Obstetric anesthesia workforce survey: twenty-year update.
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Biomedical subjects
Publications and source records attributed to James R Anderson.
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Several chemicals have been associated with risk of non-Hodgkin's lymphoma (NHL), many of which are substrates for N-acetyltransferase (NAT) and glutathione S-transferase (GST) enzymes. We investigated the association between polymorphisms in genes coding for these enzymes and NHL risk in a population-based study (389 cases and 535 controls). NAT1 slow genotype was associated with a slightly increased risk in women [odds ratios (OR) = 1.4; 95% confidence interval (CI) = 0.9-2.3], but not in men. NAT2 slow genotype was not associated with risk in either sex. The two slow genotypes of NAT1 and NAT2 combined were associated with a minor increase of risk in women (OR = 1.4; 0.8-2.4). There was no association with the GSTM1 or GSTT1 null genotype in either sex, irrespective of histological subtypes. Individuals with GSTP1 Val homozygotes had non-significant excessive risk of marginal zone lymphoma (OR = 1.8; 0.6-5.1) and 'other' B-cell NHLs (OR = 1.6; 0.7-3.6), but lower risk of diffuse large B-cell lymphoma (OR = 0.2; 0.1-0.96). Risk did not elevate with an increasing number of high-risk GST alleles in either sex. In summary, although NAT1, NAT2, GSTM1, GSTT1, or GSTP1 polymorphisms do not appear to be associated with NHL risk overall, there might be gender-specific and subtype-specific associations that require confirmation.
BACKGROUND: Both early stress testing and cardiac troponin I (cTnI) measurements are useful in assessing the prognosis of patients with acute coronary syndrome (ACS). We sought to determine the accuracy and prognostic value of wall motion analysis (WMA) and myocardial perfusion analysis (MPA) with real-time myocardial contrast echocardiography (RTMCE) during dobutamine stress in this patient population. METHODS: We performed dobutamine stress RTMCE to assess perfusion in 158 consecutive patients (mean age: 61 +/- 13 years) with chest pain and possible ACS. Of these, 119 had normal cTnI, while 39 had isolated elevations of cTnI (range: 0.5-9.0 ng/ml). Quantitative angiography was performed within 1 month of RTMCE in 61 patients. Patients were followed for 16 months (range: 6-46 months). Cardiac events included death, nonfatal myocardial infarction, recurrent unstable angina, or need for urgent revascularization. RESULTS: The sensitivity, specificity, and accuracy of MPA for detecting a >50% coronary stenosis were 92%, 77%, and 88%, respectively, while they were 62%, 85%, and 67% for WMA. Three-year event-free survival was 87% in patients with negative WMA and MPA, 49% in those with positive WMA and MPA, and 51% in patients with negative WMA but positive MPA. Age-adjusted multivariate analysis demonstrated that the only independent predictors of cardiac events were a positive MPA (hazard ratio = 3.23; 95% CI = 1.23-8.49) and male sex (hazard ratio = 3.29; 95% CI = 1.21-8.97). CONCLUSIONS: In patients suspected of having an ACS, RTMCE improved the accuracy of dobutamine stress echocardiography for detecting coronary artery disease, and was an independent predictor of outcome.
OBJECTIVE: This study sought to compare the accuracy of myocardial contrast echocardiography (MCE) and wall motion analysis (WMA) during submaximal and peak dobutamine stress echocardiography (DSE) for the diagnosis of coronary artery disease (CAD). BACKGROUND: The relative merits of MCE and WMA for the detection of CAD during DSE have not been studied in a large number of patients. METHODS: We studied 170 patients who underwent dobutamine (up to 50 microg/kg/min)-atropine stress testing and coronary angiography. The WMA and MCE (using repeated boluses of Optison [Mallinckrodt, St. Louis, Missouri] or Definity [Bristol-Myers Squibb, New York, New York]) were performed at rest, at intermediate stress (65% to 75% of maximal heart rate), and at peak stress. The diagnosis of CAD (>/=50% stenosis in >/=1 coronary artery) was based on reversible wall motion and perfusion abnormalities. RESULTS: Coronary artery disease was detected in 127 (75%) patients. Sensitivity of MCE was higher than that of WMA at maximal stress (91% vs. 70%; p = 0.001) and at intermediate stress (84% vs. 20%; p = 0.0001). Specificity was lower for MCE compared with WMA (51% vs. 74%; p = 0.01). Overall accuracy was higher for MCE than for WMA (81% vs. 71%; p = 0.01). Sensitivity for detection of CAD based on abnormalities in >/=2 vascular regions was higher for MCE than for WMA (67% vs. 28%; p < 0.01). CONCLUSIONS: The majority of inducible perfusion abnormalities occur at an intermediate phase of the stress test, without wall motion abnormalities. Myocardial contrast echocardiography provides better sensitivity than WMA, particularly in patients with submaximal stress and in identifying patients with multivessel CAD.
Six adult female chimpanzees were shown video scenes of chimpanzees repeatedly yawning or of chimpanzees showing open-mouth facial expressions that were not yawns. Two out of the six females showed significantly higher frequencies of yawning in response to yawn videos; no chimpanzees showed the inverse. Three infant chimpanzees that accompanied their mothers did not yawn at all. These data are highly reminiscent of the contagious yawning effects reported for humans. Contagious yawning is thought to be based on the capacity for empathy. Contagious yawning in chimpanzees provides further evidence that these apes may possess advanced self-awareness and empathic abilities.
PURPOSE: More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome. EXPERIMENTAL DESIGN: This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3-week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1, and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2 g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy was administered at week 0 (parameningeal tumors with intracranial extension) or week 12 or 15 (all others). RESULTS: Between October 1996 and August 1999, 115 eligible patients were enrolled. Three of 15 patients treated at dose level 2 experienced life-threatening dose-limiting toxicity (typhlitis +/- other severe toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients were treated at this level. The 3-year failure-free and overall survival estimates for patients treated at the maximum-tolerated dose were 52% (95% confidence interval, 41-64%) and 67% (95% confidence interval, 56-77%), respectively, at a median follow-up of 3 years. CONCLUSIONS: A 64% increase in the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was tolerated. However, outcomes were similar to those observed at lower dosages, suggesting that alkylator dose intensification does not benefit patients with intermediate-risk rhabdomyosarcoma.
This study attempted a new manipulation to prompt mirror self-recognition in a monkey species through simultaneous exposure to two mirrors. Four capuchin monkeys (Cebus apella) were exposed to one large and one small mirror object with different reflective or configurational properties, which was thought to deepen their understanding of mirrors. The monkeys predominantly engaged in looking behaviours towards the large mirror, which decreased over sessions. There was also an increase in looking behaviours towards the small mirror object when it reflected an undistorted image compared to the control condition. No instances of self-directed responses, oblique looks or manipulations of both mirror objects in combination were observed. The results confirm and expand on previous reports of failure to find evidence of mirror self-recognition in monkeys.
Squirrel monkeys (Saimiri sciureus) and capuchin monkeys (Cebus apella) were tested using an expectancy violation procedure to assess whether they use an actor's gaze direction, signaled by congruent head and eye orientation, to predict subsequent behavior. The monkeys visually habituated to a repeated sequence in which the actor (a familiar human or a puppet) looked at an object and then picked it up, but they did not react strongly when the actor looked at an object but then picked up another object. Capuchin monkeys' responses in the puppet condition were slightly more suggestive of expectancy. There was no differential responding to congruent versus incongruent look-touch sequences when familiarization trials were omitted. The weak findings contrast with a strongly positive result previously reported for tamarin monkeys. Additional evidence is required before concluding that behavior prediction based on gaze cues typifies primates; other approaches for studying how they process attention cues are indicated.
BACKGROUND: Although age <1 year at diagnosis has been associated with a worse prognosis in rhabdomyosarcoma (RMS), the relationship of age at diagnosis to clinical presentation and outcome has not been evaluated carefully. We reviewed data from recent Intergroup Rhabdomyosarcoma Study Committee (later called Group, IRSG) trials to examine this relationship in order to estimate prognosis more accurately and further refine treatment. PROCEDURE: We used data from IRS-III, -IV Pilot, and -IV (1983-97, N=2,343) to study the relationship of patient age with clinical features and prognosis in a large cohort of patients treated with contemporary therapy. RESULTS: We showed that, after adjusting for important prognostic factors, age was an independent risk factor for treatment failure and patients could be classified into three failure-risk categories based on age (i.e., <1 year; 1-9 years; >10 years). Infants and adolescents were more likely to have unfavorable features, including alveolar or undifferentiated tumors and advanced Group and Stage, and also had significantly poorer failure-free survival (FFS) than did children aged 1-9 (53 and 51% vs. 72%, P<0.001). Although there was a difference in FFS among age categories, there was no evidence that age influences outcome within the three categories. CONCLUSIONS: Since age relates independently to outcome after adjustment for known risk factors, it is likely that other factors, including perhaps patients' tolerance of protocol-specified therapy, explain this relationship.
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BACKGROUND: Urinary tract infections (UTIs) are the most common nosocomial infection experienced by patients in United States hospitals and are responsible for significant morbidity and excess hospital costs. The purpose of this study was to determine the efficacy of a silver alloy, hydrogel-coated, urinary catheter in the prevention of catheter-associated UTI, to assess the cost effectiveness of the coated catheter, and to test for the emergence of silver-resistance in urinary microbial isolates. METHODS: A 2-year prospective surveillance study in 10 patient care units was conducted to determine the rate of catheter-associated UTI. Historic control data was utilized to assess the effect of the coated catheter. A cost-effectiveness analysis was conducted using a range of cost estimates. Silver susceptibility was determined for microbes responsible for catheter-associated UTI. RESULTS: Data were analyzed using a Poisson regression model. The rate of catheter-associated UTI fell from 6.13/1000 catheter-days during the period 1999-2000 to 2.62/1000 catheter-days during 2001-2002 ( P = .002). Calculated cost savings varied widely. Modest savings were achieved at the realistic lower cost estimates. No silver-resistant microbes were recovered in the susceptibility tests. CONCLUSIONS: The introduction of a silver alloy, hydrogel-coated urinary catheter was associated with a significant decline in nosocomial UTI and cost savings over the range of cost estimates. Silver-resistant urinary pathogens were not recovered from patients experiencing catheter-associated UTI during the study period.
The aim of our study was to describe late failures in children who initially survived event-free five years from a diagnosis of rhabdomyosarcoma. Charts of children enrolled in the Intergroup Rhabdomyosarcoma Study Group (IRSG) trials III, IV pilot and IV (1984-1997) who survived five years event-free and subsequently experienced an adverse event (disease recurrence, second malignant neoplasm or death from other causes) were reviewed. Of the 2534 enrolled patients, 1160 were event-free at five years and 48 subsequently experienced a late event. The estimated 10-year event rate for the 1160 patients who were alive and event-free at five years was 9% (95% Confidence Interval (CI) 5%, 13%). Patients with both advanced disease (Group III/IV) and large primary tumours at diagnosis (> 5 cm) were at the highest risk for late events (19%; 95% CI 8%, 30%). Late events after successful treatment for rhabdomyosarcoma occur in 9%. Those with advanced disease and large primary tumours have the highest risk of late events.
We identified all children enrolled in the Intergroup Rhabdomyosarcoma Study Group-IV with neurofibromatosis type I (NF1) and rhabdomyosarcoma. Among 1025 eligible patients, 5 (0.5 %) had NF1. Three children had relapses, two of whom died of progressive disease. Patients with NF1 and rhabdomyosarcoma should be treated with intensive contemporary therapy protocols.
Squirrel monkeys (Saimiri sciureus) that had learned to reach toward 1 piece of food instead of 4 in a reverse-reward contingency were tested after an 8-month delay with no intervening relevant experiences. All monkeys except 1 continued to show inhibitory control by reliably reaching toward the smaller quantity, most of them doing so within 2 sessions. Performance was maintained when a low-preference food replaced prized foods as arrays and rewards. When the quantities 1 and 4 were replaced with different ones, there was strong evidence of transposition at group level, although individual differences in bias toward the smaller quantities became apparent. Individual differences in mastering the original task more than 8 months previously were quite stable, suggesting robustness in the operations required for this form of self-control.
PURPOSE: To identify risk factors associated with outcomes in children with metastatic rhabdomyosarcoma (RMS) treated on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV). PATIENTS AND METHODS: Patients with metastatic RMS were treated with one of two regimens that incorporated a window of either ifosfamide and etoposide (IE) with vincristine, dactinomycin, and cyclophosphamide (VAC) or vincristine, melphalan (VM) and VAC. Study end points were failure-free survival (FFS) and overall survival (OS). Clinical factors including age, histology, sites of primary and metastatic disease, and number of sites of metastatic disease were correlated with those end points. RESULTS: One hundred twenty-seven patients were eligible for analysis. The estimated 3-year OS and FFS for all patients were 39% and 25%, respectively. By univariate analysis, 3-year OS was significantly influenced by histology (47% for embryonal v 34% for all others, P =.026) and increasing number of metastatic sites (P =.028). By multivariate analysis, the presence of two or fewer metastatic sites was the only significant predictor (P =.007 and.006, respectively). The combination of embryonal histology with two or fewer metastatic sites identified a subgroup with 3-year FFS of 40% and OS of 47%. CONCLUSION: Children with group IV RMS treated on the IRS-IV study had improved OS and FFS if they had two or fewer metastatic sites and embryonal histology. This favorable subset of patients has outcomes approaching those observed in selected patients with localized, nonmetastatic disease. Thus, these patients might not be appropriate candidates for regimens that include experimental agents with substantial toxicities or unproven antitumor activity.
We reviewed the clinical characteristics, treatment, and outcome of 67 children with localized and 212 with disseminated large-cell lymphoma (LCL) treated during a 20-year period in 5 consecutive Children's Cancer Group (CCG) non-Hodgkin's lymphoma (NHL) trials. Clinical outcomes for patients treated on the four earlier studies with moderate-dose chemotherapy administered over 12-18 months were compared with patients treated most recently with short, intensive therapy. Median age at diagnosis was 12 years (range: 0-19 years). Male to female ratio was 1.8:1.0. Five-year event-free survival (EFS) was 92% +/- 3.3% and 50 +/- 3.5% for patients with localized LCL and disseminated LCL, respectively. After adjustment for lactate dehydrogenase (LDH), age at diagnosis, and BM involvement, short and intensive therapy as delivered on the most recent study, CCG-5911, was associated with an improved outcome (P< 0.05) compared to the four previous studies. Elevated LDH (> or = 500 IU/L) at diagnosis and young age (<5 years) were both significant independent predictors of poorer long-term EFS (P< 0.05). Long-term survival after relapse or other treatment failure was only 31% +/- 4.7%. In summary, more recent shorter and intense therapy appears to be associated with superior event-free survival for children and adolescents with disseminated LCL. Large numbers of patients treated with shorter and intense therapy are required to confirm these preliminary observations.
The ability of 4 olive baboons (Papio anubis) to use human gaze cues during a competitive food task was investigated. Three baboons used head orientation as a cue, and 1 individual also used eye direction alone. As the baboons did not receive prior training with gestural cues, their performance suggests that the competitive paradigm may be more appropriate for testing nonhuman primates than the standard object-choice paradigm. However, the baboons were insensitive to whether the experimenter could actually perceive the food item, and therefore the use of visual orientation cues may not be indicative of visual perspective-taking abilities. Performance was disrupted by the introduction of a screen and objects to conceal food items and by the absence of movement in cues presented.
Historically, the survival of children and adolescents with Burkitt's and Burkitt-like lymphoma had been poor. Recently, short and intensive chemotherapy appears to have improved disease outcome. We therefore reviewed the results of four successive Children's Cancer Group trials conducted on 470 children with disseminated Burkitt's and Burkitt-like lymphoma. Of the patients studied, the median age was 8 years (0-21 years), the male:female ratio was 4:1, 58% had lactate dehydrogenase (LDH) > or = 500 IU/l, 23% had M2 or M3 bone marrow (BM), and 12% demonstrated central nervous system involvement. In a multivariate analysis, the 4-year event-free survival (EFS) in patients > or = 15-years-old compared with < 15-year-old was 34 +/- 7 versus 59 +/- 2% (P < 0.05), the 4-year EFS of M2/M3 compared with M1 BM was 38 +/- 5 versus 63 +/- 3% (P < 0.001), and the 4-year EFS with LDH > or = 500 IU/l compared with LDH < 500 IU/l was 49 +/- 3 versus 71 +/- 4% (P < 0.001). Furthermore, patients treated on the most recent protocol, which was short and more intensive, had a significantly improved survival compared with those on previous trials (4-year EFS 80 +/- 6 versus 54 +/- 2%, P < 0.001). In summary, the outcome for childhood Burkitt's and Burkitt-like lymphoma has recently improved with the use of short and intensive B-cell non-Hodgkin's lymphoma-directed therapy.