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.

Sharp and round shapes of seen objects have distinct influences on vowel and consonant articulation.

The shape and size-related sound symbolism phenomena assume that, for example, the vowel [i] and the consonant [t] are associated with sharp-shaped and small-sized objects, whereas [ɑ] and [m] are associated with round and large objects. It has been proposed that these phenomena are mostly based on the involvement of articulatory processes in representing shape and size properties of objects. For example, [i] might be associated with sharp and small objects, because it is produced by a specific front-close shape of articulators. Nevertheless, very little work has examined whether these object properties indeed have impact on speech sound vocalization. In the present study, the participants were presented with a sharp- or round-shaped object in a small or large size. They were required to pronounce one out of two meaningless speech units (e.g., [i] or [ɑ]) according to the size or shape of the object. We investigated how a task-irrelevant object property (e.g., the shape when responses are made according to size) influences reaction times, accuracy, intensity, fundamental frequency, and formant 1 and formant 2 of vocalizations. The size did not influence vocal responses but shape did. Specifically, the vowel [i] and consonant [t] were vocalized relatively rapidly when the object was sharp-shaped, whereas [u] and [m] were vocalized relatively rapidly when the object was round-shaped. The study supports the view that the shape-related sound symbolism phenomena might reflect mapping of the perceived shape with the corresponding articulatory gestures.

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.

Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased occurrence of cardiac valve abnormalities. However, the prevalence of cardiac abnormalities in patients with a uniform genotype of ADPKD has not been previously reported. We performed M-mode and color Doppler echocardiography on 109 patients from 16 families with polycystic kidney disease type 1 (PKD1). Findings were compared with those of 73 unaffected family members and 73 healthy controls. Mitral valve prolapse was found in 26% of patients with PKD1, 14% of unaffected relatives, and 10% of control subjects. The prevalence of hemodynamically significant mitral regurgitation (grade 2 or 3) was 13%, 4%, and 3%, respectively. Prevalences of grade 2 or 3 aortic regurgitation (8%, 4%, and 3%, respectively) and tricuspid regurgitation (4%, 6%, and 7%, respectively) were not significantly different among the three groups. Left ventricular hypertrophy (LVH) was found in 19% of subjects with PKD1, 6% of unaffected relatives, and 4% of control subjects. Systolic blood pressure and severity of renal insufficiency were related to mitral regurgitation and LVH in subjects with PKD1. The prevalence of cardiac valve abnormalities did not differ between unaffected relatives and control subjects. Mitral valve prolapse is a characteristic finding in patients with PKD1. Conversely, mitral regurgitation and LVH are likely to be secondary to elevated blood pressure in these patients.

Variation at the cholesteryl ester transfer protein gene in relation to plasma high density lipoproteins cholesterol levels and carotid intima-media thickness.

BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a major role in lipoprotein metabolism. We have screened the CETP gene for mutations and polymorphisms regulating high density lipoproteins cholesterol (HDL-C) levels and the development of atherosclerosis, and found some polymorphisms (I405V and R451Q) to have minor effects. DESIGN: The purpose of this study was to investigate the combined effect of the several polymorphisms of the CETP gene so far found on HDL-C levels and carotid intima-media thickness (IMT), and, in addition, to study whether the recently found functional polymorphism in the promoter region of the CETP gene (C to A, - 629 relative to the first transcribed nucleotide) explains the previous associations due to linkage disequilibrium. The genotypes were determined in a population sample of 481 men and women. RESULTS: There were no significant differences in plasma CETP activity or carotid IMT between the genotypes of the promoter polymorphism. The women with the CC genotype of the promoter polymorphism had the lowest HDL-C levels (P < 0.001), but no such difference was seen in men. Detected polymorphisms of the CETP gene explained about 8% of the variation in HDL-C in women and about 7 and 10% of the variation in carotid IMT in women and men, respectively. The associations of the promoter, I405V and R451Q-A373P polymorphisms with HDL-C and carotid IMT seemed to be independent of each other. The associations with IMT were independent of total HDL-C levels, suggesting that HDL subfractions may have more effect on IMT. CONCLUSION: The CETP gene locus was found to be polymorphic and its polymorphisms explained a reasonable proportion of the variation in the degree of carotid atherosclerosis.

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.

Characterization of two unusual RS1 gene deletions segregating in Danish retinoschisis families.

Over 100 distinct retinoschisis gene (RS1) mutations, of which approximately 10% are single exon deletions, have been described to date. In this paper we have characterized in detail two dissimilar RS1 gene deletions which are accountable for RS in one-third of Danish patients. First, a 136 kb deletion, spanning from the 5' region of the RS1 gene to intron 3, was identified. Unexpectedly this large deletion abolishes exons of three adjacent genes: serine-threonine phosphatase gene (PPEF-1)/serine-threonine protein phosphatase gene (PP7), retinoschisis gene (RS1), and serine-threonine kinase gene (STK9). We demonstrate that the RS1 and STK9 genes are partly overlapping and the sequences of the PP7 and PPEF-1 genes are identical. This is the first study which reports of retinoschisis patients who also suffer from deletions in genes adjacent to RS1. The 136 kb deletion is also the first gross deletion of the retinoschisis gene deleting three exons. It results from a recombination between two repetitive sequences of the Alu family, one in 5' region of the RS1 gene and the other in RS1 intron 3. The second alteration, the actual Danish RS founder mutation, is a 4.4 kb noncontiguous two-part deletion composed of two deleted 1.5 and 2.9 kb segments, separated by an intact 1.2 kb segment. It extends from the 5' flanking region of the retinoschisis gene to RS intron 1. RS1 gene deletions of this type have not been identified previously. Despite these two unique deletions, which either lead to severely defective transcription or total absence of the retinoschisin and PPEF-1 protein, all the patients have a typical retinoschisis phenotype.

Gamma-glutamyl transpeptidase and the metabolic syndrome.

OBJECTIVE: To analyse the associations between serum gamma-glutamyl transpeptidase activity (GTP) and the components of the metabolic syndrome. DESIGN: Cross-sectional, observational study of hypertensive patients and controls. SETTING: The participating subjects visited the research laboratory of the Department of Internal Medicine, University of Oulu, Oulu, Finland. SUBJECTS: A total of 1045 Caucasians, 40-59 years of age, consisting of 261 drug-treated hypertensive men, 258 drug-treated hypertensive women and 526 age- and sex-matched controls. MAIN OUTCOME MEASURES: The associations between GTP and the cardiovascular risk factors were analysed through multiple regression and logistic methods and by GTP tertiles. The independent effect of GTP on different insulin measures, calculated from the values of 2 h of oral glucose tolerance test, was estimated after concurrent adjustment for age, obesity and alcohol consumption. RESULTS: GTP correlated highly significantly with the components of the metabolic syndrome. The correlation coefficient were 0.33 between GTP and body mass index, 0. 25 between GTP and systolic blood pressure in control men (P = 0. 0001), 0.39 between GTP and triglycerides, and 0.32 between GTP and fasting insulin in hypertensive women (P = 0.0001). The association between GTP and blood pressure remained significant only at upright measurements in controls. All insulin measures had a significant positive association with increasing GTP tertiles in all the study groups (e.g. fasting insulin 8.1 mU L-1 in the lowest and 11.0 mU L-1in the highest tertile in control women, P = 0.0001), with the exception of fasting insulin in control men. In a pooled logistic analysis after adjustment for age, body mass index, alcohol consumption and gender, the independent predictors of the metabolic syndrome were body mass index, uric acid, total cholesterol and GTP (for log-transformed GTP odds ratio 4.0, 95% CI: 2.80-5.69). CONCLUSIONS: There are significant associations between GTP and the components of the metabolic syndrome. Elevated levels of GTP may not always indicate increased alcohol consumption, but may also suggest the existence of the metabolic syndrome with its subsequent deleterious consequences.

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.

Cholesteryl ester transfer protein gene polymorphisms are associated with carotid atherosclerosis in men.

BACKGROUND: The cholesteryl ester transfer protein (CETP) is involved in the reverse cholesterol transport and is therefore a candidate gene for atherosclerosis. DESIGN: The prevalences of the I405V and the R451Q polymorphisms were studied in a population sample of 515 men and women. Genotypes were determined by PCR and carotid atherosclerosis by ultrasonography as the mean intima-media thickness (IMT) of the carotid arteries. RESULTS: The Q451 allele was associated with significantly lower intima media thickness in men (P = 0.001). The Q451 allele was, in our earlier study, associated with high plasma CETP activity in men. The VV405 genotype was associated with lower plasma CETP activity compared with the II405 genotype (P < 0.01 for the difference). In the general linear model general factorial procedure the interaction between alcohol consumption and the I405V genotype on IMT was significant (P = 0.013) in men, and when the interaction term was taken into the model the I405V genotype also significantly affected IMT (P = 0.008). The VV405 genotype seems to be most harmful for men with the highest alcohol consumption. CONCLUSIONS: We describe two polymorphisms of the CETP gene associated with intima media thickness in men. A significant interaction was found between alcohol consumption and the I405V genotype on IMT.

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.