Clostridium difficile infections in teaching hospital in northern Finland.

BACKGROUND: The aim of this study to compare the incidence of Clostridium difficile (CD) infections in the five university hospital districts in Finland based on national register. The clinical findings of CD cases in the Oulu University Hospital (OUH) in one-year cohort were also analyzed. METHODS: The numbers of the CD cases from the national register were used for the hospital district comparison. A retrospective cohort study was conducted among all adult (> 16 years) patients treated in the OUH in 2013, who had positive CD toxin B gene test in stools. The selection of the cohort was based on the data from the OUH microbiology laboratory and the clinical characteristics were collected from hospital records. RESULTS: The incidence of CD findings in 2013 was higher in the OUH district than in the other four university hospital districts: 159 vs. 70 to 84 per 100,000 inhabitants. In 2013, 261 patients had CD infection treated in the OUH. The yearly number of CD cases treated in the OUH in 2009-2016 varied between 221 and 287, and the corresponding proportion of positive CD findings out of all samples taken varied from 10.0 to 17.8%. A recurrent infection was seen in 58 patients (22%) while the all-cause 30 day mortality was 7.3%. CONCLUSIONS: Diagnostic strategies differed nationally, which may explain the differences in CD incidence between the university hospital districts. In the OUH, no increase in the number of CD infections was seen in 2009-2016. Main characteristics of the patient cohort in the OUH were in harmony with earlier literature.

Warfarin-induced calciphylaxis in patients with normal renal function.

WHAT IS KNOWN AND OBJECTIVE: Calciphylaxis is a rare and potentially life-threatening cause of skin necrosis and is poorly recognized by clinicians in non-uraemic patients. CASE DESCRIPTION: We report five cases of warfarin-induced calciphylaxis in patients with normal renal function. In four cases, sodium thiosulphate was successfully used as a treatment. No other predisposing factors besides obesity and warfarin were found in these patients. WHAT IS NEW AND CONCLUSION: Previously only few cases of solely warfarin-induced calciphylaxis have been described. Treatment with sodium thiosulphate has shown promising results, and there is thus a need to improve the recognition of calciphylaxis.

Impact of multiplex respiratory virus testing on antimicrobial consumption in adults in acute care: a randomized clinical trial.

OBJECTIVES: Inappropriate use of antibiotics is associated with development of antimicrobial resistance. In respiratory infections it is often difficult to differentiate between viral and bacterial infections, and empirical treatment is common. Enhanced viral testing is expected to clarify clinical decision-making and reduce the prescription of antibacterial agents, but the impact of such information on patient care is unclear. METHODS: We conducted a (1:1) randomized controlled clinical trial involving 998 adults with respiratory symptoms, fever, chest pain or poor general condition in the emergency unit of a tertiary hospital. Multiplex PCR results for 496 patients were available in 24 hours (intervention group) and those for the remaining 502 patients were available in 7 days (control group). Our primary outcome measures were the duration of hospitalization and the consumption of antibiotics within 30 days of enrolment. RESULTS: In all, 841 of 998 (84%) patients had respiratory symptoms at study entry. A respiratory virus was detected in 175 (17.5%). The mean duration of hospitalization was 4.2 days (SD 5.4) in the intervention group and 4.1 days (SD 4.9) in the control group (difference 0.1, 95% CI -0.5 to 0.6, p 0.810). The mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD 11.4) in the control group (difference 0.9, 95% CI -0.6 to 2.4, p 0.235). CONCLUSIONS: Multiplex PCR testing for respiratory viruses with results available within 24 hours did not reduce the consumption of bacterial antibiotics or the length of hospital stay in adults presenting with respiratory symptoms, fever, chest pain or reduced general condition in acute care.

Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Invsestigators.

The associations between six genetic polymorphisms in the hepatic lipase (HL) gene (LIPC) and variation in postheparin HL activity and fasting serum lipoproteins were evaluated in 395 male Finnish coronary heart disease patients with HDL cholesterol concentrations

Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects.

BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed. METHODS AND RESULTS: A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. CONCLUSIONS: The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy.

Baroreflex sensitivity and variants of the renin angiotensin system genes.

OBJECTIVES: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND: Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS: Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS: In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS: Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.

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.

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.

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.

Heart rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic features of insulin resistance syndrome.

Both abnormal autonomic control of heart rate, assessed by heart rate variability (HRV) and baroreflex sensitivity (BRS), and insulin resistance syndrome are common in hypertensive patients. It is not known, however, whether abnormalities in HRV and BRS in hypertension are related to the insulin-resistance syndrome. Therefore, we compared HRV and BRS in hypertensive subjects with and without metabolic features of the insulin-resistance syndrome. HRV was analyzed using the autoregressive method from a 45-min electrocardiographic recording (15 min lying, sitting, and standing) and BRS using the Valsalva maneuver. The groups were matched for age, sex, and antihypertensive medication, and age- and sex-matched normotensive subjects served as a control group (n = 69 in each group). The insulin-resistance syndrome was defined using the criteria of 1) hypertension (blood pressure >160/90 mm Hg), 2) hypertriglyceridemia (fasting serum triglycerides > or =2.0 mmol/L), and 3) hyperinsulinemia (fasting serum insulin > or =12 mU/L). Standard deviation of RR intervals, total, very-low-, and low-frequency power of HRV were significantly lower in hypertensive subjects with insulin-resistance syndrome compared to hypertensive subjects without the syndrome and to normotensive controls (P < .001 for all), but the hypertensive group without the syndrome did not differ from the normotensive group. High-frequency power of HRV (P < .01) and BRS (P < .05) were reduced in both hypertensive groups compared to the normotensive group. In multiple regression analysis, systolic blood pressure (P < .01) and serum triglyceride level (P < .001) were independent predictors of reduced total power of HRV, but BRS was related only to systolic blood pressure (P < .01). Thus, most of the abnormalities in overall HRV seem to be confined to the subgroup of hypertensive subjects with insulin-resistance syndrome, but baroreflex and respiratory modulation of heart rate are impaired also in hypertensive subjects without metabolic features of insulin-resistance syndrome.

Apolipoprotein E phenotype determines the effect of alcohol on blood pressure in middle-aged men.

Apolipoprotein E (apoE) has an essential role in lipoprotein metabolism, but recent studies have also revealed other functions associated with it, eg, neurologic and malignant diseases. We studied the association between apoE phenotypes E2/3, E3/3, and E4/3 and blood pressure after adjustment for covariates, as well as the association between phenotypes and adjusted plasma glucose and insulin levels in the standard oral glucose tolerance test in a random middle-aged population-based cohort of 259 men and 267 women. Systolic blood pressure was associated with apoE phenotype in the men with moderate or heavy alcohol consumption (>115 g/week), the mean systolic blood pressure value being 16 mm Hg higher in the E2/3 and 11 mm Hg higher in the E3/3 phenotypes than in the E4/3 phenotype, P = .04. No association was seen in occasional drinkers or teetotalers (lowest tertile <24 g/week), whereas in the middle tertile the association was intermediate. The same association was seen with diastolic blood pressure. In men, there was a significant correlation between systolic blood pressure and alcohol consumption in the E2/3 phenotype (rs = 0.71, P < .01) and in the E3/3 phenotype (rs = 0.25, P < .01), but not in the E4/3 phenotype (rs = 0.03, NS). No association between apoE phenotypes and insulin resistance was observed. In conclusion, in middle-aged men, apoE phenotype significantly influences the blood-pressure-increasing effect of alcohol consumption. This gene environment interaction may have marked implications for the prevention and treatment of hypertension.

Increased pulse pressure is associated with reduced baroreflex sensitivity.

Although pulse pressure (PP), heart rate variability (HRV) and baroreflex sensitivity (BRS) have been shown to predict cardiovascular events and mortality in various populations, their relationships have not been clarified. We examined these associations in two separate population-based samples of healthy middle-aged subjects. In population 1, data were obtained from 149 subjects (71 men and 78 women) aged 35-64 (mean 47.7) years, and in population 2, from 214 subjects (88 men and 126 women) aged 40-62 (mean 50.5) years. Increased 24-h ambulatory PP was related to decreased cross-spectral BRS independent of age and gender (beta=-0.28, P<0.001 for population 1; beta=-0.22, P=0.003 for population 2). This association remained significant when 24-h ambulatory diastolic blood pressure, body mass index, smoking and alcohol intake were added as covariates in the multivariate analysis. Increased ambulatory PP was also associated with increased beat-to-beat systolic arterial pressure variability. Associations between ambulatory PP and HRV were not significant after controlling for age and gender. Our results suggest that elevated PP does not affect overall HRV, but it interferes with baroreflex-mediated control of the heart rate. This association may be due to a common denominator, such as arterial stiffness, for PP and BRS.

Effect of hypertension, diabetes and other cardiovascular risk factors on kidney size in middle-aged adults.

The aim of the study was to investigate in a population-based series (1031 subjects, age range 40-60 years) whether the renal size of hypertensive subjects differs from that of control subjects and whether the difference might be due to hypertension itself or risk factors associated with hypertension. The renal measurements were performed by abdominal ultrasound. The genders were analyzed separately. Hypertensive men had slightly larger kidneys than controls (70.1+/-8.9 cm2 vs. 67.9+/-8.7 cm2, p <0.008). The difference was, however, mediated mainly through the body mass index (BMI), whereas hypertension, blood pressure or hypertensive medication did not affect renal size. High serum concentrations of uric acid and creatinine were associated with smaller kidney size (p <0.001 and p <0.05, respectively). Alcohol users had slightly larger kidneys than abstainers, but the difference was not significant. Renal size increased with pack years of smoking. Diabetics had 4.8% larger kidneys (p <0.039), but no difference was observed between the subjects with impaired glucose tolerance and those with normal test results. In multivariate analysis, the most significant factors associated with enlarged kidney size were the fasting blood glucose concentration (p < or = 0.0001), smoking (p < or = 0.0001) and atherosclerotic lesions in carotid arteries (p <0.002). The kidneys were also slightly larger in hypertensive women than in control subjects, but the difference was only of borderline significance (p <0.08). Women on hormone replacement therapy had smaller kidneys than other women (p <0.05), but there was no difference in renal measures between premenopausal and postmenopausal women. In multivariate analysis, the most significant factors contributing to large kidney size were blood glucose concentration (p <0.0001) and smoking (p <0.05), while age and serum creatinine concentration were associated with smaller kidney size (p <0.0001 and p <0.0001). We conclude that renal size is related to sex and the subject's height and weight. Smoking, abnormal glucose tolerance, blood uric acid, creatinine, carotid atherosclerosis and hormone replacement therapy in women were also significant factors for renal size. Hypertensive subjects had larger kidneys than controls, mainly because of their more frequent obesity and abnormal glucose test.

Plasma ghrelin concentrations are positively associated with carotid artery atherosclerosis in males.

BACKGROUND: Ghrelin, a peptide hormone from stomach, stimulates food intake and decreases fat utilization. Ghrelin binds to growth hormone secretagogue receptor (GHSR). GHSR density has been shown to be upregulated in atherosclerotic lesions, but the relationship between ghrelin concentration and atherosclerosis has not yet been studied. We, therefore, characterized the association between ghrelin concentration and carotid artery intima-media thickness (IMT) in a population-based cohort of 1024 middle-aged (40-60 years) men and women. METHODS: Intima-media thickness and the number of atherosclerotic plaques were determined ultrasonographically. Fasting plasma ghrelin concentrations were analysed using RIA-kit (PhoenixPeptide). RESULTS: There was a positive association between mean IMT and ghrelin concentration in the analysis of males before and after adjustments for the traditional risk factors of atherosclerosis [age, systolic blood pressure, LDL cholesterol, body mass index (BMI), and smoking (ancova, P = 0.004 and P = 0.007, respectively)]. However, no such association was found in females (P = 0.985 and P = 0.915). There was no correlation between ghrelin and CRP concentrations or ghrelin and smoking. CONCLUSION: Ghrelin concentrations and carotid artery atherosclerosis are positively associated in males even after adjustment for the commonly recognized risk factors of atherosclerosis. Experimental and prospective studies are warranted to elucidate the role of ghrelin in atherosclerosis.

Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia when added to the standard treatment: a prospective and randomized clinical trial of 381 patients.

OBJECTIVES: To study whether levofloxacin, added to standard treatment, could reduce the high mortality and complication rates in Staphylococcus aureus bacteraemia. DESIGN: A prospective randomized multicentre trial from January 2000 to August 2002. SETTING: Thirteen tertiary care or university hospitals in Finland. SUBJECTS: Three hundred and eighty-one adult patients with S. aureus bacteraemia. Patients with meningitis, and those with fluoroquinolone- or methicillin-resistant S. aureus were excluded. INTERVENTIONS: Standard treatment (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n = 191). Supplementary rifampicin was recommended if deep infection was suspected. MAIN OUTCOME MEASURES: Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points. RESULTS: Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69-5.54). CONCLUSIONS: Levofloxacin combined with standard treatment in S. aureus bacteraemia did not decrease mortality or the incidence of deep infections, nor did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia appeared to be more common than previously reported.

The negative association between plasma ghrelin and IGF-I is modified by obesity, insulin resistance and type 2 diabetes.

AIMS/HYPOTHESIS: Ghrelin is a natural growth hormone-releasing peptide thought to be involved in the regulation of energy metabolism. The recent studies concerning the association between ghrelin and insulin-like growth factor-I (IGF-I) concentrations have shown either negative correlation or no correlation at all. The aims of this study were to clarify the association between ghrelin and IGF-I concentrations in a large cohort and to characterize whether obesity, insulin resistance and type 2 diabetes affect this association. METHODS: We analysed fasting plasma ghrelin and IGF-I concentrations of 1,004 middle-aged subjects of the population-based OPERA study. Insulin resistance was estimated using QUICKI. RESULTS: IGF-I concentrations were negatively associated with ghrelin concentrations in the analysis of all subjects before (beta=-0.32, p<0.001) and after adjustments for BMI, insulin levels, sex and age (beta=-0.40, p<0.001). The association was particularly strong in males and in the higher BMI tertiles. The degree of association varied in relation to the glycaemic status: no insulin resistance: r(2)=6.5% (p<0.001), insulin resistance without type 2 diabetes: r(2)=21.0% (p<0.001), type 2 diabetes: r(2)=25.4 (p<0.001). IGF-I levels explained larger proportion (r(2)=9.8%) of the variation in ghrelin concentrations compared to fasting insulin concentration (r(2)=3.0%) and BMI (r(2)=1.5%). CONCLUSIONS/INTERPRETATION: There is a negative and independent association between ghrelin and IGF-I concentrations in middle-aged subjects. The interaction between IGF-I and ghrelin is modified by obesity, IR and type 2 diabetes. Further studies are warranted to elucidate the role of ghrelin in the development of these states.

Therapeutic effect of heme arginate in myelodysplastic syndromes.

In order to investigate, whether heme would induce a response in myelodysplastic syndromes (MDS), 14 symptomatic patients (4 RA, 3 RARS and 7 RAEB) were treated with infusions of heme arginate 3 mg/kg body weight on 4 consecutive days, mostly for six cycles at 2-week intervals. Three of 14 patients (21%) showed an improvement in anemia (97-152, 79-120 and 92-114 g/l) within a few weeks, and 1 showed a milder increase in hemoglobin level (102-118 g/l). Of the 2 responders with marked thrombocytopenia, 1 showed an improvement in the platelet count (7-37 x 10(9)/l) and her regular need for red cell and platelet transfusions ceased. Some regression in bone marrow (BM) cytology was seen in all 3 responders. One of the responders is still in remission 41 months after cessation of the treatment, while in the other 2 the response lasted for 26 and 5 months. Four patients progressed during the treatment: 1 RA to RAEB, 1 RAEB to RAEBt and 2 RAEB, both with very complex chromosomal abnormalities at the beginning of the therapy, to acute erythroleukemia (AML-M6). Pretreatment delta-aminolevulinic acid synthase and heme synthase activities were generally low. Five patients had mild thrombophlebitis, but not after the infusion procedure was changed. No other side-effects common to growth factors occurred. In conclusion, it is likely that heme arginate has a therapeutic effect on some MDS patients, obviously by stimulating erythropoiesis. The response may be long-lasting.