de novosynthesis of LH, which apparently is not altered by increased levels of adrenal andorgens, may be the cause of the more pronounced and prolonged increase of LH in female subjects following the administration of the LH-RH-analogue.


Inhibitory effects on gonadotrophin secretion and gonadal function in men during chronic treatment with a potent stimulatory luteinizing hormone-releasing hormone analogue. Long-term treatment with the potent and long-acting stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was given to 4 healthy men to study its effects on pituitary gonadotropin secretion and gonadal function. Five micrograms of the LRH agonist was self-administered sc once daily over 17 weeks. Weekly basal blood samples were obtained for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolacting (PRL) and testosterone. The gonadotrophin responses to the LRH analogue were also determined during the treatment period. LRH tests were performed after treatment. Seminal fluid specimens were collected during and after treatment. A reduction of the basal serum gonadotrophin and testosterone levels were observed during the treatment period. The FSH and LH responses to the analogue were also diminished. After discontinuation of treatment the gonadotrophin and testosterone concentrations returned to pre-treatment levels within a week. The PRL levels and the seminal fluid specimens did not show any significant changes during the study period. The results suggest that chronic treatment with D-Ser(TBU)6-EA10-LRH has an inhibitory effect on the pituitary gonadotrophin secretion in healthy men. It seems likely that the reduced testosterone level is secondary to the diminished gonadotrophin secretion.


Effects of active and passive immunization with LH-RH on gonadotrophin secretion and reproductive function in female rats. In order to get information about the physiological role played by LH-RH in the regulation of tonic and phasic secretion of gonadotrophins, and about the existence of FSH-RH distinct from LH-RH, we attempted to neutralize endogenous LH-RH by passive and active immunization with LH-RH in female rats. Anti-LH-RH serum prevented pre-ovulatory gonadotrophin surges at proestrus and ovulation, and it suppressed gonadotrophin increase induced by oestradiol benzoate or progesterone in ovariectomized rats. Elevated serum gonadotrophin concentrations in long-term ovariectomized rats were lowered by anti-LH-RH serum injection. The decrease in FSH levels was less than that in LH levels. Serum FSH rose without significant changes in serum LH level for 6 h after ovariectomy on pro-oestrus or dioestrus. The post-ovariectomy rise of FSH was not suppressed by the anti-LH-RH serum which was enought to inhibit serum LH to undetectable levels. Active immunization with LH-RH resulted in decreasing LH levels but failed to alter FSH levels in both serum and pituitary. Seven out of 10 rats immunized with LH-RH became constantly di-oestrous. The weights of anterior pituitary, ovary and uterus of the LH-RH immunized rats were significantly smaller than those of BSA immunized controls. Ovaries of LH-RH immunized rats contained few fresh corpora lutea. These results indicate that LH-RH plays a significant role in the control of both plastic and tonic secretion of LH and FSH. The existence of FSH-RH distinct from LH-RH or mechanism which specially controls the basal FSH secretion is indicated.


LH and testosterone release in developing bulls following LH-RH treatment. Effect of gonadectomy and chronic testosterone propionate pre-treatment. LH and testosterone release after LH-RH treatment was studied in male calves from 1 week to 8 months of age. Total LH release, LH peak values and duration of the discharge increased from 1 week to 4 months of age by 406, 453 and 110%, respectively. Significant decreases of 54, 48 and 24% were observed at 6 months of age compared to 4 months of age. This was followed by steep increases in those variables of 344, 129 and 69% at 8 months compared to 4 months. A testosterone response following an LH increase was first seen at 4 months of age when a weak discharge occurred in 2 out of 5 calves. In older calves strong and LH-correlated testosterone responses were always observed. In a second experiment the LH response to LH-RH was studied in 6 months old calves castrated 2 months previously. The total LH response was 61% greater than in intact controls. When animals were castrated and pre-treated briefly with testosterone propionate the response was increased by 183% and the time to reach the LH peak was increased by 360%. From these and other results a synthesis of endocrine events during the first year of life is proposed. In particular it seems that the period between 4 and 8 months of age is crucial since interactions between steroid feedback and pituitary sensitivity to LH-RH change and eventually reach an equilibrium.


Dynamic changes in hypothalamic LH-RH levels associated with the ovarian steroid-induced gonadotrophin surge. Pro-oestrous-type LH surges were induced by treating ovariectomized rats (day 0) with either oestradiol benzoate (OeB, 40 micrograms/rat) or oestrogen (10 micrograms/rat followed by progesterone (4 mg/rat, day 2, OeBP). To characterize the temporal changes associated with the LH surge on day 2, LH-RH levels in the medial basal hypothalamus (MBH) and the pre-optic area (POA) were analyzed by RIA in rats sacrified at hourly intervals between 10.00--19.00 h. Following these treatments the LH-RH content of POA fluctuated somewhat but no definite pattern was observed. In OeB rats, the MBH LH-RH levels were unchanged through the initial LH surge period (13.00--15.00 h) declining significantly, as in the OeBP group, near the end of the surge period (19:00 h). However, in OeBP rats, the MBH LH-RH contents decreased at 14.00 h and these were followed by markedly elevated levels between 15.00--17.00 h coincident with maximal increments in serum LH. The OeBP group alone showed a surge of serum FSH.


Effect of rapid variation of renal function on plasma calcitonin and parathyroid hormone in man. Plasma levels of immunoreactive calcitonin (iCT) and parathyroid hormone (iPTH) have been measured sequentially in 6 patients following successful renal transplantation (RT) and in 3 patients during the recovery phase of acute renal failure (ARF). iCT and iPTH returned to normal values within a few days when glomerular filtration improved; both hormones rose in cases of acute graft rejection. Unlike iPTH iCT did not follow closely the variations of creatinine, iCT even rising before creatinine in one graft rejection. These observations could possibly be explained by a dissociation between the renal metabolism of iCT and the glomerular filtration.


Inhibitory effect of somatostatin on insulin secretion during alpha-adrenergic blockade in three different species. It has recently been suggested from experiments in dogs that somatostatin suppresses insulin release via a stimulation of the inhibitory alpha-adrenoceptors of the pancreatic B-cell. The effect of somatostatin on insulin secretion during alpha-adrenergic blockade with phentolamine was therefore studied in three different species; the rat, the cat and the mouse. It was found that somatostatin significantly depressed insulin release during alpha-adrenoceptor blockade in all three species. In the rat, infusion of somatostatin at a dose of 0.3 microgram/kg/min decreased basal plasma insulin concentration by 92%. In the presence of phentolamine, the same dose of somatostatin lowered plasma insulin by 85%. In the cat, a similar infusion of somatostatin lowered basal plasma insulin concentration by 87%, but its depressive effect during alpha-adrenergic blockade was comparatively less pronounced (68%) than in the rat. In the mouse, a single iv injection of somatostatin induced a short-lasting depression of plasma insulin concentration during alpha-adrenergic blockade. From these results it seems unlikely that somatostatin should inhibit insulin release simply by stimulation of alpha-adrenoceptors on the B-cell. It cannot be ruled out, however, that a more complex interaction exists between somatostatin and the sympatho-adrenal system with regard to the control of insulin secretion.


LH-secretory responses caused by continuous infusion of LH-RH in pseudopregnant rats. The LH-secretory response (LH-S.R.), caused by (standard) infusion of LH-RH, was estimated throughout pseudopregnancy (PSP) as well as on dioestrus - 1 and - 2 of the 4-day oestrous cycle. The LH-S.R. was judged according to 3 parameters: (1) mean maximal plasma LH concentration ("height", expressed in ng LH-RP-1/ml plasma), (2) mean area under the curve (AUC, expressed in "area units"), and (3) a composite, dimensionless, parameter: RQ ("response quotient"), defined as height/AUC. This latter parameter informs on the shape of the curve. The LH-S.R.'s on day 1 of PSP and dioestrus-1 were both relatively low (about 350 ng LH-RP-1/ml plasma) and characterized by the same RQ about 12). On days 2, 5, 7 and 9 of PSP the LH-S.R.'s were essentially the same and appeard to have characteristics of the LH-S.R.'s of both PSP-1 and dioestrus-1 (RQ) and dioestrus-2 (height; about 1000 ng LH-RP-1/ml plasma). From day 10 on the LH-S.R.'s became increasingly higher (PSP 11: about 1900 ng LH-RP-1/ml plasma; PSP 12: about 3300 ng LH-RP-1/ml plasma) and steeper (RQ equals about 22). At the end of PSP the spontaneous LH-surges were measured. These appeared to be very high if compared to those which are generated in 4-day cyclic rats (about 5800 ng LH-RP-1/ml plasma). The results indicate that a period of PSP is not simply an ovulatory cycle of which the dioestrous phase is extended by about a week and it is suggested that "active" corpora lutea secrete, next to progesterone, substances which play a key role in the regulation of the secretion of LH in the course of PSP.


A possible role of corpora lutea with regard to oestrogen-induced changes in pituitary responsiveness to LH-RH. The effect of oestradiol benzoate (OeB; 3 micrograms sc) on LH-RH-induced LH-secretory responses was investigated in: (1) long-term ovariectomized (OVX) rats; (2) intact (i.e. sham-OVX) and 24 h-OVX persistent oestrous (PO) rats (intact PO rats do not possess corpora lutea); (3) intact and 24 h-OVX cyclic (dioestrous) rats (intact cyclic rats possess "not-activated" corpora lutea), and (4) intact and 24 h-OVX phase-2-pseudopregnant (phase-2-PSP) rats (phase 2 of PSP lasts from day 2 to day 10. Experiments were performed on days 7--8. Intact phase-2-PSP rats possess "activated" corpora lutea). A "positive" effect of OeB was observed in: (1) long-term OVX rats; (2) intact and 24 h-OVX PO rats; (3) 24 h-OVX cyclic rats and (4) 24 h-OVX phase-2-PSP rats. In intact cyclic and phase-2-PSP rats OeB was completely ineffective. From these observations it is concluded that only in the absence of corpora lutea OeB can exert a "positive" effect on LH-RH-induced LH-secretory responses. Ovariectomy alone, however, may have a negative impact on LH-RH-induced LH-secretory responses. This holds for PO- and phase-3-PSP rats (phase 3 of PSP begins once the corpora lutea come to lysis, i.e. on or shortly before day 10, and lasts until the end of PSP), but not for phase-2-PSP rats. In cyclic rats, on the other hand, ovariectomy performed on dioestrus-1 "only" interferes with the normal development of pituitary responsiveness to LH-RH and this can be nullified by OeB. Our observations suggest that (1) relatively long-acting products of corpora lutea "stabilize" (phase-2-PSP rats), c.q. limit the (almost certainly oestrogen-dependent) development of pituitary responsiveness to LH-RH (cyclic and phase-3-PSP rats); (2) in ovariectomized rats the influence of these products vanishes and that (3) this results in a situation in which OeB can become effective. It is also suggested that in the course of the ovulatory cycle and phase 3 of PSP a similar disappearance of corpora luteal products occurs "spontaneously" as a result of the process of luteolysis with as a consequence that the pituitary responsiveness to LH-RH, under the influence of endogenous oestrogens, develops continuously until, on pro-oestrus, an LH-surge occurs. Evidence is presented that the corpora luteal products, postulated in this paper, are not identical to progesterone.


Suppression of prolactin secretion by lisuride throughout the menstrual cycle and in hyperprolactinaemic menstrual disorders. Normally menstruating volunteers as well as patients with hyperprolactinaemic menstrual disorders were treated with lisuride hydrogen maleate (200 micrograms b.i.d.), an ergoline derivative with dopaminergic properties. Within 3 h after an oral dose of 200 micrograms lisuride, PRL levels decreased significantly in all subjects to a plateau which lasted up to 3 h. Thereafter a gradual increase of serum PRL was noted. In the normally menstruating volunteers lisuride treatment did not result in any significant change of gonadotrophin or of sex steroid secretion, while both, basal as well as metoclopramide (MTCL) stimulated PRL release were significantly diminished. The inhibition of PRL secretion in patients with short luteal phases resulted in an increase of luteal progesterone output. In both treated groups ovulation occurred 1 to 5 days earlier in cycles on lisuride than in control cycles. LF-RH/MTCL tests performed in the patient bearing a pituitary prolactinoma before and after lisuride treatment revealed a continuous increase of pituitary LH pools, while PRL secretion decreased under lisuride therapy. Subsequently ovulation and menstruation occurred. The data presented demonstrate that lisuride is a potent inhibitor of PRL secretion and has proven its clinical usefulness for treatment of hyperprolactinaemic menstrual disorders. Application of lisuride resulted in an increase of luteal progesterone secretion in previously demonstrated corpus luteum insufficiency as well as in restoration of normal cyclical feedback mechanisms in tumorous hyperprolactinaemic anovulation. The MTCL-PRL stimulation test is suitable to monitor PRL suppression during lisuride treatment, while LH-RH testing reveals the effectiveness of lisuride by demonstrating an increase of pituitary gonadotrophin pools.


[Presence of antisinusoid antibodies in alcoholic hepatitis. Its probable pathogenic implications]. In nine patients with histological diagnosis of alcoholic hepatitis, in-situ deposition of autologous immunoglobulins (IgG, Iga, IgM) were investigated by inmmuno fluorescent techniques (IF). In three patients a linear fluorescent pattern was seen on the sinusoidal walls. The bound inmunoglobulins could be eluted by treatment with low pH buffers. In the same patients circulating antibodies against liver structures were investigated by indirect IF using normal murine or human liver as targets. In the same patients showing bound immunoglobulins in their liver, curculating antibodies against human sinusoids and not against murine liver could be found. On the basis of these findings the probable pathogenetic role of immune mechanism in alcoholic liver damage is discussed.


[Effect of hypoxia on gastric secretion of hypovolemic rats]. Gastric secretion was checked in two groups of rats with pyloric ligature and experimental hypovolemia subjecting one of the groups to acute hypoxia; in this group there was significant decrease in volume, acid and pepsin secretion and potassium concentration in gastric contents. In gastric mucosa pepsinogen was increased. We wish to emphasise in these changes, the importance of water and hypoxia in electrolytic balance.


[Comparative study of the gastric response in rats with pyloric ligation -- normovolemic rats and rats made hypovolemic by acute hemorrhage -- subjected to hypoxia]. Gastric secretion was studied in two groups of rats in which pyloric ligature was made according to Dai's method. Both groups were put in a hypopressure chamber. One of the groups was normovolemic. The other group was made hypovolemic by acute bleeding. The following parameters were checked in gastire contents: volumen, acid and pepsin secretion, U.P./g. of stomach, chloride, potassium and sodium; in gastric mucosa total U.P. and pepsinogen concentration were measured. In the rats subjected to acute hypovolemia and hypoxia it was found a significant decrease in acid secretion, chloride and potassium mEq/1; there were no statistically significant changes in volume, pepsin secretion; U.P./g. of stomach and sodium mEq/1. Total U. P. and U.P./. of stomach increased in the gastirc mucosa.


Efficient treatment of gastric ulcer with proglumide (Milid) in outpatients (double blind trial). Eleven male and five female gastric ulcer outpatients as well as twenty eight male and seven female duodenal ulcer outpatients received Proglumide (1200 mg/day) or magnesiumtrisilicate (1320 mg/day) in a prospective double blind study. The sizes of the ulcers were assessed by endoscopy before and after 4 weeks therapy. A complete healing of gastric ulcers was observed in 75% (n = 8) of the patients receiving Proglumide and 25% (n = 8) of the antacid treated controls (p less than 0.05; x2 test). The healed area was significantly (p less than 0.05) larger in the Proglumide 91 mm2) than in the anticida group (23 mm2). In addition, the half time of the ulcer-healing was significantly (p less than 0.05) shorter in the Proglumide treated patients (18 days and 26 days respectively). There was no significant effect of the drug on the duodenal ulcers. The spontaneous healing rate was 61% in the antacid (n = 18) and 59% in the Proglumide treated (n = 17) patients. The drug does not effect the basal and pentagastrin stimulated gastric secretion nor the serum gastrin concentration. No side effects on blood pressure, blood cell count, transaminases or blood glucose concentrations could be observed.


Double blind comparison between cimetidine and gefarnate in cases of duodenal ulcer. Thirty outpatients suffering from duodenal ulcer of recent onset were given cimetidine 1 g/day or gefarnate 250 mg/day for 6 weeks in a double blind trial, randomly balances between the groups. Endoscopic assessment was carried out at 4 and 6 weeks; patients healed after 4 weeks were withdrawn from the trial. In all parameters considered, cimetidine showed a highly significant difference. The healing rate at 4--6 weeks was 67--93% after cimetidine treatment and 27--53% after gefarnate treatment. The effect of cimetidine on the disappearance of symptoms, mainly the nocturnal ulcer pain, and on antacid consumption was greater than that after medication wity gefarnate. After 4--6 weeks of a full dose cimetidine regimen, both basal and pentagastrin stimulated gastric acid secretion were reduced and peptone meal stimulated serum gastrin increased; the basal gastrinaemia remained unchanged.


Scleroderma-heart and conduction disturbances. Disturbances of impulse formation and conduction may arise in the early stage of scleroderma, as a sign of cardiac involvement, termed "scleroderma heart". The incidence of various intraventricular conduction disturbances and their association with other disorders of cardiac rhythm were analysed in 193 scleroderma-patients by age. The presence of ventricular conduction abnormalities was found to carry an increased hazard of the production of disorders of atrioventricular conduction and of abnormal impulse formation. The patients were also followed up for deviation of the R axis in the frontal plane. Septal hypertrophy was found more frequently in patients with intraventricular conduction disturbances than in those free from disorders of this type.


Lymphokine activity in the aqueous humour and in the subretinal fluid in various ophthalmic diseases. The aqueous humour and the subretinal fluid were studied for migration-inhibition factor (MIF) activity by the capillary migration technique. The retrospective conclusions are based on the results obtained with 15-fold dilutions of aqueous humour and subretinal fluid of 12 patients. Under the conditions of the experiment a MIF activity over 30% was regarded as indicative of an active cell-mediated immune reaction. In case of a lower activity, the process was in general amenable to local treatment. In the light of further clinical observations, study of MIF activity is likely to prove a useful indicator of the local immune status and to provide therapeutic guidelines in various syndromes. In retinal detachment due to inflammatory uveitis it may furnish clues to the optimum time for surgery.


The origin of alpha-1-acid glycoprotein (AGP) in human gastric juice. In order to answer the question whether acid alpha 1-glycoprotein (AGP) is produced by the healthy human gastric mucosa, column chromatography of neutralized, pooled, and papain digested normal human gastric juice was performed on DEAE-cellulose using Varigrad NaCl elution gradients. Four glycoprotein fractions were obtained, one of which (fraction III) contained AGP. Its antibody raised in rabbits did not give immunofluorescence with any of the cells of the human gastric mucosa, only a reaction with AGP located in the intercellular spaces of gastric glands. These results indicate the extragastric origin of AGP, probably from serum.


Side effects of sodium valproate during long-term treatment in epilepsy. Side effects of sodium valproate during long-term treatment have been evaluated retrospectively in 55 patients suffering from refactory epilepsy. The side effects discovered in the study were slight and transient. In three of the 55 patients CNS side effects were noticed. Gastrointestinal symptoms were uncommon. One patient suffered from loss of hair which could have been attributed to sodium valproate. Severe side effects such as abnormal blood counts or organ damage were not discovered. The frequency of side effects was similar to those already reported in the literature except for gastrointestinal symptoms which were more infrequent than previously reported. No direct correlation could be established between the serum concentration of sodium valproate and the side effects.


Audiologic findings after stereotactic radiosurgery in nine cases of acoustic neurinomas. Nine cases of acoustic neurinoma were treated by stereotactic radiosurgery between 1969 and 1974. The follow-up period can now be regarded as sufficiently long for a preliminary evaluation of the results. An arrest of growth or shrinkage of the tumour was observed in 8 of the 9 cases. In one case open surgery was performed 2 years after irradiation and histological examination showed regressive changes of the type expected after irradiation. Audiological examination revealed that in the majority of cases radiosurgery could be performed without causing serious damage to the hearing function. The average hearing loss present before treatment increased on average only 20.0 dB in the most successful 7 cases. None of the patients suffered facial nerve involvement. In small and medium-sized acoustic tumours this method offers a satisfactory therapeutic alternative worthy of consideration.


Immunopathology of the glomerular changes in chronic pyelonephritis. To investigate the presence of intraglomerular immunoprotein deposition in chronic pyelonephritis (CPN), 29 renal specimens from patients with various urological diseases were examined by immunofluorescence. The relationship between immunohistological findings and types of glomerular changes which were classified according to Heptinstall's criteria was studied. Only type 2 glomeruli, which were considered to be ischemic changes, demonstrated granular and globular depositions of IgM and C3 in the collapsed and solidified shrunken tufts. IgM was positive in 117 of 258 (45.3%), and C3 in 122 of 264 (46.2%) type 2 glomeruli. The distribution patterns of IgM and C3 were much the same. IgG and IgA were rarely observed and neither fibrinogen nor albumin was observed in the tufts of type 2 glomeruli. Normal glomeruli and other types of glomerular changes in CPN showed few or no intraglomerular immunoprotein deposition.


[Activated astrocytes and epileptogenic focus. Histoenzymology]. The author reports the discovery of an original entity, the activated astrocyte, which is an essential component and the first anatomical sign of the epileptogenic focus. The importance of the activated astrocyte is demonstrated by the fact that it is observed before the clinical signs appear and as soon as the first spikes are recorded on the electrocortigram. Cautious conclusions are drawn. The authors recognizes the essential role of the neurons and does not suggest that astrocytes are the cause of epilepsy. However, since astrocyte activation is observed before the first electrical signs announce the beginning of an epileptogenic focus, he suggests that activated astrocytes probably offer morphological evidence of certain mechanisms closely concerned in the formation of the epileptogenic focus. The metabolic activation of the astrocyte is not surprising, and is probably related to the increase in loco-regional metabolism due to neuronal hyperactivity, the starting point of epilepsy. It confirms current opinion, especially in biochemistry, on the importance of the glial cells in the neuronastrocyte association. This work opens up certain prospects. First, the significance of the activated astrocyte in the context of current biochemical, neuro-physiological and morphological studies of the glial compartment is a promising research field. Second, from the clinical angle, it is very important to be able to identify an epileptogenic gliosis on the basis of activated astrocytes. Used in conjunction with modern neuro-physiological techniques to locate the epileptogenic focus, the search for activated astrocytes in biopsy material obtained stereotactically should permit better detection of the affected area and thus ensure more successful surgery in cases of focal epilepsy resistant to medication.


Some problems on the histopathological diagnosis of non-Hodgkin's malignant lymphoma -- a proposal of a new type. A new classification for non-Hodgkin's malignant lymphoma is proposed as the one suited for the Lymphomas in Japan, which is to provide a new subtype "pleomorphic" for those more or less rapid-growing lymphomas of peripheral T-cell nature, along with another subtype lymphoblastic, after Nathwani et al. for those of central T-cell nature. The proposal is based on the result of the investigation by the Study Group for Histopathological Diagnosis on Malignant Lymphoma that (1) the presence of a significant number of T-cell lymphomas with peculiar "pleomorphism" is responsible for the very low reproducibility rate of histopathological diagnosis on the diffuse, mixed L&H type of Rappaport classification, and (2) the relative incidence of lymphoms as peripheral T-cell nature including the so-called adult T-cell leukemia is much higher in Japan than in the Western countries.


Generalized aspergillosis showing a granulomatous pattern. An autopsy case of a very rare form of generalized aspergillosis with a prominent granulomatous pattern simulating sarcoidosis was presented. The patient was a forty-year-old Japanese female with a four years' clinical course. Kveim's test was positive. Multiple epithelioid cell granulomata as well as necrotizing and suppurative lesions were recognized in generalized lymph nodes, liver, epicardium, gall bladder, adrenals, kidneys and duodenal mucosa. Fungal elements in the epithelioid cell granulomata and necrotizing lesions were identified as Aspergillus by fluorescent antibody technique (indirect method). Predisposing factors for the generalized fungal infection could not be clarified in this case. There was neither underlying disease nor evident immunodeficiency state, so far as examined.


Resistance types in Escherichia coli. I. Occurrence and resistance to ampicillin, carbenicillin and cephalothin. An investigation of the resistance types in lactose fermenting E. coli is presented. The frequency and sensitivity to beta-lactam antibiotics of different resistance types was investigated. The strains were divided into three groups according to sensitivity to penicillin derivatives. Group 1 contained the ampicillin-carbenicillin sensitive (A-s/Ca-s), group 2 the ampicillin resistant-carbenicillin sensitive (A-r/Ca-s) and group 3 the ampicillin-carbenicillin resistant (A-r/Ca-r). A-s/Ca-r were not observed. One third of the A-r strains were sensitive to carbenicillin. The distribution of resistance types was different in the three groups. Group 1 was dominated by the usual sensitive E. coli. Group 3 contained a very high proportion of multiresistant types. The IC50 against ampicillin, carbenicillin and cephalothin of 55 strains was determined. Group 3 (A-r/Ca-r, 25 strains) was much more ampicillin resistant than group 2 (A-r/Ca-s, 16 strains). Group 2 was less sensitive to carbenicillin than group 1 (A-s/Ca-s, 14 strains). Group 3 did not differ significantly from group 1 with respect to cephalothin sensitivity, while group 2 was much more resistant than the others.


Electron microscopy of treponemes subjected to the Treponema pallidum immobilization (TPI) test. II. Immunoelectron microscopy. The experiments were carried out in order to investigate whether human IgG globulin is absorbed on to the surface of T. pallidum cells during incubation with human syphilis serum in the Treponema pallidum immobilization (TPI) test. Cells of T. pallidum Nichols subjected to the TPI test were further incubated with ferritin conjugated rabbit antihuman IgG globulin. Human IgG globulin could only be demonstrated on immunoimmobilized cells, i.e. cells incubated with human syphilis serum and unheated guinea pig serum (GPS). The surface of the swollen cells was completely covered by a fuzzy layer on to which the ferritin molecules appeared to be attached. In ultrathin sections of cells obtained from the same suspensions the surface of the outer cell membrane was outlined by ferritin molecules. In these cells a rather wide gap was observed between the outer membrane and the cytoplasmic membrane. The ribosomes seemed to have disappeared from the cytoplasm of the immunoimmobilized treponemes, but were present in motile cells obtained from control incubations.


Direct effects of Corynebacterium parvum and BCG on human monocyte-mediated tumour cell cytostasis in vitro. Four strains of Corynebacterium parvum (Cp) and BCG induced low levels of cytostatic ability to a human tumour cell line in human monocytes when added directly to conventional monocyte cultures. The cytostatic ability induced by mediators from autologous lymphocytes stimulated with the same agents was greater than that produced by direct addition to monocytes. BCG was more efficient in stimulating lymphocyte DNA-synthesis and lymphokine release than any of the Cp strains tested. In order to test the influence of contaminating adherent lymphocytes on the direct induction of cytostasis, monocyte cultures of greater than 99.9% purity were prepared by adherence purification. Cp induced low levels of cytostatic ability in such highly purified monocytes when added directly to the monocytes. Addition of BCG and Candida albicans had an adverse effect on the cytostatic ability of purified monocytes. A morphological study of Cp interaction with purified monocytes was performed. Cp, but not BCG, would seem to be able to induce low levels of cytostatic ability in human monocytes without lympohcyte cooperation. Human monocyte activation by the more effective lymphokine pathway is more efficiently triggered in vitro by BCG than by Cp.


Characterization of heat eluates of human malignant tissues. Eluates of 13 malignant and 17 normal tissues were prepared at 56 degrees C using the continuous flow technique. Albumin was detected in all the eluates. IgG, IgA, C3 or haptoglobin were detected in most of the malignant and some of the normal tissues. Carcinoembryonic antigen, beta 2-microglobulin, alpha 1-antitrypsin or alpha 1-antichymotrypsin were detected in some of the eluates of the malignant tissues only. IgM, IgD, C1q, C4, Cl-INH, alpha 1-macroglobulin, beta 2-lipoprotein, fibrinogen and alpha 1-foetoprotein were not detected in any of the eluates. The ratio of the concentration of albumin to the concentration of IgG was similar in extracts and eluates of all the normal tissue and in 3 of the malignant tissues indicating non-specific binding of IgG.


Symptom reduction in depression after treatment with L-tryptophan or imipramine. Item analysis of Hamilton rating scale for depression. Thirty-eight in-patients with endogenous- and 20 in-patients with non-endogenous depression, took part in a multi-centre 3-week double-blind trial where patients were randomly allocated to treatment with either 6 g L-tryptophan or 150 mg imipramine daily. Item analysis of Hamilton ratings, before the investigation and weekly during the trial period demonstrated few statistically different mean scores on individual items between the two treatment groups. After 3 weeks' treatment a statistically significant item mean reduction on the 0.1% level was found in the item Agitation in favour of imipramine-treated, and in the item Work and Activities in favour of L-tryptophan-treated endogenously depressed patients. After 3 weeks' treatment a statistically significant item mean reduction on the 5% level was found in the item Suicide in favour of imipramine-treated non-endogenously depressed patients. The present study has shown that, after 3 weeks' treatment, imipramine and L-tryptophan has decreased the mean score on individual items of HRS in about the same degree.


Trends in suicide in Sweden 1749-1975.

Trends in suicide in Sweden 1749-1975. Changes in the suicide rate in Sweden have been studied over the period 1749-1975. It has risen from about 2 per 100,000 inhabitants at the middle of the 18th century to about 20 per 100,000 during the period 1971-1975. Thus a more than tenfold increase is evident. From the non-standardized figures a real and substantial increase can be demonstrated which becomes even more apparent after standardization. This increase is independent of variations in the age composition of the population. The increase has occurred in the younger age groups: between the ages of 20 and 35 years, i. e.during the most active years of life, suicide is the leading cause of death today. An account of legislative measures for suicide prevention during this period is also presented. There is considerable support for the assumption that the low suicide rate registered in Sweden up to the beginning of the 19th century was an effect of the powerful influence of religion over the population.


Production of biologicals by plant cell cultures. The biologicals currently produced from plants are generally low molecular weight chemicals such as drug compounds rather than high molecular weight compounds such as proteins. The reasons for considering a fermentation technology based on plant cell cultures have been described. The state of technology of plant cell cultures is sufficiently advanced to suggest that the major questions remaining are economic rather than primarily technical. Limited analysis of the economics of commercial production of biologicals by plant cell cultures shows that a commercial process is certainly feasible.


The effect cystamine on gastric secretion in the rat. The effects of cystamine on gastric secretion were studied in conscious and anaesthetized rat preparations. In the conscious gastric fistula rat cystamine inhibited the basal acid output but increased pepsin output. This pepsinogogue action was inhibited by both atropine and metiamide. In the anaesthetized rat cystamine stimulated gastric acid output, an effect blocked by cimetidine which had an inhibitory E.D. 50 which was not significantly different from that obtained against histamine-stimulated secretion in this preparation. Atropine at high doses failed to inhibit the response. Depletion of mast cell histamine by compound 48/80 the secretory response to cystamine. In the light of these results possible mechanisms of action for the secretagogue effects of cystamine are discussed.


The role of prostaglandins in experimental ocular inflammations. Intraocular inflammations (uveitis) were produced in rabbits by intravitreal injection of killed and dried Mycobacterium butyricum or E. coli endotoxin, or paracentesis of the anterior chamber. The increase in permeability of the blood-aqueous barrier and the leucocyte migration into the aqueous humor were observed after these stimuli, although the leucocyte did not migrate after paracentesis. Topically applied indomethacin reduced these inflammatory parameters in the latter two models. However, ththacin, though the leucocyte was not affected by indomethacin, though the leucocyte migration was reduced. On the other hand, prostaglandin-like substances in thces of these substances were detected in the former model. These results indicated that, unlike the increase in the permeability of the blood-aqueous barrier after endotoxin injection andparacentesis, the response after M. butyricum injection is not mediated by prostaglandins. The role of prostaglandins in the leucocyte migration in these ocular inflammations was also discussed.


Rabbit lung microsomes: a rapid method for assaying simultaneously drug effects on thromboxane and prostacyclin synthesis. A radiochemical method is described which allows simultaneous determination of the in vitro effects of chemical substances on thromboxane and prostacyclin synthesis. The method utilizes the capacity of a combination of bovine seminal vesicle microsomes (BSVM) and rabbit lung microsomes (TbLM) to transform arachidonic acid into TXB2, 12-hydroxy-heptadecatrienoic acid (HHT), 6-keto-PGF1 alpha (6K-PGF1 alpha), PGF2 alpha, and PGE2 in the ratio of 1:0.80:0.63:0.13:0.05, respectively. Imidazole and burimamide, and to some degree also dipyridamole and L8027, were found to be selective thromboxane inhibitors. The preferential alternative pathways following thromboxane inhibition with these drugs were towards PGE2 and PGF2 alpha, and the algebraic sum of arachidonic acid metabolism was not affected by imidazole and burimamide. The assay is a convenient method for identification of drugs which interfere with specific pathways of arachidonic acid metabolism.


The role of thromboxane A2 in endotoxin-induced aggregation of guinea-pig platelets in vitro. Large concentrations of endotoxin lipopolysaccharides (LPS) E. coli O127:B8 and E. coli O26:B6 were needed for induction of platelet aggregation in citrated platelet rich plasma (PRP) from normal guinea-pigs. When guinea-pigs were actively immunized with LPS E. coli O127:B8 their PRP became more sensitive to the aggregatory effects of this type of LPS. The increase in sensitivity was rather selective since the responses to ADP and LPS E. coli O26:B6 remained unchanged. In endotoxin-stimulated PRP from normal guinea-pigs thromboxane A2 (TXA2) was not detectable by bioassay. Thus biosynthesis of TXA2 seemed to be of little importance in endotoxin-induced platelet responses in normal citrate PRP. LPS E. coli O127:B8, but not LPS E. coli O26:B6, was a potent inducer of the biosynthesis of TXA2 in sensitized PRP. Under those conditions endotoxin-induced aggregation seemed to be dependent on the endogenous biosynthesis of TXA2 by the platelets.


Modulation of granulomatous inflammation by prostaglandin E. Involvement of mononuclear cells. The effects of exogenous PGE, administered locally to carrageenan sponge-induced granulomata in rats, have been studied in relation to changes in PGE-like material (PGL) and cell counts in exudates. Levels of PGL achieved a peak within 24h, declining thereafter. Administration of PGE during the acute phase led to irregular slight enhancement of subsequent granuloma formation. In contrast, administration of exogenous PGE to pre-formed granuloma, inhibited its formation. The early administration of PGE1, on day 1, inhibited mononuclear cell counts in 24h exudates. This inhibition was still present in 8 day exudates, together with reduced PGL levels. A significant correlation was also observed between phagocytosing macrophages and PGL levels in 8 day exudates after exogenous PGE1 treatment of pre-formed granuloma, suggesting that the exogenous PGE was inhibiting macrophage function, including PGL production. Further studies are necessary to establish whether the observed pharmacological effects indicate that PGE, released during granulomatous inflammation, modulates the process through actions on infiltrating leucocytes.


Abnormal mitral valve motion associated with ventricular septal defect following acute myocardial infarction. It is often difficult to make the clinical distinction between acute mitral regurgitation caused by papillary muscle dysfunction or rupture and ventricular septal defect complicating an acute myocardial infarction. A case of a patient with rapidly progressive congestive heart failure and a loud murmur is presented. Echocardiography strongly suggested the presence of a flail posterior mitral leaflet. However, the patient was subsequently found to have rupture of the interventricular septum. This diagnosis was made with bedside right heart catheterization and was later confirmed by left ventriculography and direct inspection at the time of surgery. The mitral valve apparatus was completely normal. Thus this case demonstrates the apparent lack of specificity of the accepted echocardiographic criteria for flail mitral leaflet and acutely ruptured interventricular septum, and the potential necessity of cardiac catheterization to distinguish between these entities.


Report on carcinogenesis bioassay of 1,2-dibromoethane (EDB). In a carcinogenesis bioassay of the brominated hydrocarbon 1,2-dibromoethane (also called ethylene dibromide or EDB), a gasoline and antiknock additive and soil and grain fumigant, oral administration by stomach tube caused cancers in rats and mice. In both sexes of both species, EDB induced squamous cell carcinomas of the forestomach. Blood vessel cancers in male rats, liver cancers in female rats, and lung cancers in male and female mice also were attributed to EDB dosage.


Role of vasoconstrictor mechanisms in the control of left ventricular performance of the normal and damaged heart. The effect on the left ventricle of changes in the state of the arterial vasculature is best identified by utilizing calculations of pulsatile rather than steady flow phenomena. Impedance is the most satisfactory term to describe this effect. The normal ventricle compensates for changes in impedance largely by changes in preload, but the damaged heart loses this compensatory ability and its stroke volume becomes inversely related to outflow resistance. Patients with heart failure behave in a similar fashion and pharmacologic vasodilation may induce marked improvement in left ventricular pump function. Inappropriate vasoconstriction in heart failure may result from stimulation of the sympathetic or renin-angiotensin system. Early experience with converting enzyme inhibitors suggests that blockade of the formation of angiotensin II may be a useful means of treating some patients with heart failure.