An animal model for the study of prostate carcinoma. We report here the development of the Dunning R-3327 prostate adenocarcinoma of the Copenhagen rat as a suitable model of human prostate cancer. Tumors, produced by sc or intraprostate injection of viable cells, had the macroscopic and microscopic characteristics of the human disease. The histologic picture of these tumors was of a well-differentiated adenocarcinoma with the formation of glands and acid secretions within the acini. The intraprostate tumor, although initially confined to the injected lobe, grew to involve the surrounding tissues and eventually metastasized to the lymph nodes and lungs. Occasional metastatic lesions were found in other organs as well. During investigation of the tumor, a fast-growing line arose that grew equally well in females as in males. The histology of this tumor was of an undifferentiated anaplastic tumor. A tissue culture line derived from R-3327 was capable of producing tumors in recipient rats with characteristics similar to the original Dunning tumor.


Growth characteristics and immunogenicity of the R-3327 rat prostate carcinoma. The transplantable R-3327 prostate adenocarcinoma (Dunning tumor) has been studied in the Copenhagen rat. We present information about androgen-dependent and hormone-independent tumors in regard to metastasis, growth rate, extrapolated cell kinetics, and response to treatment.


Immunogenicity of N-[-4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced bladder cancer. Five transplantable TCC initially induced by the carcinogen FANFT were systematically tested for individual immunogenicity and then for the presence of cross-reacting tumor antigens. The classic amputation challenge technique was used. Three of the 5 tumors were immunogenic, as determined by their ability to reduce the growth of a challenge tumor dose in mice immunized with the same bladder tumor. Prior immunization with one of the immunogenic tumors failed to reduce the incidence or growth of primary bladder tumors induced by the ingestion of 0.1% FANFT in C3H/HeJ mice. The lack of cross-reacting tumor antigens has important implications for the use of allogeneic tumor cells as an antigen source in immunotherapy.


Spontaneous urinary bladder and ureter tumors in the Brown Norway rat. Cell lines have been developed in Brown Norway rats from 3 primary uroepithelial tumors and from 2 in vivo transplanted uroepithelial tumors. After sc injection, cells of all cell lines gave rise to progressively growing tumors that eventually kill the host.


Teratoma and teratocarcinoma in experimental animals. Different models of spontaneous and experimentally induced teratomas and teratocarcinomas were presented. The role of various control mechanisms operating in the tumor-bearing host is outlined.


A teratoma model system.

A teratoma model system. The technique of genital ridge transplantation in mice was described. The use of this model system for the study of teratomas is stressed.


Adjuvant immunotherapy in superficial bladder cancer. The use of BCG as an intracavitary form of immunotherapy in human bladder cancers is discussed. The result of a clinical trial in which BCG is administered in the treatment of human bladder cancers is reported. Possible uses of this tumor model in the study of immunotherapy employing BCG are suggested.


Effectiveness of long-term chemotherapy and/or BCG on murine bladder cancer. Cure following surgery of bladder cancer is limited by recurrence of the original tumor or by the development of new primary tumors. TCC of the bladder induced in C3H/HeJ mice by FANFT closely resemble their human counterpart and have been used to evaluate the effect of chemotherapy and/or BCG on the induction and growth of these tumors. Three hundred five mice were divided into a control group of 30 and 11 treatment groups of 25. Therapy was initiated at 5 and 7 months after FANFT. The first tumors in this system are observed at 8 months with an expected incidence of 70-90% by 11 months. Therapy consisted of: 1) BCG; 2) cyclophosphamide; 3) cyclophosphamide + BCG; 4) cyclophosphamide + 5-FU; 5) cyclophosphamide + adriamycin; and 6) adriamycin. All mice were killed after 11 months on FANFT. Bladders were wieghed and the tumors were staged. Tumor incidence was reduced by only two regimens: adriamycin and cyclophosphamide + adriamycin. Cyclophosphamide significantly reduced subsequent tumor volume compared with the control group, with the effect being more pronounced in mice beginning treatment at 5 months. The combination regimens were superior to cyclophosphamide alone. BCG did not potentiate the antitumor action of cyclophosphamide and, when used alone, actually enhanced tumor growth (P less than 0.025). The use of BCG immunotherapy should be cautioned, but the effectiveness of the antineoplastic drugs suggests their use in clinical trials in patients with bladder cancer.


A bladder tumor model response to immunotherapy. The author presented results of BCG and Corynebacterium parvum treatment of the transplantable mouse FANFT bladder tumor carried in the host's leg. A comparison was made of the results of treatment with BCG alone and C. parvum alone or either used in conjunction with Cytoxan upon effectiveness in increasing animal survival and retarding tumor growth.


Lymphocyte-mediated cytotoxicity in patients with renal and transitional cell carcinoma receiving BCG. Our modified lymphocyte-mediated microcytotoxicity assay, which allows the serial estimation of lymphocyte cytotoxicity, was used to evaluate the immune response of patients with advanced renal cell and transitional cell carcinoma who were receiving BCG therapy. Preliminary data suggested that this assay may be useful in monitoring cancer patients receiving BCG.


Treatment of hypernephroma with xenogeneic immune RNA. The treatment of patients with hypernephroma with xenogeneic immune RNA was discussed. The toxicity from xenogeneic immune RNA therapy was minimal in patients receiving simple doses from 4 to 64 mg intracutaneously and with cumulative doses of 450 mg during a 30-month period.


Prostate carcinoma: immunostaging and adjuvant immunotherapy with BCG. Thirty-three patients with histologic diagnosis of adenocarcinoma of the prostate were entered into separate protocols: 1) immunostaging, and 2) BCG adjuvant immunotherapy. Immunostaging is a new method of assessing patients immunologically prior to and after immunotherapy. Thirty of these patients were immunostaged with the use of humoral and cellular immune parameters. A positive correlation was noted between the patient's immunostage and the clinical stage of his cancer. The 33 patients with a histologic diagnosis of adenocarcinoma of the prostate were entered into an ongoing protocol of adjuvant BCG immunotherapy in addition to conventional therapy (19 patients received BCG and 14 served as controls). The patients receiving BCG had a longer mean survival time; minimal morbidity and no mortality resulted from this therapy.


The concept of induction and elicitation as an immunotherapeutic approach. The concept of "induction and elicitation," propounded by Stuart Mudd, circumvents the dangers of infecting the immunologically impaired individual without abrogating the effectiveness of the antigenic stimulus provided by an initial infection with living organisms. Mudd's concept utilizes the ubiquitous and naturally established delayed type hypersensitivity to Staphylococcus aureus as the primary induction step for the more effective use of bacterial fractions, such as staphylococcal phage lysate, a potent immunizing agent, commercially licensed and available, in the subsequent elicitation of a nonspecific, cell-mediated immune response. The results of an exploratory study in which induction and elicitation were applied as an immunotherapeutic modality, in combination with surgery, in a metastasizing animal tumor model (the F344 rat) are presented.


Cryosurgery in prostate carcinoma: clinical evidence of immunostimulation of host versus tumor. Results of cryosurgery in the manipulation of prostate cancer in a rabbit animal model is discussed. Clinical application of cryosurgery in the treatment of prostate cancer in man and its effect on metastases is presented.


Tumor immunity following cryosurgery or electrocauterization. Cryosurgery of MCA-10 in C57BL mice resulted in significantly greater humoral and lymphocyte-mediated cytotoxicity to MCA-10 target cells than in untreated, tumor-bearing mice or animals which had undergone tumor amputation. This result was tumor specific and could be reproduced by treatment of the tumor-bearing and amputated mice with frozen exogenous tumor antigen. A similar response was produced by electrocauterization of tumor.


Immunostimulation by cryosurgery: an orthotopic model of prostate and bladder cancer in the rat. In patients with prostate cancer, cryosurgery has been highly effective in eradication of the primary tumor. Certain clinical observations have suggested the presence of an additional systemic anticancer effect, presumably immunologic in nature, but proof is lacking. To study this problem further, we developed two animal tumor models. Instead of using the classical subcutaneous site, we transplanted the 11095A and R-3327 prostate tumors into rat prostate, the 4909 bladder tumor into rat bladder. In these respective orthotopic locations, the 3 tumors displayed favorable growth characteristics with good accessibility for cryosurgery. This model should be considered for studies involving any localized treatment of an established urologic tumor.


Testis carcinoma: transplantation into nude mice. Heterotransplantation of primary and secondary human testis tumors and the established cell lines, tera-1 and tera-2, into nude mice has been performed. The cell lines have been successfully grown subcutaneously and in the anterior chamber of the eye, without further immunosuppression, and this has contributed to the characterization of the lines. Growth has not been obtained with the fresh tumor material.


Isolation of lymphocyte populations.

Isolation of lymphocyte populations. Lymphocytes are smaller than most mammalian cells. Although their densities are heterogeneous and overlap those of other mammalian cells, the average lymphocyte is less dense than the vast majority of mammalian cells. Because of these physical properties, lymphocytes sediment less rapidly than most mammalian cells during velocity sedimentation in the isokinetic gradient. Our separations of lymphocytes from several kinds of tissues including human blood, transplantable tumors, and the tumor of Hodgkin's disease are described.


Cryopreservation of lymphocytes to standardize in vitro immune functions. The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared with the use of samples collected on five occasions from 1 normal donor. The day-to-day variation seen with the fresh cells was eliminated by the use of frozen cells. Thawed cells from 1 donor, collected once but studied on five occasions and compared with fresh cells on the same days, fluctuated from day to day as well, confirming that the day-to-day variation seen is due to technical and not biologic phenomena. Cryopreserved cells showed a decrease in responses to specific microbial antigens, a slight shift in the PHA dose-response curve, but no significant difference in responses to Con A or PWM. The relative proportion of lymphocyte subpopulations changed with freezing and thawing. The proportion of T- and B-cells increased and decreased, respectively.


Function of cryopreserved human effector cells in antibody-dependent, cell-mediated cytotoxicity. Cells active in an ADCC model were studied for their ability to withstand cryopreservation. For this model, we used the [3H]proline microcytotoxicity assay with fibroblast target cells and a serum containing lymphocyte-dependent antibody reactive with the alloantigens on those target cells. Human blood effector cells active in this system can be successfully cryopreserved with minor dimunition in function with standard techniques and concentrations between 9 and 12% DMSO.


Influence of surgery, irradiation, chemotherapy, and immunotherapy on growth of a metastasizing rat mammary adenocarcinoma. Based upon the hypothesis that a factor most pertinent to the absence of an effective immune response in cancer is the inadequacy of the antigenic stimulus provided by the neoplasm, either in terms of weak immunogenicity of the tumor antigen or of the necessary antigen mass available to the reticuloendothelial tissues at any one time for effective sensitization, the host immune response capabilities were stimulated within a time frame synchronous with a greater release of tumor antigens. In the treatment of a metastasizing, solid tumor model syngeneic with F344 rats, immunotherapy was most effectively applied in combinations with chemotherapy and/or localized radiotherapy, therapeutic modalities that induced a degree of oncolysis and tumor resorption. Surgery combined with chemotherapy permitted evaluation of therapeutic effects against metastases. The methanol-soluble fraction of Mycobacterium butyricum was used as the nonspecific immunologic adjuvant.


Central nystagmus and its interaction with optokinetic and reversive postoptokinetic forms of nystagmus. Interaction of central nystagmus (CN) with optokinetic (OKN) and reversive postoptokinetic (RPN) forms of nystagmus was studied in chronic experiments on rabbits. During interaction of CN with OKN or RPN not in the same direction, the latter are inhibited and CN is manifested during the next 5 sec. The reverse process is observed after a cessation of electrical stimulation. If CN coincides in direction with OKN and RPN, the period from the beginning of electrical stimulation until establishment of regular resultant nystagmus is considerably shortened. Furthermore, the period from the moment of cessation of electrical stimulation until establishment of regular OKN and RPN also is shortened.


What constitutes a School Readiness examination? The component parts. The School Readiness medical examination is probably the single most important examination a child has outside of the infancy period. This examination helps to determine whether or not the child is physically, emotionally and intellectually ready to handle a more structured, academic environment. The physician should devote enough time and effort to do a thorough evaluation. The physician also, should be appropriately compensated for this medical evaluation based upon time, training, experience, and length of discussion with the family.


Skin testing for allergic diseases: techniques, indications and interpretations. Despite significant strides in serologic methodologies, the skin test, when properly done, has remained the single most sensitive and practical assay for specific dermal-bound reaginic antibody. Its value could further be enhanced if and when characterization and standardization of the allergen extracts become a reality. While the technique is simple, the indications and interpretations of allergy skin tests required the expertise of well-trained allergists. A positive skin reaction is no more than a mere supportive laboratory aid in the diagnosis of allergic disease, which is arrived at through a carefully taken detailed history and a meticulously done physical examination.


An approach to office pediatric ophthalmology. Recognition of common eye problems affecting children is essential in the everyday practice of pediatrics. The physician should become familiar with a systematic approach for all ocular problems, including the examination of the newborn as well as trauma cases. The eye is a very accessible organ and the diagnosis of many problems is relatively easy. Management is often straightforward, cure is usually rapid, and satisfaction is great for the patient and pediatrician alike.


The energy metabolism of adult Haemonchus contortus, in vitro. A comparison was made of the major excretory products when adult Haemonchus contortus worms were incubated with D-[U-14C]glucose under aerobic and anaerobic conditions. Catabolites measured were propan-1-ol, acetate, n-propionate and CO2 and the only major difference was that nearly twice as much CO2 both in terms of quantity and radioactivity was excreted under aerobic than anaerobic conditions. The worms were also much more physically active under aerobic conditions. When worms were incubated under aerobic conditions with increasing amounts of fluoroacetate their CO2 production was progressively reduced to the anaerobic level. Their movement and their ability to clump together was also progressively reduced. After aerobic incubation with fluoroacetate and D-[U-14C]glucose the quantity and radioactivity of citrate within worms increased greatly. When worms were similarly incubated anaerobically no increase in citrate occurred, no radioactivity was associated with the citrate and the worms appeared physically unaffected. When worms were incubated aerobically with fluoro[1(-14)C]acetate they produced radioactive fluorocitrate.


Relations between immunological and neurological memory: learning ability in rats during immunostimulation. The effect of an immunostimulator, Freund's complete adjuvant (FCA), on the ability of Wistar rats to learn in a visual discrimination test was studied by foodgetting and electric-shock avoidance methods. A significant improvement in learning ability was demonstrated under the influence of FCA when the negative reinforcement method was used, but a worsening when the positive reinforcement method was used. Analysis of the dynamics of extinction of the reflexes formed gave similar results. The possible relations between immunogenesis and memory forming processes are discussed.


The effect of concurrent infection with Trichinella spiralis on Hymenolepis microstoma in mice. The intestinal changes brought about by rejection of Trichinella spiralis from mice were studied in relation to their effects on a concurrent infection with Hymenolepis microstoma, a cestode not normally rejected from mice. The rejection phase of T. spiralis was associated with a marked stunting of growth of H. microstoma given just before, during, or just after rejection of the nematode. The survival of H. microstoma was affected only when rejection of T. spiralis coincided with the intestinal phase of the cestode: if T. spiralis rejection was timed to occur after the scolex of the cestode had entered the bile duct there was no loss of H. microstoma. It is suggested that the adverse effects on growth and establishment of H. microstoma were due to the non-specific inflammatory component of the host's response to infection with T. spiralis.


Behavioral hyperreactivity in the spontaneously hypertensive rat compared to its normotensive progenitor. The spontaneously hypertensive rat (SHR) is an excellent model of essential hypertensive disease. Hyperreactivity has been postulated as a contributing factor in the development of high blood pressure in the SHR and in man. In the maturing organism recurring hypertensive stesss responses may promote permanent vascular changes and result in a fixed hypertension. Simple behavioral activity and emotionality rating scales were used to compare a large number of SHR with equally large groups of closely-related and distantly-related normotensive rats. As predicted, the SHR were clearly more active and emotional than their ancestral Wistar Kyoto (WKY) strain. However, the distantly-related normotensive Wistars did not differ from the SHR in either activity or emotionality. These results indicate that behavior and hypertension are not necessarily related in the rat. Nonetheless, the behavioral differences between the SHR and their closest genetic match, the WKY, suggest that arousal and blood pressure levels may be causally linked in this case of naturally occurring hypertension.


A vigilance model for latent learning.

A vigilance model for latent learning. The author proposes a heuristic model for latent learning. It is concluded that to regard academic learning as qualitatively different from other forms of learning is to deny evolutionary continuity. Academic learning is not a unitary process governed by a single set of parameters. In addition, it is observed that the problem of student motivation may very well turn out to be purely academic. The instructional technique for a captive audience of a class may be so structured as to make the direction of attention irresistible, the performance of a response, when needed, compelling, and the acquisition of knowledge inevitable. Vigilance is an instance of innate foundation. Its most striking characteristics are its universality in the animal world, its ready evocation by a wide range of stimuli, and its apparent behavior and physiological manifestations. The last two are the natural resources for objective investigation, and the first may well be the basis of broad and valid generalizations.


Total peripheral resistance changes in dogs during aversive classical conditioning. The arterial pressure, heart rate, stroke volume, cardiac output and total peripheral resistance of laboratory dogs were monitored continuously before and during a 30 min period in which aversive classical conditioning procedures were applied. The experimental stimulation generated inhibition of behavioral activity ("freezing") together with sustained increases in arterial pressure averaging 30%, and increases in heart rate anc cardiac output of 60-70%. The calculated total peripheral resistance decreased by an average of 20%. The behavioral and cardiovascular responses were sustained during the aversive conditioning period. The results suggest that significant peripheral vasodilation occurred under these conditions which was probably not due to metabolic byproducts of behavioral activity, but probably reflected sympathetic cholinergic effects upon blood vessels in the skeletal muscles. These data document the significance of the skeletal muscle circulation in the total peripheral resistance to blood flow in unanesthetized animals.


The effect of cul length and hippocampal lesions on maze learning in the rat. Twenty-four rats, 8 with bilateral hippocampal lesions, 8 with cortical lesions and 8 unoperated rats, were tested on one of 2 mazes. Half of each group were run in a conventional 5 choice multiple Y maze. The other half were run in a symetrical, long cul maze in which distance and number of successive choice point were equal for a right or wrong choice before the animal reached an cul end or the goal box. The correct path in the long cul maze was identical to that of the short cul maze. S's were run one trial a day for 15 days. On the symetrical, long cul maze there were no differences between groups. On the short cul maze, hippocampals were significantly worse than control S's and looked similar to control S's on the long cul maze. The results are interpreted in terms of frustration theory.


Measurement of neo-Pavlovian properties of higher nervous activity by motor reaction-time tasks. A preliminary study involving 80 paid subjects, 40 of each sex, investigated the usefulness of motor response-time tasks as measures of three neo-Pavlovian properties of higher nervous activity, excitatory strength, dynamism, and mobility. Six independent factors were extracted from a set of variables measuring those properties. These factors demonstrated the independence of the three properties, of the excitatory and inhibitory processes in dynamism and mobility, and of strength and sensitivity at least when such tasks are used as measures of properties in the auditory modality. These findings are promising, however, further investigation is required to validate these tasks against the classical tests of properties of higher nervous activity.


[Electrocardiographic changes in rheumatoid arthritis]. The clinical course of 50 patients with rheumatoid arthritis has been reviewed with special emphasis on the electrocardiographic changes. Thirty two of 50 of these patients presented electrocardiographic abnormalities and two cases had myocardial infarction. Electrocardiographic changes were associated with activity of the sickness. It is possible that the electrocardiovasculars manifestations represent the first manifestation of the rheumatoid arthritis therefore it is convenient to check them the whole time, even in case the patient does not present clinical abnormalities.


[Generalized peritonitis. Morbidity and mortality with respect to the development of oncotic pressure in the early postoperative period]. A group of forty patients with generalized peritonitis was studied comparing their clinical evolution and mortality with the plasma coloidosmotic pressure values (COP). Twentynine patients survived without complications (Group I) this patients had the higher mean COP values, 17.56 mm Hg at the beggining and 19.06 mm Hg at the end of the study. Three patients showed complications directly related with peritonitis but finally survived (Group II). Their mean COP values were 16.08 mm Hg at the beggining and 13.44 mm Hg at the end. Eight patients died (Group III) lower mean COP values were obtained in this group; 13.5 at the begging and 11.94 at the end. Despite the same kind of medical and surgical treatment, response was very different in each group. Lower values of COP were found as clinical avolution worsened. A very low inicial value or failure to raise it despite the treatment may be considered as a bad prognosis sing.


[Familial neoplasms and childhood dermatomyositis]. Familial frequency of malignant neoplasms from 20 children with dermatomyositis was investigated and compared with 225 controls. Eight patients with dermatomyositis (40 per cent) had nine family members with a malignant tumour; this frequency is significantly higher than those found in the controls with juvenile rheumatoid arthritis (P less than 0.01), neoplasms (P less than 0.01), and a variety of diseases (P less than 0.05). This finding and the known association of neoplasm-dermatomyositis might suggest an hereditary predisposing factor, possibly a subtle inmune deficiency, common for tumours and dermatomyositis.


Preparation of radioactive labelled (57Co) sulfitocobalamin. Farquharson and Adams (Br. J. Nutr. 36, 127-135 (1976)) have identified sulfitocobalamin (SO3-Cb1) as one of the naturally occurring cobalamins (Cb1s) in foods. We have devised a method of making radioactive labelled SO3-Cb1 for in vivo and in vitro studies of this form of Cb1. 57Co labelled cyanocobalamin (57Co CN-Cb1) was acid photolyzed to 57Co hydroxocobalamin (57Co OH-Cb1) followed by ligand substitution with SO3-2 ion from aqueous sodium (meta) bisulfite in the dark. The resulting 57Co SO3-Cb1 was purified by organic extraction and cation exchange chromatography. The final preparation was greater than 99% 57Co SO3-Cb1 with an overall yield of greater than 70%, stable for up to four weeks at 20 degrees C in the dark, and capable of binding to the human Cb1 binding proteins Transcobalamin II (TC II), Intrinsic factor (IF) and Salivary R. This method allows a simple 1 day preparation of high specific activity labelled 57CO SO3-Cb1 for biological studies.


Purification of hepatic phosphoenolpyruvate carboxykinase by affinity and hydrophobic chromatography. Phosphoenolpyruvate carboxykinase has been purified by a procedure involving chromatography on norleucine-Sepharose, using a decreasing (NH4)2 SO4-inorganic phosphate concentration gradient, followed by chromatography on GMP-Sepharose. The enzyme is eluted from the affinity column with 2.5 X 10(-5)m IDP. The same procedure is applicable to hog mitochondrial and cytosol enzymes yielding the enzyme as a single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The corresponding molecular weight is 65,000 for each enzyme. Discontinuous polyacrylamide gel electrophoresis of the mitochondrial enzyme gave two sharp bands that were found to contain carboxykinase activity upon assay of gel slices. Similar analysis of the cytosol enzyme showed a much different staining pattern and four regions of carboxykinase activity. Plots of relative mobility of the two mitochondrial bands vs. per cent polyacrylamide in the gels gave parallel lines, confirming that the two bands did not result from enzyme aggregation. Elution of the enzyme upon analytical Sephacryl S-200 chromatography did, however, produce some resolution of the two bands without change in specific activity. The purification procedure described above has been applied also to the human mitochondrial enzyme with similar results. The molecular weight, similarly is 68,000.


[Uremia and hypothyroidism. Report of a case]. It was diagnosed hypothyroidism in a 53-year-old man with chronic renal failure, with blood urea of 306 mg/dl and serum creatinine of 14.9 mg/dl. At three months of triiodothyronine therapy, the patient became asymptomatic and blood urea and serum creatinine diminished to 49 and 1.1 mg/dl respectively. The possible mechanisms responsible of that reversible uremia of such unusual amount in this hypothyroid patient are discussed.


[Non-parasitic calcified hepatic cyst. Report of a clinical case and review of the literature]. A case is presented of a 40 years old female, with an illness of three weeks duration, characterized by right upper quadrant fullness, pain and tenderness to palpation. Subsequently, her X ray studies showed a radiolucenly in the liver, with calcified solitary-hepatic cyst. A review is made of the pertinent literature, and it is stressed the diagnostic clues between a congenital and a parasitic hepatic cyst, in order to proceed to its proper therapy. Brief considerations of the present knowledge of the congenital calcified hepatic cyst and management are done.


Electrophoresis in gels suspended in hydrophobic solvents. Protein components in mixtures may be separated by zone electrophoresis in columns of gel suspended in hydrophobic solvents. The method is useful for the location of specific antibodies in IgG electrophoretic spectra.


Purification of adenine phosphoribosyltransferase by affinity chromatography. The purine salvage pathway enzyme adenine phosphoribosyltransferase (AMP: pyrophosphate phosphoribosyltransferase EC 2.42.7) has been purified to greater than 85% homogeneity from crude rat liver 100,000 x g supernatant in one step by affinity chromatography. The enzyme binds to an AMP-agarose column and is eluted off the column by 1 mM 5-phosphoribosyl pyrophosphate with a 50 to 80% recovery. Enzyme kinetics indicate that the mechanism of the specific elution is due to competition of the product AMP and substrate 5-phosphoribosyl pyrophosphate for the same site on the enzyme.


A method for the increased extraction of cholesterol from human red blood cells by modified plasma lipoprotein. The in vitro extraction of cholesterol from erythrocytes by plasma lipoproteins of reduced cholesterol content would be expected to be free of cholesterol-unrelated alterations of the cell membrane. The earlier application of this method utilized whole blood plasma in which the major part of the lipoprotein cholesterol was esterified by the plasma enzyme lecithin-cholesterol acyl transferase (LCAT) in a preliminary incubation. Because of the cholesterol remaining unesterified in the plasma, only 35% of the cell cholesterol could be removed. The method reported here uses HDL3, a plasma lipoprotein which is the preferred substrate for LCAT, instead of whole plasma for the extraction. Multiple extractions with LCAT treated HDL3 resulted in the removal of up to 77% of the erythrocyte cholesterol with only minor hemolysis.


[Production of exocellular amylase by pseudomonads]. Over 400 strains of Pseudomonads, when cultivated on starch media, were examined with respect to their capacity for extracellular production of amylases. Seven strains were selected that accumulated up to 6 g/l dry biomass and secreted amylase with an activity of up to 5.4 mg maltose/ml medium. The total and specific growth rate of the cultures was measured. Their physiological and biosynthetic activity in the course of development was evaluated. The economic coefficient was calculated. The dependence of the above parameters on the substrate concentration was demonstrated.


[Effect of serotonin and malate benzyl hydrazine on glutathione peroxidase and lipid peroxidation by rat heart and liver mitochondria]. The effect of serotonin and malate benzyl hydrazine (inhibitor MAO) on the activity of glutathione peroxidase and intensity of ascorbate-dependent peroxidation of lipids in mitochondria was investigated. Serotonin injected intraperitoneally at a concentration of 20 m/kg increased activity of glutathione peroxidase in liver mitochondria and nonfermented ascorbate-dependent peroxidation of lipids in heart mitochondria. In experiments in vitro serotonin and malate benzyl hydrazine decreased activity of glutathione peroxidase an inhibited nonfermented ascorbate-dependent peroxidation in mitochondria of the heart and liver of rats.


Inhalation lung imaging with radioactive aerosols and gases. Krypton lung-imaging is considered the ventilation procedure of choice when it is available. Aerosol and krypton wash-in images both reveal regional abnormalities of ventilation, but the aerosol images also disclose evidence of major airways disease. Xenon wash-out images are probably the most sensitive indicators of regional abnormalities of ventilation and/or small airways obstruction, whereas xenon wash-in images are far less sensitive and may be frequently misinterpreted. The Tc-DTPA aerosol inhalation procedure is perferred over xenon and krypton ventilation imaging for routine use immediately after a perfusion examination in pulmonary embolism suspects. This combined method provides the referring physician with the necessary diagnostic information quickly and with around-the-clock availability. In our opinion, this new aerosol procedure deserves wider application in the diagnosis and management of pulmonary disease. Lung imaging procedures, performed after th inhalation of 99mTechnetium labeled aerosols, 133Xenon and and 81mKrypton gases, were used to visualize the sites of airway obstruction and regional abnormalities of ventilatory function in normal volunteers, patients with obstructive airway disease and pulmonary embolism suspects. This chapter presents intercomparisons of these three methods regarding their functional significance, diagnostic merits, and limitations. A new nebulizer-radioaerosol delivery system is described. Test agent kits are inexpensive and readily available for on site assembly. Currently, we consider radioaerosol imaging in multiple views as more informative and suitable for routine use than xenon methods to detect regional abnormalities of the airways and ventilatory function. The krypton procedure is preferred in pulmonary embolism suspects because it requires far less patient cooperation than the xenon and aerosol methods and the lung images disclose regional ventilatory impairment quickly and accurately. However, krypton gas is cyclotron-produced and not yet commercially available.


Xenon-127.

Xenon-127. The ventilation perfusion study is of proven value in the diagnosis of patients with lung disease. The technique would be even more useful if the ventilation study could be performed after the perfusion lung scan. Then only those patients with a perfusion defect would require a ventilation study and the study could be performed in the position which best demonstrates the lesion. This cannot be done satisfactorily with 133Xe. Because of its physical properties, 127Xe is the isotope of choice for ventilation studies. With this gas, the ventilation study can be performed after the perfusion lung scan with no interference from the 99mTc. The resolution of lesions within the lung is better with 127Xe than with 133Xe. Finally, the reduced tissue absorption and high photon yield permit the use of small amounts of 127Xe and therefore reduced cost and a smaller radiation dose to the patient.


N13-N2(1).

N13-N2(1). 13N when coupled with a positron camera allows excellent quantification and imaging of regional lung function. The studies can be readily repeated since the half-life of the 13N is uncer 10 min and the radiation dose to the patient with each study is low. The very low solubility of 13N not only enhances lung imaging but reduces total body radiation by remaining confined to the lung.


Serum relaxin levels in prostaglandin E2 induced abortions. Relaxin, a peptide hormone produced only by the corpus luteum of pregnancy, can be used as a marker of luteal function in human pregnancy. Serum immunoreactive relaxin levels were measured serially in six women having second trimester abortions induced with intravaginal prostaglandin E2 (PGE2) suppositories. All patients aborted within 17 hours of the first suppository. No significant changes were detectable in serum relaxin levels in any of the patients. It is concluded that PGE2 does not interfere with the corpus luteum's ability to secrete relaxin in the second trimester of human pregnancy.


The action of prostaglandin E2 and F1alpha on myocardial ischaemia-infarction arrhythmias in the dog. Prostaglandin E2 and F1alpha infusions have been tested for their ability to reduce the arrhythmias associated with occlusion of the left descending coronary artery in the anaesthetised dog. At 1 microgram/kg/min both PGs reduced the incidence of premature ventricular contractions occurring during 25-min occlusions, while not reducing the incidence of ventricular fibrillation occurring on occlusion release. When infused for 5-min periods at 1 to 16 microgram/kg/min, neither PGE2 nor PGF1alpha effectively reduced the frequency of ventricular arrhythmias occurring 24 hr after a permanent coronary occlusion.


The effect of physiological levels of non-esterified fatty acids on the radioimmunoassay of prostaglandins. Non-esterified fatty acids (NEFA) can significantly interfere with the radioimmunoassay of PGE and PGF2alpha using commercially available anti-sera. PGB1 antigen-antibody binding is 50% inhibited by 110 pg of PGB1, 48 ng of PGE1, 3.5 microgram of PGF2alpha, or 9.0 microgram linoleic, 14 microgram arachidonic, 22 microgram delta-linoleic, 40 microgram palmitoleic or 45 microgram oleic acids. PGF2alpha antigen-antibody binding is 50% inhibited by 270 pg of PGF2alpha, 70 ng of PGE1, or 4.2 microgram arachidonic, 14 microgram delta-linoleic, 22 microgram linoleic, 70 microgram palmitoleic or 110 microgram oleic acids. Physiological levels of NEFA, such as the quantities found in small volumes of plasma, are sufficient to prohibit accurate prostaglandin measurements. Chromatography on small columns of silicic acid proved to be an effective technique for separation of NEFA and prostaglandin from lipid extracts, however, the results of this study suggest that the interference produced by the presence of NEFA in the measurement of prostaglandin from certain physiological fluids may be avoided if the prostaglandins are not extracted prior to radioimmunoassay.


Prostaglandin production and lipolysis in isolated rat adipocytes as affected by dietary fat. The influence of dietary fat on prostaglandin production and lipolysis was tested in basal and norepinephrine stimulated adipocytes isolated from the epididymal fat pads of fasted rats. Seven diets varying in fat calories and polyunsaturation were utilized. No basal differences were noted for prostaglandin E2 production or lipolysis. Norepinephrine stimulated prostaglandin E2 and F2alpha production was significantly (P less than 0.01) increased with greater polyunsaturation of fat, but not by increased fat calories. Norepinephrine stimulated lipolysis was depressed by an increase in fat calories but was unaffected by the degree of polyunsaturation of fat. This is in vitro evidence against the concept that prostaglandins play a feedback regulator role in fat cell lipolysis since no correlation could be made between the two parameters.


Prostaglandin-mediated hyperemia and renin-mediated hypertension during acute ureteral obstruction. Acute elevation of ureteral pressure to 100 mm Hg in anesthetized dogs (n=7) resulted in an increase (P less than 0.005) in systemic blood pressure form 151 +/- 7 to 163 +/- 7 mm Hg, a transient (approximately 15 min) increase (P less than 0.05) in renal blood flow from 413 +/- 27 to 465 +/- 27 ml/min and a rise (P less than 0.05) in plasma renin activity from 6.0 +/- 1.6 to 10.3 +/- 2.1 ng/ml/hr. Pretreatment with a competitive inhibitor of angiotensin II, i.e. sar1gly8AII, abolished the hypertensive response to acute ureteral obstruction, and pretreatment with 2 mg/kg of either indomethacin (n=6) or meclofenamate (n=3), 15 min before obstruction, prevented the hyperemic response. These results suggest that acute ureteral obstruction leads to hypertension via activation of the renin-angiotensin system and hyperemia via a prostaglandin-initiated mechanism.


Influence of short term dietary supplementation of different lipids on aggregation and arachidonic acid metabolism in rabbit platelets. Semisynthetic diets containing 8% by weight of either corn oil or butter were fed to male New Zealand rabbits for three weeks. The plasma cholesterol values were determined, the threshold concentrations for aggregation of platelet rich plasmas were measured for collagen and Na arachidonate, and the conversion of 14C arachidonic acid to thromboxane B2 and hydroxy fatty acids (HETE and HHT) at 10, 20 and 40 microM substrate concentrations were studied. The thresholds for arachidonate induced aggregation were lower and the amplitudes of collagen induced aggregations were greater in the butter fed than in the corn oil fed rabbits. Conversions of arachidonic acid to thromboxane B2 but not to hydroxy fatty acids were greater in the butter fed rabbits at 10 and 20 microM substrate. The observed changes were accompanied by only slight modifications of plasma cholesterol levels.


Arachidonic acid in amniotic fluid after extra-amniotic instillation of rivanol for midtrimester abortion. Free arachidonic acid was measured by gas liquid chromatography in amniotic fluid in 13 women during induction of midtrimester abortion. The abortions were induced by extraamniotic instillation of 0.1% Rivanol. Serial sampling of amniotic fluid were performed through a transabdominal catheter up to 22 hrs. Free, total arachidonic acid showed a significant increase from 26 +/- 8 ng/ml to 293 +/- 102 ng/ml at 22 hrs. The percentage of free arachidonic acid in total free fatty acids increased significantly from 2.2 +/- 0.5 to 6.1 +/- 1.6+ during the same time. The results suggest a selective release of arachidonic acid during Rivanol-induced abortion.


Induction of second trimester abortion: comparison between vaginal 15-methyl-PGF2alpha methyl ester and intra-amniotic PGF2alpha. The efficiency and acceptability of a single-dose, long-acting vaginal suppository containing 3.0 mg of 15-methyl PGF2alpha methyl ester was compared with intra-amniotic administration of 50 mg of PGF2alpha in 100 patients with a second trimester pregnancy termination. Within 24 hours, 78 per cent of the patients in the vaginal group and 92 per cent in the intra-amniotic group had aborted. The mean induction-abortion interval was 17.9 hours in the vaginal group and 15.8 hours in the intra-amniotic group. Gastrointestinal side-effects were more frequent, but the procedure was less painful, with vaginal 15-methyl PGF2alpha methyl ester than with intra-amniotic PGF2alpha. The vaginal route is technically simple for adaptation to large-scale use, but the high frequency of gastrointestinal side-effects still limits the acceptability of 15-methyl PGF2alpha methyl ester in vaginal administration.


[The correlation between radiological and haemodynamic pictures in the diagnosis of pulmonary hypertension in chronic obstructive diseases (author's transl)]. A comparison between the radiographical findings and the haemodynamic data was made in 53 cases of chronic bronchial obstruction. The results were used in an assessment of the reliability of standard chest X-rays in the diagnosis of pulmonary hypertension. Reference is also made to quantitative indices. Several cases are presented by way of example.


[Use of a standard radioactive paste in the study of esophago-gastric kinesis (author's transl)]. The behaviour of esophago-gastric kinesis has been studied comparatively by administering BaSO4 and normal food respectively, labelled with 1 mCi of 99mTc-DTPA. The results are discussed and the differences observed are stressed. These confirm the non-physiological nature of the conventional opaque paste employed in X-ray diagnosis.


[Computerized axial tomography. Technical principles, clinical application, organizational aspects]. The technical principles, clinical application and organisational problems associated with computerised axial tomography are discussed. Numerous examples of pictures obtained on the brain and the whole body and in the normal subjects and various diseases are presented.


[The intra-arterial use of lidocaine to reduce pain in aorto-femoral arteriography (author's transl)]. In 50 patients subjected to aorto-femoral arteriography, the examination was carried out with and without the addition of 1 cm3 of 2% lidocaine per 10 cm3 of contrast medium; in 43/50 lidocaine led to a more or less notable reduction in pain without side-effects.


[Papillary cancer of the thyroid: biological behaviour and therapeutic planning (author's transl)]. Out of about 600 thyroid tumors treated from 1956 to 1976, a series of 216 papillary cancers were selected at an hystological reevaluation. The correlation between survival rate and clinical features as well as extent of the primary tumor and presence of regional and distant metastases was investigated. An improvement in results may be expected by more extensive surgery on the thyroid, adequate post-operative X-ray and 131I radiation therapy, associated with suppression of TSH production in case of endocrine-dependent tumors.


[A biological approach to the problem of dose fractionation in radiotherapy (author's transl)]. The role of what has come to be called "the four R's" of modern radiobiology is reviewed from a general and applied point of view. Especially, repair of subletal damage, redistribution of cells within their cycle, tissue repopulation, cell reoxygenation, are considered with attention to their intervention in the sterilization of tumor clonogenic cells in human radiotherapy.


[Evaluation of radiotherapy treatment planes in terms of iso-TDF curves (author's transl)]. The usefulness of working out radiotherapy treatment planes using radiobiological iso-effect curves instead of only iso-dose curves is explained. Examples of the application of iso-TDF curves are presented with reference to the method of Ellis.


[Old and new in diagnostic radiology (author's transl)]. Recent advances in diagnostic radiology are reviewed. Reference is also made to the question of keeping down the extent of exposure of the patient. Emphasis is placed on the need for continuous instruction of radiologists on account of the rapid updating of techniques and the state of the art.


[Old and new in obstetrics radiodiagnosis (author's transl)]. After recalling the techniques in use prior to the sixties, the possibilities of employing teleradiopelvimetry and echography are reported. Amniography and its therapeutic applications is discussed in detail.


[Renal agenesia: angiographic diagnosis (author's transl)]. The existence of renal agenesia was noted in 25 cases of about 1,500 abdominal angiographic examinations. Clinical symptomatology and radiological findings are discussed and some cases reported.


[First clinical results with isobutyl-2-cyanoacrylate in the arterial embolisation of cancer of the kidney (author's transl)]. Preoperative embolisation with isobutyl-2-cyanoacrylate by means of an intra-arterial catheter during selective angiography was experimented in 2 cases of carcinoma of the kidney. The technique and the results obtained are described and discussed.


[Outcome of pregnancy and prenatal care among immigrant women (author's transl)]. A retrospective survey on a representative sample of births in France in 1972 relating to more than 11000 women showed the amount of perinatal pathology among immigrants as compared with French women: a higher rate of foetal or neonatal distress, a three to four times higher stillbirth rate among Portuguese and North African women, a prematurity rate more than twice as higher among North African women. When differences in parity and socio-cultural level between immigrant and French women were allowed for, there remained a higher rate of perinatal pathology among immigrants. Prenatal care was also more often inadequate among immigrants, even when taking into account their low socio-cultural standard. Attitude towards prenatal care was highly influenced by the level of adaptation in France. But, even with equal prenatal care, perinatal pathology was higher among immigrant women: being an immigrant is a risk factor in itself.


[Relationship between psychiatric diagnosis and social or medical data in a child mental health center (author's transl)]. The aim of the present study is to point out the most significant sociodemographic and medical parameters related to psychiatric diagnoses, such as registered at the Alfred-Binet Child Mental Health Center (Paris). Statistical analysis shows the specific tendencies of each diagnosis and their similarities. Some diagnoses are particularly associated to negative aspects of the investigated parameters. This is true for psychotic disorders whereas normal variations are linked to positive aspects. Between these two extremes, neurotic disorders, the most numerous, are located in a middle position for all the investigated variables.


[Origin and frequency of the serotypes of Salmonella received in the French national center during the years 1973--1976 (author's transl)]. 38,343 strains of Salmonella (34,138 isolated in Metropolitan France) were examined at the national Salmonella Centre (Pasteur Institute, Paris), during the years 1973 to 1976. The origins are scheduled in this report according to the serotypes classified in alphabetical order with O groups of Kauffmann-White schema. Incidence of II and IV subgenera is low. One serotype of the sub-genus III, S. arizonae 18 : z4, z32 : has appeared in poultry plants, specially in turkeys. The most frequent serotype remains S. typhi-murium, followed by S. wien (appeared in France in 1970), S. saint-paul the numbers of which increase. S. panama is at 4th place. S. isangi and S. ordonez, probably imported from West Africa are in expansion. 29 new serotypes, 5 of which from France, have been discovered.


[Mathematical model of the propagation of a vulpine rabies epizootic (author's transl)]. A mathematical model of propagation of a vulpine rabies epizootic has been worked out in order to build a prediction tool and to fix a suitable prophylaxis. The main ecological hypotheses and their mathematical expression are presented. This consists of a system of two integro-differential equations which have been discretizited to approximate their solution numerically. The results of the simulation of this model are consistent with the data observed in the field.


[The development of potential years of life lost as an indicator of premature mortality (author's transl)]. The indicator of potential years of life lost between ages 1 and 70 (PYLL) is proposed with the primary objective of ranking major causes of premature mortality. This proposal is based on a review of existing mortality indicators and indices and of the history of the concept of potential years of life lost. The method of calculation along with the corresponding rate and the age-adjusted rate are discussed and presented with applications to canadian data and interpretation. Several methodological aspects are discussed, particularly the comparison with more sophisticated approaches based on life tables, which do not appear to alter the ranking of major causes of premature death. This indicator fits well into the category of social indicators and can help health planners define priorities for the prevention of premature deaths. Epidemiological studies could also make use of this indicator of premature mortality. The simplicity of calculation and ease of comprehension should facilitate its use.


[Survival of Yersinia enterocolitica in the environment (author's transl)]. Laboratory experiments have proved that at ambiant temperature in shade Y. enterocolitica can survive in surface water as well as in a dried state. Survival time is variable: (1) In sea water, some strains disappeared in a few days while other strains survived several weeks (2) In spring water, with little organic matter, the number of living organisms diminished rapidly and none could be cultivated after one and a half months, (3) In dry chemically pure sand, the number of living organisms began to fall off after three months and fell to zero after six months, (4) The longest survival time was observed in surface water, rich in organic matter, such as pond waters. After more than 900 days, living organisms could still be isolated. The facts give some insight into the survival of Y. enterocolitica in the environment and help us to understand some epidemiological observations.


[Drinking waters and drug resistant bacteria. Implications for water quality standards (author's transl)]. A systematic investigation of antibiotic sensibility has been carried out on 1,000 strains of enterobacteria and Aeromonas isolated from drinking water. 81,6% are resistant to one or more antibiotics. The incidence of this resistance and its epidemiological consequences are discussed.


Cancer in Cameroon: a relative frequency study. Some 1,390 male and 1,418 female cancer cases examined histologically in Cameroon--1969-1973--were analysed. The relatively most frequent cancers were: Males: skin 30%, malignant lymphomas 13%, primary liver cancer 11%. Females: skin 20%, uterine cervix 16%, breast 10%. Kaposi's sarcoma comprised 31% of all male skin cancer with a high male-female ratio (157/14). Tumours of the lung and intestinal tract were rare. Ethnic differences were noted with regard to cancer of the liver, skin, buccal cavity, lung and bladder. Possible sources of bias are discussed.


[Longitudinal study of vital capacity during the growth of 69 poliomyelitics (author's transl)]. A longitudinal study of vital capacity (VC) during the growth of 69 children with poliomyelitis was made starting shortly after the end of the period of muscular recovery until they attained 17 years. VC was compared with two theoretical values (VCT). The beginning of puberty was determined by the acceleration of growth of total height and the appearance of pubic hair. Statistical analysis of VC/VCT between the beginning and the end of the study reveals that intercostal paralysis, costal deformities, dorsal scoliosis over 30 degrees and atelectasis were significantly more frequent among the 46 children with unfavourable evolution than among the 23 children with favourable evolution. Comparison of the VC/VCT means at different periods of growth reveals that the growth of VC in poliomyelitics does not undergo the same acceleration as that of height during the two years after the beginning of puberty. In normal subjects, this phenomen has not been clearly seen in cross sectional studies which do not take into account the stage of puberty.


[Reducing the burden of hypertension on the community. From control to prevention (author's transl)]. Hypertension is a powerful and widespread cardiovascular risk factor, that can be effectively treated, but is still considerably undertreated. Better control of hypertension could be achieved by enhancing case finding, stimulating antihypertensive drug prescription, and improving patient compliance through a better doctor-patient relationship. Whatever the effectiveness of the current programmes of control of hypertension in the community, it remains to develop a preventive approach based on reducing salt intake and preventing overweight in young adults.


[The health image among the inhabitants of Lorraine. A psycho social approach to the representations of health (author's transl)]. How does the population define health? To put to the test the techniques of a socio-psychological approach to this question, a study was made on a sample of the population of Lorraine who underwent a medical examination: a straight forward question on the best definition of health put to 4,000 participants received 6,172 replies which were classified according to 41 principal themes (or definitions), themselves logically grouped under 10 headings (or groups of definitions). In the different socio-professional categories, which proved to be the most relevant, there was a gradded series of health definitions. It thus appears that the health image varies according to the relationship of the individual to society through his job, since among manual workers the health image is more negative and socialized than among white collar workers where the image is more positive and personalized.


[Effect of atypical mycobacteria infections on BCG immunization in man (author's transl)]. The influence of atypical mycobacteria infections on BCG responses was studied in 1,038 schoolchildren. A comparaison of the sizes of the scars and a study of control tuberculin tests 10 weeks later confirm the experimental results and suggest that there is a protective effect against tuberculosis induced by atypical mycobacteria.


[Health assessment of managers 63 and 64 years old. (Results of the first step of a prospective study on the adaptation to retirement) (author's transl)]. A cross-sectional study has been carried out on a group of 180 male preretired managers and top executives in order to investigate their health status. This study is the first part of a longitudinal survey undertaken to analyze the adjustment to retirement among managers. These 180 subjects were 63 or 64 years old, still working at full time. The study included a standardized medical questionnaire, a medical examination as well as various biological, physiological and psychological measurements. For each main ICD categories of diseases, the prevalence rate was assessed; for each subject two indices of global morbidity were established. Furthermore, some risk factors of cardio-vascular diseases were assessed.


[Water hardness and cardiovascular mortality. Discussion of evidence from geographical pathology (author's transl)]. The existence of a significant negative correlation between hardness of drinking water and mortality rates from cardiovascular disease has been established by numerous authors. The intensity of this relationship varies according to the country concerned, the size of the areas studied, and the confounding factors taken into consideration. Nevertheless, the problem concerning the interpretation of the correlation has not yet been resolved. In particular the methodological problem resulting from the contiguity of the geographic units has been generally neglected. It is shown that these difficulties weaken the conviction that the relationship is a causal one.


[Water hardness and cardiovascular mortality. A study of 947 alsatian communities (author's transl)]. In Alsace (France) drinking water is supplied from two different sources. This situation is favourable to study the effects on human health of various water characteristics, among which hardness. However it would be misleading to consider the 947 towns or villages as independent units of observation because of their geographical adjacencies. An aggregation algorithm of these units has been set up. It consists in a progressive regrouping of adjacent areas, similar "enough" from the point of view of the parameters studied, the aim of the procedure being to get final areas with contrasted values of water characteristics. This partition is then used to compute rank correlation coefficients between water parameters and various mortality rates. With this method, no significant correlation was found between water hardness and mortality, in spite of the existence of a sharp gradient of hardness.


The ascertainment of psychiatric cases in a developing country. This artricle suggests procedures for locating these individuals in a developing country who have mental health problems. It assumes minimum facilities, e.g. that there is no mental hospital and no qualified psychiatrist and is based on experience in Tonga. The register of those involuntarily admitted to an institution looking after the mentally sick is invaluable for a variety of reasons and will well repay detailed study. Voluntary health and Welfare organisations may also supply valuable data. Home visiting often achieves much more than prearranged hospital or clinic appointments which are often not kept. A study of neglected cases may indicate the need to educate a community to recognize the value of medical treatment for the mentally sick.


A method of mortality analysis: application to breast cancer. A regression analysis of mortality can benefit from the introduction of certain apparently redundant factors. Following a description of the method of calculating the regression coefficients, data on mortality from breast cancer in England and Wales for 1951-1970 are analysed as a function of age group, quinquennium of birth and quinquennium of death.


In vitro and in vivo studies on the ovicidal activity of fenbendazole. The in vitro ovicidal activity of fenbendazole against eggs of Ostertagia ostertagi, Haemonchus contortus and Trichostrongylus colubriformis was observed using different concentrations of active principle. The optimum concentration for ovicidal activity is evidently 0.5 ppm fenbendazole. A further increase in concentration results in a decrease in activity which is probably due to physical causes. Ovicidal activity of the product is assessed by the proportion of non embryonated eggs as well as embryonated eggs which are not capable of hatching. By this method of evaluation a higher ovicidal activity is recorded. Ten h after treating sheep with fenbendazole (dose 5 mg/kg) a large number of eggs whose development was inhibited, as well as atypical eggs were detectable in the faeces. Twelve h after treatment, the capacity for development of the eggs was largely suppressed.


Decreased plasma testosterone concentrations in rams affected by ryegrass staggers. Feeding ryegrass, cut from pasture that had caused an outbreak of ryegrass staggers, to 10 mature rams caused a significant decrease in plasma testosterone concentrations in six animals. Six rams also developed staggers, but these did not all have decreased testosterone levels. This discrepancy suggests that toxic pasture could cause these two effects independently.


Effect of repeated injections of iron dextran on the haematological, serological and pathological changes in experimental avian tuberculosis. Eight intramuscular injections of 200 mg/kg of iron (DFe), given as iron dextran twice weekly in the week before and the three weeks after intravenous infection with about 10(7.5) colony-forming units of Mycobacterium avium, significantly prolonged (by about 11 days) the mean 'time-to-death' of immature male fowl (Gallus domesticus) compared with corresponding regimes using dextran (Dx) only or saline, When a proportion of the birds were examined 21 days after infection many of the abnormalities associated with the disease, including a marked hypochromic anaemia, were less severe in DFe-treated than in the Dx- or saline-treated chicks and there were about 10- to 85-fold fewer viable tubercle bacilli in the liver and spleen of the DFe-treated birds.


The efficacy of febantel on gastrointestinal nematodes in sheep. Febantel (Bay h 5757, Rintal) is a broad-spectrum anthelmintic of a new type. A single oral dose of 5 mg/kg is fully effective against larval and adult stages of Haemonchus contortus, Trichostrongylus colubriformis, Oesophagostomum columbianum, Ostertagia circumcincta and Bunostomum trigonocephalum in sheep.


Observations on thyroid hormones in the blood of thoroughbreds. During an investigation of a group of clinically well thoroughbreds housed in the same stable, it was noted that seven of the 14 had no detectable thyroxine in the plasma (less than 5 nmol/litre). An investigation of thoroughbreds in this stable over a five month period suggested that the thyroids were functioning normally and that the thyroxine was excreted in the urine. Thyroxine binding studies on the blood of these horses suggested that the major part of the circulating thyroxine was bound to albumin. The thyroxine had been displaced resulting in an apparent absence of plasma thyroxine since the limit of detection for normal radioimmunoassay is 5 nmol/litre. It is concluded that the measurement of plasma thyroxine as an indication of thyroid function in the thoroughbred can prove unreliable.


Changes in blood values of sheep suffering from acute and chronic helminthiasis. Systematic blood changes in two groups of sheep, one suffering from acute and the other from chronic helminthiasis were studied. In the group with acute infection, there was a rapid increase in helminth egg output coupled with rapid decline in the values of packed cell volume (PCV), haemoglobin (Hb) and red blood cells (RBC). Fluctuations were observed in the value of white blood cells (WBC). In the group with chronic infection, a slow and unsteady increase in helminth egg output was accompanied by a slow and steady fall in the values of PCV, Hb and RBC. As with acute infection, the value of WBC was unsteady.


Effects of rapeseed meal on laying hens (Gallus domesticus) in relation to fatty liver-haemorrhagic syndrome and egg taint. Fatty liver-haemorrhagic syndrome (FLHS) occurred in the controls and was modified in hens that received a diet containing 10 per cent rapeseed meal. This diet increased the extent and severity of the hepatic haemorrhage without affecting the reticulin content of the liver but decreased the body weight and liver lipid levels and so weakened the correlation between these parameters and haemorrhage score found in FLHS. Plasma aspartate transaminase and beta-glucuronidase activities tended to increase with the score. The rapeseed meal diet also produced thyroid hypertrophy and since this was greater in the hens that produced tainted eggs and was positively correlated with the trimethylamine (TMA) content of the eggs it was postulated that rapeseed meal goitrogens may be involved as secondary factors in producing the disturbance in TMA metabolism that causes the egg taint. This abnormality was associated with a reduction in the soluble protein content of the liver, which reflected a decrease in TMA oxidase activity, but was not related to hepatic haemorrhage, steatosis or reticulolysis, or to lipid levels and the activities of lysosomal enzymes and transaminases in the plasma.


Histopathology of the heart from rats fed rapeseed oils. The cardiopathogenicity of oils from new, low erucic acid (EA) rapeseed, Brassica napus, cv Tower (0.88 per cent EA) and Brassica napus, cv 1788 (3.6 per cent EA) were tested on rats following 18 weeks of feeding. Oil from Brassica napus, cv Target, with 38.9 per cent EA served as a positive control and corn oil as the negative control. Tower and 1788 rapeseed oils showed noticeable cardiopathogenicity, and a few mild lesions were also noted in the corn oil group. The main pathological change was from fresh to relatively old foci of myocardial necrosis. The presence of droplets accompanying the platelet aggregates suggested the possibility of their involvement in the development of the lesions. The pathological changes in the small and minute blood vessel walls were interpreted as one of the predisposing factors for the development of fatty embolism and subsequently of myocardial necrosis.


Attempts to demonstrate cell-mediated immune response during Mycoplasma suipneumoniae infection of pigs. Measurements of lymphocyte transformation and skin sensitivity were used to investigate whether pigs previously inoculated with Mycoplasma suipneumoniae would show a T-lymphocyte-mediated immune response. In the lymphocyte transformation test blood lymphocytes, obtained at various intervals after intranasal inoculation of M suipneumoniae cultures, were incubated with specific antigen and the degree of transformation was assessed by 14C-thymidine uptake. Reaction to intradermal antigen was assessed both grossly and histologically. Significant lymphocyte transformation was first obtained at approximately 15 weeks and was demonstrable up to the maximum observation period of 44 weeks after inoculation; this corresponded to the stage of progressive recovery from infection earlier described. Skin hypersensitivity, characterised histologically by perivascular mononuclear cell accumulation in the dermis, was demonstrated in all tests performed between 20 and 46 weeks after inoculation on previously infected pigs, and was apparently enhanced by repeated intranasal inoculation. Both types of responses were more marked in pigs inoculated with pathogenic M suipneumoniae than in pigs inoculated with attenuated M suipneumoniae.


Haematology, weight and condition of captive red grouse (Lagopus lagopus scoticus) infected with caecal threadworm (Trichostrongylus tenuis). Red grouse infected with the caecal threadworm Trichostrongylus tenuis developed a mild anaemia. Haemoglobin and albumin levels in the blood fell but there were no significant changes in the number of red blood cells or their size. In infected birds the numbers of circulating eosinophils and heterophils increase, as did the concentration of alpha, beta and gamma globulin. Body weights did not change but muscle masses shrank. Birds that subsequently died had the lowest concentration of haemoglobin and packed cell volumes and the highest counts of eosinophils. The survivors were affected little by worms and their haematology showed small deviations from normal.


Failure to demonstrate resistance in goats, sheep and cattle to Fasciola hepatica after infection with Cysticercus tenuicollis. Goats, sheep and cattle given 1000--1500 eggs of Taenia hydatigena and challenged orally 12 weeks later with 400 Fasciola hepatica metacercariae, showed no evidence of resistance. The fluke burdens were not significantly different from those in control animals.


The biochemical characteristics of Campylobacter-like organisms from cattle and pigs. Examination of catalase-positive Campylobacter-like organisms from cattle and pig abortions, indicated the existence of two distinct biochemical groups. The group 1 strains, predominantly of intestinal origin, were identified as C fetus subspecies intestinalis whereas the group 2 strains appeared similar but not identical to C fetus subspecies venerealis. This second group of organisms was recovered from fetal and placental tissue of animals which aborted, however, the majority of strains were isolated only at 30 degrees C in media not generally employed for Campylobacter isolation. All of the strains from group 2 became aerotolerant on subculture.


Physiological characteristics of free-living and parasitic stages of strains of Haemonchus contortus, susceptible or resistant to benzimidazole anthelmintics. The effect of changes in genetic constitution (associated with developing benzimidazole resistance) on the physiological characteristics of Haemonchus contortus was investigated. Benzimidazole resistant H contortus were significantly more infective for sheep (20 per cent) than benzimidazole susceptible strains. Pathological changes were more severe in sheep infected with resistant H contortus as measured by packed cell volume, plasma protein concentration and haemoglobin levels. Faecal egg output was significantly higher for resistant strains as was the development and survival of eggs and free-living stages on pasture. Infective third stage larvae of benzimidazole resistant H contortus had a significantly faster exsheathment rate in rumenal fluid than did susceptible strains. These adaptive changes in response to continuing anthelmintic selection of resistant worm populations are discussed and the implications of these findings for worm control programmes indicated.


Characterisation of the antibodies detected by the film inhibition test for Mycoplasma bovis. The class of antibody detected by the film inhibition test was determined. Density gradient ultracentrifugation and disulphide-bond reduction showed it to be 7S(IgG) immunoglobulin. Antibody absorption and ion exchange chromatography studies confirmed this and indicated that IgG2 is probably the major type of antibody involved.


Protection of cattle against Babesia major by the inoculation of irradiated piroplasms. Two experiments were carried out on Babesia major in splenectomised calves. In the first one, the parasite was titrated and a linear relationship was observed between infective dose (10(2)--10(7) parasites) and onset of disease. In the second experiment aliquots of 1.2 X 10(10) parasites were irradiated at doses of 24, 28, 32, 36 and 40 krads and inoculated into groups of calves, while control calves received 1.2 X 10(7) or 1.2 X 10(4) parasites. Animals which received parasites irradiated at 24 or 28 krads had mild reactions and were immune to homologous challenge. Animals receiving parasites irradiated at the higher dose levels had limited ability to resist the challenge.


A technique for measuring hepatic blood flow and oxygen consumption in the anaesthetised pig. A technique for implanting a catheter in the hepatic vein of anaesthetised pigs is described. Hepatic blood flow (mean 1100 ml/min +/- 180 ml/min SEM) was estimated by the hepatic uptake of indocyanine green and the oxygen consumption by the liver (mean 62 ml/min +/- 3.4 ml/min SEM) was calculated from the difference in oxygen content between arterial and hepatic venous blood.


The haemoglobin types of northern Nigerian sheep. The haemoglobin type of 515 sheep from various areas in northern Nigeria was determined. The gene-frequency of the Hb-B type was 1.00 in Uda and Balamy sheep and 0.998 in Yankassas.


The susceptibility of strains of mice to infection with Trypanosoma congolense. The survival times of a number of strains of mice after infection with a stabilate of Trypanosoma brucei or of T congolense were examined. The mean survival times of all the strains when infected with T brucei TREU 667 ranged from 27 to 63 days. Greater disparity was observed after infection with T congolense GVR1 where the mean survival time ranged from seven (BALB/c) to 74 days (C57 Bl). It is suggested that the C57 Bl mouse might provide a laboratory model for the study of trypanotolerance in cattle.


Liquid nitrogen storage of Anaplasma marginale complement-fixation antigen by a multiple small aliquot technique. Anaplasma marginale complement fixation test antigens were frozen as drops in liquid nitrogen using an easily constructed apparatus. Economy in the use of antigen was achieved as the frozen drops were retrieved from storage in any required volume. The potency of the antigen was unaffected by the freezing and thawing technique. The technique is useful for storing other biological reagents.


[Tomographic study in humans of blood flow and oxygen consumption of the brain by continuous inhalation of oxygen 15. Preliminary findings in cerebral ischemic accidents]. Transverse axial tomographic imaging of regional cerebral blood flow (rCBF) and regional oxygen extraction fraction (rOEF) were obtained in 13 patients hospitalizedfor ischemic strokes (eleven middle cerebral artery territory infarcts, one capsular or pontine lacune, one transient hemispheric attack) by continuous inhalation of 15O2 and C15O2 to equilibrium and exclusive detection of the gamma rays emitted in coincidence by means of a tomograph for positron emitting agents. In the transient ischemic attack and in the case of lacune the rCBF and the rOEF images were found to be normal, and they were abnormal in all cases of middle cerebral artery territory infarcts. In recent infarcts, rOEF was always strikingly decreased in the clinically suspected area, whilst the rCBF was either decreased, normal or increased. In infarcts older than 30 days rCBF was always clearly decreased over the clinically suspected area whilst rOEF was in most cases normal or only slightly decreased. These results are briefly discussed. Some practical and theoretical limitations of this method are mentioned. The potential of the present technique appears great however, since it is possible to simultaneously visualize in tomographic fashion the blood flow and the oxygen metabolism in areas of the brain that are of small volume, and however deep they are. A quantification of these parameters is presently under investigation, as well as the verification of the theoretical model on which such method is based. The non-invasiveness of the present method, the feasibility of repeating it at regular intervals of time, and the possibility of measuring the immediate effects of a given therapeutic mode on the regional metabolism of brain all constitute further advantages whose action apply preeminently in the field of the cerebral ischemic diseases.


[Quasi-aphasia associated with thalamic lesions: relation between the language disorder and elective activation of the left hemisphere in 4 cases of left and right thalamic lesions]. The authors report on four patients with vascular lesions of the thalamus, three on the left side and one on the right, two of which were due to haemorrhage and two to infarcts. Language difficulties were observed in those cases with left thalamic lesions only. Speech was either slower or faster than normal, and there were verbal perseveration, semantic paraphasia, and more especially, reduction in verbal fluency with loss of control of logic, causing a true jargon in some tests in certain cases. Articulation, and phonemic programming were unaffected, as were comprehension, reading and writing. A comparison is made between these findings and those reported in the literature. Among the hypo-theses suggested, the authors subscribe to that which accepts the predominant role played by the interruption of the activating system of the left hemisphere by the thalamic lesion. The relative inactivation resulting from this could produce modifications in language dynamics and disturbances in attention in relation to language. The semantic paraphasia could be related to the intrusion of the right hemisphere apparatus into language, because of the lack of balance between the activation of each of the two hemispheres. The fact that thalamic lesions are characterized by language disorders would tend to show that sub-cortical dynamic factors constantly regulate the activation of the hemispheres.


[Frequency and symptomatology of disorders of micturition during cerebrovascular accidents. Interest of complementary examinations (author's transl)]. A total of 228 patients with cerebrovascular accidents have been studied since 1975. Micturition disorders were present in 124 cases (54 p. 100), including total incontinence in 45 p. 100, imperative micturition in 37 p. 100, and complete retention in 18 p. 100 of the patients. They are associated in a significant manner with severe psycho-intellectual disorders, an extensive hemiplegia, bilateral pyramidal signs, and ruological abnormalities. Useful complementary examinations and some therapeutic modalities are briefly reviewed.


[Anatomical and clinical considerations in aphasia: the value of tomodensitometry (author's transl)]. Tomometric tests were carried out in 54 patients with a clinical picture of stabilized or regressive aphasia, some time after the initial episode. The correlation between clinical and topographic findings were satisfactory in 90 p. 100 of the cases. The frequency of lesions extending into several lobes (70 cases) and of multiple lesions is stressed. There is a significant relationship between the severity of the clinical findings  during tomometric testing and the volume or multiplicity of the lesions. The progression of the disease after 6 months, as studied in 31 patients, was also related to the volume of the lesion, but was not influenced by the presence of diffuse atrophy, except where the disease was deteriorating. The value of tomometry in the study of aphasia involves 3 factors: precise clinical and lesional correlation, and the effect of the volume of the lesion on its initial severity and progression. In the future, tomometry should enable a correlative symptomatic study of aphasic disorders to be made.


[Tomodensitometric aspects of 3 cases of acute bismuth encephalopathy (author's transl)]. A study of 3 cases of acute bismuth encephalopathy by C. T. scanner revealed indisputable evidence of abnormal hyperdensity in certain brain regions. These hyperdensities, or rather hyperattenuations, are very typical in case no. 1, where the central grey nuclei, especially the caudate nuclei and cerebral cortex, have an important hyperdence appearance. The images are heterogenous, sometimes granular, and are not modified by the injection of a contrast medium. There are also ventricular and cisternal dilatations which are even more remarkable when the age of the patients (less than 45 years) is considered. Cases Nos. 2 and 3 showed hyperdensity which was mainly in the cortical hemispheres. Blood bismuth levels vary according to the date of bismuth stoppage, lying between 850 and 1.350 microgram p. 1.000 ml. The pathogenesis of these tomodensitometric images are discussed as a function the of atomic number of bismuth metal and its unequal distribution in the cerebral parenchyma and the meninges.


[Electro-oculographic study of a case of abolition of horizontal saccades with viscosity of eye movements in hereditary cerebellar degeneration]. A case of familial cerebellar ataxia is reported during the course of which horizontal ocular movements were slow, and "viscous". The electro-oculographic study showed complete abolition of horizontal jerks, induced by either voluntary, automatic (optokinetic nystagmus), or reflex (vestibular) stimuli. Slow movements, however, were normal, and voluntary vertical jerks were conserved while being slightly slowed towards the top. The physiopathological interpretation of these facts remains a point for discussion. Results from animal experiments and neuropathological studies suggest that the abolition of jerks in such cases is probably due to loss of facilitating influences from the cerebral cortex and central grey nuclei.


[Non-syringomelic medullary syndrome with Arnold-Chiari malformation (author's transl)]. The authors present 15 observations of a medullary syndrome of the non-syringomelic type, in patients with Arnold-Chiari's malformation (type I; 13 times - type II; twice), verified surgically, and without severe malformations of the occipito-vertebral articulation. Brown-Sequard's disease was present in 6 cases, subacute combined degeneration in 2 cases, and pyramidal lesions were very predominant in two other cases. The last 5 cases had cordonal signs associated with signs of disturbance of the anterior horns in the medulla, affecting all four limbs, and more especially the lower limbs. In four cases the medullary cavity was exposed, and in two cases extended along the whole length of the cord up to the terminal cone. The literature is reviewed and diagnostic and pathogenic problems raised by these myelopathies are discussed. They merit systematic investigation.


[Carbon monoxide poisoning of the fetus. Apropos of a clinico-pathological case]. Anatomical and clinical observations are described in a case of carbon monoxide poisoning which caused the death of the baby rapidly. The anatomical lesions are comparable to those observed in 8 other cases reported in the literature. The physiopathological mechanism involved is discussed in relation to previously reported clinical, toxicological, and experimental data.


[Neuropathy in long term treatment with metronidazole (author's transl)]. Two patients developed a sensory neuropathy while under treatment with Metronidazole for Crohn's disease. Recovery took place within a few months after drug withdrawal but was still incomplete in one patient one year after cessation of Metronidazole intake. The incidence of neuropathy appears to be high in long term use of this drug. The morphological study of a sural nerve biopsy showed a severe loss of myelinated fibers (1 800 par mm2). Quantitative teased fibers preparation showed that 56 per cent of the fibers were undergoing wallerian degenerations ; segmental demyelination with subsequent remyelination was found in 4 per cent of the fibers and seem to be secondary to axonal involvement.


[Clinical and epidemiological aspects of human trichostrongyloidosis]. In the course of parazitological investigations in a rural environment, including 2349 subjects, infestation with different helminths was found in 927 persons (39%), i.e. in 49.9% with Ascaris lumbricoides, in 24.1% Trichuris trichiura, in 4.2% Strongyloides stercoralis, in 3.6% Giardia intestinalis, in 2.1% Enterobius vermicularis and in 1.6% Trichostrongylus. There were several cases of associated parasites : Ascaris-Trichuris in 11.1%, Ascaris-Trichostrongylus in 0.2%, Trichostrongylus-Trichuris in 0.3% and other associations in 3% of cases. The patients with trichostrogyliasis were repeatedly examined clinically, radiologically and coproparazitologically throughout the duration of the treatment and after recovery. The treatment consisted of 25 mg Mintezol/kg body weight/day.


[Current possibilities of optimizing emergency tetanus immunization]. Retrospective analysis of the tetanus cases, admitted over a six year period, shows the high risks involved by the insufficient immunoprotection. The failure of emergency immunization, with its effects on the incidence and evolution of the disease, may be accounted for by : the difficulty in establishing the vaccination past history, probable decrease of protection with time due to basal immunization, inconstant response to the booster dose, immunodepressive side effects, the drawbacks of antitoxic serum. With reference to their own experience and the published data concerning the methods applied for obtaining a more rapid response to anatoxin and possible optimizing of the protective titre concurrent with the incubation period of tetanus. Experimental investigations have demonstrated the superiority of repeated, multifocal inoculations for obtaining an earlier antitoxic immunity.


[Incidence of lambliasis in the child population of an urban district]. A study was carried out on the infestation with Giardia lamblia in 9316 children within the district served medically by the Titan University Polyclinic, in 1976. The mean annual infestation was 13.1% with slight monthly differences, except September and October when the proportion of children with G. lamblia exceeded 16%. The infestation was of 4.1% in the 0--1 year age-group, reaching a peak of 16.8% in the 3--5 years age-group, then gradually falling to 6.3% after the age of 14 years. In September and October the incidence increased to 16.9% and 16.4% respectively, but it should be emphasized that in the sick children referred for medical treatment during this period the incidence of infestation was within the mean monthly values for 1976, whereas in the children without clinical symptoms, examined for admission to children's communities, the infestation index rose to 19%. The fact that infestation with G. lamblia is greater in healthy than in sick children renders the control of giardiasis more difficult.


[Normal values of the neutrophil granulocyte adhesion test in the peripheral blood of adults]. After emphasizing the importance of adhesion of cells to a substrate as fundamental biological phenomenon, the authors discuss recently published data concerning adhesion of human neutrophil granulocytes and the clinical implications of its deficiency, showing the method developed in the Center of Haematology, Bucharest, based upon the Taga-Sturdza procedure and the works of Gifford and Malawista. The study included 82 young healthy subjects. The normal mean adhesion index in women was 5.10 +/- 0.34 and in men 4.61 +/- 0.27; the statistical difference between the sexes is not significant. The proportion of NBT-positive adherent cells was 40--60% in both groups.


[Action of some chemical products--insecticides and detergents--on the larvae of mosquitoes of Anopheles labranchiae atroparvus and Culex pipiens autogenicus species]. The larvicide effects of some insecticides and detergents on the Anopheles labranchiae atroparvus species--laboratory colonie--and Culex pipiens autogenicus species, living in flooded basements of some block-houses in the town of Slobozia, were estimated. These products were classified in some categories, depending on their effects: 1. knock-down effect products ; 2. products having a relatively strong effect ; 3. products having a slow effect ; 4. products with a slight effect. Remanence tests were performed on Culex pipiens autogenicus, which showed that Toxid and Lindatox have a longer remanence than the other substances used. In mosquito larvae field control 1 ppm pyrethrum products like Decis and Isathrine, trichlorfon products like Clorofos, Dipterex and Dimetox and organophosphorus carbetox on both species are recommended.


[Histopathology of bone lesions in 9 cases of algodystrophy of the hip]. The authors present the results of histo-pathological observations made in 9 cases of sympatic algodystrophy reflex of the hip, subjected to a punch biopsy of the head and neck of the femur. The punch biopsy was decided upon, either because of difficult diagnosis, or because of the abnormally long duration of the pain syndrome. In all cases, there were bone lesions. The most common were in the marrow tissue, with stasis (9 cases), fibrosis (7 cases) and necrosis at small, isolated points (5 cases). There was osteoclastic resorption in the bones in 3 cases, and rapid osteogenesis in 6 cases. The latter anomaly revealed the rapid reconstruction characterizing the syndrome. Finally, the authors comment on the relationship between algodystrophy and necrosis of the hip, and the advantages of punch biopsy.


[Zinc and enzymes in the synovial fluid and blood in various types of rheumatism]. It appears that in rheumatoid arthritis and, to a lesser extent, in the other forms of inflammatory rheumatism, the level of zinc in the blood serum is lowered, whereas synovial zinc is increased. In the synovial fluid, there is a very significant correlation between enzyme activity and the concentration of zinc. Practical experiments aimed at demonstrating in vitro the action of zinc on lacticodeshydrogenase, acid phosphatase, lysozyme and beta-glucuronidase did not produce the anticipated results and do not explain the metabolic disorders of zinc seen during inflammatory rheumatisms.


[The synovial membrane in articular chondrocalcinosis. Clinico-pathological data]. The study of 25 samples of synovial membrane taken from 118 subjects with articular chondrocalcinosis makes it possible to identify three histological aspects : the complete forms showing a crystalline deposit of calcium pyrophosphate of variable volume and alterations of an inflammatory or degenerative type ; incomplete forms showing no calcium deposit, but in which one can observe two sorts of modifications : forms of chondroid metamorphism or inflammatory stigmatas causing an indeterminate chronic synovitis ; finally, forms of superficial fibrosis of the chorion are sometimes encountered. In all, the synovial membrane in articular chodrocalcinosis is often little different from an arthrosic or senile one. However, the presence of crystalline deposits rich in calcium and phosphorous and varying in size can, in the face of certain articular manifestations of uncertain cause, point to the existence of an articular chondrocalcinosis.


Respiratory cycle time duration during exercise in patients with chronic obstructive lung disease. Respiratory cycle time components during rest and graded exercise were measured in 18 patients with chronic obstructive lung disease, and compared with controls matched for sex and age. For a given exercise level (50 W) increased minute ventilation was present in the patients. This was due to shorter cycle time. Both inspiratory and expiratory time shortened to the same degree rendering the ratio inspiratory time/total respiratory cycle time similar in the two groups. At maximal exercise total respiratory cycle time and inspiratory time was shorter in the patients than in the control group, but the ratio between them was still similar. However, for a given total cycle time during maximal exercise inspiratory time was shorter. Inspiratory time and the ratio inspiratory time/total cycle time as measured during 50 W exercise, were positively correlated with the patient's exercise capacity, but not of sufficient accuracy for useful prediction of the latter. The difference in concomitant variation of tidal volume and inspiratory time during exercise ventilation between the patients and the control subjects seemed satisfactorily explained by the different lung volumes at which the two groups were breathing.


[Possibilities and limitations of immunotherapy in the treatment of malignant neoplasms]. The goal of cancer immunotherapy is to achieve cure when the more usual means of treatment fail to do so. This can be achieved in some animal models where tumor rejection antigens have been demonstrated. In man, the contribution of immunotherapy to the treatment of minimal residual but disseminated disease has been exceedingly poor. This discrepancy should be analyzed, in an effort to detect and define in vitro putative tumor rejection antigens in human tumors.


[Therapeutic advances in breast neoplasms achieved through multimodal treatment]. The epidemiology of breast cancer and the frustrating stagnation of present primary care by local means such as surgery (with or without postoperative radiotherapy) are reviewed. The unsolved problem of early occult micrometastases in breast cancer--as in many other tumors--renders unlikely any real further progress towards higher curability in mammary carcinoma by "optimizing" or even "minimizing" local therapy alone. In contrast, higher remission rates and prolonged tumor control in metastatic breast cancer have been achieved during the last 10 years by advances in combination chemo- or chemo-hormono-therapy. Current controlled studies with adjuvant chemotherapy added to radical mastectomy show encouraging results, such as decreased over-all recurrence rates within 3--4 years and possibly also increased survival. Recent data of Swiss and foreign randomized adjuvant studies in primary breast cancer are reviewed and analyzed. Since mode of administration, duration and patient selection are not yet sufficiently clarified and standardized, routine use of "adjuvant chemotherapy" cannot be advocated on a large scale basis at the present time. There is, however, an urgent need for controlled patient trials with the inclusion of hormonal and possibly immunological "adjuvant regimens", to assure critical evaluation of clinical benefit and protect future patient cohorts from the possible long-term risks of additional primary cytotoxic therapy.


[Interdisciplinary therapeutic planning in the treatment in malignant lymphoma and its results]. The development of curative treatment for malignant lymphoma over the last few years is described. Hodgkin's disease and non-Hodgkin lymphomas are discussed separately. The current improved cure rates for Hodgkin's disease have become possible only with more exact determination of disease stage and a clinically relevant histological classification and definition of other risk factors. These prognostic criteria provide the basis for determining whether radiotherapy alone, chemotherapy alone, or a combination of radiotherapy and chemotherapy offers the best chance for cure. --For the much more heterogenous disease group of non-Hodgkin lymphomas, a similar line of development is in progress. Here better forms of chemotherapy have been of primary importance and have significantly improved the prospects of cure, especially for cases in stage III and IV with unfavorable histologies. Combination treatment with radio- and chemotherapy is still in the developmental stage for non-Hodgkin lymphomas. The place of large volume radiotherapy such as total body or total abdominal irradiation has still to be determined.


[Curability of advanced malignant lymphoma under conditions of modern combination chemotherapy]. 102 patients from the same oncologic center with malignant lymphomas (52 with Hodgkin's disease, 50 with non-Hodgkin lymphomas) have been analyzed. One population received monochemotherapy only and the other polychemotherapy: the first remission and survival results were published in 1975 on the basis of calculated life expectancy. Now, 3 years later, the same populations are again analyzed and "real" survival data are compared with those calculated. All patients now have a minimal observation time of 6 years. Even if our first published data were too optimistic, polychemotherapy still appears to offer the better life expectancy.


[Simultaneous hormonal and drug therapy, compared to hormonal therapy, followed by chemotherapy, in the treatment of metastasizing breast neoplasms. Preliminary results of an ongoing study]. The preliminary results of a still ongoing phase III study in patients with previously untreated metastatic breast cancer are reported. 210 cases are already evaluable. In this study patients are randomized to hormonotherapy either concurrently with combination chemotherapy or alone, chemotherapy being delayed until the occurrence of tumor progression. In both groups patients are further randomly allocated to 3 chemotherapy programs. So far there appear to be differences between remission rates, but not with regard to survival course.


[Effect of anti-inflammatory agents on chemotaxis of human neutrophils studied in vitro]. Using a modified Boyden chamber the effect of three antiinflammatory drugs on the chemotaxis of human neutrophils has been tested in vitro. Gold salt produced a reduction of both neutrophil migration and the ability of plasma to attract this cell. Betamethasone decreased chemotaxis by an action on the cell itself but not on the plasma. Aspirin had no effect on this function. These data suggest that antiinflammatory drugs act through different mechanisms and that the reduction of neutrophil chemotaxis may contribute to the antiinflammatory action of gold salts.