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Biomedical subjects

K Huttunen

Publications and source records attributed to K Huttunen.

At least 19 recordsLinked to original sources

Bacterial strains from moldy buildings are highly potent inducers of inflammatory and cytotoxic effects.

UNLABELLED: We aimed to identify inflammatory and cytotoxic potential of individual indoor air bacterial and fungal strains, as well as extracts of indoor air filter samples containing bacteria and fungi. Mouse RAW264.7 macrophages were exposed in vitro to four bacterial strains; Streptomyces californicus, Mycobacterium terrae, Bacillus cereus and Pseudomonas fluorescens, and three fungal strains; Penicillium spinulosum, Aspergillus versicolor and Stachybotrys chartarum. Furthermore, RAW264.7 macrophages were exposed to indoor air filter sample extracts representing 'low' (n = 21) and 'high' (n = 20) exposure to viable fungi or bacteria. Production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as cell viability were measured after 24 h exposure. The results show that the bacterial strains induce more profound production of NO, TNF-alpha and IL-6 than the studied fungal strains. They also decrease the viability of mouse macrophages. Similarly, the indoor air filter samples with high concentration of bacteria induced a statistically significant increase in TNF-alpha and IL-6 production as well as a decrease in cell viability. Altogether, these results suggest that indoor air bacterial strains are potent inducers of inflammatory responses and thus possibly related to adverse health effects of the inhabitants. PRACTICAL IMPLICATIONS: There is abundant documentation of the association between building dampness and mold and adverse health effects on occupants, but the causal agents of the effects are still unclear. In order to reveal these causal links, experimental studies with in vitro and in vivo methods are needed. The present findings shed new light on studies of the microbial constituents of indoor air in moldy buildings responsible for adverse health effects. These results imply that bacteria should also be monitored in cases of suspected microbial contamination of indoor air.

Air Microbiology↗

Inflammatory responses in mice after intratracheal instillation of spores of Streptomyces californicus isolated from indoor air of a moldy building.

Microbial growth in buildings is associated with respiratory symptoms in the occupants. However, the specific effects of the microbes and the way they provoke clinical manifestations are poorly understood. In the current study, mice were exposed via intratracheal instillation to single doses of the spores of Streptomyces californicus, isolated from indoor air of a moisture-damaged building (2.2 x 10(7), 1.1 x 10(8), and 3.3 x 10(8) spores), or lipopolysaccharide (50 microg). Inflammation and toxicity in lungs were evaluated 24 h later. The time course of the effects was explored with the dose of 1.1 x 10(8) spores for up to 7 days. The microbial spores elevated proinflammatory cytokine (i.e., TNFalpha and IL-6) levels in bronchoalveolar lavage fluid (BALF) and in serum in a dose- and time-dependent manner and evoked expression of inducible nitric oxide synthase in BAL cells. Both TNFalpha and IL-6 responses peaked at 6 h after instillation, but TNFalpha leveled off more quickly than IL-6. The cytokine surge was followed by inflammatory cell recruitment into airways. Moreover, the spores increased dose- and time-dependently total protein, albumin, hemoglobin, and lactate dehydrogenase concentrations in BALF during the first 24 h. Histopathological examination of lungs confirmed the inflammatory changes. With the exception of macrophage and lymphocyte numbers, all parameters returned to control level at 7 days. In summary, these observations indicate that the spores of S. californicus are capable of provoking an acute inflammation in mouse lungs and can cause cytotoxicity. Thus, S. californicus can be considered as a species with potential to cause adverse health effects in occupants of moisture-damaged buildings.

Air Microbiology↗

HI-SIMv1.0--towards the virtual reality of hearing impairments.

The virtual reality of hearing impairments has obvious practical applications in areas such as audiology, speech therapy and hearing aid technology and serves as an informational tool for the family members of the hearing impaired. To simulate hearing impairment, a CD-ROM with filtered speech material accessible through a graphical user-interface was produced; the user-interface was created with standard multimedia tools. The CD-ROM, HI-SIMv1.0, intended as an interactive educational tool, offers a virtual experience of the effects of a selection of common types of hearing impairment. The options available in this simulation include grade of hearing impairment, audiometric configuration and the type and level of background noise. Word recognition scores can be computed for standard Finnish audiometric material.

Acoustic Stimulation↗

Comparison of mycobacteria-induced cytotoxicity and inflammatory responses in human and mouse cell lines.

Environmental mycobacteria, which are ubiquitous in nature, are also detected in moisture-damaged buildings. Their potential role inducing the adverse health effects associated with living in moisture damaged buildings requires clarification. To establish a model for these studies, we evaluated inflammatory responsiveness in different cell lines exposed to environmental mycobacterial species. Four mycobacterial isolates belonging to Mycobacterium avium complex and Mycobacterium terrae, recovered from the indoor air sampled when a moldy building was being demolished, were studied for their cytotoxicity and ability to stimulate the production of inflammatory mediators in mouse RAW264.7 and human 28SC macrophage cell lines, and human A549 lung epithelial cell line. Lipopolysaccharide (LPS) was used as a positive control. Production of cytokines (tumor necrosis factor alpha, TNF-alpha; interleukin 6, IL-6; and interleukin beta, IL-1beta) was analyzed immunochemically, nitric oxide (NO) by the Griess method, expression of inducible NO synthase with Western blot analysis, and cytotoxicity with the MTT test. Both human and mouse cells produced NO and IL-6 after mycobacterial exposure. Mouse macrophages also showed production of TNF-alpha induced by both mycobacteria and LPS, whereas the human cell lines failed to produce TNF-alpha after mycobacterial exposure and the human epithelial cell line also failed to respond to LPS. Similarly, only mouse macrophages produced IL-1beta. Mycobacterial exposure was not cytotoxic to human cells and was only slightly cytotoxic to mouse macrophages. The results indicate that environmental mycobacterial isolates from moldy buildings are capable of activating inflammatory mechanisms in both human and murine cells. The human and mouse cell lines, however, differ significantly in the grade and type of the responses.

Air Pollution, Indoor↗

Inflammatory responses in RAW264.7 macrophages caused by mycobacteria isolated from moldy houses.

Mycobacterial strains (nonpathogenic Mycobacterium terrae, potentially pathogenic Mycobacterium avium-complex and Mycobacterium scrofulaceum), isolated from a moldy building, were studied with respect to their ability to stimulate macrophages (RAW264.7) to produce inflammatory mediators, and to cause cytotoxicity. Reactive oxygen species (ROS) were measured by chemiluminescence, cytokines (TNF-alpha, IL-6, IL-1, IL-10) immunochemically, nitric oxide (NO) by Griess-method, expression of inducible NO-synthase (iNOS) with Western Blot analysis and cytotoxicity with MTT-test. All the strains induced dose- and time-dependent production of NO, IL-6 and TNF-alpha in macrophages, whereas IL-1 or IL-10 production was not detected. The production of ROS and cytotoxicity was increased with the highest doses. Interestingly, different strains had significant differences in their ability to induce these responses, M. terrae being the most potent and M. avium-complex the weakest one. These results indicate that both non- and potentially pathogenic strains of mycobacteria present in moldy buildings are capable of activating inflammatory mechanisms in macrophages.

Journal Article↗

Can the impact of hearing impairments be modelled?

The effects of two simulated hearing impairments (presbyacusis) on speech perception were investigated in two groups of normally hearing subjects (30 and 48 subjects, respectively). Eight patients with presbyacusis with similar hearing impairment to those in the latter simulation served as the clinical material. Word recognition scores were measured in quiet and in cocktail party noise (S/N + 18 dB and + 12 dB). The recognition scores deteriorated in the less favourable listening conditions. Somewhat surprisingly, the hearing impaired subjects showed better word recognition scores in quiet and especially in moderate noise. Subjective complaints on speech perception difficulties in noise on a visual analogue scale behaved quite logically; the hearing impaired subjects' subjective experiences were no milder than those of the normally hearing during the simulation. The better results in word recognition shown by the hearing aid candidates may be explained by habituation to the hearing impairment.

Adolescent↗

Neurohumoral responses to a single haemodialysis in chronic renal patients.

The effect of volume reduction on vasoactive substances and their role in estimating dry weight in haemodialysis patients was studied. Plasma atrial natriuretic peptide (ANP), catecholamines, antidiuretic hormone, renin activity and serum aldosterone were measured in 12 patients before and after bicarbonate haemodialysis. Haemodynamical changes were registered and cardiac function and diameter of the inferior vena cava were measured by echocardiography before and after dialysis. Plasma concentration of ANP was significantly reduced by haemodialysis from 209 +/- 51 to 69 +/- 13 pg mL(-1) (n = 12, P < 0.05), whereas concentrations of the other hormones were unchanged. The change in the concentration of ANP did not have significant correlation with weight reduction. The concentration of ANP correlated positively with the diameter of the inferior vena cava (r = 0.70, P < 0.05) after dialysis, but not before dialysis. The concentration of ANP before or after haemodialysis or its change during dialysis did not correlate with any other biochemical parameter. The results show that plasma ANP level is decreased after volume reduction in patients with chronic renal failure, whereas other hormonal systems are unresponsive. However, plasma concentration of ANP seems to have no role in estimating dry weight in chronic haemodialysis patients.

Adult↗

Do we know the real need for hearing rehabilitation at the population level? Hearing impairments in the 5- to 75-year-old cross-sectional Finnish population.

The cross-sectional population sample studied here was randomly selected from the population register of northern Finland. The subjects comprised 10 different age groups between 2 and 75 years of age. Pure tone averages over the frequencies of both 0.5, 1 and 2 kHz and 0.5, 1, 2 and 4 kHz - i.e. better ear hearing levels (BEHL) of BEHL0.5-2kH and BEHL0.5-4kHz - were calculated. The prevalence of various grades of hearing impairment was investigated among the 3518 people who participated in audiometric measurements. Two different classifications were used to grade the hearing impairment. According to the World Health Organization (WHO) classification (1991), 94.3% of the subjects had normal hearing, whereas 3.8% had mild hearing impairment, 1.3% had moderate impairment, 0.4% severe impairment and 0.1% profound impairment. When the more recent EU definition (1996) was used, 85.3% of the subjects had normal hearing. Mild impairment was found in 11.5% of the subjects, moderate impairment in 2.8%, severe impairment in 0.3%, and profound in 0.1%. The difference between the two definitions mentioned above (resulting in different prevalence figures of hearing impairments) is clear. The WHO classification reveals the need for rehabilitation and can thus be used as a basis of resource allocation, whereas the EU proposal reveals even the mildest hearing impairments and hence better illustrates the real prevalence of impairment. The need for the current and future audiological services may be estimated from the prevalence rates of hearing impairments. The proportion of the Finnish elderly - the people most frequently using health services - is expected to increase from today's 15% to 23% within the next 20 years. The same phenomenon is to be expected in other Western societies.

Adolescent↗

The use of myoglobin/carbonic anhydrase III ratio as a marker for myocardial damage in patients with renal failure.

To evaluate the clinical significance of myoglobin and myoglobin/CA III ratio as a biochemical marker for acute myocardial infarction (AMI) in patients with renal failure; we studied 300 patients admitted to the hospital with a history of symptoms characteristic of AMI, and 33 renal failure patients who were undergoing chronic maintenance dialysis treatment and who did not have clinical or electrocardiographic evidence of AMI. Fifteen of 300 patients admitted to the hospital had AMI based on the WHO criteria, and a concomitant value of serum creatinine concentration (S-Crea) over 140 mumol/l indicating renal failure. Fourteen of these 15 patients (93%) had serum myoglobin concentration over 70 micrograms/l and myoglobin/CA III ratio over 2.20 as measured by time-resolved fluoroimmunoassay (TR-FIA); these values were cutoff values for AMI diagnosis. Twenty-two of 300 patients admitted to the hospital had S-Crea over 140 mumol/l in the absence of myocardial injury. Sixteen of these 22 (73%) patients had increased serum myoglobin concentration, but only four of 22 (18%) had myoglobin/CA III ratio over 2.20. A positive correlation between serum myoglobin and CA III concentrations (rs = 0.933, P < 0.001) was observed in hemodialyzed patients with chronic renal failure. The values for serum myoglobin/CA III ratio observed in this group were similar to those measured in the 22 non-AMI patients with S-Crea over 140 mumol/l admitted to the hospital and differed statistically from that for patients with AMI (P < 0.001). We conclude that serum myoglobin, as well as CA III values, are elevated in patients with renal failure, and therefore S-myoglobin can not be used as a marker for AMI in these patients. Our results suggest that the serum myoglobin/CA III ratio is a reliable AMI marker even in renal failure patients, and therefore provides a tool for AMI diagnosis in this patient group.

Acute Disease↗

Decreased clearance of low-density lipoprotein in uremic patients under dialysis treatment.

The clearance of low-density lipoprotein (LDL) was studied in eleven patients on hemodialysis (HD) treatment and nine patients on continuous ambulatory peritoneal dialysis (CAPD) treatment and compared with the clearance of LDL in nine control subjects. The clearance rates for LDL (fractional catabolic rate, FCR) in all the uremic patients (FCR for LDL 0.305 +/- 0.075 pools/day, mean +/- SD) were significantly lower than the clearance of LDL in the control subjects (FCR for LDL 0.376 +/- 0.045 pools/day; P = 0.01). The clearance of LDL in the HD patients (FCR for LDL 0.334 +/- 0.066 pools/day) was only mildly decreased in comparison to the control subjects (P = 0.122), but the clearance of LDL in the CAPD patients was markedly decreased (FCR for LDL 0.268 +/- 0.072 pools/day) in comparison to the control subjects (P = 0.001). The FCR for LDL among all the patients was negatively related to the plasma total cholesterol (r = -0.56, P = 0.01) and LDL cholesterol concentration (r = -0.76, P = 0.0002) and LDL apolipoprotein B concentration (r = -0.48, P = 0.03). In conclusion, the clearance of LDL is decreased in uremic patients on dialysis treatment. This alteration in the LDL metabolism of the uremic patients may contribute to their accelerated atherosclerosis.

Adult↗

Bone mineral density evaluated by dual-energy X-ray absorptiometry after one-year treatment with calcitriol started in the predialysis phase of chronic renal failure.

Thirteen patients in the predialysis phase of chronic renal failure (CRF) were treated with calcitriol (0.25 micrograms/day) and 12 with placebo. After 1 year of study, an increase in bone mineral density in the calcitriol group measured by dual-energy X-ray absorptiometry was seen for the femoral neck and lumbar spine when compared to the placebo group (p < 0.001 and p < 0.01, respectively). We conclude that a steady low dose of calcitriol started in the predialysis phase of CRF is beneficial to the patients with CRF. This may be partly due to suppression of secondary hyperparathyroidism.

Absorptiometry, Photon↗

Decreased clearance of low-density lipoprotein in patients with chronic renal failure.

The clearance of low-density lipoprotein (LDL) isolated from uremic patients (autologous-LDL) and from a control subject (control-LDL) was studied in 12 uremic patients on conservative management and compared to the LDL clearance in control subjects. The clearances of autologous-LDL and control-LDL were almost the same in the patients. However, the fractional catabolic rate (FCR) of the autologous-LDL (0.307 +/- 0.094 pools/day, mean +/- SD) and the control-LDL (0.289 +/- 0.081 pools/day) were significantly lower (P < 0.05 and P < 0.01, respectively) than the FCR for LDL in the control subjects (0.376 +/- 0.045 pools/day). Moreover, one-half of the patients had an abnormally low LDL clearance rate ranging from 0.146 to 0.282 pools/day. The FCR for the autologous-LDL varied from 0.146 to 0.416 pools/day between the patients and was negatively related (r = -0.68, P = 0.02) to the serum urea concentration (from 11.8 to 39.2 mmol/liter) and tended to correlate positively with the glomerular filtration values (from 9.2 to 48.3 ml/min/1.73 m2; r = 0.57, P = 0.096, non-linear relationship). In conclusion, the clearance of LDL in patients with advanced uremia on conservative management is frequently decreased. This alteration in the metabolism of the most atherogenic particle in plasma may contribute to the accelerated atherosclerosis in uremic patients.

Apolipoproteins B↗

Decreased clearance of uraemic and mildly carbamylated low-density lipoprotein.

Low-density lipoprotein (LDL) was in vitro carbamylated with potassium cyanate and the clearance was studied in man. A minor carbamylation of LDL decreased the clearance of LDL by 41% (94% of amino groups free) and by 18% (90% of amino groups free). When LDL was extensively carbamylated its clearance was substantially accelerated. Moreover, the clearance of LDL isolated from 14 haemodialysis patients (uremic-LDL) was studied in rabbits. Uraemic-LDL, injected into rabbits simultaneously with the LDL of a healthy control subject, was cleared more slowly than the control-LDL (difference in fractional catabolic rate -6.5%, P = 0.02). We also examined the lipid peroxidation of the carbamylated LDL by measuring the amount of thiobarbituric-acid reactive substances (TBARS) and formation of conjugated dienes during exposure of carbamylated LDL to 5 microM Cu2+. The carbamylated and native LDL had similar lipid peroxidation and propensity for oxidation. In summary, both the uraemic-LDL and minimally carbamylated LDL had a decreased clearance in vivo, which may contribute to the accelerated atherosclerosis in uraemic patients.

Adult↗

Effects of three treatment modes on plasma lipids and lipoproteins in uraemic patients.

Plasma lipids, chemical composition of various lipoprotein fractions, apolipoprotein B concentrations and apolipoprotein E phenotypes were studied in 12 uraemic patients on conservative treatment (CT), in 16 patients on haemodialysis (HD) and in 18 patients on continuous ambulatory peritoneal dialysis treatment (CAPD). Plasma total cholesterol and triglyceride concentrations were increased in the CAPD patients in comparison to the HD patients and the control subjects. Moreover, the CAPD patients had higher LDL cholesterol concentration than the CT and HD patients. The HDL cholesterol concentration was lower in the HD and CAPD patients than in the control subjects. The chemical composition of lipoproteins in all fractions of the CT and HD patients and in VLDL, IDL and LDL fractions of the CAPD patients differed from those of the control subjects. The main differences were the increased proportion of triglycerides in VLDL and LDL fractions of all the patient groups and in HDL fraction of the CT and HD patients in comparison to the control subjects. Moreover, the proportion of cholesterol was increased in VLDL and IDL fractions of the CT and the CAPD patients and decreased in HDL fraction of the CT and HD patients compared to the control subjects. In conclusion, in addition to the alterations in the lipoprotein concentrations in uraemic patients there are also marked changes in the chemical composition of the lipoprotein particles that may further contribute to the accelerated atherosclerosis among uraemic patients. The abnormalities are particularly prevalent in CAPD patients.

Adult↗

Diffuse renal disease. Diagnosis by ultrasound-guided cutting needle biopsy.

The results of ultrasound (US)-guided renal parenchymal cutting needle biopsies in 101 consecutive patients were reviewed. The biopsies were done with the automated Biopty device mounted with a 2.0-mm needle. One or 2 needle passes yielded sufficient material for histologic analysis in 94% (95/101). Three or more passes were required in 6% (6/101) to obtain an adequate specimen. Mesangioproliferative glomerulonephritis, IgA-nephropathy, nephrosclerosis, diabetic nephropathy, secondary amyloidosis, lupus nephritis, minimal change glomerulonephritis and interstitial nephritis accounted for 79% of the final histologic diagnoses. The high quality and quantity of the tissue specimens yielded a definitive histologic diagnosis in renal parenchymal diseases of unknown etiology. Four major complications occurred, but no deaths or loss of kidney function were recorded. US proved useful as a guide to suitable biopsy site and in the detection of clinically significant complications. Prebiopsy screening of coagulation variables did not seem to prevent complications. Special attention should be paid to post-biopsy clinical observation.

Adolescent↗

Peripheral tissue energy metabolism during recovery from hypothermia after cardiopulmonary bypass: effect of amino-acid infusions.

We studied the effects of amino-acid administration on the leg exchange of energy substrates and amino-acids during recovery from hypothermia after open heart surgery. Glucose (G, n = 5), glucose and conventional amino-acids (CA, n = 5) or glucose and branched chain amino-acids (BC, n = 5) were infused during recovery from hypothermia after open heart surgery. The leg exchange of energy substrates and amino-acids were measured after arrival at the intensive care unit, after rewarming, and 2h and 4h after rewarming during increasing amino-acid intake. Despite a normal stress response to surgery, reflected by increased energy expenditure and increased concentrations of insulin and catabolic hormones, amino-acids had no effect on the leg exchange of branched chain amino-acids, glutamine, alanine and energy substrates. This suggests that the transport of amino-acids and energy substrates into the cell are impaired after hypothermic cardiopulmonary bypass and intracellular substrates are utilised for the increased demand for energy during rewarming.

Journal Article↗