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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.

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.

Aims: To evaluate risk factors for major adverse cardiac event (MACE) after the first acute coronary syndrome (ACS) and to examine the prevalence of risk factors in post-ACS patients., Methods: We used Finnish population-based myocardial infarction register, FINAMI, data from years 1993-2011 to identify survivors of first ACS ( n  = 12686), who were then followed up for recurrent events and all-cause mortality for three years. Finnish FINRISK risk factor surveys were used to determine the prevalence of risk factors (smoking, hyperlipidaemia, diabetes and blood pressure) in post-ACS patients ( n  = 199)., Results: Of the first ACS survivors, 48.4% had MACE within three years of their primary event, 17.0% were fatal. Diabetes (p = 4.4 × 10 -7 ), heart failure (HF) during the first ACS attack hospitalization (p = 6.8 × 10 -15 ), higher Charlson index (p = 1.56 × 10 -19 ) and older age ( p  = .026) were associated with elevated risk for MACE in the three-year follow-up, and revascularization ( p  = .0036) was associated with reduced risk. Risk factor analyses showed that 23% of ACS survivors continued smoking and cholesterol levels were still high (>5mmol/l) in 24% although 86% of the patients were taking lipid lowering medication., Conclusion: Diabetes, higher Charlson index and HF are the most important risk factors of MACE after the first ACS. Cardiovascular risk factor levels were still high among survivors of first ACS.

Aim: To examine trends in incidence and 28-day case fatality of myocardial infarction (MI) in persons aged 75-99 years in four areas of Finland., Methods and Results: The Finnish Acute Myocardial Infarction (FINAMI) register is a population-based MI register study, which during 1995-2012 recorded 30561 suspected acute coronary syndromes in persons aged ≥75 years. Of them, 16229 fulfilled the American Heart Association criteria for a definite, probable or possible MI or coronary death. This age-group contributed 56.8% of all MIs of which 62.7% occurred in women. The incidence of MI decreased by -3.3%/year (95% CI -4.2; -2.4) in women aged 75-84 years, and by -1.2%/year (-1.9; -0.5) in women aged 85-99 years, but among men in these age-groups, only a non-significant reduction occurred. The 28-day case fatality of MI was high. In the age-group 75-84 years, it decreased non-significantly by -1.6%/year in men, and significantly by -2.4%/year (-3.9; -0.8) in women. In the age-group 85-99 years, the decrease was more remarkable: -5.1%/year (-7.8; -2.3) and -3.9%/year (-5.5; -2.2), respectively., Conclusions: In Finland, more than half of MIs occur in the age-group 75-99 years, and most of them in women. The incidence of MI decreased significantly in elderly women but non-significantly in elderly men. The 28-day case fatality decreased especially in the age-group 85-99 years. Key Messages In Finland, more than one half of all myocardial infarctions (MIs) occur in the age-group of 75 years or older. Furthermore, 62.7% of MIs among elderly patients occur among women, although 58.0% of the elderly population are women. The incidence of MI decreased significantly in elderly women but not in elderly men. The 28-day case fatality in elderly patients was high but decreased significantly during the study period 1995-2012. This study provides population-based data on treatment strategies and trends in incidence, event rate, mortality and case fatality of MI in elderly individuals. Elderly patients with acute coronary syndromes still present a remarkable burden to the healthcare system in Finland as well as in many other developed countries. Especially considering the modern trend of reducing hospital resources and shifting patient care to outpatient clinics, the epidemiology of MI in elderly patients remains an important issue for the future planning of the healthcare system.

Background: Puumala hantavirus (PUUV) causes haemorrhagic fever with renal syndrome characterized by thrombocytopenia, capillary leakage and acute kidney injury (AKI) with proteinuria and haematuria. Although the typical histologic lesion is acute tubulointerstitial nephritis, the amount of glomerular proteinuria predicts the severity of upcoming AKI. Here, we studied the associations of haematuria and proteinuria with the severity of emerging AKI, thrombocytopenia and markers of coagulation and fibrinolysis in PUUV infection., Methods: We examined 205 consecutive patients treated for serologically confirmed acute PUUV infection at Tampere University Hospital during 1997-2014. The patients were divided into three groups according to the combined positive result in urine haemoglobin and albumin dipstick tests: 0-2 + (n = 58), 3-4 + (n = 100) and 5-6 + (n = 47)., Results: The medians of maximum creatinine concentrations in the three groups were: 0-2 + 100 μmol/L (range 52-1499), 3-4 + 204 μmol/L (range 65-1071) and 5-6 + 361 μmol/l (range 51-1285) (p < .001). The number of blood platelets (p = .069), and the levels of fibrinogen, prothrombin fragments F1 + 2 and d-dimer (p = .602, p = .113, p = .289, respectively) were not significantly different between the groups. When the amount of haematuria in the dipstick test was examined separately, no association with thrombocytopenia was detected (p = .307 between groups 0, 1+ and 2-3+)., Conclusions: Combined positive result of haematuria and proteinuria in the dipstick test at hospital admission predicted the severity of upcoming AKI in acute PUUV infection. As haematuria was not associated with the severity of thrombocytopenia, it did not indicate increased bleeding tendency, but was rather a marker of acute kidney injury.

Acute kidney injury (AKI) remains a predominant clinical expression of nephropathia epidemica (NE). Its pathogenesis is not yet fully understood. Here, we describe the tissue injury comprehensively and present new data aimed to characterize the injury and explain its pathophysiology. When compared to tubulointerstitial nephritis of a wide variety of other aetiologies, a high degree of proteinuria is a distinguished trait of NE, a finding that is also helpful in the clinical suspicion of the disease. Recently, novel biomarkers for the prediction of severe AKI, including neutrophil gelatinase-associated lipocalin (NGAL), have been identified and ultrastructural tissue changes have been more accurately described. A role for soluble urokinase-type plasminogen activator (suPAR) in the pathogenesis of NE has been suggested, and data on gene polymorphisms, in relation to the severity of AKI have been presented. Smoking is a risk factor for NE and smoking is also associated with aggravated AKI in NE. Although no specific treatment is in sight, recent case reports concerning therapy directed against vascular permeability and vasodilation are of interest. In fact, future work trying to explain the pathophysiology of AKI might need concentrated efforts towards the mechanisms of increased vascular permeability and vasodilatation, which irrespective of organ manifestation, are two major determinants of NE.

Background: Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans. Hantavirus infections are characterized by thrombocytopenia. Our objective was to assess the association of thrombocytopenia with disease severity in HFRS induced by Puumala hantavirus (PUUV)., Methods: Altogether 546 patients treated for acute serologically confirmed PUUV infection during 1982-2013 at Tampere University Hospital, Finland, were examined. Blood platelet count was determined daily and analysed in relation to different variables reflecting disease severity. The patients were divided into two groups according to the minimum platelet count: severe thrombocytopenia (<69 × 10(9)/L, i.e. below median) and no severe thrombocytopenia (≥69 × 10(9)/L)., Results: Thrombocytopenia (platelet count <150 × 10(9)/L) was detected in 90% of patients, and in 28% of patients platelet count was <50 × 10(9)/L. Patients with severe thrombocytopenia had longer stay (8 versus 7 days, p = 0.002) and greater weight gain (2.8 versus 2.0 kg, p < 0.001) at the hospital, higher blood leukocyte count (11.2 × 10(9)/L versus 9.6 × 10(9)/L, p < 0.001), plasma C-reactive protein (81 versus 59 mg/L, p < 0.001), maximum hematocrit (0.44 versus 0.42, p < 0.001), urinary protein excretion (1.7 versus 1.1 g/24 h, p = 0.002), and lower plasma albumin concentration (27 versus 32 g/L, p < 0.001) than patients without severe thrombocytopenia (comparisons between medians). Maximum creatinine concentration did not differ between patients with or without severe thrombocytopenia (median 235 versus 214 μmol/L, p = 0.217)., Conclusions: The severity of thrombocytopenia associates with the degree of inflammation and variables reflecting capillary leakage, but not with the severity of acute kidney injury in PUUV infected Finnish patients.

Early identification of patients at risk of a severe course of hantaviral disease and lack of effective medication represent a global challenge in the treatment of this emerging infection. We describe a 67-year-old female patient with a history of chronic lymphoproliferative disease involving the spleen and an extremely severe acute Puumala hantavirus infection. She was treated with the bradykinin receptor antagonist icatibant and recovered. She is the second patient with a spleen abnormality and severe Puumala infection treated with icatibant in our hospital. We suggest that patients with spleen abnormalities may be more susceptible to severe hantavirus disease. The activation of the kinin-kallikrein system and the formation of bradykinin in hantavirus-infected endothelial cells indicate that the role of bradykinin receptor antagonist icatibant in the treatment of hantavirus disease is worth studying.

A patient with severe capillary leakage syndrome caused by a Puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. We suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.

Background: Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland., Objective: To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland. Patients and methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in 306 unrelated Finnish patients with HCM from the regions covering a population of ∼4,000,000., Results: The TPM1-D175N mutation was found in 20 patients (6.5%) and the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations showed regional clustering. TPM1-D175N was prevalent in central and western Finland, and MYBPC3-Q1061X in central and eastern Finland., Conclusion: The TPM1-D175N and MYBPC3-Q1061X mutations account for a substantial part of all HCM cases in the Finnish population, indicating that routine genetic screening of these mutations is warranted in Finnish patients with HCM.

Introduction: Hantaviruses are important human pathogens that cause clinical diseases characterized by renal and cardiopulmonary manifestations. Their pathogenesis is currently poorly understood. We have studied the role of the complement system in the pathogenesis of Puumala (PUUV) hantavirus infection., Material and Methods: We studied the activation of complement by measuring the terminal complement complex SC5b-9 and complement component C3 and C4 levels in patients with acute PUUV infection. Several laboratory parameters and clinical findings reflecting the severity of PUUV-HFRS were evaluated with regard to complement activation., Results: The levels of SC5b-9 were significantly increased and C3 decreased in the acute stage as compared to the levels at full recovery (P < 0.001). We found that SC5b-9 levels were higher in patients with chest X-ray abnormalities than in patients with a normal X-ray during the acute stage (P = 0.028). Furthermore, SC5b-9 and C3 levels showed significant correlation with several clinical and laboratory parameters that reflect the severity of the acute PUUV infection., Conclusions: We showed that the complement system becomes activated via the alternative pathway in the acute stage of PUUV infection and the level of activation correlates with disease severity. The results further suggest that complement activation may contribute to the pathogenesis of acute PUUV infection.

The clinical picture of nephropathia epidemica (NE), a rodent-mediated Puumala virus (PUUV) zoonosis, appears to be different in paediatric and adult patients, since severe complications are seen only in adults. To confirm this clinical impression, we made a systematic literature review to determine whether the severity of NE is similar in children and adults. We searched PubMed for articles dealing with the clinical symptoms, physical signs and outcomes of patients with NE, published in English or the Nordic languages during the y 1968-2008, and found 53 containing sufficient original data in serologically confirmed cases. Forty-one of these described individual cases, 11 a series of consecutive patients and 1 both. The total number of patients was 537, of which 80 were paediatric cases. The frequency of benign symptoms and transient physical signs was quite similar in adults and children. However severe complications were reported only in adult patients (n = 26), of whom 9 died. The literature review confirmed the clinical impression that NE is milder in children than in adults. Children with PUUV infection rarely, if ever, need any invasive therapy.

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.

Objective: To non-invasively measure central haemodynamics, arterial stiffness, cardiac function and vascular resistance, with the subject in the supine position and during head-up tilt, in order to examine the haemodynamic changes associated with alterations in the augmentation index, and to investigate repeatability and reproducibility of the measurement protocol., Material and Methods: Thirty-three healthy volunteers (21-51 years) were investigated using continuous pulse wave analysis from the radial artery with a tonometric sensor, whole-body impedance cardiography and plethysmographic blood pressure (BP) recordings from the fingers. The measurements were performed with the subject supine and during passive head-up tilt, and repeated during the same session and on four separate days., Results: During the head-up tilt, diastolic BP (5.2+/-0.6%), heart rate (27.6+/-1.9%) and vascular resistance (12.5+/-1.7%) increased (all p<0.05), while systolic BP (-3.2+/-0.6%), aortic pulse pressure (-23.3+/-1.4%), augmentation index (-11.6+/-0.7%), aortic reflection time (-7.0+/-1.0%), ejection duration (-21.4+/-0.7%), stroke volume (-26.1+/-1.2%) and cardiac output (-5.0+/-1.5%) decreased (all p<0.05). Augmentation index at rest correlated with aortic systolic BP (r = 0.423), aortic reflection time (r = -0.647), pulse wave velocity (r = 0.287) and age (r = 0.480). The change in augmentation index during head-up tilt correlated with the change in aortic systolic BP (r = 0.469), aortic pulse pressure (r = 0.606), ejection duration (r = 0.374) and heart rate (r = -0.445). According to Bland-Altman and repeatability index analyses, repeatability and reproducibility of the measurements were good during the same session and on separate days., Conclusions: Combined pulse wave analysis and impedance cardiography with the subject in the supine position and during head-up tilt is a repeatable and reproducible method for comprehensive investigation of the cardiovascular function.

This study was conducted to determine the frequency, severity and outcome of cardiac findings in patients with acute Puumala hantavirus-induced nephropathia epidemica (NE). 70 consecutive, hospital-treated patients with serologically confirmed NE were prospectively examined using serial electrocardiograms (ECG), plasma troponin I, tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and echocardiography (ECHO). Examinations were repeated after 3 and 12 months. ECG changes were observed in 57% of patients. Plasma troponin I levels remained normal in all. In six patients, ECHO showed left ventricular contraction abnormalities, and 1 patient had mild pericardial effusion. There were no differences in clinical or standard laboratory findings or in plasma TNF-alpha and IL-6 concentrations between patients with and without ECG or ECHO changes. During the follow-up, all acute-phase changes in ECG and ECHO reverted to normal, which probably reflects their benign nature. We conclude that abnormal cardiac findings are surprisingly common during NE.

Different host genetic factors causes imbalance in the immune response. The purpose of this study was to establish whether pathological findings in chest radiography are related to the various host-related immunological factors in nephropathia epidemica (NE). Chest radiography findings, human leukocyte antigen (HLA) alleles B8, DR3, B27, genotypes of the genes of tumour necrosis factor alpha (TNFalpha), interleukin -1alpha (IL-1alpha), IL1beta and IL-1 receptor antagonist (IL1RA) were analysed in 114 patients with serologically confirmed acute NE. Both the presence and severity of abnormal NE-related chest radiography findings associated with the B8, DR3 and TNF2 alleles are known to form a frequent extended HLA haplotype in European populations. Pleural effusion showed the strongest association with these genetic factors. Pathological findings in chest radiography are related to host genetic factors in NE. Pleural effusion is a sign of increased capillary permeability, an important feature in NE. Host genetic factors may contribute to increased capillary permeability observed in NE patients.

Objective: To assess the mortality and causes of death in a cross-sectional population-based study of 1042 patients with rheumatoid arthritis (RA)., Methods: In 1988, 604 RA patients [470 females (F), 134 males (M)] and 457 age- and sex-matched controls (352 F, 105 M) were examined prospectively (participants) and 438 (183 F, 81 M) non-participant RA patients retrospectively. In 1999, vital status and causes of death were determined. Mortality in the total RA population was compared to that in the general population, and that among participant RA patients to their matched controls., Results: A total of 384 (37%) RA patients and 71 (16%) controls died. RA patients had increased mortality compared to the general population (standardized mortality ratios SMR 2.64) or controls (1.71). This was observed in both sexes. Over 40% of deaths in all groups were due to cardiovascular diseases. RA patients were at increased risk of dying of urogenital, gastrointestinal, respiratory and cardiovascular diseases, infections, and cancers when compared to the general population or controls., Conclusions: Our results show that a cross-sectional cohort of RA patients had an increased risk of death from various causes.

The biallelic polymorphisms in the tumour necrosis factor-alpha (TNF-alpha) gene promoter region were studied in patients with nephropathia epidemica (NE). The rarer TNF2 allele, associated with a high TNF-alpha producer phenotype, was more frequently found in hospitalized NE patients (42%) than in healthy controls (15%; p=0.0064). The putative role of TNF2 as an independent risk factor for NE is discussed.

A prospective study was made of sequential changes in the metabolism of vitamin D and calcium in 19 allograft recipient during the first year after successful renal transplantation. All but one of the patients received cyclosporine A combined with corticosteroids and azathioprine as immunosuppressive therapy. Shortly after transplantation most patients showed transient hypocalcemia and hypophosphatemia. At the time of transplantation 17 of 19 patients had an elevated plasma intact parathyroid hormone (PTH) level, and at the close of follow-up one in four patients. In six other patients intact PTH was within the reference range, but high in relation to simultaneously measured serum ionized calcium. According, one year after transplantation less than half of the patients showed complete resolution of hyperparathyroidism. The change towards normal in the metabolism of vitamin D began within the first post-transplantation week irrespective of the onset of diuresis. One to two weeks after transplantation 1,25(OH)2D3 and 24,25(OH)2D3 reached the lower limit of normal range. In these renal allograft recipients who received cyclosporine A the long-term values of serum 1,25(OH)2D3 did not differ from those of normal subjects.

A total of 126 (99 males, 27 females) serologically confirmed hospital-treated adult cases of nephropathia epidemica (NE) were studied. The initial diagnosis suggested by the referring physician was correct in only 28%. Some rare clinical manifestations of NE were observed; acute myopericarditis in 3 patients and encephalitis in 1. Pulmonary involvement due to vascular congestion was observed in 16% and liver involvement in 34% of the patients. Thrombocytopenia was present in 75%, leukocytosis in 50% and anemia in 50%. Erythrocyte sedimentation rate (ESR) was 2-108 (mean 38) mm/h and C-reactive protein (CRP) 0-126 (mean 52) mg/l. Proteinuria was observed in 94%, hematuria in 58% and pyuria in 28%. Electrolyte abnormalities (hyponatremia, hypokalemia, hypocalcemia, hyperphosphatemia) were all common but rarely serious. Serum lipid changes caused by the acute infection and renal failure included very low total and HDL-cholesterol as well as high triglyceride levels. Renal function was transiently impaired in 94% of the patients and 7 needed transient dialysis therapy. All recovered.

Escherichia coli strains isolated from the urine in 49 consecutive episodes of community-acquired pyelonephritis in adult women were characterized for adhesins and hemolysin production. The mean age of the patients was 56 years and 47% had at least 1 compromising condition. P fimbriae was found in 67% and hemolysin production in 35% of the strains; these figures were significantly (p < 0.001) higher than the corresponding figures (11% for each) among 287 strains isolated from stool of healthy adults (Siitonen A. J Infect Dis 1992; 166: 1058-1065). The prevalence of Non-P mannose-resistant adhesins and type 1C fimbriae was low (4 and 8%, respectively) and did not differ significantly from the corresponding prevalences (1 and 7%) in healthy adults. 74% fo the pyelonephritic (but only 22% of the stool) isolates had at least 1 of these 4 virulence factors (p < 0.001) and 37% and 7%, respectively, had at least 2 (p < 0.001). Nevertheless, the strains represented a wide variety of O:K serotypes without any indication of specially virulent clones. Of the 49 patients 15 had concomitant bacteremia, and in all except 2 compromised elderly patients the urinary and blood isolates were identical.

A 12 week randomised, double blind, placebo controlled study on the effect of enalapril (5-20 mg daily) on the concentration of plasma atrial natriuretic peptide level and activity of the sympathetic nervous system and renin angiotensin system was done on 27 patients who had suffered an uncomplicated acute myocardial infarction two to six months earlier. None of our patients needed drug treatment for heart failure, but their exercise capacity was markedly limited. Plasma neurohormone concentrations at baseline and after 12 weeks of treatment were also compared with those of healthy controls. Concentrations of plasma atrial natriuretic peptide concentrations remained high throughout the study in those patients on beta-blockers. Enalapril treatment had no definite effect on the concentrations of plasma atrial natriuretic peptide or other neurohormone.

Diabetic patients may have various abnormalities in left ventricular systolic and diastolic function not attributable to coronary heart disease, hypertension or other known cardiac disease. Although the exact causes of this diabetic heart muscle disease or "diabetic cardiomyopathy" are still incompletely understood, several mechanisms may contribute to it including disturbed myocardial energy metabolism, microvascular changes, structural changes in collagen, increased myocardial fibrosis, and cardiac autonomic neuropathy. Perhaps the most typical feature of diabetic heart muscle disease is an abnormal filling pattern of the left ventricle, suggesting reduced compliance or prolonged relaxation. Left ventricular systolic function is commonly normal at rest in asymptomatic diabetic patients, but it frequently becomes abnormal during exercise. The abnormalities in left ventricular systolic function may be partly reversible along with an improvement of metabolic control of diabetes. It is not known how frequently subclinical abnormalities in left ventricular function in diabetic patients result in clinically manifest heart failure.