The varied clinical and radiological manifestations of contrast-induced encephalopathy following coronary angiography.

Contrast-induced encephalopathy (CIE) is a rare complication of imaging using ionidated contrast media. Its pathogenesis remains unknown, and its clinical presentation is variable. We present two cases of CIE following coronary angiography (CAG) that underscore the multitude of clinical manifestations and imaging findings associated with the disorder. In patient 1, CIE manifested during the CAG with agitation and decreased consciousness, followed by left hemiparesis and visual neglect. Native computed tomography (CT) of the head was unremarkable but CT perfusion (CTP) showed extensive hypoperfusion of the right hemisphere with corresponding slow-wave activity in the electroencephalogram (EEG). These findings were more pronounced the next day. Magnetic Resonance Imaging (MRI) revealed multiple small dot-like ischemic lesions across the brain. By day 6, she had fully recovered. Patient 2 developed transient expressive aphasia during the CAG followed by migraineous symptoms. Native head CT showed a large area of parenchymal edema, sulcal effacement and variable subarachnoid hyperdensity in the right hemisphere. He developed mild left-side hemiparesis, spontaneous gaze deviation and inattention. Brain MRI showed small dot-like acute ischemic lesions across the brain. The next morning, he had a generalized tonic-clonic seizure (GTCS) after which native head CT was normal, but the EEG showed a post-ictal finding covering the right hemisphere. His hemiparesis resolved within 2 months. The diversity in clinical and radiographic presentations suggest that CIE involve many pathophysiological processes.

The presence of intraperitoneal, retroperitoneal and pleural fluid in acute Puumala hantavirus infection.

BACKGROUND: Puumala hantavirus (PUUV) causes most cases of haemorrhagic fever with renal syndrome (HFRS) in Europe. PUUV infection is characterised by acute kidney injury, thrombocytopenia and increased capillary leakage. Typical symptoms are fever, headache, nausea, abdominal and back pain. This study aimed to evaluate the amount and distribution of intraperitoneal, retroperitoneal and pleural fluid and the association of fluid collections to the symptoms and clinical findings in patients with acute PUUV infection. METHODS: Abdominal magnetic resonance imaging (MRI) was performed on 27 hospitalised patients with acute PUUV infection. The clinical and laboratory findings and patients' symptoms were analysed in relation to the imaging findings. The thickness of the fluid collections was measured in millimetres (mm) from axial images. RESULTS: Fluid collections were found in all patients. The amount of intraperitoneal fluid correlated positively with plasma C-reactive protein (CRP) level (r = 0.586, p = .001), while it had an inverse correlation with serum creatinine concentration (r = -0.418, p = .030). Retroperitoneal fluid also correlated inversely with serum creatinine and cystatin C concentrations (r = -0.501, p = .008 and r = -0.383, p = .048, respectively). The amount of fluid was not greater in patients with abdominal or back pain. Patients with back pain had higher serum creatinine compared with patients without back pain, 452 µmol/L (range 88-1071) vs. 83 µmol/L (range 60-679), p = .004. CONCLUSIONS: Fluid collections were found in all patients. A greater amount of intraperitoneal fluid associates with higher CRP concentrations but not with higher serum creatinine levels. Back pain associates with higher creatinine level but not with the presence of fluids.

Primary aldosteronism: Higher volume load, cardiac output and arterial stiffness than in essential hypertension.

BACKGROUND: The diagnostics of primary aldosteronism (PA) are usually carried out in patients taking antihypertensive medications. We compared haemodynamics between medicated PA, medicated essential hypertension (EH), never-medicated EH and normotensive controls (n = 130 in all groups). METHODS: The hypertensive groups were matched for age (53 years), sex (84 male/46 female) and body mass index (BMI) (30 kg m-2 ); normotensive controls had similar sex distribution (age 48 years, BMI 27 kg m-2 ). Haemodynamics were recorded using whole-body impedance cardiography and radial pulse wave analysis, and the results were adjusted as appropriate. Radial blood pressure recordings were calibrated by brachial blood pressure measurements from the contralateral arm. RESULTS: Radial and aortic systolic and diastolic blood pressure was similar in PA and never-medicated EH, and higher than in medicated EH and normotensive controls (P ≤ 0.001 for all comparisons). Extracellular water balance was ~ 4% higher in PA than in all other groups (P < 0.05 for all), whilst cardiac output was ~ 8% higher in PA than in medicated EH (P = 0.012). Systemic vascular resistance and augmentation index were similarly increased in PA and both EH groups when compared with controls. Pulse wave velocity was higher in PA and never-medicated EH than in medicated EH and normotensive controls (P ≤ 0.033 for all comparisons). CONCLUSIONS: Medicated PA patients presented with corresponding systemic vascular resistance and wave reflection, but higher extracellular water volume, cardiac output and arterial stiffness than medicated EH patients. Whether the systematic evaluation of these features would benefit the clinical diagnostics of PA remains to be studied in future.

Ultrasound Screening of Men with Coronary Artery Disease for Abdominal Aortic Aneurysms: A Prospective Dual Center Study.

BACKGROUND AND AIMS: According to the heterogeneous results of previous studies, the prevalence of abdominal aortic aneurysm seems high among men with coronary artery disease. The associating risk factors for abdominal aortic aneurysm in this population require clarification. Our objective was to assess the prevalence of non-diagnosed abdominal aortic aneurysms in men with angiographically verified coronary artery disease and to document the associated co-morbidities and risk factors. MATERIAL AND METHODS: Altogether, 407 men with coronary artery disease were screened after invasive coronary angiography in two series at independent centers. Risk factor data were recorded and analyzed. RESULTS AND CONCLUSION: The mean age of the study cohort was 70.0 years (standard deviation: 11.0). The prevalence of previously undiagnosed abdominal aortic aneurysms in the whole screened population of 407 men was 6.1% (n = 25/407). In a multivariate analysis of the whole study population, the only significant risk factors for abdominal aortic aneurysm were age (odds ratio: 1.04, 95% confidence interval: 1.00-1.09) and history of smoking (odds ratio: 3.13, 95% confidence interval: 1.26-7.80). Non-smokers with abdominal aortic aneurysm were significantly older than smokers (mean age: 80.7 (standard deviation: 8.0) vs 68.0 (standard deviation: 11.1), p = 0.003), and age was a significant risk factor only among non-smokers (p = 0.011; p = 0.018 for interaction). Among smokers, the prevalence of abdominal aortic aneurysm was 8.8%, and 72% (n = 18/25) of all diagnosed abdominal aortic aneurysm patients were smokers. Prevalence of undiagnosed abdominal aortic aneurysms among patients with coronary artery disease is high, and history of smoking is the most significant risk factor for abdominal aortic aneurysm. Effectiveness of selective screening of abdominal aortic aneurysm in male patients with coronary artery disease warrants further studies.

Urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection.

OBJECTIVES: Urokinase-type plasminogen activator receptor (uPAR) is upregulated during inflammation and known to bind to ß3 -integrins, receptors used by pathogenic hantaviruses to enter endothelial cells. It has been proposed that soluble uPAR (suPAR) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating ß3 -integrin in kidney podocytes. Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection. DESIGN: A single-centre, prospective cohort study. SUBJECTS AND METHODS: Urinary suPAR levels were measured twice during the acute phase and once during convalescence in 36 patients with serologically confirmed PUUV infection. Fractional excretion of suPAR (FE suPAR) and of albumin (FE alb) was calculated. RESULTS: The FE suPAR was significantly elevated during the acute phase of PUUV infection compared to the convalescent phase (median 3.2%, range 0.8-52.0%, vs. median 1.9%, range 1.0-5.8%, P = 0.005). Maximum FE suPAR was correlated markedly with maximum FE alb (r = 0.812, P < 0.001) and with several other variables that reflect disease severity. There was a positive correlation with the length of hospitalization (r = 0.455, P = 0.009) and maximum plasma creatinine level (r = 0.780, P < 0.001) and an inverse correlation with minimum urinary output (r = -0.411, P = 0.030). There was no correlation between FE suPAR and plasma suPAR (r = 0.180, P = 0.324). CONCLUSION: Urinary suPAR is markedly increased during acute PUUV infection and is correlated with proteinuria. High urine suPAR level may reflect local production of suPAR in the kidney during the acute infection.

Glomerular filtration rate and parathyroid hormone are associated with 1,25-dihydroxyvitamin D in men without chronic kidney disease.

BACKGROUND AND AIM: Vitamin D, estimated glomerular filtration rate (eGFR) and parathyroid hormone (PTH) are related to cardiovascular disease risk. We examined the associations between the levels of 25-hydroxyvitamin D (25-D) and 1,25-dihydroxyvitamin D (1,25-D) and both eGFR and PTH. DESIGN AND SETTING: Cross-sectional population-based study in Kuopio, Eastern Finland. SUBJECTS: A total of 909 men without known chronic kidney disease (CKD) and not receiving antidiabetic medication, aged from 45 to 73 years, were included in the study. Main outcome measures. Fasting levels of 25-D, 1,25-D, creatinine and PTH were measured, and an oral glucose tolerance test (OGTT) was performed. RESULTS: High levels of 25-D were associated with low levels of eGFR and PTH (ß = -0.17, P = 9 × 10(-7) and ß = -0.28, P = 6 × 10(-17) , respectively, adjusted for age, body mass index and levels of calcium, phosphorus and glucose in a 2-h OGTT, and also for either eGFR or PTH). By contrast, high 1,25-D levels were associated with high levels of eGFR and PTH (ß = 0.17, P = 2 × 10(-6) and ß = 0.19, P = 5 × 10(-8) , respectively, adjusted as mentioned earlier and additionally for 25-D). Eighteen per cent of men in the highest 25-D quartile were in the lowest 1,25-D quartile and also had a lower eGFR than men with high levels of both 25-D and 1,25-D (P = 4 × 10(-5) ). Finally, 15% of men in the lowest 25-D quartile were in the highest 1,25-D quartile and also had higher PTH levels than men with low levels of both 25-D and 1,25-D (P = 2 × 10(-3) ). CONCLUSION: Our findings suggest that both eGFR and PTH are significantly associated with vitamin D metabolism in men without known CKD.

High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica.

Our aim was to investigate whether plasma levels of the long pentraxin-3 (PTX3) associate with the severity of Puumala hantavirus-induced nephropathia epidemica (NE). Sixty-one prospectively identified consecutively hospitalized NE patients were examined. Plasma PTX3, interleukin (IL)-6, terminal complement complex SC5b-9, complement component C3, C-reactive protein (CRP), creatinine, sodium, kynurenine, and tryptophan levels, as well as the blood cell count, were determined for up to five consecutive days after hospitalization. Receiver operating characteristic (ROC) analysis revealed that the maximum PTX3 level >101.6 ng/ml (high PTX3) showed a sensitivity of 71% and a specificity of 89% for detecting platelet level <50 × 10(9)/l, with an area under the curve (AUC) value of 0.78 (95% confidence interval [CI] 0.63-0.94). High PTX3 level was also associated with several other variables reflecting the severity of the disease: patients with high PTX3 level had higher maximum blood leukocyte (16.1 vs. 9.7 × 10(9)/l, p < 0.001), plasma IL-6 (16.9 vs. 9.0 pg/ml, p = 0.007), and creatinine (282 vs. 124 µmol/l, p = 0.007) levels than patients with low maximum PTX3 level. They also had longer hospital stays (8 vs. 5 days, p = 0.015) compared to patients with low PTX3 level. High plasma PTX3 levels are associated with thrombocytopenia and the overall severity of NE.

Impact of coronary artery bypass surgery on ischemic mitral regurgitation.

INTRODUCTION: To determine the course of ischemic mitral regurgitation (IMR) after coronary artery bypass grafting (CABG), and evaluate preoperative factors which predict the development of the severity of IMR after CABG. METHODS: Between 1992-2005, 1995 patients underwent CABG and 170 of them had IMR. Data of 131 patients were retrospectively analyzed and living patients (n = 112) had a clinical follow-up visit. The mean follow-up time was 6.5 years. RESULTS: At the time of CABG, 66% of the 131 cases analyzed had mild, 31% had moderate, and 3% had severe IMR. At the time of follow-up, 52% of patients had either no IMR or mild IMR, 27% had moderate IMR, 6% had severe IMR and 15% suffered from cardiac related death. During follow-up IMR grade reduced in 25% of study patients. None of the patient had re-operation due to the mitral regurgitation. Multivariate analysis showed that left ventricular ejection fraction (LVEF) was an independent predictor of good prognosis (O.R. 1.4, 95% C.I. 1.15-1.83/ 10% increase of LVEF, p = 0.02). CONCLUSION: Half of the patients, who have IMR at the time of CABG, have no IMR or only mild IMR postoperatively. Good LVEF adds to the probability that CABG only can reduce IMR.

Reactive arthritis in a population exposed to an extensive waterborne gastroenteritis outbreak after sewage contamination in Pirkanmaa, Finland.

OBJECTIVES: To assess the occurrence, clinical picture, and triggering infections of reactive arthritis (ReA) associated with a large waterborne gastroenteritis outbreak. METHODS: After an extensive sewage contamination of the water supply system, an estimated 8453 of the 30 016 inhabitants of the town of Nokia fell ill. General practitioners and occupational physicians were advised to refer any patients with suspicion of new ReA to rheumatological examination including faecal culture, human leucocyte antigen (HLA)-B27 and antibody tests for Campylobacter, Salmonella, and Yersinia. RESULTS: Forty-five patients (33 females, 12 males) aged 16-77 years (median 53) were referred. ReA was diagnosed in 21, postinfectious arthralgia in 13, and other musculoskeletal conditions in 11 patients. HLA-B27 was positive in five out of 44 patients (11%). Of the 21 patients with ReA, possible triggering infections were observed in seven (33%), Campylobacter in four, Yersinia in three, and Salmonella in one, who also had Campylobacter infection. ReA was mild in all but one patient who presented with persistent Salmonella enterica serotype enteritidis infection. CONCLUSIONS: Taking into account the large population contaminated with potentially arthritogenic agents, the occurrence of ReA was rare and mild in character.

Glomerulonephritis emerging shortly after Puumala hantavirus infection: a report on 7 patients.

AIMS: Nephropathia epidemica (NE) is mild type of hemorrhagic fever caused by Puumala (PUU) hantavirus. Renal biopsy typically shows acute tubulointerstitial nephritis and complete recovery is the usual outcome. We previously described 5 patients with membranoproliferative glomerulonephritis (MPGN) after acute NE. We now report on 7 more patients who developed biopsy-confirmed glomerulonephritis (GN) during the convalescent phase of NE. MATERIAL AND METHODS: We present case histories of 7 patients with nephrotic-range proteinuria concomitant with hematuria after serologically verified NE. RESULTS: Renal biopsy specimens disclosed MPGN in 5 patients, membranous GN (MGN) in 1 and mesangial GN (MesGN) in 1. All patients achieved remission of nephrotic syndrome within a median time of 0.6 years (range 0.5 - 5.5 y). The median follow-up time was 1.7 years (0.7 - 15.6 y). CONCLUSIONS: As a rare phenomenon, nephrotic syndrome may emerge during the convalescent phase of acute PUU hantavirus infection. In most cases the prognosis of GN caused by NE seems to be favorable.

An extensive gastroenteritis outbreak after drinking-water contamination by sewage effluent, Finland.

An inappropriate cross-connection between sewage- and drinking-water pipelines contaminated tap water in a Finnish town, resulting in an extensive waterborne gastroenteritis outbreak in this developed country. According to a database and a line-list, altogether 1222 subjects sought medical care as a result of this exposure. Seven pathogens were found in patient samples of those who sought treatment. To establish the true disease burden from this exposure, we undertook a population-based questionnaire investigation with a control population, infrequently used to study waterborne outbreaks. The study covered three areas, contaminated and uncontaminated parts of the town and a control town. An estimated 8453 residents fell ill during the outbreak, the excess number of illnesses being 6501. Attack rates were 53% [95% confidence interval (CI) 49.5-56.4] in the contaminated area, 15.6% (95% CI 13.1-18.5) in the uncontaminated area and 6.5% (95% CI 4.8-8.8) in the control population. Using a control population allowed us to differentiate baseline morbidity from the observed morbidity caused by the water contamination, thus enabling a more accurate estimate of the disease burden of this outbreak.

The effects of pre- and post-pregnancy inflammatory bowel disease diagnosis on birth outcomes.

BACKGROUND: Inflammatory bowel diseases are frequent in women at their optimum age for reproduction. Possible effects on pregnancy are therefore of interest. AIM: To assess pregnancy outcomes in 212 women: 135 of whom were diagnosed with inflammatory bowel disease before pregnancy and 77 after pregnancy. METHODS: A clinical birth database was examined retrospectively. Odds ratios (ORs) for the main outcomes were calculated with 95% confidence intervals; these were adjusted for confounding factors. RESULTS: Overall, pregnancy outcomes were good. No increased risk of preterm births or need for neonatal intensive care was observed. However, women with inflammatory bowel disease had more growth-retarded newborns, at an adjusted OR of 2.08 (1.26-3.44) and the mode of delivery was more frequently Caesarean section, with an OR of 2.75 (1.82-4.16). In the women who were diagnosed with inflammatory bowel disease after the pregnancy, we found no difference in the obstetric outcome as compared with the general obstetric population. CONCLUSIONS: Most women with inflammatory bowel disease have a normal pregnancy outcome and, overall, inflammatory bowel disease during pregnancy poses low-to-moderate risks, the main concern being increased risk of impaired foetal growth. Normal maternal weight gain during pregnancy, possibly indicating a more stable disease, appeared to protect against adverse outcomes.

Diverse associations of 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D with dyslipidaemias.

BACKGROUND AND AIM: Previous studies have suggested a link between circulating levels of 25-hydroxyvitamin D (25-D) and dyslipidaemias. However, it is not known whether 25-D and the active hormone 1,25-dihydroxyvitamin D (1,25-D) have similar associations with dyslipidaemias. Therefore, we studied the associations between both 25-D and 1,25-D and total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides in a population-based study. DESIGN: Cross-sectional population-based study. SETTING: Kuopio, Eastern Finland. SUBJECTS: A total of 909 men, aged from 45 to 70 years, who were not receiving antidiabetic medication were enrolled. MAIN OUTCOME MEASURES: Fasting serum samples were obtained for measurement of 25-D, 1,25-D and lipid levels. An oral glucose tolerance test was performed, and insulin sensitivity was evaluated using the Matsuda insulin sensitivity index (Matsuda ISI). RESULTS: We found a significant inverse association between 25-D and total-C, LDL-C and triglycerides (ß = -0.15, -0.13 and -0.17, respectively, P < 0.001), but no association between 25-D and HDL-C was observed. By contrast, 1,25-D was associated with HDL-C (ß = 0.18, P < 0.001), whereas no relationship was found between 1,25-D and LDL-C or triglycerides. The associations remained significant after the exclusion of subjects receiving statin treatment and after adjustment for age, waist circumference, body mass index, alcohol consumption, smoking, renal function, glucose tolerance and Matsuda ISI. CONCLUSION: Low levels of active vitamin D (1,25-D) are associated with low HDL-C levels, whereas low levels of the storage form 25-D are associated with high levels of total-C, LDL-C and triglycerides. Our findings may provide new insights into the understanding of the link between vitamin D deficiency and cardiovascular disease.

Hormonal deficiencies during and after Puumala hantavirus infection.

Previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (HFRS), but the prevalence of hormonal deficiencies after nephropathia epidemica (NE), a milder form of HFRS, has not been studied. This study was conducted in order to determine the prevalence of hormonal defects in patients with acute NE and during long-term follow-up. Fifty-four patients with serologically confirmed acute NE were examined by serum hormonal measurements during the acute NE, after 3 months, and after 1 to 10 (median 5) years. Thirty out of 54 (56%) patients had abnormalities of the gonadal and/or thyroid axis during the acute NE. After a median follow-up of 5 years, 9 (17%) patients were diagnosed with a chronic, overt hormonal deficit: hypopituitarism was found in five patients and primary hypothyroidism in five patients. In addition, chronic subclinical testicular failure was found in five men. High creatinine levels and inflammatory markers during NE were associated with the acute central hormone deficiencies, but not with the chronic deficiencies. Hormonal defects are common during acute NE and, surprisingly, many patients develop chronic hormonal deficiencies after NE. The occurrence of long-term hormonal defects cannot be predicted by the severity of acute NE.

Renal safety of initial combination versus single DMARD therapy in patients with early rheumatoid arthritis: an 11-year experience from the FIN-RACo Trial.

OBJECTIVE: To evaluate the renal safety of traditional disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). METHODS: One hundred and ninety-five DMARD-naïve patients with recent-onset RA were randomised to receive combination DMARD therapy (n=97) starting with sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone (COMBI) or monotherapy (n=98), initially with sulfasalazine, with or without prednisolone (SINGLE). After two years, the choice and dosing of DMARDs and prednisolone were not restricted, but the treatment was still targeted to achieve or maintain remission. Urinalysis, serum creatinine and glomerular filtration rate (GFR; estimated according to the Cockcroft-Gault formula [eGFRCG]) were analysed at baseline and at months 6, 9, 12, 18, 24 and thereafter yearly up to 11 years. RESULTS: The cumulative incidence of repeated (>or=3 times) abnormal renal findings during the 11-year follow-up period were as follows (COMBI versus SINGLE; p-values adjusted for age and sex): proteinuria (dipstick positive) 4.8% (95%CI 1.8-12.2) vs. 5.3% (95%CI 2.0-13.7, p=0.93), haematuria (dipstick positive) 14.1% (95%CI 8.0-24.2) vs. 22.1 % (95%CI 14.5-33.0, p=0.14), raised serum creatinine (>or=100 micromol/l in females and >or=115 micromol/l in males) 4.4% (95%CI 1.7-11.4) vs. 6.7% (3.0-14.3, p=0.87) and eGFRGC<60 ml/min/1.73 m2 11.9% (95%CI 6.8-20.5) vs. 10.5% (95%CI 5.8-18.7, p=0.85). CONCLUSION: Initial remission targeted therapy with the FIN-RACo DMARD combination in early RA is safe for kidneys and does not induce more short- or long-term renal complications compared to traditional therapy with a single DMARD.

Long-term prognosis after coronary artery bypass surgery.

OBJECTIVE: To analyse the risk of coronary heart disease (CHD) events and total mortality among patients who had coronary artery bypass graft (CABG) surgery during 1988-1992. METHODS: A population-based myocardial infarction (MI) register included data on invasive cardiac procedures among residents of the study area. The subjects aged 35-64 years were followed-up for 12 years for non-fatal and fatal CHD events and all-cause mortality, excluding events within 30 days of the CABG operation. CABG was performed on 1158 men and 215 women. RESULTS: The overall survival of men who underwent CABG was similar to the survival of the corresponding background population for about ten years but started to worsen after that. At twelve years of follow-up, 23% (n=266, 95% CI 234-298) of the men who had undergone the operation had died, while the expected proportion, based on mortality in the background population, was 20% (n=231, 95% CI 226-237). The CHD mortality of men who had undergone the operation was clearly higher than in the background population. Among women, the mortality after CABG was about twice the expected mortality in the corresponding background population. In Cox proportional hazards models age, smoking, history of MI, body mass index and diabetes were significant predictors of mortality. CONCLUSIONS: The prognosis of male CABG patients did not differ from the prognosis of the corresponding background population for about ten years, but started to deteriorate after that. History of MI prior to CABG and major cardiovascular risk factors was a predictor of an adverse outcome.