Trend differences in men and women in rural and urban U.S. settings.

BACKGROUND: Smoking prevalence is declining at a slower rate in rural than urban settings in the United States (U.S.), and known predictors of smoking do not readily account for this trend difference. Given that socioeconomic and psychosocial determinants of health disparities accumulate in rural settings and that life-course disadvantages are often greater in women than men, we examined whether smoking trends are different for rural and urban men and women. METHOD: We used yearly cross-sectional data (n = 303,311) from the U.S. National Survey on Drug Use and Health (NSDUH) from 2007 through 2014 to compare cigarette smoking trends in men and women across rural and urban areas. Current smoking status was modelled using logistic regression controlling for confounding risk factors. RESULTS: Regression derived graphs predicting unadjusted prevalence estimates and 95% confidence bands revealed that whereas the smoking trends of rural men, urban men, and urban women significantly declined from 2007 to 2014, the trend for rural women was flat. Controlling for demographic, socioeconomic and psychosocial predictors of smoking did not explain rural women's significantly different trend from those of the other three groups. CONCLUSION: Rural women lag behind rural men, urban men and urban women in decreasing smoking, a health disparity finding that supports the need for tobacco control and regulatory policies and interventions that are more effective in reducing smoking among rural women.

Efficient biologically inspired photocell enhanced by delocalized quantum states.

Artificially implementing the biological light reactions responsible for the remarkably efficient photon-to-charge conversion in photosynthetic complexes represents a new direction for the future development of photovoltaic devices. Here, we develop such a paradigm and present a model photocell based on the nanoscale architecture and molecular elements of photosynthetic reaction centers. Quantum interference of photon absorption and emission induced by the dipole-dipole interaction between molecular excited states guarantees an enhanced light-to-current conversion and power generation for a wide range of electronic, thermal, and optical parameters for optimized dipolar geometries. This result opens a promising new route for designing artificial light-harvesting devices inspired by biological photosynthesis and quantum technologies.

Early-onset prescription drug misuse in Indiana youth.

BACKGROUND: Based on 2018 national estimates, approximately 5-10% of youth between the ages of 12-17 report past year prescription drug misuse (PDM) in the United States. PDM among adolescents is associated with negative health outcomes and risk behaviors. The current study examined both the prevalence of PDM among diverse groups of adolescents and the association of alcohol and cigarette use with early PDM. METHODS: Data came from the cross-sectional state-based 2018 Indiana Youth Survey of students from grades 6-12, ranging in age from 10 to 17 years (n = 80,926). Lifetime PDM, alcohol, and cigarettes were assessed by self-report, including ages at first use. A series of analyses were conducted separately for non-Hispanic Black, non-Hispanic White, and Hispanic students. We estimated the prevalence of PDM. Likelihood of PDM was estimated using the Kaplan-Meier survivor function. Cox proportional hazards regression models estimated age at first PDM from ages at first use of alcohol and cigarettes. RESULTS: Three percent of non-Hispanic Black, 4% of non-Hispanic White, and 5% of Hispanic students reported PDM. Onset of smoking was associated with first PDM across adolescence for all groups. Onset of drinking was associated with first PDM among Hispanic students across adolescence. For Non-Hispanic Black and Non-Hispanic White students, likelihood of PDM was most pronounced during very early adolescence. CONCLUSIONS: Onset of alcohol and cigarette use were associated with of PDM among Indiana youth, suggesting that interventions aimed at preventing early smoking and drinking may also reduce PDM among youth.

Staging and operability of primary lung cancer in Western Cape Province, South Africa.

Background: Lung cancer is the leading cause of cancer-related death globally and in South Africa. Historically, the majority of patients diagnosed with lung cancer are incurable at presentation. Objectives: To assess the tumour, nodes, metastasis (TNM) staging of lung cancer in a centre with access to both positron emission tomography-computed tomography (PET-CT) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) using a structured diagnostic approach and to compare results with a historical cohort from 2009 from the same hospital. Methods: A retrospective descriptive observational study was performed using the registry of a high-volume tertiary hospital's weekly multidisciplinary thoracic oncology meeting (MDT). A structured diagnostic approach was used for staging purposes. All patients with a tissue diagnosis of primary lung cancer and adequate imaging (chest CT and/or PET-CT) who presented at the MDT during the period from 1 January - 31 December 2019 were included. Final staging and tissue diagnoses were documented and compared with a historical cohort from 2009 from the same institution. Results: Adenocarcinoma was the most common subtype (38.8%; n=116). Less than a tenth of patients (6.3%; n=16/254) with non-small cell lung cancer had potentially curable lung cancer (stage IA to IIIA) at presentation, significantly less than the 2009 cohort (14.5%; n=25/173; p=0.007). The most common procedure administered on patients was transthoracic needle aspiration (37.54%; n=112), followed by conventional bronchoscopic needle aspiration or biopsy (20.4%; n=61), and EBUS-TBNA (17.1%; n=51/299). After PET-CT, 19/30 cases were upstaged including 9/18 from potentially resectable to unresectable. Two of these cases were down-staged to potentially resectable following EBUS-TBNA. Conclusion: There was a significant decline in resectable and potentially curable lung cancer at presentation over a 10-year period. PET-CT and EBUS-TBNA improved the accuracy of non-small cell lung cancer staging among patients with resectable and potentially curable lung cancer but have exposed a higher stage profile.

The Menstrual Disorder of Teenagers (MDOT) Study No. 2: Period ImPact and Pain Assessment (PIPPA) Tool Validation in a Large Population-Based Cross-Sectional Study of Australian Teenagers.

STUDY OBJECTIVE: To validate the Period ImPact and Pain Assessment (PIPPA) self-screening tool for menstrual disturbance in teenagers. DESIGN: Cross-sectional study. SETTING: Three senior high schools in the Australian Capital Territory (ACT), Australia. PARTICIPANTS: A total of 1066 girls between 15 and 19 years of age. INTERVENTIONS AND MAIN OUTCOME MEASURES: A quantitative paper survey collected self-reports of menstrual bleeding patterns, typical and atypical symptoms, morbidities, and interference with daily activities. Multiple correspondence analysis was used to examine associations between PIPPA questions. Generalized linear models compared total score and subscores by validation criteria: pain, school absence, and body mass index (BMI). Receiver operating characteristic curves were used to evaluate the predictiveness of menstrual disturbance indicators by total PIPPA score. RESULTS: Reports of pain, interference, and concern within the PIPPA items and between both the MDOT and PIPPA questionnaires were significantly correlated (P < .0001). The indicator "missing school" was highly associated (P < .0001) with pain and interference. Obesity (BMI ≥30) was associated with higher PIPPA scores, as was underweight (BMI≤18.4). Where 0 = no disturbance, 5 = high disturbance, aggregated PIPPA scores found 75% scoring 0-2 (out of 5) and 25% scoring 3-5 (257/1037). High scores of 4 or 5 (out of 5) were 7% (72/1037) and 3.7% (38/1037), respectively. CONCLUSION: PIPPA is a valid screening tool for pain-related menstrual disturbance that affects functioning in young women. PIPPA subdomains of pain/interference have good validity relative to indicators of pain and interference and are responsive to age, BMI, and school absence differences.

Bacterial infection, antibiotic use and COVID-19: Lessons from the intensive care unit.

BACKGROUND: Empirical broad-spectrum antibiotics are frequently prescribed to patients with severe COVID-19, motivated by concern about bacterial coinfection. There is no evidence of benefit from such a strategy, while the dangers of inappropriate antibiotics are well described. OBJECTIVES: To investigate the frequency, profile and related outcomes of infections by bacterial pathogens in patients admitted to an intensive care unit (ICU) with severe COVID-19 pneumonia. METHODS: This was a prospective, descriptive study in a dedicated COVID-19 ICU in Cape Town, South Africa, involving all adult patients admitted to the ICU with confirmed COVID-19 pneumonia between 26 March and 31 August 2020. We collected data on patient comorbidities, laboratory results, antibiotic treatment, duration of admission and in-hospital outcome. RESULTS: We included 363 patients, who collectively had 1 199 blood cultures, 308 tracheal aspirates and 317 urine cultures performed. We found positive cultures for pathogens in 20 patients (5.5%) within the first 48 hours of ICU admission, while 73 additional patients (20.1%) had positive cultures later during their stay. The most frequently isolated pathogens at all sites were Acinetobacter baumannii (n=54), Klebsiella species (n=13) and coagulase-negative staphylococci (n=9). Length of ICU stay (p<0.001) and intubation (p<0.001) were associated with positive cultures on multivariate analysis. Disease severity (p=0.5), early antibiotic use (p=0.5), diabetes mellitus (p=0.1) and HIV (p=0.9) were not associated with positive cultures. Positive cultures, particularly for tracheal aspirates (p<0.05), were associated with longer ICU length of stay and mortality. Early empirical antibiotic use was not associated with mortality (odds ratio 2.5; 95% confidence interval 0.95 - 6.81). CONCLUSIONS: Bacterial coinfection was uncommon in patients at the time of admission to the ICU with severe COVID-19. Avoiding early empirical antibiotic therapy is therefore reasonable. Strategies to avoid coinfection and outbreaks in hospital, such as infection prevention and control, as well as the strict use of personal protective equipment, are important to improve outcomes.

The menstrual disorder of teenagers (MDOT) study: determining typical menstrual patterns and menstrual disturbance in a large population-based study of Australian teenagers.

OBJECTIVE: The aim of this study was to: (1) establish the typical experience of menstruation for senior high school girls and (2) determine how many experience considerable menstrual disturbance that could require further investigation and management of underlying pathology. DESIGN: Cross-sectional study. SETTING: Senior High Schools in the Australian Capital Territory (ACT), Australia. POPULATION: A total of 1051 girls aged between 15 and 19 years. METHODS: Data based on a quantitative survey. MAIN OUTCOME MEASURES: Self-reports of menstrual bleeding patterns, typical and atypical symptoms and morbidities. RESULTS: Typical menstruation in adolescence includes pain (93%), cramping (71%), premenstrual symptoms (96%) and mood disturbance (73%). Highly significant associations were found between increasing severity of menstrual pain, number of menstrual-related symptoms, interference with life activities and school absence. These associations indicate that approximately 25% of the sample had marked menstrual disturbance: 21% experienced severe pain; 26% school absence; 26% suffering five or more symptoms; > or =24% reporting moderate to high interference with four out of nine life activities. Approximately 10% reported atypical symptoms associated with menstruation. Diagnosis of menstrual pathology in the sample was low, even though 33% had seen a GP and 9% had been referred to a specialist. CONCLUSIONS: Menstrual pain and symptoms are common in teenagers. Girls indicating moderate to severe pain in association with a high number of menstrual symptoms, school absence and interference with life activities should be effectively managed to minimise menstrual morbidity. Those girls who do not respond to medical management should be considered for further investigation for possible underlying pathology, such as endometriosis.

Giant Magnetoresistance at Low Fields in Discontinuous NiFe-Ag Multilayer Thin Films.

A series of sputtered multilayers of Ni(80)Fe(20)-Ag was prepared to examine the giant magnetoresistance effect before and after annealing. For a wide range of NiFe and Ag thicknesses, no giant magnetoresistance was observed in the unannealed films. After annealing, a large, negative magnetoresistance was observed of order 4 to 6% in applied fields of order 5 to 10 oersteds at room temperature. The appearance of giant managetoresistance is concurrent with the breakup of the NiFe layers, which is attributable to a magnetostatic interaction that favors local antiparallel alignment of the moments in adjacent layers. These structures may be of significant practical importance as sensors that require large changes in resistance at low fields, such as magnetoresistive heads used in magnetic recording systems.

Autosegmentation of the rectum on megavoltage image guidance scans.

Autosegmentation of image guidance (IG) scans is crucial for streamlining and optimising delivered dose calculation in radiotherapy. By accounting for interfraction motion, daily delivered dose can be accumulated and incorporated into automated systems for adaptive radiotherapy. Autosegmentation of IG scans is challenging due to poorer image quality than typical planning kilovoltage computed tomography (kVCT) systems, and the resulting reduction of soft tissue contrast in regions such as the pelvis makes organ boundaries less distinguishable. Current autosegmentation solutions generally involve propagation of planning contours to the IG scan by deformable image registration (DIR). Here, we present a novel approach for primary autosegmentation of the rectum on megavoltage IG scans acquired during prostate radiotherapy, based on the Chan-Vese algorithm. Pre-processing steps such as Hounsfield unit/intensity scaling, identifying search regions, dealing with air, and handling the prostate, are detailed. Post-processing features include identification of implausible contours (nominally those affected by muscle or air), 3D self-checking, smoothing, and interpolation. In cases where the algorithm struggles, the best estimate on a given slice may revert to the propagated kVCT rectal contour. Algorithm parameters were optimised systematically for a training cohort of 26 scans, and tested on a validation cohort of 30 scans, from 10 patients. Manual intervention was not required. Comparing Chan-Vese autocontours with contours manually segmented by an experienced clinical oncologist achieved a mean Dice Similarity Coefficient of 0.78 (SE < 0.011). This was comparable with DIR methods for kVCT and CBCT published in the literature. The autosegmentation system was developed within the VoxTox Research Programme for accumulation of delivered dose to the rectum in prostate radiotherapy, but may have applicability to further anatomical sites and imaging modalities.

Delivered dose can be a better predictor of rectal toxicity than planned dose in prostate radiotherapy.

BACKGROUND AND PURPOSE: For the first time, delivered dose to the rectum has been calculated and accumulated throughout the course of prostate radiotherapy using megavoltage computed tomography (MVCT) image guidance scans. Dosimetric parameters were linked with toxicity to test the hypothesis that delivered dose is a stronger predictor of toxicity than planned dose. MATERIAL AND METHODS: Dose-surface maps (DSMs) of the rectal wall were automatically generated from daily MVCT scans for 109 patients within the VoxTox research programme. Accumulated-DSMs, representing total delivered dose, and planned-DSMs, from planning CT data, were parametrised using Equivalent Uniform Dose (EUD) and 'DSM dose-width', the lateral dimension of an ellipse fitted to a discrete isodose cluster. Associations with 6 toxicity endpoints were assessed using receiver operator characteristic curve analysis. RESULTS: For rectal bleeding, the area under the curve (AUC) was greater for accumulated dose than planned dose for DSM dose-widths up to 70Gy. Accumulated 65Gy DSM dose-width produced the strongest spatial correlation (AUC 0.664), while accumulated EUD generated the largest AUC overall (0.682). For proctitis, accumulated EUD was the only reportable predictor (AUC 0.673). Accumulated EUD was systematically lower than planned EUD. CONCLUSIONS: Dosimetric parameters extracted from accumulated DSMs have demonstrated stronger correlations with rectal bleeding and proctitis, than planned DSMs.

Automatic contour propagation using deformable image registration to determine delivered dose to spinal cord in head-and-neck cancer radiotherapy.

To determine delivered dose to the spinal cord, a technique has been developed to propagate manual contours from kilovoltage computed-tomography (kVCT) scans for treatment planning to megavoltage computed-tomography (MVCT) guidance scans. The technique uses the Elastix software to perform intensity-based deformable image registration of each kVCT scan to the associated MVCT scans. The registration transform is then applied to contours of the spinal cord drawn manually on the kVCT scan, to obtain contour positions on the MVCT scans. Different registration strategies have been investigated, with performance evaluated by comparing the resulting auto-contours with manual contours, drawn by oncologists. The comparison metrics include the conformity index (CI), and the distance between centres (DBC). With optimised registration, auto-contours generally agree well with manual contours. Considering all 30 MVCT scans for each of three patients, the median CI is [Formula: see text], and the median DBC is ([Formula: see text]) mm. An intra-observer comparison for the same scans gives a median CI of [Formula: see text] and a DBC of ([Formula: see text]) mm. Good levels of conformity are also obtained when auto-contours are compared with manual contours from one observer for a single MVCT scan for each of 30 patients, and when they are compared with manual contours from six observers for two MVCT scans for each of three patients. Using the auto-contours to estimate organ position at treatment time, a preliminary study of 33 patients who underwent radiotherapy for head-and-neck cancers indicates good agreement between planned and delivered dose to the spinal cord.

Hepatocellular carcinoma results from chronic cyclin D1 overexpression in transgenic mice.

Cyclin D1 is a known oncogene and a key regulator of cell cycle progression. Amplification of the cyclin D1 gene and its overexpression have been associated with aggressive forms of human hepatocellular carcinoma (HCC). In this study, two independent lines of transgenic mice have been generated that express cyclin D1 under the control of the rat liver fatty acid binding protein promoter. This transgene specifically directs expression in the liver and the intestines. RNA and protein analysis demonstrated increased expression of the cyclin D1 gene product in the liver and bowel when compared with wild-type siblings. Both transgenic lines developed progressive liver disease. Examination of H&E stained sections of the liver and bowel revealed hyperplastic changes in the liver by 3 months of age. By 6 months of age, transgenic mice had obvious hepatomegaly and histological evidence of dysplasia in the liver. These early changes were significantly more dramatic in male animals when compared with female animals. By 9 months of age adenomas of the liver appeared, progressing to HCC over the ensuing 6-month period. By 15-17 months of age, 87% of male and 69% of female animals had either adenomatous nodules or HCCs. By 17 months of age, 31% of male and female animals had disease that had progressed to HCC. These animals represent a unique and significant new model for the study of human HCC. This study demonstrates that overexpression of cyclin D1 is sufficient to initiate hepatocellular carcinogenesis.

Nuclear magnetic resonance study of doxorubicin binding to cardiolipin containing magnetically oriented phospholipid bilayers.

Doxorubicin (DOX) is a potent anthracycline cancer drug whose interaction with anionic membrane phospholipids, such as cardiolipin (CL), is thought to contribute to its cytotoxicity as well as induce cardiotoxic side effects. We have studied the interaction of DOX with a CL containing model membrane system using high resolution, oriented sample (31)P and (2)H NMR. The model membrane system is composed of a bilayer forming phospholipid and a detergent that breaks the extended bilayers into disc-shaped micelles (bicelles) that can orient in a magnetic field. The effects of DOX on the phospholipid bilayer were monitored using samples containing dimyristoylphosphatidylcholine (DMPC), selectively deuterated in either headgroup or acyl chain positions, and measuring the changes in (2)H quadrupolar splittings as DOX was added. Changes in quadrupolar splittings upon DOX addition provide evidence for interaction with both surface and buried sites within the membrane bilayer.

Cloning and expression of the axolotl proto-oncogene ski.

In vitro and in vivo overexpression studies have demonstrated that the c-ski proto-oncogene can influence proliferation, morphological transformation and myogenic differentiation. We report the isolation and expression of an axolotl (Ambystoma mexicanum) c-ski (aski) gene. Sequence analysis revealed a high degree of nucleotide and predicted amino acid (AA) homology with mammalian and anuran c-ski, showing the highest conservation to Xenopus laevis c-ski (74% nucleotide and 87% AA). Northern analysis showed that axolotl c-ski is expressed in unfertilized eggs and at increasing levels in embryos from blastula to tadpole stage. c-ski expression was also detected in larval limb muscle and in several stages of regenerating limb blastemas. These data indicate that axolotl c-ski is highly conserved among amphibians and mammals and suggests that it plays a role in urodele embryogenesis and limb regeneration.

Early assessment of myocardial salvage by contrast-enhanced magnetic resonance imaging.

BACKGROUND: Myocardial salvage after acute myocardial infarction is defined clinically by early restoration of flow and long-term improvement in contractile function. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI), performed early after myocardial infarction, indexes myocardial salvage. We studied the relationship between the transmural extent of hyperenhancement by contrast-enhanced MRI, restoration of flow, and recovery of function. METHODS AND RESULTS: The left anterior descending coronary artery was occluded in dogs (n=15) for either 45 minutes, 90 minutes, or permanently. Cine and contrast-enhanced MRI were performed 3 days after the procedure; cine MRI was also done 10 and 28 days after the procedure. The transmural extent of hyperenhancement and wall thickening were determined using a 60-segment model. The mean transmural extent of hyperenhancement for the 45-minute occlusion group was 22% of the 90-minute group and 18% of the permanent occlusion group (P:<0.05 for both). The transmural extent of hyperenhancement on day 3 was related to future improvement in both wall thickening score and absolute wall thickening at 10 and 28 days (P:<0.0001 for each). For example, of the 415 segments on day 3 that were dysfunctional and had <25% transmural hyperenhancement, 362 (87%) improved by day 28. Conversely, no segments (0 of 9) with 100% hyperenhancement improved. The transmural extent of hyperenhancement on day 3 was a better predictor of improvement in contractile function than occlusion time (P:<0.0001). CONCLUSIONS: A reduction in the transmural extent of hyperenhancement by contrast-enhanced MRI early after myocardial infarction is associated with an early restoration of flow and future improvement in contractile function.

Relationship of heart rate variability to parasympathetic effect.

BACKGROUND: Baroreflex-mediated parasympathetic stimulation has variable effects on heart rate variability (HRV). We postulated that a quadratic function would describe the relationship between HRV and parasympathetic effect better than a linear function. METHODS AND RESULTS: Twenty-nine normal volunteers (15 women; mean age 39+/-12 years) were studied after beta-adrenergic blockade with intravenous propranolol. Five-minute ECG recordings were made during graded infusions of phenylephrine and nitroprusside to achieve baroreflex-mediated increases and decreases in parasympathetic effect, respectively. Time- and frequency-domain measures of HRV were calculated from the R-R interval tachograms. The R-R interval and the vagal-sympathetic effect (VSE=R-R interval/intrinsic R-R interval) were used as indices of parasympathetic effect. The data were fit to both quadratic and linear models. In each case, the quadratic model (with a negative coefficient for the squared term) was superior to the linear model. There was some evidence that age influenced the responsiveness of the HRV parameters with changing parasympathetic effect, although the regression analysis was significant only in the models for MSSD (P<0.03) and pNN50 (P<0.001). CONCLUSIONS: The relationship between HRV and parasympathetic effect is best described by a function in which there is an ascending limb where HRV increases as parasympathetic effect increases until it reaches a plateau level; HRV then decreases as parasympathetic effect increases. Because there is marked interindividual variation in this relationship, differences in HRV between individuals may reflect differences in this relationship and/or differences in autonomic effects.

Improvement in hypertension in patients with diabetes mellitus after kidney/pancreas transplantation.

BACKGROUND: Hypertension persists in many patients with diabetes mellitus after kidney transplantation. However, the impact of control of diabetes as well as kidney failure on hypertension by combined kidney and pancreas transplantation has not been studied. METHODS AND RESULTS: Between March 1993 and August 1998, 111 patients with type 1 diabetes mellitus underwent successful pancreas transplantation (108 kidney/pancreas transplantation) and another 28 patients with type 1 diabetes mellitus underwent isolated kidney transplantation. Blood pressure measurements and all antihypertensive medications were determined for both groups before transplantation and at 1, 3, 6, and 12 months and at the most recent outpatient evaluation after transplantation. At baseline, the mean blood pressure was 151/88 and 151/83 mm Hg for the kidney/pancreas and isolated kidney transplant patients, respectively. The mean blood pressure decreased to 134/77 mm Hg 1 month after kidney/pancreas transplantation (P<0.001) and decreased further to 126/70 mm Hg (P<0.001) at a mean follow-up of 18 months. This reduction in blood pressure after transplantation occurred despite a decrease in antihypertensive medications and the institution of immunosuppressive agents. At 1 month after kidney/pancreas transplantation, the average number of antihypertensive medications per patient was 0.9+/-1.0, compared with 2.5+/-1.1 before surgery (P<0.001). At 18 months after transplantation, 34% of patients were both normotensive (blood pressure

Limits of detection of regional differences in vasodilated flow in viable myocardium by first-pass magnetic resonance perfusion imaging.

BACKGROUND: Perfusion imaging techniques intended to identify regional limitations in coronary flow reserve in viable myocardium need to identify 2-fold differences in regional flow during coronary vasodilation consistently. This study evaluated the suitability of current first-pass magnetic resonance approaches for evaluating such differences, which are 1 to 2 orders of magnitude less than in myocardial infarction. METHODS AND RESULTS: Graded regional differences in vasodilated flow were produced in chronically instrumented dogs with either left circumflex (LCx) infusion of adenosine or partial LCx occlusion during global coronary vasodilation. First-pass myocardial signal intensity-time curves were obtained after right atrial injection of gadoteridol (0.025 mmol/kg) with an MRI inversion recovery true-FISP sequence. The area under the initial portion of the LCx curve was compared with that of a curve from a remote area of the ventricle. Relative LCx and remote flows were assessed simultaneously with microspheres. The ratio of LCx and remote MRI curve areas and the ratio of LCx and remote microsphere concentrations were highly correlated and linearly related over a 5-fold range of flow differences (y=0.96 x+/-0.07, P<0.0001, r(2)=0.87). The 95% confidence limits for individual MRI measurements were +/-35%. Regional differences of >/=2-fold were consistently apparent in unprocessed MR images. CONCLUSIONS: Clinically relevant regional reductions in vasodilated flow in viable myocardium can be detected with 95% confidence over the range of 1 to 5 times resting flow. This suggests that MRI can identify and quantify limitations in perfusion reserve that are expected to be produced by stenoses of >/=70%.

Effect of physiologic and pharmacologic adrenergic stimulation on heart rate variability.

OBJECTIVES: The aim of this study was to evaluate and compare the effects of physiologic and pharmacologic sympathetic stimulation on time and frequency domain indexes of heart rate variability. BACKGROUND: Measurements of heart rate variability have been used as indexes of sympathetic tone. To date, the effects of circulating catecholamines on heart rate variability have not been evaluated. METHODS: Fourteen normal subjects (eight men, six women, mean [+/- SD] age 28.5 +/- 4.8 years) were evaluated. Five-minute electrocardiographic recordings were obtained in triplicate after physiologic and pharmacologic sympathetic stimulation: during upright tilt, after maximal exercise, during epinephrine and isoproterenol infusions at 50 ng/kg body weight per min, during beta-adrenergic blockade and during combined beta-adrenergic and parasympathetic blockade. RESULTS: Beta-adrenergic stimulation resulted in a significant decrease in time domain measures of heart rate variability. The frequency domain indexes showed variable responses, depending on the individual stimulus. Tilt caused an increase in low frequency power and in the ratio of low to high frequency power. These changes were not necessarily observed with other conditions of beta-adrenergic stimulation. Double blockade suppressed baseline heart rate variability, but beta-adrenergic blockade had no significant effect. Time domain measures of heart rate variability demonstrated excellent reproducibility over the three recordings, but the frequency domain variables demonstrated fair to excellent reproducibility. CONCLUSIONS: These findings suggest that different modes of beta-adrenergic stimulation may result in divergent heart rate variability responses. Thus, current heart rate variability techniques cannot be used as general indexes of "sympathetic" tone. Studies utilizing heart rate variability to quantify sympathetic tone need to consider this.

Prognostic implications of myocardial contractile reserve in patients with coronary artery disease and left ventricular dysfunction.

OBJECTIVES: This study was performed to assess the prognostic implications of myocardial contractile reserve (MCR) in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND: MCR during dobutamine stress echocardiography (DSE) identifies viable myocardium that may improve in function after revascularization. Whether revascularization influences prognosis of patients with MCR has not been determined. METHODS: We performed DSE in 80 patients with CAD and LV dysfunction (ejection fraction < or =40%). Viable myocardium was defined in dysfunctional myocardial segments as enhanced thickening and contraction during low-dose dobutamine (5 to 10 mcg/kg/min). Serial prospective follow-up was obtained in all patients (mean follow-up 2.2 +/- 1.1 years). RESULTS: Among 52 patients treated medically, there were 20 cardiac deaths. By multivariate analysis, the number of dysfunctional segments demonstrating MCR was the strongest predictor of survival (p < 0.03). Patients with MCR had better initial survival during medical therapy than did those without MCR, but this survival advantage was not maintained beyond three years. In contrast, survival was excellent in patients with MCR who underwent myocardial revascularization. Among 58 patients with MCR in > or =5 myocardial segments, survival at three years was 93 +/- 6% in the 24 patients who were revascularized but only 49 +/- 15% in the 34 treated medically (p < 0.02). CONCLUSIONS: Myocardial contractile reserve is a significant predictor of survival in patients with CAD and LV dysfunction undergoing medical therapy. Although patients with MCR have an initial survival advantage, this advantage is lost over the course of three years. In contrast, survival in patients with significant MCR is enhanced by revascularization.