Analysis of homozygous TGF beta 1 null mouse embryos demonstrates defects in yolk sac vasculogenesis and hematopoiesis.
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Animals↗
Biomedical subjects
J S Martin
Publications and source records attributed to J S Martin.
Confounding variables affecting in vitro fertilization success: a decade of experience.
PURPOSE: To evaluate etiology of infertility, female age, ovarian response and stimulation protocol in affecting in vitro fertilization (IVF) success. METHODS: Retrospective analysis was used. Computer records of all 5209 cycles initiated in 2391 couples from February 1, 1984 to December 31, 1993 were analyzed. RESULTS: There were 644 intrauterine, 24 solely ectopic and 7 heterotopic pregnancies. Pregnancy rates increased with number of embryos transferred with a significant increase still found between transfer of three or four embryos. Multiple gestations also increased in association with an increasing number of embryos transferred. Pregnancy rates per cycle did not decline with repeated cycles. Reduced pregnancy rates were associated with a primary diagnosis of male infertility. Covariates associated with a better pregnancy rate were younger age of the female partner or higher peak preovulatory serum estradiol. Routine administration of GnRH-agonist was associated with a reduced cycle cancellation rate, an increase in oocytes retrieved and an improved pregnancy rate. CONCLUSIONS: Couples with male infertility and increased female age should be counselled regarding the reduced prognosis for success.
Age Factors↗
Resource utilization in treatment of acute myocardial infarction: staff-model health maintenance organization versus fee-for-service hospitals. The MITI Investigators. Myocardial Infarction Triage and Intervention.
OBJECTIVES: This study sought to compare the use of invasive procedures and length of stay for patients admitted with acute myocardial infarction to health maintenance organization (HMO) and fee-for-service hospitals. BACKGROUND: The HMOs have reduced costs compared with fee-for-service systems by reducing discretionary admissions and decreasing hospital length of stay. It has not been established whether staff-model HMO hospitals also reduce the rate of procedure utilization. METHODS: Using data from a retrospective cohort, we performed univariate and multivariate comparisons of the use of cardiac procedures, length of stay and hospital mortality in 998 patients admitted to two staff-model HMO hospitals and 7,036 patients admitted to 13 fee-for-service hospitals between January 1988 and December 1992. RESULTS: The odds of undergoing coronary angiography were 1.5 times as great for patients admitted to fee-for-service hospitals than for those admitted to HMO hospitals (odds ratio 1.5, 95% confidence interval [CI] 1.3 to 1.9). Similarly, the odds of undergoing coronary revascularization were two times greater in fee-for-service hospitals (odds ratio 2.0, 95% CI 1.6 to 2.5). However, higher utilization was strongly associated with the greater availability of on-site cardiac catheterization facilities in fee-for-service hospitals. The length of hospital stay, by contrast, was approximately 1 day shorter in the fee-for-service cohort (7.3 vs. 8.0 days, p < 0.05). CONCLUSIONS: Physicians in staff-model HMO hospitals use fewer invasive procedures and longer lengths of stay to treat patients with acute myocardial infarction than physicians in fee-for-service hospitals. This finding, however, appears to be associated with the lack of on-site catheterization facilities at HMO hospitals.
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ECG findings in acute myocardial infarction. Are there sex-related differences?
Women with acute myocardial infarction are less likely than men to receive thrombolytic therapy. It is not known whether sex-related differences in the presenting 12-lead electrocardiogram (ECG) account for this relative underutilization of acute reperfusion therapy in women. The authors examined the initial ECGs of 188 men and 185 women matched for age and history of previous acute myocardial infarction randomly selected from the Myocardial Infarction Triage and Intervention registry who presented with 4 hours of confirmed acute myocardial infarction. There were no sex-related differences in the number of leads with ST elevation, the presence of diagnostic ST elevation, or the overall magnitude of ST elevation. In addition, there was no sex-related difference in associated ECG findings that might effect physicians' utilization of acute reperfusion therapy, including the location of ST elevation (anterior vs inferior), the presence of abnormal Q waves in leads with ST elevation, the association of ST depression with ST elevation (reciprocal changes), or the presence of confounding factors, such as bundle branch block or hypertrophy. Differences in the presenting ECG do not explain the underutilization of acute reperfusion therapy in women.
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Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice.
Transforming growth factor beta 1 (TGF beta 1) is shown here to be required for yolk sac haematopoiesis and endothelial differentiation. Mice with a targeted mutation in the TGF beta 1 gene were examined to determine the cause of prenatal lethality, which occurs in 50% of homozygous TGF beta 1 null (TGF beta 1-/-) conceptions. 50% of TGF beta 1-/- and 25% of TGF beta 1-+-) conceptions. 50% of TGF beta 1-/- and 25% of TGF beta 1+/- conceptuses were found to die at around 10.5 dpc. The primary defects were restricted to extraembryonic tissues, namely the yolk sac vasculature and haematopoietic system. The embryos per se showed developmental retardation, oedema and necrosis, which were probably secondary to the extraembryonic lesions. The defect in vasculogenesis appeared to affect endothelial differentiation, rather than the initial appearance and outgrowth of endothelial cells. Initial differentiation of yolk sac mesoderm to endothelial cells occurred, but defective differentiation resulted in inadequate capillary tube formation, and weak vessels with reduced cellular adhesiveness. Defective haematopoiesis resulted in a reduced erythroid cell number within the yolk sac. Defective yolk sac vasculogenesis and haematopoiesis were present either together, or in isolation of each other. The phenotypes are consistent with the observation of abundant TGF beta 1 gene expression in both endothelial and haematopoietic precursors. The data indicate that the primary effect of loss of TGF beta 1 function in vivo is not increased haematopoietic or endothelial cell proliferation, which might have been expected by deletion of a negative growth regulator, but defective haematopoiesis and endothelial differentiation.
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Outcomes in African-American women with suspected acute myocardial infarction: the Myocardial Infarction Triage and Intervention Project.
Increasing attention has been given to the investigation of cardiovascular disease in women, although African-American women have received little attention. This study compares characteristics and outcomes in women admitted to coronary care units for suspected acute myocardial infarction (MI). Between January 1988 and December 1991, a total of 554 (5%) African-American and 9738 (95%) white women with suspected acute MI were admitted to coronary care units in metropolitan Seattle, Washington. Relevant demographic socioeconomic, clinical, and outcome data were abstracted from the medical record and entered in the Myocardial Infarction Triage and Intervention registry. African-American women were younger, more often single and unemployed, and were less likely to have health insurance than their white counterparts. In addition, a higher proportion of African-American women reported a history of hypertension and diabetes mellitus. After adjustment for age, African-American women were equally as likely to develop acute MI and were more likely to die in the hospital. In addition, a higher proportion of African-American women were readmitted to coronary care units for suspected MI. Compared with their white counterparts, African-American women with suspected acute MI were considerably worse off from both socioeconomic and clinical standpoints, and their relative disadvantage was apparent in poor outcomes.
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The pregnancy rates of cohorts of idiopathic infertility couples gives insights into the underlying mechanism of infertility.
OBJECTIVES: To determine causes of "idiopathic" infertility, the IVF-ET experience of three cohorts of couples with this diagnosis was examined. DESIGN: Three cohorts of idiopathic infertility couples undergoing IVF-ET: a "failed IUI" group, three previous controlled ovarian hyperstimulation (COH)-IUI cycles with no pregnancies; a "conversion" group, patients converted during a COH-IUI cycle to IVF-ET because of excess follicle numbers; and a "direct IVF" group, patients proceeding directly to IVF-ET were compared. SETTING: A tertiary referral reproductive medicine unit. PARTICIPANTS: Forty-one idiopathic infertility couples. INTERVENTION: In vitro fertilization-ET. MAIN OUTCOME MEASURES: Number of oocytes retrieved, percent oocytes fertilized, number embryos per ET, implantation rate, percent pregnancy per cycle. RESULTS: The cohorts had similar fertilization rates and mean (+/- SD) number of pre-embryos transferred. The conversion group demonstrated a higher pregnancy rate (PR) per cycle and a higher E2 concentration than the other groups. The PR of 35.0% in the direct IVF group appeared higher than the 16.7% rate observed in the failed IUI group. CONCLUSIONS: Our observation of a lower PR in couples in the failed IUI group (16.7%) than in couples in the direct IVF group (35.0%) suggests pre-embryo developmental problems or implantation problems as likely important etiologies for a large proportion of idiopathic infertility couples. However, as the conversion group demonstrated both a significantly higher E2 concentration ([E2]) and per cycle PR than the other cohorts with similar fertilization and pre-embryo transfer rates. Subjects converted in a COH-IUI cycle to IVF-ET are thus either more likely to produce pre-embryos more genetically capable of continued development to implantation stage (i.e., better oocytes recruited and fertilized) or due to the higher [E2] to have endometrium more receptive to implantation. Neither undiagnosed tubal factors nor fertilization problems appear to be major etiologic contributors.
Adult↗
Randomized trial of partial zona dissection for male infertility.
OBJECTIVES: To compare IVF rates using partial zona dissection versus zona intact insemination in couples with male infertility. To analyze pregnancy rates relative to sperm characteristics, fertilization rates, and treatment. DESIGN: Randomized prospective comparison of fertilization in sibling oocytes. Transfer of the three best quality embryos from one or both treatments. SETTING: Department of Gynaecology and Reproductive Medicine, University Hospital, London, Ontario, Canada. PARTICIPANTS: Thirty-two couples undergoing IVF with a principal diagnosis of male infertility. INTERVENTION: Treatment with partial zona dissection. MAIN OUTCOME MEASURES: Fertilization and pregnancy. RESULTS: Fertilization rates were 26% and 9% after partial zona dissection and IVF, respectively. Polyspermy was < 1% in each treatment. There were five singleton pregnancies in 29 completed cycles, three in cycles with fertilization only by partial zona dissection and two in cycles with both partial zona dissection and IVF fertilization. There were no pregnancies after fertilization by IVF only. Stepwise logistic regression analysis indicated that pregnancy was related to partial zona dissection, initial sperm concentration, and total acrosin activity. CONCLUSION: Partial zona dissection was associated with minimal polyspermic fertilization and higher normal fertilization rates than sibling oocytes treated by modified IVF. Pregnancy occurred only after transfer of embryos from partial zona dissection or combined partial zona dissection and IVF.
Adult↗
Influence of external defibrillator electrode polarity on cardiac resuscitation.
Eight hundred forty-seven consecutive patients discovered in cardiac arrest by first responding firefighters received initial defibrillation attempts using automatic external defibrillators. The effect of electrode polarity on defibrillation and resuscitation was determined in the subset of 289 (34%) with ventricular fibrillation in a prospective, randomized trial. The ECG was recorded in 205 consecutive patients whose initial rhythm was ventricular fibrillation. Eighty-seven of 114 patients (76%) in whom the apex chest electrode was positive were defibrillated with the first 200-joule shock, compared to 70 of 91 patients (77%) in whom the apex electrode was negative. There was no difference in the type of rhythm established, e.g., organized versus brady-asystole following defibrillation with either electrode polarity. Resuscitation was possible in 56% of patients in whom the apex electrode was positive and 60% of those in whom the apex electrode was of negative polarity. Hospital survival rates (26% vs 27%) were also similar for both treatment groups. Unlike results during experimental external defibrillation of animals or those obtained using implantable defibrillators, this randomized trial of external defibrillation conducted during attempted out-of-hospital resuscitation showed no difference in outcomes related to electrode polarity.
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Gender differences in the treatment and outcome of acute myocardial infarction. Results from the Myocardial Infarction Triage and Intervention Registry.
BACKGROUND: The objective of this study was to compare treatment and outcome of acute myocardial infarction in women and men. METHODS: In this survey, patient hospital records were reviewed, and information about patient characteristics, treatments, and hospital events was entered in the Myocardial Infarction Triage and Intervention Registry. Between January 1988 and June 1990, a total of 4891 consecutive patients, including 1659 women, were hospitalized for acute myocardial infarction in 19 hospitals in the Seattle (Wash) metropolitan area. In-hospital thrombolytic therapy, coronary angiography, angioplasty, and bypass surgery were examined, as were in-hospital complications and death. RESULTS: Women were older and more often had histories previous hypertension and previous congestive heart failure. Thrombolytic therapy was used less often in women, although information about eligibility for treatment was not available to determine if this difference was due to treatment bias or differences in eligibility. Both coronary angiography and coronary angioplasty were used less frequently in women. However, of patients who had coronary angiography, equal proportions of women and men received angioplasty and/or coronary bypass surgery. Hospital mortality was 16% for women and 11% for men, although this difference was diminished by age adjustment. Mortality was higher in women undergoing bypass surgery, but this difference, too, was less apparent after age adjustment. CONCLUSIONS: Despite high levels of risk factors and mortality, coronary angiography and angioplasty were used less often in women, although among those who underwent coronary angiography, there were no gender differences in the use of angioplasty or bypass surgery. Clearly, more needs to be known about decision making for coronary angiography, as this process seems to differ for women and men with acute myocardial infarction.
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Characteristics of black patients admitted to coronary care units in metropolitan Seattle: results from the Myocardial Infarction Triage and Intervention Registry (MITI).
Since 1988, 641 black and 11,892 white patients with chest pain of presumed cardiac origin have been admitted to coronary care units in 19 hospitals in metropolitan Seattle. Black men and women were younger (58 vs 66, p less than 0.0001), more often admitted to central city hospitals (p less than 0.0001), and developed evidence of acute myocardial infarction (AMI) less often (19 vs 23%, p = 0.01). In the subset of 2,870 AMI patients, blacks (n = 121) were younger (59 vs 67, p less than 0.0001) and had less prior coronary artery bypass graft surgery (2 vs 10%, p = 0.005) and more prior hypertension (67 vs 46%, p less than 0.0001). During hospitalization, whites (n = 2,749) had higher rates of coronary angioplasty (18 vs 10%, p = 0.03) and coronary artery bypass graft surgery (10 vs 4%, p = 0.04), although thrombolytic therapy and cardiac catheterization were used equally in the 2 groups. Hospital mortality was 7.4% for black and 13.1% for white patients (p = 0.07). However, after adjustment for key demographic and clinical variables by logistic regression, this difference was not as apparent (p = 0.38). Questions about the premature onset of coronary artery disease, excess systemic hypertension, and the differential use of interventions in black persons have been raised by other investigators. Despite differences in age, referral patterns and the use of coronary angioplasty and bypass surgery, black and white patients with AMI in metropolitan Seattle had similar outcomes.
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Accuracy of computer-interpreted electrocardiography in selecting patients for thrombolytic therapy. MITI Project Investigators.
A prehospital computer-interpreted electrocardiogram (ECG) was obtained in 1,189 patients with chest pain of suspected cardiac origin during an ongoing trial of prehospital thrombolytic therapy in acute myocardial infarction. Electrocardiograms were performed by paramedics 1.5 +/- 1.2 h after the onset of symptoms. Of 391 patients with evidence of acute myocardial infarction, 202 (52%) were identified as having ST segment elevation (acute injury) by the computer-interpreted ECG compared with 259 (66%) by an electrocardiographer (p less than 0.001). Of 798 patients with chest pain but no infarction, 785 (98%) were appropriately excluded by computer compared with 757 (95%) by an electrocardiographer (p less than 0.001). The positive predictive value of the computer- and physician-interpreted ECG was, respectively, 94% and 86% and the negative predictive value was 81% and 85%. Prehospital screening of possible candidates for thrombolytic therapy with the aid of a computerized ECG is feasible, highly specific and with further enhancement can speed the care of all patients with acute myocardial infarction.
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Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction. The MITI Project Group.
The findings in 3,256 consecutive patients hospitalized for acute myocardial infarction were tabulated to assess the history, treatments and outcome in the elderly; 1,848 patients (56%) were greater than 65 years of age, including 28% who were aged greater than or equal to 75 years. The incidence of prior angina, hypertension and heart failure (only 3% of patients less than 55 years of age had a history of heart failure compared with 24% greater than or equal to 75 years old) was found to increase with age. Twenty-nine percent of patients less than 75 years of age were treated with a systemic thrombolytic drug compared with only 5% of patients older than 75 years. Mortality rates increased strikingly with advanced age (less than 2% in patients less than or equal to 55, 4.6% in those 55 to 64, 12.3% in those 65 to 74 and 17.8% in those greater than or equal to 75 years). Both the incidence of complicating illness and a nondiagnostic electrocardiogram (ECG) increased with age. In a multivariate analysis of outcome in older patients (greater than or equal to 65 years), adverse events were related to both prior history of heart failure (odds ratio 3.9) and increasing age (odds ratio 1.4 per each decade of age). Outcome was not improved by treatment with thrombolytic drugs, but these agents were prescribed to only 12% of patients greater than 65 years of age, thereby reducing the power for detecting such an effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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Time delays in the diagnosis and treatment of acute myocardial infarction: a tale of eight cities. Report from the Pre-hospital Study Group and the Cincinnati Heart Project.
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.
Electrocardiography↗
Particulate inhalation during the removal of amalgam restorations.
An aerosol that contains amalgam particles is created when a high-speed hand-piece is used to remove an existing amalgam restoration. Those particles smaller than 10 microns are considered to be fully respirable. This means that a significant percentage of the particles have the potential to travel to the terminal alveoli, where they may become lodged. Long-term exposure to fully respirable particles may compromise a person's respiratory function. Amalgam restorations were placed in the typodont teeth of a mannequin designed to simulate the head and the respiratory tract of a patient. The amalgam restorations were removed under three experimental conditions: dry cut (control), wet cut (water spray) with high-velocity evacuation, and wet cut with high-velocity evacuation and a rubber dam. Particulate exposure was evaluated in the simulated respiratory tracts of the patient and the dentist that were equipped with ambient particle sizing samplers. Use of water spray and high-velocity evacuation significantly reduced patient exposure to particles. The use of a rubber dam, together with water spray and high-velocity evacuation, was responsible for a further significant reduction of exposure to particles when compared with water spray and high-velocity evacuation alone. The dentist, however, was exposed to moderate levels of fully respirable particles for all conditions tested. It is therefore recommended that all dental personnel wear face masks while removing existing amalgam restorations.
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Myocardial Infarction Triage and Intervention Project--phase I: patient characteristics and feasibility of prehospital initiation of thrombolytic therapy.
Prehospital initiation of thrombolytic therapy by paramedics, if both feasible and safe, could considerably reduce the time to treatment and possibly decrease the extent of myocardial necrosis in patients with acute coronary thrombosis. Preliminary to a trial of such a treatment strategy, paramedics evaluated the characteristics of 2,472 patients with chest pain of presumed cardiac origin; 677 (27%) had suitable clinical findings consistent with possible acute myocardial infarction and no apparent risk of complication for potential thrombolytic drug treatment. Electrocardiograms (ECGs) of 522 of the 677 patients were transmitted by cellular telephone to a base station physician; 107 (21%) of the tracings showed evidence of ST segment elevation. Of the total 2,472 patients, 453 developed evidence of acute myocardial infarction in the hospital; 163 (36%) of the 453 had met the strict prehospital screening history and examination criteria and 105 (23.9%) showed ST elevation on the ECG and, thus, would have been suitable candidates for prehospital thrombolytic treatment if it had been available. The average time from the onset of chest pain to prehospital diagnosis was 72 +/- 52 min (median 52); this was 73 +/- 44 min (median 62) earlier than the time when thrombolytic treatment was later started in the hospital. Paramedic selection of appropriate patients for potential prehospital initiation of thrombolytic treatment is feasible with use of a directed checklist and cellular-transmitted ECG and saves time. This strategy may reduce the extent and complications of infarction compared with results that can be achieved in a hospital setting.
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Early recognition and treatment of the patient suffering from acute myocardial infarction. A description of the Myocardial Infarction Triage and Intervention Project.
Involving emergency medical personnel in the evaluation and treatment of the AMI patients is feasible. A standard, organized approach saves time. Obtaining an ECG in the prehospital setting is also feasible and decreases the delay to diagnosis and subsequent treatment for patients after hospital arrival. Early findings from the MITI registry suggests that only 20% to 30% of patients with AMI are currently eligible to receive thrombolytic medications. This seems to indicate that either current treatment guidelines need to be broadened or that thrombolytic therapy is not appropriate for all AMI patients and, therefore, alternative acute treatment approaches need to be investigated further.
Humans↗
Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest.
The automatic external defibrillator is a simple device that can be used by nonprofessional rescuers to treat cardiac arrest. In 1287 consecutive patients with out-of-hospital cardiac arrest, we assessed the results of initial treatment with this device by firefighters who arrived first at the scene, as compared with the results of standard defibrillation administered by paramedics who arrived slightly after the firefighters. Of 276 patients who were initially treated by firefighters using the automatic defibrillator, 84 (30 percent) survived to hospital discharge (expected rate according to a logistic model, 17 percent; P less than 0.001), as compared with 44 (19 percent) of 228 patients when fire-fighters delivered only basic cardiopulmonary resuscitation and the first defibrillation was performed after the arrival of the paramedic team. Few patients with conditions other than ventricular fibrillation survived. In a multivariate analysis of characteristics that influenced survival after ventricular fibrillation, a better survival rate was related to a witnessed collapse (odds ratio, 3.9; 95 percent confidence interval, 2.0 to 7.6), younger age (odds ratio, 1.2; 95 percent confidence interval, 1.0 to 1.4), the presence of "coarse" (higher-amplitude) fibrillation (odds ratio, 4.2; 95 percent confidence interval, 1.6 to 11.0), a shorter response time for paramedics (odds ratio, 1.4; 95 percent confidence interval, 1.0 to 2.1), and initial treatment by firefighters using an automatic external defibrillator (odds ratio, 1.8; 95 percent confidence interval, 1.1 to 2.9). These findings support the widespread use of the automatic external defibrillator as an important part of the treatment of out-of-hospital cardiac arrest, although the overall impact of the use of this device on community survival rates is still uncertain.
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