The STAFF studies of the first 5 minutes of percutaneous coronary angioplasty balloon occlusion in man

The Staff Studies comprise a database of 228 patients undergoing elective 5 minute coronary artery balloon occlusion angioplasty at a single center in the pre-stent era in whom standard and high-frequency electrocardiographic and nuclear information was obtained immediately before, during and after balloon occlusion. The data were then analyzed by multiple investigators at different international academic centers from different perspectives. Simulating in a clinical setting the first 5 minutes of a heart attack, this database, now in digital format, is the largest database to date documenting standard and high-frequency ECG changes from the onset and for 5 minutes during acute coronary artery occlusion, with resting and occlusion imaging in a subset of these patients. The history, methodology, and legacy of these studies are discussed in this paper.     

The delicate balance in genetically engineering live vaccines

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.     

Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

Invasive Salmonella infections for which improved or new vaccines are being developed include enteric fever caused by Salmonella enterica serovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidal Salmonella (NTS) serovars, particularly S. enterica serovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developed in vitro assays to quantify serum bactericidal antibody (SBA) activity induced by S. Typhi, S. Paratyphi A, S. Typhimurium, and S. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. For S. Enteritidis, S. Typhimurium, and S. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast, S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administered S. Typhimurium, S. Enteritidis, and S. Paratyphi A but not S. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited by Salmonella vaccine candidates.     

Extensive cutaneous metastatic breast carcinoma of the hand and upper extremity: a case report

Cutaneous metastatic breast carcinoma involving the hand is extremely rare. We report a case of a 39-year-old woman with a history of recurrent invasive ductal adenocarcinoma of the breast who had a right modified radical mastectomy, chemotherapy, and radiation therapy before presenting to our institution with extensive cutaneous metastasis to the upper limb including the hand. The presentation, pathogenesis, incidence, prognosis, management, and differential diagnosis of cutaneous metastatic breast carcinoma to the hand and upper limb are discussed.