Extralevator versus standard abdominoperineal excision in locally advanced rectal cancer: a retrospective study with long-term follow-up.

PURPOSE: To analyze the results of abdominoperineal excisions (APE) for locally advanced rectal cancer at our institution before and after the adoption of extralevator abdominoperineal excision (ELAPE) with a special reference to long-term survival. METHODS: A retrospective cohort study conducted in a tertiary referral center. All consecutive patients operated for locally advanced (TNM classification T3-4) rectal cancer with APE in 2004-2009 were compared to patients with similar tumors operated with ELAPE in 2009-2016. RESULTS: Forty-two ELAPE and 27 APE patients were included. Circumferential resection margin (CRM) was less than 1 mm (R1-resection) in 10 (24%) of ELAPE patients and 11 (41%) of APE patients (p = 0.1358). Intraoperative perforation (IOP) occurred in 4 (10%) patients and 6 (22%) patients in ELAPE and APE groups, respectively (p = 0.1336). There were 3 (7%) local recurrences (LRs) in ELAPE group and 5 (19%) in APE (p = 0.2473). There were no statistical differences in adverse events, overall survival, or disease-free survival between ELAPE and APE groups. CONCLUSIONS: We found a non-significant tendency to lower rates of IOP and positive CRM as well as lower rate of LR in the ELAPE group. Long-term survival and adverse events did not differ between the groups. ELAPE is beneficial for the surgeon in offering better vicinity to the perineal area and better work ergonomics. These technical aspects and the clinically very important tendency to lower rate of LR support the use of ELAPE technique in spite of the lack of survival benefit.

Adoption of single incision laparoscopic cholecystectomy in small-volume hospitals: initial experiences of 51 consecutive procedures.

BACKGROUND AND AIMS: Laparoscopic cholecystectomy (LC) via three or four ports has been the standard operation for gallstone disease. Recently, the development of multichannel port devices has allowed LCs to be performed through a single fascial incision in the umbilicus. Here, we report our experiences of the adoption of the single incision laparoscopic cholecystectomy (SILC) in two small-volume community hospitals. MATERIAL AND METHODS: From January until July 2010, 51 consecutive patients (41 females and 10 males, the mean age 44 (21-75) years, BMI 26 (18-35)) underwent elective SILC for symptomatic gallstone disease in Salo (n = 29) and Loimaa (n = 22) hospitals. RESULTS: Of the 51 operations, 42 (82%) were accomplished without additional troacars. Seven (14%) procedures were converted to multiple-port technique and two (4%) to open cholecystectomy. In 25 (49%) operations, transabdominal retraction sutures through the gallbladder were used to maintain a good view of the triangle of Calot. The mean operative time was 74 (31-155) min. No major intraoperative complications occurred. The mean hospital stay was 0.6 (0-3) days. During a mean follow up of 4 (1-7) months, five (10%) patients had wound infection, and one (2%) had hematoma and prolonged pain in the insertion site of the retraction suture. One (2%) patient was reoperated for continuous pain in umbilical wound without findings at operation but with good results. One (2%) patient had subphrenic abscess seven months postoperatively. CONCLUSIONS: Our initial experiences indicate that SILC can be adopted without major complications in small-volume hospitals but the rate of wound infections seems to increase with the introduction of SIL.

Interleukin-6-174 G/C promoter polymorphism is associated with persistence of Chlamydia pneumoniae antibodies in young men.

A promoter polymorphism -174 G/C in the inflammatory cytokine interleukin-6 (IL-6) gene has been associated with differences in serum IL-6 levels and a risk for inflammatory conditions, such as cardiovascular diseases. We investigated whether this polymorphism is associated with Chlamydia pneumoniae, a common causative agent of respiratory infection with tendency for persistent infections, in 867 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible prolonged or chronic infection. The -174C allele was significantly associated with IgG seropositivity (P = 0.0002) and the persistence of IgG antibodies (P = 0.0002) as well as with slightly elevated C-reactive protein (CRP) levels (P = 0.003). In addition, the association was stronger when persistent C. pneumoniae antibodies were present together with elevated CRP than when either of them was positive alone (OR; 95% CI: 3.45; 2.00-5.98 and 1.41; 1.00-1.99, respectively). Our data suggest that IL-6 -174 G/C polymorphism is associated with persistence of C. pneumoniae antibodies and may be linked to the chronic or prolonged infection with systemic low-grade inflammation.

Quality of life after surgery for rectal cancer with special reference to pelvic floor dysfunction.

AIM: Conventional outcomes such as survival, tumour recurrence and complication rates after surgery for rectal cancer have been rigorously assessed, but the importance of maintaining quality of life (QOL) after surgery for rectal cancer has received less attention. The aim of the current study was to analyse QOL and the occurrence of pelvic dysfunction after the surgical treatment of rectal cancer. METHOD: Between May 2005 and May 2008, 150 patients with rectal cancer underwent abdominoperineal resection (APR) or anterior resection (AR). Seventy-four answered two preoperative questionnaires. At a follow up of 1 year, 65 were alive without sign of recurrence and answered the same questionnaires: (a) validated RAND 36-item health survey QOL questionnaire; and (b) self-administered disease-related questionnaire with special reference to anorectal and urogenital function. RESULTS: The postoperative general QOL was similar after surgery, and mental functioning was better (P < 0.001). Problems with physical functions were associated with anal dysfunction after AR (P < 0.001) and problems with social functioning were associated with urinary dysfunction (P = 0.038). At 1 year after surgery, urinary incontinence was worse (P = 0.026) after all operations, and the incidence of dysuria was higher after APR than AR (P = 0.001). Male sexual function also worsened (P = 0.060). Anorectal dysfunction caused more inconvenience among patients who underwent AR (P = 0.028). Preoperative radiation was associated with postoperative ejaculation problems (P = 0.028) and anal incontinence (P = 0.012). CONCLUSION: Factors affecting QOL and pelvic floor function should be taken into account when making treatment decisions in rectal cancer.

Elective laparoscopic cholecystectomy without routine intraoperative cholangiography: a retrospective analysis of 1101 consecutive cases.

BACKGROUND: Laparoscopic cholecystectomy (LC) is today the operation of choice for symptomatic gallstone disease. Before the laparoscopic era intraoperative cholangiography (IOC) was generally considered as a fundamental step in cholecystectomy while nowadays the role of IOC is controversial: is there a need for IOC to specify anatomy of biliary tree in order to avoid bile duct injuries (BDI) and to detect possible common bile duct (CBD) stones or not? PATIENTS AND METHODS: We studied retrospectively all the elective LCs done in Turku City Hospital for Surgery during the ten years (1992-2001). Cholecystectomy was performed to 1101 patients, 874 (79%) female and 227 (21%) male patients, mean age 53y (range 15-89). LC was possible in 1022 (93%) cases while 79 (7%) had to be converted to open procedure. The number and severity of bile duct injuries were recorded. The cases with endoscopic retrograde cholangiopancreatography (ERCP) and/or magnetic resonance cholangiopancreatography (MRCP) during the follow-up and the findings in ERCP and MRCP were recorded from patient records and radiological database. RESULTS: IOC was performed in 32 operations (20 in LC and 12 after conversion) and CBD stones were found in seven patients. There were four primary BDIs: two CBD injuries and two minor bile leaks. During a mean follow-up of 72 months (range 36-144) ERCP was performed in 16 and MRCP in three patients. Three patients underwent both MRCP and ERCP. CBD stones were detected in ten patients and a postoperative late CBD stricture was found in one case. CONCLUSIONS: According to our data, both the incidence of BDIs (0.5%) and symptomatic postoperative CBD stones (0.9%) remain low without the routine use of IOC.

Chlamydia pneumoniae infection is associated with elevated body mass index in young men.

Chlamydia pneumoniae infection is said to be associated with obesity. We studied the association between C. pneumoniae infection and inflammation and increased BMI in 891 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible indication of chronic infection. Persistently high C-reactive protein (CRP) level (elevated on arrival and departure) (OR 2.2, 95% CI 1.3-3.9), and persistent C. pneumoniae antibodies (OR 2.1, 95% CI 1.5-2.8) were significant risk factors for overweight (BMI 25 kg/m2). In addition, those who had persistent antibodies and persistently elevated CRP levels, or those who had either of them, had a significantly higher BMI (kg/m2) compared to those who had neither of them (25.8 vs. 24.6 vs. 23.5, respectively; P<0.001). These results provide new information about the association between possible chronic C. pneumoniae infection and obesity in young men.

Thromboprophylaxis following surgery for colorectal cancer - is it worthwhile after hospital discharge?

BACKGROUND: The efficacy of low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) after surgery for colorectal cancer is well documented, but the optimal duration of postoperative thromboprophylaxis is not known. The aim of this retrospective study was to assess the occurrence of symptomatic VTE after surgery for colorectal cancer in patients in whom LMWH was continued only until hospital discharge. METHODS: During 2003-2006 a total of 494 patients underwent abdominal surgery for colorectal cancer at our institution. Enoxaparin (Klexane 40mg s.c.) prophylaxis was started 12 hours before surgery and continued once a day until hospital discharge. The median duration of thromboprophylaxis was 11 days. The follow-up data were collected retrospectively from electronic archives and analyzed up to three months after the operation. RESULTS: Only three (0.6%) symptomatic VTEs occurred during the follow-up period. One patient presented with pulmonary embolism, while the remaining two had proximal deep-vein thrombosis. The 30-day-mortality was 1.6%. None of the deaths were obviously associated with VTE. CONCLUSION: LMWH given for a median of 11 days until hospital discharge seems to provide sufficient thromboprophylaxis after surgery for colorectal cancer combined with the use of graded compression stockings and early mobilization.

Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer.

Vascular endothelial growth factor (VEGF) has been shown to stimulate angiogenesis and myocardial perfusion. The short-term safety of VEGF gene therapy is excellent. However, there are only limited results regarding the long-term effects. The Kuopio Angiogenesis Trial (KAT) studied the efficiency and short-term safety of the local VEGF-A(165) gene transfer in 103 patients with coronary artery disease. Three patient groups received either VEGF as an adenoviral (n=37), or as a plasmid/liposome vector (n=28), or as a placebo (n=38), during coronary angioplasty and stenting (percutaneous coronary intervention, PCI)AQ1. The aim of this study was to examine the long-term effects and safety of VEGF gene therapy. Patients were interviewed by telephone or with a questionnaire on their current status of health, coronary and other cardiovascular events and symptoms, working ability, exercise tolerance, other diseases, such as cancer and diabetes, as well as their personal experience of the treatment. Causes of death were clarified from hospital records. The total follow-up time was 8.1 years (range 6.9-9.7 years). Overall 82% of the patients were reached across the study. Eight (7.5%) of the patients died during the follow-up, but there was no significant difference in mortality between the groups (3/32 vs 2/26 vs 3/31 VEGF-adenovirus vs VEGF-plasmid/liposome vs placebo, respectively; P=0.88). The incidence of major adverse cardiovascular events (MACEs) (10 vs 11 vs 15; P=0.85), cancer (1 vs 4 vs 2; P=0.38) or diabetes (2 vs 2 vs 2; P=0.97) did not differ between the groups. Local intracoronary VEGF gene transfer is safe and does not increase the risk of MACE, arrhythmias, cancer, diabetes or other diseases.

Population-based study of the surgical workload and economic impact of bowel obstruction caused by postoperative adhesions.

BACKGROUND: Intestinal obstruction is the most severe consequence of adhesion formation. This study examined the annual surgical workload and costs of intestinal obstruction caused by postoperative intra-abdominal adhesions. METHODS: The study was a retrospective case-note review of patients hospitalized for intestinal obstruction caused by postoperative adhesions in a well defined geographical area. The surgical workload and direct costs of inpatient care were analysed. RESULTS: There were 138 admissions for postoperative adhesion-related intestinal obstruction during the study with a total of 1118 inpatient days. The median hospital stay was 4 (range 1-58) days among patients who had non-operative treatment and 11 (range 2-34) days for those who had surgery. Surgery was necessary in 40 patients (29.0 per cent). The mean operating time (time from skin incision to last stitch) and the mean time spent in the operating theatre were 79 and 141 min respectively. The cumulative operating time for the surgical group was 52 h 20 min and the cumulative theatre time was 93 h 44 min. The annual direct hospital cost for postoperative adhesional intestinal obstruction was pound 181 653 in the district studied and the estimated cost for the whole of Finland was pound 2 077 796. CONCLUSION: This population-based study indicates that the workload and costs associated with bowel obstruction caused by postoperative adhesions are substantial.

Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction.

OBJECTIVES: To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO). DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels. CONCLUSIONS: The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.

Comparison of echocardiography and radionuclide ventriculography in the follow-up of left ventricular systolic function in adult lymphoma patients during doxorubicin therapy.

OBJECTIVES: To compare echocardiography (ECHO) and radionuclide ventriculography (RVG) in the monitoring of left ventricular systolic function during doxorubicin therapy in adult lymphoma patients. DESIGN: Prospective study. SETTINGS: University hospital. SUBJECTS: A total of 28 adult patients who received doxorubicin to a cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: ECHO and RVG were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: At baseline, the mean (+/-SE) left ventricular ejection fractions (LVEF) were 58 +/- 1.3, 71 +/- 1.8 and 58 +/- 1.7% as determined by RVG, M-mode ECHO and two-dimensional (2D) ECHO, respectively. After the cumulative doxorubicin dose of 500 mg m(-2) LVEF decreased to 49.6 +/- 1.7% (RVG) (P < 0.001), 62 +/- 1.6% (M-mode) (P=0.006) and 52.5 +/- 1.3% (2D ECHO) (P=0.036). Although a significant correlation between LVEF determined by RVG and M-mode ECHO (r=0.615, P=0.002) and a trend between RVG and 2D ECHO (r=0.364, P=0.096) were observed, there were substantial differences in the results of individual patients. In the agreement analysis using the method of Bland and Altman there was a mean difference of 12% units with the upper limit of agreement +26% units and the lower limit of agreement -2.1% units for LVEF determinations with M-mode ECHO and RVG, and a mean difference of 3.3% units with upper and lower limits of agreement +19.6 and -13.1% units for LVEF determinations with 2D ECHO and RVG, respectively. CONCLUSION: We found only a moderate agreement between left ventricular systolic function determined by ECHO and RVG methods. Thus, in the follow-up of left ventricular function in adult patients during doxorubicin therapy, the guidelines based on LVEF measurement by RVG cannot be applied to ECHO. Consequently, RVG remains the method of choice in this context.

Effect of hypertension and risk factors on diameters of abdominal aorta and common iliac and femoral arteries in middle-aged hypertensive and control subjects: a cross-sectional systematic study with duplex ultrasound.

There is a general tendency towards atherosclerosis and arterial dilatation in older age, and high blood pressure also tends to increase arterial diameters. The purpose of this study was to examine the effect of hypertension and other cardiovascular risk factors on aortic, common iliac and common femoral artery diameters. The diameters of the abdominal aorta and the iliac and femoral arteries and the extent of echogenic plaques in the aorta and the iliac arteries down to groin level were evaluated with ultrasound in 1007 middle-aged (40-60 years) men (505) and women (502), 496 with arterial hypertension and 511 controls. Twenty-eight subjects were excluded because of poor visualization. Men had significantly larger diameters of the abdominal aorta (mean 21.3+/-2.8 vs. 17.8+/-1.3 mm) and the common iliac (13.4+/-2.0 vs. 12.2+/-1.2) and common femoral arteries (11.0+/-1.4 vs. 9.7+/-0.9) than women (P for all <0.001), but arterial diameter was also related to the subject's size. Atherosclerotic plaques, age and height were associated with the diameter of the abdominal aorta in men, while high body mass index (BMI) had less significance. The diameter of the aorta was larger in hypertensive men aged 56-60 than in controls of the same age. In women, height, BMI and diastolic blood pressure (DBP) were associated with the diameter of the aorta, while systolic blood pressure (SBP) had less and age no effect. Age, plaques, height, BMI, DBP and SBP were associated with the diameters of the common iliac arteries in both genders, while smoking had an inverse correlation. The results on lipid values were inconsistent and an abnormal glucose tolerance test proved nonsignificant. In conclusion, arterial size measured as a diameter related to the subject's size was larger in men. Age, arterial plaques and blood pressure increased arterial diameter significantly. However, the hypertensive disease itself had only a minimal effect. The changes were smaller in women than in men.

Dietary and other non-pharmacological treatments in patients with drug-treated hypertension and control subjects.

OBJECTIVE: To study the nutrient intakes and other lifestyle patterns of drug-treated hypertensives and control subjects. DESIGN: A cross-sectional population-based epidemiological study. SETTING: The participating study subjects visited the research laboratory of the Department of Internal Medicine of the University of Oulu, Oulu, Finland. PARTICIPANTS: A total of 1045 Finnish men and women aged 40-60 years, of whom 716 (69%) completed 7-day food records. MAIN OUTCOME MEASURES: Intakes of energy, protein, total fat, saturated, monounsaturated and polyunsaturated fatty acids, carbohydrate, alcohol, fibre, calcium, magnesium, potassium and sodium were assessed from 7-day food records. The study also included measurements of blood pressure, blood glucose and plasma lipids, and anthropometric variables. Information about alcohol consumption, smoking habits and physical activity was collected by interviewing. RESULTS: Obesity was common amongst the hypertensive subjects, whose body mass indices were significantly higher than those of the control subjects. Only minor differences existed in the energy intake levels and nutrient intakes of the hypertensive and control cohorts, but the control subjects performed more physical activity than the hypertensive subjects. The dietary recommendations concerning the intakes of total and saturated fats, carbohydrate and fibre were poorly met by both the hypertensive and the control subjects. Alcohol consumption was high amongst the hypertensive men, especially amongst the smokers. CONCLUSIONS: Non-pharmacological treatment, including dietary management, of hypertensive patients at high risk for cardiovascular complications seems still to be inadequate. Additional well-focused efforts are needed to intensify the dietary treatment as well as to reduce alcohol consumption and smoking amongst hypertensives.

Effect of dobutamine on splanchnic carbohydrate metabolism and amino acid balance after cardiac surgery.

BACKGROUND: As a predominant beta-adrenergic agonist, dobutamine may modify blood flow distribution and increase metabolic demands. The authors investigated the effect of a dobutamine-induced increase in cardiac output on splanchnic and femoral blood flow and metabolism in patients after cardiac surgery. METHODS: Seventeen stable patients were randomized to receive dobutamine or placebo (n = 8 per group, one dropout). After baseline measurement for systemic, splanchnic, and femoral blood flow (by dye dilution); oxygen consumption; gastric mucosal pressure of carbon dioxide (Pco2); total and splanchnic glucose production (by stable isotope tracer dilution); and regional lactate and amino acid balance, patients received either dobutamine, at a dosage (6 microg x kg(-1)min(-1)) sufficient to increase cardiac index by at least 25%, or placebo. A second set of measurements was performed 60 min after the start of dobutamine or placebo infusion. RESULTS: Dobutamine increased cardiac index (3.0+/-0.6 to 4.4+/-1.0 l x min(-1)m(-2), mean +/- SD; P < 0.05), splanchnic blood flow (from 0.8+/-0.2 to 1.0 + 0.2 l x min(-1)m(-2); P < 0.05), femoral blood flow (from 0.2+/-0.1 to 0.3+/-0.1 l x min(-1)m(-2); P < 0.05), and the arterial-gastric mucosal Pco2 gap (from 11.4+/-9.5 to 11.9+/-8.0 mmHg; P < 0.05). Dobutamine increased systemic oxygen consumption (from 132+/-14 to 146+/-13 ml x min(-1) x m(-2); P < 0.05) but not splanchnic or femoral oxygen consumption. Splanchnic glucose production and lactate and amino acid balance did not change. CONCLUSION: After coronary artery bypass surgery, dobutamine increased systemic and regional blood flow and decreased systemic and regional oxygen extraction. Dobutamine did not affect splanchnic glucose production or lactate or amino acid balance. This suggests that dobutamine increases splanchnic blood flow without a concomitant increase in hepatosplanchnic metabolism.

QT dispersion and late potentials during doxorubicin therapy for non-Hodgkin's lymphoma.

OBJECTIVES: To investigate effects of doxorubicin therapy on cardiac electrophysiology, with special emphasis on QT dispersion and late potentials, in lymphoma patients. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult non-Hodgkin's lymphoma patients who received doxorubicin to a cumulative dose of 400-500 mg m-2. MAIN OUTCOME MEASURES: Standard 12-lead electrocardiogram (ECG) and signal-averaged ECG (SAECG) recordings were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m-2. RESULTS: Heart rate-corrected QT interval (QTc) increased from 402 +/- 4 to 416 +/- 5 ms (P = 0.002) during the study period. QT dispersion (variability in QT interval duration amongst the different leads of the standard 12-lead ECG) increased from 24.1 +/- 2.5 to 35.0 +/- 2.8 ms (P = 0.041) and QTc dispersion increased from 26.5 +/- 2.5 to 39.0 +/- 3.5 ms (P = 0.039). Five patients (18%) developed QT dispersion exceeding 50 ms. In addition, two patients (7%) developed late potentials during doxorubicin therapy. The changes in QTc duration, QT dispersion and late potentials occurred independently of the impairment of left ventricular function. CONCLUSIONS: Prolongation of QTc, increased QT dispersion and development of late potentials are indicative of doxorubicin-induced abnormal ventricular depolarization and repolarization. QT dispersion and late potentials are both known to be associated with increased risk of serious ventricular dysrhythmias and sudden death in various cardiac diseases. Thus, follow-up of these parameters might also be useful in assessing the risk of late cardiovascular events in cancer patients treated with anthracyclines.

Prevalence of the metabolic syndrome in drug-treated hypertensive patients and control subjects.

OBJECTIVES: To determine the prevalence of the metabolic abnormalities associated with hypertension and to define the predictors of the metabolic syndrome by different definitions in random population-based samples. DESIGN: A cross-sectional epidemiological study of hypertensive patients and controls. SETTING: The participating study subjects visited the research laboratory of the Department of Internal Medicine, University of Oulu, Oulu, Finland. SUBJECTS: Six hundred treated male and female hypertensives aged 40-59 years and 600 age- and sex-matched controls were randomly selected by age stratification from population registers. MAIN OUTCOME MEASURES: A wide range of laboratory analyses were conducted. After fasting blood had been drawn, the subjects were given a 75 g glucose load except previously known insulin-treated diabetics. Both 1 h and 2 h glucose and insulin concentrations were determined. During the same visit, a standardized health questionnaire covering the past medical history, current and former medication use, physical activity, smoking habits, alcohol consumption and family history was completed. Ten different definitions of the metabolic syndrome were applied to achieve a wide perspective of the prevalence of the different combinations. RESULTS: The prevalence of the metabolic syndrome in different samples varied depending on the definition from 0.8 to 35.3%, being lowest in the control men and women and highest in the hypertensive men. Three-quarters of a random, middle-aged, urban population show at least one cardiovascular risk factor and 91.3% of all the hypertensive subjects show at least one cardiovascular risk factor in addition to hypertension itself. The independent predictors of the metabolic syndrome were waist circumference, uric acid, total cholesterol and gamma-glutamyl transpeptidase in logistic analysis after adjustment for age, measure of obesity and gender. CONCLUSIONS: This cross-sectional, epidemiological study shows that the magnitude of the prevalence rates of the metabolic syndrome is at the same level in various populations, being less than one-third in population-based samples in spite of the different definitions. The cluster of several cardiovascular risk factors, especially in the hypertensives, leads to an increased relative risk of cardiovascular diseases.

Apolipoprotein E phenotype determines the effect of alcohol on blood pressure in middle-aged men.

Apolipoprotein E (apoE) has an essential role in lipoprotein metabolism, but recent studies have also revealed other functions associated with it, eg, neurologic and malignant diseases. We studied the association between apoE phenotypes E2/3, E3/3, and E4/3 and blood pressure after adjustment for covariates, as well as the association between phenotypes and adjusted plasma glucose and insulin levels in the standard oral glucose tolerance test in a random middle-aged population-based cohort of 259 men and 267 women. Systolic blood pressure was associated with apoE phenotype in the men with moderate or heavy alcohol consumption (>115 g/week), the mean systolic blood pressure value being 16 mm Hg higher in the E2/3 and 11 mm Hg higher in the E3/3 phenotypes than in the E4/3 phenotype, P = .04. No association was seen in occasional drinkers or teetotalers (lowest tertile <24 g/week), whereas in the middle tertile the association was intermediate. The same association was seen with diastolic blood pressure. In men, there was a significant correlation between systolic blood pressure and alcohol consumption in the E2/3 phenotype (rs = 0.71, P < .01) and in the E3/3 phenotype (rs = 0.25, P < .01), but not in the E4/3 phenotype (rs = 0.03, NS). No association between apoE phenotypes and insulin resistance was observed. In conclusion, in middle-aged men, apoE phenotype significantly influences the blood-pressure-increasing effect of alcohol consumption. This gene environment interaction may have marked implications for the prevention and treatment of hypertension.

Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients.

Idarubicin has been shown to have similar or superior antileukemic activity to daunorubicin with less cumulative cardiotoxicity. However, data of acute cardiovascular effects of idarubicin are scanty but may have clinical significance in predicting late cardiovascular complications. In the present study we evaluated prospectively acute neurohumoral and cardiovascular effects of idarubicin containing induction chemotherapy in 10 patients with newly diagnosed AML or MDS. Idarubicin was administered intravenously 12 mg/m2 on d 1, 3 and 5 as a part of the induction chemotherapy. Serial measurements of plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were performed at baseline and the day following each idarubicin infusion. Echocardiography was performed to assess cardiac systolic and diastolic function. Signal averaged electrocardiography (ECG) was recorded to observe myocardial late potentials associated with possible myocardial injury. In addition, ambulatory ECG recording was performed to assess arrhythmias. Plasma concentrations of ANP increased from 18.2 +/- 1.5 pmol/l to 27.8 +/- 3.5 pmol/l (p = 0.011), to 30.2 +/- 3.0 pmol/l (p = 0.002) and to 40.8 +/- 6.0 pmol/l (p = 0.006) after the first, second and third doses of idarubicin, respectively. Similarly, plasma concentration of BNP increased from 6.2 +/- 1.9 to 9.0 +/- 1.8 pmol/l (p = 0.049) and 17.5 +/- 8.1 pmol/l (p = 0.203) after the first and third idarubicin infusion. Concomitantly, there was a trend towards an increase in left ventricular end diastolic diameter (LVEDD) (50.2 +/- 1.8 to 54.4 +/- 2.2 mm, p = 0.070). The increase in plasma BNP concentrations correlated significantly with the increase in LVEDD (r = 0.624; p = 0.002). No significant ECG changes or arrhythmias were associated with idarubicin infusions except in 1 patient who developed abnormal myocardial late potentials. Our results show that idarubicin causes acute neurohumoral activation associated with increased LVEDD indicating subclinical myocardial dysfunction. Whether these acute changes predict late clinical cardiomyopathy should be evaluated in prospective studies with larger number of patients and with higher cumulative anthracycline doses.

Effect of hypertension, diabetes and other cardiovascular risk factors on kidney size in middle-aged adults.

The aim of the study was to investigate in a population-based series (1031 subjects, age range 40-60 years) whether the renal size of hypertensive subjects differs from that of control subjects and whether the difference might be due to hypertension itself or risk factors associated with hypertension. The renal measurements were performed by abdominal ultrasound. The genders were analyzed separately. Hypertensive men had slightly larger kidneys than controls (70.1+/-8.9 cm2 vs. 67.9+/-8.7 cm2, p <0.008). The difference was, however, mediated mainly through the body mass index (BMI), whereas hypertension, blood pressure or hypertensive medication did not affect renal size. High serum concentrations of uric acid and creatinine were associated with smaller kidney size (p <0.001 and p <0.05, respectively). Alcohol users had slightly larger kidneys than abstainers, but the difference was not significant. Renal size increased with pack years of smoking. Diabetics had 4.8% larger kidneys (p <0.039), but no difference was observed between the subjects with impaired glucose tolerance and those with normal test results. In multivariate analysis, the most significant factors associated with enlarged kidney size were the fasting blood glucose concentration (p < or = 0.0001), smoking (p < or = 0.0001) and atherosclerotic lesions in carotid arteries (p <0.002). The kidneys were also slightly larger in hypertensive women than in control subjects, but the difference was only of borderline significance (p <0.08). Women on hormone replacement therapy had smaller kidneys than other women (p <0.05), but there was no difference in renal measures between premenopausal and postmenopausal women. In multivariate analysis, the most significant factors contributing to large kidney size were blood glucose concentration (p <0.0001) and smoking (p <0.05), while age and serum creatinine concentration were associated with smaller kidney size (p <0.0001 and p <0.0001). We conclude that renal size is related to sex and the subject's height and weight. Smoking, abnormal glucose tolerance, blood uric acid, creatinine, carotid atherosclerosis and hormone replacement therapy in women were also significant factors for renal size. Hypertensive subjects had larger kidneys than controls, mainly because of their more frequent obesity and abnormal glucose test.

Hyperinsulinemia and carotid atherosclerosis in hypertensive and control subjects.

OBJECTIVE: To analyze the relationships between carotid atherosclerosis measured as intima-media thickness (IMT) and different measures of insulin in a population-based case-control study of men and women. RESEARCH DESIGN AND METHODS: Carotid ultrasonographic measurements and 2-h oral glucose tolerance tests were performed in a random sample of 513 hypertensive subjects, aged 40-59 years, and in 518 age- and sex-matched control subjects. The associations between IMT and the different measures of insulin were analyzed through multiple regression and by insulin quintiles. The independent effect of insulin was estimated after concurrent adjustment for age, obesity, LDL cholesterol, and systolic blood pressure. RESULTS: The most powerful correlates with IMT were LDL cholesterol, age, systolic blood pressure, pack-years of smoking, and of the different insulin parameters, 2-h post-load insulin. In stepwise regression analysis, the independent predictors of the mean IMT were LDL cholesterol, systolic blood pressure, pack-years of smoking, and age (P < 0.0001) after adjustment for the independent predictors. In analysis of variance, no positive association of insulin parameters with IMT was found between the 2-h insulin quintiles after adjustment for the independent variables. The exclusion of diabetic subjects did not change the results. CONCLUSIONS: The present study of a population-based sample of men and women found inconsistent associations between different insulin measures and IMT after adjustment for the independent variables.