Studies in chronic allergic bronchopulmonary aspergillosis. 3. Immunological findings. Precipitin tests by two different methods, double-diffusion (DD) and counterimmunoelectrophoresis (CIE), and measurements of total and specific IgE against Aspergillus fumigatus were made in 50 patients with chronic allergic bronchopulmonary aspergillosis and in three control groups--atopics with a positive immediate prick test to A. fumigatus but no evidence of allergic aspergillosis, atopics with a negative prick test to A. fumigatus, and non-atopics. Precipitins were found in 84% and 78% of the patients with aspergillosis by the DD and CIE methods respectively. Precipitins were also found in 6 out of 27 (22%) patients with a positive prick test to A. fumigatus but no evidence of aspergillosis and in 1 of 24 patients with a negative prick test to A. fumigatus. The means of specific and total IgE values were significantly higher in the group of patients with aspergillosis than in the three other groups of patients. The increase in specific but not total IgE showed a statistically significant correlation with positive precipitin tests in the patients with aspergillosis. Total IgE but not specific IgE values were significantly higher (0-02 less than P less than 0-05) in patients who had had a transient radiographic shadow in the previous three months. Positive precipitin tests were also significantly correlated with the number of transient shadows in the past and with the interval of time since the last transient shadow.


A computer system for processing data from routine pulmonary function tests. In larger pulmonary function laboratories there is a need for computerised techniques of data processing. A flexible computer system, which is used routinely, is described. The system processes data from a relatively large range of tests. Two types of output are produced--one for laboratory purposes, and one for return to the referring physician. The system adds an automatic interpretative report for each set of results. In developing the interpretative system it has been necessary to utilise a number of arbitrary definitions. The present terminology for reporting pulmonary function tests has limitations. The computer interpretation system affords the opportunity to take account of known interaction between measurements of function and different pathological states.


[Studies for the presence of Salmonella in the bone marrow of normal slaughtered pigs (author's transl)]. Of sixty pigs in which the tonsils, mesenteric lymph nodes, caecal contents, liver and bile, urinary bladder and bone marrow were examined for the presence of Salmonella, thirty-six (60 per cent) were found to be positive. The results were as follows: tonsils alone one, mesenteric lymph nodes alone five, tonsils plus mesenteric lymph nodes two, mesenteric lymph nodes plus caecal contents seven, tonsils plus caecal contents six, tonsils plus mesenteric lymph nodes plus caecal contents six, caecal contents plus liver and bile one, mesenteric lymph nodes plus caecal contents plus liver and bile one. Salmonella was not found to be present in the urinary bladder and bone marrow. It is oncluded that in the manufacture of "meat" (muscular tissue obtained by scraping bones), the bone marrow fraction does not contribute to contamination of this meat with Salmonella. Of the total number of seventy-eight strains isolated, fifty-two were of the sero-type S. typhimurium (66 2/3 per cent).


[Assessment of bacterial counts in the meat-processing industry. II. The plate-loop method and the droplet method (author's transl)]. Two methods used in making bacterial counts of meat and surfaces are discussed. When the plate-loop method is used, dilutions are prepared with calibrated loops in spotting tiles. These loops are also used to swab droplets of these dilutions on quadrants of previously dried agar plates. A formula is presented, which may be used in calculating bacterial counts. When the droplet method is adopted, an apparatus is used to prepare dilutions in tubes containing liquid agar. Drops of agar then are transferred into empty Petri dishes by this apparatus. After incubation, the colonies which have grown in these droplets are counted by a viewer included in the apparatus. Both the plate-loop method and the droplet method (if slightly modified) were found to satisfy the criteria simplicity, reliability and saving time and material. This only holds good when accurate counts are made and when bacterial counts are more than 2,500 bacteria per gram or per sq. cm. When these conditions are complied with, the two methods are suited for routine studies of large numbers of samples.


[Botulism in a number of yearlings (author's transl)]. An outbreak of botulism in four yearlings of a single herd is reported. One animal recovered spontaneously. The other animals underwent euthanasia (animal A) or were slaughtered (animals B and C). Cl. botulinum toxin type C was detected in the sera of animals A and B as well as in the liver and abomasal contents of animal A. In addition, Cl. botulinum was isolated from the liver of animal A. The symptoms are described. Total muscular weakness, also resulting in lingual paralysis and inability to swallow, was the most important clinical feature. The mechanism of action of Cl. botulinum toxin, possible methods of treatment and aspects of meat inspection are discussed.


An apparatus for the simultaneous demineralization of fifty-four specimens. An apparatus designed to demineralize 54 specimens simultaneously is described. A drum with built-in specimen holders rotates continuously through a bath of acid, allowing a free exchange of demineralizing fluid over the specimens. Individual specimens can be easily introduced or withdrawn from the apparatus without disturbing others.


The atrioventricular node, His bundle and bundle branches-a new histologic technique. A technique for examination of the conducting system of the heart is described. A block of tissue embracing the ostium of the coronary sinus, the pars membranacea, the septal leaflet of the tricuspid valve, and appropriate amounts of interatrial and interventricular septum is flattened and fixed in a Kaiserling I solution. Blocks are subsequently cleared in methyl salicylate and trimmed. Sections are cut from the blocks after paraffin embedding beginning from the endocardial surfaces of the right heart chambers. The sections are mounted and stained on 35 mm unperforated leader film and covered with an acrylic preservative. For examination of the conducting system many fewer sections are required than with previous techniques.


Ultrastructure of cells cultured on polycarbonate membranes. A method is described for preparing undisturbed cell cultures for both scanning and transmission electron microscopy. Cells were propagated on polycarbonate membranes with pores of 0.2 micrometer or less. Cultured cells together with their supports were prepared for both scanning electron microscopy and transmission electron microscopy using routine methods. For transmission electron microscopy a rapid schedule of infiltration and polymerization was used. The method described in this report yielded good results and it allowed the fine structure of cultured cells to be viewed in situ by both scanning electron microscopy and transmission electron microscopy.


A hydrostatic device for tissue dehydration. A simple device for mixing water and organic solvents can be easily constructed to dehydrate tissue for electron microscopy. The device utilizes hydrostatic leveling between a reservoir and a mixing chamber to produce a continuously increasing concentration of dehydrating solvent. The rate of dehydration may be regulated by geometry and/or outflow rate. A prototype model is described which compactly incorporates the solvent reservoirs and a tissue tray that can accommodate ten tissue specimens in stainless steel mesh baskets. The device can be fabricated cheaply and replaces manual dehydration.


Clinical evaluation of a new anthelmintic - C. 9333 Go./CGP 4540 in human hookworm infection. A new antihookworm compound, C.9333 Go./CGP 4540, was evaluated clinically in 65 adult patients with hookworm infection. Several dosage schedules were evaluated to determine an effective, well tolerated and convenient regime. The lowest effective dose was 125 mg administered at four-hourly intervals for three doses. The compound was generally well tolerated; mild giddiness was observed in nine patients and severe giddiness was present in one patient. Clinical and biochemical monitoring revealed no other toxicity of the compound.


The traffic of mononuclear phagocytes through renal allografts in sheep. Five to ten per cent of the cells in lymph draining renal allografts in sheep have the morphology of mononuclear phagocytes (MNP). These cells have been examined by light and electron microscopy and their functional characteristics investigated. The vast majority of MNP were of recipient origin. Their traffic increased from about 10(6)/hr immediately after grafting to between 2 and 4 X 10(7)/hr just prior to rejection. During the 1st 2 to 3 days, the majority of MNP had the morphology of monocytes, but the proportion of mature macrophages increased steadily to 30%. During the later stages, many of these large macrophages showed features of activation in terms of their spreading and phagocytic capacities. No NDA synthesis was observed in MNP until the latest stages, when a small proportion (less than 1%) of MNP labelled in vitro. Short-term cultures of lymph cells from kidneys undergoing rejection gave rise to numerous giant cells. It is suggested that there is continual traffic of MNP through the grafted kidney and that a proportion of MNP differentiate within the kidney and show features of activation.


Hypothermic perfusion of rabbit kidneys with solutions containing gelatin polypeptides. Rabbit kidneys were perfused with a solution of extracellular electrolyte composition, made hypertonic with glucose and containing the gelatin polypeptide preparation Haemaccel (Hoechst) as the only colloid. Perfusions were carried out at 5 and 10 C for 19 hr, and function was tested by autografting. All of the kidneys perfused at the higher temperature showed immediate life-sustaining function after transplantation and contralateral nephrectomy, whereas only one graft of five perfused at the lower temperature showed any function. The suitability of the Haemaccel solution as a vehicle for introducing the cryoprotective agent glycerol was tested by perfusing kidneys for 4 hr with a solutiont containing 2% glycerol; the function of these organs was similar to that of kidneys transplanted without perfusion. Ultrastructural examination of kidneys perfused for 24 hr at 10 C showed excellent structural preservation, but measurements of water and ion contents and the penetration of marker molecules in nonmetabolizing kidneys showed 2.8% Haemaccel to be somewhat less effective than 6% bovine serum albumin in stabilizing these values. The Haemaccel perfusate is considered to be highly suitable for the introduction and removal of cryoprotective agents, and the results of hypothermic preservation by continuous perfusion are encouraging.


Antitubular basement membrane antibodies in renal allograft rejection. In a patient with an episode of acute renal allograft rejection, antibodies to tubular basement membranes (TBM) were noted by direct immunofluorescence in a renal biopsy and by indirect immunofluorescence in the serum. The serum antibodies decreased gradually and became undetectable 3 months after the rejected kidney was removed. Anti-RBM antibodies eluted from the rejected kidney were capable of binding in vitro to TBM but not to glomerular basement membranes (GBM) in 39 of 40 human kidneys and various animal kidneys. The specificity was confirmed by blocking studies showing inhibition with ultrasonicated human TBM but not with GBM preparations. Passive transfer experiments showed that anti-TBM antibodies were able to bind in vivo to normal rabbit kidneys, although they could not elicit an inflammatory response. The possible mechanisms of production of anti-TBM antibodies and their potential significance in graft loss are discussed.


Recurrent idiopathic membranous glomerulonephritis. This study reports the clinical and pathological findings in a patient with recurrent membranous glomerulonephritis following transplantation of an HLA-identical kidney. Such a recurrence has been previously reported only once, although membranous glomerulonephritis is a common cause of nephrotic syndrome in adults. This case confirms that membranous glomerulonephritis may occasionally recur following renal transplantation and demonstrates that immunofluorescence and electron microscopic studies may be necessary to distinguish recurrent, membranous glomerulonephritis from the membranous changes frequently seen with chronic rejection. In light of the apparent low incidence of recurrent membranous glomerulonephritis, renal transplantation remains an excellent therapeutic option in this disease.


[Coated vesicles and their functional role in animal cells]. A review is made of the structural organization of coated vesicles, their contents, mode of formation and of destruction and intracellular routes in different cells of various species. Special attention is given to the participation of coated vesicles in the segregation and transferring of diverse substances in the cytoplasm, as well as to the final biological effects of these substances on cell metabolizm. The participation of coated vesicles in intracellular digestion, secretion and neurosecretion, in vitellogenesis and some other cellular function is considered in details.


[Effect of fixation in Carnoy's solution on nucleic acid and protein concentration in the rabbit superior cervical sympathetic ganglion]. By means of biochemical techniques, the stability of RNA, DNA and protein contents has been demonstrated in the rabbit superior cervical sympathetic node fixed in Carnoy's solution for 2 hours at 4 degrees C. A 2 hour fixation in Carnoy's fluid at room temperature, results, however, in a considerable loss of RNA (21%). The loss of DNA and protein did not exceed 2% of the total amount of the fresh ganglion tissue. Fixation at a higher temperature (37%) increased the loss percentage protein and of nucleic acids: 3.1, 5.5 and 42%, for protein, DNA and RNA, resp.


[Electron microscopic study of the interaction of shigellae with cell cultures. III. Functional-structural changes in transplanted amniotic cells exposed to extracellular Flexner shigellae]. A quantitative changes of RNA and proteins and structural peculiarities of compensative-regenerative character were discovered in amnion cells subjected to the action of extracellular virulent shigellas by means of successive cytophotometry and electron microscopy. The long contact with the bacteria lead to increased degenerative changes in the cell cytoplasm. The arising changes seem to involve toxicity caused by the action of exometabolites of Shigella flexneri.


[Preparation and characteristics of antisera to individual histone fractions]. A method is described of preparation and characterization of antisera to pure individual histone fractions not conjugated with other proteins or haptens. Rabbits were given two injections of the antigen and the whole immunization schedule took only three weeks. The antisera were characterized by immunofluorescent technique using mouse liver sections and smears of rat liver nuclei.


Advantages of megavolt electron microscopy in biological research. New electron microscopes, operating within the megavolt range have opened important prospects for scientific research. These microscopes were, at first, mainly used by physicists and metallurgists; but nowadays more and more biologists are interested in high voltage electron microscopy: they have obtained important and significant results. The present paper gives more information concerning experiments that have been achieved in Toulouse with our two big instruments working at 1 million volts (1 MV) and three million volts (3 MV).


Malignancies associated with renal transplantation. An increased incidence of cancer occurs in renal homograft recipients. Malignancies may be inadvertently transplanted with the kidney from donors with cancer, or may arise de novo at some time after transplantation. The latter tumors occur on an average of thirty-four months after the operation. The most common tumors are carcinomas of the skin and lip, lymphomas (mostly reticulum cell sarcomas), and carcinomas of the cervix of the uterus. The lymphomas have a marked predilection for the central nervous system. Besides conventional cancer therapy, reduction or cessation of immunosuppression may be warranted. The development of malignancies is not a contraindication to renal transplantation since the over-all death rate from cancer in kidney homograft recipients is low.


Treatment of complicated urinary tract infections. Comparative study of sisomicin and gentamicin. The efficacy and safety of the two aminoglycoside antibiotics, sisomicin and gentamicin, were investigated in a prospective randomized study of 100 elderly male patients with complicated urinary tract infections. Both drugs were administered intramuscularly, sisomicin twice daily and gentamicin three times daily according to body weight. All bacteria isolated from the urine were sensitive to both antibiotics by disk sensitivity method. Seventy per cent of the patients treated with sisomicn and 63 per cent of those treated with gentamicin were cured of infection. There was no apparent toxicity noted from either drug. The twice daily sisomicin administration appeared to be as effective and safe as the three times daily administration of gentamicin in the treatment of complicated urinary tract infections.


Intrarenal mycotic aneurysm.

Intrarenal mycotic aneurysm. A case is presented of a sixty-seven-year-old man in whom Escherichia coli septicemia developed after catheterization, followed by left renal hemorrhage due to an intrarenal mycotic aneurysm. Because of clinical circumstances that prevailed, treatment was nonsurgical consisting of multiple blood transfusions and intravenous antibiotics. The aneurysm healed spontaneously as proved by subsequent renal arteriography.


The historical development of the staging of bladder tumors: personal reminiscences. Since 1943 we have attempted to stage infiltrating tumors of the bladder. This original grouping required minor revisions as time went on in order to furnish information of prognostic value. The original classification of tumors into A, B1, B2, and C, widely used in the United States and abroad, was improved by Marshall's addition fo O and D, and especially by its conversion into the Tumor Nodes and Metastasis (TNM) System. This latter now appears to be standard for the western World. It is disappointing that the surgical results are not better for the superficial group, even after external radiotherapy. Most probably a markedly improved success rate will depend on new anticancer agents.


Retinal neovascularization in sickle cell retinopathy. Neovascularization of the retina occurs in several types of sickle cell hemoglobinopathies and is highly characteristic in appearance. It arises in the equatorial plane of the fundus following preliminary arteriolar occlusions and arteriolar-venular anastomoses. Neovascular sea fans arise at the interface of perfused and nonperfused portions of the retina, starting during the first decade of life and continuing for many years thereafter. Although some sea fans undergo spontaneous autoinfarction, most show progressive growth and constant intravitreal transudation of plasma components. Traction on the sea fans and the retina results in bleeding into the vitreous, retinal tears, and retinal detachment. Therapeutic intervention with a variety of coagulative techniques is feasible and is usually indicated whenever sea fans are discovered. All therapeutic modalities are capable of inducing significant complications. This is particularly true of argon laser photocoagulation when energy is concentrated into small areas (less than 200 mu) for short durations (less than 0.2 second). With appropriate precautions, photocoagulation results in a high rate of successful obliteration of neovascular tissue. Both vitrectomy and scleral buckling are valuable therapeutic procedures, but both have disproportionately high complication rates in eyes with the propensity for intravascular sickling of erythrocytes. Specific prophylactic measures are therefore indicated when these operative techniques are employed in patients with sickle cell diseases.


A review of exertional rhabdomyolysis in wild and domestic animals and man. Exertional rhabdomyolysis is a condition arising in several species of newly captured wild animals after some form of physical exertion and stress. It is characterized by muscle necrosis and myoglobinuria. Death may result from secondary renal failure, acute or chronic heart failure and progressive emaciation.


Reproductive failure in the pig: diagnosis and control. An approach to reproductive failure in pigs, based on the regular collection and analysis of performance records is proposed. Inovlvement at this level gives veterinary surgeons familiarity with herd mangement and economics. The use of control charts to monitor performance is also advocated for detecting problems as they arise. When failure occurs, a stage-by-stage clinical investigation of the whole breeding programme is advisable. Post mortem studies may also be useful in detecting specific pathological changes. Diagnostic tests should only be used to confirm diagnoses. Having established the source and extent of the failure, and its likely cost, if uncorrected, appropriate measures can be considered. Three principal methods of control are discussed.


Medicare-Medicaid reimbursement policies: report of a study conducted by the Institute of Medicine. On contract with the Social Security Administration, a special steering committee of the institute of Medicine was appointed to (1) study and report on equitable methods of reimbursement for physician's services under Titles 18 and 19 in teaching hospitals; (2) determine to what extent funds from the act are supporting training in specialties in excess supply; (3) determine how funds could be expended to support a more rational distribution of physician manpower both geographically and by specialty; (4) determine the extent these federal funds are being used to encourage teaching programs attracting disproportionate numbers of foreign medical graduates; and (5) determine the extent to which these funds are expended to meet the salaries of interns and residents. Ninety-six hospitals were field studied and 1,400 hospitals studied by questionnaire. These studies have now been completed and reports forwarded to Congress, the Health, Education and Welfare Department (HEW), and the Social Security Administration.


Anaerobic and aerobic bacteriology in head and neck cancer surgery. A prospective study of wound infections following major head and neck cancer surgery was undertaken to define a rational approach to trials of antibiotic prophylaxis and initial therapy of these infections. Preoperative aerobic cultures were taken from the planned site of skin incision and from the oropharynx. Both aerobic and anaerobic cultures were obtained from all wound infections. Patients receiving prophylactic antibiotics were excluded from the study. The data indicate that preoperative cultures are not usually predictive of the bacteriology of subsequent wound infection. Mixed aerobic and anaerobic flora were cultured from most wound infections, and usually reflected normal anaerobic oropharyngeal flora, exogenously acquired Staphylococcus aureus, or both. Bacteroides fragilis was not cultured in this series. Antibiotics selected for trials of prophylaxis or initial treatment of these infections should cover both the resident oral aerobic and anaerobic flora and S aureus. Coverage for B fragilis does not appear necessary. Antibiotic choices might include penicillin G plus a penicillinase-resistant penicillin or a parenteral cephalosporin.


A case of tracheal collapse in the dog.

A case of tracheal collapse in the dog. An eight-year-old male Yorkshire terrier which had had a cough for two years was presented and a diagnosis of tracheal collapse was made after examination with a bronchoscope. It was decided to try to correct the tracheal defect by plication. Two weeks after the operation the dog was examined under general anaesthesia. Although traction had exposed a part of the thoracic trachea it was not sufficient in this case to achieve a complete repair. In view of a grave prognosis, the dog was destroyed.


[Primary free dermatoplasty in surgical treatment of skin melanoma]. At the P. A. Herzen Research Institute of Oncology since 1967 to 1974 during surgical treatment of 108 patients with skin melanoma 114 plastic operations were performed, using free skin plasty with full-sickness graft perforated after the B. V. Parin technic. An analysis of the immediate results of the treatment indicated that complete healing of the graft was gained in 85 (76.4+) cases, partial necrosis being noted in 18 (15.8%), total necrosis--in 8 (7%), suppuration--in 3 (2.6%). Late results of the treatment were followed up in 105 of 108 patients. Recurrences in the graft were observed in 3 patients. Disseminated skin proximal to the transplanted graft--in 6 patients, recurrences in a scar above the graft--in 2.


[Immunologic reactivity in different courses of stomach cancer]. The immunological status was examined in 106 patients with cancer of the stomach, who were subjected to different operative interventions. 74 of them were considered to be operable and 32-inoperable. The immunological activity was compared (according to the tests of cell immunity and general immunological reactivity) in aggressive--unfavourable and torpid-favourable course of the disease. A torpid course of the lesion after surgery for gastric cancer was associated with stabilization and some activation of immune response indices. However, radical operations fail to provide the normalization of these tests, and the state of immune depression in the patients would persist. An aggressive course of the lesion after surgery for gastric cancer was associated with considerable shifts in immunological tests indices toward their suppression, these being increased with the approach of patient's death.


[Permeability of dextran-bound nuclease through the vascular barrier and tumor cell membrane]. Under study was the permeability of nuclease Ser marcescens, bound covalently by the method of diazocombinations with m-amino benzyloxymethyl-dextran of the molecular weight 20 000, 40 000, 60 000 via the vascular barrier and the membrane of tumor cells. It is shown that dextran-bound nuclease as well as the native enzyme would penetrate into the intacts cells of Ehrlich ascites carcinoma. The rate of the modified nuclease penetration is dependent on dextran molecular weight. Along with the native enzyme also nuclease bound to dextran of the molecular weight 20 000 and 40 000 penetrates the vascular barrier. The permeability of the vascular barrier for dextran-bound nuclease is found to be considerably higher in tumor-bearing animals than in intact ones.


Metabolic activation of haloalkanes and tests in vitro for mutagenicity. 1. During incubation of 14CCl4, 14CHCl3, [14C]halothane, or 14CCl3F with liver microsomes and NADPH, considerable radioactivity is bound irreversibly to endoplasmic protein and lipid. However, no 14C was detected in the ribosomal RNA. 2. None of the four haloalkanes studied induced mutations after incubation with liver microsomes and the bacterial tester strains S. typhimurium TA 1535 and TA 1538. 3. Very low or no activity was associated with soluble protein or RNA added to incubation mixtures of the four haloalkanes with liver microsomes.


[Regulation of the endocrine system].

[Regulation of the endocrine system]. The universal significance of the endocrine system for the regulation of the vital functions and the extra ordinarily high biological activity of the hormones require sensitive mechanisms of regulation within this system. The central nervous system is integrated into these regulatory processes and controls by neurotransmitters and hypothalamic releasing and inhibiting of the hormones the secretion of the hypophyseal and peripheral hormones. Central and peripheral feed-back mechanisms making possible the adaptation of the neuroendocrine system to changing external and internal conditions are operative between the peripheral endocrine glands and the hypothalamo-hypophyseal system as well as during synthesis, transport, action and metabolism of hormones. The knowledge of the fundamental regulatory mechanisms is a presupposition for the effective diagnosis and therapy of endocrine dysfunctions.


[Intensive supervision of labor with the help of the computor (author's transl)]. A system of supervision which we developed was described. With this system it is possible to make on-line evaluations of the CTG and postpartal blood analyses from the cord blood via computors (AEG 60-10 and AEG 60-50). The computed parameters together with all obstetrical data collected during the pregnancy (results from ultrasonic tests, estrogen and HPL analyses, anamnestic data and additional "clinical findings") as well as off-line evaluated CTG findings made during the course of the pregnancy were scored. The CTG is evaluated on-line via the "cross correlation function" and can be produced in a wide variety of parameters at any time during labor. The complete system is demonstrated on the basis of an individual case analysis. The first statistical individual case analyses of deceleration in CTG were compared with the classical Hon and Caldeyro-Barcia method of calculation.


The effects of cobra venom factor, an inhibitor of the complement system, on the sequence of morphological events in the rat kidney in experimental pyelonephritis. Acute experimental pyelonephritis has been produced by a combination of mechanical ureteral obstruction and intravenous injection of E. coli (strain IMRU-54). The effects of administration of cobra venom factor, an inhibitor of the complement system, on the sequence of morphologic events in the kidneys have been studied by light and electron microscopy.Pronounced bacterial colonization and suppression of the infiltration of acute inflammatory cells into the kidney were present in the cobra venom factor treated rats on day 2. In these rats, in which the infiltration of polymorphonuclear leukocytes was inhibited, renal structural damage was significantly reduced. The findings appear to indicate that the polymorphonuclear leukocytes infiltrating into the kidney play some role in damaging the renal parenchymal tissue in the early phase of E. coli induced acute pyelonephritis in rats.


[Some new aspects on appendicitis (author's transl)]. 50% of all perforations of the vermiform appendix happen 12 hours or less after onset of the disease. Due to the fact that appendectomy is often done too late that the total mortality rate is still to high. This refers especially to infants and elderly people. Prae-, intra- and postoperative mistakes are analysed. Bacteriologically there are some new aspects concerning anaerobic infections with Bacteroides and Yersinia enterocolitica.


The possible role of prolactin in pre-eclampsia. The primary feature of pre-eclampsia is the pregnancy-associated rise in arterial pressure. Oedema and proteinuria also frequently occur. There is increased responsiveness to pressor agents. Prolactin is present in elevated amounts in human pregnancy and is found in very large quantities in amniotic fluid. Prolactin can cause renal retention of fluid and electrolytes, can elevate arterial pressure and can protentiate responses to pressor agents. It is suggested that either elevated prolactin levels or an increased responsiveness to normal prolactin levels may play a key role in the pathogenesis of preeclampsia.


Hemolysis induced by streptolysin S: kinetics of hemoglobin and 86Rubidium release. Hemolysis of human erythrocytes produced by streptolysin S (SLS) was investigated. Kinetic studies of hemoglobin (Hb) release exhibited typical for SLS latent phase with hemolysis 30-60 minutes after addition of the toxin. Hb release was preceded by efflux of 86Rubidium (86Rb) which started at 5th-15th minutes after addition of the toxin. In erythrocytes treated with 2 HU/ml of SLS about 100% of 86Rb was released after 15 minutes; no hemolysis was observed at this time. Incubation of blood cells in 0.3 M sucrose or 6% DMSO prevented SLS induced hemolysis. Trypan blue was also inhibitory. Bovine serum albumin acclerated 86Rb and Hb release. The possible mechanism of this phenomenon is discussed. The results obtained indicate that SLS-produced hemolysis of human erythrocytes is an osmotic process.


R-factor-mediated antibiotic resistance in E. coli strains isolated from piglets in Sweden. E. coli strains, isolated from piglets over the periods 1964-1968 and 1974-1975, were investigated and compared with respect to antibiotic resistance. The frequency of monoresistant strains decreased from 50% in 1964-68 to 27% in 1974-75, while that of strains showing double or multiple resistance increased from 13% to 22%. The proportions of the different resistance determinants were as follows (figures for 1964-68 within parentheses): Tetracycline 23% (49%), sulphaisodimidine 38% (24%), streptomycin 9% (3%), ampicillin 6% (1%), chloramphenicol 6% (0.5%) and neomycin 4% (0%). All the strains were sensitive to trimethoprim. In 1974-75 the resistance determinants were R factor-carried to the percentage numbers as follows: Tetracycline 53%, sulphaisodimidine 64%, streptomycin 77%, neomycin 65%, ampicillin 95% and chloramphenicol 90%. These determinants were with the exception of tetracycline and sulphaisodimidine predominantly present in multiply resistant strains.


[The growth curves of enterobacteriaceae and the estimation of L-forms under the influence of cephalosporin antibiotics]. The antibacterial effectiveness of cephalothin, cefazolin, cephacetrile and cephradine was investigated on growing cultures of Klebsiella pneumoniae recording the growth curves with a biophotometer. Thereby cefazolin has a greater antibacterial activity than the other cephalosporins. By raising the dose to 100 microgram/ml after initial bactericidal effect a second growth phase was observed. Phase microscopic observation showed that this was caused by an increasing number of L-forms. This phenomenon could be observed with two other strains and seems to be a strain-specific characteristic. It occurs only using cephalosporins and isotonic nutrient media. The medical importance of the described ability of some bacteria as a factor of pathogenicity is discussed.


[Seroepidemiological investigations on the incidence of Brucella canis antibodies in man (author's transl)]. 1915 serum samples of humans were examined in the serum tube agglutination test for antibodies to Brucella canis. 1400 random samples were from blood-donors, 480 samples from clinical patients and 35 samples from persons, exposed to dogs and material infected with Br. canis. Agglutinating antibodies to Br. canis antigen were detected in 6 sera (titers 1 X 1:400, 2 X 1:200, 3 X 1:100). In 3 cases positive results were confirmed by complement fixation and indirect immunofluorescence tests. All serum samples with agglutinating antibodies were from healthy blood-donors. Serum samples from patients, and from 7 veterinary surgeons, 9 laboratory assistants and 19 animal care-takers had no agglutinating antibodies to Br. canis in a serum dilution of 1:50.


[Psychopathometrical results of follow-up studies of trichloroethylene-exposed persons (author's transl)]. Seven clinical healthy volunteers were exposed to trichloroethylene concentration in air with 520 mg/m3 (100 ppm) at an average 6 hours a day on 5 consecutive days. Corresponding volunteers were exposed to a placebo for the same period. --The persons were examined psychopathometrically and biochemically at the beginning and after every day of exposure. The trichloroethylene-metabolites in blood and urine were dated in order to quantify the loads. --Purpose of the psychopathometrical testing methods was the observation, whether a psychological impairment in the sense of a "psychoorganic syndrome" may occur under these exposition-conditions. --Standardized achievement-tests and self-report rating scales were used in order to demonstrate reversible physical provable psychosis that may be possible. Comparing the psychopathometrical results of the exposed and non-exposed volunteers no statistical significant difference was visible in spite of the analytically proved considerable incorporation of the solvent.


[A contribution on the existence of salmonella in surgical wounds (author's transl)]. In a female patient with metastasizing carcinoma S. typhimurium was identified in the laparotomy wound during a period of roughly three weeks. Agglutinating antibodies were not detected. Pathogenetic and hygienic aspects are discussed.


[Investigations made to test the demarcation line method (DLM) after Dienes for its suitability in the epidemiology of Proteus mirabilis (author's transl)]. In 1946, DIENES observed that non-identical Proteus-strains, when swarming towards each other, were froming distinctly demarcated lines ("DIENES' phenomenon", demarcation (=AGL) phenomenon). Strains of the same origin were amalgamating without demarcation. In 1970, STURDZA studied this phenomenon and commented on its relevance for the epidemiology of nosocomial Proteus-infections. An increased number of Proteus-infections in Berlin was the reason that this procedure was tested for epidemiological purposes. Approx. 300 Proteus mirabilis-strains, tested on normal meat fluid agar, could be divided into 52 AGL-groups. When tested by several investigators, the coordination to any AGL-group seemed to be very subjective. Consequently, a DNase-agar with o-toluidinblue as an indicator, as had been mentioned by CHAMBERS in 1975, was used in order to give a more exact demonstration of AGL. This resulted in a reduction from 52 to 42 AGL-groups. Another 140 newly isolated Proteus-strains belonged to the 42 known as well as to another 42 new AGL-groups. Whether these 84 AGL-groups possess the constancy which is imperative for practical purposes, is however, still rather doubtful.


The effect of luteinizing hormone releasing hormone and steroids on the release of LH and FSH from incubated turkey pituitary cells. The secretion of immunoreactive luteinizing hormone (IR-LH) and follicle stimulating hormone (IR-FSH) by turkey pituitary cell suspensions has been investigated. No significant effects of synthetic ovine luteinizing hormone-releasing hormone (LH-RH) on gonadotrophin release were found with cells from 17 to 19 weeks old birds, though IR-LH secretion was elevated with tissue from young (13 weeks) birds. Although IR-FSH secretion was increased in the presence of progesterone alone, effects of oestradiol and testosterone on IR-FSH release and of oestradiol, progesterone and testosterone on LH-RH release were observed when the steroid treatment was combined with that of LH-RH.


Total and "activated" peripheral blood T lymphocytes in patients with thyroid disorders. The percentage of total and "activated" peripheral blood T lymphocytes was measured in patients with (i) hyperthyroid Graves' disease selected for absence of ophthalmopathy, (ii) treated Graves' disease, with ophthalmopathy, and (iii) other thyroid disorders including subacute thyroiditis, using sheep red blood cell rosette tests. No patient had significantly increased levels of either total or "activated" T lymphocytes. On the other hand, the percentage of total T cells was below normal in 8 of 18 patients with hyperthyroid Graves' disease and in 6 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Similarly, low levels of "activated" T cells were demonstrated in 5 of 18 patients with hyperthyroid Graves' disease and in 10 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Three of four patients with subacute thyroiditis tested had depressed levels of total T lymphocytes whilst only one had low levels of "activated" T lymphocytes. Levels returned to normal during the recovery phase in the two patients with positive tests who were retested. Depressed levels of T lymphocyte populations in patients with Graves' disease and subacute thyroiditis may be due to feedback suppression and/or "exhaustion" in association with the thyroidal and orbital immunological reactions.


Current concepts in intrahepatic cholestasis. The investigations on experimental intrahepatic cholestasis of the last 10 years suggest that any of several different functional alterations may lead to cholestasis. In most studies very high doses of cholestatic compounds have been used. The relevance of these studies to clinical syndroms of cholestasis which usually are observed at much lower doses, is unclear. One target of cholestatic compounds may be the lipid phase of several cell structures such as the sinusoidal and canalicular membrane, the endoplasmic reticulum and the mitochondria. By their capacity to interact with the lipid layer and proteins of membranes these compounds impair specific cellular functions: the activity of carrier proteins, the activity of the hydroxylating system and the energy supply. Another target may be the binding proteins in the cytoplasma and possibly the microfilaments. One may suggest that other factors such as interference with regulatory processes in the cell may be of interest in the future. So far the primary event of drug-induced intrahepatic cholestasis is still unknown and it is not even clear whether the increased bile acid levels are cause or consequence of the cholestatic condition.


Perfusion fixation of kidneys in adult pigs for electron microscopy. In five female pigs, weighing approximately 100 kg, laparotomy was made under surgical anesthesia. One kidney was removed for immersion fixation and enzyme histochemistry, while the other kidney was fixed by vascular perfusion without prior interruption of the blood flow. A step-by-step description is given of the perfusion procedure, which requires three assistant. Prior to perfusion, heparin was given in order to prevent intravascular coagulation. 1% glutaraldehyde in Tyrode's solution was used as perfusion fluid. Polyvinylpyrrolidone 2.5% was added in order to adjust the colloid osmotic pressure of the perfusion fluid to that of the blood. Perfusion was maintained for 5 min. The tubules appeared with open lumina, and the proximal tubular cells had evenly arranged brush borders and both lateral and intercellular spaces were narrow and of constant width.


PHA dose dependent defect in lymphocyte stimulation and E-rosette-forming cells in untreated Hodgkin's disease. 14 untreated patients with Hodgkin's disease were tested for lymphocte reactivity in vitro to optimal and suboptimal doses of PHA. A PHA dose-dependent defect in lymphocyte stimulation was demonstrated in patients when compared with a group of normal individuals. No correlation between the in vitro defect and decreased absolute number of E-rosette-forming cells (T-lymphocytes) in peripheral blood was found.


Microbial aggregate contamination of water lines in dental equipment and its control. Water from some dental clinics has been examined and found to be discoloured, badly tasting and with a foul odour. Moreover, brown or black flakes were often present in tap water, as well as in the water lines of dental equipment. Examination by phase-contrast and electron microscope showed the flakes to consist of aggregated fungi and bacteria, and similar structures were found in a layer on the inner surfaces of the clinics water tubes and pipes. The ultrastructure of some aggregating microorganisms, including fungal hyphae and sheath-forming and stalked bacteria, was studied in detail, and several modes of aggregation were suggested. Cultivation of contaminated water samples revealed the presence of filamentous fungi, including Cladosporium and Cephalosporium, and of non-fluorescent Pseudomonas, Aeromonas, Acinetobacter, Alcaligenes, Flavobacterium, and Moraxella (?). Removal of microorganisms from the walls of the tubing was effectively accomplished by rinsing with the non-corrosive solution of 4 per cent Tween 80, coloured with Ponceau 4 R.


Ultrastructural localization of tellurite reduction in Acholeplasma species. Aerobic reduction of tellurite by five Acholeplasma species and two Mycoplasma species was investigated by light and electron microscopy. Among the Acholeplasma species, colonies of A. laidlawii and A. oculi exhibited a heavy, macroscopically visible reduction of tellurite, whereas the reaction of A. axanthum was weaker. A. granularum and A. modicum did not reduce the substrate under the experimental conditions employed. The two subspecies of M. mycoides also reacted with tellurite, as did also the investigated strain of M. bovigenitalium although to a lesser extent. Ultrastructurally, reduction sites were localized to the cytoplasmic membrane in the three tellurite positive Acholeplasma species and apparently to the cytoplasm of M. mycoides subsp. mycoides. Reduction sites could not be demonstrated in M. mycoides subsp. capri and in M. bovigenitalium. The results support previous evidence obtained by biochemical methods which indicates membrane localization of redox enzymes in Acholeplasmas.


The tendency of smooth and rough Salmonella typhimurium bacteria and lipopolysaccharide to hydrophobic and ionic interaction, as studied in aqueous polymer two-phase systems. In aqueous two-phase system, the partition of bacteria and lipopolysaccharide from a rough (R) strain (Rd-mutant) of Salmonella typhimurium is influenced by polymers with covalently linked hydrophobic groups indicating hydrophobic structures accessible at the cell surface. Furthermore, the partition of the R bacteria is influenced by a number of inorganic positive and negative ions, presumably as a consequence of interaction with negatively charged surface structures. In contrast, smooth (S) bacteria and lipopolysaccharide from the parent strain do not seem to participate in either hydrophobic or charge interaction indicating extensive hydrophilicity without charge. Thus, the S-specific polysaccharide side chain of S. typhimurium might serve the purpose of blindfolding aspecific host defence mechanisms dependent on hydrophobicity and charge. On the contrary, the R bacteria and R lipopolysaccharide have physico-chemical properties which predispose to interaction with several types of cells, organelles and molecules.


Observations on the morphology at the transition between the peripheral and the central nervous system in the cat. I. A preparative procedure useful for electron microscopy of the lumbosacral dorsal. A preparatory method, considered to preserve the ultrastructure of the transitional region of lumbosacral dorsal roots in a "useful" way has been tested out. The method consists of vascular perfusion with 5% glutaraldehyde dissolyed in a 300 mOsm Millonig buffer containing 200 mOsm sucrose and 2.7% low molecular dextran, a postfixation in the same medium, a rinse overnight in a normoton phosphate buffer containing 200 mOsm sucrose, an asmication in 2% OsO4 dissolved in a phosphate buffer, an extensive stepwise dehydration starting in 10% acetone and, finally, embedding in Vestopal W.


IgA immunocytes in tonsils.

IgA immunocytes in tonsils. Dimeric IgA-forming cells were studied by a secretory component (SC) affinity test on 20 palatine and 7 pharyngeal tonils from children. This study also included an investigation on the immunoflurescent localization of IgA immunocytes and IgA and SC deposits. The results showed that IgA immunocytes capable of binding SC in tissue sections are present in both palatine and pharyngeal tonsils. However, the number of cells positive for the SC affinity test was significantly lower than that of IgA immunocytes not binding SC. IgA immunocytes were located mainly in the subepithelial area, medullary portion, and occasionally the intraepithelial layer. SC determinants were detected only in some epithelial cells of the pharyngeal tonsils. The findings of the present study suggest that the pharyngeal tonsils share in the local immunological mucosal resistance regulated by secretory IgA, although its activity might be limited.


Psychological approaches to the treatment of the elderly. Various psychological approaches to the treatment of elderly patients (including activity and stimulation programmes, reality orientation, environmental approaches and behabiour modification) are discussed with regard to their efficacy and those features that approaches claiming success have in common. The importance of the attitudes of the care staff is discussed, especially in relation to the consistency and intensity of application of treatment programmes. It is argued that the behavioural model is a useful starting point for future progress, and that much of the present literature is comprehensible in this framework.


The differential effects of meclofenoxate on memory loss in the elderly. A double-blind study of the effects of meclofenoxate on memory performance of fit, able, elderly subjects was carried out. A number of performance measures, designed to measure various aspects of memory function were employed. These revealed that meclofenoxate appears to increase the consolidation of new information into long-term memory, but does not affect other aspects of remembering. It was also found that significantly more of the subjects receiving meclofenoxate reported an increased level of mental alertness.


Nutritional effects of salmonellosis in mice. Mice infected with a standard challenge of Salmonella typhimurium manifest a number of changes associated with endotoxemia. These changes result in profound alterations in the nutritional and metabolic status of the host. Food and water intake approaches levels of total inanition, blood glucose declines more rapidly than in fasted controls, hepatic phosphoenolpyruvate carboxykinase (the enzyme that is rate limiting in gluconeogenesis) shows diminished activity and loss of cortisol inducibility, and hypothermia, rather than hyperthermia, becomes acute. These changes occur at a time when bacteremia is first demonstrable. This occurs on the 3rd day after infection under the conditions employed. Death occurs in most mice within the next 24 to 48 hr. Mice vaccinated with a highly immunogenic ribosomal preparation and subsequently infected with the standard number of organisms did not manifest the above changes. Other work from this laboratory has established that effects of the type described are elicited by bacterial endotoxin as a result of mediating substances released into the blood by cells of the reticuloendothelial system. Presumably these substances appear in blood of infected mice as well.


The sequelae of group B beta-hemolytic streptococcal meningitis in early infancy. The group B beta-hemolytic streptococcus is responsible for an escalating frequency of neonatal meningitis. Of the 18 consecutive cases we report in this study, the mortality was 17%. Among the 15 survivors, there were two children with extensive neurological and psychological impairment. There were no major differences between the survivors and controls in tests of hearing and language function, social skills, and psychological testing. There was a greater number of minor neurological signs among the study group. The mortality and morbidity of group B beta-hemolytic streptococcal meningitis is apparently substantially less than that of all other types of neonatal bacterial meningitis.


Comparison between fenoterol and salbutamol in asthmatic patients. A comparative study was carried out on 76 asthmatic outpatients concerning their immediate response to the inhalation of Salbutamol and Fenoterol. Bronchodilation was evaluated by repeated peak-flow rate (PFR) determinations. All the patients inhaled two puffs of each of both drugs dispensed by metered aerosols. 131 assays were made and in 18 patients both bronchdilators were used. The mean increase of PFR after Salbutamol (200 microgram) was 15.2% and after Fenoterol (400 microgram), 19.5% this difference not being significant. In 18 patients where both drugs were used the increase in PFR was 19.9% after Fenoterol and 16.7% after Salbutamol. No differences between Fenoterol and Salbutamol in subjective clinical improvement and on pulse rate were observed after the use of these bronchodilators.


Overwhelming postsplenectomy infection.

Overwhelming postsplenectomy infection. One of the more intriguing aspects of the spleen is the protection against certain bacterial infections afforded by its unique vascular and immune function. There have been extensive clinical surveys which indicate an incidence of overwhelming postsplenectomy infection (OPSI) above that of the disease for which the splenectomy was done. In the absence of the spleen, either congenital or subsequent to surgical removal, this overwhelming sepsis has a 50% case fatality rate. The most common infective organism has been Diplococcus (tstreptococcus) pneumoniae (D. pneumoniae). Intensive investigations indicated loss of phagocytic function of the spleen, depression of serum IgM levels, a possible suppression of the lymphocyte responsiveness, and changes in opsonin-alternative complement system as potential causes of OPSI. Preventive measures against OPSI include trials of prophylactic Phenoxymethyl Penicillin (penicillin) and pneumococcal vaccine.


Evidence that Aspergillus fumigatus growing in the airway of man can be a potent stimulus of specific and nonspecific IgE formation. Serum IgE levels in patients with allergic bronchopulmonary aspergillosis are elevated but the degree of elevation varies markedly. Serum IgE levels in patients with aspergillomas may be strikingly elevated or normal. Absorption of serums with antigens of Aspergillus fumigatus combined with a solid phase radioimmunoassay technic demonstrated that both immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody activity against A. fumigatus were markedly reduced without a parallel reduction in serum total IgE. These results indicate that the very high levels of serum IgE found in allergic bronchopulmonary aspergillosis and aspergilloma are not all specific IgE. These results are similar to those observed in rats infested with Nippostrongylus brasiliensis. An explanation for the elevations of IgE levels in infestations with A. fumigatus may be analogous to the postulate that parasite-produced materials may result in T cell stimulatory factors for IgE-producing cells. Alternatively, A. fumigatus organisms may produce materials that inhibit T suppressor lymphocytes.


Enteric pathogens: use of flow diagrams for identification. A protocol is presented for the cultural processing of stool specimens. Flow diagrams were developed which allow all stool cultures to be processed in a consistent and efficient manner. Criteria have been established to indicate when definitive identification and antimicrobial susceptibility testing are required. A review of the food-poisoning syndrome and infective gastrointestinal disease due to bacterial agents is included.


Projective assessment of personal space among retarded and nonretarded children. A figure-placement method was used to examine the personal space usage of 60 mildly retarded and 60 nonretarded children of comparable MA. Spatial distance between a self-figure and second figure for both groups was least when the second figure was designated with positive affect, greater when designated with neutral affect, and greatest when the designation involved negative affect. Retarded children used less spatial distance than nonretarded children when the interaction involved a self and teacher figure, supporting Zigler's (1973) positive- and negative-reaction tendency formulation. More space was used by both groups when the second figure was designated as not smart than when designated as smart.


Fluorinated corticosteroid toxicity in infants. An 11-month-old girl died from complications of Cushing's syndrome. The latter was the result of routine topical and periocular dosages of fluorinated corticosteroids following corneal homografts for sclerocornea.


Bishop Harmon forceps with tying platform. A smooth platform added to the Bishop Harmon forceps makes these forceps ideal for tying larger sutures and holding the sclera during detachment surgery.


The role of cell-mediated immunity in the induction of inflammatory responses. Parke-Davis Award Lecture, 1977. Reactions of cell-mediated immunity fall into two broad categories: those that involve direct participation of intact lymphocytes in the effector mechanism of the reaction and those that involve mediation by soluble lymphocyte-derived factors known as lymphokines. The first kind of reaction is essentially limited to lymphocyte-dependent cytotoxicity, although certain aspects of T cell-B cell cooperation may fall into this category as well. The second category appears to comprise the bulk of the so-called cell-mediated immune response and provides a link between this system and the inflammatory system. Various lymphokines have been shown to exert profound influence upon inflammatory cell metabolism, cell surface properties, patterns of cell migration, and the activation of cells for various biologic activities involved in host defense. Although substantial information is now available about various physicochemical as well as biologic properties of lymphokines, purification and characterization data are as yet too incomplete to allow us to ascribe all of these activities to discrete mediator molecules. Current work involving the development of antibody-based techniques for mediator assay may shed light on this issue. Information on the kinds of cells capable of lymphokine production is now available. Contrary to prior expectation, T cells are not unique in their capacity for lymphokine production. Under appropriate circumstances, B cells and even nonlymphoid cells can do so as well. The unique property of lymphocytes in this regard appears to relate to their ability to respond to certain specialized signals such as specific antigen or an appropriate mitogen. Mediator production per se may represent a general biologic phenomenon. Although lymphokines have been defined mainly in terms of in vitro assays, early speculations about their in vivo importance are proving correct. Evidence for the role of lymphokines comes from studies involving detection of lymphokines in tissues, studies involving injection of exogenous lymphokines, and studies involving suppression of in vivo reactions by various techniques. The use of antilymphokine antibodies has proven useful in the latter kinds of experiments. Work in many laboratories is beginning to relate these findings to clinically relevant situations. A major unsolved problem relates to the regulation and control of lymphokine production and activity. At present only a limited body of information is available on this point. This is a potentially fruitful area for future investigation since it may provide techniques for manipulating the immune system in ways that are clinically useful.


The relationship of a serum protein, C1t, to a common nonfibrillar constituent of amyloid (P component) as revealed by immunohistochemical studies. C1t, a serum protein isolated by affinity chromatography on Sepharose bears a remarkable ultrastructural and physiocochemical resemblance to P component, a common constituent of amyloid. This study provides further evidence for their similarity by the demonstration of immunologic identity and by the presence of C1t in amyloid deposits of various types using immunoperoxidase and immunofluorescent techniques. In addition, subcomponents of C1, as well as C3, C4, C5, and properdin, were demonstrated to a limited extent. The possible role of C1t/P component in amyloidogenesis is discussed in the light of recent advances in our knowledge of the nature of amyloid substance.


Phagocytosis. Clinical disorders of recognition and ingestion. Tentative conclusions concerning the role of recognition and ingestion of microorganisms by phagocytes in host defense and the consequences of disorders of phagocytosis can be derived by correlating a) knowledge about recognition and ingestion derived from studies in vitro, b) investigations of the clearance of particulate matter from the circulation of animals and man, and c) analyses of the behavior of phagocytes in patients susceptible to recurrent pyogenic infections. Deficiency of the major serum recognition-conferring (immunoglobulins and complement proteins that deposit a fragment of C3 on microbes) prevents the optimal clearance of virulent encapsulated pathogens by fixed mononuclear phagocytes. Confrontation of phagocytes with particulate matter appearing in pathologic states (viruses, immune complexes, damaged erythrocytes in sickle cell anemia and other hemoglobinopathies) diverts them from their normal task of clearing opsonized encapsulated microorganisms. Corticosteroids impair the phagocytic capacity by an unknown mechanism. Major impediments to progress in this field are inadequate assays for phagocytosis and the difficulty in measuring phagocytosis in the intact organism.


Functional abnormalities of islets of Langerhans of obese hyperglycemic mouse. Glucose-induced insulin release was studied in vitro with isolated islets of Langerhans obtained from obese hyperglycemic C57Bl/6J-ob/ob (ob/ob) and lean C57Bl/6J-+/+ (control) mice. The threshold concentrations of glucose for insulin release were determined. In addition, the effect of total fast and of chronic food restriction on in vitro insulin release were studied. The following was observed: 1) with fasting, islet volume decreased. Islets obtained from ob/ob mice were larger than control islets, except for the chronic food restricted group. 2) Ob/ob islets were more sensitive to glucose than were controls in that the threshold for glucose-induced insulin release occured at lower glucose concentrations. 3) Fasting for 48 h completely abolished glucose-induced insulin release in control islets, whereas glucose-induced insulin release was maintained in 48-h and 7-day fasted ob/ob islets. 4) The increased glucose sensitivity of the ob/ob islets was maintained despite chronic food restriction.


Neurogenic regulation of renal tubular sodium reabsorption. The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies have demonstrated adrenergic nerve terminals in direct contact with basement membranes of mammalian (rat, dog, and monkey) renal tubular epithelial cells. Low-level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. Antinatriuresis was prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Rat kidney micropuncture studies have localized a site of enhanced tubular sodium reabsorption to the proximal tubule. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney on renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. The possible effects of anesthesia and uncertainties about the completeness of surgical renal denervation and other tubular segmental sites of action are critically analyzed. The clinical implications of this mechanism in pathologic conditions of sodium and water retention are discussed and and a prospectus for future work is presented.


Effect of the ionophore A23187 on chloride transport across isolated frog cornea. The ionophore A23187 at a concentration of 10(-7) to 10(-5) M stimulated active transport of Cl across the isolated frog cornea. The ionophore had no effect in a Cl-free medium. Both unidirectional Cl fluxes were increased by A23187. The electrical resistance was decreased, and this can be totally accounted for by the increment in passive Cl fluxes. The effect of A23187 on Cl transport and permeability mimicked the effects of cyclic AMP, isoproterenol, and epinephrine. A23187 had no effect when the corneas were fully stimulated by epinephrine or isoproterenol. A23187 produced normal stimulation of the SCC in corneas pretreated with alpha- and beta-adrenergic blockers. The stimulation of the SCC by A23187 was dependent on the presence of Ca in the Ringer solution. Excess Ca (10 mM) resulted in a reduced response. Increasing the Mg concentration in the medium reduced the stimulation of the SCC with Ca concentrations of 0.1-5 mM, but prevented the relative inhibition of 10 mM Ca. Intracellular Ca concentration seemed to regulate Cl permeability of the cornea.


Construction of a multipolar needle electrode for activation study of the heart. The study of transmural activation of the intact heart requires placement of multipolar needle electrodes through the wall of the beating heart. This report describes a method developed for constructing lightweight multipolar needles with 10-30 leads mounted 1 mm apart. The electrodes are constructed from readily available materials and no special equipment is required. The electrodes are well suited to the intraoperative mapping studies required to surgically correct arrhythmias.


Notes from "Pavlov's Wednesdays": sensory preconditioning. Sensory preconditioning was first demonstrated in Pavlov's laboratory in 1931/32, rather than discovered by Brogden in 1939. Pavlov included nonassociative controls, forward pairing of the indifferent stimuli before reinforcing the second one with shock, and he avoided the development of inhibition to the compound by using a moving visual stimulus and a sound like that of scurrying mice, which both had persistent orienting reactions. Pavlov concluded that the indifferent stimuli were associated by temporal contiguity similar to human associations between successively spoken works. He did not consider the possibility of mediation via the orienting reactions.


Malaria endemicity among Orang Asli (Malaysian aborigines) as determined by indirect fluorescent antibody tests. Fluorescent antibodies were detected in 89% of 288 Orang Asli (Malaysian aborigines) with Plasmodium falciparum antigen and in 62% with P. brasilianum (for P. malariae) antigen. Blood films from 18 donors were positive for P. falciparum; 2 of them had mixed infection with P. vivax. Seven of the P. falciparum-positive blood films were from children in the 2- to 9-year age group. Of 17 sera from cord blood, 16 had significant levels of P. falciparum antibody and 14 of P. malariae antibody, the levels being the same as those of the mothers. None of these babies had congenital malaria. A higher percentage of male donors reacted to both antigens. There was an age dependent increase in the number positive and the maximum titers.


Morphologic variants of Anopheles albimanus and susceptibility to Plasmodium vivax and P. falciparum. Three morphologically different, true-breeding phenotypes have been isolated from a strain of Anopheles albimanus from Lake Apastepeque, El Salvador. Studies with coindigenous strains of Plasmodium vivax and P. falciparum show that these phenotypes differ significantly in their susceptibility to malaria parasites. This difference is apparent both in the number of mosquitoes that become infected and the level of infection obtained. Variations in malaria susceptibility are markedly greater with P. vivax than with P. falciparum. The significance of genetic variants within a local vector population with respect to the epidemiology of malaria is discussed.


Historical note on Loa loa: a reinterpretation. Loa loa, also known as the African eye worm, is a common parasite in the central part of West Africa. As Chrysops silacea and C. dimidiata, the only important vectors of loaiasis, are found exclusively in the tropical rain forests of West Africa, the parasite's transmission is confined to this region. References by early writers to the extraction of Loa loa from the eye of a man on the Island of Ormus (today known as Hormuz or Hormus) in the Persian Gulf apparently were based on a misinterpretation of an illustration by de Bry (1595) of the blinding of a royal relative.


Elution of renal antischistosome antibodies in human schistosomiasis mansoni. Elution of complexed immunoglobulins was carried out in renal tissue obtained at autopsy from schistosomiasis mansoni and control cases. Substantial amounts of IgG were found in acid eluates of 2 of 5 schistosomiasis cases and 2 of 3 controls. The IgG from schistosomiasis cases produced specific indirect immunofluorescence reactions in gut and tegument of sections of adult Schistosoma mansoni; no reactivity was present against egg granulomas, cercariae, or mouse liver tissue. Control case eluates produced no fluorescence with S. mansoni antigens.


Immunosuppression mediated by adult worms in chronic schistosomiasis mansoni. A marked reduction in the number of plaque-forming cells from spleens of mice infected with Schistosoma mansoni to sheep erythrocytes (SRBC) and lipopolysaccharide from Escherichia coli was observed. This reduction coincided with the late stages of the infection and was also observed in unisexual infection with male worms. Treatment of the animals with a schistosomicidal compound (oxamniquine) almost completely abolished the immunosuppression. The suppression could be induced by administration of 60 microgramg protein from worm membrane preparations (24 h before SRBC injection), but not by egg-extract injection. When the crude membrane preparation was injected 48 h before or 0 to 24 h after the SRBC challenge, the immunosuppression was not observed. Significant reduction of footpad swelling was also noted in infected mice when injected with SRBC.


An evolving pattern of human hydatid disease transmission in the United States. Echinococcus granulosus infection was being acquired in the contiguous United States by Virginia sharecroppers and small-holders by the turn of the century. The last recorded human infection from that general area was diagnosed in 1947. By 1920 human infections were also being acquired in the lower Mississippi valley. Apparently, infection in both of these areas was maintained chiefly in swine. By 1940 a third transmission area definitely existed in the Central Valley of California, with its reservoir intermediate host sheep. Seemingly, infection has been disseminated from these California foci into Utah and more recently into northern New Mexico and Arizona. Human populations now at unusual risk in the western United States are transhumant sheep ranchers, including Basque-Americans in California, Mormons in central Utah, and Navajo and Zuni Indians in New Mexico and Arizona. Conditions highly favorable to E. granulosus transmission, intensification and spread now exist throughout relatively large areas of the American West.


Vein grafts: an historical perspective.

Vein grafts: an historical perspective. The use of autogenous vein for vascular grafting has been traced historically. Although vein remains the graft of chocie for smaller vessels, the results are imperfect and the need to identify an "ideal" graft is becoming critical.


The draping of the surgical field for major head and neck surgery. Due to the complexities involved in extensive resections and primary reconstruction necessary in the management of head and neck cancer, a standard draping of the sterile surgical field has been adopted to allow the performance of the anticipated surgical plan or alternatives in an orderly fashion, without disrupting the function of other members of the surgical team.


Aspirin intolerance--a review.

Aspirin intolerance--a review. 1. Association of bronchial asthma, nasal pathology and intolerance to aspirin is a unique syndrome. Aspirin-induced prolongation of bleeding time, and a tendency for diabetes, may exist with it. 2. The syndrome occurs most often in the middle-aged female. 3. Progression of asthma and nasal polyposis is not prevented by avoidance of aspirin. 4. Salicylates other than aspirin are well tolerated but cross-reactivity with other analgesics, and with tartrazine, may occur. 5. The underlying mechanism is unknown. An immunologic basic is most unlikely.


The 1977 Bela Schick Memorial Lecture: disorders of suppressor cells in the pathogenesis of immunodeficiency, autoimmune and allergic diseases: human disease associated with disorders of an immunological breaking system. A series of suppressor cell systems regulate virtually all immunological processes. Disorders of suppressor cells have been identified, including an increased number of activated suppressor T cells in some patients with hypogammaglobulinemia or with selective IgA deficiency. At the other end of the spectrum of immunological response a reduction in suppressor T cell activity has been implicated in the pathogenesis of autoimmune and possibly allergic diseases.


The status of immunotherapy in children--what are the problems? Immunotherapy, widely used in the treatment of atopic disease, poses many problems. In asthma the multiple etiologic factors involved make clinical trials of its efficacy difficult to evaluate and immunological studies are badly needed. Allergen extracts of standard potency are essential. The author feels that practicing allergists must improve their knowledge of and expertise in immunotherapy if the patient is to derive maximum benefit from it.


Method for evaluation of Mycobacterium bovis purified protein derivative tuberculin in experimentally infected cattle. A method for the evaluation of Mycobacterium bovis purified protein derivative (PPD) tuberculin in experimentally infected cattle is presented. The development of skin test responses in M bovis-infected cattle was determined for International Standard PPD-S, M bovis PPD-2, and M bovis PPD-5 at 24, 48, and 72 hours. Significantly larger reactions (dermal thickness) were observed at 48 and 72 hours than at 24 hours (P = 0.001). Statistically significant differences were not detected in the responses obtained with M bovis PPD-2, M bovis PPD-5, and International Standard PPD-S if comparisons were made at approximately the same concentrations in M bovis-infected cattle (P greater than 0.25). In Mycobacterium avium-infected cattle, M bovis PPD-2 produced skin test responses that were significantly smaller than responses obtained using M avium PPD-2 (P = 0.001). Significant variation was not observed in the PPD-S responses in 2 groups of M bovis-infected cattle (P greater than 0.1).


Isolation and identification of anaerobes in the veterinary diagnostic laboratory. In a 1-year survey (1975 to 1976) of anaerobic bacteria recovered from diseased animals, anaerobes were as follows: Clostridium spp, 50%; gram-positive nonspore-forming anaerobic bacilli, 19%; gram-negative anaerobic bacilli, 19%; Actinomyces spp, 10%; and anaerobic cocci, 1%. Anaerobes were in approximately 61% of the specimens that were culturally positive for any bacteria. Approximately 25% of the specimens did not yield any bacteria (sterile specimens). The method for isolating and identifying anaerobes was based upon the use of reducible solid mediums and was specially designed for veterinary diagnostic laboratories. Emphasis was placed on the selection, collection, and transportation of specimens.


Defective monocyte leukotaxis in sarcoidosis: possible relationship to a plasma factor. Monocyte leukotactic function was studied in 25 untreated patients with histologically confirmed sarcoidosis. Monocyte leukotactic responses were significantly depressed (P less than 0.001), most strikingly in patients with stage I disease; however, the severity of the leukotactic defect did not correlate with duration, activity, or extrathoracic dissemination of disease. Preincubation of normal monocytes in sarcoid plasma, but not normal plasma, resulted in partial inhibition of leukotactic responsiveness. The leukotactic inhibition was not reversed by washing the cells after preincubation or by subsequent exposure to normal plasma. The inhibitory activity, which was found in all sarcoid plasma samples, was nondialyzable, was heat stable, and could be localized to the 25 to 35 per cent saturated ammonium sulfate fraction of plasma. Lesser amounts of similar inhibitory activity were detected in comparable fractions of normal plasma. A highly significant correlation between monocyte leukotactic responses and plasma leukotactic inhibitory activity was found in patients with sarcoidosis, suggesting an important in vivo modulatory nole for this substance.


Acetaminophen.

Acetaminophen. Acetaminophen is an effective mild analgesic and antipyretic agent. In double-blind, controlled experimental pain studies of short duration, acetaminophen is superior to placebo and produces analgesia comparable to that produced by aspirin. The frequency of adverse reactions to therapeutic doses of acetaminophen is low, as is that of aspirin. Overdosage with acetaminophen, however, may result in irreversible hepatotoxicity. Since clinical manifestations of intoxication can be of slow onset, physicians may tend to delay initiation of definitive therapy. Intravenous cysteamine, and possibly oral methionine, appear to be effective in preventing hepatotoxicity if they are administered with 10 h of drug ingestion. Physicians should be aware of the potential danger of acetaminophen overdosage and alerted to its clinical manifestations.


NIH conference. Pathophysiology of immune hemolytic anemia. Studies of the pathophysiology of autoimmune hemolytic anemia emphasize the important role of cell membrane receptors for various immunologically active proteins in the clearance of foreign or damaged particulate materials from the blood stream. Receptors for the Fc fragment of immunoglobulin G (IgG) antibodies and for opsonically active fragments of the third component of complement on cells of the reticuloendothelial system function to clear from the circulation erythrocytes coated with these proteins. Our studies show the key role that complement plays in the biologic function of immunoglobulin M (IgM) antibodies like many cold agglutinins and isoagglutinins. They show how complement may contribute to IgG-mediated cell destruction. The IgG and IgM antibodies have dramatically different effects on erythrocyte survival, and these effects explain many of the clinical differences between IgG- and IgM-mediated hemolytic diseases. These studies also show that many of the factors that influence the course of autoimmune hemolytic anemia act by altering the level of immunologic sensitization required to mediate clearance.


Acute severe aortic regurgitation. Pathophysiology, clinical recognition, and management. Acute severe aortic regurgitation is a relatively unfamiliar, though life-threatening, disease. We review its diverse causes, anatomic faults, and hemodynamic sequelae and set the stage for an understanding of the clinical manifestations in light of their physiologic mechanisms. Clinical information includes the natural history, physical signs (physical appearance, systemic arterial pulse, jugular venous pulse, precordial palpation, auscultation), electrocardiogram, and chest roentgenogram. Echocardiographic features are especially emphasized and the need for prompt diagnosis and surgical intervention underscored, even in the setting of active infective endocarditis.


[Teachers in the public primary schools from 1881 to 1918 in France were the 1st pedagogues and the 1st child and juvenile psychologists of the nation]. The scientific history of Humanity can gather from the data coming from the comprehensive account of the existence of austere ways of life of a private person director of a public primary school in the Limousin country around the corner between the past century and the 20e century, illustrating: The work can be hailed as a typical major reform characterised by mastering heart and mind of the juvenile during the period of 1881 to 1918, who became soldiers of the National Army. The teachers of the public primary schools have had the significance of the pacemakers of civic duties and practised what one preaches to the civil population behind battle-front. Teachers of the public primary schools have been the first pioneers pedagogs and child psychologists to the large scale of the French Nation. They have illustrated a holy cause, the national idealism of Victor Duruy.


[The psychiatrist, physician in question]. This article presents a comparative study of the respective fields of medicine and psychiatry resulting from the connection between the meaning of death and that of insanity. It deals, in particular, with the study of the position of certain mental and infections illnesses in the pathological sphere. This is the case, amongst others, of the possible viral etiology of the Kreutzfeld-Jacob disease.


The brain and hearing: auditory discriminations affected by brain lesions. After bilateral ablation of the auditory areas of the cerebral cortex, experimental animals have a severe deficit in ability to discriminate between temporal patterns of tonal stimuli and to localize sound in space. These two kinds of discrimination are basic for communication and for attack or avoidance of prey and predator. Recognition of which ear is stimulated may also depend upon excitation of auditory cortex contralateral to the given ear. Binaural discriminations are dependent upon interaction of nerve impulses from the two ears at a low level in the auditory nervous system. Similar hearing losses have been reported for human patients.


Otosclerotic stapes: morphological and microchemical correlates. An electron microscopic and x-ray analytical investigation. A total of 32 otosclerotic stapes is thin-sectioned without decalcification and examined using transmission and scanning electron microscopes, with a nondispersive x-ray analyzer attached to the latter. These otosclerotic stapes are classified as spongiotic, sclerotic, or preotosclerotic, accoring to their pathologic characteristics and state of mineralization. Either diffuse or patchy demineralization in the ground substance appears to be the initial stage of otosclerosis, and this area coincides with preotosclerotic lesions (also known as blue mantle) in light microscopy. Therefore, it is interpreted that demineralization precedes the destruction of ground substance in the preotosclerotic lesion. Bone mineral deposits in new otosclerotic bone appear to be related to the collagen fibrils that are embedded in the ground substance. No mineral deposit could be seen without the ground substance deposition; therefore, it is suggested that this ground substance is the single most important factor in the poor mineralization of the otosclerosis. The sclerotic lesions are well mineralized and show a typical pattern of hydroxyapatite by x-ray diffraction study. We could not confirm the notion that the sclerotic lesion is hypermineralized as compared to the normal stapes. The spongiotic lesions are poorly mineralized, with low calcium salt. Using the Ca/P ratio and x-ray diffraction pattern as criteria, it was determined that spongiotic lesions belong to unstable, immature bone.


Chemotherapy in bronchogenic carcinoma.

Chemotherapy in bronchogenic carcinoma. The effects of three different chemotherapeutic treatment regimens on the survival of one hundred inoperable lung cancer patients was studied in a randomized clinical trial. Of the patients 36 received cyclophosphamide as a single agent, 31 patients actinomycin D--vincristine combination and 33 patients cyclophosphamide--methotrexate--vincristine combination. Epidermoid carcinoma was the most sensitive to the actinomycin D--vincristine combination, whereas small cell anaplastic carcinoma responded to cyclophosphamide alone, and to the cyclophosphamide--methotrexate--vincristine combination. In spite of shrinkage of the tumour no differences were, however, observed in the survival times of the eifferent groups.


Psychomotor skills during acute and two-week treatment with mianserin (ORG GB 94) and amitriptyline, and their combined effects with alcohol. Twenty paid healthy volunteers took a placebo, 10 mg of mianserin and 25 mg of amitriptyline, t.i.d. for two weeks each, in a double-blind cross-over manner. There was one week's "wash-out" between the treatments. Several psychomotor tests were done on the first, 7th and 14th days of each period with either alcohol (0.5 g/kg) or a placebo drink. Co-ordinative and reactive skills and critical flicker frequency were affected by all the drug-drink combinations while attention was slightly impaired only after amitriptyline alone or mianserin together with alcohol. Drug actions and drug-alcohol interactions were most obvious on the first day but declined towards the end of the drug periods. After mianserin the skills were impaired on the first day only, but after amitriptyline up to the 7th day in most of the tests. Both drugs seemed to interact additively with alcohol. Impairment of flicker fusion by amitriptyline + alcohol remained constant over the whole 2-week period. Psychomotor effects of antidepressants have practical importance in the acute phase of treatment. Their concurrent use with alcohol must increase accident risk in traffic.


The efficacy of single dose of pindolol in hypertension. The effect of pindolol was studied in 32 patients suffering from hypertension of WHO grad I or II. 25 of these patients respondered to pindolol administered three times daily, and were thereafter treated with a single 20-40 mg dose of pindolol. Normotension was achieved in 15 patients and a satisfactory result in five patients but three patients did not respond to the single dose and two had to interrupt their treatment because of side effects. The side effects were generally mild. As a significant observation NaCl retention was found. It may be due to the preceeding diuretic treatment in most patients, but nevertheless needs further investigations.


[Antibiotics sensitivity of "hospital" strains of S. typhimurium]. Sensitivity of Styphimurium strains isolated under conditions of a hospital infection to antibiotics were studied in comparison with the strains of the given serological type isolated from other sources and with the strains of other serological types of groups B, C, D and E. It was shown that the strains causing outbreaks of hospital infections were characterized by polyresistance to 7 out of 9 antibiotics tested. All the Salmonella strains tested were sensitive to gentamicin and about a half of them was sensitive to polymyxin M.


[Development of a method for the quantitative assessment of the microorganism sensitivity to antibiotics by using discs. A study of the patterns of doxycycline diffusion from discs into the nutrient agar]. Doxycycline concentrations provided by the antibiotic diffusion from paper discs into sterile agarized medium and the medium plated with staphylococci and Coli bacteria were studied at different distances from the disc center. Infection of the nutrient medium with the test cultures had no effect on the antibiotic diffusion rate. A linear relation between the logarithm of the antibiotic concentration in the agar and distance from the disc centre were found. Probably it is possible to determine the MIC of the antibiotic with respect to various microorganisms by the value of the radius of the growth inhibition zone around the disc using diagrams expressing such a relation.


[Effect of furosemide on the pharmacokinetics of benzylpenicillin and its penetration through the hematoencephalic barrier in experimental and clinical meningococcic meningitis]. Pharmacokinetics of sodium benzylpenicillin after intramuscular administration in a dose of 250 000 gamma/kg and simultaneous intramuscular injection of furosemid (lazix) in doses of 0.5--1--2 mg/kg was studied in experiments on a model of meningococcal meningitis of rabbits and in clinics on patients with meningococcal meningitis. A pronounced effect of furosemid on pharmacokinetics of benzylpenicillin as dependent on a number of factors was found. Furosemid and meningococcal endotoxin had a synergic effect and decreased benzylpenicillin excretion with urine resulting in prolongation of the antibiotic effect in the blood. An increase in benzylpenicillin blood levels and inflammation of the soft brain membranes increased permeability of the hemato-encephalic barrier for the antibiotic.


[Electron microscopic study of the combined action of ampicillin and cephalexin on E. coli]. The data of electron microscopy study of morphological variation of E. coli, strain 423 in the logarithmic phase after exposure to ampicillin (2 gamma/ml) and cephalexin (4 gamma/ml) are presented. Pronounced ultrastructural changes not only in the cell wall but also in the cytoplasm were found. After exposure to ampicillin alone changes of the same type were observed. However, after exposure to the combination of the 2 antibiotics these changes were more pronounced and observed in the predominating part of the cells. Examination of ultrathin slices of the strain treated with cephalexin revealed no ultrastructural changes. The morphological changes in the cells of E. coli, strain 423 after its treatment with ampicillin and cephalexin combination were due mainly to ampicillin effect, while cephalexin increased the level of the changes.


[Effectiveness of gentamicin sulfate in suppurative-inflammatory processes of varying localization]. Antibiotic sensitivity of 486 strains of grampositive and gramnegative organisms isolated from patients with purulent infections was studied in vitro. Gentamicin was shown to be highly active as compared to kanamycin and other antibiotics against the main causative agents of purulent inflammatory infections including multiresistant E. coli, Proteus, Ps. aeruginosa, Staphylococcus. High efficiency of gentamicin in therapy of peritonitis, septic conditions, purulent postoperative wounds, infections of the urinary tract, pneumonia, etc. (197 patients) was shown. Positive results were obtained in 87.4 per cent of the cases. Side effects, such as albuminuria, hyperthermic reaction, rash, pruritus were registered in 3 per cent of the patients.


[Use of aminoglycosides and other antibacterial preparations in gastroenterology]. Kanamycin and monomycin were used in the treatment of 945 severe surgical patients. Examination of antibiograms showed that the microflora of the patients was moderately and highly sensitive. The antibotic blood levels defined the tactics of the drug administration rate and route. The antibiotic treatment was accompanied by complex therapy for increasing the host protective forces. The antibiotic treatment was well tolerated by the patients. No impairements of the kidneys or the VIII pair of the cranial nerve were observed. Allergic reactions in the form of urticaria were registered in several patients.


[Structure of the antibiotic resistance of the salmonellae found in Transcarpathia]. Resistance of 1280 strains of Salmonella of various serological types isolated in the Zakarpatskaya region within 1967-1976 was studied with respect to benzylpenicillin, streptomycin tetracycline, levomycetin, monomycin, neomycin, erythromycin and oleandomycin. An Increase in the resistance of Salmonella to streptomycin, tetracycline, levomycetin, monomycin and neomycin was shown. During the last years Salmonellae carrying 4-8 resistance determinants were spreading in the region. Among S. typhimurium strains with 7-8 resistance determinants predominated (58.8 per cent). The cases of salmonollosis were mainly due to these strains.


[Morphological changes in experimental infection in guinea pigs under the influence of prodigiozan and S-methylmethionine]. The effect of prodigiozan and S-methylmethionine on the level of histomorphological changes in the organs and tissues of guinea pigs with experimental typhoid fever, dysentery and staphylococcal infections, as well as the effect of prednizolone with respect to dysentery and staphylococcal infections were studied. In the control animals the highest histomorphological changes were observed on the 4th day after the infection in the liver, kidneys and spleen. In the animals with staphylococcal infection such changes were also observed in the lung tissue. In the animals treated with prodigiozan or S-methylmethionine in a dose of 20 mg or 0.3 ml of a 5 per cent solution respectively simultaneously with or 2 days after the infection the changes in the organs were less pronounced than those in the control. Under the effect of prednizolone used in a dose of 10 mg according to the same schedule the inflammatory-dystrophic changes in the internal organs of the animals with dysentery and staphylococcal infections were much higher as compared to the control.


[Results of determining the sensitivity of hypernephroid cancer to cytostatic agents in vitro and clinically]. Sensitivity of the cells of 57 human hypernephromas was determined with respect to 8 drugs, i.e. tiodipin, fluorbenzotef, mithramycin, cyclophosphan, tiotef, rubomycin, 5-fluoruracyl and olivomycin with the help of the method of primary plasma cultures. Because of the changes introduced earlier into the estimative concentrations used in vitro, coincidence of the results of the sensitivity determined in vitro with the results obtained during the treatment of the same patients in clinics, significantly increased (up to 90 per cent).


Novel R-plasmid-mediated beta-lactamase from Klebsiella aerogenes. A novel beta-lactamase with a broad spectrum of activity against penicillins and cephalosporins has been detected in a strain of Klebsiella aerogenes. Its synthesis is mediated by an R-plasmid of molecular weight 64 x 10(6).


Antagonistic action of lipid components of membranes from Candida albicans and various other lipids on two imidazole antimycotics, clotrimazole and miconazole. The growth-inhibitory activity of two imidazole antimycotics, clotrimazole and miconazole, against Candida albicans was significantly reversed when lipid extracts from protoplast membranes of the same organism were added to the assay medium together with the drugs. Of four major classes of lipids further separated from them, viz., phospholipids, triglycerides, sterol esters, and free sterols, the former two were capable of counteracting both drugs, whereas the latter two were not. However, even with phospholipids or triglycerides, no antagonism was noted when they were saturated by catalytic hydrogenation before use. The antagonistic effect of varying classes of commercial lipids, including phospholipids, acylglycerides, sterols, and fatty acids, was also studied by means of the agar diffusion technique. Significant antagonism to both drugs was observed with: (i) phospholipids with an unsaturated acyl group; (ii) acylglycerides, the ester portion of which consists of unsaturated fatty acid; (iii) ultraviolet-activated sterols; and (iv) unsaturated fatty acids of cis-configuration. By contrast, none of the saturated phospholipids and acylglycerides nor sterols was effective as an antagonist. With the exception only of lauric acid, all of a series of saturated fatty acids and unsaturated trans-fatty acids ranging from C(8) to C(18) in chain length were either minimally effective or completely ineffective. Essentially, there was no qualitative difference between clotrimazole and miconazole in the response to these various lipids.


Mutagenic studies of folic acid antagonists. Compounds that compete with folic acid (folic acid antagonists [FAAs]) become limited in their usefulness in the treatment of leukemia, malaria, and bacterial infections by the rapid development of resistance. Assays of the plasma levels of certain of these FAAs led to the observation, in about 25% of the determinations, that a higher density of growth of Streptococcus faecium var. durans (ATCC 8043) was obtained at an FAA concentration just below the completely inhibitory level than at one-half this concentration. This and other considerations suggested that FAAs may act not only as selective agents for resistant organisms but also as mutagens. Seven FAAs including amethopterin, pyrimethamine, trimethoprim, chlorguanide triazine, an experimental quinazoline, WR-158,122, and two experimental triazines, WR-99,210 and WR-38,839, were tested for mutagenicity in the Salmonella reversion assay developed by Ames et al. (1975). All were found to be negative for strains TA1535, TA1537, TA1538, TA98, and TA100, both with and without microsomal activation. These compounds were then tested as mutagens for three traits in the folic acid-requiring S. faecium. FAAs were shown to cause mutations to folic acid independence, rifampin resistance, and FAA resistance. It is postulated that the FAAs induce mutations by causing thymine deprivation in the folic acid-requiring host.


Rapid detection of microbial contamination in frozen vegetables by automated impedance measurements. Automated impedance measurements can be used to rapidly assess whether a sample of frozen vegetables contains greater or less than 10(5) organisms per g. Microorganisms growing pureed food samples cause a change in the impedance of the medium when the organisms reach a threshold concentration of between 10(6) and 10(7) organisms per ml. Estimates of the concentration of microorganisms initially present in the food sample can be made by recording the time required for the organisms in the sample to replicate to threshold levels. In this study, the detection times for 357 samples of frozen vegetables were compared with standard plate counts for each sample. The agreement between the two methods in distinguishing samples containing more than 10(5) organisms per g was 92.6% for 257 assorted frozen vegetables and somewhat higher (93 to 96%) when separate cutoff times were used for each type of vegetable. The time required for analysis was about 5 h, compared to the 48 to 72 h required for standard plate counts.