Exploring reasons for overuse of contralateral prophylactic mastectomy in Canada.

Background: Contralateral prophylactic mastectomy (cpm) in women with known unilateral breast cancer (bca) has been increasing despite the lack of supportive evidence. The purpose of the present study was to identify the determinants of cpm in women with unilateral bca. Methods: This qualitative descriptive study used semi-structured interviews informed by the Theoretical Domains Framework. We interviewed 74 key informants (surgical oncologists, plastic surgeons, medical oncologists, radiation oncologists, nurses, women with bca) across Canada. Interviews were analyzed using thematic analysis and an analysis for shared and discipline-specific beliefs. Results: In total, 58 factors influencing the use of cpm were identified: 26 factors shared by various health care professional groups, 15 discipline-specific factors (identified by a single health care professional group), and 17 factors shared by women with unilateral bca. Health care professionals identified more factors discouraging the use of cpm (n = 26) than encouraging its use (n = 15); women with bca identified more factors encouraging use of cpm (n = 12) than discouraging its use (n = 5). The factor most commonly identified by health care professionals that encouraged cpm was lack of awareness of existing evidence or guidelines for the appropriate use of cpm (n = 44, 75%). For women with bca, the factor most likely influencing their decision for cpm was wanting a better esthetic outcome (n = 14, 93%). Conclusions: Multiple factors discouraging and encouraging the use of cpm in unilateral bca were identified. Those factors identify potential individual, team, organization, and system targets for behaviour change interventions to reduce cpm.

Wait times for diagnosis and treatment of lung cancer: a single-centre experience.

BACKGROUND: Multiple clinical practice guidelines recommend rapid evaluation of patients with suspected lung cancer. It is uncertain whether delays in diagnosis and management have a negative effect on outcomes. METHODS: This retrospective study included 551 patients diagnosed with lung cancer through the diagnostic assessment program at the Institut universitaire de cardiologie et de pneumologie de Québec between September 2013 and March 2015. Median wait times between initial referral, diagnosis, and first treatment were calculated and compared with recommended targets. Analyses were performed to evaluate for specific factors associated with longer wait times and for the effect of delays on the outcomes of progression-free survival (pfs), relapse-free survival (rfs) after primary surgical resection, and overall survival (os). RESULTS: Most patients were investigated and treated within recommended targets. Of the entire cohort, 379 patients were treated at our institution. Of those 379 patients, 311 (82%) were treated within recommended targets. In comparing patients within and outside target times, the only statistically significant difference was found in the distribution of treatment modalities: patients meeting targets were more likely to be treated with surgery or chemotherapy rather than with radiation. The pfs on first treatment modality was influenced by clinical stage, but not by time to therapy [hazard ratio (hr): 1.10; p = 0.65]. The os for the entire cohort was also influenced by stage, but not by delays (hr: 1.04; p = 0.87). For the 209 patients treated by surgery with curative intent, a significant reduction in rfs was associated with male sex and TNM stage, but not with delays (hr: 1.11; p = 0.83). The os after primary surgical resection was also associated with TNM stage, but not with delays (hr: 1.82; p = 0.43). CONCLUSIONS: Recommended targets for wait times in the investigation and treatment of lung cancer can be achieved within a diagnostic assessment program. Compared with radiation treatment, treatment with surgery or chemotherapy is more likely to be completed within targets. Delays in investigation and treatment do not appear to negatively affect the clinical outcomes of os, rfs, and pfs. Prospective studies are needed to evaluate whether efficient work-up and treatment influence other important variables, such as quality of life, cost of care, and access to therapies while performance status is adequate.

Long-term nutritional impact of sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) has become a predominant bariatric procedure throughout the world. However, the long-term nutritional impact of this procedure is unknown. OBJECTIVES: To describe the nutritional deficiencies before and after SG and to analyze the influence of baseline weight on nutritional status. SETTING: University-affiliated tertiary care center. METHODS: All patients who underwent SG as a standalone procedure between 2008 and 2012 were included in this study. Patients were given multivitamin supplementation. Data were obtained from our prospectively maintained electronic database and are reported as mean ± standard deviation and percentage. Bivariate analyses were conducted to evaluate the influence of selected variables on outcomes. RESULTS: The mean age of the 537 patients was 48.0 ± 11.3 years, with an initial body mass index of 48.1 ± 8.7 kg/m2. Excess weight loss and total weight loss were 56.2% and 28.0% at 1 year and 43.0% and 21.1% at 5 years, respectively (P<.0001). Percentage of follow-up was 74% at 5 years (n = 79). The mean follow-up time was 34.3 ± 17.2 months. Hypoalbuminemia was present in 1.1% preoperatively and 4.2% at 5 years (P = .0043), low ferritin levels in 8.6% and 37.8% (P<.0001), low vitamin B12 in 30.3% and 16.4% (P<.0001), low vitamin D 63.2% and 24.3% (P<.0001), and hyperparathyroidism in 23.4% and 20.8% (P<.0001). There was no significant difference in the prevalence of anemia over time (P = 0.4301). The prevalence of vitamin A insufficiency peaked from 7.9% preoperatively to 28.7% at 3 months (P<.0001) and returned to baseline thereafter. Baseline weight was negatively correlated with vitamin B12 and vitamin D. CONCLUSION: Nutritional deficiencies are common in patients with morbid obesity before and after surgery. Preoperative supplementation and long-term nutritional follow-up are required to prevent nutritional deficiencies.

Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease.

BACKGROUND: Studies have shown that lipoprotein(a) [Lp(a)], an important carrier of oxidized phospholipids, is causally related to calcific aortic valve stenosis (CAVS). Recently, we found that Lp(a) mediates the development of CAVS through autotaxin (ATX). OBJECTIVE: To determine the predictive value of circulating ATX mass and activity for CAVS. METHODS: We performed a case-control study in 300 patients with coronary artery disease (CAD). Patients with CAVS plus CAD (cases, n = 150) were age- and gender-matched (1 : 1) to patients with CAD without aortic valve disease (controls, n = 150). ATX mass and enzymatic activity and levels of Lp(a) and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) were determined in fasting plasma samples. RESULTS: Compared to patients with CAD alone, ATX mass (P < 0.0001), ATX activity (P = 0.05), Lp(a) (P = 0.003) and OxPL-apoB (P < 0.0001) levels were elevated in those with CAVS. After adjustment, we found that ATX mass (OR 1.06, 95% CI 1.03-1.10 per 10 ng mL-1 , P = 0.001) and ATX activity (OR 1.57, 95% CI 1.14-2.17 per 10 RFU min-1 , P = 0.005) were independently associated with CAVS. ATX activity interacted with Lp(a) (P = 0.004) and OxPL-apoB (P = 0.001) on CAVS risk. After adjustment, compared to patients with low ATX activity (dichotomized at the median value) and low Lp(a) (<50 mg dL-1 ) or OxPL-apoB (<2.02 nmol L-1 , median) levels (referent), patients with both higher ATX activity (≥84 RFU min-1 ) and Lp(a) (≥50 mg dL-1 ) (OR 3.46, 95% CI 1.40-8.58, P = 0.007) or OxPL-apoB (≥2.02 nmol L-1 , median) (OR 5.48, 95% CI 2.45-12.27, P < 0.0001) had an elevated risk of CAVS. CONCLUSION: Autotaxin is a novel and independent predictor of CAVS in patients with CAD.

Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity.

BACKGROUND AND OBJECTIVES: By studying cardiometabolic risk factors in children born after maternal biliopancreatic diversion bariatric surgery (AMS) compared with those in children born before maternal surgery (BMS), we tested the hypothesis that significant maternal weight loss may modify obesity-related factors transmitted via the intrauterine environment. DESIGN: Anthropometry and fasting blood levels were studied in 49 mothers who had lost 36 +/- 1.8% body weight sustained for 12 +/- 0.8 yr and their 111 children (54 BMS and 57 AMS) aged 2.5-26 yr. RESULTS: AMS children had lower birth weight (2.9 +/- 0.1 AMS vs. 3.3 +/- 0.1 kg BMS, P = 0.003) associated with a reduced prevalence of macrosomia (1.8 AMS vs. 14.8% BMS, P = 0.03) with no difference in underweight. At the time of follow-up, AMS children exhibited 3-fold lower prevalence of severe obesity (11 vs. 35%, P = 0.004), greater insulin sensitivity (homeostasis model assessment of insulin resistance index 3.4 +/- 0.3 vs. 4.8 +/- 0.5, P = 0.02), improved lipid profile (cholesterol/high-density lipoprotein cholesterol 2.96 +/- 0.11 vs 3.40 +/- 0.18, P = 0.03; high-density lipoprotein cholesterol 1.50 +/- 0.05 vs. 1.35 +/- 0.05 mmol/liter, P = 0.04), lower C-reactive protein (0.88 +/- 0.17 vs. 2.00 +/- 0.34 microg/ml, P = 0.004), and leptin (11.5 +/- 1.5 vs.19.7 +/- 2.5 ng/ml, P = 0.005) and increased ghrelin (1.28 +/- 0.06 vs.1.03 +/- 0.06 ng/ml, P = 0.005) than BMS offspring (AMS vs. BMS, respectively, for all). CONCLUSIONS: This unique study of children aged 2.5-26 yr born before and after maternal antiobesity surgery demonstrated improvements in cardiometabolic markers sustained into adolescence, attributable to an improved intrauterine environment.

Impact of high-fat /low-carbohydrate, high-, low-glycaemic index or low-caloric meals on glucose regulation during aerobic exercise in Type 2 diabetes.

AIMS: A decrement in blood glucose (BG) may be observed in patients with Type 2 diabetes (T2DM) when exercise is performed after a meal, in contrast to fasting. We determined the impact of different pre-exercise meal macronutrient compositions with modulation of the glycaemic index (GI) on glucose regulation during exercise in patients with T2DM. METHODS: Using a randomized, single-blind crossover design, 10 sedentary men performed five exercise sessions, once after an overnight fast, and also after each of four test meals, consisting of a high-fat/low-carbohydrate meal, a high-GI meal, a low-GI meal, and a low-calorie meal. RESULTS: Pre-exercise BG and insulin levels were comparable for all four meals. Exercise decreased BG and insulin levels during all meal conditions (all P < 0.001) compared with the fasting state in which BG levels did not change. The magnitude of BG and insulin decrements was similar after consuming the low-calorie, the high-GI and the high-fat/low-carbohydrate meals, whereas the low-GI meal induced the lowest BG fall. Adrenaline response was higher after consumption of the high-, the low-GI and the low-caloric meals compared with the high-fat/low-carbohydrate meal and with the fasting state (P < 0.05). CONCLUSIONS: This study underlines the beneficial effect of low-GI foods and the differential impact of pre-exercise meal macronutrient composition on BG decrease. This may protect against exercise-induced hypoglycaemia, and reiterates the safety of exercising while fasting in T2DM patients.

Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue.

Obesity and insulin resistance are independent risk factors for metabolic syndrome, diabetes, and cardiovascular disease. Adipose tissue samples from nonobese (NO), insulin-sensitive obese (ISO), and insulin-resistant obese (IRO) subjects from subcutaneous (SC) and omental (OM) adipose tissue (n = 28) were analyzed by microarray and confirmed by real-time PCR. Insulin signaling gene expression changes were greater in OM than in SC tissue and were related to insulin resistance rather than to obesity; few genes correlated with body mass index. Insulin receptor and insulin receptor substrate 1 (IRS-1) increased in the IRO versus pooled insulin-sensitive (NO+ISO) subjects. In glucose transport, PI3Kalpha and PDK2 decreased in IRO subjects, whereas PI3Kgamma, Akt2, GLUT4, and GLUT1 increased. IRS-1 regulators Jnk and IKK increased in IRO (P < 0.01 and P < 0.001 respectively). In protein synthesis, most genes examined were downregulated in IRO subjects, including mTor, Rheb, and 4EBP and eIF members (all P < 0.05). In proliferation, SHC, SOS, and Raf1 (P < 0.05) were increased, whereas Ras and MEK1/2 kinase 1 (P < 0.05) were decreased, in IRO subjects. Finally, in differentiation, PPARgamma, CEBPalpha, and CEBPbeta decreased, whereas PPARdelta, CEBPgamma, and CEBPepsilon increased, in IRO subjects (P < 0.05). Together, microarray and real-time PCR data demonstrate that insulin resistance rather than obesity is associated with altered gene expression of insulin signaling genes, especially in OM adipose tissue.

Impact of fasting and postprandial state on plasma carnitine concentrations during aerobic exercise in type 2 diabetes.

The effects of metabolic states of fasting and post-absorption on plasma concentrations of free carnitine (FC), acylcarnitine (AC) and total carnitine (TC) were compared during submaximal exercise in subjects with type 2 diabetes mellitus. Ten sedentary men (54+/-5 years) treated with oral hypoglycaemic agents were tested on two separate occasions: following an overnight fast and 2 h after a 395-kcal standardised breakfast. Exercise was performed at 60% of [Formula: see text]O(2peak) on a cycle ergometer for 60 min. Blood samples were drawn at rest for baseline values and following 60 min of exercise and 30 min of recovery. Our results show that: (1) baseline levels of TC, FC and AC were similar in fasted and postprandial groups, (2) TC and AC levels were increased during exercise in the fasted group only, (3) FC levels were decreased during exercise in both fasted and postprandial state and (4) the AC/FC ratio increased during exercise in the fasted group. Our results indicate that the metabolic state of the diabetic patient is associated with a different plasma carnitine status. These patterns may reflect differences in energy metabolism associated with fasting and postprandial hyperglycaemia.

Reduction of discomfort at sheath removal during transradial coronary procedures with the use of a hydrophilic-coated sheath.

Some patients experience discomfort at sheath removal during transradial procedures. We hypothesized that the use of a hydrophilic-coated sheath (HCS) would reduce the traction force needed at withdrawal and therefore the pain experienced by patients. Patients referred for coronary intervention were randomized to undergo transradial procedure with the use of HCS or with nonhydrophilic sheath (NHS). At removal of the sheath, peak traction force was recorded using an electronic traction gauge and patients were asked to quantify their pain. A total of 90 patients participated in the study. The mean +/- SD peak traction force at sheath removal was 265 +/- 167 g and 865 +/- 318 g in the HCS and NHS groups, respectively (69% reduction; P < 0.001). Mean maximal pain score was 0.6 +/- 1.2 and 4.8 +/- 2.9 in the HCS and NHS groups, respectively (88% reduction; P < 0.0001). Use of HCS for transradial procedures reduces considerably the traction force needed for sheath removal as well as pain experienced by patients when compared to NHS.

Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer.

STUDY OBJECTIVES: To estimate the prevalence of insomnia, describe clinical characteristics of sleep difficulties, assess the influence of cancer on the insomnia course, and identify potential risk factors involved in the development of insomnia among women who had received radiotherapy for non metastatic breast cancer. DESIGN: A sample of 300 consecutive women who had been treated with radiotherapy for non metastatic breast cancer first completed an insomnia screening questionnaire. Participants who reported sleep difficulties were subsequently interviewed over the phone to evaluate further the nature, severity, duration, and course of their insomnia. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Nineteen percent (n=56) of the participants met diagnostic criteria for an insomnia syndrome. In most cases (95%), insomnia was chronic. The onset of insomnia followed the breast cancer diagnosis in 33% of the patients and 58% of the patients reported that cancer either caused or aggravated their sleep difficulties. Factors associated with an increased risk for insomnia were sick leave, unemployment, widowhood, lumpectomy, chemotherapy, and a less severe cancer stage at diagnosis. Among women with insomnia symptoms, the risk to meet diagnostic criteria for an insomnia syndrome was higher in those who were separated and had a university degree. CONCLUSIONS: Insomnia is a prevalent and often chronic problem in breast cancer patients. Although it is not always a direct consequence of cancer, pre-existing sleep difficulties are often aggravated by cancer. It is therefore important to better screen breast cancer patients with insomnia and offer them an appropriate treatment.

Biological profiles in subjects with recurrent acute coronary events compared with subjects with long-standing stable angina.

BACKGROUND: At one end of the clinical spectrum of coronary artery disease (CAD) are subjects who have had repeated acute ischemic events, and at the other end are those with long-standing angina who have never been unstable. This study tests the hypothesis that a specific biological profile can distinguish these 2 extreme groups and predict acute coronary events. METHODS AND RESULTS: Blood levels of lipoprotein(a), homocysteine, tissue plasminogen activator, plasminogen activator inhibitor-1, C-reactive protein (CRP), fibrinogen, and von Willebrand factor were compared in 3 groups of 50 subjects each: (1) those with previous multiple acute coronary events, (2) age-matched subjects with >/=3 years of stable angina and no prior acute coronary events, and (3) matched controls without evidence of atherosclerotic disease and a normal coronary angiogram. All subjects were followed for 4.0 years. Lipoprotein(a), homocysteine, tissue plasminogen activator, and plasminogen activator inhibitor-1 were similar in both CAD groups and significantly higher than in the control group. However, compared with subjects with long-standing stable angina, those with previous multiple coronary events had higher values of CRP (5.7+/-5.4 versus 3.0+/-5.2 mg/L, P=0.012), fibrinogen (3.38+/-0.75 versus 2.92+/-0.64 g/L, P=0.001), and von Willebrand factor (1.60+/-0.55 versus 1.25+/-0.36 U/mL, P=0.0003). On follow-up, myocardial infarction and unstable angina occurred in 42% of the group with multiple events, 4% of the stable angina group (P<0.0001), and none of the control subjects. In the 100 patients with CAD, CRP was 4.9 mg/L in those with and 1.8 mg/L in those without new instability (P<0.0001). In a multivariate analysis, only CRP distinguished those with follow-up acute coronary events (adjusted odds ratio 5.9, 95% CI 2.0 to 17.9; P=0.002). A baseline CRP >3.5 mg/L had a relative risk of 7.6 (2.6 to 21.7, P=0.0002) for subsequent acute events. CONCLUSIONS: An inflammatory biological profile distinguished patients with previous multiple acute coronary events from those with long-standing stable angina and predicted acute coronary instability.

Plasma-volume contraction and exercise-induced hypoxaemia modulate erythropoietin production in healthy humans.

This study examined exercise-induced hypoxaemia (EIH) and plasma volume contraction as modulators of serum erythropoietin (Epo) production. Five athletes cycled for 3 min at supra-maximal power outputs, at each of two different elevations (1,000 m and 2,100 m). Five subjects were exposed to normobaric hypoxia (F(I)O(2)=0.159), seven subjects underwent plasmapheresis to reduce plasma volume and eight subjects were time controls for Epo levels. Oxyhaemoglobin saturation was significantly reduced during exercise and during normobaric hypoxia. The time period of haemoglobin oxygen saturation <91% was 24+/-29 s (mean+/-S.D., n=5) for exercise at 1000 m, 136+/-77 s (mean+/-S.D., n=5) for exercise at 2100 m and 178+/-255 s (mean+/-S.D., n=5) with resting hypoxic exposure. However, significantly increased serum Epo levels were observed only following exercise (24+/-3%; mean+/-S.D., n=5 at 1,000 m and 36+/-5%; mean+/-S.D., n=5 at 2,100 m). Volume contraction also resulted in increased serum Epo (35+/-6%; mean+/-S.D., n=7) in spite of a significant rise in haematocrit of 2.2%. Despite similar degrees of arterial desaturation, only the hypoxaemia induced by exercise was associated with an increase in serum Epo. This finding indicates that other factors, in addition to hypoxaemia, are important in modulating the production of Epo in response to exercise. Volume depletion in the absence of exercise resulted in increases in Epo levels that were comparable with those observed in response to exercise. The paradoxical responses of the increased haematocrit and the increase in Epo in subjects undergoing plasmapheresis suggests that plasma volume may also modulate the production of Epo.

Liver pathology and the metabolic syndrome X in severe obesity.

The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of adipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbohydrate, lipid, and steroid metabolism, we investigated the relationships between liver pathology and the metabolic syndrome. Blood chemistry, anthropometry (waist/hip circumference ratio), and intraoperative routine knife biopsies of the liver were obtained in 551 (112 men) severely obese patients (body mass index, 47 +/- 9; mean +/- SD) undergoing antiobesity surgery. Steatosis was found in 86%, fibrosis in 74%, mild inflammation or steatohepatitis in 24%, and unexpected cirrhosis in 2% (n = 11) of the patients. The risk of steatosis was 2.6 times greater in men than in women (P < 0.0001). With each addition of 1 of the 4 components of the metabolic syndrome, elevated waist/hip ratio, impaired glucose tolerance, hypertension, and dyslipidemia, the risk of steatosis increased exponentially from 1- to 99-fold (P < 0.001). Fibrosis correlated with steatosis (r = 0.56; P < 0.0001), whereas patients with diabetes or impaired glucose tolerance had a 7-fold increased risk of fibrosis (P < 0.0001). Diabetes, steatosis, and age were all significant indicators of cirrhosis, whereas inflammation was only associated with age. We conclude that the metabolic syndrome via impaired glucose tolerance is strongly correlated with steatosis, fibrosis, and cirrhosis of the liver.

Atherogenic, hemostatic, and other potential risk markers in subjects with previous isolated myocardial infarction compared with long-standing uncomplicated stable angina.

BACKGROUND: Several atherogenic, hemostatic, inflammatory, and genetic parameters and markers have been implicated as risk factors in coronary artery disease, although whether they are risk factors for acute as opposed to chronic coronary disease is unclear. METHODS AND RESULTS: Fifty subjects with an isolated myocardial infarction >3 months previously were compared with 50 subjects with a minimum 3-year history of stable angina, documented coronary artery disease, normal electrocardiogram and normal ventricular wall motion, and no episode suggesting infarction or unstable angina. Biologic variables analyzed included apolipoprotein B (apo B), lipoprotein (a), C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (TPA) and inhibitor (PAI-1), thrombin-antithrombin (TAT), fragment 1+2 (F1+2), von Willebrand factor (vWF), activated protein C resistance, homocyst(e)ine, anticardiolipin antibodies, blood group, and the angiotensin-converting enzyme insertion/deletion (I/D) and angiotensin II receptor gene polymorphisms. There were no significant differences between the 2 groups for any of the variables studied, although fibrinogen and F 1+2 tended to be slightly higher in the angina group (P = .09 for each). These significant correlations were present: age with fibrinogen, homocyst(e)ine, and vWF; factor VII with apo B, homocyst(e)ine, and TPA; apo B with TPA and CRP; CRP with fibrinogen, TPA, PAI-1, and factor VII; fibrinogen with vWF. CONCLUSIONS: Examination of atherogenic, hemostatic, inflammation, and genetic variables in the clinically quiescent state permitted no distinction between subjects with a previous isolated myocardial infarction in contrast to those with long-standing uncomplicated stable angina, favoring the notion that acute coronary events occur at random on a varying background of atherosclerosis. The multiple correlations found among these variables also underscore their complex interaction in the atherosclerotic process.

Attenuation of myocardial ischemia with repeated exercise in subjects with chronic stable angina: relation to myocardial contractility, intensity of exercise and the adenosine triphosphate-sensitive potassium channel.

OBJECTIVES: This study characterized the attenuation of myocardial ischemia observed with re-exercise to determine whether: 1) a differing exercise intensity modifies this attenuation; 2) it could be explained by contractile down-regulation or stunning; 3) it is mediated by activation of ATP-sensitive potassium channels (K+-ATP). BACKGROUND: Subjects with ischemic heart disease (IHD) frequently note less angina with re-exercise after a brief rest. Potential mechanisms of this 'warm-up' phenomenon have been little explored. METHODS: IHD subjects with a positive exercise test were studied. Groups I and II (12 subjects each) underwent 2 successive Naughton protocol exercise echocardiography tests (with 1 min instead of 2 min stages for Group II). Group D (10 subjects) had type II diabetes, were on > or =10 mg daily of the K+-ATP blocker, glibenclamide, and underwent the group I exercise protocol. The ischemic threshold or rate-pressure product at 1 mm ST segment depression, ST depression corresponding to the peak rate-pressure product of the first exercise (maximum ST depression equivalent), and left ventricular wall motion indexes before and immediately after each exercise were analyzed. RESULTS: Exercise-induced myocardial ischemia with re-exercise was similarly attenuated in groups I, II, and D. The ischemic threshold was raised by nearly 20% with re-exercise (p=0.001, p=0.02, and p=0.02, respectively) and the maximum ST depression equivalent was nearly halved on re-exercise (p=0.005, p=0.006, and p=0.001, respectively). Exercise-induced wall motion dysfunction was attenuated with re-exercise. In group I, wall motion returned to the initial baseline score prior to exercise 2, whereas in the more intense protocol of group II, wall motion dysfunction persisted prior to exercise 2. CONCLUSIONS: Thus, the attenuation of myocardial ischemia observed with re-exercise appears to be independent of the intensity of the exercise protocol and is not explained by down-regulation of myocardial contractility induced by the initial ischemic stimulus. Since results were similar in diabetic subjects on robust doses of glibenclamide, this phenomenon does not appear to be mediated by K+-ATP activation.

Biliopancreatic diversion with duodenal switch.

In 1990 Scopinaro's technique of biliopancreatic diversion with distal gastrectomy (DG) and gastroileostomy was modified. A sleeve gastrectomy with duodenal switch (DS) was used instead of the distal gastrectomy; and the length of the common channel was made 100 cm instead of 50 cm. A questionnaire and a prescription for blood work were sent to 252 patients who underwent DG a mean 8.3 years ago (range 6-13 years) and 465 patients who underwent DS 4.1 years ago (range 1.7-6.0 years). The questionnaire response rate was 93%, and laboratory work was completed for 65% of both groups. The mean weight loss after DG was 37 +/- 21 kg and after DS 46 +/- 20 kg. There were fewer side effects after DS: The number of daily stools was lower (p < 0.0002), as was the prevalence of diarrhea (p < 0.01), vomiting (p < 0.001), and bone pain (p < 0.001). Greater benefits related to several aspects of life were reported after DS than DG (p < 0.0001). The mean serum levels of ferritin, calcium, and vitamin A were higher (p < 0.001), and parathyroid hormone was lower. The yearly revision rate for excessive malabsorption was 1.7% per year after DG and 0.1% per year after DS. The two procedures were equally efficient for treating co-morbid conditions such as diabetes, hypertension, and hypercholesterolemia. Biliopancreatic diversion with sleeve gastrectomy/duodenal switch and a 100-cm common limb was shown to produce greater weight loss with fewer side effects.

A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates.

OBJECTIVES: We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings. BACKGROUND: In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear. METHODS: We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized. RESULTS: Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent. CONCLUSIONS: In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.

Central endotoxin induces different patterns of interleukin (IL)-1 beta and IL-6 messenger ribonucleic acid expression and IL-6 secretion in the brain and periphery.

Centrally injected endotoxin induced high levels of interleukin (IL)-6 in serum, but the mechanisms of this induction and the signal conveying the information from the brain to the periphery are not yet known. To help characterize the pathway of centrally mediated induction of IL-6 in periphery, the cytokine levels were measured in rat serum and cerebrospinal fluid at different times after intracerebro-ventricular endotoxin (LPS, 2.5 micrograms/rat). In the same experiments, IL-6 and IL-1 beta messenger RNA (mRNA) expression, measured by Northern blot analysis, were evaluated in the periphery (adrenals, lymph nodes, and mononuclear cells) and brain (hypothalamus, hippocampus and striatum). In serum, IL-6 levels were highest after 2h; then they rapidly decreased. IL-6 mRNA showed the same time-course in adrenals and lymph nodes. The pattern in the central nervous system was different: in the cerebrospinal fluid, IL-6 was detectable starting from 2h, reaching a plateaux at 4-8h and remaining detectable until 16 h. IL-6 mRNA expression in the brain areas showed a similar time-course, reaching a maximum at 4-8 h. IL-1 beta mRNA induction started at the same time in brain and periphery, i.e. 1 h after LPS, but the maximal effect was reached at 2 h in mononuclear cells, adrenals, and lymph nodes, and at 8 h in brain regions. The results indicate that circulating IL-6 induced by central LPS is produced mainly peripherally and that synthesis of IL-6 and IL-1 beta are regulated differently in the brain and periphery.