Exotoxin activity associated with the Legionnaires disease bacterium.

Hemolysis occurred around growth of the Legionnaires disease bacterium on supplemented Mueller-Hinton agar containing sterile defibrinated blood from each of five mammalian species. Hemolysis was most pronounced with guinea pig or rabbit blood, was less intense with horse or sheep blood, and was slight with blood from a human donor. Sterile filtrates of allantoic fluid from embryonated hen's eggs that had been infected with this organism displayed hemolytic activity in a radial hemolysis assay with guinea pig cells in agar. Growth of the Legionnaires disease bacterium on F-G agar with 5% hen's egg yolk was surrounded by a zone of clearing and more circumscribed zones of iridescence and increased opacity on and in the medium. Attempts to detect activity analogous to that of Escherichia coli heat-labile or heat-stable enterotoxin in allantoic fluid from infected eggs or in cultures of the Legionnaires disease bacterium were not successful.     

Meningococcal Polysaccharide A O-Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized,Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ≥1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ≥1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.     

Using science to advance wound care practice: lessons from the literature

Wound care professionals can improve clinical, patient-oriented wound outcomes and do so cost-effectively by using scientific evidence to meet patient and wound care goals and needs. A review of the literature was conducted to define evidence-based wound management, describe the potential of science to improve outcomes in wound care, and sum- marize strategies, tactics, and tools for wound care providers and recipients to utilize science to their mutual benefit. In addition, changes in the availability of randomized and nonrandomized and clinical and preclinical evidence during the past 50 years were examined using MEDLINE database searches of English-language publications, combining the search terms wound, ulcer, or burn limited by the terms randomized or clinical for each decade since 1960. The number of published, nonrandomized wound studies has increased exponentially during the last five decades but, more recently, evidence from randomized controlled trials also has become available. Moreover, while many questions remain unan- swered, a substantial number of publications have shown the use of available evidence-based guidelines and wound care strategies improves outcomes of care while saving time and money. The application of science-based wound care in clinical practice is increasing slowly; expensive techniques supported by limited or inconsistent evidence are still in use and add to wound care costs without certainty they improve outcomes. The literature provides compelling evidence that patients with a wide variety of diagnoses benefit when opinion-based care is replaced by clinical wisdom applied on a substrate of best available evidence. Patients with wounds deserve no less.     

Simple and reproducible hepatectomy in the mouse using the clip technique

AIM: To investigate the reliability of massive hepatectomy models by using clip techniques.METHODS: We analyzed anatomical findings in 100 mice following massive hepatectomy induced by liver reduction > 70%. The impact of various factors in the different models was also analyzed, including learning curves, operative time, survival curves, and histopathological findings.RESULTS: According to anatomical results, models with 75%, 80%, and 90% hepatectomy produced massive hepatectomy. Learning curves and operative times were most optimal with the clip technique. Each hepatectomy performed using the clip technique produced a reasonable survival curve, and there were no differences in histopathological findings between the suture and clip techniques.CONCLUSION: Massive hepatectomy by the clip technique is simple and can provide reliable and relevant data.     

Effect of specific activation of γ‐aminobutyric acid receptor in vivo on oxidative stress‐induced damage after extended hepatectomy

Aim: γ‐Aminobutyric acid (GABA) is a multifunctional molecule with various physiological effects throughout the body. The regulation of GABA receptor (GABAR) plays a key role in reducing the damage mediated by oxidative stress (OS). Extended hepatectomy causes fatal OS‐induced injury in the liver remnant. We aimed to investigate the effect of a GABAR agonist in extended hepatectomy. Methods: Saline or a GABAR agonist (43.56 nmol/g bodyweight of muscimol) was administrated intravenously at 4 h preoperatively. C57BL/6 mice were divided into three groups: laparotomy only, 90% hepatectomy with saline and 90% hepatectomy with a GABAR agonist. Liver samples were obtained at 6 h after surgery. Results: Survival curves were prolonged by the GABAR agonist. Histopathological findings and biochemical profiles showed that the GABAR agonist reduced liver damage. Immunohistological assessment demonstrated that the GABAR agonist prevented apoptotic induction. As shown by 4‐hydroxynonenal, which reflects OS‐induced damage, 90% hepatectomy caused OS and the GABAR agonist reduced OS. We measured ataxia‐telangiectasia mutated kinase (ATM), H2AX, Akt and free radical scavenging enzymes because they may be affected by GABAR regulation, and found that Akt was greatly decreased after 90% hepatectomy, but it recovered with the GABAR agonist. Conclusion: GABAR is activated by a specific agonist in the liver in vivo. This activation reduces OS‐mediated damage after extended hepatectomy in vivo, and the mechanism via an Akt‐dependent pathway may be a key.     

Systematic screening of secondary diagnoses in Medicare administrative data to identify candidate risk factors for the principal diagnosis

PURPOSE: Secondary diagnoses in Medicare hospital discharge claims may include risk factors for the principal diagnosis. However, risk ratios for the principal diagnosis as a function of secondary diagnoses cannot be calculated because no comparable data exist for beneficiaries who are not hospitalized. METHODS: Hospital discharge rates, as proxies for incidence rates, can be calculated by race and sex from Medicare claims and denominator files. If the prevalence of a risk factor is higher in one population group than another, that risk factor will be overrepresented among patients from the group at higher risk. RESULTS: This imbalance is reflected in what is termed the odds difference, OD=[(r+r')/r][f(2)/(1- f(2))-f(1)/(1-f(1))], in which r is the background incidence rate, and r' is the additional risk conferred by a factor that is present in fractions f(1) and f(2) in the two groups. Unlike the risk ratio, the odds difference can be calculated from claims data. Given f(1) and f(2), the odds difference is directly proportional to the risk ratio, RR=(r+r')/r. CONCLUSIONS: Ranking common secondary diagnoses by the magnitude of their odds difference between groups with disparate discharge rates for a given principal diagnosis may disclose secondary diagnoses that merit evaluation as candidate direct or indirect risk factors.     

Laparoscopic sterilization with spring-loaded clips: double-puncture technique.

The application of a spring-loaded clip to each fallopian tube using a second-incision clip applicator is a safe and effective method of laparoscopic sterilization. The operation is quick and easy to perform and is suitable for use with local anesthesia. The method avoids the dangers of hemorrhage, for the clip only alters 3 mm of the fallopian tube and does not transect the tube or mesosalpinx. No pregnancies have followed the sterilization procedure. An intrauterine pregnancy has occurred after a reversal procedure in one patient.     

Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia.

We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all-trans retinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d-dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor 1 (PAI-1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin-1 beta (IL-1 beta). The mean plasma levels of fibrin d-dimer, F1.2, TAT and FPA were markedly elevated prior to therapy and declined during the first 30 days of treatment with either ATRA or chemotherapy, but more rapidly and to a greater extent in patients treated with ATRA. ATRA treatment was associated with a significant decrease in TF gene expression in bone marrow cells during the first 30 days of treatment, whereas IL-1 beta gene expression, which decreased in the cells of six patients treated with either chemotherapy or ATRA, actually increased in the remaining six patients treated with either chemotherapy or ATRA. In patients with APL, treatment with either chemotherapy or ATRA rapidly ameliorates the coagulopathy, as indicated by an abrupt decline in markers of clotting activation. An increase in cytokine gene expression (e.g. IL-1 beta) may provide an explanation for the persistent hypercoagulability observed in some patients with APL, regardless of therapeutic approach. Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.