Platelets as immunogens.

An immune response to human platelet antigens (HPA), as in neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP), is the exception rather than the rule and evidence is accumulating for the importance of human leucocyte antigen (HLA) class II restriction in this situation. Platelets have only HLA class I antigens and do not cause primary HLA alloimmunization; in platelet transfusions this is due to the contaminating leucocytes. Autoimmune thrombocytopenia is more common than the alloimmune conditions. The main target antigens for platelet autoantibodies are glycoproteins (Gp) IIb/IIIa and Ib/IX. The mechanism of drug-induced immune thrombocytopenia has been re-examined in relation to the target cell orientation of the antibody and of the drug.     

An Evaluation of a Mixed-Gender Sexual Assault Prevention Program

This study evaluated the short-term effectiveness of a mixed-gender sexual assault prevention program developed for college students. Program participants (n = 177) were compared to non-program participants (n = 132) prior to the program and during a 2-week follow-up period on measures of rape myths, victim empathy, perceived negative consequences and estimated likelihood of committing rape, sexual communication, sexual assault awareness, and risky dating behavior. The prevention program was effective at increasing men’s victim empathy and decreasing their adherence to rape myths but ineffective at changing women’s assault-related knowledge, participation in risky dating behaviors, and sexual communication strategies. Limitations of the study and directions for future research in sexual assault prevention are addressed. Editors’ Strategic Implications: This study provides an important example of the limitations of a single session prevention programming approach (even if it is well designed and executed) in addressing a systemic and pervasive problem like sexual assault on college campuses.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Survival after gastric adenocarcinoma resection: Eighteen-year experience at a single institution

Gastric adenocarcinoma is the second leading cause of cancer death worldwide. In Western series, survival rates vary widely and are generally lower than those reported from Eastern series. We performed a retrospective analysis of cases operated on at the Johns Hopkins Hospital over the past 18 years and collected data on demographics, tumor characteristics, pathologic stage, treatment methods, complications, survival time, and other relevant factors. Survival according to stage of disease, Lauren tumor type, tumorlocation,time period, andadministration of adjuvant therapy wasanalyzed, andresultswerecompared with those of other Western series. During this period, 436 patients with gastric adenocarcinoma underwent resection. We have shown a statistically significant association between survival and margin status, stage of disease, and Lauren tumor type. Overall 5-year survival was 26%, and 5-year survival after R0 resection was 33%. No significant difference was detected between survival and tumor location, time period of treatment, or administration of adjuvant therapy. Analysis of various Western series reveals major differences between the cohorts under study, such as stage of disease, extent of resection, tumor type, and tumor location. Many of the reported differences among Western series may be due to cohort differences, such as stage of disease, extent of resection, tumor type, and tumor location.     

Diagnosing osteoporosis by using dental panoramic radiographs: the OSTEODENT project.

OBJECTIVES: Measurement of cortical thickness and subjective assessment of cortical porosity on panoramic radiographs are methods previously reported for diagnosing osteoporosis. The aims of this study were to determine the relative efficacy of the mandibular cortical index and cortical width in detecting osteoporosis, both alone and in combination, and to determine the optimal cortical width threshold for referral for additional osteoporosis investigation. STUDY DESIGN: Six hundred seventy-one postmenopausal women 45 to 70 years of age were recruited for this study. They received dual energy x-ray absorptiometry (DXA) scans of the left hip and lumbar spine (L1 to L4), and dental panoramic radiographic examinations of the teeth and jaws. Three observers separately assessed the mandibular cortical width and porosity in the mental foramen region of the mandible. Cortical width was corrected for magnification errors. Chi-squared automatic interaction detection analysis (CHAID) software was used (SPSS AnswerTree, version 3.1, SPSS Inc., Chicago, IL). RESULTS: Chi-squared automatic interaction detection analysis showed that the cortical porosity was a poorer predictor of osteoporosis than mandibular cortical width. For the 3 observers, a mandibular cortical width of <3 mm provided diagnostic odds ratios of 6.51, 6.09, and 8.04. The test is therefore only recommended in triage screening of individuals by using radiographs made for purposes other than osteoporosis. CONCLUSION: When evaluating panoramic radiographs, only those patients with the thinnest mandibular cortices (i.e., <3 mm) should be referred for further osteoporosis investigation.     

Prevention of nosocomial pressure ulcers: a process improvement project.

Nosocomial pressure ulcers (PU) occur in approximately 12% of all hospitalized patients. The risk can be determined by a variety of intrinsic and extrinsic factors. As a first line of defense against nosocomial PU, we use the Braden Scale to determine the potential risk of PU development during hospitalization. Once risk was identified, our standard was to implement an individualized plan of care. However, consistent implementation of PU preventative measures was lacking. As a result, a process improvement project was developed and implemented. The purpose of this process improvement project was to increase communication about and awareness of the need to vigorously intervene and document whenever there is risk of, or development of, a nosocomial PU. By initiating consistent use of a PU Tracking Form, developing unit-based wound champions that serve as experts in ulcer prevention, and creating an individual case analysis process, PU prevention and tracking was institutionalized. Results indicate that our nosocomial PU rate has declined from 7% to 4%.     

Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.     

Enhancement of in vivo and in vitro immune functions by a conformationally biased,response-selective agonist of human C5a: Implications for a novel adjuvant in vaccine design

A conformationally biased, agonist of human C5a_65–74 (EP67) was assessed for its adjuvant activities in vitro and in vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). EP67 did not induce the release of these cytokines from splenic APCs obtained from C5a receptor knockouts (CD88^−/−). Serum from mice immunized with EP67–ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like Ab class switch. Spleen cell cultures from wild type mice but not CD88^−/− mice showed an enhanced OVA-specific proliferative response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant.