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Summary:. The optimal treatment for full-thickness burn injuries involves surgical intervention, which may include skin grafting or reconstruction by flap. The complexity of treatment arises from the need for both effective temporary wound coverage and permanent skin restoration while also considering the potential risk of finger amputation in the case of hand burn. A 22-year-old woman sustained a thermal burn of three fingers while participating in an art activity involving wax hand molding. Initial treatment with a standard oily dressing did not yield satisfactory results, and the option to try HEMHealing was offered, a new oxygenating biological gel dressing, resulting in progressive debridement, granulation, and epithelialization of the wound. Complete healing was achieved within 10 and 15 days for the second and fourth fingers, respectively, and within 8 weeks for the third finger. The use of HEMHealing, in this case, most likely contributed to accelerating wound healing, promoting the growth of new tissues, improving local tissue oxygenation, and avoiding a disabling distal amputation.

ABSTRACT: Background: Venous anatomy of the digits and the hand is poorly reported in the literature compared to arterial anatomy. While knowledge of the venous anatomy is crucial to ensure safe skin incisions, skin flap design, or blood return restoration for digital replantations, data in anatomical and clinical textbooks are rather limited. The purpose of this anatomical study was to describe the venous anatomy of the digits and the hand. Method: Our series reports descriptive results from 10 non-embalmed hand dissections from 5 different corpses. Hands were previously co-injected by arteries followed by veins with a different colored latex before being dissected under optical magnification (x4). Each anatomical specimen was photographed before being analyzed. Results: Each injection revealed both arterial and venous vascular systems. Latex injections were a useful technique to show the dorsal, volar superficial, and deep venous system. There was a constant and reliable topographic vascular anatomy of the superficial venous system of the digits and hand. However, we could not observe a high density of dorsal superficial venous valves as previously reported. Conclusion: The knowledge of the arrangement of the venous system of the digits and the hand should help the surgeon when performing surgical procedures in the hand. The surgeon should take into consideration this venous anatomy when performing skin incisions, skin flaps, or replantation procedures which would preserve the normal venous physiology as much as possible.

Abstract Background The national ranking examination (NRE) marks the end of the second cycle (6th university year) of French medical studies and ranks students allowing them to choose their specialty and city of residency. We studied the potential predictive factors of success at the 2015 NRE by students attending a French School of Medicine. Methods From March 2016 to March 2017, a retrospective study of factors associated with the 2015 NRE success was conducted and enrolled 242 students who attended their sixth year at the school of medicine of Reims. Demographic and academic data collected by a home-made survey was studied using univariate and then multivariate analysis by generalized linear regression with a threshold of p

Objectives: To evaluate how urologists in various subspecialties view the climate for female urologists, comparing perceptions of gender inequity based on characteristics including gender, subspecialty training, faculty status, parental status, and years in practice. Despite growth in female representation in urology, gender inequalities in career opportunities and compensation continue to exist., Methods: An IRB approved survey was sent out to the following list-serves: Society of Urological Oncology (SUO), Society of Endourology (ENDO), Genitourinary Reconstructive Surgeons (GURS), Society of Pediatric Urology (SPU), Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU), and American Urogynecologic Society (AUGS). A validated study, the Culture Conducive to Women's Academic Success (CCWAS) was used, and scores analyzed using Wilcoxon Rank-Sum and Kruskal-Wallace tests., Results: There were 430 survey responses (35.3% female, 64.7% male). There was a statistically significant difference in CCWAS score for gender, parental status, and society. On multiple regression analysis controlling for gender, parental status and society were not statistically significant. Years in practice and practice type were not significant. Male urologists perceived practice culture toward women as more equitable than their female colleagues, (median [interquartile range] CCWAS score, 203.5 [184.25, 225.0] vs 162.5 [130.75, 188.0]; P < .0001). This discrepancy in perception between genders was consistent across all subcategories; equal access, work-life balance, freedom of gender bias, and leadership support., Conclusions: This study suggests that there are gender-based differences in how gender inequities are perceived and experienced in urology. Acknowledgment of these differences is the first step in identifying opportunities for improvement., Competing Interests: Conflicts of interest statement This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Only 9.9% of practicing urologists in the United States are women. This percentage is even smaller in leadership positions and high-ranking appointments. Endourology is one of the least reported fellowships completed by women urologists. We sought to evaluate how endourologists perceived the climate for women physicians and compare perceptions and experiences of gender equity. Materials and Methods: An IRB approved and validated survey, Culture Conducive to Women's Academic Success (CCWAS) questionnaire was sent out to the Endourological Society listserve. Subcategories of equal access, work-life balance, freedom of gender bias, and leadership support were analyzed. An open comment section was provided for respondents to include their own experiences. Wilcoxon rank-sum and Kruskal-Wallis tests were used to compare CCWAS scores between groups. Results: A total of 104 completed surveys were received. Response rate was 7% (104/1492), 26.9% of which were female. There was a statistically significant difference between male and female respondent CCWAS scores; p  < 0.05. The male CCWAS score median was 196.0 (interquartile range [IQR] 176.75-214.0) vs female CCWAS score median of 166.5 (IQR 127.5-210.0). There was no significant difference in CCWAS scores based on years in practice, parental status, or academic vs private practice. Discussion: In this study, male endourologists' perceptions of gender equity were incongruent with the reported experiences of their female colleagues. This indicates that male respondents perceive the culture in their department toward women more positively than their female colleagues. This is suggestive that there are gender-based differences in how gender inequities are perceived and potentially experienced.

Purpose of Review: To discuss perineal and robotic approaches to gender-affirming vaginoplasty., Recent Findings: The Davydov peritoneal vaginoplasty has its origins in neovaginal reconstruction for vaginal agenesis. It has been adapted as a robotic-assisted laparoscopic procedure and provides an alternative to perineal canal dissection in gender-affirming vaginoplasty. Both techniques represent variations of penile inversion vaginoplasty with successful outcomes and overall low rates of major complications reported in the literature. However, there are differing advantages and considerations to each approach. A perineal approach has been the gold standard to gender-affirming vaginoplasty for many decades. Robotic peritoneal gender-affirming vaginoplasty (RPGAV) is an emerging alternative, with potential advantages including less reliance on extragenital skin grafts in individuals with minimal genital tissue, especially among patients presenting with pubertal suppression, and safer dissection in revision vaginoplasty for stenosis of the proximal neovaginal canal. Additional risks of RPGAV include those associated with robotic abdominal surgeries., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction  Prehospital therapy of ST-elevation myocardial infarction (STEMI) with αIIbβ3 antagonists improves clinical outcomes, but they are difficult to use in prehospital settings. RUC-4 is a novel αIIbβ3 antagonist being developed for prehospital therapy of STEMI that rapidly achieves high-grade platelet inhibition after subcutaneous administration. Standard light transmission aggregometry (LTA) is difficult to perform during STEMI, so we applied VerifyNow (VN) assays to assess the pharmacodynamics of RUC-4 relative to aspirin and ticagrelor. Methods  Blood from healthy volunteers was anticoagulated with phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) or sodium citrate, treated in vitro with RUC-4, aspirin, and/or ticagrelor, and tested with the VN ADP + PGE 1 , iso-TRAP, and base channel (high concentration iso-TRAP + PAR-4 agonist) assays. The results were correlated with both ADP (20 µM)-induced LTA and flow cytometry measurement of receptor occupancy and data from individuals treated in vivo with RUC-4. Results  RUC-4 inhibited all three VN assays, aspirin did not affect the assays, and ticagrelor markedly inhibited the ADP + PGE 1 assay, slightly inhibited the iso-TRAP assay, and did not inhibit the base channel assay. RUC-4's antiplatelet effects were potentiated in citrate compared with PPACK. Cut-off values were determined to correlate the results of the VN iso-TRAP and base channel assays with 80% inhibition of LTA. Conclusion  The VN assays can differentiate the early potent anti-αIIbβ3 effects of RUC-4 from delayed effects of P2Y12 antagonists in the presence of aspirin. These pharmacodynamic assays can help guide the clinical development of RUC-4 and potentially be used to monitor RUC-4's effects in clinical practice., Competing Interests: Conflict of Interest B.S.C receives royalties from Instrumentation Laboratories on the sales of the cartridges for the VerifyNow PRUTest assay. He is also an inventor of RUC-4, a founder and equity holder in CeleCor Therapeutics, the company to which RUC-4 has been licensed by Rockefeller University, and a consultant to CeleCor., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Introduction/objective: Women constitute more than 50% of medical students in the United States. However, only 9.9% of practicing urologists are women, with much fewer numbers in high ranking appointments and positions of leadership. With a growing number of women in pediatric urology, we sought to evaluate how pediatric urologists perceive the climate for women physicians and compare perceptions and experiences of gender equity based on characteristics including gender, practice type, parental status, and years in practice., Study Design: An IRB approved survey was sent out to the Society of Pediatric Urology (SPU) listserve of active members. We utilized a validated study, the Culture Conducive to Women's Academic Success questionnaire (CCWAS, higher scores indicating better perceived culture toward women). Subcategories (equal access, work-life balance, freedom of gender bias, and leadership support) were also analyzed. A comment section was provided for respondents to include their own experiences. Descriptive statistics were used for demographics and clinical characteristics. Wilcoxon Rank-Sum and Kruskal-Wallace tests were used to compare CCWAS scores between groups., Results: A total of 116 practicing physicians returned completed surveys for analysis (response rate, 116/355 (33%) [ n = 41,35.3%] female [n = 75,64.7%] male). There was a statistically significant difference in total CCWAS score between male and female genders, indicating male physicians perceived the culture of their department toward women more positively than their female counterparts (median [ interquartile range] CCWAS score, 208.0 [189.0-228.0] vs 164.0 [136.0-190.3]; P < 0.0001). There was no significant difference in CCWAS scores based on years in practice, parental status, or academic versus private practice., Discussion: Limitations of our survey include both participation and non-response bias. Those with strong opinions may have been more likely to respond to the survey. Male respondents comprised 64.7% (n = 75) of overall respondents, representing 25% active male SPU members. Whereas the response rate of active female members of the SPU was 70%. The survey was designed to assess gender equity in academia, and may not be as generalizable to the private practice community. Yet, the differences in perceptions and experiences of gender equity of this study have been noted by studies in other specialties, as well as the 2018 AUA Census report, and may provide insight into the presence and perpetuation of unconscious or systemic biases within medicine., Conclusion: In this study, male physician perceptions of gender equity were different from those reported by female physicians, suggesting there are gender-based differences in how gender inequities are perceived and experienced., (Published by Elsevier Ltd.)

Background Despite reductions in door-to-balloon times for primary coronary intervention, mortality from ST-segment-elevation myocardial infarction has plateaued. Early pre-primary coronary intervention treatment of ST-segment-elevation myocardial infarction with glycoprotein IIb/IIIa inhibitors improves pre-primary coronary intervention coronary flow, limits infarct size, and improves survival. We report the first human use of a novel glycoprotein IIb/IIIa inhibitor designed for subcutaneous first point-of-care ST-segment-elevation myocardial infarction treatment. Methods and Results Healthy volunteers and patients with stable coronary artery disease receiving aspirin received escalating doses of RUC-4 or placebo in a sentinel-dose, randomized, blinded fashion. Inhibition of platelet aggregation (IPA) to ADP (20 μmol/L), RUC-4 blood levels, laboratory evaluations, and clinical assessments were made through 24 hours and at 7 days. Doses were increased until reaching the biologically effective dose (the dose producing ≥80% IPA within 15 minutes, with return toward baseline within 4 hours). In healthy volunteers, 15 minutes after subcutaneous injection, mean±SD IPA was 6.9%+7.1% after placebo and 71.8%±15.0% at 0.05 mg/kg (n=6) and 84.7%±16.7% at 0.075 mg/kg (n=6) after RUC-4. IPA diminished over 90 to 120 minutes. In patients with coronary artery disease, 15 minutes after subcutaneous injection of placebo or 0.04 mg/kg (n=2), 0.05 mg/kg (n=6), and 0.075 mg/kg (n=18) of RUC-4, IPA was 14.6%±11.7%, 53.6%±17.0%, 76.9%±10.6%, and 88.9%±12.7%, respectively. RUC-4 blood levels correlated with IPA. Aspirin did not affect IPA or RUC-4 blood levels. Platelet counts were stable and no serious adverse events, bleeding, or injection site reactions were observed. Conclusions RUC-4 provides rapid, high-grade, limited-duration platelet inhibition following subcutaneous administration that appears to be safe and well tolerated. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NTC03844191.

Background Bullous pemphigoid has been associated to dipeptidase-4 inhibitors. Objectives Addressing the potential Bullous pemphigoid-dipeptidase-4 inhibitors association based on pharmacovigilance data currently available in Spain in order to obtain a composite disproportionality estimator from all the data generated by the case-non case studies conducted to this date. Setting The Spanish Pharmacovigilance System for Human Use Drugs database. Method Case-non case study based on the Spanish Pharmacovigilance System for Human Use Drugs notifications submitted between 2007 and 2018 (n = 169,280), using the Medical Dictionary for Regulatory Activities term (Preferred Term) 'pemphigoid' for sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin (n = 1952). As negative control, we used acetaminophen, while furosemide was the positive control. A pooled reported odds ratio analysis in the French, Japanese, and Spanish national pharmacovigilance databases was performed. On The Spanish Pharmacovigilance System for Human Use Drugs, we conducted a bullous pemphigoid-metformin association analysis within the period 1982-2018. Main outcome measure Adverse reaction cases in pharmacovigilance databases and the disproportionality through the reporting odds ratio. Results Within The Spanish Pharmacovigilance System for Human Use Drugs, we found 45 cases of bullous pemphigoid in dipeptidase-4 inhibitors patients. Median age was 77 years (range 72-82). The median latency period was 7 months (range 0.23-86). The Bullous pemphigoid-dipeptidase-4 inhibitors association was established with a reporting odd ratio = 70.0 (95% confidence intervals 49.1-10.1). In the combined analysis of the three aforementioned pharmacovigilance databases, the pooled reporting odd ratio was 81.0 (95% confidence intervals 69.5-94.4). Conclusion The composite estimator for the three national pharmacovigilance databases yields clear evidence of a Bullous pemphigoid-dipeptidase-4 inhibitors association, which was statistically significant for both the pharmacological class as a whole and each of the dipeptidase-4 inhibitors agents under investigation. Metformin's role in the incidence of bullous pemphigoid appeared casual rather than causal. No differences between Caucasian and Asian populations were noted.

Background: Streptococcus pyogenes (group A Streptococcus, Strep A) is a widespread pathogen that continues to pose a significant threat to human health. The development of a Strep A vaccine remains an unmet global health need. One of the major vaccine strategies is the use of M protein, which is a primary virulence determinant and protective antigen. Multivalent recombinant M protein vaccines are being developed with N-terminal M peptides that contain opsonic epitopes but do not contain human tissue cross-reactive epitopes., Methods: We completed a Phase I trial of a recombinant 30-valent M protein-based Strep A vaccine (Strep A vaccine, StreptAnova™) comprised of four recombinant proteins containing N-terminal peptides from 30 M proteins of common pharyngitis and invasive and/or rheumatogenic serotypes, adjuvanted with aluminum hydroxide. The trial was observer-blinded and randomized in a 2:1 ratio for intramuscular administration of Strep A vaccine or an alum-based comparator in healthy adult volunteers, at 0, 30 and 180 days. Primary outcome measures were assessments of safety, including assays for antibodies that cross-reacted with host tissues, and immunogenicity assessed by ELISA with the individual vaccine peptides and by opsonophagocytic killing (OPK) assays in human blood., Results: Twenty-three Strep A-vaccinated participants and 13 controls completed the study. The Strep A vaccine was well-tolerated and there was no clinical evidence of autoimmunity and no laboratory evidence of tissue cross-reactive antibodies. The vaccine was immunogenic and elicited significant increases in geometric mean antibody levels to 24 of the 30 component M antigens by ELISA. Vaccine-induced OPK activity was observed against selected M types of Strep A in vaccinated participants that seroconverted to specific M peptides., Conclusion: The Strep A vaccine was well tolerated and immunogenic in healthy adults, providing strong support for further clinical development. [ClinicalTrials.gov NCT02564237]., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elodie Pastural is a former project manager for PREVENT, a funder of the study. Luis H. Martin is a former officer of PREVENT. Scott Halperin is a member of the Board of Directors of PREVENT. James B. Dale is an inventor on patent applications licensed to, and owns shares of, Vaxent, a funder of the study. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: The use of gastroprotective agents has allowed significant progress in the prevention of upper gastrointestinal bleeding (UGIB) associated with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents. Nevertheless, some concerns remain regarding the gastroprotective dosage and treatment duration. Our aim was to study the effect of gastroprotective agents in UGIB induced by NSAIDs and single- or dual-antiplatelet therapy., Methods: A multicenter case-control study was conducted including 577 cases diagnosed with UGIB and 1343 sex-, age-, and hospital-matched controls. To estimate exposure to NSAIDs and gastroprotective agents, consumption was calculated for the 4 weeks prior to hospital admission in terms of defined daily doses (DDDs). Risk groups for UGIB induced by NSAIDs and single- or dual-antiplatelet therapy were defined as a function of each drug dose, use of gastrointestine-damaging drugs, and risk factors for UGIB. Odds ratios (ORs) with 95% confidence intervals (CIs) were adjusted for single- (model 1) and dual- (model 2) antiplatelet therapy., Results: Full adherence (> 0.80DDD) to proton pump inhibitors (PPIs) was the only gastroprotective therapy that significantly reduced the risk of UGIB, considering NSAID risk (OR: 0.53; 95% CI: 0.30-0.95) and dose (OR: 0.48; 95% CI: 0.27-0.87) with ORs adjusted for single-antiplatelet therapy (model 1) and NSAID risk (OR: 0.55; 95% CI: 0.31-0.98) and dose (OR: 0.49; 95% CI: 0.28-0.89) with ORs adjusted for dual-antiplatelet therapy (model 2)., Conclusions: These results reinforce the recommendation of adding a PPI at effective doses (full adherence) to prevent UGIB induced by NSAIDs, or single- or dual-antiplatelet therapy.

Accurate staging of oral squamous cell carcinoma (oral SCC) is essential. Some clinicians delay diagnostic biopsy until after magnetic resonance imaging (MRI). We retrospectively studied the clinical records and histopathological databases of 58 patients with SCC of the tongue; 39 had biopsy before MRI and 19 afterwards. In the group who had the biopsy first, eight were up-staged, nine were down-staged, and in 22 the T stage was accurate. In those who had MRI first, the corresponding figures were two, six, and 11, respectively. The time between initial biopsy and excision was significantly longer in the MRI group (43 days), than in the biopsy group (16 days) (p<0.001). Differences in staging between the two groups were not significant. Whether the biopsy was taken before or after MRI does not seem to affect the accuracy of clinical staging, and to delay biopsy until after staging may be unnecessary., (Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

An imaging concept is proposed for the phase identification and segmentation of elemental map images from energy dispersive spectroscopy. The procedure starts with presegmentation using common clustering algorithms, continues with automated identification of the chemical compositions, followed by their screening by professional expertise. The ultimate phases are finally clustered by applying a minimum Euclidean distance classifier. The potential, performance and limitations of the approach are presented on energy dispersive spectroscopy maps acquired by a scanning electron microscope and conducted on samples produced from cement clinker, natural rock and hydrated cement mortar. Nevertheless, the technique is suitable for arbitrary types of materials and general devices for energy dispersive spectroscopy acquisition. It is an approach for extending common energy dispersive spectroscopy analysis by means of visual examination and ratio plots towards quantitative rating., (© 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.)

Developing early detection biosensors for disease has been the long‒held goal of the Human Genome Project, but with little success. Conversely, the biological properties of the mitochondrion coupled with the relative simplicity of the mitochondrial genome give this organelle extraordinary functionality as a biosensor and places the field of mitochondrial genomics in a position of strategic advantage to launch significant advances in personalized medicine. Numerous factors make the mitochondrion organelle uniquely suited to be an early detection biosensor with applications in oncology as well as many other aspects of human health and disease. Early detection of disease translates into more effective, less expensive treatments for disease and overall better prognoses for those at greater risk for developing diseases.

Large-scale community-level behavior change programs designed to improve breastfeeding practices were implemented in Bolivia, Ghana, and Madagascar. These programs reached sizable populations: Bolivia, 1 million; Ghana, 3.5 million; and Madagascar, 6 million. Over 3 to 4 years, timely initiation of breastfeeding (within 1 hour of birth) increased from 56% to 74% (P < .001) in Bolivia, 32% to 40% (P < .05) in Ghana, and 34% to 78% (P < .001) in Madagascar. Marked increases in exclusive breastfeeding of infants 0 to 6 months of age were also documented: from 54% to 65% (P < .001) in Bolivia, 68% to 79% (P < .001) in Ghana, and 46% to 68% (P < .001) in Madagascar. In Ghana and Madagascar, significant results were seen within 1 year of community interventions. The authors conclude that large-scale programs designed to improve breastfeeding practices are feasible and should be a central component of any child survival strategy.

Background: Inhibition of platelet aggregation with parenteral glycoprotein (GP) IIb/IIIa receptor blockers can reduce the ischemic complications of angioplasty. Sustained efficacy and safety of protracted GP IIb/IIIa blockade with an orally administered agent have not previously been determined. This study is the first randomized, dose-ranging, single-blind, placebo-controlled trial of xemilofiban, an oral platelet GP IIb/IIIa receptor antagonist, administered to patients after intracoronary stent deployment. The pharmacodynamic efficacy of xemilofiban-induced platelet inhibition and clinical safety of this agent was evaluated during chronic therapy., Methods and Results: After elective intracoronary stent deployment, patients were randomized to receive placebo (250 mg ticlopidine P.O. BID) or xemilofiban in doses of 5, 10, 15, or 20 mg P.O. BID. All patients received 325 mg aspirin P.O. QD. Inhibition of ex vivo platelet aggregation in response to 20 micromol/L ADP and 4 microg/mL collagen was measured over time after the initial dose of study drug and at 1 and 2 weeks of chronic therapy. Study drug was discontinued after 2 weeks, and all patients were followed clinically for > or = 30 days. Oral xemilofiban resulted in a dose-dependent inhibition of platelet aggregation in response to both agonists that was sustained through 2 weeks of chronic therapy. Doses of xemilofiban required to achieve > or = 50% inhibition of platelet aggregation were > or = 10 mg, and the duration of inhibition was 8 to 10 hours. No significant hemorrhagic episodes or blood transfusions were observed in this trial., Conclusions: Oral xemilofiban in doses of > or = 10 mg produced > or = 50% inhibition of platelet aggregation in response to ADP and collagen for 8 to 10 hours after dosing. Platelet inhibition was sustained through 2 weeks of chronic therapy. The optimal duration of oral GP IIb/IIIa blockade to effectively suppress recurrent ischemic events after coronary intervention remains to be determined.

Heat shock protein synthesis was examined in mouse thymocytes at three stages of development: early embryonic thymocytes, which are CD4-CD8-, adult thymocytes, which are primarily CD4+CD8+, and mature spleen T cells, which are CD4+CD8- or CD4-CD8+. After either a 41 degrees C or 42 degrees C heat shock, the synthesis of the major heat-inducible protein (hsp68) was elevated during the first hour of recovery but then decreased abruptly in thymocytes from adult mice. In contrast, the synthesis of hsp68 continued for up to 4 h after heating embryonic mouse thymocytes or mature spleen T cells. The more rapid termination of the heat shock response in the adult thymocytes was not the result of either less heat damage or more rapid repair since the recovery of general protein synthesis was more severely delayed in these cells. As well, the double positive CD4+CD8+ cells were more sensitive to hyperthermia than either the double negative CD4-CD8- or single positive CD4+CD8- or CD4-CD8+ cells. Exposure of fetal thymus organ cultures to elevated temperature revealed that the double negative thymocytes were able to survive and differentiate normally following a heat shock treatment that was lethal for the double positive thymocytes. Exposure of thymocytes from adult mice to elevated temperatures induced apoptotic cell death. This was evident by the cleavage of DNA into oligonucleosome-sized fragments. Quantitation of the extent of DNA fragmentation and the number of apoptotic cells by flow cytometry demonstrated that the extent of apoptotic cell death was related to the severity of the heat stress. Double positive (CD4+CD8+) thymocytes are selected on the basis of their T-cell antigen receptor (TCR). Most of these cells are negatively selected and die within the thymus by an active process of cell deletion known as apoptosis. Restricting hsp synthesis in response to stress might be essential during developmental processes in which cell maturation is likely to result in death rather than functional differentiation.

Cluster of differentiation 1 (CD1) antigens are a family of non-MHC but Class I-like molecules that have been identified in humans and rodents. Although their function(s) remains unknown, it has been proposed that CD1 may present antigens to specific subsets of peripheral T-cells. We now provide evidence in support of this hypothesis through the demonstration by in situ hybridization that Paneth cells of the mouse intestine express CD1 mRNA. These cells are thought to be involved in the immunological regulation of intestinal flora and could accomplish this task through interactions with intestinal intraepithelial lymphocytes. The expression and localization of CD1 mRNA was confirmed by both autoradiographic and non-isotopic techniques. The relevance of these results to CD1 function as well as to Paneth cell biology is discussed.

A brief exposure to elevated temperatures elicits, in all organisms, a transient state of increased heat resistance known as thermotolerance. The mechanism for this thermotolerant state is unknown primarily because it is not clear how mild hyperthermia leads to cell death. The realization that cell death can occur through an active process of self destruction, known as apoptosis, led us to consider whether thermotolerance provides protection against this mode of cell death. Apoptosis is a common and essential form of cell death that occurs under both physiological and pathological conditions. This mode of cell death requires the active participation of the dying cell and in this way differs mechanistically from the alternative mode of cell death, necrosis. Here we show that mild hyperthermia induces apoptosis in a human leukemic T cell line. This is evidenced by chromatin condensation, nuclear fragmentation and the cleavage of DNA into oligonucleosome size units. DNA fragmentation is a biochemical hallmark of apoptosis and requires the activation of an endogenous endonuclease. The extent of DNA fragmentation was proportional to the severity of heat stress for cells heated at 43 degrees C from 30 to 90 minutes. A brief conditioning heat treatment induced a resistance to apoptosis. This was evident as a resistance to DNA fragmentation and a reduction in the number of apoptotic cells after a heat challenge. Resistance to DNA fragmentation developed during a recovery period at 37 degrees C and was correlated with enhanced heat shock protein (hsp) synthesis. This heat-induced resistance to apoptosis suggests that thermotolerant cells have gained the capacity to prevent the onset of this pathway of self-destruction. An examination of this process in heated cells should provide new insights into the molecular basis of cellular thermotolerance.

Substantial time delays from symptom onset to diagnosis and treatment of patients with acute myocardial infarction have been demonstrated. To determine the relative importance of prehospital mode of patient transport and the relative impact of emergency medical system transport with or without a prehospital cellular electrocardiogram (ECG) on hospital time delays to initiation of thrombolytic therapy, four prospective parallel groups of patients with acute myocardial infarction were evaluated. The median hospital time delay to treatment median (twenty-fifth and seventy-fifth percentiles) was 64 minutes (46 and 87 minutes, respectively, for twenty-fifth and seventy-fifth percentiles) for patients transported by private automobile ("walk-in"); 55 minutes (45 and 68 minutes, respectively) for patients transported by local ambulance; 50 minutes (38 and 81 minutes, respectively) for patients transported by the emergency medical system without a prehospital ECG; and 30 minutes (27 and 35 minutes, respectively) for patients transported by the emergency medical system who had a 12-lead ECG transmitted from the field. Patients transported by the emergency medical system were randomized to receive cellular telephone transmission of a prehospital 12-lead ECG. Specialized emergency medical system transport alone did not facilitate in-hospital initiation of thrombolytic therapy in patients with acute myocardial infarction when compared with those brought by local ambulance or by private automobile. A significant reduction in hospital time delay to treatment was observed only in patients transported by the emergency medical system who had cellular transmission of a prehospital 12-lead ECG from the field.

Coronary bypass surgery was performed prior to hospital discharge in 303 (22%) of 1387 consecutive patients enrolled in the TAMI 1 to 3 and 5 trials of intravenous thrombolytic therapy for acute myocardial infarction. Bypass surgery was of emergency nature (less than 24 hours from treatment with intravenous thrombolytic therapy) in 36 (2.6%) and was deferred (greater than 24 hours) in 267 (19.3%) patients. The indications for bypass surgery included failed angioplasty (12%); left main or equivalent coronary disease (9%); complex or multivessel coronary disease (62%); recurrent postinfarction angina (13%); and refractory pump dysfunction, mitral regurgitation, ventricular septal rupture or abnormal predischarge functional test (1% each). Although patients having bypass surgery were older (59.5 +/- 9.8 versus 56.0 +/- 10.2 years, (p less than 0.0001), had more extensive coronary artery disease (46% with three-vessel disease versus 11%, (p less than 0.0001), had more frequent diabetes mellitus (19% versus 15%, (p = 0.048), had more prior infarctions (p less than 0.0001), had more severe initial depression in global left ventricular ejection fraction (48.0 +/- 11.9% versus 51.8 +/- 11.9%, p = 0.0002), and regional infarct zone (-2.7 +/- 0.94 versus -2.5 +/- 1.1 SD/chord, p = 0.02) and noninfarct zone function (-0.36 +/- 1.8 versus 0.43 +/- 1.6 SD/chord, p less than 0.0001) than patients not having coronary bypass surgery, no difference in the incidence of death in hospital (7% surgical versus 6% nonsurgical) or death at long-term follow-up of hospital survivors (7% surgical versus 6% nonsurgical) was noted between groups. Surgical patients demonstrated a greater degree of recovery in left ventricular ejection fraction (3.4 +/- 9.8% versus 0.16 +/- 8.5%, p = 0.036) and infarct zone regional function (0.71 +/- 1.1 versus 0.34 +/- 0.99 SD/chord, p = 0.001) when immediate (90 minutes following initiation of thrombolytic therapy) and predischarge (7 to 14 days after treatment) contrast left ventriculograms were compared than did patients who received only intravenous thrombolytic therapy with or without coronary angioplasty. These data suggest a beneficial influence of coronary bypass surgery on left ventricular function and possibly on the clinical outcome of patients initially treated with intravenous thrombolytic therapy for acute myocardial infarction.

The cluster of differentiation-1 (CD1) antigens are major histocompatibility complex (MHC) class I-like glycoproteins belonging to the immunoglobulin supergene family. Initially described in humans, more recently putative CD1 encoding genes have been identified in several other species, including the mouse where it has been clearly demonstrated that CD1 mRNA is expressed. However, in the mouse both its unusually wide tissue distribution and the prevalence of incompletely spliced RNA have raised the possibility that the mRNA did not encode a functional protein. We have utilized a rabbit polyclonal antiserum raised against an Escherichia coli-expressed recombinant murine CD1 fusion protein to characterize the murine CD1 protein. Here we demonstrate that the antiserum binds specifically to a set of glycoproteins (49,000-55,000 MW) which contain a common core protein with both a size (36,000 MW) and tissue distribution in accordance with those predicted. During thymic ontogeny, this protein is highly expressed by Day 14 of embryonic development and persists into adulthood, while its pattern of expression in other organs changes significantly during development. Thus, the mouse provides an amenable model system for the study of CD1 function.

The incidence of minimal residual atherosclerotic coronary obstruction after successful intravenous thrombolytic therapy was evaluated in 799 patients with acute myocardial infarction. Minimal residual coronary obstruction (less than or equal to 50%) was observed on selective coronary angiography performed 90 min after initiation of thrombolytic therapy in 43 patients (5.5%). In 42 other patients (5.4%), a greater than 50% but less than 100% residual stenosis noted at 90 min demonstrated further resolution of obstruction to less than 50% at an angiographic follow-up study 7 to 10 days later. Patients with minimal residual coronary obstruction were significantly younger (52 +/- 10.7 versus 56.7 +/- 10 years; p = 0.002) and had less multivessel coronary disease (p less than 0.001), better initial left ventricular ejection fraction (54 +/- 12% versus 50.2 +/- 11.4%; p = 0.006) and a lower in-hospital mortality rate (1% versus 7%; p = 0.04) than did patients who had a significant (greater than 50%) residual coronary obstruction after intravenous thrombolysis. Long-term follow-up study of patients with a minimal coronary lesion (average 1.5 +/- 0.6 years) and those with significant residual stenosis (average 1.6 +/- 0.7 years) demonstrated that the incidence of death (2.4% in patients with minimal stenosis versus 3.5% in those with significant stenosis) and recurrent myocardial infarction (5% each) were similar in both groups. New strategies are needed to prevent coronary rethrombosis in patients with minimal atherosclerosis after thrombolytic therapy for acute myocardial infarction.

To establish the magnitude of prehospital and hospital delays in initiating thrombolytic therapy for acute myocardial infarction, the time from telephone 911 emergency medical system (EMS) activation to treatment and its components were analyzed from eight separate ongoing trials. This included estimates of ambulance response time, prehospital evaluation and treatment time, and time from admission to the hospital to initiation of thrombolytic therapy. The average time from EMS activation to patient arrival at the hospital was prospectively determined to be 46.1 +/- 8.2 minutes in 3715 patients from eight centers. The time from admission to the hospital to initiation of thrombolytic therapy was retrospectively determined to be 83.8 +/- 55.0 minutes in a separate group of 730 patients from six centers. Both the prehospital and hospital time delays were much longer than those perceived by paramedics and emergency department directors. Shorter hospital time delays were observed in patients in whom a prehospital ECG was obtained as part of a protocol-driven prehospital diagnostic strategy and a diagnosis of acute infarction made before arrival at the hospital (36.3 +/- 11.3 minutes in 13 patients). These results show that the magnitude of time required to evaluate, transport, and initiate thrombolytic therapy will preclude initiation of treatment to most patients within the first hour of symptoms. Implementation of a protocol-driven prehospital diagnostic strategy may be associated with a reduction in time to thrombolytic therapy.

The CD1 human antigens are a family of at least three components, CD1a, CD1b, and CD1c, that are characteristic of the cortical stage of thymocyte maturation. CD1a was originally named HTA1 or T6 and thought to be the human equivalent of mouse Tla. The genes coding for all three have now been identified by transfection into mouse cells. The transfectants express the surface antigens that can then be recognized by the corresponding cluster of monoclonal antibodies used to define the three members of CD1. The full sequence of the genomic DNA is described for all three. The intron-exon structure of CD1a is deduced by comparison with a near-full-length cDNA clone. Similar structures are proposed for the other two, largely based on sequence homology. An unusually long 5'-untranslated exon (280 bases long) is highly conserved between the three genes, suggesting an important but unknown function. CD1c has a duplicated form of this exon that is thought to be spliced out. The major homology between the three antigens is in the beta 2-microglobulin-binding domain. The general relatedness to major histocompatibility complex class I and class II molecules is significant but low, with no section of higher homology to mouse Tla.

The emergency department plays a pivotal role in the identification, selection, and treatment of candidates for thrombolytic therapy. Organized treatment protocols offer direction to the emergency staff and enhance their efficiency and success. However, the process of drug administration is not a one person job. It requires the efforts of a "support team," all of whom must be educated regarding protocol goals and expectations. With the creation of special tools, implementation becomes an achievable task, and staff demands are reduced proportionately. As patient outcomes are known, it is essential to pass these data on to all team members. There is no greater payback for a dedicated caregiver than to realize his positive impact on patient outcome.