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Biomedical subjects

B Styrt

Publications and source records attributed to B Styrt.

At least 19 recordsLinked to original sources
PubMed1995

Hepatotoxicity of antiviral agents.

Because most therapeutic agents used for viral infections are relatively new, experience with their adverse effects is still evolving. Hepatic toxicity has not been among the most important concerns with this class of drugs so far. Liver damage has been increasingly noted with accumulating experience, especially with antiretroviral drugs and those used to treat chronic hepatitis (e.g., fialuridine), but it is often difficult to distinguish between effects of therapy and of the underlying disease. It is important for clinicians to be aware of the possibility of hepatotoxicity in such situations, and further reporting of adverse experiences should contribute to more definitive evaluation of the potential influence of antivirals on liver function.

Animals↗
PubMed1994

Symptoms and rate of temperature change in febrile outpatients.

Although patient comfort is a frequent rationale for antipyretic therapy, there have been few systematic studies of relationships between temperature and comfort. In this study, adult outpatients with febrile illnesses were asked to complete a symptom diary at multiple time points at which temperature was recorded. Temperature readings showed modest correlation (0.316) with scores of "feeling better or worse" and moderate correlation (0.586) with aggregate symptom scores. Rate of temperature change showed low levels of correlation (< 0.25) with both measurements. Direction of temperature change was not significantly associated with overall subjective score of "feeling better or worse" although aggregate symptom scores were slightly higher with rising than falling temperature. These findings suggest that temperature is a partial determinant of morbidity in minor febrile illnesses but contribution of temperature change to well being may be small. Further study is needed to determine the appropriate priority of temperature reduction in symptomatic therapy.

Adult↗
PubMed1991

Chemorepulsion of trichomonads by products of neutrophil oxidative metabolism.

To determine whether secreted neutrophil products affect the migration of motile microorganisms such as Trichomonas vaginalis, stimulated human neutrophils and cell-free oxygen metabolites were used as stimuli in a multiwell filter chemotaxis assay using tritiated T. vaginalis. When stimulated neutrophils were present on the opposite side of the filter, migration of T. vaginalis into the filter was significantly diminished, and this reduction varied with the dose of neutrophil stimulus. The reduction of movement was abrogated by the addition of catalase and superoxide dismutase to scavenge oxygen metabolites. Studies with cell-free hydrogen peroxide or hypochlorite preparations indicated that the reduction in trichomonal trapping in the filter was due to chemorepulsion and not to a nonspecific decrease in motility or adherence. These findings suggest that active migration away from neutrophil products might be a means by which trichomonads avoid the microbicidal functions of host phagocytes.

Animals↗
PubMed1990

Degranulation of human neutrophils after exposure to bacterial phospholipase C.

Because an endogenous phospholipase C (PLC) participates in neutrophil activation and because many bacterial pathogens produce PLCs, these studies examined the effect of PLC from Bacillus cereus on the release of the granule enzyme lysozyme from human neutrophils. Bacillus cereus PLC caused dose-dependent lysozyme release, and combined stimulation of neutrophils with PLC and fluoride led to increased secretion. Stimulation of neutrophil degranulation is a potential contributing factor for tissue damage in infections caused by PLC-producing organisms.

Bacillus cereus↗
PubMed1990

Time and temperature dependence of granulocyte damage by leucotoxic supernatants from Pasteurella haemolytica A1.

Bacterial exotoxins may contribute to the pathogenic potential of micro-organisms through interactions with cells of the host defence system as well as by directly damaging host tissue. The present studies were designed to explore mechanisms of interaction between bovine granulocytes and the leucotoxin produced by Pasteurella haemolytica, a major cause of bovine respiratory disease. Leucotoxin-containing supernatant from P. haemolytica A1 caused rapid cell death in isolated bovine granulocytes that was close to half-maximal by 5 min and nearly 90% complete after 30 min at 37 degrees C. Maintaining granulocytes at ice-water temperature markedly attenuated or prevented the toxic effect; furthermore, if exposed to supernatants at ice-water temperature and then washed, most cells remained viable even after rewarming to room temperature. However, even a very brief exposure (about 5 s) at 37 degrees C led to extensive cell death even after immediate cold dilution and washing. Granule enzymes such as arylsulphatase were released far more slowly than cytosol contents. Leucotoxin purified by column chromatography showed temperature dependence and divergence between cytosol and granule marker release similar to those observed with the crude supernatant preparation. These findings indicate that irreversible interaction between P. haemolytica leucotoxin and bovine granulocytes is initiated very rapidly at 37 degrees C but markedly impeded at low temperature, while granule enzyme release follows cytosol marker release over a much longer period. The results suggest either a requirement for target cell metabolic activity to initiate toxin effects or a temperature-dependent receptor conformation, with granule enzyme release following as a secondary consequence of granulocyte death.

Animals↗
PubMed1990

Infection associated with asplenia: risks, mechanisms, and prevention.

The risk of overwhelming sepsis in asplenic patients has been recognized increasingly over the past several decades, but the underlying mechanisms are not fully understood, and there is controversy over the true magnitude of risk and the value of specific interventions. Review of recent series indicates that postsplenectomy sepsis is more likely after splenectomy in childhood than after splenectomy in adulthood but may occur after splenectomy at any age. In some cases, sepsis has been documented many years after surgery. The pneumococcus remains the predominant organism, and the characteristic course is rapid progression to multisystem involvement with high morbidity and mortality. Predisposition to pneumococcal sepsis and to other infections reflects the role of the spleen in mechanical filtration of particulate material in the bloodstream, generation of opsonins and other soluble mediators of phagocytosis, and anatomic juxtaposition of different elements of the immune system. Whereas pneumococcal vaccine is indicated in asplenic patients, the value of other interventions requires further evaluation.

Bacterial Infections↗
PubMed1990

Antipyresis and fever.

While understanding of the mechanisms of fever has progressed in recent years, much uncertainty remains as to whether fever in itself (as distinct from its cause) is beneficial or harmful, and what circumstances warrant antipyretic therapy. This review was designed to identify studies providing information on the effects of fever and of pharmacologic and physical therapy. Fever or analogous behavioral thermal upregulation apparently has positive effects on defense against infection in some animal models. Retrospective studies in humans suggest that failure to mount a febrile response is associated with poor outcome in certain infections but do not establish a causal relationship. Induction of fever apparently had therapeutic value in infections such as syphilis before specific antimicrobials were developed. Fever may have deleterious effects in the context of borderline cardiovascular or neurologic function or pregnancy, but data in most instances cannot separate effects of fever per se from that of underlying disease. Antipyretic drugs are effective in diminishing fever, but they have significant side effects and may suppress signs of ongoing infection. Physical cooling is important when physiologic thermoregulatory mechanisms are overwhelmed, but may sometimes increase discomfort and metabolic stress in fever. Antipyretic therapy should not be instituted routinely for every febrile episode but should be based on evaluation of relative risks in the individual case and reassessed if anticipated benefits are not achieved.

Animals↗
PubMed1990

Granulocyte plasma membrane damage by leukotoxic supernatant from Pasteurella haemolytica A1 and protection by immune serum.

Bovine respiratory disease caused by Pasteurella haemolytica may be partially mediated by a leukotoxin secreted by the microorganism. We examined the effect of leukotoxic Pasteurella supernatants on leakage of the cytosol enzyme lactate dehydrogenase and the lysosomal enzyme arylsulfatase from bovine granulocytes. Lactate dehydrogenase release (94%) was much higher than arylsulfatase release (38%) over 30 minutes of incubation. The Pasteurella supernatants inhibited superoxide production by stimulated granulocytes at concentrations which also caused substantial cell death as measured by failure to exclude trypan blue. Both toxic effects were prevented by serum from aerosol-immunized calves, and protection appeared to be antibody-specific by comparison with fetal bovine serum or with serum absorbed against intact P. haemolytica. These findings suggest that the leukotoxin may selectively disrupt the granulocyte plasma membrane, and that antibody directed against a surface component of the microorganism is also capable of protecting against the leukotoxin effect.

Animals↗
PubMed1989

History and implications of the neutrophil glycoprotein deficiencies.

This review focuses on the initial clinical descriptions and subsequent investigation of the syndrome of recurrent infections associated with neutrophil membrane glycoprotein deficiencies. Characterization of the missing group of three glycoprotein heterodimers and their role in adhesion-related neutrophil function is summarized. Study of the clinical consequences of these genetically determined membrane glycoprotein defects has also contributed to the understanding of the role of normal neutrophils in both host defense and host tissue damage.

Glycoproteins↗
PubMed1989

Neutrophil oxidative metabolism after exposure to bacterial phospholipase C.

The effects of phospholipase C (PLC) from Clostridium perfringens and Bacillus cereus on bovine neutrophil oxidative metabolism were studied by measuring superoxide production and oxygen consumption in response to PLC alone or in combination with other stimuli. PLC from both species elicited superoxide production and enhanced the response to stimulation by NaF when the two stimuli were given simultaneously. However, oxygen consumption in response to latex beads was markedly inhibited by pretreatment of cells with B. cereus PLC. The results suggest that some bacterial PLC exoenzymes may initially activate neutrophils but leave the cells relatively unresponsive to subsequent stimuli.

Animals↗
PubMed1988

Prevention of recurrent staphylococcal skin infections with low-dose oral clindamycin therapy.

We conducted a double-blind, controlled trial of low-dose (150 mg/d) oral clindamycin hydrochloride vs placebo to prevent recurrent staphylococcal skin infections. Twenty-two patients (11 in both the placebo and clindamycin treatment groups) completed the trial and were assessable. The two groups did not differ as to age, sex, race, or the number of recurrent abscesses preceding the trial. In pretrial evaluations, no patient had hypogammaglobulinemia or abnormal neutrophil function. Sixty-four percent (7/11) of the placebo-treated patients had a recurrent abscess within three months of enrollment whereas 82% (9/11) of the patients treated with clindamycin were free of any infection during the three-month treatment period. Of the nine patients who responded to clindamycin treatment, six did not have a recurrent infection for at least nine months after discontinuing antibiotic therapy. All patients tolerated the regimen without side effects. We conclude that a three-month course of low-dose oral clindamycin is an effective, convenient, well-tolerated, and often durable approach to prevention of recurrent staphylococcal skin infections.

Administration, Oral↗
PubMed1988

Calcium release associated with discharge of specific granule contents from human neutrophils.

Neutrophil discharge of calcium into the ambient medium was measured, using an ion-sensitive electrode, after cells were stimulated with phorbol myristate acetate. Dose-dependent calcium efflux was observed over the same range of stimulus concentrations associated with specific granule marker release. Calcium efflux was preserved when cells were treated with vanadate to inhibit the plasma membrane calcium ATPase. However, less calcium was released than in previous studies employing a complete secretagogue to discharge both specific and azurophil granule contents. These studies suggest that calcium is stored in both the azurophil and the specific granules of the neutrophil, and can be mobilized from both sites during degranulation.

Calcium↗
PubMed1988

Lysosomotropic behavior of adrenergic antagonists in interactions with human neutrophils.

Autonomic neurohormones affect the secretory activity of neutrophils by modulating release of lysosomal enzymes in response to immunologic stimuli. Autonomic agents are also weak bases which might modify cell function by accumulating in the acidic interior of the lysosome, in addition to their receptor-mediated activity. We examined the association of the beta-adrenergic antagonist [3H]dihydroalprenolol with human neutrophils and lysosome and membrane fractions derived from neutrophils, and the subcellular distribution of the photoaffinity-labeled beta-adrenergic ligand [3H]azidobenzylcarazolol after incubation with intact cells. Isolated neutrophil lysosomes accumulated significantly more [3H]dihydroalprenolol than isolated membrane preparations. Decreasing the transmembrane pH gradient markedly reduced [3H]dihydroalprenolol accumulation by intact cells or lysosomes but not by membranes. Since [3H]dihydroalprenolol accumulated by intact cells remained rapidly exchangeable, the photoaffinity ligand [3H]azidobenzylcarazolol was used to assess ligand distribution after association with whole cells. After cell disruption, 18.5 +/- 1.3% of this ligand appeared in the lysosome fraction as compared to 2.2 +/- 0.6% in the membrane fraction. The secretagogue phorbol myristate acetate caused release of the ligand as well as lysosomal enzymes from cells. These findings suggest that there is significant pH-dependent lysosomal accumulation of beta-antagonists. This lysosomotropic interaction may be important both as it affects the sequestration and redistribution of the drugs, and as it might in some circumstances affect host defense functions of the neutrophil.

Adrenergic beta-Agonists↗
PubMed1988

Lysosomotropic amines modulate neutrophil calcium homeostasis.

Lysosomotropic amines can raise the acidic internal pH of the neutrophil lysosome and inhibit neutrophil function. Because pH and calcium regulation are intimately connected in various types of excitable cells, we studied the effects of several lysosomotropic weak bases on neutrophil calcium homeostasis. Base-treated cells had normal to minimally elevated resting cytosol free calcium, but weak bases produced significant release of calcium from organelles when this release was directly measured in permeabilized cells, even after depletion of inositol-triphosphate-sensitive stores. Collapse of transmembrane pH gradients with monensin similarly released organelle calcium. The initial cytosol calcium response to f-met-leu-phe was enhanced by some of the lysosomotropic amines but the calcium rise was more transient in base-treated cells than in control samples. These findings suggest that existence of an acidic intracellular compartment, such as the lysosome, is important to normal calcium homeostasis in the neutrophil and that pH sensitivity and inositol triphosphate sensitivity may define two pools of releasable organelle calcium. The effect of pH perturbation on calcium homeostasis may partially account for the inhibition of neutrophil function by lysosomotropic amines.

Adult↗