Infection-stimulated infraosseus inflammation and bone destruction is increased in P-/E-selectin knockout mice. (73/6004)

Infections of the dental pulp commonly result in infraosseus inflammation and bone destruction. However, the role of phagocytic leucocytes in the pathogenesis of pulpal infections has been uncertain. In this work we used P/E-/- selectin-deficient mice, which lack rolling adhesion of leucocytes to endothelium and mimic the human syndrome, leucocyte adhesion deficiency II (LAD-II), to test the hypothesis that phagocytic leucocytes protect against pulpal infection and subsequent periapical infraosseus bone resorption. P/E-/- mice and P/E+/+ wild-type controls were subjected to surgical pulp exposure, and both groups were infected with a mixture of pulpal pathogens including Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros and Streptococcus intermedius. Animals were killed after 20 days, and the extent of infraosseus bone destruction was quantified by histomorphometry. In two separate experiments, P/E-/- mice had significantly greater bone resorption than P/E+/+ controls. The increased bone destruction correlated with a twofold decrease in polymorphonuclear (PMN) infiltration into periapical inflammatory tissues of P/E-/- mice. P/E-/- mice had higher tissue levels of the bone resorptive cytokine, interleukin (IL)-1alpha. Tissue levels of IL-2, IL-4, IL-10, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were all higher in P/E-/- mice, but the increases were not statistically significant. Only IL-12 was higher in P/E+/+ mice, possibly reflecting a greater number of infiltrating monocytes in wild-type mice. These findings demonstrate that phagocytic leucocytes are protective in this model, and suggest that elevated expression of inflammatory cytokines is responsible for the observed bone destruction.  (+info)

Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood. (74/6004)

BACKGROUND: Serum levels of lipoprotein(a) [Lp(a)] are determined largely by genetic variation in the gene encoding for apolipoprotein(a) [apo(a)], the specific protein component of Lp(a) that is very homologous to plasminogen. High plasma levels of Lp(a) increase the risk for premature atherosclerotic vessel diseases. We investigated the little-characterized role of Lp(a) as a risk factor for venous thromboembolic diseases, alone and in conjunction with established thrombophilic risk factors of proteins regulating blood coagulation and fibrinolysis. METHODS AND RESULTS: Serum levels of Lp(a) and lipids, protein C, protein S, and antithrombin, as well as the size of apo(a) isoforms and the presence of the factor V:Q(506) mutation, were determined in 186 consecutively admitted children from neonates to 18 years old with a history of venous thrombosis and in 186 age- and disease-matched control subjects. Children with a history of venous thrombosis had a significantly higher median Lp(a) level (19 versus 4.4 mg/dL) than control subjects. The risk for thromboembolic events in children with Lp(a) levels in the upper quartile, ie, >30 mg/dL, was 7.2 (95% CI, 3.7 to 14.5). The size of apo(a) isoforms was inversely related to Lp(a) levels and to the risk for thromboembolic events. Compared with the highest quartile of the apo(a) size distribution, the lowest quartile was associated with a risk of 8.2. In addition, multivariate statistical analysis gives evidence that the factor V:Q(506) mutation (OR/CI, 2.8/1.6 to 4.9), protein C (OR/CI, 6.5/2.1 to 19), and antithrombin deficiency (OR/CI, 10.4/1.2 to 90) were independent risk factors of childhood venous thrombosis. Coincidence of elevated Lp(a) with factor V:Q(506) mutation or deficiencies of protein C or antithrombin further increased the risk for thromboembolic events to 8.4. CONCLUSIONS: Lp(a) >30 mg/dL is a risk factor for venous thromboembolism in childhood. Lp(a) measurements should be included in the screening of causal factors in children with venous thromboembolic events.  (+info)

Endogenous endophthalmitis: case report and brief review. (75/6004)

Endogenous endophthalmitis is a potentially blinding ocular infection resulting from hematogenous spread from a remote primary source. The condition is relatively rare but may become more common as the number of chronically debilitated patients and the use of invasive procedures increase. Many etiologic organisms (gram-positive, gram-negative and fungal) have been reported to cause endogenous endophthalmitis. Risk factors are well defined and include most reasons for immune suppression. A high clinical suspicion is needed for early diagnosis and treatment. Early intravenous antibiotic therapy remains the cornerstone of treatment. The roles of intravitreal antibiotics and vitrectomy are evolving and may become more widely accepted as therapeutic modalities. The authors report a case of endogenous endophthalmitis and provide a brief review of the literature.  (+info)

Hypothesis on the role of sub-clinical bacteria of the endometrium (bacteria endometrialis) in gynaecological and obstetric enigmas. (76/6004)

Unexplained infertility, recurrent abortion, dysfunctional uterine bleeding, pelvic pain, premenstrual syndrome, premature labour, placental insufficiency and pre-eclampsia are examples of common obstetric and gynaecological problems that frequently defy adequate explanation. Bacterial vaginosis, a non-inflammatory condition, is associated with premature labour, but antibiotics administered topically provide less effective prophylaxis than those administered orally. This would indicate that bacterial vaginosis might be a marker for significant genital tract bacteria, but some pathology is dependent on micro-organisms ascending out of reach of topical antibiotics. The author was led to consider the hypothesis that micro-organisms, possibly those associated with bacterial vaginosis, surreptitiously inhabit the uterine cavity (bacteria endometrialis) where they are culprits of some common gynaecological and obstetric enigmas. The objective of this review is to provide an initial theoretical examination of this hypothesis. Bacteria in the endometrium have been associated with infertility. Antiphospholipids have been linked to recurrent miscarriage and pre-eclampsia and with infections including Mycoplasma. Pre-eclampsia might be explained by an exaggerated host response to intrauterine micro-organisms or bacterial toxins. The hypothesis that one common factor, bacteria endometrialis, could provide a plausible explanation for a variety of obstetric and gynaecological mysteries is particularly intriguing. There is sufficient evidence to justify further investigation.  (+info)

Proteinase 3 mRNA expression is induced in monocytes but not in neutrophils of patients with cystic fibrosis. (77/6004)

Proteinase 3 (PR3), a serine proteinase which can degrade lung tissue, is present in the cystic fibrosis (CF) sputum. In the present study, PR3 protein and mRNA expression was determined in circulating neutrophils and monocytes. CF neutrophils contained similar PR3 concentrations as healthy controls and poorly expressed PR3 mRNA. In contrast, CF monocytes showed significantly higher PR3 concentrations than controls, together with an upregulation of PR3 mRNA expression especially during pulmonary exacerbation. Interestingly, antibiotic treatment fully abrogated PR3 mRNA expression and decreased PR3 protein in monocytes. Our findings highlight a potential role of monocyte-derived PR3 in CF-associated airway inflammation.  (+info)

Self-medication of antibacterials without prescription (also called 'over-the-counter' use). A report of a Working Party of the British Society for Antimicrobial Chemotherapy. (78/6004)

The availability of antimicrobial agents for self-medication may increase and could include antibacterial agents for oral or topical use. Wholesale deregulation of antibacterials would be undesirable and likely to encourage misuse of classes of agents currently important in the management of serious infections. Changed regulation from Prescription-Only Medicine (POM) to Pharmacy (P) medicine of selected agents with indications for short-term use in specific minor infections and illness is likely to have advantages to the user. However, safeguards to their use would need to be included in the Patient Information Leaflet (PIL). Agents and indications for self-medication are discussed. Any alteration in licensed status from POM to P will require careful risk-benefit assessment, including the likely impact on bacterial resistance. Safety issues also include concerns relating to age of the user, pregnancy, underlying disease and the potential for drug interactions. The importance of appropriate information with the PIL is emphasized, as is the role of the pharmacist, while ways of improving adverse event notification and monitoring are discussed. The paucity of good denominator-controlled data on the prevalence of in-vitro resistance is highlighted, and recommendations for improving the situation are made. There are currently no levels of resistance accepted by regulatory bodies on which to base a licensing decision, be it for granting a product licence, renewal of a licence or a change in licensed status from POM to P. Due consideration should be given to: the validation of user-defined indications in comparison with those medically defined; the enhancement of pharmacy advice in the purchase of such agents; improved safety monitoring; the establishment of systematic surveillance of susceptibility data.  (+info)

Ceftriaxone versus vancomycin prophylaxis in cardiovascular surgery. (79/6004)

The efficacy of antibiotic prophylaxis in cardiac surgery was compared between 97 patients receiving a single 2 g dosage of ceftriaxone and 103 receiving 500 mg of vancomycin i.v. every 6 h for 48 h. The overall infection rate was 13.4% in the ceftriaxone and 10.7% in the vancomycin group. Four (4%) wound infections, including one mediastinitis, occurred in the ceftriaxone group and five (5%) in the vancomycin group, with no statistically significant difference. The findings of this study support the adequacy of a simple single dose of ceftriaxone prophylaxis in cardiac surgery, at least in hospitals with low incidence of vancomycin-resistant staphylococcal infections.  (+info)

Surveillance of antimicrobial use and antimicrobial resistance in United States hospitals: project ICARE phase 2. Project Intensive Care Antimicrobial Resistance Epidemiology (ICARE) hospitals. (80/6004)

The search for the means to understand and control the emergence and spread of antimicrobial resistance has become a public health priority. Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) has established laboratory-based surveillance for antimicrobial resistance and antimicrobial use at a subset of hospitals participating in the National Nosocomial Infection Surveillance system. These data illustrate that for most antimicrobial-resistant organisms studied, rates of resistance were highest in the intensive care unit (ICU) areas and lowest in the outpatient areas. A notable exception was ciprofloxacin- or ofloxacin-resistant Pseudomonas aeruginosa, for which resistance rates were highest in the outpatient areas. For most of the antimicrobial agents associated with this resistance, the rate of use was highest in the ICU areas, in parallel to the pattern seen for resistance. These comparative data on use and resistance among similar areas (i.e., ICU or other inpatient areas) can be used as a benchmark by participating hospitals to focus their efforts at addressing antimicrobial resistance.  (+info)