Characterization of infecting strains and superantigen-neutralizing antibodies in Staphylococcus aureus bacteremia

Staphylococcus aureus superantigens (SAgs) are highly potent T cell mitogens. Antibodies against non-enterotoxin gene cluster (non-egc) SAgs are common in healthy adults, whereas neutralizing antibodies against egc SAgs are rare. We investigated the infecting S. aureus strains and the anti-SAg antibody response during S. aureus bacteremia (SAB). This prospective clinical study (www.clinicaltrials.gov, NCT00548002) included 43 injection drug users (IDUs) and 44 group-matched nonaddicts with SAB. spa genotypes and SAg gene patterns (multiplex PCR) of the S. aureus isolates were determined. The neutralizing capacities of sera obtained at the acute phase and the convalescent phase of SAB were tested against the SAg cocktail of the respective infecting strain and a panel of recombinant SAgs. The lineages CC59 and CC30 were more prevalent among bacteremia strains from IDUs than among strains from nonaddicts. SAg gene patterns in isolates from IDUs and nonaddicts were similar. At the acute phase of bacteremia, IDUs had more neutralizing antibodies against non-egc SAgs than did nonaddicts. Antibody titers frequently increased during infection. In contrast, there were no neutralizing antibodies against egc SAgs at disease onset and such antibodies were not induced by SAB. SAB triggers an antibody response only against non-egc SAgs. Preimmunization in IDU patients is probably due to previous exposure to the infecting strain.     

Inflammatory response against different carbon fiber-reinforced PEEK wear particles compared with UHMWPE in vivo

Poly(ether ether ketone) (PEEK) and its composites are recognized as alternative bearing materials for use in arthroplasty because of their mechanical properties. The objective of this project was to evaluate the biological response of two different kinds of carbon fiber-reinforced (CFR) PEEK compared with ultra-high molecular weight polyethylene (UHMWPE) in vivo as a standard bearing material. Wear particles of the particulate biomaterials were injected into the left knee joint of female BALB/c mice. Assessment of the synovial microcirculation using intravital fluorescence microscopy as well as histological evaluation of the synovial layer were performed 7 days after particle injection. Enhanced leukocyte–endothelial cell interactions and an increase in functional capillary density as well as histological investigations revealed that all tested biomaterials caused significantly (P < 0.05) increased inflammatory reactions compared with control animals (injected with sterile phosphate-buffered saline), without any difference between the tested biomaterials (P > 0.05). These data suggest that wear debris of CFR-PEEK is comparable with UHMWPE in its biological activity. Therefore, CFR-PEEK represents an alternative bearing material because of its superior mechanical and chemical behavior without any increased biological activity of the wear particles, compared with a standard bearing material.     

The influence of dynamic fatigue loading on the separate components of the bracket-cement-enamel system

PURPOSE: To evaluate the influence of cyclic loading and type of adhesive on the shear bond strength of the bracket-cement-enamel bond. METHODS: The materials studied were: Transbond XT (a Bis-GMA resin composite cement), Fuji Ortho LC (a resin-modified glass-ionomer cement), and Fuji IX Fast (a conventional glass-ionomer cement). The shear bond strength (SBS) and the shear bond fatigue limits (SBFL) were determined after 72-hour storage in 37 degrees C water for the cement itself, the button-cement interface, the cement-enamel interface, and the bracket-cement-enamel system. The SBFL was determined with the aid of the "staircase method" at 10,000 cycles. The results were analyzed using ANOVA and Tukey HSD post hoc test (P < 0.05). RESULTS: ANOVA showed significant differences between the SBS of the materials. Fatigue was observed in all substrate combinations, with the exception for the Fuji IX Fast cement-enamel and the Fuji Ortho LC bracket-cement-enamel combinations.     

Elevated pretreatment serum concentration of YKL‐40—An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer

BACKGROUND:

The glycoprotein YKL‐40 is synthesized both by cancer cells and by tumor‐associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL‐40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL‐40 has not been established in nonsmall cell lung cancer (NSCLC).

METHODS:

Pretreatment serum levels of YKL‐40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41‐76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV disease. Ninety‐eight patients received combined gemcitabine and vinorelbine, and 91 received combined gemcitabine, vinorelbine, and cisplatin as first‐line chemotherapy. The median overall survival was 37 weeks.

RESULTS:

Patients had a median serum YKL‐40 level of 209 ng/mL (range, 19‐2153 ng/mL). No correlation was observed between overall survival and the type of chemotherapy regimen used, tumor stage, sex, or histologic types. Patients with high serum YKL‐40 levels (greater than the median level for all patients [209 ng/mL]) had a significantly shorter survival than patients with serum YKL‐40 levels below the median (median survival, 32 weeks vs 41 weeks; P = .007). In multivariate analysis, the serum YKL‐40 level, the presence of bone lesions, and the serum lactate dehydrogenase level were independent, statistically significant prognostic factors.

CONCLUSIONS:

The pretreatment serum YKL‐40 level was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients. Cancer 2010. © 2010 American Cancer Society.     

Stress susceptibility predicts the severity of immune depression and the failure to combat bacterial infections in chronically stressed mice

Chronic psychological stress has been suggested to play a role in disorders in which the immune system unexpectedly fails to respond in a protective manner. Chronic combined acoustic and restraint stress compromises the anti-bacterial defense mechanisms of female BALB/c mice. The immunodeficiency is characterized by an apoptotic loss of lymphocytes, reduced ex vivo-inducibility of TNF but increased inducibility of IL10, reduced T-cell proliferation, and impaired phagocyte functions. Stressed mice develop depression-like behavior that was monitored by a stress severity score (SSS). Besides a strain (BALB/c>CBA) and gender (male>female) dependent susceptibility to chronic stress, inbred mice have an individual coping ability. Importantly, the individual SSS strongly correlates with Escherichia coli dissemination after infection as well as with IL10-inducibility and circulating corticosterone levels of each animal.     

Infant orthopedics in UCLP: effect on feeding, weight, and length: a randomized clinical trial (Dutchcleft).

OBJECTIVE: To study the effects of infant orthopedics (IO) on feeding, weight, and length. DESIGN: Prospective two-arm randomized controlled trial in three academic Cleft Palate Centers. Treatment allocation was concealed and performed by means of a computerized balanced allocation method. SETTING: Cleft Palate Centers of Amsterdam, Nijmegen, and Rotterdam, the Netherlands. PATIENTS: Infants with complete unilateral cleft lip and palate (UCLP), no other malformations. INTERVENTIONS: One group (IO+) wore passive maxillary plates during the first year of life, but the other group (IO-) did not. All other interventions were the same for both groups. MAIN OUTCOME MEASURES: Bottle feeding velocity (mL/min) at intake, 3, 6, 15, and 24 weeks (T0 to T24); weight-for-age, length-for-age, and weight-for-length using z scores; reference values from the Netherlands' third nationwide survey on growth. RESULTS: Feeding velocity increased with time from 2.9 to 13.2 mL/min in the IO- group and from 2.6 to 13.8 mL/min in the IO+ group; no significant differences were found between groups. Weight-for-age, length-for-age, and weight-for-length (z scores) did not differ significantly between groups, but overall the infants with unilateral cleft lip and palate in both groups had significantly lower mean z scores for weight-for-age and height-for-age than the reference during the first 14 months, and had lower mean values for weight-for-length after soft palate closure. CONCLUSION: Infant orthopedics with the aim of improving feeding and consequent nutritional status in infants with unilateral cleft lip and palate can be abandoned.