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Biomedical subjects

A Schaffner

Publications and source records attributed to A Schaffner.

At least 91 records · Page 5Linked to original sources
PubMed1992

Cytofluorometry as a diagnosis of protoporphyria.

Protoporphyria is a disorder that usually has cutaneous symptoms. Only in a few cases liver disease develops, invariably progressing to cirrhosis and liver failure. A case of a patient who suffered from photosensitivity as a result of protoporphyria since the age of 2 is described. At age 33, she first presented with cholestatic hepatitis. At age 40, liver failure developed requiring liver transplantation. Quantitative cytofluorometry proved to be a quick and simple method in the follow-up of her erythrocyte protoporphyrin levels before, during, and after transplantation. Fluorescence correlated well with the protoporphyrin levels obtained by high-performance liquid chromatography (r = 0.98), a comparably cumbersome and complicated method for the determination of protoporphyrin. In addition, single cell analysis enabled us to follow the effects of transfusion therapy on protoporphyrin levels of the patient's own erythrocytes, which has not been possible by previous methods. Thus, cytofluorometry might prove to be elegant and useful for screening and future studies on therapy and pathophysiology of protoporphyria.

Adult↗
PubMed1992

Milestone Action Plans. Empowering nurses to manage care.

Confronted by continuing financial losses that could not be simply staunched by further reductions in the operations budget, a medical center implemented an innovative cost-cutting program that offered quick results and simplicity of design while assuring quality patient care. The authors describe the initiative known as Clinical Resource Management (CRM), which unites the expertise of physicians, nurses, and other care providers in a collaborative approach.

California↗
PubMed1991

Safety of stringent prophylactic platelet transfusion policy for patients with acute leukaemia.

Early studies suggested that the risk of haemorrhagic complications become unacceptable when platelet counts drop below 20 x 10(9)/l. Because there are insufficient data to define 20 x 10(9)/l as the threshold for prophylactic platelet transfusions, the practicability of a more restrictive transfusion policy has been assessed prospectively in 102 consecutive patients being treated for acute leukaemia. Besides platelet count, the transfusion protocol took into consideration factors such as presence of bleeding, fever, coagulation disorders, and intention to do therapeutic procedures. 31 major bleeding episodes occurred on 1.9% of the study days when platelet counts were 10 x 10(9)/l or less and on 0.07% of study days when counts were 10-20 x 10(9)/l. The findings indicate that the threshold for prophylactic transfusions can safely be set at 5 x 10(9)/l in patients without fever or bleeding manifestations and at 10 x 10(9)/l in patients with such signs. For patients with coagulation disorders or anatomical lesions, or for those on heparin, the threshold should be at least 20 x 10(9)/l. Such a restrictive platelet transfusion policy, which is applicable not only to thrombocytopenia associated with acute leukaemia but also to other forms of hypoproliferative thrombocytopenia, reduces exposure of such patients to blood donors and results in substantial health-care savings.

Adolescent↗
PubMed1991

[Antimycotic therapy in clinical practice].

Mycoses commonly encountered in outpatients in Europe are usually limited to body surfaces and are no threat to the patient. Topical or systemic therapy with modern antimycotics is usually effective. Improved pharmacokinetic properties of newer azoles have shortened and simplified treatment of the mucosal forms of candidiasis for which a single dose of fluconazole (150 or 200 mg) or a short course with two doses of itraconazole (2 x 100 mg) are recommended. For patients with an uncorrectable predisposition to thrush, guidelines are provided for prophylaxis or self-initiated therapy. Whenever possible dermatophytoses should be treated topically to avoid long-term exposure to the new keratinotropic azoles and allylamines, for which insufficient long-term toxicological data are at present available. Ketoconazole should be avoided for these indications because of its potentially serious hepatotoxicity. For many indications requiring prolonged treatment griseofulvin remains the favoured systemic drug due to its extensive safety record.

Administration, Topical↗
PubMed1991

Humoral immune response to pneumococcal antigen 23-F in an asplenic patient with recurrent fulminant pneumococcaemia.

Host defence mechanisms were analysed in a patient with three episodes of fulminant pneumococcaemia and one episode of bacteraemic epiglottitis with Haemophilus influenzae type b. The first episode took place 11 years after splenectomy for blunt abdominal trauma. Investigations revealed several host defence mechanisms to be impaired. In addition to the patient's asplenia, an inherited C2-deficiency was noted. Assessment of IgG subclasses repeatedly revealed markedly low IgG4 concentrations. These were not due to an increased turnover of IgG4, as could be shown following infusion of intravenous IgG. In addition, IgG2 concentrations were low in the patient who lacked G2M(23). Opsonic mediating antibodies against type 23-F pneumococci were in the range of those of non-immune volunteers 6 months after vaccination with a 23-valent pneumococcal vaccine. These antibodies did not increase after a septic episode with 23-F capsular-type pneumococci. Neutrophil function was apparently normal.

Adolescent↗
PubMed1991

Detection of capsular polysaccharide in serum for the diagnosis of pneumococcal pneumonia: clinical and experimental evaluation.

To improve diagnostic options for pneumococcal pneumonia, an ELISA system was developed that can detect less than or equal to 6 ng/ml capsular polysaccharide in serum. The test was limited to 39 serotypes causing greater than 95% of pneumococcal infections. In clinical evaluation the test identified 14 of 15 cases (missing one serotype not included). No false-positive reaction occurred. However, the duration and level of antigenemia were variable (greater than or equal to 500-2.5 ng/ml) and seemed not to depend solely on the severity of infection. Therefore, the question of whether the extent of antigenemia was determined by a serotype-dependent variation in the elimination rates of polysaccharides was investigated. Clearance rates for 12 serotypes varied in rabbits and rats by a factor of greater than 250. This remarkable variability appeared to affect the extent of clinical antigenemia. Thus, only very sensitive systems can detect circulating antigen from rapidly cleared polysaccharide serotypes. Furthermore, the question arises whether slow polysaccharide clearance contributes to the virulence of some pneumococcal serotypes.

Animals↗
PubMed1991

Transient pure red cell aplasia caused by antilymphoblast globulin after cadaveric renal transplantation.

Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (less than 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by autoantibodies to erythroblasts, this type of PRCA could be viewed as "heteroimmune disease."

Adolescent↗
PubMed1991

Fatal fungal pericarditis after cardiac surgery and immunosuppression.

The cases of two patients with fulminant pericarditis after cardiac surgery are reported. Both fungal infections developed after rethoracotomy for open-chest cardiac resuscitation and high-dose glucocorticoid treatment. Although the time course of both infections from the inoculation of fungi during rethoracotomy and immunosuppression with glucocorticoids to the lethal outcome was strikingly similar, histopathologic studies disclosed the disparate character of the two fungal pathogens responsible: the yeast Candida albicans and the angiotropic mold Aspergillus fumigatus.

Aged↗
PubMed1990

Pure red cell aplasia of long duration complicating major ABO-incompatible bone marrow transplantation.

In 3 of 15 consecutive patients receiving a human leukocyte antigen (HLA)-identical but major ABO incompatible bone marrow transplant (BMT), pure red cell aplasia (PRA) lasting 5 to 8 months was observed. Titers of the incompatible anti-A agglutinin before infusion of the red blood cell (RBC)-depleted BMT was very high in one, and in the usual range in two patients. Decrease of agglutinin titers during the first 4 weeks after BMT were comparable between PRA patients and those of ABO-incompatible BMT recipients with timely RBC recovery. However, in PRA patients, agglutinin titers rose again and remained elevated for 19 to 28 weeks. RBC engraftment and reticulocyte recovery ultimately occurred spontaneously and coincided with the decrease of agglutinin titers below 16. These observations indicate that PRA is antibody-dependent in this setting. Furthermore, it is conceivable that cyclosporine facilitates recipient-derived antibody synthesis after major ABO-incompatible BMT.

ABO Blood-Group System↗
PubMed1990

[Antimycotic therapy].

Because deep opportunistic mycoses are relatively rare, clinicians frequently lack routine in the application of antimycotics. It is the purpose of this review to summarize, from a practical point of view, rationale, indications, applications and toxicity of antimycotic therapy for the mycoses autochthonous to Europe. Amphotericin B remains the standard therapy for most deep opportunistic mycoses, while the newer azoles are the first line agents to be used for superficial forms of candidiasis.

Amphotericin B↗
PubMed1989

Endotoxin suppresses the generation of O2- and H2O2 by "resting" and lymphokine-activated human blood-derived macrophages.

In evaluation of macrophage-activating principles other than lymphokines, we systematically investigated the effects of endotoxin on the formation of reactive oxygen intermediates measured by chemiluminescence. Surprisingly, endotoxin exposure of human blood monocytes cultured in vitro for 36 h lessened in a dose-dependent manner the amount of O2- and H2O2 secreted in response to phagocytosis of opsonized particles or to PMA, a soluble stimulant. Blunting of the respiratory burst by endotoxin was independent from the state of macrophage activation. Endotoxin thus impaired formation of reactive oxygen metabolites before, during, or after activation of macrophages by IFN-gamma. The median effective concentration (EC50) was 1.95 ng/ml LPS in resting macrophages and 7.22 ng/ml in IFN-gamma-activated macrophages with as little as 0.1 ng/ml reproducibly giving detectable inhibition. Lipid A, but not "detoxified" monophosphoryl lipid A gave an inhibition comparable to that of complete LPS. The inhibitory effect of endotoxin was attenuated by dexamethasone, but not by inhibitors of arachidonic acid metabolism. Because endotoxin induces and dexamethasone inhibits production of some monokines, it is tempting to speculate that endotoxin is part of an autoregulatory system of mononuclear phagocytes for the control of excessive production of potentially harmful oxidants. The two monokines identified to be secreted in response to LPS and to be inhibited by dexamethasone, IL-1 and TNF, had, however, no comparable effect on chemiluminescence.

Animals↗
PubMed1989

Experimental basis for the clinical epidemiology of fungal infections. A review.

Based on the concept that the agents of deep fungal infections can be divided into primary pathogens and opportunists the experimental basis for the clinical epidemiology of mycoses is outlined. Kinetics of experimental infections with opportunists and primary pathogens discriminate between the two fungal categories. Natural resistance eliminates opportunists and prevents the establishment of progressive infection in the normal host. Primary pathogens call upon mechanisms of adoptive cell mediated immunity for their control. Therefore athymic mice which are not more susceptible to opportunists than control mice, cannot control infection with primary pathogens. In order to induce comparable overwhelming opportunistic mycoses with reasonable challenge doses, non-specific phagocytic resistance has to be eliminated. In agreement with in vivo studies, in vitro studies of the susceptibility of fungi to killing by phagocytes point out, that the susceptibility of the tissue phase of fungi to killing by "immunologically unarmed" phagocytes discriminates between opportunists and primary pathogens. In order to restrain primary pathogenic fungi, phagocytes have also in vitro to call upon adoptive, T cell-dependent immune mechanisms, which appear superfluous for control of opportunists. This difference explains the discrepant opportunistic proclivities of the two fungal categories. Patients with defective phagocytic defenses are prone to opportunistic mycoses, while deficient cell mediated immunity results in a greater vulnerability to primary pathogens.

Animals↗
PubMed1989

A new experimental model of localized candidosis for the study of antifungal chemotherapy.

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed and was used to test the efficacy of various antifungal drugs. The results were similar regardless whether cortisone or cyclophosphamide was used for immunosuppression. The highest efficacy was shown by amphotericin B in relatively high doses (2 mg/kg s.c.). The new triazole derivatives also showed good chemotherapeutic activity (fluconazole, ICI 195, 739, SDZ 89-485). Flucytosine was also highly effective despite its short half-life. The model thus gives a valuable indication of the chemotherapeutic efficacy against Candida thrush in humans.

Animals↗
PubMed1989

Comparison of immunosuppressive effects of cyclosporine A in a murine model of systemic candidiasis and of localized thrushlike lesions.

Candida albicans is an opportunistic human pathogen preferentially causing invasive and disseminated infection in patients with defective phagocytic defenses and serious mucocutaneous infection in patients with deficient T-cell function. Phagocytes appear to protect the host from fungal invasion even in the absence of adaptive immune mechanisms, while as-yet-undefined T-cell-dependent factors seem necessary for control of C. albicans on body surfaces. To study host defense mechanisms on body surfaces, we developed a new model of thrush in artificial pneumatized cysts in mice. Cyclosporine A, a relative selective suppressor of T-cell-mediated immunity and natural killer cell activity, promoted the formation of thrushlike lesions on cyst surfaces and impeded elimination of C. albicans from such lesions. As expected from the absence of an impairment of antimicrobial phagocytic activity, cyclosporine A had no effect on systemic candidiasis induced by intravenous inoculation. Surprisingly, athymic nude mice were not more susceptible to superficial candidiasis than control mice and were comparably affected by cyclosporine A. In contrast, beige mice, which in addition to phagocytic dysfunction have reduced natural killer cell activity, were more susceptible to thrushlike lesions, and cyclosporine A was correspondingly less active in this mouse strain. Immunosuppression with cyclosporine A affects host defense mechanisms which are operative against superficial candidiasis but appear superfluous in resistance to the invasive form of this mycosis, an indication for the divergent nature of host defense against the two forms of candidiasis.

Animals↗
PubMed1988

Gamma-interferon restores listericidal activity and concurrently enhances release of reactive oxygen metabolites in dexamethasone-treated human monocytes.

By preventing macrophages from destroying phagocytized microorganisms, glucocorticoids lower natural resistance of the host against many pathogens. gamma-Interferon has an opposite effect and restores activity of dexamethasone-treated mononuclear phagocytes against some but not all microorganisms. In the present studies we show that dexamethasone impairs activity of human blood monocytes kept in culture for 36 h against Listeria monocytogenes, without impairing H2O2 or O2- secretion. Likewise dexamethasone does not interfere with activation of systems generating oxygen metabolites by lymphokines. Thus gamma-interferon increases three- to fivefold the capacity of dexamethasone-treated monocytes to secrete O2- or H2O2 upon stimulation by opsonized zymosan, live bacteria, or phorbol myristate acetate. Concurrently gamma-interferon restores listericidal activity of dexamethasone-treated monocytes. After gradual activation by exposure to gamma-interferon for progressive time periods, listericidal activity becomes tightly correlated (r = 0.922-0.994) with the amount of H2O2 or O2- secreted by dexamethasone-treated monocytes. Activation of oxidative systems by the lymphokine is, however, not correlated with the restoration of activity against Aspergillus spores, lost during dexamethasone treatment, which does not depend on antimicrobial oxygen metabolites. Taken together, these observations lend to the hypothesis that glucocorticoids impair nonoxidative defense mechanisms of "resting" macrophages, while gamma-interferon restores macrophage function impaired by glucocorticoids by activating alternate killing systems, which are at least partly of oxidative nature.

Blood Bactericidal Activity↗