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.

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.

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.

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.

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.

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.

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.

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.

Dispersion of the QT interval and autonomic modulation of heart rate in hypertensive men with and without left ventricular hypertrophy.

Left ventricular hypertrophy is an independent risk factor for sudden cardiac death in hypertension, but the mechanisms of electrical instability associated with hypertrophy are not well known. We studied dispersion of the QT interval, an index of inhomogeneity of repolarization, and heart rate variability, a measure of cardiac autonomic modulation, in a randomly selected population of 162 men with systemic hypertension and made comparisons between the patients with echocardiographic evidence of left ventricular hypertrophy (left ventricular mass index > or = 131 g/m2, n = 44) and those without hypertrophy (left ventricular mass index < 131 g/m2, n = 118). The heart rate-corrected QT dispersion (67 +/- 37 versus 53 +/- 21 milliseconds, P < .05) and QT apex dispersion (55 +/- 22 versus 44 +/- 16 milliseconds, P < .01) were significantly longer in the patients with left ventricular hypertrophy than in those without hypertrophy. Thirteen of the 44 patients (30%) with hypertrophy versus 7 of the 118 patients (6%) without hypertrophy had an abnormally long QT apex dispersion ( > 70 milliseconds) (P < .001). The time and frequency domain measures of heart rate variability did not differ significantly between the patient groups with and without left ventricular hypertrophy. The measures of heart rate variability were not related to QT dispersion or left ventricular mass index but had a negative correlation with blood pressure values (eg, r = -.30 between the low-frequency component of heart rate variability and systolic pressure, P < .001). Age, body mass index, antihypertensive medication, and the other demographic variables were similar between the groups, but the patients with left ventricular hypertrophy had higher systolic (P < .01) and diastolic (P < .01) pressures compared with the patients without hypertrophy. Left ventricular hypertrophy in hypertensive men is associated with inhomogeneity of the early phase of ventricular repolarization, favoring susceptibility to reentrant ventricular tachyarrhythmias. Abnormalities in cardiac autonomic function, which may trigger a spontaneous onset of arrhythmias, are related to elevated blood pressure but not specifically to left ventricular hypertrophy.

Variation at the angiotensin-converting enzyme gene and angiotensinogen gene loci in relation to blood pressure.

To investigate whether the polymorphisms in the angiotensin-converting enzyme and angiotensinogen genes are associated with hypertension, we carried out a case-control study of 508 hypertensive and 523 control subjects randomly selected from the Social Insurance Institution register. The cohorts were well characterized and matched for age and sex. The insertion/ deletion polymorphism of the angiotensin-converting enzyme gene and the methionine-->threonine variant at position 235 of the angiotensinogen gene were determined by the polymerase chain reaction technique. The allele frequencies and genotype distributions of both polymorphisms were similar in hypertensive and control subjects. Systolic and diastolic pressures adjusted for age, body mass index, and alcohol consumption did not differ significantly between the different genotypes of the angiotensin-converting enzyme and angiotensinogen genes. The variation at the angiotensinogen and angiotensin-converting enzyme genes did not have any statistically significant synergistic effect on blood pressure levels. In conclusion, the polymorphisms in the reninangiotensin cascade genes do not confer a significantly increased risk for the development of hypertension in this middle-aged, population-based cohort.

Three widespread founder mutations contribute to high incidence of X-linked juvenile retinoschisis in Finland.

X-linked juvenile retinoschisis (RS) is a recessively inherited disorder causing progressive vitreoretinal degeneration in males. The gene defective in retinoschisis, XLRS1, has recently been identified and characterised. This gene consists of six exons encoding a protein with a putative role in cell-cell adhesion and phospholipid binding. Juvenile retinoschisis has been actively studied in Finland over the past 30 years, with over 300 diagnosed RS patients. Based on genealogical studies, approximately 70% of the Finnish RS patients originate from Western Finland and 20% from Northern Finland. In this study, one third of the known Finnish RS patients were screened for mutations of the XLRS1 gene. Haplotype analysis, using nine microsatellite markers spanning 1 cM in Xp22.2, suggested the segregation of eight different mutations in these families. To identify mutations, the six exons were amplified by PCR and analysed by single strand conformation analysis, followed by direct sequencing of the PCR products. We identified seven distinct missense mutations, all in exons 4 and 6. The mutations in exon 4, 214G > A and 221G > T, are accountable for RS in Western Finland. A third mutation in exon 4, 325G > C, gives rise to RS in Northern Finland. These three founder mutations are the predominant cause of RS in Finland and their existence explains the high incidence of the disease. The identification of mutations common in genetically isolated populations, such as Finland, allows the diagnosis of patients with an atypical RS phenotype and enables nationwide carrier testing and improved genetic counselling.

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.

Prevalence of carotid atherosclerosis in middle-aged hypertensive and control subjects. A cross-sectional systematic study with duplex ultrasound.

BACKGROUND: Arterial hypertension has been found to increase atherosclerotic lesions, although contradictory results have suggested that hypertension has little or no effect. These discrepancies are probably caused by differences in populations. OBJECTIVE: To examine the effect of hypertension on carotid atherosclerosis in a population-based series of patients with an established diagnosis of arterial hypertension and controls. METHODS: Carotid intima-media thickness (IMT) and plaques were evaluated with duplex ultrasound in 1031 middle-aged (aged 40-60 years) men (n = 511) and women (n = 520), 513 with arterial hypertension and 518 controls. IMT was measured in the internal carotid artery, bifurcation and proximal, middle and distal common carotid artery, determining mean and maximal values for each patient. RESULT: Male sex, age, smoking and cholesterol were the most significant risk factors for combined plaque and intima-media thickness (CPIMT); hypertension and and abnormal glucose test result were further significant risk factors. There was a significant difference in CPIMT between the hypertensive and control subjects, but this was caused by the differences in the men; there were no statistically significant differences among the women. Plaques were found more frequently in the hypertensive men than they were in their controls (62.8 versus 49.8%), the corresponding percentages for the hypertensive and control women being 38.0 and 32.1%. There was a larger proportion of male subjects with a long duration of hypertension (> or = 7 years) who had plaques and greater CPIMT than there was of those with a short duration of hypertension. CONCLUSION: Hypertension had a significant effect on CPIMT and on the prevalence of plaques in men, but its effect in women was not significant. A long duration of hypertension resulted in greater CPIMT values and a higher prevalence of plaques, particularly in men.

Association between angiotensin converting enzyme gene polymorphism and carotid atherosclerosis.

OBJECTIVE: Variations in the angiotensin converting enzyme (ACE) gene have been implicated in cardiovascular pathology. Therefore, the association between the intima-media thickness (IMT) of the carotid artery and the insertion/ deletion (I/D) polymorphism of the ACE gene was investigated. SUBJECTS: Three hundred men and 300 women were selected randomly from the middle-aged population living in the town Oulu, Finland, of whom 515 subjects (85.8%) participated. METHODS: The IMT of the carotid arteries was determined by bilateral B-mode ultrasonography. IMT values were adjusted for gender, age, height, plasma low-density lipoprotein cholesterol level, smoking and systolic blood pressure. The I/D polymorphism of the ACE gene was determined by polymerase chain reaction. RESULTS: Among non-smokers, the subjects with the DD genotype had significantly higher carotid IMT than did those with II or ID. The association was found also in combined IMT plaque values. In the total population the association was weaker and it was absent in current smokers. Genotype could explain 1.3-2.7% of the variance of carotid IMT in non-smokers. No association between the amount or size of carotid plaques and genotype was observed. CONCLUSIONS: Variations at the ACE gene locus contribute to the degree of the early changes in carotid atherosclerosis in the population. The gene effect is, however, masked by stronger effects of environmental factors such as smoking. The lack of association between atherosclerotic plaques and genotypes may reflect different mechanisms being involved in plaque development and early arterial wall thickening.

Baroreflex sensitivity in drug-treated systemic hypertension.

Baroreflex sensitivity is impaired in patients with systemic hypertension. The persistence of abnormal baroreflex sensitivity despite adequate blood pressure control may be one of the reasons why the effect of antihypertensive therapy on coronary artery disease mortality has been less than expected on the basis of the achieved blood pressure levels.

Heart rate variability in systemic hypertension.

Low heart rate (HR) variability is a risk factor for cardiac mortality in various patient populations, but it has not been well established whether patients with long-standing hypertension have abnormalities in the autonomic modulation of HR. Time and frequency domain measures of HR variability were compared in randomly selected, age-matched populations of 188 normotensive and 168 hypertensive males (mean age 50 +/- 6 years for both). The standard deviation of the RR intervals was lower in the hypertensive subjects than in the normotensive ones (52 +/- 19 vs 59 +/- 20 mss; p <0.01), and the very low and low-frequency spectral components of HR variability analyzed as absolute units were reduced in the hypertensive patients relative to the normotensive controls (p <0.001 for both). Hypertensive subjects also had blunted changes of the normalized low- and high-frequency components in response to an upright (sitting) posture (NS) as compared with normotensive subjects (p <0.001 for both). Multiple regression analysis showed the standard deviation of the RR intervals to be predicted most strongly by systolic blood pressure, both in the patients with hypertension (beta--0.20, p=0.01) and in the normotensive subjects (beta--0.28, p=0.0002). After adjustment for the baseline differences in blood pressure and body mass index, none of the absolute measures of the HR variability or the responses of the normalized units of HR variability to a change in the body posture differed between the hypertensive subjects and normotensive controls. These data show that long-standing hypertension results in reduced overall HR variability and blunted autonomic responses to a change in body posture. Altered autonomic modulation of HR in hypertension is mainly due to elevated blood pressure and obesity in males with long-standing hypertension as compared with normotensive subjects.

Pulmonary inactivation of 5-hydroxytryptamine is decreased during cigarette smoke ventilation of rat isolated lungs.

1 The effect of cigarette smoke ventilation on the inactivation of [14C]-5-hydroxytryptamine (5-HT) was studied in isolated perfused lungs of the rat. 2 [14C]-5-HT 9.6 nmol was infused into the pulmonary circulation of rat lungs in 3 min. The nonrecirculating perfusion effluent was collected during the 5-HT infusion in three consecutive 1 min fractions. The amount of metabolites of 5-HT was determined from the perfusion effluent and from the perfused lungs. 3 The amount of metabolites of 5-HT in the perfused lungs was also decreased by cigarette smoke ventilation, although the total amount of radioactivity in the lung tissue was not significantly changed. 5 The decreased pulmonary inactivation of 5-HT may cause increased circulating levels of 5-HT, which would explain some cardiovascular changes during smoking.

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.