Utilization of bone mineral density testing among breast cancer survivors in British Columbia, Canada.

Breast cancer survivors are at high osteoporosis risk. Bone mineral density testing plays a key role in osteoporosis management. We analyzed a historical utilization of bone mineral density testing in breast cancer survivors. The utilization remained low in the 1995-2008 period. Lower socio-economic status and rural residency were associated with lower utilization. INTRODUCTION: To evaluate the utilization of bone mineral density (BMD) testing for female breast cancer survivors aged 65+ surviving ≥ 3 years in British Columbia, Canada. METHODS: A retrospecitve population-based data linkage study. Trends in proportion of survivors with ≥ 1 BMD test for each calendar year from 1995 to 2008 were evaluated with a serial cross-sectional analysis. Associations between factors (socio-demographic and clinical) and BMD testing rates over the period 2006-2008 for 7625 survivors were evaluated with a cross-sectional analysis and estimated as adjusted prevalence ratios (PRadj) using log-binomial models. RESULTS: Proportions of survivors with ≥ 1 BMD test increased from 1.0% in 1995 to 10.1% in 2008. The BMD testing rate in 2006-2008 was 26.5%. Socio-economic status (SES) and urban/rural residence were associated with BMD testing rates in a dose-dependent relationship (p for trend< 0.01). Survivors with lower SES (PRadj = 0.66-0.78) or rural residence (PRadj = 0.70) were 20-30% less likely to have BMD tests, compared with survivors with the highest SES or urban residence. BMD testing rates were also negatively associated with older age (75+) (PRadj = 0.47; 95% CI = 0.42, 0.52), nursing home residency (0.05; 0.01, 0.39), recent osteoporotic fractures (0.21; 0.14, 0.32), and no previous BMD tests (0.26; 0.23, 0.29). CONCLUSION: Utilization of BMD testing was low for breast cancer survivors in BC, Canada. Lower SES and rural residence were associated with lower BMD testing rates. IMPLICATION FOR CANCER SURVIVORS: Female breast cancer survivors, especially those with lower SES or rural residence, should be encouraged to receive BMD tests as recommended by Canadian guidelines.

Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of InterLymph case-control studies.

BACKGROUND: Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. DESIGN: Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. RESULTS: Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69-0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54-0.80) and FL (pooled OR = 0.82, 95% CI 0.66-1.01). CONCLUSION: Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL.

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph).

BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case-control studies.

BACKGROUND: The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. MATERIALS AND METHODS: Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. RESULTS: Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled OR(trend) = 0.88, 95% CI 0.81-0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04-1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65-1.16). CONCLUSIONS: Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Metabolomics and cancer preventive behaviors in the BC Generations Project.

Metabolomics can detect metabolic shifts resulting from lifestyle behaviors and may provide insight on the relevance of changes to carcinogenesis. We used non-targeted nuclear magnetic resonance to examine associations between metabolic measures and cancer preventive behaviors in 1319 participants (50% male, mean age 54 years) from the BC Generations Project. Behaviors were dichotomized: BMI < 25 kg/m2, ≥ 5 servings of fruits or vegetables/day, ≤ 2 alcoholic drinks/day for men or 1 drink/day for women and ≥ 30 min of moderate or vigorous physical activity/day. Linear regression was used to estimate coefficients and 95% confidence intervals with a false discovery rate (FDR) of 0.10. Of the 218 metabolic measures, 173, 103, 71 and 6 were associated with BMI, fruits and vegetables, alcohol consumption and physical activity. Notable findings included negative associations between glycoprotein acetyls, an inflammation-related metabolite with lower BMI and greater fruit and vegetable consumption, a positive association between polyunsaturated fatty acids and fruit and vegetable consumption and positive associations between high-density lipoprotein subclasses with lower BMI. These findings provide insight into metabolic alterations in the context of cancer prevention and the diverse biological pathways they are involved in. In particular, behaviors related to BMI, fruit and vegetable and alcohol consumption had a large metabolic impact.

Cancer and aplastic anemia in British Columbia farmers.

For evaluation of occupational mortality in agriculture, age-standardized proportional mortality ratios (PMR) were calculated for 28,032 male farmers with the use of British Columbia (B.C.) death registrations collected from 1950 to 1978. Farmers had significantly elevated risks of death from cancer of the lip (PMR = 191, P = .05), stomach (PMR = 119, P less than .0001), and prostate gland (PMR = 113, P less than .001). In addition, leukemia was higher than expected (PMR = 122, P less than .01), as was aplastic anemia (PMR = 174, P less than .01). The elevated risks were fairly consistent over the 29-year period for stomach, prostate gland, and lip cancer, as well as for leukemia. The PMR for aplastic anemia was highest for the years 1950-59 and declined over the next 19 years. Farmers also showed significant mortality deficits for several important cancer sites, including esophagus (PMR = 59, P less than .0001), colon (PMR = 84, P less than .001), larynx (PMR = 62, P less than .01), and lung (PMR = 66, P less than .0001) for the period 1950-78. More detailed studies in B.C. will be necessary to confirm and extend these cancer-agriculture associations.

Socioeconomic status, sunlight exposure, and risk of malignant melanoma: the Western Canada Melanoma Study.

In a study of 261 male melanoma patients and age-and sex-matched controls, a strong positive univariate association between socioeconomic status, as determined by usual occupation, and risk of melanoma was detected. This association, however, was substantially explained by host constitutional factors and occupational, recreational, and vacation sunlight exposure. The study demonstrated an increased risk of melanoma in draftsmen and surveyors and a reduced risk of melanoma in construction workers and individuals employed in the finance, insurance, and real estate industry even after control for the effect of host factors and sunlight exposure.

Risk factors for ocular melanoma: Western Canada Melanoma Study.

Between April 1, 1979, and March 31, 1981, 90 individuals in the four western provinces of Canada were diagnosed as having ocular melanomas. Of 87 age-eligible cases (age 20-79 yr), 65 (75%) were interviewed along with age- and sex-matched controls chosen at random from the provincial populations. Individuals with blue eyes had a significantly greater crude risk of ocular melanoma than those with brown eyes [odds ratio (OR)=3.0, P=.04]. Subjects with red or blonde hair were at higher risk of having ocular melanoma than those with black or dark-brown hair (OR=7.7, P=.03). Indoor workers appeared to be at elevated risk for ocular melanoma even after controlling for eye and hair color (OR=3.5, P=.006).

Fluid intake and hydration status in obese vs normal weight children.

BACKGROUND/OBJECTIVES: Little is known on the relationship between obesity and hydration levels in children. This study assessed whether and by which mechanisms hydration status differs between obese and non-obese children. SUBJECTS/METHODS: Hydration levels of 86 obese and 89 normal weight children (age: 7-11 years) were compared. Hydration was measured as the average free water reserve (FWR=urine output/24 h minus the obligatory urine output [total 24 h excreted solutes/97th percentile of urine osmolality of children with adequate water intake, that is, 830 mOsm/kg]) over 2 days. Three days of weighed dietary and fluid intakes were recorded. Non-parametric tests were used to compare variables that were skewed and to assess which variables correlated with hydration. Variables mediating the different hydration levels of obese and normal weight children were assessed by co-variance analysis. RESULTS: Obese children were less hydrated than normal weight peers [FWR=median (IQR): 0.80 (-0.80-2.80) hg/day vs 2.10 (0.10-4.45) hg/day, P<0.02; 32% of obese children vs 20% of non-obese peers had negative FWR, P<0.001]. Body mass index (BMI) z-score (z-BMI) and water intake from fluids correlated with FWR (ρ=-0.18 and 0.45, respectively, both P<0.05). Water intake from fluids completely explained the different hydration between obese and normal weight children [FWR adjusted for water from fluids and z-BMI=2.44 (0.44) hg vs 2.10 (0.50) hg, P=NS; B coefficient of co-variation between FWR (hg/day) and water intake from fluids (hg/day)=0.47, P<0.001]. CONCLUSIONS: Obese children were less hydrated than normal weight ones because, taking into account their z-BMI, they drank less. Future prospective studies are needed to explore possible causal relationships between hydration and obesity.

Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves systolic function in heart failure patients with ventricular conduction delay by stimulating the left ventricle (LV) or both ventricles (biventricular, BV). Optimal LV site selection is of major clinical interest for CRT device implantation; however, the dependence of hemodynamics on LV stimulation site has not been established. Thus, the objective of this study was to compare the hemodynamic response to CRT for 2 LV coronary vein sites: the free wall and anterior wall. Methods and Results- A total of 30 patients (mean NYHA class, 2.7; mean QRS interval, 152 ms; mean PR interval, 194 ms) enrolled in the PATH-CHF-II trial were studied. CRT was administered with LV and BV stimulation in VDD mode at 4 AV delays. LV stimulation was at the lateral free wall or anterior wall, whereas right ventricular stimulation was fixed near the apex. LV+dP/dt(max) and aortic pulse pressure changes from baseline during CRT were compared for LV sites. Free wall sites with LV and BV stimulation yielded significantly larger LV+dP/dt(max) (14% versus 6%, P<0.001 for LV; 12% versus 5%, P<0.001 for BV) and pulse pressure (8% versus 4%, P<0.001 for LV; 9% versus 5%, P<0.001 for BV) compared with anterior sites. In one third of patients, CRT at free wall sites increased LV+dP/dt(max), whereas it decreased at anterior sites over most AV delays. CONCLUSION: CRT with LV free wall stimulation produced significantly better LV systolic performance compared with anterior stimulation. Further studies are warranted to prove the clinical superiority of the LV free wall as a site for long-term CRT.

Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block.

BACKGROUND: Left ventricular or biventricular pacing/stimulation can acutely improve systolic function in patients with dilated cardiomyopathy (DCM) and intraventricular conduction delay by resynchronizing contraction. Most heart failure therapies directly enhancing systolic function do so while concomitantly increasing myocardial oxygen consumption (MVO(2)). We hypothesized that pacing/stimulation, in contrast, incurs systolic benefits without raising energy demand. METHODS AND RESULTS: Ten DCM patients with left bundle-branch block (ejection fraction 20+/-3%, QRS duration 179+/-3 ms, mean+/-SEM) underwent cardiac catheterization to measure ventricular and aortic pressure, coronary blood flow, arterial-coronary sinus oxygen difference (DeltaAVO(2)), and MVO(2). Data were measured under sinus rhythm or with left ventricular or biventricular pacing/stimulation at the same heart rate. These results were then contrasted to intravenous dobutamine (n=7) titrated to match systolic changes during LV pacing. Systolic function rose quickly and substantially from LV pacing (18+/-4% rise in arterial pulse pressure, which correlates with cardiac output, and 43+/-6% increase in dP/dt(max); both P<0.01). However, DeltaAVO(2) and MVO(2) declined -4+/-2% and -8+/-6.5%, respectively (both P<0.05). Similar results were obtained with biventricular activation. In contrast, dobutamine raised dP/dt(max) 37+/-6%, accompanied by a 22+/-11% rise in per-beat MVO(2) (P<0.05 versus pacing). CONCLUSIONS: Ventricular resynchronization by left ventricular or biventricular pacing/stimulation in DCM patients with left bundle-branch block acutely enhances systolic function while modestly lowering energy cost. This should prove valuable for treating DCM patients with basal dyssynchrony.

Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. The Pacing Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group.

BACKGROUND: Previous studies of pacing therapy for dilated congestive heart failure (CHF) have not established the relative importance of pacing site, AV delay, and patient heterogeneity on outcome. These variables were compared by a novel technique that evaluated immediate changes in hemodynamic function during brief periods of atrial-synchronous ventricular pacing. METHODS AND RESULTS: Twenty-seven CHF patients with severe left ventricular (LV) systolic dysfunction and LV conduction disorder were implanted with endocardial pacing leads in the right atrium and right ventricle (RV) and an epicardial lead on the LV and instrumented with micromanometer catheters in the LV, aorta, and RV. Patients in normal sinus rhythm were stimulated in the RV, LV, or both ventricles simultaneously (BV) at preselected AV delays in a repeating 5-paced/15-nonpaced beat sequence. Maximum LV pressure derivative (LV+dP/dt) and aortic pulse pressure (PP) changed immediately at pacing onset, increasing at a patient-specific optimal AV delay in 20 patients with wide surface QRS (180+/-22 ms) and decreasing at short AV delays in 5 patients with narrower QRS (128+/-12 ms) (P<0.0001). Overall, BV and LV pacing increased LV+dP/dt and PP more than RV pacing (P<0.01), whereas LV pacing increased LV+dP/dt more than BV pacing (P<0.01). CONCLUSIONS: In this population, CHF patients with sufficiently wide surface QRS benefit from atrial-synchronous ventricular pacing, LV stimulation is required for maximum acute benefit, and the maximum benefit at any site occurs with a patient-specific AV delay.

Prognostic variables in patients with diffuse large-cell lymphoma treated with MACOP-B.

One hundred twenty-six patients with diffuse large-cell lymphoma were treated with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between April 1981 and June 1986. Univariate and multivariate analyses were performed using overall survival as of September 1989 as the end point. Four independent negative predictors of survival were identified: presence of B symptoms; more than two involved lymph node sites; more than one extranodal site (variables related to tumor burden), and age older than 60, a variable related to the patient's ability to tolerate treatment. Each variable contributed the same relative risk of dying and, accordingly, this simple predictive formula was developed empirically: (4-N) x 30 = the approximate percentage of chance of survival at 5 years. "N" is the number of predictive variables present. The same four predictors were also found to be significant by multivariate analysis when only those patients achieving a complete response were analyzed.

Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy.

PURPOSE: At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed. PATIENTS AND METHODS: One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission. RESULTS: The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor. CONCLUSIONS: Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.

Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy.

Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year event-free survival in this group is 17% (95% CI, 5% to 54%). Response data on the MM and CML patients will be reported subsequently. BUCY-2 plus melphalan at a dose of 90 mg/m2 before AuBMT produces acceptable toxicity in patients who are not heavily pretreated. A full evaluation of the antineoplastic effects of this regimen requires further study.

Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances.

OBJECTIVES: We sought to investigate the impact of six months of cardiac resynchronization therapy (CRT) on echocardiographic variables of left ventricular (LV) function. BACKGROUND: Cardiac resynchronization therapy has recently been introduced as a new therapeutic modality in patients with advanced heart failure (HF) and conduction abnormalities. However, most studies have only investigated the early hemodynamic effects of CRT. METHODS: Twenty-five patients (12 women and 13 men; 59.8 +/- 5.1 years old) with advanced HF caused by ischemic (n = 7) or idiopathic dilated cardiomyopathy (n = 18) and a prolonged QRS complex were analyzed. All patients underwent early hemodynamic testing with a randomized testing protocol; echocardiographic measurements were compared before implantation and after six months of CRT. RESULTS: Left ventricular end-diastolic and end-systolic diameters (LVEDD and LVESD, respectively) were significantly reduced after six months (LVEDD from 71 +/- 10 to 68 +/- 11 mm, p = 0.027; LVESD from 63 +/- 11 to 58 +/- 11 mm, p = 0.007), as were LV end-diastolic and end-systolic volumes (LVEDV from 253 +/- 83 to 227 +/- 112 ml, p = 0.017; LVESV from 202 +/- 79 to 174 +/- 101 ml, p = 0.009). Ejection fraction was significantly increased (from 22 +/- 7% to 26 +/- 9%, p = 0.03). "Nonresponders," with regard to LV volume reduction, had significantly higher baseline LVEDV, compared with "responders" (351 +/- 52 vs. 234 +/- 74 ml, p = 0.018). Overall, there was only mild mitral regurgitation at baseline, with a minor reduction by semiquantitative analysis. The results of early hemodynamic testing did not predict the volume response. CONCLUSIONS: Cardiac resynchronization therapy may lead to a reduction in LV volumes in patients with advanced HF and conduction disturbances. Volume nonresponders have significantly higher baseline LVEDV.

Detection of left ventricular regional myocardial ischaemia in dogs by intraventricular conductance catheter.

Nine adult mongrel dogs were instrumented with ultrasonic microcrystals to measure left ventricular basal anteroposterior diameter and midwall myocardial segment length near the cardiac apex. Pneumatic cuff occluders were positioned around the left circumflex coronary artery near its origin and around the left anterior descending coronary artery two thirds of the way along its length. A pressure microtransducer was implanted into the left ventricle. Ten days after instrumentation the animals were anaesthetised with morphine chlorhydrate and pentobarbital sodium. An eight electrode catheter was advanced into the left ventricle to measure ventricular apical and basal regional and total electrical conductance. Minor ischaemia caused by occlusion of the left anterior descending artery was detected only by the electrode pair located near the apex, as decreased local ejection fraction. Major ischaemia caused by left circumflex artery occlusion was detected by both apical and basal electrode pairs and by total conductance, the three conductance signals indicating reduced ejection fractions compared with control values. The basal diameter signal indicated that basal regional motility changed only during major ischaemia, thus confirming the specificity of the changes in the basal conductance signals. The apical segment length signal confirmed the altered motility indicated by the apical conductance signal. These results suggest that regional wall motion abnormalities may be detected by the use of a multielectrode conductance catheter.

Parity and carotid artery atherosclerosis in elderly women: The Rotterdam Study.

BACKGROUND AND PURPOSE: It has been postulated that physiological changes in the cardiovascular system, lipids, and glucose metabolism during pregnancy may increase subsequent risk of cardiovascular disease. Examination of the association between parity and risk factors for atherosclerosis may contribute information regarding possible mechanisms. METHODS: The relationship of parity with cardiovascular risk factors and the presence of carotid atherosclerosis was examined in the Rotterdam Study, a population-based study comprising 4878 women aged 55 years and older. Carotid atherosclerosis was assessed by ultrasonographic detection of plaques in the common carotid artery and bifurcation. Logistic regression models were used to compute odds ratios and 95% confidence intervals, adjusted for confounding factors. RESULTS: Parity was inversely associated with high-density lipoprotein cholesterol, and alcohol intake. Parity was positively associated with body mass index, total/HDL cholesterol ratio, insulin resistance, age at menopause, and socioeconomic status. Relative to nulliparous women, parous women had 36% (9% to 71%) greater risk of carotid atherosclerosis, rising to 64% in women with >/=4 children (19% to 127%). Adjustment for known cardiovascular risk factors, including insulin resistance and current lipid levels, did not diminish the magnitude of this association. CONCLUSIONS: Data demonstrated that there is a positive association between parity and risk of carotid artery plaques in elderly women and, further, that high parity is associated with lower HDL cholesterol levels and higher glucose/insulin ratios long after childbearing has ceased.

Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health.

Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% CI, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40-2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49-3.29) and to aldrin (OR, 3.42; 95% CI, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.