A conjugate vaccine composed of a heat shock protein 60 T-cell epitope peptide (p458) and Neisseria meningitidis type B capsular polysaccharide

Neisseria meningitidis type B is a major world-health problem. The Meningococcus type B capsular polysaccharide (MnB) is very poorly immunogenic and no vaccine to the antigen exists. Here, we conjugated the MnB to a T-cell carrier peptide (p458) derived from the self-60kDa heat shock protein molecule. The conjugate vaccine was effective in inducing long-lasting IgG antibodies to the MnB antigen in mice. The vaccine was also immunogenic when injected in PBS. Thus, the p458 carrier peptide can induce T-cell help for the switch to IgG Ab to the MnB antigen.     

A new pitfall on abdominal PET/CT: a retained surgical sponge

Positron emission tomography (PET)/computed tomography (CT) and multidetector CT findings of an abdominal retained surgical sponge (RSS) are presented. A PET/CT study performed for evaluation of a suspected abdominal tumor demonstrated the inconclusive finding of a hypometabolic area surrounded by increased 2-[fluorine-18] fluoro-2-deoxy-D-glucose uptake. Follow-up contrast-enhanced multidetector CT suggested the correct diagnosis of an RSS. This is the first known report of the PET/CT appearance of an RSS.     

Nighttime reflux is primarily an early event

GOALS: Our clinical impression gleaned from reading large numbers of ambulatory pH studies is that recumbent reflux episodes mostly occur in the early part of the nighttime period. In this study, we propose to test this hypothesis. STUDY: A total of 201 consecutive pH studies performed in our laboratory between November 2001 and October 2002 were analyzed. Population characteristics: 75 males and 126 females; mean age, 50.4 yrs (range, 16-88 years). Reflux was defined by a drop in pH to less than 4. Abnormal total recumbent reflux was defined as >1.2% time pH < 4. For patients with abnormal recumbent reflux, the recumbent period was divided into two halves and the reflux time in each period was calculated. In all patients, ingestion of a meal within 2 hours of retiring was also identified. RESULTS: A total of 59 patients had abnormal recumbent reflux: 24 males and 35 females; mean age, 48.9 years. In patients with abnormal recumbent reflux, acid reflux was significantly more frequent in the first half of the recumbent period compared with the second half (median, 6.3%; vs. 0.3%, respectively; P < 0.001; Wilcoxon signed rank test, two-tailed analysis). Those patients (N = 118) having had a meal within 2 hours of retiring were 2.46 times more likely to develop recumbent reflux than those whose last meal was more than 2 hours earlier (N = 83). CONCLUSION: These results support our hypothesis that nighttime reflux occurs primarily during the first half of the recumbent period. In addition, they reinforce the concept of maintaining control of early nighttime reflux and the importance of counseling patients with nocturnal symptoms against late meals and snacks.     

Comprehensive multidetector computed tomography assessment of severe cardiac contusion in a pediatric patient: correlation with echocardiography

Multidetector computed tomography (MDCT) cardiac findings in an unconscious teenager after blunt chest trauma are presented. Multidetector computed tomography enabled accurate comprehensive evaluation of the coronary arteries, myocardial perfusion, and left ventricular function. This case illustrates the full capabilities of MDCT in the evaluation of cardiac contusion in a noncooperative pediatric patient.     

Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells,down-regulates DR and CD86, and up-regulates CC chemokine receptor 7

Immature dendritic cells (iDCs) do not mature after uptake of apoptotic cells and may play a role in the induction of peripheral tolerance to self antigens derived from apoptotic material. The integrins, alphavbeta3, alphavbeta5, and the scavenger receptor, CD36, have been shown to mediate uptake of apoptotic cells by iDCs. However, it is not known whether the complement system, also takes part in this process. In this study we investigated the ability of iDCs to bind to apoptotic cells opsonized by iC3b. Monocyte-derived dendritic cells were offered apoptotic Jurkat cells opsonized by autologous iC3b and labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate. A significant increase (P < 0.001) in the amount of cleared apoptotic cells was seen at low ratios. Despite increased efficiency of uptake, interaction between iC3b-opsonized apoptotic cells and iDCs down-regulated the expression of major histocompatibility complex class II, CD86, CC chemokine receptor (CCR)2, CCR5, and beta2-integrins (P < 0.001), and up-regulated expression of CCR7 (P < 0.001). In addition, iDC maturation responses to CD40L and lipopolysaccharide were significantly inhibited. We conclude that opsonization of apoptotic cells by iC3b induces tolerant iDCs that are able to migrate to lymph nodes.     

Elongated eccentric soft coronary plaque: Major diagnostic pitfall on quantitative coronary angiography overpowered by computed tomography coronary angiography and intravascular ultrasound

We describe a significant left anterior descending coronary lesion in a patient with unstable angina pectoris. This lesion was erroneously underestimated using quantitative coronary angiography; however, CT coronary angiography correctly showed a significant, elongated, eccentric, soft plaque that was later confirmed by repeated quantitative coronary angiography with intravascular ultrasound. As showed, CT coronary angiography may offer a reliable non‐invasive alternative to quantitative coronary angiography and intravascular ultrasound by enabling a true 3‐D coronary lumenogram combined with plaque detection and characterization.     

Diagnostic sequencing to support genetically stratified medicine in a tertiary care setting

PurposeThe goal of stratified medicine is to identify subgroups of patients with similar disease mechanisms and specific responses to treatments. To prepare for stratified clinical trials, genome-wide genetic analysis should occur across clinical areas to identify undiagnosed genetic diseases and new genetic causes of disease.MethodsTo advance genetically stratified medicine, we have developed and implemented broad exome sequencing infrastructure and research protocols at Columbia University Irving Medical Center/NewYork-Presbyterian Hospital.ResultsWe enrolled 4889 adult and pediatric probands and identified a primary result in 572 probands. The cohort was phenotypically and demographically heterogeneous because enrollment occurred across multiple specialty clinics (eg, epilepsy, nephrology, fetal anomaly). New gene-disease associations and phenotypic expansions were discovered across clinical specialties.ConclusionOur study processes have enabled the enrollment and exome sequencing/analysis of a phenotypically and demographically diverse cohort of patients within 1 tertiary care medical center. Because all genomic data are stored centrally with permission for longitudinal access to the electronic medical record, subjects can be recontacted with updated genetic diagnoses or for participation in future genotype-based clinical trials. This infrastructure has allowed for the promotion of genetically stratified clinical trial readiness within the Columbia University Irving Medical Center/NewYork-Presbyterian Hospital health care system.     

Bronchoalveolar lavage and transbronchial biopsy in spondyloarthropathies.

Fourteen patients (12 men, 2 women) with spondyloarthropathies underwent bronchoalveolar lavage (BAL), transbronchial biopsy (TBB) and other respiratory investigations. BAL revealed lymphocytosis and increased nonaltered neutrophil polynuclears in a smoker and an isolated lymphocytosis in one patient with restrictive syndrome and radiographic apical fibrosis. TBB showed interstitial fibrosis in the 2 patients and in 3 others who are all nonsmokers and among whom 2 had a restrictive syndrome. Subclinical alveolitis in spondyloarthropathies is absent. Interstitial fibrosis is not rare and its frequent association in a restrictive syndrome suggests a mechanical origin.