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Biomedical subjects

A Cerny

Publications and source records attributed to A Cerny.

At least 37 records · Page 2Linked to original sources
PubMed1998

Allergy to antibacterials: the problem with beta-lactams and sulfonamides.

This paper reviews the incidence, clinical manifestations, differential diagnosis, risk factors and pathogenesis of allergic reactions of two important classes of antimicrobials: beta-lactams and sulfonamides. The diagnostic work-up of a patient with a history of an allergic reaction will be discussed as well as the possibility of safe administration of the drug in the face of an allergy using desensitization. Emerging concepts of beta-lactam side-chain allergy, the role of cellular immune mechanisms and the clinical importance of cross-reactivity of allergic reactions to different classes of beta-lactams will be emphasized.

Journal Article↗
PubMed1998

Video-assisted thoracoscopic surgery for fibrinopurulent pleural empyema in 67 patients.

BACKGROUND: The roles of different drainage procedures in the management of empyema have to be redefined now that video-assisted thoracoscopic surgery (VATS) has been introduced. The debridement of fibrinopurulent stage II empyema with the use of VATS was assessed prospectively in regard to control of infection and restoration of pulmonary function. METHODS: Between January 1992 and May 1996, all patients at our institution with fibrinopurulent empyema that did not respond to chest tube drainage and antibiotic therapy were treated by debridement with the use of VATS. The patients were followed up prospectively by clinical and radiologic assessments 3 and 6 months after the operation and by spirometry 6 months after the operation. RESULTS: Video-assisted thoracoscopic surgery was initiated in 67 patients, but conversion to open decortication was required because of the finding of advanced disease in 19 patients (28%). Forty-eight patients underwent successful debridement with the use of VATS. The mean operative time was 82.1 minutes (range, 50 to 135 minutes), the mean duration of postoperative chest tube placement was 4.1 days (range, 2 to 8 days), and the mean duration of postoperative hospitalization was 12.3 days (range, 4 to 42 days). No wound infections were observed during the postoperative course. Both the 30-day mortality rate and the recurrence (ie, need for thoracotomy) rate were 4%. The mean predicted vital capacity was 84.8% +/- 14.9% and the mean predicted forced expiratory volume in 1 second was 88.6% +/- 19.2% 6 months after the operation. CONCLUSIONS: Debridement with the use of VATS is safe and efficient for stage II empyema, but open decortication should be used for more advanced disease.

Adult↗
PubMed1997

[Susceptibility to infection].

Recurrent infections in individual patients prompt concern regarding an underlying immunodeficiency. It is often difficult to make a distinction between "normal" and abnormally frequent occurrence of infections. Infectious diseases are the result of a series of complicated interactions between host factors, pathogen properties and epidemiological circumstances. This paper reviews the role of non-specific and antigen-specific host factors relevant to the management of a patient with suspected immunodeficiency. The most important effector mechanisms of immune defence are outlined and the consequences of their failure with respect to specific infections are discussed. Analysis of the clinical presentation, pathophysiology and microorganisms involved offers clues as to which part of the immune system is failing in an individual patient. Based on this, further tests will confirm or exclude an underlying immunodeficiency. The paper concludes with an overview of relevant therapeutic and prophylactic options.

Complement Activation↗
PubMed1996

[Side effects and consequences of frequently used antibiotics in clinical practice].

Oral antimicrobial substances belonging to the beta-lactams, quinolones, macrolides, tetracyclines and the trimethoprim-sulfamethoxazole combination are among the most prescribed classes of drugs in private practice. Knowledge of the potential side effects considered in the light of various patient-associated factors such as genetic makeup, renal and liver function, underlying diseases, drug allergies and coadministered drugs, is important in order to minimize the risk of adverse reactions. This article reviews important side effect patterns and focuses on more recent aspects of antibiotic-associated diarrhea and beta-lactam allergy relevant to the practicing physician. Diarrhea occurring during antibiotic treatment raises the possibility of Clostridium-difficile-associated disease, which may evolve into life-threatening toxic megacolon. Mild cases with resolving symptoms after discontinuation of the antibiotic usually do not require further workup. More severe cases with watery diarrhea, abdominal pain, dehydration and electrolyte abnormalities warrant rapid diagnosis, cessation of antibiotic treatment and specific treatment including oral metronidazole. The use of oral vancomycin as a first line drug is discouraged because of the possibility of selecting vancomycin-resistant enterococci. Hypersensitivity reactions to beta-lactams are the most important type of side effects which can often be prevented. Patients with a history of beta-lactam associated IgE-mediated hypersensitivity (hives, wheezing or hypotension) should undergo penicillin skin testing. The frequently observed maculopapular rash associated with aminopenicillins without hives is in most cases not caused by an IgE-mediated mechanism. Patients with previous life-threatening penicillin allergy such as anaphylaxis or Lyell's syndrome should not undergo skin testing. Currently available tests do not reliably predict cephalosporin hypersensitivity. More recent data suggest that crossreactivity between penicillins and cephalosporins is infrequent. It thus seems safe to administer a cephalosporin to a penicillin-allergic patient, though excluding patients with previous life-threatening penicillin reactions.

Anti-Bacterial Agents↗
PubMed1996

Descending necrotizing mediastinitis: surgical treatment via clamshell approach.

BACKGROUND: Descending necrotizing mediastinitis requires an early and aggressive surgical approach to reduce the high morbidity and mortality associated with this disease. The clamshell incision has provided excellent exposure of the entire mediastinum and both pleural cavities and was assessed in patients suffering from descending necrotizing mediastinitis. METHODS: Three patients with descending necrotizing mediastinitis and bilateral pleural empyema due to invasive streptococcal infections were operated on with this method. Radical debridement of the mediastinum and bilateral decortication was performed through a clamshell incision, including pericardiectomy in 2 patients. All patients received initially a high dose of antibiotic regimen, 2 had bilateral chest tube drainage, and 1 had mediastinal drainage and pleural debridement via cervical mediastinotomy and thoracoscopy, respectively. All these measures alone, however, failed to control the disease. RESULTS: The clamshell incision offered an excellent exposure for bilateral decortication and debridement of the entire mediastinum including pericardiectomy. One patient, who was referred in critically ill condition, died of multiorgan failure in the postoperative period. The remaining 2 patients recovered without further interventions and without evidence of phrenic nerve palsy, sternum osteomyelitis, or sternal override. CONCLUSIONS: The clamshell approach offers an excellent exposure for a complete one-stage surgical treatment with mediastinal debridement and bilateral decortication in patients suffering from descending necrotizing mediastinitis in the absence of profound septic shock.

Adolescent↗
PubMed1995

Induction in vitro of a primary human antiviral cytotoxic T cell response.

We report herein the successful priming of human anti-viral cytotoxic T cells (CTL) in vitro using two induction strategies based on the stimulation of peripheral blood mononuclear cells isolated from uninfected donors with synthetic viral peptides. The peptides used contain HLA-A2 binding motifs and have been identified as HLA-A2-restricted CTL epitopes in patients infected by the hepatitis B and C viruses. One approach uses repetitive long-term stimulation and the other uses bulk cultures containing large numbers of naive peripheral blood mononuclear cells. Both approaches successfully induce HLA-A2-restricted CTL specific for several viral epitopes. Some CTL recognize endogenously synthesized antigen on target cells infected with recombinant vaccinia virus expressing the corresponding viral proteins. This simple technique permits easy analysis of the primary human CTL repertoire, and may be exploitable for production of specific CTL effector cells for adoptive immunotherapy and dissection of the cellular and molecular requirements for priming of naive human CTL.

Amino Acid Sequence↗
PubMed1995

Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif.

The HLA class I-restricted cytotoxic T lymphocyte (CTL) response is a major defense mechanism in viral infections. It has been suggested that the CTL response may contribute to viral clearance and liver cell injury during hepatitis C virus (HCV) infection. To test this hypothesis requires an understanding of the characteristics of HCV-specific cytotoxic effector cells and identification of the target antigens to which they respond. To begin this process we stimulated peripheral blood mononuclear cells (PBMC) from a group of HLA-A2 positive patients with chronic hepatitis C with a panel of 130 HCV-derived peptides containing the HLA-A2 binding motif. Effector cells were tested for their capacity to lyse HLA-A2-matched target cells that were either sensitized with peptide or infected with a vaccinia virus construct containing HCV sequences. Using this approach we have identified nine immunogenic peptides in HCV, three of which are derived from the putative core protein, three from the nonstructural (NS) 3 domain, two from NS4 and one from NS5. Selected responses were shown to be HLA-A2 restricted, mediated by CD8+ T cells and to recognize endogenously synthesized viral antigen. Unexpectedly, peptide-specific CTL responses could also be induced in sero-negative individuals, suggesting in vitro activation of naive CTL precursors. The precursor frequency of peptide-specific CTL was 10 to 100-fold higher in infected patients compared to uninfected controls, and the responses were greatly diminished by removal of CD45 RO+ (memory) T cells. Further quantitative studies are clearly required to establish whether a correlation exists between the HCV-specific CTL response and the clinical course of this disease. Definition of the molecular targets of the human CTL response to HCV creates this opportunity, and may also contribute to the development of a T cell-based HCV vaccine.

Amino Acid Sequence↗
PubMed1994

CTL access to tissue antigen is restricted in vivo.

MHC class I-restricted, hepatitis B surface Ag (HBsAg)-specific, CD8+ polyclonal CTL lines and clones cause a severe necroinflammatory liver disease when they are injected i.v. into transgenic mice that display widespread tissue expression of HBsAg. Surprisingly, the same CTLs fail to cause disease in any other HBsAg-positive tissue in these animals. However, the CTLs are highly cytopathic for HBsAg-positive renal tubules and choroid plexus epithelial cells when they are injected extravascularly, either beneath the kidney capsule or intracerebrally. Analysis of the microvascular anatomy of these tissues reveals that the hepatic sinusoid is characterized by a discontinuous endothelium and the absence of a basement membrane. In contrast, the vasculature of most other tissues displays a continuous endothelium and basement membrane; and the epithelial cells of many of these tissues are also surrounded by a separate basement membrane. These results suggest that viral, tumor, and normal self Ags expressed in the liver are readily accessible to class I-restricted T cells, whereas the vascular endothelium and/or the vascular and cellular basement membranes constitute an extremely effective barrier that precludes CTL access to tissue Ag at many other sites. Because class I-restricted Ag recognition occurs throughout the body in many natural diseases and disease models, the vascular barrier must be breached by other events before CTL access to endogenously synthesized epithelial Ag can occur.

Animals↗
PubMed1994

Mice with an acquired immunodeficiency (MAIDS) develop a persistent infection after injection with Listeria monocytogenes.

Mice with a retrovirus-induced immunodeficiency were challenged with Listeria monocytogenes and resistance to this facultative intracellular bacterium was analyzed. Early innate immunity was unaltered or enhanced. Although immunodeficient mice had reduced bacterial titers after these reached their peak on Day 3, infection with L. monocytogenes generally resulted in a low-grade persistent infection and occasionally there was a delayed resolution of bacterial infection. Endogenous cytokines are important in the containment of bacteria as mice often developed a high load of bacteria or succumbed to infection in the absence of cytokine action. There was a substantial heterogeneity in disease after bacterial challenge which probably reflects the variability found in retrovirus-infected mice during the later stages of this immunodeficiency syndrome.

Animals↗
PubMed1994

Immunological aspects of HCV infection.

The hepatitis C virus (HCV) commonly causes persistent infection and chronic liver disease, and it is an important risk factor for the development of hepatocellular carcinoma (HCC). The mechanisms responsible for HCV persistence and disease pathogenesis are not well understood, although it is likely that both direct (virus-induced) and indirect (immunologically mediated) mechanisms play an important role. This review focuses on current knowledge of the interactions between HCV and the host immune system, emphasizing aspects of the cellular immune response. Observations in humans infected with HCV as well as experimental HCV infection of chimpanzees suggest that natural HCV infection does not induce protective immunity at the humoral or cellular levels. Indeed, anti-HCV seroconversion does not prevent reinfection by homologous or independent viral inocula. A CD4+ T lymphocyte response directed against all of the putative viral proteins occurs in chronically infected patients despite their failure to clear the virus. While the HCV core and NS4 proteins seem to be most immunogenic at the CD4+ peripheral blood T cell level during chronic HCV infection, there is some evidence that the NS4-specific response is preferentially compartmentalized in the liver. Similarly, the CD8+ cytotoxic T lymphocyte (CTL) response is remarkably polyclonal and multispecific during chronic HCV infection, since epitopes located in all of the putative proteins are recognized by the CTL present in the peripheral blood and/or the intrahepatic lymphocyte populations during this disease.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed1993

HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection.

Inasmuch as the hepatitis B virus (HBV) is not directly cytopathic for the infected hepatocyte, it is generally presumed that viral clearance and liver cell injury during viral hepatitis are due to a CTL response to HBV encoded Ag presented by HLA class I molecules. We have previously examined the peripheral blood CTL response to two HBV nucleocapsid epitopes in patients with acute and chronic viral hepatitis, one of which is restricted by HLA-A2, whereas the other is dually restricted by HLA-A31 and Aw68. In this study, we defined the HLA-A2-restricted CTL response to the hepatitis B surface Ag (HBsAg) by using a panel of HBsAg-derived synthetic peptides containing the ideal HLA-A2.1 binding motif (-L------V). Several novel aspects of HBV immunobiology and pathogenesis are evident from this study. First, the peripheral blood CTL response to HBV-encoded Ag is remarkably polyclonal and multispecific in most patients with acute hepatitis. Indeed, HLA-A2-restricted CTL specific for as many as four envelope epitopes and one nucleocapsid epitope were found to be present simultaneously in individual patients with acute viral hepatitis. Second, HBV-specific CTL are not detectable in the peripheral blood in a minority of patients with acute hepatitis, nor have we detected a CTL response in any of the patients with chronic hepatitis that we have studied thus far. Although the cellular and molecular basis for CTL nonresponse remains to be determined, the data suggest that it may contribute to viral persistence. Third, the diversity and the specificity of the CTL response is determined in part by the coding sequence of the viral genome present in each infected patient. Indeed, the apparent nonresponse of some acutely infected patients to at least one HBsAg-specific CTL epitope actually reflects infection by a viral variant that contains a critical substitution in one of the anchor residues within the epitope. Finally, at a fundamental level, the data suggest that the presence of the HLA-A2.1-binding motif in a peptide may not be sufficient for binding; and the capacity of a peptide to bind the class I molecule does not guarantee that it will be immunogenic.

Amino Acid Sequence↗
PubMed1992

[Livedo reticularis and multiple vascular occlusions in a patient with HLA-B27-negative spondyloarthrosis and antiphospholipid antibodies].

We report the case of a 74-year-old patient with HLA-B27 negative spondylarthropathy presenting with acute disseminated vascular occlusions. The presence of livedo reticularis prompted a search for antiphospholipid antibodies which were found to be markedly elevated. Histopathological examination revealed noninflammatory vascular obstruction. The clinical evolution was rapidly fatal in spite of corticosteroid treatment. Livedo reticularis can be an important diagnostic clue to various types of underlying disease. Increased levels of antiphospholipid antibodies have been associated with thrombosis and thromboembolism, especially in the context of autoimmune diseases such as systemic lupus erythematosus. This paper reports antiphospholipid antibody-associated noninflammatory vascular occlusions in a patient with HLA-B27 negative spondylarthropathy. The pathogenetic mechanism of antiphospholipid antibody-mediated vascular occlusions is not completely understood and optimal therapy remains to be defined.

Aged↗