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The epithelial-mesenchymal transition (EMT) and colorectal cancer progression.

During embryonic development, epithelial cells must escape the structural constraints imposed by tissue architecture and adopt a phenotype more amenable to cell movement, a process known as the epithelial-mesenchymal transition (EMT). The progression of carcinomas to invasive and metastatic disease may also involve localized occurrences of EMT. However, data that support the actual occurrence of EMT in specific carcinomas and the relevance of this process to the progression of these tumors had been scant. This review highlights recent studies that substantiate the importance of the EMT to colorectal carcinoma. Specifically, a novel model for studying the EMT of colorectal carcinoma has been used to gain insight into the nature of the EMT itself and to identify molecular events that contribute to disease progression. Although loss of E-cadherin function is a primal event for the EMT, the expression of specific integrins such as alpha(v)beta6 as a consequence of the EMT enables invasive cells to interact with interstitial matrices and to sustain activation of TGF-beta. Of note, alpha(v)beta6 expression in tumors is a marker of cells that have undergone an EMT and it is prognostic for tumors that will progress more rapidly to terminal disease. The EMT also induces autocrine signaling involving VEGF and Flt-1 that enable invasive cells to become 'self-sufficient' for survival. Thus, the EMT appears to be an integral component of colorectal cancer progression and its analysis can yield novel targets for prognosis and therapy.

Animals↗

Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT.

Epithelial-mesenchymal transformation (EMT) is an important process in development that is characterized by loss of E-cadherin, beta-catenin relocalization, and acquisition of elongated cell shape and ability to invade ECM. beta-catenin has been shown to activate LEF-1 transcription during EMT induced in vitro by c-Fos. Here, we ask whether or not LEF-1 directly introduced into epithelial cells in an adenovirus construct can induce EMT. In normal epithelial cell lines, such as HCE and MDCK cells, that contain functional APC, nuclear beta-catenin induced by exogenous LEF-1 is rapidly exported and EMT is not induced. Leptomycin-B blocks beta-catenin nuclear export, but no EMT occurs due to toxicity. Addition of Wnt-1 to normal epithelial cell lines stabilizes cytoplasmic beta-catenin that LEF-1 then transports to nuclei, causing a small amount of EMT. Our experiments demonstrated, however, that overexpressed LEF-1 upregulates nuclear beta-catenin and promotes dramatic EMT in DLD-1 epithelial tumors that retain nuclear beta-catenin. This EMT is reversible if the LEF-1 virus is removed. Thus, our results demonstrate that LEF-1 can induce EMT directly when its transcription activity is activated by stable nuclear beta-catenin. Normal adult epithelial cells appear to use APC to keep beta-catenin out of the nucleus, thereby avoiding pathologies such as metastases due to LEF/beta-catenin-induced EMT.

3T3 Cells↗

Protection of bone-marrow granulocyte-macrophage colony-forming units in mice bearing in vivo alkylating-agent-resistant EMT-6 tumors.

The survival of bone-marrow granulocyte-macrophage colony-forming units (CFU-GM), an alkylating-agent-sensitive normal tissue, was assessed in mice bearing the EMT-6 parental tumor or the in vivo resistant EMT-6/CDDP, EMT-6/CTX, EMT-6/Thio, and EMT-6/Carbo tumors. The survival pattern of the bone-marrow CFU-GM recapitulated the survival of the tumor cells, mimicking the development of resistance and reversion to sensitivity upon removal of the selection pressure for each of the four alkylating agents. When the EMT-6 parental tumor was implanted in the opposite hind limb of animals bearing the EMT-6/CDDP or EMT-6/CTX tumor, the survival of the parental tumor cells after treatment of the animals with the appropriate antitumor alkylating agent was enhanced. The EMT-6/CDDP tumor was cross-resistant to CTX and high-dose L-PAM, whereas the EMT-6/CTX tumor was somewhat resistant to CDDP and markedly sensitive to VP-16. In each case, the survival pattern of the bone-marrow CFU-GM reflected the survival of the tumor cells. These results indicate that the presence of an alkylating-agent-resistant tumor in an animal can affect the drug response of tissues distal to that tumor.

Alkylating Agents↗

The prevalence of occupational injuries in EMTs in New England.

OBJECTIVE: To characterize the prevalence and morbidity of injuries to emergency medical technicians EMTs) in New England [United States]. DESIGN: A survey was mailed to a 2% random sample of all registered EMTs in the six New England States. The identity of the EMTs remained anonymous, and a second mailing was used to improve return rate. The EMTs were requested to recall events that occurred during the previous six months. RESULTS: A total of 439 of the 786 (56%) surveys were returned representing 13,875 hours of duty time in the six-month period. Seventy-one percent of the EMTs were male with a mean age of 35 years. Sixty-six percent were basic-EMTs. Injury attack rates (number of injuries/100 EMTs/6 months) were: stress, 11.2; back, 10.5; extremity, 9.8; assault, 8.4; ambulance collision, 4.1; hearing loss, 2.5; and eye injury, 1.4. Twelve percent of the EMTs were injured more than once in the six-month period. The paramedics more frequently were involved in ambulance collisions, suffered from stress, and were less likely to injure their back. There were minor interstate differences. Disability due to back injury affected 2.5% of those surveyed, four EMTs lost duty time secondary to an assault, and 0.5% of the EMTs were out of work due to stress. CONCLUSIONS: This survey begins to characterize the occupational risks of EMTs. The prevalence of back injuries, assault, stress, and extremity injuries seems to be too high. Educational programs and preventive interventions should be designed to minimize back injuries, stress, and assault. There is a need for more research nationwide in order to better characterize these injuries.

Accidents, Occupational↗

Outcomes of sudden cardiac arrest treated with defibrillation by emergency medical technicians (EMT-Ds) or paramedics in a two-tiered urban EMS system.

OBJECTIVE: Controversy exists as to the effectiveness of defibrillation by emergency medical technicians (EMT-Ds) in reducing mortality from cardiac arrest in two-tiered EMS systems. This study was performed to assess the impact of EMT-Ds on outcome of sudden cardiac death in a small, urban, modified two-tiered EMS system. METHODS: This was a retrospective, unmatched case-control study comparing the outcomes of patients suffering sudden cardiac death treated by EMT-Ds with paramedic (EMT-P) backup with the outcomes of patients treated by EMT-Ps as first responders. Outcomes were defined as survival to the following endpoints: hospital admission, hospital discharge, and discharge with normal neurologic function (neurologic survival). Differences between groups were considered significant if p < or = 0.05 by Fisher's exact test or t-test. RESULTS: Three hundred twenty-two patients suffered out-of hospital sudden cardiac deaths over a three-year period and met study inclusion criteria. There were no significant differences in mean age, sex distribution, or incidence of ventricular fibrillation as the presenting rhythm between the groups. Rates of survival to admission, survival to discharge, and neurologic survival were 25.8%, 8.1%, and 5.6%, respectively. Corresponding survival rates for 46 patients treated first by EMT-Ds were 19.6%, 8.7%, and 4.3%. For 276 patients treated by EMT-Ps as first responders, the rates were 26.8%, 8.0%, and 5.8%. There were no significant differences in survival rates between the two response modes, despite a significantly shorter response interval for EMT-Ds (3.6 +/- 1.8 min, vs 4.6 +/- 2.0 min for EMT-Ps). There were likewise no significant differences in survival rates between the two response modes when only patients in ventricular fibrillation or ventricular tachycardia were considered. There were no significant differences in survival rates grouped by presenting rhythm, with the exception of 9.6% neurologic survival in witnessed ventricular fibrillation as compared with 0% in asystole. CONCLUSION: EMT defibrillation had no impact on outcome of sudden cardiac death in this small, urban, two-tiered EMS system. Survival rates were similar to those reported for other such systems. However, power to detect significant differences was low, and further study is indicated. Controlled multicenter trials are recommended.

Aged↗

Human Emt tyrosine kinase is specifically expressed both in mature T-lymphocytes and T-cell associated hematopoietic malignancies.

The pattern of expression of the human Emt tyrosine kinase was established in healthy individuals and hematological malignancies by RT-PCR from bone marrow and blood samples, fractionated into T-cells, B-cells, monocytes, granulocytes and thrombocytes. Previously studied mostly in murine samples or established human cell lines, the in vivo correlation was here further clarified. In hematopoietic cells, expression of the EMT gene was associated with T-cell fractions, but Emt was not detected in cord blood CD34+ cells. In fetal tissues, Emt mRNA was strongly expressed in thymus, no expression could be detected in non-hematopoietic tissues. The expression pattern of the 48 malignant bone marrow samples (23 ALL, 1 PLL, 9 AML, 7 CLL and 8 CML cases) paralleled the findings from normal hematopoietic cells: 9/11 T cell associated ALLs, as well as one T-PLL sample, but only 1/12 samples of B-ALL expressed Emt markedly. Only minor signs of Emt expression could be shown in the AML samples, while CML and CLL samples were totally devoid of expression. In addition the Emt protein could be detected by Western blotting from T-lymphocytes and T-cell associated ALL, corresponding to mRNA expression. In conclusion, Emt (Itk) is T-cell associated both in normal and leukemic cells, but is not expressed in cord blood CD34+ cells, suggesting that Emt expression is switched on only later in T-cell development. In addition, an association between Emt and CD2 expression remains even in malignancies.

Adolescent↗

Improved prehospital pediatric ALS care after an EMT-paramedic clinical training course.

The objective was to determine the association between the performance rates of pediatric advanced life-support procedures, intubation and vascular access, by emergency medicine technician-paramedics (EMT-P), and introduction of an EMT-P pediatric advanced life support (PALS) clinical course. Prehospital EMT-P care records from January 1990 to December 1991 were retrospectively reviewed to determine endotracheal intubation and vascular access performance rates. These rates were compared with intubation and vascular access performance rates by EMT-Ps from January 1983 to June 1985. In 1986, an EMT-P PALS clinical course was introduced that included rotations during which an EMT-P trainee performed endotracheal intubation of children, under the supervision of a pediatric anesthesiologist, and vascular access, under the supervision of pediatric emergency medicine nurses and physicians. The trainees and all active EMT-Ps were taught the intraosseous infusion procedure. During January 1990 to December 1991, 193 children received prehospital endotracheal intubation attempts and 167 (87%) were intubated. Intubation performance rates for 90 children younger than 18 months of age was 90% and was 83% for 103 children > or = 18 months of age. Vascular access, intravenous or intraosseous, was established in 130 (73%) of the children; no attempt was made in 14 children. The vascular access performance rate was 64% for children younger than 18 months of age and 79% for children > or = 18 months old. Intubation performance rates of EMT-Ps before the EMT-P PALS clinical course (January 1983 to June 1985) were 48% for children younger than 18 months of age and 85% for children > or = 18 months old.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Results of a 4-hour endotracheal intubation class for EMT-basics.

STUDY OBJECTIVE: In 1994, the Department of Transportation made endotracheal intubation an optional EMT-Basic skill. To data, there have been no studies addressing the ability of this group to learn or perform this skill. We used a standarized mannequin test to perform a prospective evaluation of this intubation skills of basic EMTs immediately after a 4-hour course on endotracheal intubation. We hypothesized that the intubation success rates would be comparable with those of other types of providers newly trained in this skill. METHODS: Eighty-three EMTS were selected/recruited from four EMS provider agencies. Ninety-six percent of the EMTs were men, and the average age was 38 years; average length of EMT experience was 9.4 years. Training was provided in classes of 6 to 14 persons and included 1 hour of didactic instruction, a 1-hour demonstration of intubation techniques, and 90 minutes of supervised practice with the mannequins in groups of 2 to 4 persons. Testing followed American Heart Association guidelines. Interrater reliability of test criteria was assessed. RESULTS: Ninety-four percent (95% confidence interval 86% to 98%) of the EMTs passed the examination by intubating the mannequin within 35 seconds within 3 attempts. Of the successful EMTs, 94% succeeded on their first attempt, 3% on their second attempt, and 3% on their third. There were three esophageal intubations; all were detected immediately. Interrater agreement was 100% on the pass/fail decision. CONCLUSION: This 4-hour class trained basic EMTs to perform endotracheal intubation on mannequins with a success rate of 94%. Further research should confirm the ability of EMT-Basics to detect esophageal intubation and address the retention of intubation skills, the applicability of these skills to the field, and the components of this course that were responsible for its success.

Adult↗

Ability of EMT-Bs to determine which wounds can be repaired in the field.

INTRODUCTION: In certain emergency medical services (EMS) systems, emergency medical technicians-paramedics (EMT-Ps) repair lacerations in the field. This practice is supported by studies showing equivalence between nonphysicians and physicians regarding infection rates and cosmetic outcomes. OBJECTIVE: To evaluate the ability of emergency medical technicians-basic (EMT-Bs) to identify wounds repairable in the field or requiring tetanus prophylaxis. METHODS: This was a prospective, double-blind convenience sample study at an urban teaching hospital. Eleven EMT-B volunteers, trained by a one-hour lecture and bedside teaching, evaluated lacerations for prehospital repair by answering three questions: Could this wound be repaired in the field, and if no, why not? If on an adult forearm, could this wound be repaired in the field, and if no, why not? Does this patient need tetanus prophylaxis, and if no, why not? A blinded principal investigator also answered these questions, and a person uninvolved in the study correlated results. Statistical evaluation was performed using kappa statistics. RESULTS: The EMT-Bs identified 17 of 17 potentially repairable wounds and 163 of 163 wounds excluded from prehospital repair. Placing the wound on the forearm, the EMT-Bs identified 82 of 87 potentially repairable wounds and 93 of 93 wounds excluded from prehospital repair (sensitivity 94%, specificity 100%, positive predictive value 100%, negative predictive value 95%, kappa 0.97). For five of five wounds, physicians disagreed with the EMT-Bs and thought the wound repairable prehospital. The EMT-Bs and physicians agreed on individual wound exclusion criteria in 207 of 239 (86.6%) instances. Finally, the EMT-Bs identified 108 of 108 patients requiring tetanus prophylaxis. CONCLUSIONS: Basic EMTs can accurately identify wounds eligible for prehospital repair and/or requiring tetanus prophylaxis.

Adolescent↗

EMT knowledge of ambulance traffic laws.

OBJECTIVE: The safe operation of ambulances using warning lights and siren requires both the public and emergency medical technician (EMT) drivers to understand and obey relevant traffic laws. However, EMTs may be unfamiliar with these laws. The purpose of this study was to evaluate EMTs' knowledge of traffic laws related to the operation of ambulances with warning lights and sirens. METHODS: North Carolina EMTs participating in a statewide EMS conference October 6-8, 1995, completed a five-question survey. Knowledge of ambulance speed limits, yielding at intersections, yielding in roadways, and following distances was assessed using a multiple-choice format. Demographic data pertaining to EMT age, years of experience, paid vs volunteer status, driver's education courses, and past accident involvement were also obtained. Proportions were compared using chi-square analysis, alpha = 0.05. RESULTS: Two-hundred ninety-three of 308 (95%) EMTs attending the conference completed questionnaires. The median number of correct responses to the five knowledge questions was 1 (range 0-4). Thirty-three percent of the EMTs knew that other vehicles are required by law to yield while either approaching or being overtaken by an ambulance with warning lights and sirens; 2% knew that due regard for safety is the only requirement of an ambulance approaching a red light at an intersection; 14% knew that the minimum following distance behind an ambulance is one city block; and 28% knew that there is no speed limit on ambulances with warning lights and sirens. Respondents were more likely to score above the median if they had taken one or more emergency driver's education courses or had nine years or more of EMS experience. CONCLUSION: In this sample, EMT knowledge of basic traffic laws pertaining to ambulance operation is poor. Emergency driver's education courses and increased experience appear to be related to increased knowledge scores. Increased training for EMTs about traffic laws may improve the safe operation of ambulances.

Accidents, Traffic↗

TGF-beta1-induced EMT can occur independently of its proapoptotic effects and is aided by EGF receptor activation.

Apoptosis and epithelial-mesenchymal transdifferentiation (EMT) occur in stressed tubular epithelial cells and contribute to renal fibrosis. Transforming growth factor (TGF)-beta(1) promotes these responses and we examined whether the processes were interdependent in vitro. Direct (caspase inhibition) and indirect [epidermal growth factor (EGF) receptor stimulation] strategies were used to block apoptosis during TGF-beta(1) stimulation, and the subsequent effect on EMT was assessed. HK-2 cells were exposed to TGF-beta(1) with or without preincubation with ZVAD-FMK (pan-caspase inhibitor) or concomitant treatment with EGF plus or minus preincubation with LY-294002 (PI3-kinase inhibitor). Cells were then assessed for apoptosis and proliferation by flow cytometry, crystal violet assay, and Western blotting. Markers of EMT were assessed by microscopy, immunofluorescence, real-time RT-PCR, Western blotting, PAI-1 reporter assay, and collagen gel contraction assay. TGF-beta(1) caused apoptosis and priming for staurosporine-induced apoptosis. This was blocked by ZVAD-FMK. However, ZVAD-FMK did not prevent EMT following TGF-beta(1) treatment. EGF inhibited apoptosis and facilitated TGF-beta(1) induction of EMT by increasing proliferation and accentuating E-cadherin loss. Additionally, EGF significantly enhanced TGF-beta(1)-induced collagen I gel contraction. EGF increased Akt phosphorylation during EMT, and the prosurvival effect of this was confirmed using LY-294002, which reduced EGF-induced Akt phosphorylation and reversed its antiapoptotic and proproliferatory effects. TGF-beta(1) induces EMT independently of its proapoptotic effects. TGF-beta(1) and EGF together lead to EMT. EGF increases proliferation and resistance to apoptosis during EMT in a PI3-K Akt-dependent manner. In vivo, EGF receptor activation may assist in the selective survival of a transdifferentiated, profibrotic cell type.

Apoptosis↗

Transforming growth factor beta (TGFbeta) signalling in palatal growth, apoptosis and epithelial mesenchymal transformation (EMT).

Formation of the medial edge epithelial (MEE) seam by fusing the palatal shelves is a crucial step of palate development. The opposing shelves adhere to each other at first by adherens junctions, then by desmosomes in the MEE. The MEE seam disappears by epithelial mesenchymal transformation (EMT), which creates confluence of connective tissue across the palate. Cleft palate has a mutifactorial etiology that often includes failure of adherence of apposing individual palatal shelves and/or EMT of the MEE. In this review, we first discuss TGFbeta biology, including functions of TGFbeta isoforms, receptors, down stream transcription factors, endosomes, and signalling pathways. Different isoforms of the TGFbeta family play important roles in regulating various aspects of palate development. TGFbeta1 and TGFbeta2 are involved in growth, but it is TGFbeta3 that regulates MEE transformation to mesenchyme to bring about palatal confluence. Its absence results in cleft palate. Understanding of TGFbeta family signalling is thus essential for development of therapeutic strategies. Because TGFbeta3 and its downstream target, LEF1, play the major role in epithelial transformation, it is important to identify the signalling pathways they use for palatal EMT. Here, we will discuss in detail the mechanisms of palatal seam disappearance in response to TGFbeta3 signalling, including the roles, if any, of growth and apoptosis, as well as EMT in successful MEE adherence and seam formation. We also review recent evidence that TGFbeta3 uses Smad2 and 4 during palatal EMT, rather than beta-Catenin, to activate LEF1. TGFbeta1 has been reported to use non-Smad signalling using RhoA or MAPKinases in vitro, but these are not involved in activation of palatal EMT in situ. A major aim of this review is to document the genetic mechanisms that TGFbeta uses to bring about palatal EMT and to compare these with EMT mechanisms used elsewhere.

Animals↗

Spirituality of EMTs: a study of the spiritual nature of EMS workers and its effects on perceived happiness and prayers for patients.

INTRODUCTION: There is reason to believe that traumatic events experienced on the job make emergency medical services (EMS) workers more skeptical about their spiritual beliefs. Little is known about the spiritual lives and experiences of emergency medical technicians (EMTs). No studies have measured the responses of EMTs to the spiritual needs of their patients. PURPOSE: This study investigates whether EMS workers are less spiritual than the average U.S. citizen, and what effect this has on prayer for patients and perceived happiness. METHODS: Data were collected in a major metropolitan EMS system from 125 EMTs and paramedics through a questionnaire about their beliefs and behaviors regarding their spirituality. Pearson product-moment correlation coefficients (r) were used to analyze variables. The religious attitudes of EMTs were compared with those of the general population as defined in the Gallup studies. RESULTS: Ninety-one percent of the EMS workers interviewed and 94% of Gallup's sample of the general population said they believe in God. The findings on other measures in the EMT sample also were very similar to those defined in the general population. Of the EMTs, 60% said they never have doubted the existence of God. Eighty-four percent believe God still works miracles, and 80% of the EMTs believe in life after death. Eighty-seven percent of EMS workers pray; 62% pray for their patients, and 54% pray for their coworkers. Frequency of church or synagogue attendance is positively and significantly correlated with the degree of perceived life happiness (r = 0.226, p < 0.025 > 0.005). Frequency of prayer also is correlated positively to perceived life happiness (r = 0.182, p < 0.025 > 0.005). CONCLUSION: Emergency medical services workers are interested and willing to talk about their spiritual lives. They do have more doubts about the existence of God than does the average civilian, but are just as spiritual. Those EMTs with more active spiritual lives perceive themselves as happier. The majority of EMS workers pray for their patients.

Adult↗

Src activation is not necessary for transforming growth factor (TGF)-beta-mediated epithelial to mesenchymal transitions (EMT) in mammary epithelial cells. PP1 directly inhibits TGF-beta receptors I and II.

Epithelial to mesenchymal transitions (EMTs) are key events during embryonic development and cancer progression. It has been proposed that Src plays a major role in some EMT models, as shown by the overexpression of viral Src (v-Src) in epithelial cells. It is clear that Src family kinases can regulate the integrity of both adherens junctions and focal adhesions; however, their significance in EMT, especially in the physiological context, remains to be elucidated. Here we showed that Src is activated in transforming growth factor-beta1 (TGF-beta1)-mediated EMT in mammary epithelial cells and that the Src family kinase inhibitor, PP1, prevents EMT. However, neither a more specific Src family kinase inhibitor, SU6656, nor a dominant-negative Src inhibited TGF-beta1-mediated EMT, leading us to speculate that Src activation is not an essential component of TGF-beta1-mediated EMT. Unexpectedly, PP1 prevented Smad2/3 activation by TGF-beta1, whereas SU6656 did not. Most interestingly, an in vitro kinase assay showed that PP1 strongly inhibited the TGF-beta receptor type I, and to a lesser extent, the TGF-beta receptor type II. Taken together, our data indicated that PP1 interferes with TGF-beta1-mediated EMT not by inhibiting Src family kinases but by inhibiting the Smad pathway via a direct inhibition of TGF-beta receptor kinase activity.

Activin Receptors, Type I↗

EMTs' attitudes' toward death before and after a death education program.

OBJECTIVE: To test the hypothesis that emergency medical technicians' (EMTs') attitudes toward death will change after exposure to a death education program. METHODS: A convenience sample of 83 rural EMTs participated in this pretest-posttest study after exposure to an educational program related to death. Intact groups of EMTs were randomly assigned to one of three conditions. The short-intervention group received a two-hour class solely on making death notifications. The long-intervention group received a 16-hour, two-day workshop based on the Emergency Death Education and Crisis Training (EDECT(SM)) program. The control group received a program about toxicology. Each participant completed a questionnaire with items structured in a Likert five-point format with "strongly agree" and "strongly disagree" as the anchors. RESULTS: Before the training programs, most (77%) participants reported that an EMT's actions impact the family's grief. Less than half (43%) reported that an EMT's role should include making a death notification. The majority (84%) reported that their training was inadequate to make a death notification or to help the family with their grief. Most (84%) felt uncomfortable making a death notification. Those EMTs in the long-intervention group were significantly more likely (92%) to feel that their training was adequate after the intervention when compared with those EMTs in the short-intervention group (43%) or those in the control group (21%). CONCLUSION: The data showed that EMTs' attitudes toward death changed after exposure to a training program about death.

Attitude of Health Personnel↗

Molecular characterization of the in vivo alkylating agent resistant murine EMT-6 mammary carcinoma tumors.

The expression of several early-response genes and genes associated with malignant disease was assessed in the EMT-6/parent tumor and the EMT-6/CTX and EMT-6/CDDP in vivo resistant tumor lines growing as tumors or as monolayers in culture. In the absence of treatment the levels of mRNA for the genes c-jun, c-fos, c-myc, Ha-ras and p53 were increased in the EMT-6/CTX and EMT-6/CDDP as compared with the EMT-6/parent tumor, whereas the expression of erb-2 was similar in all three tumors. Although the cells from each of the three tumors show increased expression of early response genes after exposure to cisplatin (CDDP; 100 microM, 2 h) or 4-Hydroxyperoxycyclophosphamide (4-HC; 100 microM, 2 h) in culture, in mRNA extracted from tumor tissue these changes are absent or very small. Both C-jun and erb-2 were detectable in liver. There was increased expression of both of these genes in the livers of tumor-bearing animals as compared with non-tumor-bearing animals. The highest expression of both c-jun and erb-2 occurred in the livers of animals bearing the EMT-6/CDDP tumor. Treatment of the animals with CDDP or cyclophosphamide, in general, resulted in increased expression of both genes at 6 h post treatment. The increased expression of these genes may impart metabolic changes in the tumors and/or hosts that contribute to the resistance of these tumors to specific antitumor alkylating agents.

Alkylating Agents↗

EMT-defibrillation: the Wisconsin experience.

The survival rate for patients with prehospital cardiac arrest has improved in some communities with early defibrillation by emergency medical technician-defibrillators (EMT-Ds). In rural areas, previous studies on survival with defibrillation by EMT-Ds have been variable. We conducted an EMT-D study to determine effectiveness in various prehospital settings. Sixty-four ambulance services from communities ranging in size from rural areas to city suburbs participated in our prospective study. EMTs were trained in rhythm recognition and the use of a manual defibrillator during a standardized 20-hour course. Over 18 months, data were collected locally for central analysis. Five hundred sixty-six patients with primary cardiac arrest were included in our study: 36 (6.4%) survived. Retrospective review revealed survival before EMT-D implementation to be 3.6% (P less than .02). Three hundred four patients (54%) had an initial rhythm of ventricular fibrillation, with 33 (11%) surviving. The survival rate for EMT-D-witnessed arrest with an initial rhythm of ventricular fibrillation was 42%. Patients with asystole were countershocked in our study; however, there were no survivors from this group. The neurologic status of survivors at time of hospital discharge was normal in 72%. The average response time, defined as time of emergency medical services activation to the time of EMT-D arrival, was 7.3 +/- 5.8 and 3.7 +/- 2.0 minutes for nonsurvivors and survivors, respectively (P less than .002). There were no survivors when the response time was more than eight minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

EMT domestic violence knowledge and the results of an educational intervention.

The objective of this study was to determine levels of knowledge regarding domestic violence (DV), and the effectiveness of formal instruction about DV. A general knowledge survey of DV was given before and approximately 4 to 6 months after 3 hours of instruction given by Emergency Medicine and Law Enforcement faculty. A Emergency medical service (EMS) consisting of 73% paramedic-level providers in a metropolitan urban/suburban area. Differences in DV knowledge before and after the instruction were the main outcome measures. In the preinstruction series, 46 emergency medical technicians (EMTs) participated. After the instruction 19 EMTs participated (42%). Thirty-five percent of EMTs before instruction and 37% after instruction correctly identified the prevalence of DV against women as 15% to 30%. Thirty-five percent of EMTs before instruction and 63% after instruction (P < .05) correctly identified the prevalence of DV against men as 0% to 15%. Before instruction 54% knew that DV is equal among races, and 79% after instruction (P < .05). Before instruction 37% of EMTs knew that DV is equal in different socioeconomic groups and 68% after instruction (P < .05). The percent of EMTs who knew that the victim is not responsible for the abuse was 50% before instruction and 89% after instruction (P < .05). Before instruction, the results on a knowledge questionnaire were 54% correct, after instruction, results improved to 71% correct. Improvement in understanding of DV was shown for 4 of 11 questions after 3 hours of instruction. These results indicate the need for more instruction on DV for EMTs.

Adult↗