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Biomedical subjects

H Savolainen

Publications and source records attributed to H Savolainen.

At least 19 recordsLinked to original sources
PubMed2007

An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension.

OBJECTIVES: To assess perioperative outcomes and blood pressure (BP) responses to an implantable carotid sinus baroreflex activating system being investigated for the treatment of resistant hypertension. METHODS: We report on the first seventeen patients enrolled in a multicenter study. Bilateral perivascular carotid sinus electrodes (CSL) and a pulse generator (IPG) are permanently implanted. Optimal placement of the CSL is determined by intraoperative BP responses to test activations. Acute BP responses were tested postoperatively and during the first four months of follow-up. RESULTS: Prior to implant, BP was 189.6+/-27.5/110.7+/-15.3 mmHg despite stable therapy (5.2+/-1.8 antihypertensive drugs). The mean procedure time was 202+/-43 minutes. No perioperative strokes or deaths occurred. System tests performed 1 or up to 3 days postoperatively resulted in significant (all p < or = 0.0001) mean maximum reduction, with standard deviations and 95% confidence limits for systolic BP, diastolic BP and heart rate of 28+/-22 (17, 39) mmHg, 16+/-11 (10, 22) mmHg and 8+/-4 (6, 11) BPM, respectively. Repeated testing during 3 months of therapeutic electrical activation demonstrated a durable response. CONCLUSIONS: These preliminary data suggest an acceptable safety of the procedure with a low rate of adverse events and support further clinical development of baroreflex activation as a new concept to treat resistant hypertension.

Adult↗
PubMed2006

Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia.

Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable.

Adult↗
PubMed2005

Host factors in occupational diisocyanate asthma: a Swiss longitudinal study.

OBJECTIVE: To investigate the usefulness of surrogates for individual susceptibility to organic diisocyanates in occupational asthma. SUBJECTS: All new cases declared to the Swiss National Accident Insurance Company (SUVA) for establishment of a case for compensable occupational disease during 1993. Sixty-nine persons, of whom three were women, were suspected of having occupational asthma due to isocyanates. Of these, 47 subjects fulfilled the criteria to be accepted as an occupational disease case. METHODS: All subjects were studied clinically and gave a blood sample for the phenotyping of their alpha-antitrypsin status and for immunological studies. The subjects were also given a peroral dose of caffeine for the determination of their N-acetylation capacity. Finally, those with an occupational disease were subjected to the methacholine provocation test. RESULTS: Forty-four persons with occupational disease, out of 47, were heterozygous antitrypsin carriers and/or slow acetylators of primary amines. In the bronchial provocation with methacholine, 12 of these subjects had an unaltered response and seven had a mild reaction, 13 a moderate one and 15 a severe reaction. INTERPRETATION: The study confirms the finding that slow N-acetylators are susceptible to asthma from exposure to common diisocyanate monomers at work. The same applies to heterozygous antitrypsin-phenotype carriers. Thus, the use of these markers may reinforce the diagnostic procedure, but they cannot completely replace the immunological tests.

Adult↗
PubMed2004

Bovine mesenteric vein graft (ProCol) in critical limb ischaemia with tissue loss and infection.

OBJECTIVES: Poor results have been reported following infrainguinal reconstructions using heterogenous grafts. The objective of this study was to assess the use of bovine mesenteric vein (ProCol) graft in patients with critical limb ischaemia (CLI), tissue loss/infection and no autologous vein available for reconstruction. METHODS: Prospective analysis of 32 patients with CLI and tissue loss/infection, in whom reconstruction with ProCol was undertaken between October 1999 and May 2002. RESULTS: The primary patency rate was 16% at 1 month. After thrombectomy, the secondary patency rate was 50% at 1 month and 26% at 14 months. No graft infections were seen. Aneurysmal dilatation of the graft occurred in 2 (6%). Limb salvage at 14 months was 47%. CONCLUSION: In patients with critical limb ischaemia, tissue loss/infection and no available vein, the ProCol graft may be an alternative. However, primary patency is a problem. In situations without tissue loss/infection, where the risk of graft infection is less, prosthetic material may be a better alternative.

Adult↗
PubMed2004

Intermediate outcome and risk factor assessment of bovine vascular heterografts used as AV-fistulas for hemodialysis access.

OBJECTIVES: This observational study was set up to prospectively follow all bovine heterograft (ProCol) fistulas implanted for hemodialysis access between 1998 and 2002. METHODS: ProCol was implanted if autogenous vein was not available or if patients presented with a history of failed, infected or otherwise complicated ePTFE grafts and/or on immunosuppressive therapy. Fistula patency was the primary outcome; secondary outcomes were clinical events and the rate of access revisions. RESULTS: Sixty-two ProCol grafts were implanted in 56 patients. The mean primary (PP) and secondary patency (SP) was 334 (SEM 57) and 528 (SEM 59) days, respectively. Coronary heart disease was associated with a significantly better SP (OR 0.2, 95% CI 0.1-0.9) whilst diabetes mellitus was associated with a significantly worse SP (OR 0.2, 95% CI 0.1-0.9). Reinterventions were performed at a mean rate of 1.23 (SEM 0.17) per fistula. The relative risk of access revision was significantly higher in patients with diabetes mellitus (OR 9.2, 95% CI 2.3-37.2). CONCLUSIONS: ProCol grafts, used for AV-fistulas, demonstrate acceptable patency rates in high-risk haemodialysis patients. Diabetes mellitus jeopardizes the patency of these fistulas and is associated with a high revision rate.

Animals↗
PubMed2004

[Vacuum-assisted Therapy in Vascular Surgery].

Since the first use of vacuum-assisted therapy (V.A.C.) in wound care, the indications of this therapy have rapidly expanded. Vascular surgery presents many types of problematic wounds. In the current cost conscious atmosphere, there is a great demand for simple and effective therapies. The V.A.C. system has a lot of potential in the management of vascular wounds. In this article we present indications for vacuum-assisted therapy in vascular surgery: chronic leg ulcers, mesh skin graft, wound care after fasciotomy for compartment syndrome, problematic inguinal wound, false aneurysms, diabetic foot gangrene and amputations with marginal circulations.

Debridement↗
PubMed2003

Common femoral artery--uncommon aneurysms.

BACKGROUND AND AIMS: Femoral artery aneurysms are rare. Their natural history, tendency to embolize or rupture are not well known. MATERIAL AND METHODS: Data of all patients seen 1996-2002 with femoral artery aneurysms at the Swiss Cardiovascular Center were analysed. Nine patients with 13 aneurysms of the common femoral artery (CFA) were identified. Only true aneurysms with a diameter of at least 2.5 cm were included. All patients were male, mean age 70 years (range: 57-85 years). Four patients had bilateral femoral aneurysms. Risk factors included hypertension (9/9), smoking (7/9). One of the aneurysms was palpable in 5/9. Four patients were asymptomatic, 5 had Fontaine class II claudication. Five patients also had an aortic aneurysm (AAA), one a thoracic aneurysm; and 6/9 popliteal aneurysms. In all patients, diagnosis was confirmed with duplex scan. Angiography was performed preoperatively. RESULTS: The aneurysms were operated on electively using aneurysm secclusion and interposition grafting. There were no significant perioperative complications. Median hospital stay was 8 days. CONCLUSION: CFA aneurysms are rare. They are palpable in nearly half of the cases. They rarely cause thrombotic or embolic complications, but are almost always connected to other aneurysms. Patients with CFA aneurysms should be screened with duplex scan. Operative therapy is straightforward, few complications can be expected. Postoperative follow-up with annual duplex scans is suggested.

Aged↗
PubMed2002

First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes.

AIMS/HYPOTHESIS: A reduced first-phase insulin response to intravenous glucose is perceived as a sign of far-advanced deterioration of beta-cell function during the development of Type I (insulin-dependent) diabetes mellitus, but data on insulin responses at the onset of diabetes-related autoimmunity are lacking. We studied the first-phase insulin responses of small children soon after observed seroconversion to autoantibody positivity. METHODS: In the Type I Diabetes Prediction and Prevention Study newborn infants are screened for HLA-DQB1-associated genetic risk for Type I diabetes and those with increased risk are followed-up for the emergence of islet-cell antibodies. If antibodies are detected, autoantibodies to three other antigens (insulin, GAD65 and IA-2) are also measured. To measure first-phase insulin responses, intravenous glucose tolerance tests were carried out in 52 (1 to 5-year-old) children who had recently seroconverted to islet-cell antibody positivity. RESULTS: The first-phase insulin response was subnormal (<38 mU/l, the 5(th) percentile of insulin responses of 20 islet-cell antibody negative healthy children at this age) in 22 of the 52 children (42%). Stepwise multiregression analysis showed that islet-cell antibody greater than 20 JDFU (p=0.0005), insulin autoantibodies (p=0.0009) and an increasing number of positive autoantibodies (p=0.0011) were independent predictors of low first-phase insulin response. CONCLUSION/INTERPRETATION: A decreased first-phase insulin response could be an early phenomenon in the course of prediabetes in young children, implying a rapid autoimmune destruction or loss of function of beta cells as well as possible metabolic compensation mechanisms, since 11 out of the 22 high risk children remain nondiabetic for a considerable period of time despite low insulin responses.

Autoantibodies↗
PubMed2001

Feasibility of genetic and immunological prediction of type I diabetes in a population-based birth cohort.

AIMS/HYPOTHESIS: Population-wide genetic screening of susceptibility to multifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified. METHODS: Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the at-risk children to frequent autoantibody follow-up were studied. Screening was offered to all families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x not equal to *02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of beta-cell autoimmunity were invited to a separate prevention trial. RESULTS: The parents of 31,526 babies born between November 1994 and April 1999 (94.4% of those eligible) agreed to genetic screening. We found that 4651 infants (14.8%) had increased genetic risk (2.5 to 15 times that of the general population) for Type I (insulin-dependent) diabetes mellitus, and 80% of them joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69, 68 and 76% of the at-risk children, respectively, attended the follow-up. A total of 17 of the 22 children (77%) who were born during the study period and have developed diabetes carry the risk genotypes we currently use for screening. CONCLUSIONS/INTERPRETATION: Population-based screening of genetic susceptibility for Type I diabetes, linked with a possibility to participate later in a prevention trial, is highly accepted in Finland and identifies about 75% of those developing diabetes at an early age. Families adhere well to the frequent measurement of signs of beta-cell autoimmunity in the children at-risk.

Alleles↗
PubMed2001

DNA copy number profiling in esophageal Barrett adenocarcinoma: comparison with gastric adenocarcinoma and esophageal squamous cell carcinoma.

We screened 18 specimens of Barrett adenocarcinoma for genetic alterations using comparative genomic hybridization (CGH) to analyze DNA copy number changes. The most common gains were at 20q (56%) and 17q (39%). High-level amplifications were observed in the same chromosomes. The most common losses were in chromosomes 4 (22%) and 5 (22%). Other recurrent changes were gains of chromosomes 8, 10q, and 13. We compared the copy number changes in Barrett adenocarcinoma and those previously reported in the intestinal type of stomach carcinoma. The similarities we found suggest a common molecular pathogenesis, whereas dissimilarities seen between Barrett adenocarcinoma and esophageal squamous cell carcinoma are in keeping with a well-known different etiology.

Adenocarcinoma↗
PubMed2001

Expression of estrogen receptor sub-types alpha and beta in acute and chronic cardiac allograft vasculopathy.

BACKGROUND: The vasculoprotective effects of estrogen are well-established not only in women with age-related atherosclerosis, but also after experimental vascular injury and in chronic allograft vasculopathy. Evidence exists that the newly discovered estrogen receptor (ER) beta, rather than the classical ERalpha is related to the vasculoprotective effect. Here we investigate whether and to what extent the two ERs are expressed in cardiac allografts in the rat and human in native state and during acute and chronic rejection. METHODS: Rat cardiac allografts were performed from male DA (AG-B4, RT1(a)) to male WF (AG-B2, RT1(v)) strain and syngeneic transplants from DA to DA strain; human male-to-male heart allograft endomyocardial biopsies came from our biopsy files. RESULTS: Under in situ hybridization, ERbeta mRNA was prominently expressed in rat vessels and stroma, whereas ERalpha mRNA was present in low levels only. In immunohistochemistry, 2 ERbeta-specific antibodies stained rat and human vessels and stroma, whereas only a weak or no signal was obtained with 2 ERalpha-specific antibodies. Interestingly, the mRNA and protein expression levels in the rat carried only a weak correlation with the intensity of acute rejection, i.e., was not related to the intensity of inflammation. CONCLUSIONS: Our results demonstrate that ERbeta is the predominant ER in rat and human cardiac allografts, and suggest that, unless additional ERs are identified, the vasculoprotective effects of estrogen derivatives in cardiac allograft vasculopathy are mediated by ERbeta rather than by the classical ERalpha.

Animals↗
PubMed2001

Determination of gallic acid in wood dust as an indicator of oak content.

A high-performance liquid chromatography (HPLC) method was developed for the detection of extracted gallic acid in wood dust. Gallic acid is a polyphenol present in carcinogenic oak wood dust, but not in beech, ash, pine or spruce dusts, as confirmed by HPLC analyses. The method involved the extraction of gallic acid from the oak dust, followed by liquid chromatographic analysis. The correlation coefficient for the share of oak dust vs. the gallic acid concentration of wood dust was 0.995. The method was tested with oak wood dust samples collected on polycarbonate membrane filters during an 8 h workshift in a floor board factory, where the dust content of the air samples was determined gravimetrically. The oak dust and the gallic acid concentrations varied from 0.2 to 13.8 mg m-3 and from 0.03 to 3.8 micrograms m-3, respectively. These parameters were linearly correlated with a correlation coefficient of 0.95. The airborne gallic acid determination is a useful technique to confirm occupational exposure to oak wood dust, a recognized human carcinogen.

Carcinogens↗
PubMed2000

Analysis of oak tannins by liquid chromatography-electrospray ionisation mass spectrometry.

Extractable tannins were analysed by liquid chromatography-electrospray ionisation mass spectrometry in two oak species, North American white oak (Quercus alba) and European red oak (Quercus robur). They mainly included various glucose gallic and ellagic acid esters. The structures were partially determined, and they included grandinin/roburin E, castalagin/vescalagin, gallic acid, valoneic acid bilactone, monogalloyl glucose, digalloyl glucose, trigalloyl glucose, ellagic acid rhamnose, quercitrin and ellagic acid.

Chromatography, Liquid↗
PubMed2000

Urinary methanol and formic acid as indicators of occupational exposure to methyl formate.

OBJECTIVE: To evaluate the validity of methanol (MeOH) and formic acid (FA) in urine as biological indicators of methyl formate (MF) exposure in experimental and field situations. METHODS: The subjects were 28 foundrymen and two groups of volunteers (20 control and 20 exposed). Exposure assessment of the workers was performed by personal air and biological monitoring. Methyl formate vapour collected on charcoal tube was analysed by gas chromatography. The concentration of MF in the exposure chamber (volunteer-study) was monitored by two independent methods [flame ionisation detection (FID) and Fourier transformation infra-red detection (FTIR)]. Urinary metabolites (MeOH and FA) were analysed separately by headspace gas chromatography. RESULTS: The volunteers exposed to 100 ppm MF vapour at rest for 8 h excreted 3.62 +/- 1.13 mg MeOH/l (mean +/- SD) at the end of the exposure. This was statistically different (P < 0.001) from pre-exposure MeOH excretion (2.15 +/- 0.80 mg/1), or from that of controls (1.69 +/- 0.48 mg/l). The urinary FA excretion was 32.2 +/- 11.3 mg/g creatinine after the exposure, which was statistically different (P < 0.001) from pre-exposure excretion (18.0 +/- 9.3 mg/g creatinine) or that of controls (13.8 +/- 7.9 mg/g creatinine). In foundrymen, the urinary FA excretion after the 8 h workshift exposure to a time weighted average (TWA) concentration of 2 to 156 ppm MF showed a dose-dependent increase best modelled by a polynomial function. The highest urinary FA concentration was 129 mg/g creatinine. The pre-shift urinary FA of the foundrymen (18.3 +/- 5.6 mg/g creatinine) did not differ from that of controls (13.8 +/- 7.9 mg/g creatinine). The urinary MeOH excretion of the foundrymen after the shift, varied from < 1 to 15.4 mg/l, while the correlation with the preceding MF exposure was poor. The foundrymen excreted more (P = 0.01) FA (2.12 +/- 3.56 mg/g creatinine) after the workshift than experimentally, once-exposed volunteers (0.32 +/- 0.11 mg/g creatinine) at a similar inhaled MF level of 1 ppm). CONCLUSIONS: In spite of its high background level in non-exposed subjects, urinary FA seems to be a useful biomarker of methyl formate exposure. The question remains as to what is the reason for the differences in chronic and acute exposure respectively.

Adult↗