[Dopamine effects on the pulmonary circulation of innervated and autotransplanted lungs (author's transl)]. The effects of dopamine on the pulmonary vascular resistance were investigated in 7 normal and 9 autotransplanted canine lungs during perfusion in situ. Dopamine (up to 13,5 gamma/kg BW, rapid injection) acts as a vasoconstrictor by alpha-receptor stimulation. Vasodilative effects could not be registered neither by very small amounts of dopamine nor during alpha-blockade with phentolamine. No difference could be detected between the vascular reactions of normal and autotransplanted lungs.


[Adhesive sealing of fissures and pits for the prevention of caries. Review]. Conformably to the order received, the present contribution aims, as desired by the editor, at meeting the information requirements of the practitioner as completely as possible. For that reason, the cruical points are stressed. This complex of questions is also analysed from the aspect of the author's opinion. This analysis is intended for aiding the reader in processing source material and in forming his own opinion. Starting from the epidemiological foundation of the necessity of caries prevention, the author integrates the method of adhesive sealing and describes the necessary materials and the various steps of the procedure. The article centers in a critical interpretation of its preventive efficiency in clinic and experiment and ends in an outlook.


[Prosthetic aids in the resection of the middle portion of the mandible]. Prosthetic aids in resections of the middle piece of the mandible. The authors describe a prosthesis which is inserted during the resection of the middle piece of the mandible. Due to its construction it prevents the soft tissues of the floor of the mouth from sinking back. Such a prosthesis has been used in 18 cases. Respiratory complications did not occur; no tracheotomy was necessary. During the postoperative phase, the prosthesis came up to expectations, but it could not prevent cicatricial contraction in the operating area. Occlusion-conformable positioning of the fragments will be achieved only it the remaining teeth are suited for function-stable prosthetic care. Consequently, secondary osteoplasty should not be abandoned.


Specificity and immunosuppressive potency of a rabbit antimouse T cell-specific antiserum. An attempt was made to prepare a specific heterologous rabbit antimouse T cell antiserum (anti-MTLA) by absorbing rabbit antimouse thymocyte globulin (ATG) with spleen cells from BALB/c TXBM mice. Cytotoxicity data showed that whereas ATG was cytotoxic to both T and B cells, anti-MTLA was highly cytotoxic to only T cells. Whereas spleen cells treated with ATG and complement (C) failed to respond in all assays studied, spleen cells treated with anti-MTLA and C: (1) responded to the B cell mitogens but failed to respond to the T cell mitogens; (2) were able to stimulate allogeneic spleen cells but failed to respond to mixed lymphocyte culture (3) failed to act as T killer cells in the CML reaction but retained their ability to kill antibody-coated target cells; and (4) did not cause a graft-versus-host reaction when injected in allogeneic mice and increased their survival significantly. Furthermore, anti-MTLA was just as immunosuppressive in vivo as ATG in its ability to suppress the immune response to sheep red blood cells and prolong skin allograft survival. Anti-MTLA was found to be different in specificities from anti-theta serum by several points: (1) it was cytotoxic for T cells from both theta-C3H and theta-AKR mice; (2) it was highly immunosuppressive in vivo when compared to anti-theta serum; (3) absorption of anti-MTLA with mouse brain did not decrease the immunosuppressive activity; and (4) rabbit antimouse brain antiserum failed to show any immunosuppressive activity. These data indicate that anti-MTLA is a specific antiserum against a unique marker on T cells distinct from the theta marker.


The role of the spleen in the rejection and enhancement of renal allografts in the rat. As rats were splenectomised up to 7 weeks before or at the time of receiving an (AS times August)F1 kidney allograft. Only 2 of 19 splenectomised recipients rejected their grafts within 12 days, and 14 of the 19 survived for more than 100 days. All 19 splenectomised recipients had a marked and often complete suppression of the lymphocytotoxic antibody response to the graft. In contrast, splenecotomy had no effect in suppressing the rejection of (AS times August)F1 renal allografts transplanted to AS recipients previously immunised with August lymphoid tissue, or in AS recipients of homozygous August renal allografts. Splenectomised recipients could be reconstituted with spleen cells from sensitised but not from normal AS rats. Splenectomy was found neither to augment nor diminish the effectiveness of passive enhancement of (AS times August)F1 or August kidneys in AS recipients. Splenectomy of AS recipients 2 or 4 days after an (AS times August)F1 renal allograft was as effective as pregraft splenectomy in suppressing rejection, but there was a deficiency of long survivors in a group splenectomised 1 day after grafting. A working hypothesis to explain these results is presented, and their clinical relevance is discussed.


The treatment of rejection. A trial of acetylsalicylic acid, dipyridamole, and heparin. Serial studies of platelet and fibrinogen survival were performed in 26 nonimmunosuppressed dogs after allogenic renal transplant operations. Treatment with acetylsalicylic acid, dipyridamole, and heparin failed to improve the selective platelet destruction which occurred in untreated animals, and it did not improve postoperative longevity. There was a high incidence of postoperative wound and intrarenal hemorrhage after heparin treatment. These results are consistent with the hypothesis that platelet destruction is a consequence rather than the cause of acute graft rejection, and it is concluded that antithrombotic therapy is not of practical benefit in preventing acute rejection.


Enhancement of skin grafts in the mouse. The combined used of specific and nonspecific immunosuppression. Enhancement of skin grafts in mice by passively administered alloantiserum was examined in conjunction with the simultaneous use of other immunosuppressive regimens. It could be clearly shown that when a "weak" antilymphocyte serum (ALS) was used, a significant further prolongation of graft survival occurred over that obtained with the enhancing antiserum alone, and these two separate effects were synergistic. When a "strong" ALS was used, no synergistic effects were apparent unless the enhancing alloantiserum was given almost continuously. A similar, but less impressive synergism was seen when the enhancing alloantiserum and azathioprine were used together. Azathioprine, like ALS, presumably acts on T cells, whereas drugs directed against B cells, such as cyclophosphamide and prednisolone, failed to show any synergistic effect.


Kidney preservation using combinations of Belzer and Collins techniques. A study was designed to test the advisability of using combined Belzer and Collins preservation in kidney-sharing programs. Dogs were randomly assigned to seven groups and no donor pretreatment was used. In group 1, left kidneys were removed from dogs; were flushed with Collins solution; and were autotransplanted immediately. In groups 2 through 7, dog kidneys were preserved for 24 hr using combined techniques. The percentage of Collins preservation included in each group was increased progressively until, in Group 7, Collins alone was used. Contralateral nephrectomies were performed at the time of autotransplantation. Between 4 and 8 dogs survived in each group, yielding 43 6-week survivors. Sixty-six per cent of group 7 animals and greater than 90% of animals in other groups survived 6 weeks after transplantation. Average creatinine and blood urea nitrogen values on days 3,7, and 42 showed a progressive increase in kidney damage from groups 1 through 7. As the percentage of time the kidneys were subjected to Collins preservation was increased, the quality of kidney preservation decreased in a progressive manner. This study suggests that Belzer and Collins techniques can be combined, but superior preservation was obtained when the majority of preservation was on the Belzer apparatus.


Characteristics of specific unresponsiveness toward kidney and skin allografts in adult rats inoculated at birth with allogenic bone marrow or kidney cells across a strong H-1 barrier. Specific unresponsiveness inducible in newborn Lewis (Le) rats by injection of bone marrow or kidney cells from (Bu x Le)F1 hybrids was tested in adults by allografting of skin or kidneys from strongly incompatible Buffalo (Bu) strain donors. High doses of bone marrow cells (10(7) or more) proved quite effective in procuring indefinite survival of subsequent Bu kidney allografts, but not Bu skin allografts. Kidney allografts remained fully functional without modulation of their inherent immunogenicity regardless whether skin allografts were acutely rejected before or after kidney grafting on bone marrow-tolerant recipients. Lower doses of bone marrow cells were either near threshold for induction of specific Bu kidney allograft tolerance (5 x 10(6)) or, conversely, led to increased immunity(1-5 x 106). A strikingly different pattern of reactivity was found in adult Le recipients of Bu skin allografts as shown by only a moderate, but stepwise increase in survival times as a function of increasing allogeneic cell dosage at birth. Allogeneic kidney cells at all doses were surprisingly ineffective in inducing tolerance of either kidney or skin allografts, so the existence of kidney-specific transplantation antigens remains problematical. Lymphocytes from kidney allograft-tolerant recipients showed much reduced but still significant antidonor activity in several tests of cell-mediated immunity in vitro and in vivo. Blocking antibody activity was also demonstrable in these animals. Acquired tolerance (i.e., essential nonreactivity) may not only exist in degrees in either T or B cell pathways but may coexist with specific immunoblocking reactions in a dynamic equilibrium. Instead of tolerance versus enhancement, a new concept of selective specific immunoregulation emerges.


Hyperacute rejection of skin allografts in the mouse. Sensitivity of ingrowing skin grafts to the action of alloantibody and rabbit complement. The destructive action of alloantiserum and exogenous complement on ingrowing skin allografts was studied. B6AF1 recipients of a B10.D2 skin graft received a single intravenous injection of B6AF1 anti-B10.D2 serum (antiserum to H-2K.31) together with rabbit complement (RC) within the first 10 days after transplantation. Different models were used: recipients without immunosuppression, recipients treated with antilymphocyte serum, x-irradiation, or enhancing antibody. If the injection was given between day 5 and 10 after grafting, hyperacute rejection occurred in all cases. The rejection seemed to be most violent when the injection was given on days 7 or 8. Injections given on days 1, 2 or 3 after grafting could not induce hyperacute-rejection, but resulted, on the contrary, in a prolongation of graft survival, probably due to immunological enhancement. Injections on day 4 produced patchy necrosis, but the grafts recovered and the residual tissue showed a prolonged survival. The results suggest that the presence of a functioning vascular network is a prerequisite for the occurrence of hyperacute rejection of skin allografts in the mouse.


Surface properties and functional characteristics of infiltrating cells harvested from acutely rejecting cardiac allografts in inbred rats. Viable, functioning effector cells exerting donor specific cytotoxic properties have been removed, with their surface properties intact, from acutely rejecting cardiac allografts in rats to define immunological events occurring within the grafts themselves. Macrophages comprised 15 to 25% of the cells harvested; lymphocytes comprised about 75%. A few polymorphonuclear leukocytes (approximately 5%) were present consistently. Lymphocytes bearing surface Ig, B cells, made up 35 to 47% of the mononuclear cells collected. The remaining lymphocytes were presumptive T cells. The surfact attributes of the infiltrating cells were compared to those of cells from recipient peripheral blood, spleen and lymph nodes, and to those from isografted controls. Many of the B lymphocytes possessed Fc receptors but were virtually unable to form erythrocyteantibody complement (EAC) rosettes, in contrast to splenocytes which formed approximately 30% EAC rosettes. Specific cytotoxicity against donor alloantigen-bearing cells, as tested in a 51Cr release assay, was shown to be a T cell function by serial fractionation experiments. Peak cytotoxicity of infiltrating T cells occurred early during the rejection process, while that of cells from recipient blood and lymphoid tissues occurred only following complete graft destruction. Antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC) was demonstrated following gentle trypsinization or overnight incubation of the cells. Differing effector cell populations could be distinguished by treatment of anti-Ig and complement; direct donor-specific lymphocyte-mediated cytotoxicity was not disrupted by this treatment, while Ab-LMC was abolished.


Effect of anti-donor serum (ADS) and donor cells on renal allograft survival in DL-A tissue-typed littermate beagles. The influence of passive and active immunization on kidney allograft survival was tested in littermate beagles differing in one and two DL-A haplotypes. Immunization by treatment of recipients with hyperimmune antidonor serum (ADS) prolonged graft survival only in a few donor-recipient combinations differing in one DL-A haplotype. All ADS batches that were tested in MLC reaction did block this reaction, but no correlation with its in vivo activities was found. Hyperimmunization of recipients with donor lymphoid cells before grafting caused a second-set rejection, whereas one injection with donor blood did so only in 14%, with antibody production and accelerated rejection. A short course of horse antidog lymphocyte serum (HADLS) prolonged kidney graft survival. The addition of intravenously given donor bone-marrow cells to this protocol did not lead to a further increase in graft survival.


Comparison of tritiated hypoxanthine, adenine and adenosine for purine-salvage incorporation into nucleic acids of the malarial parasite, Plasmodium berghei. This study was accomplished to examine the relative importance of different metabolic precursors of nucleic acid synthesis in the malarial parasite, P. berghei. Three possible pathways for incorporation of Adenine (type) compounds exist: 1) incorporation via hypoxanthine, 2) via adenine, or 3) via adenosine. The parasitized cell and erythrocyte-free malarial parasite were both examined because of possible metabolic differences that could be encountered. Hypoxanthine was clearly the best precursor at both levels with extra-incorporation in the presence of allopurinol (10(-4)M), which protects oxidative metabolism of hypoxanthine. Adenosine was less efficient in its incorporation into nucleic acids at both levels. Adenine was clearly the poorest precursor being extremely less efficient compared to hypoxanthine 1/50 at parasitized cell level and 1/100 at the free parasite level. At both levels adenine seemed to be slightly more efficient in the presence of allopurinol and this appeared to be a similar to the incorporation via adenosine with allopurinol. In both cases, part of the incorporation could be coming via conversion to hypoxanthine because allopurinol protects oxidation of hypoxanthine via inhibition of xanthine oxidase. With the prior observation of Manandhar and Van Dyke that adenosine is converted to hypoxanthine outside or on the surface of the malarial parasite one is lead to conclude that of the three pathways the hypoxanthine pathway is probably the major and possibly the almost totally important pathway making hypoxanthine's uptake and/or conversion to inosine monophosphate a key event of metabolic and chemotherapeutic importance.


[Comparative morphological studies on the kinetoplast of various species of trypanosomes, with special reference to trypanosoma cruzi (author's transl)]. Comparative electron microscope studies on the morphology of the kinetoplast DNA (K-DNA) of the epimastigotes in many trypanosome species were carried out under standardized conditions. The K-DNA shows a morphological variation during the cell cycle of culture forms of the trypanosome species under study. In longitudinal sections of the kinetoplast, the K-DNA of T. cruzi appears as a compact trabecular structure; as a relatively disaggregated unit, with a central band or in a transitional stage between these forms. The conspicuous central band of the K-DNA which occurs at the beginning of cell division when the basal body is duplicated, could be demonstrated in all the 8 T. cruzi isolates studied. This has been found in the human-pathogen strains as well as in the T. cruzi-like trypanosomes of wild animals. In contrast, in comparable developmental stages of T. conorhini, T. rangeli and two strains of T. lewisi, this structural configuration of the K-DNA could not be observed. Based on these results, the extent to which the central band of K-DNA may be used in differentiating between trypanosomes is discussed. These findings may also reflect the present state of knowledge, as based on the study of 12 trypanosome isolates, so that corrections or additions may be lateron possible.


A serological study on human Trypanosoma rhodesiense infections using a micro-scale enzyme linked immunosorbent assay. A micro-scale enzyme linked immunosorbent assay for African trypanosomiasis is described. The test uses very small quantities of sera and with T. brucei antigen is sensitive in detecting T. rhodesiense infections in man. Cross reactions occur with antisera to, and antigens of, Leishmania donovani and Trypanosoma cruzi.


[Antigenic translocation of the "carcinoembryonic antigen" in colonic neoplasms]. The localization of the carcinoembryonic antigen (CEA) in the colon tumours was studied with the indirect Coons test. The localization of CEA in malignant cells was different from that in the normal colon mucosa. In addition, an essential secretion of this antigen may occur in neoplasms. The alteretion of the antigen position in pathologically changed cells or its secretion, differing from that in normal tissue, is referred to as the antigenic translocation.


[Simple apparatus for drying cytological specimens by the "critical point" method]. A simple modification of the critical-point drying apparatus is described. This modification was effectively used for preparation of normal and malignant cell cultures using the scanning electron microscopy.


Renal transplantation in the rat. I. Studies concerning the ureteral anastomosis with special reference to the end-to-end technique. End-to-end anastomosis of the rat ureter over an in-dwelling silastic splint gives good primary results and a low frequency of complications. This technique has been used when reconstructing the ureter in situ and in renal transplantation.


Management of children with urinary tract infections: the Stanford experience. Two hundred seventy-eight female children with urinary tract infections have been evaluated at Stanford division of urology. All children were followed up for a period of not less than twelve months. Age of onset of infection, clinical presentation, and nature of infecting organisms were observed. The group consisted of 144 children without ureteral reflux and 134 children with ureteral reflux. Sixty-one of the female children with ureteral reflux had ureteral reimplantation, while 73 received medical treatment alone. A study of infection rates in each of the three groups of children indicated a similar infection rate, although those children with reflux experienced a higher incidence of clinical pyelonephritis. Correction of ureteral reflux did not alter the infection rate; however, infections after surgical correction were generally of a type usually associated with children without reflux. Twenty-nine children had urethral dilatation, and the infection rate prior to and following urethral dilatation indicated a similar rate of infection pre- and posturethral dilatation. One hundred nonrefluxing kidneys were observed radiologically: 97 were normal and 3 showed clubbing and scarring. Of 110 refluxing renal units observed, 62 were clubbed and scarred and 48 were normal. Following surgical correction of reflux, renal clubbing and scarring were not observed in previously normal renal units. Of those renal units found to be abnormal at time of surgery, 66 per cent showed progression of clubbing and scarring after surgical correction of reflux. It was observed that the greater the degree of reflux present, the higher the incidence of renal damage. This study suggests that children who experience recurrent urinary tract infections who do not have ureteral reflux are seldom at renal risk; similar children who do have ureteral reflux are at risk unless the infections are controlled or the reflux either disappears or is corrected surgically.


Hypothalamic and pituitary function in hypogonadotropic hypogonadism. Hypogonadotropic hypogonadism has been identified as a cause of partial or complete failure of puberty, may be familial and may have other associated abnormalities of hyposmia, intellectual retardation, perceptive deafness, color blindness, skeletal deformities, and gynecomastia. Pituitary function is usually normal with the primary defect believed to be hypothalamic. A twenty-year-old white male with a clinical diagnosis of hypogonadotropic hypogonadism and anosmia under-went complete endocrine evaluation with evaluation of the pituitary response to luteinizing hormone-releasing hormone. FSH (follicle-stimulating hormone) and LH (luteinizing hormone) release after luteinizing hormone-releasing hormone did occur, but the response was less than that seen in normal controls. Evaluation demonstrated that the pituitary-gonadal axis was intact with the hypothalamic-pituitary axis being defective. Therapy with the synthetic decapeptide (luteinizing hormone-releasing hormone) is correct theoretically and may be superior to therapy with exogenous gonadotropins.


Use of horseshoe kidney in renal transplantation: technical aspects. The incidence and etiology of horseshoe kidneys and their structural abnormalities are discussed. Previously, patients with horseshoe kidneys have been considered undesirable donors for renal transplantation. Two cases of horseshoe kidney transplantation are presented, apparently, the first reported utilization of such a donor for transplantation, along with important aspects of surgical technique.


Periureteric fibrosis complicating kidney transplantation. Impairment of renal function developed in a kidney transplant recipient three years after the transplant due to ureteric obstruction. At operation this was found to be due to periureteric fibrosis. Ureterolysis was performed with subsequent return of renal function.


Psychological sequelae of elective abortion. A mild, short, depressive and guilt ridden period following abortion is quite common, but a severe psychological reaction is rare. The indication for the abortion and the preabortal psychological state of the patient are the two most important factors. Almost all reported instances of postabortion psychoses have occurred in patients who had severe preabortal psychiatric problems. Women undergoing abortion for socioeconomic or psychosocial indications appear to be at minimal risk for long-term negative psychological sequelae. In contrast, women in whom abortion is carried out because of exposure to rubella and the risk of fetal malformation, maternal organic disease or the prenatal diagnosis of a genetically defective fetus are at greater risk and may need supportive psychotherapy.


[Stereotaxic longitudinal hippocampotomy and its prospects in the treatment of epilepsy]. A description is offered of a new method of stereotaxic longitudinal hippocampotomy that ensures an electrosubcorticographic precise location of an epileptogenic focus in the hippocampus and its selective destruction. A positive therapeutic effect was achieved in 13 patients operated upon by using this method.


[Titration of antibodies to lymphocytic choriomeningitis virus by the method of indirect immunofluorescence]. Antibody to lymphocytic choriomeningitis virus was determined by the indirect immunofluorescence test in immune sera of guinea pigs and immune ascitic fluids of rats and mice. Among 135 patients with aseptic meningitis serum antibody was found in 11 patients in titers of 1 : 64 to 1 : 128 and in the cerebro-spinal fluid of these patients in considerably lower titers. By the indirect immunofluorescence test antibody in maximum titers was found early after the appearance of meningeal symptoms.


Control of adenovirus acute respiratory disease in U.S. Army trainees. Although limited almost exclusively to military trainees, acute respiratory disease (ARD) caused by adenovirus types 4 and 7 had been the leading cause of hospitalization in U.S. Army personnel. This decrease which resembles influenza in clinical manifestations led to hospitalization of as many as 50% of military trainees in midwinter and imposed a heavy burden on military hospitals and training programs. In studies undertaken from 1965 to 1970, live adenovirus type 4 and subsequently type 7 vaccines were found to be safe and immunogenic and to confer protection against type specific adenovirus ARD. For the past 5 yr. military trainees have been immunized with both adenovirus vaccines during periods of expected adenovirus disease. Since 1966, use of adenovirus vaccines has been monitored through the adenovirus surveillance program which yields weekly data on incidence and etiology of ARD in basic combat trainees. Since 1973, stable adenovirus vaccines have resulted in excellent control of adenovirus ARD. Potential problems with this immunization program are discussed.


An ultrastructural study of the renal medulla in experimental acute pyelonephritis. Experimental acute pyelonephritis was produced in rats by a combination of intravenous administration of Escherichia coli, strain IMRU-54, and temporary unilateral mechanical ureteral obstruction. Structural alterations of the renal medulla were studied by light and electron microscopy. Major cellular alterations occurred in the vasa recta. Tubular and interstitial cells demonstrated minimal alterations after the brief period of acute inflammation. Polymorphonuclear leukocytes within tubular lumina contained structures resembling E. coli in nonprotoplasts-like form. Numerous protoplast-like organisms, to the exclusion of any other structural forms, were detected within the interstitium of the inner medulla. Nonprotoplast-like structures resembling E. coli were rarely observed in interstitium of the inner medulla. Following relief of ureteral obstruction, clearance of acute inflammation was rapid. In conclusion, hemoatogenous acute pyelonephritis induced by E. coli, IMRU-54, is able to inflict cytological and ultrastructural damage to structural elements of the inner and outer medulla of rats. Vasa recta incurred prominent alterations in endothelia and basement membranes, whereas tubular epithelia and interstitial cells had relatively good structural preservation. The data suggest that intravenously administered E. coli is capable to revert to a protoplast-like structure in the inner medulla.


[Stress sensitivity and adaptation].

[Stress sensitivity and adaptation]. On the basis of theoretical, clinical and experimental analyses the influence of different stress categories, especially of psycho-emotional and socio-emotional stress, upon cerebro-visceral regulation processes is investigated. Central-nervous information processing in various brain areas (neocortex, limbic system, hypothalamus, formatio reticularis mesencephali etc.) and learning processes are equally affected by stress factors as are haemodynamic and biochemical parameters. Changes of the carbohydrate and lipid metabolism, of plasma renin activity, catechol amine release and the counter-regulatory insulin enhancement are especially pronounced in "stress-sensitive risk persons", e.g. in the hypertensive as a maladaptive dysregulation-as opposed to the adaptive regulation capacity of healthy individuals. The investigated functional patterns of different systems of the organism allow the distinction of hyper- and hyporeactive forms of maladaptation. The pathogenetic efficiency of stress is determined not only by the quantity, quality, duration of exposure and basic processes of the central nervous system, but also by man's personality structure and his sensitivity to stress (genetic predisposition and/or acquired maladaptation). More insight into the neuro-biological processes underlying the motivational and psycho-emotional performance of the brain and its connection withe humoral-hormonal and cardiovascular systems is necessary to treat and to control cerebrovisceral dysregulations such as arterial essential hypertension. It will be a task of psychotherapy to help improve man's adaptive capacity and to desensibilize stress-sensitive risk persons.


[Determination of kidney circulation with radioxenon]. On 23 investigations in dogs the 133xenon eluation method was compared with the bloody measurement of the renal blood supply. The most favourable correlation presents the measurement of the initial decrease of the curves with r = 0.827 and y = 0.889x + 53.3, besides the modified hight-surface-method. Possibilities of error exist especially by the recirculation of xenon and the influence on the blood supply by the xenon-injection.


[Mumps myocarditis in a small child].

[Mumps myocarditis in a small child]. The clinical history and post-mortem findings in a five-year-old girl are reported. She died in consequence of a chronic mumps myocarditis 13 weeks after having fallen ill with mumps. The antigen specific for mumps virus could be demonstrated in the myocardium by means of immunofluorescence.


A selective coronary indicator dilution technique with fiberoptic recording. A new method of accurately measuring myocardial circulation times is described: dye injections were made selectively into the left coronary artery while the passage of dye was recorded instantaneously in the coronary sinus with a fiberoptic catheter. The appearance time was found to be shorter than previously estimated (2.2 +/- 0.8 sec). The mean transit time in patients with left coronary artery disease and/or myocardial disease was significantly prolonged (p less than 0.01) and was found in all patients to shorten with increasing heart rate (p less than 0.01). Deformed dyd dilution curves were only obtained with stenotic lesions of the left coronary artery.


[Sinus node syndrome].

[Sinus node syndrome]. Recently disorders of sinus node function have found increasing interest in clinical medicine thanks to new diagnostic and therapeutic developments. This paper represents a comprehensive review of these conditions, combined under the name "Sick Sinus Syndrome" (SSS). Besides a detailed analysis of 63 cases seen at our institution, the results of other groups are compared and extensively discussed. The clinical picture of the SSS is characterized by a wide variety of bradycardiac and tachycardic atrial arrhythmias, occurring separately or in combination. These can be classified in three subgroups: Patients with exclusive sinus bradycardia; patients with sinoatrial exit block or transient episodes of sinus arrest with or without AV escape rhythms; and finally patients with the bradycardia/tachycardia-syndrome, which are complicated by additional atrial tachyarrhythmias. The symptomatology of the SSS is multiform and extends from symptomless cases and those with only general signs of reduced cardiac function to patients with recurrent severe syncopal attacks which may lead to cerebral damage and even death. Besides the typical history, the diagnosis of the SSS primarily rests upon the ECG, especially the long term ECG recorded continuously on a 24 hrs. tape (Holter technique). Also the exercise ECG is of some value, characteristically showing an inadequate increase in the sinus rate, sometimes with AV escape systoles and -rhythms. In addition various provocative tests have been devised which are of help to differentiate between a pathologic and a normal sinus node function. Among these the determination of the sinus node recovery time following overdrive atrial pacing has gained wide acceptance. In most cases the exact etiology of the SSS is not known. In addition to coronary and inflammatory heart diseases a primarily degenerative lesion of the sinus node, comparable to cases with "primary heart block" are discussed. There is also a remarkably frequent past history diththeria. Rarer causes of the condition represent cases with cardiomyopathy, thyreotoxic heart disease, collagen and other disorders and also a familial manifestation of the SSS has been described. Therapeutically, pharmacologic treatment with vagolytic, beta-adrenergic or the common antiarrhythmic drugs is often unsuccessful, especially in the treatment of the Brady-Tachy-Syndrome. Digitalis glycosides, however, are frequently of some value, as they represent an effective prophylactic agent against atrial tachyarrhythmias without prolonging the sinus node recovery time or reducing significantly the sinus rate. While a few patients do not require any treatment, an artificial cardiac pacemaker has to be inserted in most cases. Atrial stimulation may be superior to ventricular on-demand pacing in some patients, and also a special system for the treatment of the SSS combined with significant AV block (binodal disease) has been designed, the bifocal sequential pacemaker.


[Antiarrhythmic properties of lidoflazine in the therapy of auricular fibrillation and flutter (clinical studies of 26 patients)]. Successful conversion to sinus rhythm was achieved in 20 out of 26 patients (77%) with chronic atrial fibrillation or flutter of various origin, that had existed for about 40 +/- 13 months. There was a significant relation between the converting dose of Lidoflazine and the duration of atrial fibrillation. In those patients with atrial fibrillation, that preexisted no longer than two years, restoration of sinus rhythm was achieved in 12 of 14 cases (86%) with an average dose of 109 +/- 67 mg Lidoflazine a day, whereas in the group with atrial fibrillation known for more than two years therapeutical success was obtained only in 8 of 12 cases (67%). The dose of conversion was 382 +/- 150 mg/day in this group and produced in a few patients toxic side effects. Two patients relapsed to atrial fibrillation. On this reasons conversion with Lidoflazine should only be done in patients with atrial fibrillation within two years. There were no significant changes related to: heart rate, myocardial function and intraventricular conduction process. In the presence of underlying hypokalaemic disturbances and/or additional therapy with digitalis preparations Lidoflazine may be the cause of developing premature beats. Lidoflazine may be regarded as a relatively safe drug even in large doses, if monitoring of heart rhythm and QTc-interval is available.


[Newer antimycotics. I. Derivatives of phenyl-hydrazine (author's transl)]. The author produced a number of derivatives of phenyl-hydrazine and its analogues, investigated their antimicrobial efficiency in vitro, and discussed the association of chemical structure with the fungistatic effect in the series of phenyl-hydrazine-derivatives. From the author's results it can be concluded that the halogen-substituted phenyl-hydrazines and their N-(acetyl)-derivatives exert a moderate fungistatic effect (Tab. 1). In the series of N-aryl-sulphonyl-N'-phenyl-hydrazines only the compounds derived from 3,4-dichloro-phenyl-hydrazine proved to be effective; the other representatives of this type were fully ineffective (Tab. 1). The majority of the halogen-substituted N-aroyl-N'-phenyl-hydrazines exerted a relatively strong fungistatic activity with a broad spectrum of efficiency (Tab. 2). On the contrary, their analogues having a -CO-NH- group in place of the -CO-NH-NH-group, were fully inactive (Tab. 3). From the investigated derivatives of phenyl-hydrazine, the N-benzoyl-, N-(2-chloro-benzoyl)-, N-(4-chloro-benzoyl)- and N-furoyl-derivatives of 3- and 4-chloro-phenyl-hydrazine, furthermore the N-benzoyl- and N-furoyl-derivatives of 3,4-dichloro-phenyl-hydrazine were most effective (Tab. 2). The acute toxicity in the mouse of these effective compounds was relatively small; they were found to be significantly less toxic than tetramethyl-thiuramdisulfide (Tab. 4). On the basis of an intensive fungistatic efficiency and small toxicity of the halogen-substituted N-aroyl-N'-phenyl-hydrazines, it seems that a number of representatives of these types of chemical compounds could be given a role in the chemotherapy of superficial human and animal dermatomycoses, and also in the chemoprophylaxis of certain phytomycoses.


[On the morphology of flagella and fimbriae of Escherichia strains (author's transl)]. 100 Escherichia-strains, isolated from urine and faeces, were investigated with regard to flagella and fimbriae by electron-microskopy. The flagella had a length of 3-6 mu and a diameter of ca 0.02 mu. The flagellation was different not only between to the single bacteria of the same strain, but also in the separated isolates. Of 50 strains from urine had 27 and of 50 strains from feces had 28 no flagella. Different Escherichia-strains contained fimbriae, the number of which was much higher with regard to the flagella. The length of the fimbriae differed between 0.25 and 2 mu, the diameter was constantly ca 8 nm. 21 strains of 100 (4 from 50 urine strains and 17 from 50 faeces strains) had no fimbriae.


[On the biological activity of Escherichia strains, with special reference to fimbriae (author's transl)]. According to the results of earlier investigations of other authors, there are differences between Escherichia-strains fron urinary tract infections and fron the feces of healthy persons with regard to their biochemical, hemolytic, necrotizing and pathogenic properties in mice experiments. Hemolytic Escherichia cultures are very different from non - hemolytic cultures in their necrotizing and pathogenic behaviour. In contrast to Escherichia-strains from the feces of healthy persons strains from urinary tract infections have fimbriae to a much greater extent and hemolytic strains up to 100%.


[Is the examination of drinkable water and swimming pools on presence of enteropathogenic E. coli necessary? (author's transl)]. The examination of 1950 different water samples showed that 21,5 percent of them were microbiologically not safe and had an high MPN of E. coli, 2,3 percent of these strains belonged to enteropathogenic groups. The percentage depended on the character of water establishment, and was in small water supplies as high as 8 percent, in swimming pools 11 percent. There were identified the following OK groups of EEC: O25:K11, O28:K73, O55:K59, O75:K80, O115, O126:K71, O146, which are well known as causes of acute enteric diseases of children and adults. In case of special epidemiological or other occasions, it would be useful to examine the E. coli strains, isolated from different water samples serologically, in order to identify them as enteropathogenic eventually.


[Comparative investigations on the efficacy of tap water, some detergents and ethanol on the transient flora of the hands (author's transl)]. The germ reducing efficacy of tap water, soap, pHisoHex, pHisoDerm and 70% ethanol was compared using the model of hands artificially contaminated with E. coli. Each of ten persons washed 1, 2 or 4 minutes. Reduction factors were calculated from pre- and post-values and were compared for each individual. After one minute the logarithms of the geometric means of the reduction factors amounted to 2,99, 3,23, 3,28, 3,61, 4,25 in the above used sequence (Table 2). After one minute the reductions came off more slowly and the slopes were linear and parallel as far as the mechanical germ reducing procedures are concerned (Fig. 2). In contrast, ethanol caused a steeper slope even after one minute wash. The strong reduction achieved by mechanical procedures (even with water for one minute 3 powers of ten were observed) demonstrates the high hygienic importance of hand washings for removal of the transient flora. Detergents like pHisoDerm produce further significantly higher reductions and seem to be more suitable than aggressive disinfectants for application in fields where bactericidal action is not imperative. The proposals for procedures aiming at disinfecting of the transient flora issued by the Austrian Society for Hygiene, Microbiology and Preventive Medicine require a reduction factor of at least 10(5) after two minutes hand wash. The results of this investigation show that this is practicable with ethanol and necessary, otherwise the bactericidal action would not be different from a mechanical removal of the transient flora.


[Measurement of nuclear size in cells from embryonic mouse brain in monolayer culture using automatic image analysers]. Size analyses and size classifications were made of the nuclei of embryonal mouse brain cells in monolayer culture. Measurements were made by surface analysis, using the Quantimet (1,299 nuclei), and linear analysis, using the Digiscan (1,887 nuclei). Despite the different methods of measurement and different logarithmic classification, similar distribution curves were obtained, approaching the Gaussian normal distribution. The methodical problems of karyometry as well as the problems of statistical data processing are discussed.


Observations on the intrinsic innervation of the islet of Langerhans of Rattus rattus rufescens (Indian black rat). The innervation of Langerhans' islets appeared rather profuse. Generally the nerve fibres of the peri-insular plexus formed a basket enveloping the islet of Langerhans. The peri-insular ganglia were occasionally seen. No autonomic interstitial cells of Cajal nor nerve endings were observed in the islet of Langerhans, due to the thickness of the sections. The 'complexes sympathico-neuro-insulaires' were occasionally seen. The plexuses and neural terminal network were seen connected to each other; thus they are not separate entities.


Serum lipids during oestradiol-valerate/norgestrel treatment of menopausal women. Double-blind study of a sequential preparation. Thirty-three women aged 38-56 years, all with menopausal complaints, were treated after randomization during three cycles either with oestradiolvalerate/norgestrel suquential therapy or a placebo and then during three cycles with the opposite drug. Serum cholesterol, triglycerides, glycerol as well as plasma FFA and lipoprotein electrophoresis were studied before the institution of treatment, after each cycle, and 4 weeks after the intake of the last tablet. During the treatment period the triglyceride level was significantly lower than during the placebo period, whereas no changes occurred in other parameters. The decrease was at a maximum after 8 weeks' treatment; 4 weeks after the discontinuation of treatment the levels were as before its institution. It cannot be decided whether the decrease was due to the natural oestrogen or to the gestagen.


Diazepam as a sedative in induced abortion. In 136 patients, who underwent induced abortion by the vacuum curettage method under local anaesthesia (paracervical block), the effect of 10 mg diazepam intravenously as preoperative sedative was investigated for its ability to abolish the subjective experience of pain. The trial was carried out as a paired sample, random, allocation, double-blind, fixed dose trial, and the statistical method was sequential analysis. Thirty-six pairs showed no difference and were excluded. After 32 pairs (24 A preferences and 8 O preferences), diazepam showed a significant superiority to placebo (p less than 0.05) (Fig. 1.) Amnesia for the procedure was reported by about one-quarter of the diazepam-treated patients, and in practically all cases the sedative effect had subsided 1-3 hours after the operation.


Computer discrimination between benign and malignant urothelial cells. Computer discrimination between benign and malignant cells by means of the TICAS routines and subroutines has been accomplished with a small error of classification, not greater than ten percent. One feature of major diagnostic significance, namely, nuclear texture was singled out for discussion. This study augurs well for the future of computerized cytology of the urinary tract.


Influence of absorbed dose and field size on the geometry of the radiation-surgical brain lesion. Specimens from a number of patients locally irradiated in the thalamus for intractable pain with a multiple gamma beam technique have been examined. The geometry of well circumscribed necrotic lesions was ascertained. No correlation was seen between the dimensions of the lesions and the size of the field, 3 mm X 5 mm or 3 mm X 7 mm, within the clinically useful dose range, 16 to 25 krad.


Destruction of small intracranial tumours with 60Co gamma radiation. Physical and technical considerations. The clinical and physical conditions for the destruction of small intracranial tumours by means of multiple gamma beam irradiation are evaluated. The effects of the collimation of the single beam and the spatial distribution of 179 beams on the superimposed three-dimensional dose distribution are investigated experimentally and theoretically. Techniques for selective irradiation of tumours of various types and sizes are discussed.


Errors and uncertainties in external radiation therapy. A system analysis with a cell kinetic model. The relative importance of accurate knowledge and control of various biologic and physical factors in external radiation therapy was estimated with a simple cell kinetic treatment response model for a simulated tumour therapy situation. A set of parameter values was chosen for a reference case so that the calculated probability of zero surviving tumour cells was about 0.5. The parameters were varied, one at a time, over a range that was considered representative with respect to uncertainty in dose calculation, dose delivery and the description of the pertinent patient data. Also parameters in the cell kinetic model were varied. The calculations demonstrated a strong influence on the number of surviving cells from even moderate changes in the parameters which affect the tumour dose. Predictions with regard to curability are heavily dependent on the reliability of the biologic parameters in the model.


Postoperative ventriculitis in infants.

Postoperative ventriculitis in infants. Eight consecutive cases of ventriculitis detected and treated during a four year period are reviewed. This complication represented 7.9% of all cases of spina bifida treated surgically, and 5.4% of all shunt precedures performed during the study period. Prophylactic antibiotic treatment did not reduce the incidence of ventriculitis, and in fact seemed to produce resistant strains, which led to difficulties in treatment and a worse prognosis. The presence of an intraventricular foreign body precludes permanent sterilization of the ventricular fluid. Finally, in those cases in which the antibiotic of choice penetrates poorly into the cerebrospinal fluid; intraventricular as well as systemic administration of the drug is indicated. With Gram negative organisms, Gentamicin is currently the drug of choice.


Frank vectorcardiogram in common ventricle: correlation with anatomic findings. The influence on the Frank vectorcardiogram of anatomic features in common ventricle was analyzed by comparison of Frank vectorcardiograms in 51 patients who had common ventricle with those of 36 patients who had large ventricular septal defect, 14 of whom had levotransposition of the great arteries and 22 of whom had dextrotransposition. Frank vector loops in common ventricle differed from those in ventricular septal defect by the frequent occurrence of clockwise horizontal rotation, most common in patients with type C common ventricle (no outflow chamber). There was a statistically significant difference in the amplitude of early forces between patients with common ventricle and those with large ventricular septal defect. The degree of overlap of vectorcardiographic features between the two groups is sufficiently great that the vectorcardiogram has limited usefulness in establishing the diagnosis of common ventricle in any individual patient.


Left ventricular function in ischemic heart disease: assessment by noninvasive techniques. 1. Thirty-two patients (29 men and 3 women), admitted to a coronary-care unit with either acute coronary insufficiency or acute myocardial infarction, had their systolic time intervals and the a/E ratio of the apexcardiogram studied on days 1,2, and 7 of their hospital stay. 2. Only the LVETc and PEP/LVET were found to undergo any statistically significant change. Although all figures were in the abnormal range, they had no discriminative value in individuals. None of the other commonly accepted noninvasive  indices or left ventricular function, including the a/E ratio of the apexcardiogram, were found to be of assistance in the early distinction between acute coronary insufficiency and acute myocardial infarction.


The heart in myasthenia gravis.

The heart in myasthenia gravis. The cardiac changes associated with myasthenia gravis have been reviewed and specific areas explored. There is no doubt concerning the involvement of the myocardium in this disease as indicated by clinical, ECG, vectorcardiographic, and autopsy data. The doubt lies in the precipitating factor for the pathology found. On the one hand the whole picture could be a direct result of the pathologic process of myasthenia gravis. On the other hand the patient with myasthenia gravis, during the natural history of the disease, encounters many iatrogenic and coincidental variables which could influence the nature of the clinical findings and autopsy data. One fact seems reasonably clear: The association of myocardial pathology with thymoma, especially malignant thymoma, is well established for the more severe form of the myocardial disease. Furthermore, the hypothesis that cardiac muscle antibodies give rise to such reactions is attractive, although not fully resolved. If such cases are excluded then there remain others where cardiac pathology could be due to other disease, primarily coronary heart disease, in the older group. In addition, the mode of death of some patients indicates that intercurrent respiratory problems could play a part. Most patients in this group do not seem to have cardiac abnormalities due to the pathologic process of myasthenia. There is in addition a small group where very striking cardiovascular findings suggestive of myocarditis are found. There is not necessarily a thymoma and no other specific etiologic factors can be found. These are rare cases and might still be related to disorders of immune mechanisms. In conclusion it can be stated that, although there is now a considerable body of evidence concerning the heart in myasthenia gravis, the implication of specific pathology for this neuromuscular disorder affecting the heart must be considered, in the traditional Scottish legal sense, as "not proven."


Electrophysiology and pharmacology of cardiac arrhythmias. VIII. Cardiac effects of diphenylhydantoin. B. DPH is highly effective against both atrial and ventricular arrhythmias resulting from digitalis toxicity and should be considered one of the primary antiarrhythmic drugs in this clinical situation. Clinical studies have indicated that DPH, for the most part, is effective against atrial arrhythmias and not markedly effective against ventricular arrhythmias associated with acute or chronic cardiac disease. For the latter ventricular arrhythmias, DPH is usually considered only after other antiarrhythmic drug therapy has failed. Studies on the mechanisms responsible for the antiarrhythmic effects of DPH are, as yet, inconclusive, There is good evidence that its actions differ from those of the commonly used drugs with local anesthetic effects. The extent to which it exerts direct effects on the heart which are therapeutically relevant remains to be demonstrated; further, there is solid evidence that its effects on the central nervous system may be of prime importance in its antiarrhythmic efficacy.


L-Ascorbic acid and D-isoascorbic acid in a common cold survey. In a survey of double-bind design, 3 groups of approximately 70 student volunteers took 1 g L-ascorbic acid, 1 g D-isoascorbic acid, or placebo tablets every day for 15 weeks and the incidence and duration of colds were recorded. The group taking D-isoascrobic acid suffered 34% fewer colds than the other two groups; the results were also analyzed in relation to the sex and smoking habits of the volunteers. The rationale for investigating D-isoascorbic acid, an isomer of L-ascorbic acid which has limited antiscorbutic activity, is discussed.


Cardiorespiratory, hematological and physical performance responses of anemic subjects to iron treatment. Twenty-nine adult iron-deficient anemis subjects (13 men and 16 women) with hemoglobin levels of 4.0 to 12.0 g/100 ml blood were divided into either an iron treatment or placebo group. Hematological, cardiorespiratory and performance data were collected before, during, and after treatment and compared with data from a control group of subjects (4 men and 6 women) from the same socioeconomic population. Hemoglobin levels for the iron treatment group improved from 7.7 to 12.4 g for the women and from 7.1 to 14.0 g for the men. Values for the control group were 13.9 g and 14.3 g for the women and men, respectively. The placebo group showed virtually no change over the 80-day period (8.1-8.4 g for women and 7.7-7.4 g for men). Peak exercise heart rates (5 min, 40-cm step test) were significantly reduced after treatment from 155 to 113 for the iron treatment men and 152 to 123 for the women compared with the placebo group which showed no changes. Values for the control group were 119 and 142 for the men and women, respectively. In response to the exercise test, no difference in oxygen consumption was found between the iron treatment and placebo group although 15% more O2 was delivered per pulse in the iron treatment group. Blood lactates were significantly highein the placebo than iron treatment group both at rest, 1.18 versus 0.64 mmole/liter, and 1 min after exercise, 5.30 versus 2.68 mmoles/liter. No changes in handgrip or shoulder adductor strength were observed following treatment. These results clearly support the concept that performance requiring high oxygen delivery is significantly affected by hemoglobin levels.


Indirect fluorescent antibody technic for demonstration of serum antibody in dengue hemorrhagic fever cases. One hundred eighty-three sera from two groups of children with dengue hemorrhagic fever and 37 control sera were examined for antibody against dengue virus by an indirect immunofluorescent method. When the reciprocal titer of 16 or higher was used as the diagnostic level, positive tests could be obtained in 80% of Group I and 100% of Group II sera after 3--6 days of fever. Positive tests were obtained in 100% of both groups after the first week of fever. There was no false-positive among the control sera. Preparation of the antigen is relatively easy, and the antigen may be stored for at least 3 months. The immunofluorescent method is rapid and simple, and is recommended for routine detection of serum antibody in dengue hemorrhagic fever.


Mucormycosis in a transplant recipient.

Mucormycosis in a transplant recipient. Mucormycosis classically occurs in patients who have uncontrolled diabetes who develop rhinocerebral disease. A fatal case of rhinocerebral infection caused by Rhizopus arrhizus in a 53-year-old man who had received a renal homograft three years previously is reported. Only five similar cases have been documented, all since 1970. Although direct smears of the purulent nasal exudate revealed the presence of numerous Gram-negative bacilli, later identified as Haemophilus influenzae, the diagnosis of mucormycosis was made by demonstrating the typical broad, nonseptate branched hyphae in the necrotic tissue obtained by surgical debridement of the paranasal sinuses. Culture of this material revealed growth of mold-like fungus which, upon direct microscopic examination, showed sporangiophores bearing spherical sporangia arising directly from a cluster of root-like structures of rhizoids. Despite the immediate institution of therapy with amphotericin B postoperatively, the patient died 48 hours later. Subsequently, the Rhizopus isolated was shown to be resistant to both amphotericin B and 5-fluorocytosine. The present case and two others stress the importance of an aggressive diagnostic approach to patients suspected of having mucormycosis, because the usual microbiologic technics are frequently, inexplicably, unsuccessful, and possibly even misleading in this disease.


Antacid vs placebo in hospitalized gastric ulcer patients: a controlled therapeutic study. Antacids are widely accepted as agents that promote healing and relieve pain of gastric ulcer. Well-controlled studies designed to test this belief are few. 28 patients with endoscopically proven gastric ulcer were treated for 3 weeks in hospital, 13 receiving a liquid placebo and 15 an antacid. All were followed by endoscopy to complete healing or until surgery was performed. 10 patients healed satisfactorily in the placebo group and 11 in the antacid group. All patients were free of pain during their hospitalization. From this study it is concluded that in gastric ulcer patients hospitalized for 3 weeks, the rate of healing of the ulcer and the relief of pain is not influenced by treatment with a standard antacid preparation.


Adaptive changes in vitamin B12 absorption in celiac disease and after proximal small-bowel resection in man. Resection of the proximal small bowel is known to cause mucosal hyperplasia and enhanced absorption in the ileum of experimental animals, but similar adaptive changes had not previously been studied in man. Since intrinsic-factor-bound vitamin B12 (IF-B12) absorption is confined to the ileum, as an index of ileal adaptation, we measured whole-body IF-58 Co B12 absorption in 24 control subjects, in 4 patients after proximal small-bowel resection, and in 9 patients with adult celiac disease (where mucosal damage is often limited to the proximal intestine and spares the ileum). Control subjects absorbed 20.4% (+/- 1 SD 6.2%) of the administered 5-mug dose of vitamin B12, while the corresponding 7-day retention values in patients with proximal resection (mean 42.3%; range 32-61%) and in 2 of the 9 celiac patients (44.1% and 54%, respectively), were above the normal range. The increased vitamin B12 absorption in these patients suggest that functional adaptation also occurs in the ileum in man. The results also illustrate the application of a newly developed whole-body counting technique to study vitamin B12 absorption in man.


An outbreak of salmonellosis propagated by person-to-person transmission on an Indian reservation. Between December 21, 1969, and April 14, 1970, 44 symptomatic cases of Salmonella typhimurium gastroenteritis occurred among the approximately 2500 Sioux Indians of the Lake Traverse Reservation in South Dakota. Twenty-five cases were confirmed by positive stool culture. All 19 cases not confirmed by culture had diarrhea and were epidemiologically associated with the culture-proven cases. Fourteen of these were discovered during the course of the investigation and had not been cultured previously. Twelve cases were hospital-acquired and 32 community acquired. Both the nosocomial and community-acquired infections occurred randomly during the 17-week span of the epidemic. Despite extensive investigation, no common exposure was discovered. The hospital-acquired infections all occurred in patients who shared a room or nursing personnel with patients who had active disease, or were born of a woman with active disease at the time of parturition. Twenty-nine of the 32 community acquired cases were linked to each other by person-to-person contact. This epidemic is the first documented outbreak of non-institutional salmonellosis propagated by person-to-person transmission.


Normal chemoreceptor function in obesity before and after ileal bypass surgery to force weight reduction. Ventilatory responses to progressive isocapnic hypoxia and rebreathing of carbon dioxide in oxygen were determined in four obese women before and approximately 1 year after ileal bypass surgery to force weight reduction. None of the patients was hypoventilating and all had normal pulmonary function tests. The ventilatory responses to hypoxia were normal before surgery and were not effected by weight reduction. The ventilatory responses to hypercapnia did not change in slope but a shift of the carbon dioxide response line toward a lower arterial carbon dioxide tension occurred in two subjects after weight reduction. We conclude that obesity per se does not necessarily cause loss of hypoxic ventilatory drive.


Leukemic reticuloendotheliosis. A study of the origin of the malignant cell. A highly pure preparation of neoplastic cells from the spleen of a patient with leukemic reticuloendotheliosis was studied for function, membrane characteristics and glucose metabolism. Glass adherence and phagocytosis of small particles (latex and carbon black) were demonstrated with phase contrast microscopy. Staphylocidal activity was similar to that of normal monocytes. Immunofluorescent assays revealed nonspecific uptake of antiserums to immunoglobulins G (IgG), M (IgM), A (IgA) and kappa and kappa and lambda light chains. Rosette assays indicated the presence of receptors for IgG on the surface of all cells but no receptors for complement (C3) or sheep red blood cells. Glucose metabolic studies revealed a pattern that differed from that of normal monocytes or lymphocytes with intermediate values for glycolysis, low hexose monophosphate shunt activity and high Krebs cycle activity. Increments in tritiated (3H)-thymidine uptake and glucose metabolism in response to phytohemagglutinin stimulation were minimal (5 per cent of normal lymphocyte values) and no response was noted with pokeweed mitogen stimulation. These findings suggest that the leukemic reticuloendotheliosis cell most closely resembles cells of the monocyte-histiocyte series.


Increased and prolonged LH-RH/FSH-RH activity of synthetic (D-Ala6, Des-Gly-NH210)-LH-RH-ethylamide in normal women. A synthetic LH-RH analogue (D-Ala6, Des-Gly-NH210)-LH-RH ethylamide exhibited an increased and prolonged LH-RH/FSH-RH activity in normal women. The integrated amounts of LH and FSH levels for this LH-RH analogue were about nine and five times greater than for the same doses of synthetic LH-RH. It is expected that this synthetic LH-RH analogue might yield more positive results than with LH-RH when used in infertility problems.


Change in cell type of human choroidal malignant melanoma in tissue culture. In five cases choroidal malignant melanoma spontaneously converted from epitheloid to spindle cell and vice versa. The cultured epitheloid cells divided more frequently and grew faster than the spindle cells. Cells from one tumor were cloned and developed into a cell line.


Uveitis and reticulum cell sarcoma of brain with bilateral neoplastic seeding of vitreous without retinal or uveal involvement. A 65-year-old woman had been observed for more than four years with bilateral chronic nongranulomatous uveitis and vitreous clouding of unknown cause. Her death was from reticulum cell sarcoma of the brain (microglioma). Both eyes were obtained post mortem. Histopathologic examination revealed malignant cell in the vitreous of both eyes, but no other tumor was demonstrable in the ocular tissues. Reticulum cell sarcoma should be suspected in middle-aged or older persons with chronic unilateral or bilateral uveitis of unknown cause who develop cerebral manifestations during the course of the disease.


The past 25 years of surgery.

The past 25 years of surgery. The past 25 years have seen an explosion in interest and progress in the diagnosis and treatment of vitreoretinal diseases, especially retinal detachments. This progress has paid high dividends in the prevention of blindness and the clinical care of patients. The major advances during this period are the development of a binocular stereoscopic indirect ophthalmoscope combined with scleral depression, the introduction of a scleral buckling procedure to close retinal breaks, the development of instruments capable of producing controlled focal irritation in the ocular fundus, and the advent of direct surgical removal of the vitreous.


Unintentional filtration after cataract surgery. The eyes of an 81-year-old man were obtained three and ten days after intracapsular extractions had been made through limbal incisions under limbal-based flaps of conjunctiva and Tenon's capsule. The wounds were closed with 7-0 chromic collagen. Before death from bronchopneumonia, the patient developed bilateral filtrations in association with violent coughing spells. In both specimens, the healing processes of the conjunctiva and Tenon's capsule were advanced, confining the escaping aqueous humor to the subepithelial tissues of the flap. In contrast, the stromal wounds were still inert in accordance with our earlier observations that these wounds are precariously weak during the first two weeks after surgery. In cataract surgery, flaps including both conjunctiva and Tenon's capsule should be prepared and closed to support the slower healing stromal wound. Prevention of filtrations is not a simple matter of using many sutures. This patient's eyes demonstrated that improperly placed or too tightly tied sutures may be directly responsible for leaking wounds.


Immunologic study of nonsyphilitic interstitial keratitis with vestibuloauditory symptoms. We studied four patients with the clinical entity of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms to determine whether immunologic abnormalities play a role in its pathophysiology. There was no evidence of alteration in nonspecific cell-mediated or humoral immunologic status of any of the patients studied. Three of the four patients had W-17, a histocompatibility antigen that occurs in 3 to 10% of the normal population. All four patients had increased cell-mediated immunity against normal allogenic corneal antigens compared to normal control subjects. There seems to be no apparent generalized alteration of the immune system in this syndrome.


Clinical evaluation of adenine arabinoside and idoxuridine in the treatment of ocular herpes simplex. A Double-blind clinical study comparing idoxuridine (IDU) with adenine arabinoside (ara-A) in treating 54 routine herpetic ulcers, and an open ara-A therapy study of 58 herpetic ulcers in patients intolerant of or resistant to IDU, was carried out over a four-year period. There was no significant difference in healing time between IDU-treated eyes (11.5 days) and ara-A-treated eyes (12.4 days) in the double-blind study but there were four moderate to marked adverse reactions to IDU and only two mild reactions to ara-A. In the open-drug study 21 patients who were intolerant of IDU because of allergy or toxicity and 37 patients who had ulcers resistant to or deteriorating on IDU therapy used ara-A up to 192 days without any adverse reaction. Mean healing time was 10.6 days for 49 of 57 patients in the efficacy analysis. Eight patients developed trophic ulcers that responded to soft lens therapy and one was dropped from the study because his initial disease could not be distinguished from severe IDU-induced keratitis.


Bacterial endophthalmitis following suture removal after penetrating keratoplasty. Of three cases of bacterial endophthalmitis occurring after removal of corneal sutures following penetrating keratoplasty, two were associated with wound dehiscence and one was not. Factors that may predispose to wound dehiscence and subsequent infection are: use of fine suture material, corticosteroids, and chronic topical antibiotics; early removal of corneal sutures; lack of adherence to strict asepsis prior to and after suture removal; and open suture tracts that may be kept open by incarceration of vitreous strands. Late corneal wound dehiscence may occur with subsequent development of endophthalmitis as long as three days after suture removal. The use of topical antibiotics before and after suture removal may decrease the potential for infection. In addition, early recognition of intraocular infection by the patient and the surgeon for immediate institution of antimicrobial and anti-inflammatory therapy may preserve useful vision.


Corneal holder.

Corneal holder. As a result of the widespread use of M-K (McCarey-Kaufman) medium preserved corneas, as well as other methods of preserving corneas in a viable state, I developed a corneal holder to facilitate the lamellar dissection of previously excised whole human corneas. Consisting of a moderately heavy base, cutting pedestal, scleral rim-sealing sleeve, and retaining ring, the corneal holder is economically manufactured, simple to use, and easily sterilized. Its weight and construction allow unassisted dissection of a lamellar graft of any size.


Research on variation in dental occlusion. A "state of the art" workshop conducted by the Craniofacial Anomalies Program, the National Institute of Dental Research. The following report on assessing research on variation in dental occlusion was based in part on a workshop conducted by the National Institute of Dental Research at the initiative of Richard L. Christiansen, Chief, Craniofacial Anomalies Program. The meeting was planned and developed by Robert J. Isaacson, Chairman, Touro M. Graber, Richard A. Riedel, and Richard L. Christiansen. This report is designed to provide a review of the achievements, directions, and needs of research concerning variations in dental occlusion. The workshop was held at the National Institutes of Health, Bethesda, Maryland, on Nov 22 and 23, 1972. The material presented by the workshop participants has been summarized and incorporated in this report. The subject of research related to the field of malocclusion was discussed in an article published in the American Journal of Orthodontics in January, 1971.


Interstitial therapy suing non-absorbable (Ir192 nylon ribbon) and absrobable (I125 "Vicryl") suturing techniques. Permanent and removable interstitial implantation techniques using absorbable and unabsorbable sutures are described. Most of these techniques can be performed in the clinic easily and quickly with basic instruments: needle holder, needle book, and hemoclips. Specifically, Ir192 (74-4 day half life, 300-610 keV, and 6.0 cm. hvl in tissue) nylon ribbon and I125 (60 day half life, 27-35 keV,  and 2.0 cm. hvl in tissue) Vicryl sutures are described. A major advantage of the I125 over the Ir192 see (other than the fact that it can be permanently implanted and needs less radiation protection) is that the patient does not remain highly radioactive for as long a period due to hte extremely low I125 energy and may be allowed to leave the hospital. Both nuclides have the advantage of a long shelf life, making their use practical and economically feasible.


[Postoperative astigmatism after penetrating corneal grafts (author's transl)]. 232 cases of penetrating grafts from 1961-1972 have been studied. 141 (60%) were evaluated for visual acuity and corneal astigmatism. Since the introduction of the running suture (1966) postoperative complications have markedly decreased, visual acuity is in the average good and even very good. Patients operated for keratokonus however show higher postoperative astigmatism than patients operatedfor other corneal diseases.


[Clinical picture and morphology of orbital rhabdomyosarcomas in children]. The clinical course of orbital rhabdomyosarcoma is described in seven male children. A survey of the literature on the subject is given. Particular attention is paid to certain diagnostic problems of this most frequent orbital malignant primary in childhood. An adequate combination therapy which results in cure in more than half of the patients should be employed provided that an exact morphological diagnosis is made; this still causes often great difficulty. Electron microscopy is of great value in distinguishing this type of tumor from other malignancies, including the so-called reticulosarcoma. In comparison with the case material of other authors, there was a relatively high rate of late deaths in our patients.


Immunological investigations of patients with transplanted cornea. Authors examined the role of the cellular immunity by the method (I) of lymphoblastic transformation in 26 keratoplasty cases. Only in one case did they observe significant blast transformation, in this case the keratoplasty was necessary after injury with lime. In the rest of the cases no positive result were ever obtained. They investigated the cellular immunoreactivity of 10 patients waiting for keratoplasty and 10 cataractous patients against cornea antigen by means (II) of the Leucocyte Migration Test (LMT). The change of the cellular immuno-reactivity against cornea antigen was examined on the 1st, 4th, 7th, 14th, 21st, and 28th days after keratoplasty. It could be established that after keratoplasty the LMT became positive (inhibition or stimulation of migration). The results of the LMT investigations obtained on keratoplasty patients by cornea antigen may be of some help for the understanding of the events in the postoperative phase and sometimes also may eventually require immunosuppressive therapy.


Immunological investigations on patients with transplanted cornea: the role of tissue antigens in keratoplasty. After briefly describing the conceptions of the HL-A antigens and of histocompatibility, the authors give an account of their own retrospective examinations in connection with keratoplasty. Transplantations between identical groups of the ABO-system have a greater probability of ending successfully, if at least 2 HL-A antigens of donor and recipient are identical; this being chiefly important when grafting is carried out into unfavourable, vascularized surroundings.


[Karyometric studies of the pancreas and adrenal glands of the albino-rat fed an unbalanced glucose diet or a glucose diet supplemented with thiamine]. Karyometric measurements in rats which for 30 days had received a glucose diet or a glucose diet supplemented with thiamine showed the following decrease in nuclear size in contrast to no treated controls. (see article) In both experimental groups there was a 30% loss of weight during the course of the experiment. The different decreases in nuclear volume in the examined organs cannot be explained only by a relative state of hunger. The very large decrease in activity in the fasciculated zone of the adrenal cortex is explained as an adaptation mechanism favouring glucose oxidation by insulin, and the relative increase in activity in the adrenal medulla as an adaptation mechanism to accomplish an elevated lipolysis.


Relationship among skin tests, bronchial challenge and serology in house dust and Candida albicans allergic asthma. One hundred and ninety-six asthmatic patients were examined by inhalation challenge using house dust and candida albicans; an early, dual or late bronchial response was induced where IgE, C3 and C4 were elevated. In some of late responses by candida inhalation there was a decrease or almost no increase in IgE and a fall in C3 and C4. There was a considerable correlation between skin tests and bronchial responses. An induced bronchial response, early, dual or late, was identified as Type I, While candida-induced late bronchial responses were Type I and Type III. There is some question whether Type I plus Type III mechanism may be involved in the dual bronchial response provoked with candida.


Ru-Tuss in the symptomatic treatment of allergic rhinitis. In the treatment of allergic rhinitis with a placebo only one symptom, nasal itching, was reduced significantly. Where Ru-Tuss tablets were used, all symptoms improved and statistically significant reduction of  symptoms were obtained for lacrimation, nasal itching, sneezing, itching of the mouth, itching of the pharynx, rhinorrhea and the condition of the nasal mucosa. Ridit analysis was used to evaluate differences between the Ru-Tuss Tablet and the placebo treated groups.


Isolation and identification of mycobacteria from porcine tissues: a three-year summary. Mycobacteria were isolated from 1,591 (78%) of 2,036 porcine tissues submitted to Veterinary Services Laboratories over a 3-year period (July 1, 1971, to June 30, 1974). The isolates were identified by biochemical and serologic tests. Of the 1,547 Mycobacterium avium isolates, 452 were serotype 1, 728 were serotype 2, 60 were serotyped 4, 110 were serotype 8, and 51 were serotyped 10; 36 isolates represented 11 other serotypes; 65 isolates shared antigens with more than one serotype; and 45 isolates, untypabley serologic methods, were identified by pathogenicity in chickens as M avium. Mycobacterium bovis was isolated from 15 tissues; Mycobacterium fortuitum, from 3; and Mycobacterium paratuberculosis, Mycobacterium scrofulaceum, and Mycobacterium xenopi were each isolated from single specimens.


Tissue-washing tank for histologic preparations. A small tank made of plexiglass was designed to wash tissues for histologic preparations. The tank was divided into 16 compartments in 2 rows to wash 16 tissue samples at one time. The compartments in the same row alternately intercommunicated by rows of holes in the upper or lower halves. The arrangement of holes at 2 water levels in the partition appeared to create silent water waves, making the tank more efficient for washing tissues.


A comparative study of atropine sulfate and isoproterenol hydrochloride in chronic bronchitis. Fifteen subjects with chronic bronchitis were treated with inhaled atropine sulfate, isoproterenol hydrochloride, or placebo in a double blind crossover trial. Each drug was inhaled 4 times per day for 3 weeks. Baseline forced expiratory flows, specific airway conductance, airway resistnace, and functional residual capacity were measured weekly. These measurements were repeated 15 min and 60 min after laboratory inhalation of each agent, using a separate double blind protocol. No significant differences were observed among the mean baseline function studies during the 3 treatment periods. There were no significant differences in sputum production, sputum thickness, dyspnea, or mouth dryness among the 3 treatment periods. Side effects were mild; isoproterenol treatment was associated with an increased frequency of palpitations, and atropine treatment was associated with difficulty in voiding. Significant increases in lung function were apparent in the measurements made 15 min and 60 min after inhalation of atropine or isoproterenol. Mean values of flow and specific airway conductance increased, and mean values of airway resistance and functional residual capacity decreased after inhalation of either drug. There was no significant difference between the effects of atropine and isoproterenol on lung function, although both differed significantly from the effects of placebo (P less than 0.001). Inhaled atropine sulfate was as effective a bronchodilator as inhaled isoproterenol hydrochloride, and was well tolerated during the 3-week trial of daily therapy.


Effects of smoked marijuana in experimentally induced asthma. After experimental induction of acute bronchospasm in 8 subjects with clinically stable bronchial asthma, effects of 500 mg of smoked marijuana (2.0 per cent delta9-tetrahydrocannabinol) on specific airway conductance and thoracic gas volume were compared with those of 500 mg of smoked placebo marijuana (0.0 per cent delta9-tetrahydrocannabinol), 0.25 ml of aerosolized saline, and 0.25 ml of aerosolized isoproterenol (1,250 mug). Bronchospasm was induced on 4 separate occasions, by inhalation of methacholine and, on four other occasions, by exercise on a bicycle ergometer or treadmill. Methacholine and exercise caused average decreases in specific airway conductance of 40 to 55 per cent and 30 to 39 per cent, respectively, and average increases in thoracic gas volume of 35 to 43 per cent and 25 to 35 per cent, respectively. After methacholine-induced bronchospasm, placebo marijuana and saline inhalation produced minimal changes in specific airway conductance and thoracic gas volume, whereas 2.0 per cent marijuana and isoproterenol each caused a prompt correction of the bronchospasm and associated hyperinflation. After exercise-induced bronchospasm, placebo marijuana and saline were followed by gradual recovery during 30 to 60 min, whereas 2.0 per cent marijuana and isoproterenol caused an immediate reversal of exercise-induced asthma and hyperinflation.


Highlights in the development of arterial surgery. It is concluded that progress in medicine has been maintained at such a rapid pace that the delivery system has had difficulty in keeping up. This has been excellently demonstrated by the progress in the category of vascular surgery. Achievements have placed added demands on available trained personnel, materiel, and most importantly, the financial resources of every community and the government fulfilled, the problem will continue to be a vexing one and will not be easy to solve. The success of our scientific efforts will continue to be costly.


Repair of hiatal hernia: description and long-term results of a technique. A modification of the surgical approach for the correction of hiatal hernia is presented. The technique involves use of the phrenoesophageal ligament as a structure of support for the repair, along with the strength of the deep submucosal sutures through the stomach and esophagus. An additional modification is the buffering of the sutures with teflon felt pledgets to prevent tearing through of the sutures. Long-term follow-up was obtained in 30 patients. There was one recurrence. All patients remain symptom-free to date.


T- and B-cell interactions in autoimmune syndromes. We have reviewed briefly some of the individual capabilities of T and B cells and how these can be modified by interactions between the two cell lines. Evidence that T cells have their own distinct receptors for antigens, yet under certain circumstances may bind IgM or IgG produced by B cells, has been particularly emphasized. The probability that B cells, in turn, may bind the antigen receptor of T-cell origin reflects the balanced nature of an intricate communication system in which interactions between antigens, antigen receptors, and binding sites for these receptors all serve to modulate the integrated functioning of T and B cells. It is suggested that this communication system is disturbed in patients with rheumatoid arthritis; specifically, it is proposed that defective feedback activity of IgG-antigen complexes on activated T cells may exist in some patients and could result in unchecked and harmful T-cell activity in the joint. Therapeutic implications of this idea are mentioned.


Lymphokines in rheumatoid synovitis.

Lymphokines in rheumatoid synovitis. In antigen-induced experimental arthritis of rabbits, a macrophage migration inhibitory factor was released from the inflamed synovial tissues. A migration inhibitory factor, blastogenic factor, and B-cell-stimulating factor were also found in human rheumatoid synovial fluids and culture supernatants of rheumatoid tissue explants. Joint fluids from patients with inflammatory conditions other than RA sometimes also displayed these activities. OA fluids were usually inactive. At present, little is known of the origin or role in vivo of the lymphokine-like activities observed in the joints of rheumatoid patients. In related experiments, injection of lymphokine-rich antigen-free lymphocyte supernatants into normal rabbit knee joints produced a synovitis characterized by lining layer hyperplasia and infiltration of the sublining layer by macrophages. The lymphocytic and plasmacytic components seen in active antigen-induced synovitis were absent. It seems likely that some of the changes observed in active chronic synovitis are mediated by soluble factors of the lymphokine variety.


Physiologic and pharmacologic alterations of rat leukocyte chemotaxis (Cx) in vivo. The method of adoptively transferring 51Cr-labeled rat leukocytes iv to isologous recipients was used to quantitate the extravascular accumulation of specific cell types at the site of inflammation induced by local injection of various phlogistic agents. Experiments were designed to determine whether cellular accumulation could be modified at the level of the chemotactic factor, by serum components, or by alteration of the responding cell itself. The results indicated a selective attraction of mononuclear cells to the local injection site of BCG and of neutrophils to the injection site of aggregated but not monometric gamma-globulin. Thus, leukocytic accumulation was found to be dependent upon the local generation of specific reactants that were particular to the agent employed. Leukocytic accumulation could also be modified by serum factors. Cellular accumulation was inhibited when leukocytes were exposed to serum that contained phagocytosable particles or after phagocytosis in vitro prior to adoptive transfer. Chemotaxis of lymphocytes could be induced by their preincubation with sera from adjuvant arthritic animals. These observations were confirmed by in vitro studies and by the finding that 6 days after adjuvant injection , lymphocytes but not mononuclear cells accumulated at the noninjected extremity. In the final series of experiments, it was shown that BCG immunization was capable of inducing a unique population of peritoneal mononuclear cells that after adoptive transfer had an enhanced capacity to remain in the circulation, which, in turn, resulted in a functional increase in their accumulation at an inflammatory reaction site. In conclusion, these studies indicated that the chemotactic activity of adoptively transferred cells can be modified by changes in the chemotactic stimuli, can be enhanced or depressed by serum factors, and is a function of the physiologic capability of the cell population employed.


Activation of the complement and properdin systems in rheumatoid arthritis. The classic (C1, C4, and C2) and properdin factors (D, C3b, and B) of complement generate C3 convertases that are capable of cleaving C3 and subsequently activating C5-C9. Both C1 and factor D are serine esterases, and both convertases undergo decay and regeneration. In seropositive rheumatoid arthritis, where intraarticular activation of the classic early components (C1, C4, and C2) by immunoglobulin complexes appears to predominate, findings of relative depressions in synovial fluid levels of factor B indicate recruitment of the amplification loop (D, C3b, and B), and relative declines in properdin levels suggest activation of the properdin pathway as well. Quantitative analysis of the complement system in disease states requires several different approaches: measurement of function and antigenic concentration to assess the functional integrity of the protein; determination of component metabolism to appreciate the relative contributions of hypercatabolism and hyper- or hyposynthesis to the plasma level; and for compartmentalized disease, measurement of the component in the appropriate biologic fluid and determination of local tissue synthesis.


[Sequential analysis of effectiveness of diazepam, a tranquilizer, on stress in swine (author's transl)]. To study the effectiveness of diazepam, a tranquilizer, in alleviating the problems resulting from the mixing and moving of weaned piglets from one piggery to another, two procedures, one of short-duration transport and the other of long-duration transport, are used in a double blind clinical trial. Both followed mixing the pigs, but before they entered the new piggery. Results from both groups of pigs (treated and control) are sequentially analyzed. Measurements used are growth rate and feed conversion curves during the first 18-20 days of the prefattening period. Diazepam (I mg/kg IM) reduces feed conversion when used to alleviate the effects of the long journey, but increases feed conversion after the short journey when compared to controls injected with a placebo. Worsening effects seem related to increased aggressiveness in animals treated and transported. These results indicate that a better understanding of the action mechanisms of psychotropic drugs is necessary, and they should be used with caution in husbandry.


Effect of ovine hydatid cyst fluid on the cardiovascular and respiratory systems in sheep. Rupture of the hydatid cyst in man brings about mild to severe toxic reactions including death. The present study was undertaken to investigate some of the responses resulting from administration of the ovine hydatid fluid to the sheep, which, like man, is an intermediate host of the Echinococcus granulosus. In 50 sodium pentobarbital-anesthetized sheep, the arterial blood pressure (A.B.P.), central venous pressure (C.V.P.), respiration and electrocardiogram were recorded. Intraveonus administration of 5-10 ml hydatid fluid brought about moderate to severe fall in A.B.P. and rapid respiration with or without transient apnea or permanent repiratory cessation in 80 percent of the animals. Fifty percent of the sheep died of circulatory and respiratory failure after the first injection of the hydatid fluid. Boiled hydatid fluid did not lose its potency to evoke the above responses. Pretreatment of the aminals with atropine sulfate, 0,5 mg/kg subcutaneously, did not block the reactions. Administration of the antihistamine chlorpheniramine, 4 mg/kg intravenously, caused partial prevention of the reactions in 6 out of 10 responsive sheep. The cardiovascular and respiratory responses to ovine hydatid fluid may be due to antigen-antibody reactions or some toxic component of the fluid.


Diffusion of trimethoprim and sulfamethoxazole from susceptibility disks into agar medium. The standard practice of using a single susceptibility disk for the antimicrobial combination Septra (trimethoprim/sulfamethoxazole) has been further justified by a direct measurement of the diffusion rates of each compound through agar medium. [(14)C]trimethoprim and [(35)S]sulfamethoxazole, singly and in combination, were applied to blank susceptibility disks which were incubated on 4-inch (10.16-cm) agar plates (Mueller-Hinton medium) at 37 C. The migration of each compound from the disk and diffusion through agar were measured with time by determining the radioactivity in concentric zones extending from the origin. The two compounds diffuse with similar rates, maintaining approximately a 1:20 concentration ratio which is approximately the ratio of trimethoprim to sulfamethoxazole observed in plasma during treatment. The diffusion rate is independent of the presence of the other compound; greater than 95% of the radioactivity is transferred from the disk to the agar in 24 h.


Activity of minocycline against Acinetobacter calcoaceticus var. anitratus (syn. Herellea vaginicola) and Serratia marcescens. The activity of minocycline and tetracycline against 23 isolates of Acinetobacter calcoaceticus var. anitratus (syn. Herellea vaginicola) and 178 strains of Serratia marcescens was determined by disk and microdilution methods. The results indicate that minocycline is highly active against this species of Acinetobacter, all but one strain being inhibited by 0.007 mug of the antibiotic per ml. Tetracycline was also active, though to a lesser degree, against A. calcoaceticus. Of the 178 strains of S. marcescens tested, only seven (3.9%) had a minimum inhibitory concentration of 2 mug or less of minocycline per ml. Tetracycline was less active than minocycline against S. marcescens; with 2 mug of tetracycline per ml, only 2 of 152 (1.3%) strains were inhibited. At concentrations of 8 and 16 mug of minocycline per ml, which can be achieved in the urine with the usual doses, 44.9 and 63.5% of S. marcescens strains were inhibited, which implies its possible usefulness for the therapy of urinary tract infection due to this organism.


Clinical and laboratory considerations in metabolic bone disease. An overview of the common types of metabolic bone disease is described. When the disease is present in pure form, diagnosis is not difficult. When mixed disease is present, as may be the case, the pathophysiology involved must be clearly understood for accurate diagnosis and treatment.


Bacteriocinogenic Clo DF13 minicells of Escherichia coli synthesize a protein that accounts for immunity to bacteriocin Clo DF13: purification and characterization of the immunity protein. Cloacin DF13 inhibits protein synthesis both in vivo and in vitro by inactivation of ribosomes. In this paper we describe the purification, from purified bacteriocinogenic plasmid DF13 (Clo DF13)-harboring minicells of Escherichia coli, of an acidic protein (molecular weight about 10,000) that prevents the inhibition of in vitro protein synthesis by cloacin DF13. It turned out that this protein is one of three Clo DF13 plasmid-specific polypeptides that are synthesized by the noninduced Clo DF13 plasmid in minicells. Furthermore, we observed that, after induction with mitomycin C, the amount of immunity protein is only slightly increased, whereas the cloacin DF13 synthesis is increased about 40 times. These results imply that the genes that code for immunity protein and cloacin DF13 are not located in the same regulatory unit. Under noninduced conditions, apparently an excess of immunity protein is synthesized, because this amount of immunity protein is even sufficient to neutralize the strongly increased amount of cloacin after induction, since growth of induced cloacinogenic cells is continued.


Immunologic aspects of myasthenia gravis. Clinical and pathologic features of myasthenia gravis suggest a possible autoimmune etiology. Myasthenia is found in association with other putative autoimmune diseases and autoantibodies including anti-muscle antibodies. There is also in vitro evidence for cell-mediated immunity to muscle in blood and thymic cells as well as a suggestion of antigenic disparity between blood and thymic cells. In addition, two experimental animal models are under investigation. It seems likely that the immune system plays a role in the pathogenesis, but what that role is and how it relates to neuromuscular block is not clear.


Bacteriocinogenic Clo DF13 minicells of Escherichia coli synthesize a protein that accounts for immunity to bacteriocin Clo DF16: action of the immunity protein in vivo and in vitro. The Clo DF13 plasmid-specific immunity protein is able to prevent the inhibitory effect of cloacin DF13 on in vitro protein synthesis. We have shown, by gel filtration, that direct binding of the Clo DF13 immunity protein to cloacin occurs in vitro. This cloacin DF13-immunity protein complex is rather stable, and the cloacin present in the complex is no longer able to cause inhibition of in vitro protein synthesis. The binding of immunity protein to cloacin DF13 is rather specific because the Clo DF13 immunity protein does not bind to in vitro inactive cloacin and binds very poorly to the closely related bacteriocin colicin E3. Furthermore, we present data which strongly suggest that in vitro at least a fourfold excess of immunity protein is required to ensure that every cloacin molecule is inactivated by cloacin-immunity protein complex formation. Only a fraction (an about equimolar amount) of the immunity protein molecules, however, actually binds to cloacin DF13. The existence of an immunity protein-cloacin complex in vivo was concluded from the observation that cloacin, purified by chromatography on diethyl-(2-hydroxypropyl)-aminoethyl Sephadex in the absence of urea, contains an about equimolar amount of a second protein which comigrates with immunity protein on sodium dodecyl sulfate-polyacrylamide and urea-polyacrylamide gels. In an in vitro protein-synthesizing system, this component appeared to behave identical to the Clo DF13 immunity protein. The purified immunity protein-containing cloacin was at least 80 times less active in inhibiting in vitro protein synthesis, compared to cloacin, free of immunity protein. These data imply that few, if any, cloacin DF13 molecules are present in cloacinogenic cells as active, free cloacin molecules.


Survival of frozen mycoplasmas.

Survival of frozen mycoplasmas. Cooling to -70 C killed a higher percentage of Acholeplasma laidlawii and Mycoplasma mycoides var. capri cells than cooling to -20 C. However, to preserve cell viability for prolonged periods storage at -70 C was much more preferable. The percentage of cells surviving freezing could be increased by increasing the initial cell concentration or by the addition of dimethyl sulfoxide or glycerol as cryoprotective agents. In the presence of 1.5 M of any one of these agents survival rates of up to 100% could be obtained. The optimal cooling rates for maximal survival of A. laidlawii under the experimental conditions tested were 11 C/min for cooling to -20 C and about 15 C/min for cooling to -70 C. Increasing the warming rate during thawing from 0.6 to 67 C/min increased survival by 3 log. Oleic acid enrichment of A. laidlawii membrane lipids, or reduction in the cholesterol content of M. mycoides var. capri membranes, increased the percentage of organisms surviving freezing. Hence, the composition of membrane lipids appears to have a marked influence on the susceptibility of mycoplasmas to freezing injury.