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Biomedical subjects

Heikki Saha

Publications and source records attributed to Heikki Saha.

At least 19 recordsLinked to original sources

Prediction of coronary artery disease by transesophageal echocardiographic detection of thoracic aortic plaque in patients with chronic kidney disease.

BACKGROUND/AIMS: Our aim was to examine the significance of thoracic aortic plaque detected by transesophageal echocardiography (TEE) in the prediction of coronary artery disease (CAD) in patients with chronic kidney disease (CKD). METHODS: We examined 118 patients (mean age 52 +/- 12 years) with CKD and followed them for a mean of 3.4 +/- 0.8 years. The study group included 52 predialysis patients with moderate to severe CKD (plasma creatinine > or = 200 micromol/l), 32 patients on dialysis treatment, and 34 renal transplant recipients. At baseline, TEE was performed to evaluate thoracic aortic atherosclerosis. CAD was defined by a history of a documented myocardial infarction, a coronary angiogram or a post-mortem autopsy finding showing significant occlusive CAD by the end of the follow-up period. RESULTS: CAD was documented in 31 (26%) of the 118 study patients. The presence of thoracic aortic plaque had a sensitivity of 100% and a specificity of 37% for CAD and the positive and negative predictive values were 36 and 100%, respectively. In the subset of 36 patients with morphological findings of coronary arteries by angiogram or autopsy, the presence of large thoracic aortic plaques (> or = 3 mm in diameter) had a 73% sensitivity and 90% specificity for significant coronary artery stenosis. The positive and negative predictive values were 95 and 56%, respectively. CONCLUSION: TEE may be used for detecting high-risk patients with CKD; the absence of thoracic aortic plaque predicted the absence of CAD, and the presence of large aortic plaques predicted significant coronary artery stenosis.

Adult↗

Renal insufficiency-induced bone loss is associated with an increase in bone size and preservation of strength in rat proximal femur.

Chronic renal insufficiency (CRI) results in phosphate retention and secondary hyperparathyroidism, the treatment of which is largely based on the use of calcium salts as phosphate binders. Advanced CRI causes bone fragility, but information about bone geometry and strength in moderate CRI is scarce. We assigned 39 8-week-old male Sprague-Dawley rats to sham-operation (Sham) or 5/6 nephrectomy (NTX). Four weeks later, the rats were randomized to 0.3% calcium (Sham, NTX) or 3.0% calcium diet (Sham + Calcium, NTX + Calcium). After 8 weeks, the animals were sacrificed, plasma samples collected, and femora excised for neck and midshaft analyses: dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and biomechanical testing. The NTX increased plasma urea and PTH 1.6-fold and 3.6-fold, respectively, whereas high calcium intake suppressed PTH to 30% of controls. Total femoral bone mineral content decreased (-6.3%) in the NTX group, while this deleterious effect was reversed by high calcium diet. In the site-specific analysis of the femoral neck, the volumetric bone density (-6.5%) was decreased in the NTX group but not NTX + Calcium group. However, in the nephrectomized rats, there was also a concomitant increase in the cross-sectional area (+15%), and, despite the decrease in bone density, the mechanical strength of the femoral neck was maintained. In the midshaft, NTX decreased cortical volumetric bone density (-1.2%), but similar to the femoral neck, no differences were found in the mechanical strength. In conclusion, a decrease in bone mass in moderate experimental CRI was associated with a concomitant increase in bone size, and maintenance of mechanical competence. Although high calcium diet suppressed plasma PTH to under normal physiological levels, it prevented the CRI-induced loss of bone mass without an adverse influence on bone strength.

Absorptiometry, Photon↗

High serum C3 predicts poor outcome in IgM nephropathy.

BACKGROUND: IgM nephropathy (IgMN) is an idiopathic glomerulonephritis with mesangial IgM deposition. The etiology of the depositions and possible association of serum and mesangial immunoglobulins and complement findings with renal outcome in IgMN remain unknown. Here we brought out data supplementary to our previous findings by reporting associations of immunological parameters with the outcome of IgMN. METHODS: Serum IgA, IgG, IgM, C3 and C4 were measured in 110 IgMN patients by single radial immunodiffusion or nephelometry. Mesangial IgA, IgG, IgM, C1q and C3 assessed in immunofluorescent study were graded as +/-. Seven histopathological parameters were semiquantitatively graded into three classes. The relationship of serum and mesangial immunoglobulin and complement findings with the clinical outcome and prognosis of IgMN was examined. RESULTS: We found significantly lower serum IgG and higher serum C3 levels in patients with nephrotic syndrome. Serum C3 correlated with the severity of glomerular histopathological changes. Of immunological parameters evaluated a low serum IgG/C3 ratio correlated best with the progression of renal disease. However, serum C3 was associated independently with progression in the case of patients without nephrotic syndrome. CONCLUSIONS: In addition to previously reported factors, immunological parameters may also be helpful in determining the prognosis in IgMN. High serum C3 predicts poor outcome in IgMN, being associated with high-grade proteinuria, severe histopathological changes and progression.

Adolescent↗

Bone as a possible target of chemical toxicity of natural uranium in drinking water.

Uranium accumulates in bone, affects bone metabolism in laboratory animals, and when ingested in drinking water increases urinary excretion of calcium and phosphate, important components in the bone structure. However, little is known about bone effects of ingested natural uranium in humans. We studied 146 men and 142 women 26-83 years of age who for an average of 13 years had used drinking water originating from wells drilled in bedrock, in areas with naturally high uranium content. Biochemical indicators of bone formation were serum osteocalcin and amino-terminal propeptide of type I procollagen, and a marker for bone resorption was serum type I collagen carboxy-terminal telopeptide (CTx). The primary measure of uranium exposure was uranium concentration in drinking water, with additional information on uranium intake and uranium concentration in urine. The data were analyzed separately for men and women with robust regression (which suppresses contributions of potential influential observations) models with adjustment for age, smoking, and estrogen use. The median uranium concentration in drinking water was 27 microg/L (interquartile range, 6-116 microg/L). The median of daily uranium intake was 36 microg (7-207 microg) and of cumulative intake 0.12 g (0.02-0.66 g). There was some suggestion that elevation of CTx (p = 0.05) as well as osteocalcin (p = 0.19) could be associated with increased uranium exposure (uranium in water and intakes) in men, but no similar relationship was found in women. Accordingly, bone may be a target of chemical toxicity of uranium in humans, and more detailed evaluation of bone effects of natural uranium is warranted.

Adult↗

Asbestos exposure as a risk factor for retroperitoneal fibrosis.

BACKGROUND: Retroperitoneal fibrosis (RPF) is an uncommon disease with unknown causation in most cases. The pathognomonic finding is a fibrous mass covering the abdominal aorta and the ureters. Our aim was to clarify the possible role of asbestos exposure in the development of RPF. The hypothesis was based on the ability of asbestos to cause fibrosis in pulmonary and pleural tissue. METHODS: We undertook a case-control study of 43 patients with the disease (86% of eligible cases) treated in three university hospital districts of Finland in 1990-2001. For every patient, five population-based controls were selected, matched by age, sex, and central hospital district. We assessed asbestos exposure and medical history using a postal questionnaire and a personal interview. Of the 215 eligible controls, 179 (83%) participated in the study. FINDINGS: The age-standardised incidence of RPF was 0.10 (95% CI 0.07-0.14) per 100?000 person-years. The disease was strongly associated with asbestos exposure. The odds ratio (OR) was 5.54 (1.64-18.65) for less than 10 fibre-years of asbestos exposure and 8.84 (2.03-38.50) for 10 or more fibre-years, the attributable fraction being 82% and 89%, respectively. Other risk factors were previous use of ergot derivates (OR 9.92 [1.63-60.26]), abdominal aortic aneurysm (OR 6.73 [0.81-56.08]), and smoking for more than 20 pack-years (OR 4.73 [1.28-17.41]). INTERPRETATION: Our results show that occupational asbestos exposure is an important causal factor for RPF. For patients with work-related asbestos exposure, RPF should be considered an occupational disease.

Aged↗

Homocysteine and carotid atherosclerosis in chronic renal failure--the confounding effect of renal function.

Since total homocysteine (tHcy) level is markedly elevated in patients with chronic renal failure (CRF), it has been presented as a potential factor contributing to the high risk of cardiovascular disease (CVD) in CRF. Our aim was to examine the significance of elevated tHcy level and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. In this cross-sectional study, 135 study patients with CRF (52 +/- 11 years) included 58 patients with moderate to severe predialysis CRF, 36 dialysis patients and 41 renal transplant recipients. In addition, 58 control subjects were examined. The association of tHcy level and classic risk factors for atherosclerosis with common carotid artery intima-media thickness (IMT) or carotid artery plaque score was examined. We found no association between tHcy and carotid IMT or a high carotid plaque score in the CRF patient groups. No consistent association was found between elevated tHcy and coronary artery disease, cerebrovascular disease or peripheral arterial disease. Renal function, described as creatinine clearance, was the strongest determinant for tHcy level. Significant predictors of carotid atherosclerosis were age, duration of hypertension and elevated low-density lipoprotein cholesterol level. In conclusion, the present study shows no apparent association between tHcy level and atheromatous carotid findings in patients with CRF. However, because of the changing renal function in the course of renal disease, the strong confounding effect of renal function may not be adequately controlled for the analysis of the significance of elevated tHcy level for CVD in patients with CRF.

Adult↗

Carotid atherosclerosis in chronic renal failure-the central role of increased plaque burden.

Studies on carotid artery atherosclerosis have been performed in order to understand the high risk for cardiovascular disease in chronic renal failure (CRF). The purpose of this study was to evaluate the extent and nature of carotid artery atherosclerosis in patients with CRF. Of the 135 patients with CRF (52 +/- 11 years), 58 had moderate to severe predialysis CRF (PR), 36 were on dialysis treatment (DI), and 41 were renal transplant recipients (TR). In addition, 58 control subjects (CO) were examined. Common carotid artery intima-media thickness (IMT), plaque prevalence, plaque score, and stiffness index beta were determined. Furthermore, plaque calcification and internal carotid artery stenoses were classified. Plaque prevalence (PR 64%, DI 61%, TR 51%, CO 28%; P < 0.001) and plaque score (PR 3.3 +/- 4.3, DI 3.0 +/- 3.4, TR 2.5 +/- 3.2, CO 0.8 +/- 1.7 mm; P < 0.001) were significantly greater in the CRF patient groups compared to the controls, whereas no difference in IMT was noted between the study groups. The prevalences of plaque calcification and internal carotid artery stenoses were higher among the CRF patient groups. In addition, the stiffness index beta was higher in the CRF patient groups. The present study shows that the characteristic alterations of the carotid arteries in CRF include increased plaque burden, calcification and increased arterial stiffness.

Adult↗

Risk factors for aortic atherosclerosis determined by transesophageal echocardiography in patients with CRF.

BACKGROUND: The significance of various risk factors for cardiovascular disease (CVD) in the pathogenesis of atherosclerosis in patients with chronic renal failure (CRF) is, to a great deal, unresolved. The high risk for CVD in patients with CRF may be caused by the high prevalence of recognized risk factors for CVD or by factors characteristic of CRF in these patients. In this prospective cross-sectional study, we examined risk factors for thoracic aortic atherosclerosis in a population of patients with CRF consisting of predialysis and dialysis patients, as well as renal transplant recipients. METHODS: Of 118 patients, 52 patients had moderate to severe predialysis CRF, 32 patients were on dialysis treatment, and 34 patients were renal transplant recipients. Mean age was 52 +/- 12 years, and 35 patients (30%) had diabetes. Multiplane transesophageal echocardiography (TEE) was performed using local anesthesia. RESULTS: Large aortic plaques (LAPs; > or = 3.0 mm in diameter) were found in 39 patients (33%). In univariate analysis, age, duration of hypertension, pulse pressure, low diastolic blood pressure, elevated fibrinogen level, C-reactive protein level, total cholesterol level, low-density lipoprotein cholesterol level, and duration of dialysis or a functioning renal transplant were significantly associated (P < 0.05) with LAP. In multivariate analysis, age, duration of hypertension, and total cholesterol level were associated with LAP. CONCLUSION: Results of the present TEE study suggest that in addition to duration of hypertension and renal disease, hypercholesterolemia has a role in the pathogenesis of atherosclerosis in patients with CRF.

Aged↗

IgM nephropathy: clinical picture and long-term prognosis.

BACKGROUND: Immunoglobulin M (IgM) nephropathy is an idiopathic glomerulonephritis with mesangial hypercellularity and diffuse IgM deposits. METHODS: We studied clinical presentation, morphological findings, and prognostic factors in 110 patients with IgM nephropathy without systemic diseases. The series included both pediatric and adult patients with nephrotic syndrome (NS) or minor urinary abnormalities. RESULTS: Mean postbiopsy follow-up was 8 years. During 15 years of follow-up, 36% of patients developed renal insufficiency and 23% reached end-stage renal failure. In multivariate analysis, hypertension at the time of renal biopsy was the only significant risk factor for renal insufficiency. Of histological parameters, interstitial fibrosis had the strongest prognostic value. Hypertension was diagnosed in 50% of patients with a postbiopsy follow-up of 15 years. Twenty-nine percent of nephrotic patients had disease resistant to corticosteroids, whereas 80% of patients with steroid-sensitive disease were steroid dependent. Eleven patients, 8 patients with NS and 3 patients with asymptomatic proteinuria, underwent repeated renal biopsy. In five samples, typical morphological characteristics of focal and segmental glomerulosclerosis were seen. CONCLUSION: We propose that IgM nephropathy can be divided into two subgroups with similar renal biopsy findings, but differences in sex distribution and initial presentation.

Adolescent↗

Treatment of secondary hyperparathyroidism by high calcium diet is associated with enhanced resistance artery relaxation in experimental renal failure.

BACKGROUND: Vasorelaxation is impaired in renal failure (RF) and hypertension. A high calcium diet enhances vasodilatation and reduces blood pressure in experimental hypertension. Oral calcium salts are used as phosphate binders in RF. However, the effect of increased calcium intake on arterial tone in RF is unknown. METHODS: We investigated the influence of an 8-week high calcium diet (0.3 vs 3.0%) on resistance artery tone in 5/6 nephrectomized (NTX) rats. Calcium was supplemented as carbonate salt, blood pressure measured by tail-cuff, urine collected in metabolic cages, and samples taken for blood chemistry and parathyroid hormone (PTH). Functional studies of isolated third-order branches of the mesenteric artery in vitro were performed using the Mulvany multimyograph. RESULTS: Plasma urea was elevated 1.6-fold and systolic blood pressure by 10 mmHg after NTX, while increased calcium intake was without effect on these variables. Plasma PTH and phosphate were raised following NTX, and suppressed by high calcium diet. Vasorelaxations induced by K(+) channel agonists 11,12-epoxyeicosatrienoic acid and levcromakalim were impaired after NTX. Vasorelaxation induced by acetylcholine was also reduced following NTX, and experiments with N(G)-nitro-L-arginine methyl ester, diclofenac and charybdotoxin + apamin suggested that the K(+) channel-mediated component of endothelium-dependent relaxation was deficient after NTX. Increased calcium intake corrected all impairments of vasodilatation in NTX rats. CONCLUSIONS: Deficient vasorelaxation via K(+) channels was normalized by high calcium diet in experimental RF. This effect was independent of the degree of renal impairment and blood pressure, but was associated with improved calcium metabolism: plasma levels of PTH and phosphate were decreased and ionized calcium was increased.

Animals↗

Vascular influences of calcium supplementation and vitamin D-induced hypercalcemia in NaCl-hypertensive rats.

This 8-week study investigated the effects of increasing dietary Ca2+ content from 1.0% to 3.0% and hypercalcemia induced by oral 1alpha-OH vitamin D3 (1OH-D3, 1.2 microg/kg), on arterial tone in NaCl-hypertensive rats. The high-Ca2+ diet completely prevented the increase in blood pressure induced by the 6.0% NaCl chow, while plasma total Ca2+ and body weight were not different from controls. The 1OH-D3 treatment moderately elevated plasma total Ca2+ and attenuated the NaCl-induced rise in blood pressure, but also impaired weight gain. The tone of isolated mesenteric arterial rings was examined at the end of study. The endothelium-independent relaxations to nitroprusside, isoproterenol, and cromakalim were impaired in NaCl-hypertension. Experiments with NG-nitro-l-arginine methyl ester and tetraethylammonium in vitro suggested that both the nitric oxide- and hyperpolarization-mediated components of endothelium-dependent relaxation to acetylcholine were reduced in NaCl-hypertensive rats. All of the impaired relaxations in NaCl hypertension were normalized by concomitant Ca2+ supplementation. The 1OH-D3 treatment did not affect vascular relaxation, but it attenuated maximal contractile responses induced by norepinephrine and KCl by more than 50%. The reduced vasoconstrictor responses could not be explained by increased apoptosis in the vessel wall, but calcification may have played a role, since moderate signs of medial or adventitial calcification were observed in the aortic preparations after the 1OH-D3 treatment. In conclusion, a high-Ca2+ diet, which did not cause hypercalcemia, normalized blood pressure and endothelium-dependent and endothelium-independent vasorelaxation in NaCl-hypertensive rats. In contrast, chronic hypercalcemia induced by 1OH-D3 was associated with moderately lowered blood pressure, possibly because of reduced vasoconstrictor responses in arterial smooth muscle.

Animals↗

Increased calcium intake reduces plasma cholesterol and improves vasorelaxation in experimental renal failure.

Chronic renal failure (CRF) is associated with abnormal lipid metabolism and high prevalence of vascular complications. Calcium salts are commonly used in CRF as phosphate binders. Increased calcium intake may also lower plasma cholesterol and beneficially influence vascular tone. Therefore, we investigated the influence of increasing dietary calcium from 0.3% to 3.0% for 8 wk after 5/6 nephrectomy (NTX) on plasma cholesterol and mesenteric resistance vessel tone in male Sprague-Dawley rats. The groups were Sham, Sham-Calcium, NTX, and NTX-Calcium (n = 10-11). Blood pressure was modestly elevated after NTX, whereas the plasma creatinine, urea nitrogen, phosphate, and parathyroid hormone levels were clearly increased. The high-calcium diet suppressed plasma phosphate and parathyroid hormone but was without effect on blood pressure. The NTX resulted in 1.6-fold elevation in plasma total cholesterol and 40% reduction in high density-to-low density lipoprotein ratio (HDL/LDL). However, the lipid profile in NTX rats on the high-calcium diet did not differ from sham-operated controls. The endothelium-mediated relaxations induced by acetylcholine were impaired in NTX rats, whereas the response was normalized by a high-calcium diet. No differences in vasorelaxations by the endothelium-independent vasodilator nitroprusside were detected. In conclusion, improved vasorelaxation after a high-calcium diet could be due to reduced plasma total cholesterol and ameliorated HDL/LDL ratio, although decreased plasma phosphate and parathyroid hormone may also play a significant role in the vascular effects of increased calcium intake.

Animals↗

The prevalence of peripheral arterial disease and medial arterial calcification in patients with chronic renal failure: requirements for diagnostics.

BACKGROUND: Knowledge of the prevalence of peripheral arterial disease (PAD) in patients with chronic renal failure (CRF) is limited because of a lack of uniformity in disease definition and recognition. Furthermore, little is known of the prevalence of medial arterial calcification (MAC) in patients with CRF. Our goal is to study the prevalence of PAD and MAC defined by ankle brachial index (ABI) or toe brachial index (TBI) measurements in a Finnish population of patients with CRF consisting of predialysis and dialysis patients, as well as renal transplant recipients. METHODS: We examined 136 patients with CRF and 59 control subjects. Fifty-nine of the patients with CRF had moderate to severe predialysis CRF, 36 patients were on dialysis treatment, and 41 were renal transplant recipients. Mean age of patients was 51.9 +/- 11.5 years, and 39 patients (29%) had diabetes. ABI and TBI were measured by means of photoplethysmography. The definition of PAD required an ABI value of 0.90 or less, a TBI value of 0.60 or less, or a previous positive lower-extremity angiogram result. ABI values of 1.3 or greater or incompressible arteries at ankle level indicated MAC. The presence of claudication was determined by an interview. RESULTS: Prevalences of PAD on this study were 22.0% in patients with predialysis CRF, 30.6% in patients on dialysis treatment, 14.6% in renal transplant recipients, and 1.7% in the control group (P = 0.001). Prevalences of MAC were 23.7%, 41.7%, 23.1%, and 3.4% (P < 0.001), respectively. Only 9 patients had claudication, and 6 of those patients had PAD. CONCLUSION: Both asymptomatic PAD and MAC are common in patients with CRF. Therefore, we recommend the use of both ABI and TBI measurements in the evaluation of PAD in patients with CRF.

Arteriosclerosis↗

Preserved endothelium-dependent but impaired beta-adrenergic relaxation of the resistance vessels in experimental renal failure.

Chronic renal failure is associated with increased cardiovascular morbidity and reduced arterial elasticity. Only little information is available on the functional effects of uraemia on resistance arteries. Therefore, we studied the influence of renal failure on rat small mesenteric vessels. The responses of arterial rings were investigated in a Mulvany myograph 6 weeks after 5/6 nephrectomy or sham operation. The subtotal nephrectomy resulted in a 1.9-fold elevation of plasma urea nitrogen but was without significant effect on blood pressure. Endothelium-dependent relaxations, largely mediated via arterial K(+) channels, were preserved in the resistance vessels of uraemic rats. Endothelium-independent vasorelaxations, mediated via exogenous nitric oxide and the opening of ATP-sensitive K(+) channels, were also unchanged. However, the responses induced by isoprenaline were slightly reduced, indicating impaired relaxation via beta-adrenoceptors in experimental renal failure.

Animals↗