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Biomedical subjects

M Wilken

Publications and source records attributed to M Wilken.

At least 19 recordsLinked to original sources
PubMed2005

PCDD/Fs in ambient air collected in Zagreb, Croatia.

Levels of PCDD/Fs were measured at four different sites in Zagreb, capital of Croatia. Also one sample was taken during spontaneously initiated open fire on a landfill and one sample where garden waste of unknown content was burnt. Over period 1997-2000, 28 samples were collected and levels ranged between 9 and 306 fgI-TEQm(-3), except in the sample collected during landfill fire. Air PCDD/F levels in Zagreb at four sites were different and the highest levels were observed in industrial area. Seasonal variation of levels is also evident with higher levels in winter than in summer. Our results show that PCDD/F levels in ambient air collected in Zagreb are at lower end of the published data range. In general, homologue profiles were quite similar for all locations, the concentration of PCDD homologues increased while the concentration of PCDF homologues decreased with increasing degree of chlorination. PCDD/F levels in the landfill fire sample was 13,200 fgI-TEQm(-3) which are much higher than levels in garden waste burning sample or in sample collected at industrial site. During landfill fire, the concentration of 2,3,7,8-TCDF becomes even higher than the concentration of OCDF and is equal to the concentration of 1,2,3,4,6,7,8-HpCDF.

Air↗
PubMed2004

Beta-cell function and islet morphology in normal, obese, and obese beta-cell mass-reduced Göttingen minipigs.

Herein, we bridge beta-cell function and morphology in minipigs. We hypothesized that different aspects of beta-cell dysfunction are present in obesity and obesity with reduced beta-cell mass by using pulsatile insulin secretion as an early marker. Measures for beta-cell function (glucose and arginine stimulation plus baseline and glucose-entrained pulsatile insulin secretion) and islet morphology were studied in long-term (19-20 mo) obese (n = 5) and obese beta-cell-reduced [nicotinamide + streptozotocin (STZ), n = 5] minipigs and normal controls, representing different stages in the development toward type 2 diabetes. Acute insulin response (AIR) to glucose and arginine were, surprisingly, normal in obese (0.3 g/kg glucose: AIR = 246 +/- 119 vs. 255 +/- 61 pM in control; 67 mg/kg arginine: AIR = 230 +/- 124 vs. 214 +/- 85 pM in control) but reduced in obese-STZ animals (0.3 g/kg glucose: AIR = 22 +/- 36, P < 0.01; arginine: AIR = 87 +/- 92 pM, P < 0.05 vs. control). Baseline pulsatile insulin secretion was reduced in obese (59 +/- 16 vs. 76 +/- 16% in control, P < 0.05) and more so in obese-STZ animals (43 +/- 13%, P < 0.01), whereas regularity during entrainment was increased in obese animals (approximate entropy: 0.85 +/- 0.14 vs. 1.13 +/- 0.13 in control, P < 0.01). Beta-cell mass (mg/kg body wt) was normal in obese and reduced in obese-STZ animals, with pancreatic fat infiltration in both groups. In conclusion, obesity and insulin resistance are not linked with a general reduction of beta-cell function, but dynamics of insulin secretion are perturbed. The data suggest a sequence in the development of beta-cell dysfunction, with the three groups representing stages in the progression from normal physiology to diabetes, and assessment of pulsatility as the single most sensitive marker of beta-cell dysfunction.

Animals↗
PubMed2003

Loss of beta-cell mass leads to a reduction of pulse mass with normal periodicity, regularity and entrainment of pulsatile insulin secretion in Göttingen minipigs.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with impaired insulin action and secretion, including disturbed pulsatile release. Impaired pulsatility has been related to impaired insulin action, thus providing a possible link between release and action of insulin. Furthermore, progressive loss of beta-cell mass has been implicated in the pathogenesis of Type 2 diabetes. The aim of this study was to evaluate a possible link between loss of beta-cell mass and impaired pulsatile insulin secretion with special focus on glucose responsiveness of insulin secretion. METHODS: The kinetic and dynamic profiles of insulin in Göttingen minipigs are favourable for studies on pulsatility and a model of diabetes with reduced beta-cell mass has recently been established. Pigs were studied before (n=14) and after (n=10) reduction of beta-cell mass by nicotinamide (67 mg/kg) and streptozotocin (125 mg/kg) from 17.7+/-4.7 (normal animals, n=5) to 6.1+/-2.0 mg/kg. Pulsatile insulin secretion was examined during basal (n=8 normal, n=6 beta-cell reduced) and glucose entrained (n=6 normal, n=4 beta-cell reduced) conditions. Insulin concentration time series were analysed by autocorrelation and spectral analyses for periodicities and regularity, and by deconvolution for pulse frequency, mass and amplitude. RESULTS: Reduction of beta-cell mass and secondary hyperglycaemia resulted in correspondingly (r=0.7421, p=0.0275) reduced pulse mass (42% of normal during basal and 31% during entrained conditions) with normal periodicity (6.6+/-2.2 vs 5.8+/-2.4 min, p=0.50), regularity and entrainability of insulin secretion. CONCLUSION/INTERPRETATION: Neither beta-cell loss, nor 2 weeks of slight hyperglycaemia, as seen in the beta-cell-reduced minipig, probably accounts for the disturbed insulin pulsatility observed in human Type 2 diabetes.

Animals↗
PubMed2002

The conscious Göttingen minipig as a model for studying rapid pulsatile insulin secretion in vivo.

AIMS/HYPOTHESIS: Pulsatile secretion is important for insulin action and suitable animal models are important tools for examining the role of impaired pulsatile insulin secretion as a possible link between beta-cell mass, function and morphology and insulin resistance. This study examines the vascular sampling site, insulin kinetics, pulsatility and the response to glucose pulse entrainment to evaluate the Göttingen minipig as a model for studying pulsatile insulin secretion. METHODS: Basal and glucose entrained insulin secretion was examined in normal minipigs and evaluated by autocorrelation, cross correlation and deconvolution. RESULTS: Cross correlation showed a relation between oscillations in insulin concentrations in the portal and jugular vein in anaesthetised animals ( p<0.001 in all animals), confirming the usefulness of jugular vein sampling for pulse detection. Jugular vein sampling in conscious animals showed obvious oscillations allowing estimates of burst shape and insulin kinetics. Glucose entrainment improved the pulsatile pattern (autocorrelation: 0.555+/-0.148 entrained vs 0.350+/-0.197 basal, p=0.054). Deconvolution analysis resolved almost all insulin release as secretory bursts (69+/-20 basal vs 99.5+/-1.2% entrained, p<0.01) with a pulse interval (min) of 6.6+/-2.2 (basal) and 9.4+/-1.5 (entrained) ( p<0.05) and a pulse mass (pmol/l per pulse) which was higher after entrainment (228+/-117 vs 41.2+/-18.6 basal, p<0.001). CONCLUSION/INTERPRETATION: The ability to fit kinetic parameters directly by deconvolution of peripheral endogenous insulin concentration time series in combination with the suitability of jugular vein sampling, rapid kinetics and entrainability makes the Göttingen minipig ideal for mechanistic studies of insulin pulsatility and its effects on insulin action.

Anesthesia, General↗
PubMed2001

Combined PCDD/F destruction and particulate control in a baghouse: experience with a catalytic filter system at a medical waste incineration plant.

Phoenix Services, Inc., owns and operates the Baltimore Regional Medical Waste Incinerator in Baltimore, MD. New regulations for dioxins and furans imposed a limit that was considerably below historical emission levels. To determine a method to comply with the new dioxin/furan regulations, Phoenix Services performed trials with powdered activated carbon (PAC). Although the results with carbon were acceptable, Phoenix Services decided to replace their woven fiberglass filter bags with catalytic filters that simultaneously destroy dioxins and furans and collect particulate matter (PM). The catalytic filter system offered several advantages to Phoenix Services, including destruction of dioxins and furans instead of adsorption on carbon. The catalytic filters also offered a passive solution that did not require new carbon injection equipment. In January 2000, a campaign to measure dioxins/furans and PM was undertaken. The measurements allowed the catalytic filter system to be evaluated. Some of the key findings of this investigation are The dioxin/furan emission was less than 0.1 ng toxicity equivalents (TEQ)/Nm3 at 11% O2. This concentration is approximately 2 orders of magnitude less than historical averages and it is well below the new regulatory limits, for both existing and new sources of this type; the amount of dioxin/furans destroyed by the catalytic filters was approximately 1.73 ng TEQ/Nm3 at 11% O2; and the particulate emission was 12-17 times less than the regulatory limit.

Benzofurans↗
PubMed2001

Parameters of glucose and lipid metabolism in the male Göttingen minipig: influence of age, body weight, and breeding family.

The pig is useful as a model for human physiology and pathophysiology and could be an important supplement to the many available rodent models of diabetes mellitus. Due to their small size, Göttingen minipigs are especially suitable for long-term studies. The aim of the study reported here was to establish reference values for a range of glucose and lipid homeostasis parameters of interest that could be used to identify possible diabetes-prone male Göttingen minipig individuals, families, or age groups. Plasma samples from nonfed animals were analyzed for glucose, leptin, fructosamine, insulin, C-peptide, triglyceride, free fatty acids, and total cholesterol values. Breeding family had significant effects only on plasma triglyceride concentrations (P < 0.001). Plasma concentrations of glucose (P = 0.012), fructosamine (P < 0.001) and triglycerides (P < 0.001) increased significantly with age, whereas total cholesterol concentration decreased significantly (P = 0.001) with age. Age did not influence other parameters. In conclusion, glycemia and insulinemia increased with age and body weight, possibly indicating a small deterioration in insulin sensitivity with age. It is, therefore, hypothesized that older, compared to younger animals may be more useful in the development of a model of type-2 diabetes mellitus. Furthermore, on the basis of decrease in cholesterol concentration with age, animals fed ad libitum with possibly a high calorie diet might be even more useful in the development of a type-2 diabetes mellitus model.

Aging↗
PubMed2000

Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration.

A series of very potent derivatives of the 30-amino acid peptide hormone glucagon-like peptide-1 (GLP-1) is described. The compounds were all derivatized with fatty acids in order to protract their action by facilitating binding to serum albumin. GLP-1 had a potency (EC(50)) of 55 pM for the cloned human GLP-1 receptor. Many of the compounds had similar or even higher potencies, despite quite large substituents. All compounds derivatized with fatty acids equal to or longer than 12 carbon atoms were very protracted compared to GLP-1 and thus seem suitable for once daily administration to type 2 diabetic patients. A structure-activity relationship was obtained. GLP-1 could be derivatized with linear fatty acids up to the length of 16 carbon atoms, sometimes longer, almost anywhere in the C-terminal part without considerable loss of potency. Derivatization with two fatty acid substituents led to a considerable loss of potency. A structure-activity relationship on derivatization of specific amino acids generally was obtained. It was found that the longer the fatty acid, the more potency was lost. Simultaneous modification of the N-terminus (in order to obtain better metabolic stability) interfered with fatty acid derivatization and led to loss of potency.

Acylation↗
PubMed2000

Comparison of methods of analysis of body composition in hypophysectomized rats treated with rat growth hormone.

The present study compared estimates of body composition derived from dual-emission X-ray absorptiometry (DEXA) and from chemical analyses. The primary aim was to compare the two methods because growth hormone (GH) may cause fluid retention, and DEXA does not distinguish water from lean mass. Hypophysectomized rats were fed ad libitum and were treated with continuous infusions of rat GH in doses of 0, 10, 30, and 100 microg/day for 14 days. By chemical analysis, a decrease in percentage fat from 12.9% in the control group to 11.3%, 11.0%, and 10.2% in the low, medium, and high dose groups was observed (P < 0.0001). The fat percentages were about 3-4% higher by DEXA, but showed the same decline (P < 0.03). Lean mass increased from 74.4% in the control group to 75.8%, 78.0%, and 78.6% in the treatment groups (P < 0.001). A significant increase in the wet weight of the quadriceps muscle, but no difference in dry weight was observed in all four treatment groups, indicating that the increase in muscle weight was exclusively caused by water. This accumulation of water was reflected in the total water content of the carcasses, which increased from 62.0% in the control group to 64.9%, 66.1%, and 66.8% in the GH groups (P < 0.0001). The protein content decreased from 19.8% in the control group to 19.4%, 19.1%, and 18.9% in the GH groups (P < 0.001). Regardless of the decrease in protein, the GH treated groups contained more water in relation to protein as the g water/g protein ratio was increased by 13% from 3.14 in the control group to 3.55 in the group treated with the highest GH dose (P < 0.0001). Also, a close relationship between feed intake and body weight were found, together with increases in epiphyseal growth plate width, insulin-like growth factor I (IGF-I), and insulin-like growth factor binding protein 3 (IGFBP-3). In conclusion, the study shows that estimation of lean mass by DEXA should be carefully evaluated when used in connection with treatment of drugs that cause water retention.

Absorptiometry, Photon↗
PubMed1999

A novel inhibitor of advanced glycation end-product formation inhibits mesenteric vascular hypertrophy in experimental diabetes.

AIMS/HYPOTHESIS: Previous studies in our laboratory have shown that the vascular changes in diabetes include hypertrophy of the mesenteric vasculature and that this process can be attenuated by the inhibition of advanced glycation with aminoguanidine. Since aminoguanidine can also act as an inhibitor of nitric oxide synthase, the effect of a novel inhibitor of advanced glycation end-products, formation that does not inhibit nitric oxide synthase, known as 2,3 diaminophenazine (2,3 DAP) was evaluated. METHODS: Initially, in vitro assessment of the ability of 2,3 diaminophenazine to inhibit formation of advanced glycation products was performed. Subsequently, in vivo studies evaluating 2,3 diaminophenazine and aminoguanidine were carried out. Animals were followed for 3 weeks after induction of diabetes and randomised to no treatment, aminoguanidine or 2,3 diaminophenazine. Mesenteric vessels were weighed and advanced glycation end-products were measured by radioimmunoassay in vessel and kidney homogenates. In addition, these products were assessed in mesenteric vessels by immunohistochemistry. RESULTS: When compared with control animals, diabetes was associated with an increase in mesenteric vascular weight. Treatment of diabetic rats with aminoguanidine or 2,3 diaminophenazine resulted in attenuation of vascular hypertrophy. Both aminoguanidine and 2,3 diaminophenazine reduced the formation of advanced glycation end-products as measured by radioimmunoassay and as assessed immunohistochemically in these vessels. This reduction was also observed in the kidney. CONCLUSION/INTERPRETATION: These data support the concept that the effects of aminoguanidine in reducing diabetes associated vascular hypertrophy are via inhibition of advanced glycation end-products dependent pathways.

Animals↗
PubMed1999

Suppression of mycelia formation by NO produced endogenously in Candida tropicalis.

In the experiments reported here we found that enzymatic NO synthesis in the yeast Candida tropicalis resembles the one in animal tissues with respect to the substrate arginine as well as its sensitivity to potential competitive inhibitors. Both, NO produced by the yeast's nitric oxide synthase and NO derived from an artificial donor, suppressed the formation of pseudomycelia. These results suggest to make use of NO as a tool in elucidating the mechanism controlling mycelia generation in this yeast. The apparent K(m) towards oxygen of the yeast's nitric oxide synthase (about 50 microM) was found to be high as compared to the apparent K(m) value of the yeast's respiratory chain (about 170 nM). From this observation it may be concluded that under conditions of little oxygen supply the nitric oxide synthase will unsuccessfully compete for oxygen with respiration. Therefore, the formation of mycelia spontaneously occurring in yeast cultures grown in sealed chambers can be attributed to a reduced internal NO level rather than limited respiratory activity.

Candida↗
PubMed1999

Plasma concentration of hGH and anti-hGH antibodies after subcutaneous administration of hGH for 3 weeks to immunosuppressed pigs.

OBJECTIVE: The objective of the present study was to evaluate the dosing regimen of immunosuppressants necessary to avoid the formation of anti-hGH antibodies in a pig model. ANIMALS: Sixteen pigs were divided into four groups. PROCEDURE: Three different immunosuppressive treatments were tested (group 1: Control (no treatment); group 2: 10 mg; group 3: 20 mg; and group 4: 40 mg cyclosporine; combined with 2 mg azatioprine and 2 mg prednisolone p.o./kg/day). The treatments were given from days -7 to 22. All groups were dosed subcutaneously (s.c.) with 0.5 mg hGH/kg once daily from days 1 to 22. On the first and the last days of dosing blood samples were collected to describe the hGH concentration versus time profile. Before dosing and on days 5, 10, and 15 blood samples were collected for measuring hGH antibody formation. RESULTS: A dose-dependent decrease in white blood cell counts was observed in all immunosuppressive-treated groups. Groups 1 and 2 produced antibodies against hGH during the 22 days of dosing while the formation of antibodies was suppressed in groups 3 and 4. In the control group and group 2 the pharmacokinetic parameters of hGH were influenced by the formation of anti-hGH antibodies. In groups 3 and 4, the pharmacokinetic parameters were comparable on the first and the last day of dosing. CONCLUSION: The formation of anti-hGH antibodies influenced the pharmacokinetics of hGH in pigs, but it could be prevented by immunosuppressive therapy. From the present experiment, a dose of 20 mg cyclosporine, 2 mg azatioprine, and 2 mg prednisolone p.o./kg/day was able to prevent the pigs from producing antibodies without having severe adverse effects. This model may by useful in future experiments using sustained release formulations of hGH, and possibly for other compounds that may induce antibody production in pigs.

Animals↗
PubMed1999

Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats.

The present study was undertaken to study the growth hormone-releasing properties and growth-promoting effect of a GH secretagogue ipamorelin (IPA) in rats given the synthetic glucocorticoid methylprednisolone (MP). In a first experiment, rats received either saline or MP (5.0 mg/kg) for 8 days. Treatment with MP significantly (P< 0.001) decreased body weight gain, but the acute response to either IPA or growth hormone releasing hormone (GHRH) in terms of plasma GH was not changed. In a second experiment, venous catheters were surgically implanted. On the next day, rats were randomly allocated to receive saline alone, MP alone (5.0 mg/kg) or MP plus IPA in doses of 0.4 or 1.6 mg/kg/day for 10 days. IPA was administered intravenously four times a day.MP treatment significantly (P< 0.05) retarded recovery from surgery in terms of body weight. Thus, saline treated animals lost 4.0 +/- 3.5 g over the entire experimental period, whereas animals receiving MP lost 13. 6 +/- 2.9 g. When IPA was given together with MP, losses in body weight were significantly (P< 0.05) reduced to 2.3 +/- 2.0 and 1.6 +/- 2.0 g in animals given the high and low dose of IPA, respectively. In parallel with this IGF-I levels increased. In conclusion, this work shows that MP does not disrupt the response of the GH-IGF-I axis to an exogenous stimulus like IPA, and repeated stimulation leads to increases in IGF-I and of body weight gain.

Animals↗
PubMed1999

Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats.

Ipamorelin is a new and potent synthetic pentapeptide which has distinct and specific growth hormone (GH)-releasing properties. With the objective of investigating the effects on longitudinal bone growth rate (LGR), body weight (BW), and GH release, ipamorelin in different doses (0, 18, 90 and 450 microg/day) was injected s.c. three times daily for 15 days to adult female rats. After intravital tetracycline labelling on days 0, 6, and 13, LGR was determined by measuring the distance between the respective fluorescent bands in the proximal tibia metaphysis. Ipamorelin dose-dependently increased LGR from 42 microm/day in the vehicle group to 44, 50, and 52 microm/day in the treatment groups (P<0.0001). There was also a pronounced and dose-dependent effect on BW gain. The treatment did not affect total IGF-I levels, IGFBPs, or serum markers of bone formation and resorption. The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the metaphysis of the tibia did not change significantly with treatment. The responsiveness of the pituitary to a provocative i.v. dose of ipamorelin or GHRH showed that the plasma GH response was marginally reduced (P<0.03) after ipamorelin, but unchanged after GHRH. The pituitary GH content was unchanged by ipamorelin treatment. Whether ipamorelin or other GH secretagogues may have a place in the treatment of children with growth retardation requires demonstration in future clinical studies.

Animals↗
PubMed1995

State regulatory board structure, regulations, and nurse practitioner availability.

State boards of nursing (BON) and medicine (BOM) promulgate regulations that affect nurse practitioners (NPs). Certain characteristics of board structure have an impact on two potential barriers to NP practice: the absence of direct third-party reimbursement and authority to prescribe. The percentage of consumers on BONs and BOMs increases the likelihood of direct third-party reimbursement for NPs. The presence of an NP committee providing input to a board increases the likelihood of authority to prescribe for NPs. The availability of NPs is enhanced by the presence of NP educational programs in the state, the level of effort by the state related to NP recruitment and retention, and the presence of direct third-party reimbursement.

Humans↗
PubMed1994

Continuous arteriovenous haemofiltration in critically ill children.

We report 24 children with acute renal failure treated with continuous arteriovenous haemofiltration (CAVH) between 1987 and 1991. The median age was 2.9 years (range 3 days to 9 years). The main causes of the acute renal failure were: open heart surgery (n = 11) and liver failure of different origins before and after liver transplantation (n = 10). The indication for CAVH was oliguria or fluid overload in all children. The femoral vessels were used as vascular access in most instances. Different filters were used, depending on the size of the patient and an average ultrafiltration of 130 +/- 89 ml/h was achieved, which resulted in a fluid clearance of 4.0 +/- 2.6 ml/min per 1.73 m2. In 18 patients uraemia was adequately controlled. Nine children survived after recovery of their renal function; 15 (62.5%) died as a consequence of multiorgan failure. We conclude that CAVH is an effective method to support critically ill children with acute renal failure.

Acute Kidney Injury↗
PubMed1994

Atrial baffle procedures for complete transposition of the great arteries: natural course of sinus node dysfunction and risk factors for dysrhythmias and sudden death.

359 patients after the Mustard (275) or Senning (84) operations for transposition of the great arteries were followed-up for a mean of 103.7 (range 0.4 to 204) months. 259 patients had postoperative 24-h Holter recordings. In 129 Mustard children serial (mean 4.4) postoperative Holter recordings were available for evaluation. Criteria based on Holter and scalar electrocardiograms at normal sinus node functions were used for rhythm analysis. Postoperative dysrhythmias appeared in 70% of the patients: sinus node dysfunction in 62.8%, second or third degree atrioventricular block in 3.2%, sustained atrial tachycardia or atrial flutter in 4.5%, and significant ventricular arrhythmia (Lown 2-5) in 21.4%. The prevalence of sinus node dysfunction increased slightly from 50.8% during the first 2 postoperative years to 64.4% in patients more than 10 years postoperatively. Fifteen patients (4.2%) died suddenly during follow-up. By multivariate analysis severe tricuspid regurgitation and/or right ventricular dysfunction and uncontrolled supraventricular tachydysrhythmias were identified as the two significant risk factors for sudden death.

Adolescent↗
PubMed1993

Reliability of a pulse oximeter in the detection of hyperoxemia.

To evaluate the reliability of the Nellcor N200 pulse oximeter in the detection of hyperoxemia (oxygen tension > 80 mm Hg), we obtained 213 simultaneous recordings and measurements of transcutaneous oxygen saturation (SO2) and arterial oxygen tension (PaO2) in 50 patients. During 95% of measurements with PaO2 > 80 mm Hg, SO2 was > or = 96%; SO2 was also > or = 96% in 20% of measurements with PaO2 < or = 80 mm Hg (false-positive results for hyperoxemia). With the upper alarm limit set at 95%, the pulse oximeter identified 95% of hyperoxemic instances while allowing PaO2 to be kept to > 60 mm Hg.

Child, Preschool↗