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Biomedical subjects

H Markkanen

Publications and source records attributed to H Markkanen.

At least 19 recordsLinked to original sources
PubMed2006

Determination of free tetrahydrocortisol and tetrahydrocortisone ratio in urine by liquid chromatography-tandem mass spectrometry.

OBJECTIVE: Measurement of urinary free tetrahydrocortisol and tetrahydrocortisone ratio (allo-THF+THF)/THE is clinically important in the diagnosis of hypertension caused by congenital absence of 11beta-hydroxysteroid dehydrogenase type 2 (apparent mineralocorticoid excess, AME) or inhibition of the enzyme after licorice ingestion. Although gas chromatography-mass spectrometry (GC-MS) provides reliable results, it requires derivatization and is lengthy and time-consuming. The purpose of this study was to demonstrate that detection by liquid chromatography-mass spectrometry (LC-MS) is a potentially superior method. MATERIAL AND METHODS: The analysis utilizes 1 mL urine. The samples were extracted with solid-phase extraction (SPE) using ethyl acetate as eluent. The extract was evaporated to dryness, and allo-tetrahydrocortisol (allo-THF), THF and THE concentrations were analyzed by LC-MS/MS operating in the negative mode after separation on a reversed-phase column. The calibration curves exhibited consistent linearity and reproducibility in the range of 7.5-120 nmol/L. Interassay CVs were 7.0-10 % at mean ratios of (allo-THF+THF)/THE of 0.54-1.9. The detection limit of the analytes was 0.4-0.8 nmol/L (signal-to-noise ratio = 3). The mean recovery of the three analytes ranged from 88 to 95 %. The regression equation for the free ratio using the LC-MS/MS (x) method and the total ratio using the GC-MS (y) method was: y = 0.30x+0.91 (r = 0.61; n = 25). CONCLUSIONS: The sensitivity and specificity of the LC-MS/MS method offer an advantage over GC-MS by eliminating derivatization. The high costs of equipment are balanced by higher through-put, owing also to shorter chromatographic run times.

Chromatography, Liquid↗
PubMed2006

Effects of cigarette smoking on serum fluoride concentrations and renal function integrity after 1 MAC-h sevoflurane anaesthesia.

BACKGROUND: Tobacco smoke contains various chemicals which may affect drug metabolism. Sevoflurane is metabolized to inorganic fluoride, and elevated serum fluoride concentrations (S-F(-)) may cause deterioration of renal function. Whether smokers develop high S-F(-) and associated disturbances in renal function is not known. METHODS: We investigated sevoflurane metabolism in 25 non-smoking and 25 smoking (> 10 cigarettes/day) generally healthy women, aged 19-68 years, undergoing gynaecological elective surgery under one minimum alveolar concentration-hour (1 MAC-h) standardized sevoflurane anaesthesia. S-F(-) was measured for 24 h. Glomerular and tubular function was assessed by measuring serum and urine tumour-associated trypsin inhibitor (TATI), beta(2)-microglobulin and serum creatinine for 48 h after sevoflurane inhalation. RESULTS: There were no differences between the two study groups with regard to S-F(-). It increased significantly in both groups: in non-smokers, from a baseline between 1.0 and 11 micromol/l (median, 1.6 micromol/l) to a maximum between 8.2 and 40 micromol/l (26 micromol/l) (P < 0.001) and, in smokers, from a baseline between 0.5 and 5.2 micromol/l (1.7 micromol/l) to a maximum between 19 and 71 micromol/l (25 micromol/l) (P < 0.001). In both groups, S-F(-) remained elevated for the entire sampling period (P < 0.001). In all five women (one non-smoker and four smokers) with a maximum S-F(-) of 40 micromol/l or higher and an area under the serum fluoride concentration-time curve (AUC(F0-24)) of 500 micromol/h/l or higher, serum TATI increased above the pathological concentration of 3.0 nmol/l, whereas only six of the 45 patients with S-F(-) below 40 micromol/l had serum TATI above 3.0 nmol/l (P < 0.001). Beta(2)-Microglobulin increased significantly (> 1 mg/l) in two patients with high S-F(-) relative to two of the 45 patients with S-F(-) below 40 micromol/l (P= 0.005). None of the patients developed clinically detectable renal dysfunction. CONCLUSION: Smoking did not affect S-F(-) after sevoflurane anaesthesia. Glomerular dysfunction, seen as increased serum TATI, was noted in five women with S-F(-) above 40 micromol/l. Our results suggest that the renal toxic threshold of S-F(-) seems to be lower than the earlier reported value of 50 micromol/l.

Adult↗
PubMed2005

Problematic determination of serum growth hormone: experience from external quality assurance surveys 1998-2003.

The objective of the present study was to start a new external quality assurance survey (EQAS) for the determination of serum growth hormone (GH) using pooled serum specimens as quality-assurance samples. To give good coverage of multiple forms of GH, the specimens included sera from GH-deficient and acromegalic patients as well as from persons showing a normal response in GH provocation tests. In one survey the quality-control specimens were spiked with exogenous 22-kD GH to obtain some idea of the specificity and GH recovery of the assays. The EQA surveys of 1998-2003 were organized by Labquality of Helsinki in cooperation with three university hospital laboratories in Finland. The number of participating laboratories ranged from 8 to 14. During 1998-2003, gratifying methodological harmonization occurred in the participating group, as the participants switched to the immunometric detection principle, the number of method applications decreasing from 7 to 3. In 1998 the 14 participating laboratories reported five different conversion factors (from microg/l to mU/l), whereas in 2003 7 of the 8 participants reported the same factor. Despite the harmonization trend among participating laboratories, further efforts are needed, because marked method-based differences still exist. This dialogue should include kit manufacturers, laboratory experts, EQA organizations and clinicians using the test results.

Blood Chemical Analysis↗
PubMed2004

High amniotic fluid erythropoietin levels are associated with an increased frequency of fetal and neonatal morbidity in type 1 diabetic pregnancies.

AIMS/HYPOTHESIS: In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies. METHODS: A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid erythropoietin concentration was measured in 156 diabetic singleton pregnancies at a median time of 1 day before Caesarean section without labour contractions and in 19 healthy control subjects at Caesarean section. RESULTS: The median amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156 diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations were found between amniotic fluid erythropoietin levels and umbilical artery pCO2 (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U-shaped correlation was demonstrated between amniotic fluid erythropoietin levels and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic cardiomyopathy and admission to the neonatal intensive care unit occurred significantly more often in cases with high amniotic fluid erythropoietin levels (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression analysis revealed that amniotic fluid erythropoietin was the only variable independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004). CONCLUSIONS/INTERPRETATION: Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.

Adult↗
PubMed2003

Fluoride metabolism in smokers and non-smokers following enflurane anaesthesia.

BACKGROUND: Inorganic fluoride is released by the metabolism of enflurane and the increased serum fluoride concentrations may impair renal function. Tobacco smoke consists of numerous reactive compounds that can either induce or inhibit drug metabolism. Studies on the interaction of smoking with anaesthetic drug metabolism and possible toxicity are warranted. METHODS: Sixteen non-smoking and 17 smoking (>10 cigarettes day(-1)) generally healthy women undergoing elective gynaecological surgery were given 1 MAC (minimum alveolar concentration)-hour standardized anaesthesia with enflurane in oxygen-air mixture. The serum inorganic fluoride and renal function markers beta(2)-microglobulin, tumour-associated trypsin inhibitor (TATI) and serum creatinine were measured for 48 h. RESULTS: The greatest inorganic fluoride concentration was between 8.4 and 21.0 (mean 13.8 (SD 3.4)) micromol litre(-1) in the non-smokers and between 8.6 and 38.0 (18.7 (7.0)) micromol litre(-1) in the smokers; the mean difference was 4.9 micromol litre(-1) (95% confidence interval (CI) 1.0-8.8, P<0.05). Serum beta(2)-microglobulin, TATI and creatinine were not increased. Serum inorganic fluoride concentrations were significantly greater in the smokers compared with the non- smokers 1, 2, 3 and 6 h after 1 MAC-hour inhalation with enflurane (P<0.05). Inorganic fluoride concentrations were still increased 24 h after anaesthesia in both groups. Urine beta(2)-microglobulin and TATI creatinine ratio remained at low values during the whole 48-h period in both groups. CONCLUSIONS: Regular smoking is associated with an increase in serum inorganic fluoride concentration after anaesthesia with enflurane, but there are no signs of renal damage.

Adult↗
PubMed2002

Midnight serum cortisol: comparison of healthy volunteers and hospitalized patients with Cushing's syndrome.

Diurnal variation in serum cortisol is nearly always absent in patients with Cushing's syndrome (CS), as shown by elevated levels of midnight serum cortisol (MSC). The sensitivity of MSC in the diagnosis of CS has been shown to be 96-100% measured on an inpatient basis. The purpose of this study was to state reference values for MSC measured on an outpatient basis in healthy non-sleeping controls, and to calculate the sensitivity and specificity of the test in patients with verified CS based on these data. Thirty-six healthy volunteers (11 males, 25 females) with a median age of 40.5 (range 22-60) years and a mean body mass index (BMI) of 27.0+/-5.9kg/m2 were included in the study. Serum cortisol was measured at 24.00h. In 35 CS patients (5 males, 30 females) with a median age of 44.5 (range 23-79) years and mean BMI of 28.5+/-6.9 kg/m2, MSC was measured on the first night after admission to hospital, in a non-sleeping state. All controls, with the exception of one, had MSC values below 200nmol/L. One CS patient showed an MSC level below 200nmol/L. Based on these observations, the sensitivity and specificity of the test were 97.1% and 97.2%, respectively, when 200nmol/L was used as the cut-off limit. Non-sleeping state does not seem to compromise the sensitivity or the specificity of the test.

Adult↗
PubMed2001

Paranasal sinus mucormycosis: a report of two cases.

Mucormycosis of the nose and paranasal sinuses is a rare invasive fungal infection, which often has a very fulminant course and characteristic clinical findings. The patients are usually immunocompromised, with diabetic ketoacidosis being the commonest underlying disorder. In some immunocompetent patients, the disease is associated with local predisposing factors, such as chronic sinusitis. Although the prognosis has improved in recent decades, the disease can still be fatal. The underlying disease is an important determinant of prognosis and correction of the metabolic disorder, if present, is essential. Herein we report two cases: one of our patients was immunocompetent but had earlier suffered from polypous rhinosinusitis whereas the other had mild adult-type diabetes. Both patients were successfully treated with surgical debridement and amphotericin B.

Aged↗
PubMed2000

Intramucosal pH and endotoxin and cytokine release in severe acute pancreatitis.

It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12-h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P = 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) in their plasma. Concentrations of IL-6, IL-8, and IL-10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P = 0.035, r = 0.74; P = 0.010, r = 0.91; P = 0.021, r = 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.

APACHE↗
PubMed1999

Interleukin 1 receptor antagonist and E-selectin concentrations: a comparison in patients with severe acute pancreatitis and severe sepsis.

PURPOSE: This prospective clinical study was designed to compare interleukin 1 receptor antagonist (IL-1ra) and E-selectin concentrations in patients with severe acute pancreatitis to those with severe sepsis. MATERIALS AND METHODS: Nine consecutive patients with severe acute pancreatitis and 11 consecutive patients with severe sepsis admitted to a medical/surgical intensive care unit were included in the study. Plasma concentrations of IL-1ra and E-selectin were serially measured daily for 7 days or throughout their stay in the intensive care unit if shorter. RESULTS: The concentrations of IL-1ra were significantly higher on admission in patients with severe sepsis compared with the patients with severe pancreatitis (median levels 10,500 and 2,600 pg/mL, respectively, P = .007). When the data from the first 3 days were analyzed using analysis of variance (ANOVA), the levels of IL-1ra and E-selectin were similar in both groups. The concentrations of IL-1ra and E-selectin correlated to the development of multiorgan dysfunction as assessed by sequential organ failure assessment (SOFA) score (P = .032 and .043, respectively). CONCLUSION: This study shows that IL-1ra and E-selectin are released in acute severe pancreatitis, and the levels seem to be comparable to those in patients with severe sepsis. Concentrations of IL-1ra and E-selectin correlate to the development of multiorgan failure as indicated by high SOFA scores during the first week of disease.

APACHE↗
PubMed1998

Caries in patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: The purpose of this study was to investigate the prevalence and risk factors of dental caries in patients with non-insulin-dependent diabetes mellitus and to determine whether these factors are associated with metabolic control and vascular complications of the disease. STUDY DESIGN: Both the occurrence of caries, acidogenic oral bacteria, and yeasts and salivary flow were studied in 25 patients with non-insulin-dependent diabetes mellitus whose diagnosis had been set 13 to 14 years earlier and in whom the metabolic evolution of the disease was well established. The patients' glycemic control was determined by means of analysis of the blood hemoglobin A1C concentration at the time of dental examination. The control group consisted of 40 nondiabetic subjects in the same age group. Decayed, missing, and filled teeth indices and numbers of surfaces with caries, filled surfaces, and root caries were determined by means of clinical dental caries examination. Stimulated salivary flow was measured, and levels of Streptococcus mutans, lactobacilli, and yeasts were analyzed. RESULTS: The median hemoglobin A1C concentration of the patients was 8.6%, which indicates poor metabolic control of diabetes. No association was found between the metabolic control of disease and dental caries. The occurrence of dental caries was not increased in the patients with non-insulin-dependent diabetes mellitus in comparison with the control subjects. The counts of acidogenic microbes and yeasts did not differ statistically significantly between the groups. There was no association of caries with the prevalence of coronary artery disease or hypertension in either the patients or the control subjects. In a stepwise logistic regression model, a salivary flow of at least 0.8 ml/min was related to the occurrence of dental caries in patients with non-insulin-dependent diabetes mellitus, whereas negligence with respect to dental care was the most important risk predictor in the control group. CONCLUSION: Our results showed no effect of diabetes on the prevalence of caries. However, the caries-protective effect of saliva was partly lost in patients with non-insulin-dependent diabetes mellitus.

Aged↗
PubMed1998

Periodontal findings in elderly patients with non-insulin dependent diabetes mellitus.

The periodontal status of 25 patients with non-insulin dependent diabetes mellitus (NIDDM) (age range 58 to 76) was investigated and compared with 40 non-diabetic control subjects (age range 59 to 77). Surfaces with visible plaque and bleeding after probing, calculus, recessions, and pathological pockets were examined. The total attachment loss was calculated as a sum of recessions and pockets in millimeters. Mesial and distal bone loss was measured from panoramic radiographs and mean alveolar bone loss was calculated. Periodontal disease was considered advanced when mean alveolar bone loss was over 50%, or 2 or more teeth had pockets > or = 6 mm. Microbiological analysis comprised the detection of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus by a polymerase chain reaction (PCR) method. Patients with NIDDM had significantly more often advanced periodontitis than control subjects, 40.0% and 12.5%, respectively. Diabetic patients did not harbor more pathogens than the control subjects. The HbA1C level deteriorated in patients with advanced periodontitis, but not in other patients with NIDDM, when compared to the situation 2 to 3 years earlier. Advanced periodontitis seems to be associated with the impairment of the metabolic control in patients with NIDDM, and a regular periodontal surveillance is therefore necessary.

Aged↗
PubMed1997

Plasma interleukin-8, interleukin-10, and E-selectin levels in neutropenic and non-neutropenic bacteremic patients.

Plasma interleukin-8 (IL-8) interleukin-10 (IL-10), and E-selectin concentrations were studied in 39 neutropenic and 30 non-neutropenic bacteremic patients; 54 nonbacteremic patients were analyzed as controls. Interleukin-8 concentrations were significantly higher in neutropenic than in non-neutropenic bacteremic patients (median 475 vs. 0 pg/ml, p < 0.0001). Median IL-8 and IL-10 levels were higher in bacteremic than in non-bacteremic patients (330 vs. 0 pg/ml, p < 0.0001 and 20 vs. 0 pg/ml, p = 0.04, respectively). In contrast, concentrations of IL-10 were similar in neutropenic and non-neutropenic patients. Median levels of E-selectin were not increased in any of the patient groups. Neutropenic bacteremic patients showed significantly lower concentrations of E-selectin than did non-neutropenic bacteremic patients (p < 0.0001). In conclusion, neutropenic bacteremic patients had significantly higher concentrations of IL-8 than non-neutropenic bacteremic patients. Levels of IL-10 were higher in bacteremic than in nonbacteremic patients, but neutropenic and non-neutropenic patients had similar levels of IL-10. Increased levels of E-selectin were not found in any of the patient groups, although neutropenic patients with bacteremia had lower concentrations than did non-neutropenic patients.

Adult↗
PubMed1997

Determination of urinary free cortisol by HPLC.

We here report a reversed-phase HPLC method for the determination of free cortisol in human urine, using methylprednisolone as the internal standard. Before chromatography, samples were extracted with a C18 solid-phase extraction column and the steroids were separated on a LiChrospher 100 C18 column with a mobile phase of methanol/acetonitrile/water (43/3/54 by vol). Linearity, precision, and accuracy of the method were established. The detection limit was 10 pmol of cortisol, and total CVs were < 8%. With various solid-phase extraction columns the recovery of cortisol was 36-97%; recovery of the internal standard was 43-85%. Study of interference by 6 other steroids and metabolites and 24 drugs showed that carbamazepine and digoxin partly overlapped with cortisol, but this interference could be reduced by modification of the mobile phase. The HPLC method was compared with an RIA and an automated immunoassay method. The results obtained by HPLC averaged 40% of the RIA values.

Calibration↗
PubMed1995

Plasma endotoxin and cytokine levels in neutropenic and non-neutropenic bacteremic patients.

Plasma endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 1 receptor antagonist (IL-1ra), and interleukin 6 (IL-6) concentrations in 69 bacteremic patients were compared with those in 54 nonbacteremic patients suffering from suspected bacterial infections. Only three (11%) of the 27 patients with gram-negative bacteremia showed detectable levels of endotoxin. TNF-alpha was detected in 6% of the bacteremic patients and in none of the nonbacteremic patients. Median IL-6 levels were significantly higher in bacteremic than in nonbacteremic patients (55 vs. 0 pg/ml, p = 0.0008). IL-6 concentrations were similar in neutropenic and non-neutropenic bacteremic patients (median 55 vs. 74 pg/ml). In contrast, neutropenic bacteremic patients had significantly lower concentrations of IL-1ra than non-neutropenic bacteremic patients (250 vs. 1,950 pg/ml, p < 0.0001). Patients with fatal bacteremia had significantly higher concentrations of IL-6 and IL-1ra than the survivors (median, 450 vs. 40, p = 0.012 and 7,600 vs. 420 pg/ml, p = 0.0075, respectively). Determinations of endotoxin or TNF-alpha in patients with suspected bacteremia failed to offer clinically relevant data on the prognosis of these patients. IL-6 levels correlated with both the presence of bacteremia and the risk of death. Granulocytopenic patients with bacteremia had lower levels of circulating IL-1ra than patients with normal granulocyte counts, and these levels correlated with poor outcome.

Adult↗
PubMed1994

Mineral status of skeleton and advanced periodontal disease.

Studies of the effect of general bone loss on periodontal condition and on development of periodontal pockets suggest that there is no clear correlation between periodontal health or number of teeth and the general mineral status of the skeleton. In some reports, however, deep periodontal pockets have been correlated with good mineral status in the jawbones and skeleton. The purpose of this study of 227 healthy postmenopausal women aged 48 to 56 years was to determine whether advanced alveolar bone loss, diagnosed by panoramic radiographs, and periodontal probing depths or number of remaining teeth were correlated with the bone mineral status of the skeleton and cortical bone in the mandible. The results suggest that individuals with high mineral values in the skeleton seem to retain their teeth with deep periodontal pockets more easily than those with osteoporosis. This finding may especially motivate treatment of persons suffering from advanced periodontal disease but having good mineral status.

Alveolar Bone Loss↗
PubMed1993

Plasma concentrations of phyto-oestrogens in Japanese men.

A low mortality from prostatic cancer is found in Japanese men consuming a low-fat diet with high content of soy products, a rich source of isoflavonoids. We therefore assayed four isoflavonoids in plasma of 14 Japanese and 14 Finnish men. The geometric mean plasma total individual isoflavonoid levels were 7 to 110 times higher in the Japanese than in the Finnish men. Genistein, a tyrosine kinase inhibitor, occurred in the highest concentration (geometric mean 276 nmol/L). We hypothesise that these high phyto-oestrogen levels may inhibit the growth of prostatic cancer in Japanese men, which may explain the low mortality from prostatic cancer in that country.

Chromans↗
PubMed1992

Oral mucosal changes related to plasma ascorbic acid levels.

The role of vitamin C in maintaining mucosal health is poorly documented. The purpose of this study was to examine the presence of oral mucosal lesions in subjects with low ascorbic acid (AA) levels in plasma. AA plasma levels of 843 working elderly people in six rural villages in Eastern Finland were determined. All subjects with low plasma AA levels (< or = 25 mumol/l) (n = 106) formed the study group. Controls with normal AA levels (> or = 50 mumol/l) (n = 103) were drawn from the same population. They were matched for age, sex and number of teeth. Oral mucosal lesions in all subjects were recorded clinically using a double-blind method in all subjects. Petechias, leukoplakia and lichenoid lesions were the commonest lesions of the oral mucosa. Only in leukoplakia there was a statistically significant difference between the groups (p < 0.01). Smokers had more leukoplakia than non-smokers. The prevalence of leukoplakia was higher when smoking was combined with AA deficiency.

Adult↗