Induction of CTL response by a minimal epitope vaccine in HLA A*0201/DR1 transgenic mice: dependence on HLA class II restricted T(H) response

CTL play a pivotal role in the immune response during viral infections. In this study, the HLA class II restricted T(H) requirement for optimal in vivo induction of HLA class I restricted CTL responses has been investigated. Towards this goal, transgenic mice expressing both HLA class I (A*0201 or A2.1) and class II (DRB1*0101 or DR1) molecules have been derived. Immunization of these mice with an HLA A*0201-restricted and CMV-specific CTL epitope (pp65(495-503)), and either of three different tetanus toxin-derived MHC class II-binding T(H) epitopes, resulted in a vigorous CTL response. CTL specific for the pp65(495-503) epitope were dramatically enhanced in mice expressing both the HLA-DR1 and HLA-A*0201 transgenes. Notably, preinjection of three TT peptides (TT(639-652), TT(830-843), and TT(947-967)) increased the capability of HLA A*0201/DR1 Tg mice to respond to subsequent immunization with the T(H) + CTL peptide mixture. These results indicate that the use of HLA A*0201/DR1 Tg mice constitute a versatile model system (in lieu of immunizing humans) for the study of both HLA class I and class II restricted T-cell responses. These studies provide a rational model for the design and assessment of new minimal-epitope vaccines based on their in vivo induction of a pathogen-specific CTL response.     

PCV16 Smoking Related Costs in the United States

Smoking is a high-risk behavior that affects the health and economic welfare of society. Thus, it is important to quantify the economic burden smoking places on social institutions in the United States.
OBJECTIVE: The purpose of this review paper is to analyze smoking cost studies and to provide estimates that represent the economic costs of smoking from different perspectives of society, and as a whole.
METHODS: Current Contents (1996–), Health Star (1970–), and Medline (1966–) databases were searched through the use of pertinent subject headings and key words: tobacco use, smoking, cost, and economics. The internet was utilized to identify potential sources of epidemiological and cost information on smoking. Recent cost-of-illness studies using different methodologies: human capital, incidence, and prevalence were chosen for review based on their relevance.
RESULTS: Preliminary results indicate that the published cost studies available underestimate the "true" costs of smoking. The most current articles approximate annual direct medical costs to health care payers of $50 billion (1993); inflating to 1997 equals $59 billion or $1,200 per smoker. Although the latest cost studies do not attempt to estimate indirect costs, past studies have found indirect costs to be 1.5–2 times the direct costs. Therefore, using direct and indirect costs we estimate total smoking costs to be $150 billion (1993); inflating to 1997 equals $176 billion or $3,500 per smoker.
CONCLUSION: Quantifying the cost of smoking is a difficult task due to tobacco use infiltrating many aspects of life and the dependency of cost on perspective. Cost-of-illness studies provide cost estimation data which can be useful in aiding decision-makers who are allocating health care resources.     

Gastric teratoma in newborn children

In neonates, teratomas infrequently involve the abdomen: among 51 known cases, 39 were gastric teratomas, which account for less than 2% of all germ cell tumors in the neonatal period. Associated malformations are minor, located in the region of the tumor, and apparently less frequent than in other sites. Malignancy is exceedingly rare (a single case) and well controlled as a result of the anti-tumor processes specific to the neonatal period. Gastric teratomas are diagnosed early and can be cured by tumorectomy removing a thin ring of the surrounding stomach wall.     

Fodrin and band 4.1 in a plasma membrane-associated fraction of human neutrophils

Erythrocytes possess a well-characterized submembranous filamentous network which interacts with transmembrane glycoproteins and is composed primarily of spectrin, ankyrin, band 4.1, and short actin filaments. An analogous structure was recently described in platelets. Human polymorphonuclear leukocytes (PMNs) were examined for the presence and plasma membrane association of similar proteins. Isolated PMNs, free of contamination with erythrocytes or platelets, were disrupted by nitrogen cavitation and separated into subcellular organelles on a discontinuous Percoll gradient. Detergent lysates of plasma membrane vesicles, but not azurophilic or specific granules, contained insoluble actin filaments and associated proteins. Immunoblots of detergent-insoluble plasma membrane fractions contained proteins recognized by antibodies to brain fodrin and erythrocyte band 4.1, whereas blots probed with antibodies to erythrocyte spectrin and ankyrin were negative. Fodrin and band 4.1 were not detected in granule fractions, but some fodrin was present in the cytosol. The association of proteins related to fodrin and band 4.1 with the plasma membrane suggests that PMNs contain a submembranous skeleton structurally analogous to that of erythrocytes and platelets. The specific function of these proteins and their structural organization in human PMNs await further study.     

Cutting balloon versus conventional balloon angioplasty for the treatment of in-stent restenosis: results of the restenosis cutting balloon evaluation trial (RESCUT)

OBJECTIVES: The aim of this trial was to compare cutting balloon angioplasty (CBA) with conventional balloon angioplasty (i.e., percutaneous transluminal coronary angioplasty [PTCA]) for the treatment of patients with coronary in-stent restenosis (ISR). BACKGROUND: Retrospective studies suggest CBA might be superior to conventional PTCA in the treatment of ISR. METHODS: The Restenosis Cutting Balloon Evaluation Trial (RESCUT) is a multicenter, randomized, prospective European trial including 428 patients with all types of ISR (e.g., focal, multifocal, diffuse, proliferative). RESULTS: In both groups, the majority of ISR lesions were shorter than 20 mm. The length of restenotic stents was similar (CBA: 18.6 +/- 9.7 mm; PTCA: 18.3 +/- 8.7 mm). The number of balloons used to treat ISR was lower in the CBA group: only one balloon was used in 82.3% of CBA cases, compared with 75% of PTCA procedures (p = 0.03). Balloon slippage was less frequent in the CBA group (CBA 6.5%, PTCA 25%; p < 0.01). There was a trend toward a lower need for additional stenting in the CBA group (CBA 3.9%, PTCA 8.0%; p = 0.07). At seven-month angiographic follow-up, the binary restenosis rate was not different between the groups (CBA 29.8%, PTCA 31.4%; p = 0.82), with a similar pattern of recurrent restenosis. Clinical events at seven months were also similar. CONCLUSIONS: Cutting balloon angioplasty did not reduce recurrent ISR and major adverse cardiac events, as compared with conventional PTCA. However, CBA was associated with some procedural advantages, such as use of fewer balloons, less requirement for additional stenting, and a lower incidence of balloon slippage.     

Fludarabine: a new agent with major activity against chronic lymphocytic leukemia

Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.     

Enterovirus persistence and myocardial damage detected by 111In-monoclonal antimyosin antibodies in patients with dilated cardiomyopathy

BACKGROUND: Patients with dilated cardiomyopathy in whom enteroviruses inthe myocardium are detected are more likely to die than thosein whom no viruses have been demonstrated. The presence of enterovirusRNA in the myocardium at endomyocardial biopsy has been shownto be the strongest predictor of reduced survival. These resultsraise the question as to whether persistent virus might be responsiblefor continuing myocardial damage. Detection of myocardial cell damage is assessed using ¹¹¹Indium-labelledmonoclonal antimyosin anti-bodies. The present study was undertakento address the question of whether the presence of myocardialcell damage by such antibodies in patients with dilated cardiomyopathycan be correlated with enterovirus persistence. PATIENTS AND METHODS: A series of 19 consecutive patients diagnosed as having chronicdilated cardiomyopathy who were referred for evaluation forheart transplantation were studied with ¹¹¹Indium labelled monoclonalantimyosin antibodies. These patients and 10 controls were screenedfor enterovirus RNA sequences in endomyocardial biopsy tissueby hybridization with an enterovirus group-specific cDNA probe. RESULTS: Antimyosin uptake, indicative of myocardial cell damage, wasobserved in 16 of 19 patients (84%) with dilated cardiomyopathy,and enterovirus RNA sequences were detected m endomyocardialbiopsies from four of these 16 patients (25%), but not in myocardiumfrom the remaining three patients with a negative antimyosinscan, nor from any of 10 controls. CONCLUSIONS: Although these data do not establish a causal relationship betweenvirus persistence in the myocardium and myocardial damage, theresults obtained in the preliminary study support the hypothesisthat enterovirus persistence is associated with continuing myocardialdamage in patients with dilated cardiomyopathy.     

Retroperitoneal robotic-assisted laparoscopic reimplantation of a ureter into an ileal conduit

A novel technique for managing ureteroenteric strictures is robotic-assisted retroperitoneal laparoscopic reimplantation. A 63-year-old morbidly obese male underwent a left nephroureterectomy and cystoprostatectomy after neoadjuvant chemotherapy for transitional cell carcinoma of both the bladder and left kidney. His single right ureter was anastomosed to the ileal conduit. Postoperatively, he developed acute renal failure and hydronephrosis. An antegrade pyelogram demonstrated a distal stricture that failed two attempts at endoscopic management. In an effort to avoid the morbidity of an open repair, we present a minimally invasive option that replicates the steps of an open reimplantation.