Acute renal failure in HIV patients with liver cirrhosis receiving tenofovir: a report of two cases.
Explore the source record for details and available documents.
Acute Kidney Injury↗
Biomedical subjects
Thomas Glück
Publications and source records attributed to Thomas Glück.
A patient with arthritis, severe back pain, impaired wound healing, and perforated sigmoid colon.
Explore the source record for details and available documents.
Aged↗
Ablation of the sympathetic nervous system decreases gram-negative and increases gram-positive bacterial dissemination: key roles for tumor necrosis factor/phagocytes and interleukin-4/lymphocytes.
The sympathetic nervous system is intensely activated during bacteremia, but its immediate influence on the bacterial tissue burden remains unclear. We demonstrate that prior ablation of the sympathetic nervous system decreases this dissemination of Pseudomonas aeruginosa or Escherichia coli through a mechanism of increased secretion of peritoneal tumor necrosis factor, improved phagocytic response of peritoneal cells, and increased influx of monocytes into the peritoneal cavity. When gram-positive Staphylococcus aureus strains were used, sympathectomy increased the bacterial tissue burden, which was caused by a reduction in corticosterone tonus, and decreased both interleukin-4 secretion from peritoneal cells and the influx of lymphocytes into the peritoneal cavity. In both models, the peritoneal wall was the critical border for systemic infection. These results show the dual role of the sympathetic nervous system in sepsis. It can be favorable or unfavorable, depending on the innate immune effector mechanisms necessary to overcome infection.
Animals↗
[New developments in the diagnosis and therapy of acute bacterial meningitis].
BACKGROUND: Acute bacterial meningitis is a medical emergency. Despite advances in the diagnosis and treatment it continues to have a high case-fatality rate and high rates of long-term neurologic sequelae. ETIOLOGY: Since the widespread use of the vaccine for Haemophilus influenzae type B, Streptococcus pneumoniae has replaced it as the most common cause of acute community-acquired bacterial meningitis in industrialized countries. The rising incidence of beta-lactam-resistant pneumococci has to be considered when choosing a regimen for empiric antibiotic therapy. DIAGNOSIS: The clinical diagnosis remains difficult, as absent clinical meningeal signs do not exclude bacterial meningitis. If bacterial meningitis is considered a possible diagnosis, empiric antibiotic therapy should be initiated without any delay. Prior blood cultures and, if not contraindicated, a lumbar puncture should be performed. Based on new evidence, a screening cranial computed tomography to rule out raised intracranial pressure prior to lumbar puncture is recommended only for patients with defined risk factors (age > 60 years; preexisting immunodeficiency, immunosuppression, or neurologic diseases; recent seizures; any pathologic finding in the neurologic examination other than meningism). TREATMENT: Empiric antibiotic therapy should be initiated before cranial computed tomography. Adjuvant dexamethasone therapy initiated with or prior to the antibiotic therapy reduces mortality and morbidity for patients with pneumococcal meningitis without increasing the rate of side effects.
Acute Disease↗
A designed TLR4/MD-2 complex to capture LPS.
The family of Toll-like receptors (TLRs) is involved in the defense of an organism to microbial attack. TLR4-induced signaling is involved in infectious diseases, chronic inflammatory diseases and sepsis; therefore, we aimed at modulating TLR4-signaling via ligand-binding soluble receptors. Because recognition of microbial structures shows some species-specific traits, we specifically selected the mouse model for later in vivo studies. We first prepared the N-terminally Flag-tagged mouse (m) recombinant (r) soluble (s) fusion proteins mrsTLR4-IgGFc (T4Fc) and mrsMD-2 in Drosophila melanogaster Schneider 2 (S2) cells. The function of these molecules was tested by inhibition of synthesis of pro-inflammatory cytokines after stimulation of mouse macrophage RAW 264.7 cells with purified lipopolysaccharide (LPS). T4Fc alone had no inhibitory activity; however, a T4Fc/MD-2 complex blocked LPS activity. By analogy with 'cytokine traps', we then prepared a designer molecule (LPS-Trap) by fusing MD-2 to the C-terminus of soluble TLR4 via a flexible linker. LPS-Trap significantly inhibited TNF production by LPS-stimulated RAW 264.7 cells. Thus, the T4Fc/MD-2 complex as well as the LPS-Trap blocked LPS activity in vitro and might thus represent a new therapeutic option in sepsis by neutralization of TLR4-activating ligands.
Animals↗
Immune status and risk for infection in patients receiving chronic immunosuppressive therapy.
OBJECTIVE: Chronic immunosuppressive therapy may be complicated by infections indicating a more or less profound immune defect. However, immune monitoring to estimate the risk for infection has so far not been performed routinely. The aim of this study was (1) to investigate the effects of commonly used immunosuppressive treatment regimens on lymphocyte subsets and cytokine release from stimulated whole blood cultures in patients with rheumatic or autoimmune diseases; and (2) to determine whether such measurements could be used as predictors of infection, and if so, to determine their predictive value for subsequent infectious complications. METHODS: Patients with various chronic inflammatory diseases (n = 97) treated with different immunosuppressive regimens and healthy controls (n = 36) were evaluated for T lymphocyte subsets and for cytokine release in whole blood cultures after stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) and ionomycin. RESULTS: Therapy with corticosteroids induced dose-dependent lymphocyte depletion. Concomitant application of cytotoxic disease modifying drugs and corticosteroids caused an additive effect on lymphocytopenia, but did not change CD4/CD8 ratio. Corticosteroid therapy was also associated with impaired cytokine release from mononuclear cells in whole blood assays after in vitro stimulation with LPS or PMA/ionomycin. Infections requiring hospitalization developed in 19 of 95 evaluable patients during an average followup period of 2.3 years. On logistic regression analysis, lymphocytopenia < 600/microl, in particular < 250 CD4+ T cells/microl, and therapy with corticosteroids > 10 mg prednisolone equivalent per day were predictive of infections. Multiple logistic regression analysis showed that T-helper lymphocytopenia < 250/microl was the best predictor for future infections, with a positive predictive value of 0.53 and a negative predictive value of 0.97. CONCLUSION: Patients receiving chronic immunosuppressive therapy can develop severe lymphopenia that involves all subsets. Monitoring T-helper cell counts may be useful to estimate the risk for subsequent infections in such patients.
Adrenal Cortex Hormones↗
[Infectious diseases-Part II: New agents, resistances, and treatment strategies].
A number of new antimicrobial agents have been licensed in the last years, most prominently a number of new antiviral and antimycotic agents. The development of new antibacterial agents has slowed down, new agents are mainly targeted at a small but rapidly growing number of patients infected with bacteria resistant to the current antibiotics. The rates of resistance against antibiotics are rapidly rising, especially for gram-positive cocci and, in addition, for gram-negative nosocomial agents. Rising rates of resistances are further present in chronic viral infections, e. g., HIV infection. Instruments to monitor and minimize the rates of resistances are necessary. Important changes are to be found in a number of infectious complications. For patients with sepsis a new therapeutic principle, drocretogrin, has been found to reduce mortality. Additionally, low-dose corticosteroids in selected patients, close control of blood sugar and other interventions have shown to be effective. Corticosteroids have proven to be effective as well in the reduction of complications in adults with bacterial meningitis, most pronounced in pneumococcal meningitis. With new drugs licensed for the treatment of malaria and changes in the epidemiology, the guidelines for therapy and prevention have been reformulated.
Anti-Infective Agents↗
Combined skin disinfection with chlorhexidine/propanol and aqueous povidone-iodine reduces bacterial colonisation of central venous catheters.
OBJECTIVE: Central venous catheter (CVC)-related infections may be caused by micro-organisms introduced from the skin surface into deeper tissue at the time of CVC insertion. The optimal disinfection regimen to avoid catheter-related infections has not yet been defined. This study compares three different approaches. DESIGN: Prospective randomised trial. SETTING: A tertiary care hospital. PATIENTS AND PARTICIPANTS: One hundred nineteen patients scheduled electively to receive 140 CVCs. INTERVENTIONS: Skin disinfection was performed with either povidone-iodine 10% (PVP-iodine), chlorhexidine 0.5%/propanol 70%, or chlorhexidine 0.5%/propanol 70% followed by PVP-iodine 10%. Prior to disinfection, a swab from the site of insertion was taken for culture. CVCs were removed if no longer needed or infection was suspected. All catheters were cultured quantitatively after removal. MEASUREMENT AND RESULTS: Bacteria could be isolated from 20.7% of the catheter tips. Bacterial growth was found in 30.8% of the catheters placed after skin disinfection with povidone-iodine, in 24.4% after disinfection with propanol/chlorhexidine and in 4.7% after disinfection with propanol/chlorhexidine followed by povidone-iodine ( p=0.006). In 15 cases, the same organism was isolated from the skin swab and the catheter tip. Ten of these paired isolates showed the same pattern in a pulsed-field gel electrophoresis analysis. CONCLUSIONS: Skin disinfection with propanol/chlorhexidine followed by PVP-iodine was superior in the prevention of microbial CVC colonisation compared to either of the regimens alone. These results support the concept that catheter infections can originate from bacterial translocation at the time of catheter insertion.
1-Propanol↗
[Infectious diseases-part I: epidemiology].
The outstanding issue regarding recent trends in the epidemiology of infectious diseases is the epidemic occurrence of severe acute respiratory syndrome (SARS) in 2003. SARS is caused by a novel coronavirus, presumably originating from wild cats. This new agent was rapidly identified and characterized, the outbreak was terminated in early summer 2003 after implementation of strict infectious control measures. Especially the high rate of complications and nosocomial infections has caused severe public health problems in China and Canada. The number of persons infected with HIV is still rising rapidly globally. New regions with rapid spread include the countries of the former Soviet Union in East Europe and Central Asia. The introduction of modern antiretroviral therapy in countries with high prevalence is making slow progress, with no visible impact on transmission dynamics so far. The WHO has implemented a number of programs to eradicate or eliminate targeted infectious diseases. Polio eradication and elimination of neonatal tetanus are making slow progress, obstacles to the control of these diseases are ongoing armed conflicts in regions with high prevalence and under financing of programs. Lack of funding is especially obvious regarding programs for the control and therapy of malarial infections. The numbers of patients newly identified with new variant Creutzfeldt-Jakob disease are not rising, but rather constant or even declining, making a large epidemic of vCJD unlikely.
Communicable Disease Control↗
CD14 receptor occupancy in severe sepsis: results of a phase I clinical trial with a recombinant chimeric CD14 monoclonal antibody (IC14).
OBJECTIVE: Binding of bacterial cell wall components to CD14 and co-receptors on myeloid cells results in cellular activation and production of proinflammatory mediators. A recombinant anti-CD14 monoclonal antibody (IC14) has been shown to decrease lipopolysaccharide-induced responses in animal and human models of endotoxemia. This study was performed to evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical pharmacology of IC14 in patients with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled, dose-ranging, multiple-center trial. SETTING: Six medical and surgical intensive care units located in Germany and The Netherlands. PATIENTS: Forty patients with severe sepsis. INTERVENTIONS: IC14 was administered intravenously to eight patients/cohort as single (1 mg/kg or 4 mg/kg) or multiple doses (4 mg/kg daily for 4 days, or 4 mg/kg on day 1 followed by 2 mg/kg daily for 3 days). A placebo group (two patients/cohort) was also included. MEASUREMENTS AND MAIN RESULTS: The overall incidence and types of adverse events were similar among treatment groups. One patient in the group receiving multiple-dose IC14 4 mg/kg daily for 4 days experienced an anaphylactic reaction after receiving the first dose of study drug. IC14 did not induce antibody formation or increase the incidence of secondary bacterial infection. A mean IC14 serum concentration of approximately 1 microg/mL was required to achieve 50% of maximum membrane-bound CD14 receptor occupancy on peripheral blood monocytes. The pattern of proinflammatory and anti-inflammatory cytokines, chemokine, soluble receptor, soluble E-selectin, and acute phase proteins in response to treatment was highly variable by patient and IC14 treatment group. CONCLUSIONS: Single and multiple doses of IC14 were generally well tolerated and did not induce antibody formation or increase the incidence of secondary bacterial infection. The results suggest that CD14 blockade with IC14 warrants further clinical investigation to determine its ability to attenuate the proinflammatory response due to infection.
Acute-Phase Proteins↗
Advances in sepsis therapy.
During the past 3 years new insights have been gained into the fundamental elements that underlie the pathogenesis of sepsis, and after years of frustrating failures, progress in the basic understanding of sepsis has translated into successful new therapies. These new treatment strategies have significantly improved the outcome of patients experiencing the puzzling syndrome of severe sepsis. More effective supportive therapies with early, goal-oriented therapy including volume resuscitation, catecholamine therapy and transfusion improve the chances for survival in septic shock. Novel endocrine management with hydrocortisone replacement therapy for relative adrenal insufficiency in septic shock patients and strict blood glucose control provide a survival advantage in critically ill patients. Administering appropriate antimicrobial therapy, nutritional support and ventilation protocols with low tidal volumes have now been shown to benefit septic patients. Finally, human recombinant activated protein C (drotrecogin alfa), which ameliorates sepsis-induced disseminated intravascular coagulation and exerts several other favourable effects on endothelial cells, has been shown to reduce mortality in patients with severe sepsis. On the basis of newly discovered pathophysiological mechanisms of sepsis, several other adjuvant therapies for sepsis are in various stages of preclinical and clinical development. Individualised and optimal supportive care with efforts to reverse the precipitating cause of sepsis remains the mainstay of therapy for severe sepsis. How these new and often expensive regimens will fit into the standard treatment approach to sepsis remains to be defined by future clinical investigations.
Animals↗
[Piercings and tattoos--a health risk?].
Explore the source record for details and available documents.
Humans↗
Maxillary actinomycosis in an immunocompromised patient with longstanding vasculitis treated with mycophenolate mofetil.
Explore the source record for details and available documents.
Actinomycosis↗
[28-Year-Old Patient with Elevated Serum IgE Levels and Multiple Refractory Epidural and Paravertebral Abscesses. Clinical manifestation of a Job's Syndrome?].
BACKGROUND: The hyper-IgE syndrome is a rare primary immunodeficiency characterized by recurrent staphylococcal infections and high levels of serum IgE. CASE REPORT: The case of a 28-year-old man with epidural and paravertebral abscesses and a markedly elevated serum IgE level of 2,609 U/ml is reported. There was no allergic diathesis, nor had the patient a history of other diseases, which might explain the high serum IgE level. In a blood culture, Staphylococcus aureus was detected. Since early childhood, the patient has suffered from recurrent skin infections. CONCLUSION: The presented study case discusses the diagnosis of a Job's syndrome in this patient and reviews previously published cases. It also summarizes the current knowledge about pathogenesis and diagnostic criteria of this rare syndrome.
Adult↗
Fatal outcome of constrictive pericarditis in rheumatoid arthritis.
This is a report of a 39-year-old patient diagnosed with seropositive rheumatoid arthritis at the age of 17. The patient died 2 years after the onset of extra-articular cardiac symptoms. This case demonstrates the devastating course of progressive constrictive pericarditis under sole medical therapy and emphasizes the importance of early radical pericardectomy to avoid progression of disease and secondary complications with fatal outcome. Further, we discuss risk factors, diagnostic caveats, diagnostic tests and therapy of hemodynamically relevant contrictive pericarditis.
Adult↗
Endotoxin as a drug target.
OBJECTIVE: To review the preclinical and clinical evidence that antiendotoxin therapeutic strategies are potentially useful in the prevention and treatment of septic shock. STUDY DESIGN: A critical review of the literature over the past 30 yrs relating basic and clinical research on the therapeutic value of endotoxin as a target for the prevention and treatment of severe sepsis and septic shock. MAIN RESULTS: Bacterial endotoxin is a potent and predominant microbial mediator that induces an intense inflammatory and procoagulant response by elements of the innate immune response. This macromolecule is capable of inducing lethal septic shock in experimental animals, and a large number of preclinical studies consistently demonstrate the survival advantage of endotoxin inhibition in experimental models of sepsis. Clinical studies indicate that endotoxin may be found in the systemic circulation in the majority of humans with septic shock. Endotoxemia is largely independent of the nature of the infecting microorganism despite the fact that this molecule is specifically found in the outer membrane of Gram-negative bacteria only. Antiendotoxin strategies studied thus far have not provided reproducible survival benefits in clinical trials in septic patients. CONCLUSIONS: Despite compelling evidence of the critical importance of endotoxin in the pathogenesis of Gram-negative bacterial sepsis in preclinical investigations and numerous clinical interventional trials, the utility of antiendotoxin approaches to significantly reduce the mortality rate in human septic shock remains unproven. Ongoing clinical trials with specific endotoxin inhibitors should determine the potential value of this therapeutic approach to the management of septic shock.
Animals↗
During a corticotropin-releasing hormone test in healthy subjects, administration of a beta-adrenergic antagonist induced secretion of cortisol and dehydroepiandrosterone sulfate and inhibited secretion of ACTH.
OBJECTIVE: In chronic inflammatory diseases, serum levels of dehydroepiandrosterone (DHEA) sulfate (DHEAS) are low. Interestingly, several non-inflammatory diseases display similarly low levels of DHEAS which points to other inhibitory factors such as an activated sympathetic nervous system (SNS) (e.g. in patients with heart failure, fibromyalgia, or cancer cachexia). We aimed to identify the influence of the SNS tone on stimulated adrenal steroid secretion in 16 male and 12 female healthy subjects. METHODS: One group were given oral propranolol 2 h before a corticotropin-releasing hormone (CRH) test, and levels of adrenocorticotropin (ACTH), cortisol, 17-hydroxyprogesterone (17OHP), androstenedione, DHEA, and DHEAS were measured. RESULTS: Propranolol treatment decreased heart rate (by 20%), diastolic blood pressure (by 20%), and plasma ACTH, and increased serum cortisol, serum DHEAS, and the molar ratio of cortisol/17OHP, cortisol/DHEA, and DHEAS/DHEA similarly in female and male subjects. CONCLUSIONS: A beta-adrenergic influence seems to decrease CRH-stimulated cortisol in relation to ACTH and 17OHP, and decreases DHEAS in relation to DHEA. Although other workers have found beta-adrenergic stimulation of steroid secretion in cultured adrenocortical cells, the overall systemic influence of the SNS via beta-adrenoceptors seems to inhibit adrenal steroids under unstimulated and stimulated conditions. Sympathetic hyperactivity may be a common denominator for low levels of DHEAS in inflammatory and non-inflammatory diseases.
17-Hydroxysteroid Dehydrogenases↗
Clinical determinants for the recovery of fungal and mezlocillin-resistant pathogens from bile specimens.
We conducted a retrospective analysis of all bile specimens obtained for routine cultures from January 1995 through December 1999 at our tertiary care hospital. Results of microbiologic testing were linked to clinical parameters gathered by means of chart review. A total of 722 isolates were cultured from 345 of 454 bile specimens obtained from 288 individual patients. Prior receipt of a >7-day course of antibiotics (odds ratio [OR], 5.7), extensive leukocytosis (leukocyte count, >20,000 cells/microL) on admission (OR, 7.8), endoscopic or percutaneous biliary manipulation during the previous 14 days (OR, 2.9), and treatment in an internal medicine ward (OR, 2.5) were independent factors significantly associated (Pless-than-or-eq, slant.05) with recovery of Candida species from bile specimens. Culture of mezlocillin-resistant bacteria from bile specimens was independently associated with the specimen having been obtained >1 week after admission (OR, 3.8), lack of history of endoscopic biliary drainage (OR, 3.2), and high serum aspartate aminotransferase levels (>72 U/L) on admission (OR, 2.6). Prospective studies are warranted to evaluate accordingly adjusted empiric therapies for biliary infections.
Bacteria↗