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Biomedical subjects

J Heinonen

Publications and source records attributed to J Heinonen.

At least 19 recordsLinked to original sources
PubMed2002

Exact and efficient discrete random walk method for time-dependent two-dimensional environments.

We present an exact method for speeding up random walk in two-dimensional complicated lattice environments. To this end, we derive the discrete two-dimensional probability distribution function for a diffusing particle starting at the center of a square of linear size s. This is used to propagate random walkers from the center of the square to sites which are nearest neighbors to its perimeter sites, thus saving O(s(2)) steps in numerical simulations. We discuss in detail how this method can be implemented efficiently. We examine its performance in the diffusion limited aggregation model which produces fractal structures, and in a one-sided step-growth model producing compact, fingerlike structures. We show that in both cases, the square propagator method reduces the computational effort by a factor proportional to the linear system size as compared to standard random walk.

Journal Article↗
PubMed2002

Bisphenol A accumulation in the freshwater clam Pisidium amnicum at low temperatures.

Toxicokinetics of (14)C-labeled bisphenol A (BPA) was studied in the small freshwater clam Pisidium amnicum at four ecologically relevant low temperatures (2, 6, 8, and 12 degrees C). The uptake clearance (k(u)) of BPA increased from 1.49 to 6.55 ml x g(-1) x h(-1) as temperature increased from 2 to 8 degrees C but decreased slightly again at the highest temperature. The depuration of BPA was very slow and statistically insignificant at 2 degrees C, but the depuration rate ( k(d)) increased linearly as temperature increased from 2 to 12 degrees C. The longest half-life of BPA in clam tissues, 221 h, was found at the lowest temperature, and the highest bioconcentration factor of 144 was measured at 8 degrees C. Data show that P. amnicum accumulates BPA so that the bioconcentration factor rises over 100 at each temperature tested. Further, the data demonstrate the importance of temperature on the processes that control both the uptake and elimination of this compound.

Animals↗
PubMed2001

Instability and wavelength selection during step flow growth of metal surfaces vicinal to fcc(001).

We study the onset and development of ledge instabilities during growth of vicinal metal surfaces using kinetic Monte Carlo simulations. We observe the formation of periodic patterns at [110] close packed step edges on surfaces vicinal to fcc(001) under realistic molecular beam epitaxy conditions. The corresponding wavelength and its temperature dependence are studied in detail. Simulations suggest that the ledge instability on fcc(1,1,m) vicinal surfaces is controlled by the strong kink Ehrlich-Schwoebel barrier, with the wavelength determined by dimer nucleation at the step edge. Our results are in agreement with recent continuum theoretical predictions, and experiments on Cu(1,1,17) vicinal surfaces.

Journal Article↗
PubMed2001

Toxicokinetics of waterborne bisphenol A in landlocked salmon (Salmo salar m. sebago) eggs at various temperatures.

Eye-pigmented eggs of landlocked salmon were exposed to waterborne [14C]-labeled bisphenol A at four temperatures (2, 6, 8, and 12 degrees C). Both in accumulation and depuration experiments, the eggs were exposed to a bisphenol A concentration of 1 microg/L for 196 h. In the depuration experiment, the exposed eggs were placed into clean water for 96 h. At each sampling time, the eggs were dissected into three parts (eggshell, embryo, and yolk sac), and all of these parts were weighed and analyzed separately in a liquid scintillation counter. The results show that waterborne bisphenol A accumulates in developing salmon eggs. Accumulation of bisphenol A showed a clear trend both in whole eggs and in dissected parts: the higher the temperature, the higher the uptake rate constant and the concentration of bisphenol A. Steady state was reached only in the embryos at the lowest temperature; in other cases, accumulation was linear. Depuration was significant only in the embryos at 2 and 6 degrees C. As the accumulation and the depuration results show, the elimination of bisphenol A was evidently more significant at lower temperatures.

Animals↗
PubMed2001

Temperature- and parasite-induced changes in toxicity and lethal body burdens of pentachlorophenol in the freshwater clam Pisidium amnicum.

Seasonal variation in abiotic and biotic environments may modify the toxicity of organic chemicals for aquatic organisms. In present study, survival of the freshwater clam Pisidium amnicum was studied in laboratory exposures to pentachlorophenol (PCP) in April (at 5 degress C) and July (at 19 degress C). Behavioral responses, mean survival times (MSTs), and the lethal body burdens (LBBs) of PCP for uninfected clams and for clams infected by digenean trematodes were determined separately in two PCP concentrations, 100 and 300 microgram/L. Analysis of data revealed reduced behavioral activity of the clams in the PCP exposure compared to that in the control. The time needed for toxic responses was greatly affected by temperature; MSTs were 5 to 15 times longer in winter than at summer temperatures. Unexpectedly, the infected clams in summer were more tolerant to PCP than the uninfected clams. Despite the differences in survival times, the LBBs between the seasons were constant. However, in summer, the infected clams had significantly higher LBBs than the uninfected clams. The differences in survival and LBBs between the infected and uninfected clams are suggested to be caused by the high lipid contents found in parasites, which may change the internal distribution of PCP.

Animals↗
PubMed2000

Toxicokinetics of 2,4,5-trichlorophenol and benzo(a)pyrene in the clam Pisidium amnicum: effects of seasonal temperatures and trematode parasites.

Several biotic and abiotic stress factors may affect aquatic organisms simultaneously. However, not much is known about the effects of, e.g., low temperatures and parasite infections on the toxicokinetics of organic hydrophobic chemicals. Here we studied the accumulation and depuration of [(14)C]2,4,5-trichlorophenol (TCP) and [(3)H]benzo(a)pyrene (BaP) in the sediment-dwelling freshwater clam Pisidium amnicum. Experiments were made in October (+15 degrees C), April (+4 degrees C), and July (+15 degrees C) both with uninfected clams and clams infected with Bunodera luciopercae (Trematoda). The accumulation rate for both chemicals was slower at 4 degrees C than at 15 degrees C. The depuration of TCP was biphasic, and the slowest depuration occurred at 4 degrees C. For BaP, the depuration was very slow and monophasic at all temperatures. The highest BCFs for both chemicals were found in July at 15 degrees C. Surprisingly, the BCFs for TCP were higher in April at 4 degrees C than in October at 15 degrees C. For BaP, no steady-state was reached in April. Differences in chemical toxicokinetics between the infected and uninfected clams were only minor. However, for both chemicals a trend of slightly lower BCFs in the infected clams was found. In conclusion, low temperatures modify the toxicokinetics of organic chemicals in P. amnicum and the effects depend on hydrophobicity of the chemical. The effects of parasites on toxicokinetics seem to be small.

Algorithms↗
PubMed1997

Effects of hypoxia on valve-closure time and bioaccumulation of 2,4,5-trichlorophenol by the freshwater clam Sphaerium corneum [L].

The effects of hypoxia and 2,4,5-trichlorophenol (TCP) on the behavior of the freshwater clam Sphaerium corneum (L.) and the accumulation and elimination rates of 2,4,5-trichlorophenol were studied in the laboratory at 20 degrees C. After an initial high activity period, the shell valves were held closed for significantly longer periods in hypoxia than in normoxia. At the end of the 36-hr exposure period, the number of individuals with closed valves increased under normoxic conditions as well. The accumulation of TCP into clam tissues in normoxia was rapid and an uptake rate constant of 27.97 (+/-6.64) ml/g/hr was measured. An apparent steady state was achieved within 12 to 24 hr and the bioconcentration factors varied between 115 and 139. The depuration rate constant (kd) based on the accumulation data was 0.2717 (+/-0.07) hr-1. However, the much lower kd of 0.0137 (+/-0.0019) hr-1 measured over the depuration period from 24 to 120 hr suggests biphasic depuration kinetics. After a 6-hr exposure to TCP in both hypoxia and normoxia, the highest body burdens were found in clams exposed under normoxic conditions. A significant correlation was found between body burden and length of time the valves were open during the exposure. Results suggest that in short-term experiments, S. corneum can reduce the bioaccumulation of TCP by closing their shell valves.

Anaerobiosis↗
PubMed1996

From local to global in quasiconformal structures.

We exhibit a large class of metric spaces whose infinitesimal quasiconformal structure is strong enough to capture the global quasiconformal structure. A sufficient condition for this to happen is described in terms of a Poincaré-type inequality.

Journal Article↗
PubMed1995

Structure and function analysis of Escherichia coli inorganic pyrophosphatase: is a hydroxide ion the key to catalysis?

Using site-directed mutagenesis, we have completed replacing all 17 putative active site residues of Escherichia coli inorganic pyrophosphatase (PPase). We report here the production of 11 new variant proteins and their initial characterization, including thermostability, hydrophobicity, oligomeric structure, and specific activity at pH 8. Studies of the pH-rate profiles of 12 variants containing substitutions for potentially essential residues showed that the effect of the mutation was always to increase the pKa of a basic group essential for both substrate binding and catalysis by 1-3 pH units. The D70E variant had the lowest activity at all pHs; the K29R, R43K, and K142R variants also had low kcat/Km values. The principal effect seen in the other variant proteins was higher and sharper pH optima; their pH-independent kcat and kcat/Km values changed at most by a factor of 8. Our results suggest that the most likely candidate for the essential basic group affected by all mutations in the active site is a hydroxide ion stabilized by coordination to the essential Mg2+ ions. Analyzing our results using the structure recently obtained for E. coli PPase [Kankare et al. (1994) Protein Eng. 7, 823-830] led us to identify a group of residues, centered around Asp70 and including Tyr55, Asp65, Asp67, Asp102, and Lys104, that we believe binds the magnesium ions that are critical for the activity, possibly by stabilizing the essential hydroxide. Others, including Lys29, Arg43, and Lys142, are more spread out and more positively charged. They appear to be involved in binding substrate and product. Tyr55 is also a key part of the hydrophobic core of E. coli PPase; when it or residues that interact with it are conservatively mutated, there are changes in the overall structure of the enzyme as assayed by thermostability, hydrophobicity, or oligomeric structure.

Bacterial Proteins↗
PubMed1995

Extradural, paravertebral and intercostal nerve blocks for post-thoracotomy pain.

Forty-five patients were allocated randomly to receive either a single intrathoracic block of four intercostal nerves, a continuous thoracic extradural infusion or a continuous paravertebral infusion of bupivacaine. Patients were allowed additional i.v. boluses of morphine via a PCA device. Segmental spread of pinprick analgesia was comparable in the groups for up to 20 h. Up to 2 h after the block, plasma concentrations of bupivacaine were greater in the intercostal group and there was large interindividual variation. There were no significant differences between the groups in pain, morphine consumption, respiratory function or adverse events. Moderate to severe respiratory depression was detected in 14 patients more than 2 h after operation.

Adult↗
PubMed1994

Plasma concentration and protein binding of alfentanil during high-dose infusion for cardiac surgery.

We have studied plasma protein binding of alfentanil in 10 patients given a mean total dose of 949 micrograms kg-1 as the principal anaesthetic agent for coronary artery bypass grafting. The mean unbound fraction of plasma alfentanil increased from 0.09 to 0.16 after administration of heparin and to 0.26 after beginning cardiopulmonary bypass (CPB). After CPB until the end of surgery, the unbound fraction decreased to 0.12. These changes in the unbound fraction were associated with significant changes in plasma total and unbound concentrations of alfentanil also. Within the first 1 min of CPB, total alfentanil concentration had decreased by more than the unbound concentration and the decrease observed in the latter disappeared rapidly. From induction of anaesthesia until awakening of the patient, plasma protein binding of alfentanil was related significantly (P = 0.0166) to the serum concentration of orosomucoid (alpha 1-acid glyco-protein).

Aged↗
PubMed1993

Pulmonary vascular effects of trinitroglycerin and isosorbide dinitrate after cardiopulmonary bypass.

We have compared the systemic and right ventricular haemodynamic effects of trinitroglycerin (TNG) and isosorbide dinitrate (ISDN) in patients recovering from coronary artery bypass grafting. Each of the 16 patients was given increasing i.v. doses of the two nitrates in a random order and double blind fashion until the target of a 25% decrease in mean pulmonary artery pressure (MPAP) was achieved. Total doses of TNG 9 (6-12) micrograms kg-1 (mean, 95% confidence interval) and ISDN 148 (76-220) micrograms kg-1 were given during infusions of 22 (18-25) min and 34 (28-41) min duration, respectively. The target decrease in MPAP was produced with infusion rates of TNG 0.5 (0.4-0.7) micrograms kg-1 min-1 and ISDN 5.8 (4.1-7.5) micrograms kg-1 min-1. These doses produced similar acute decreases in MPAP and similar effects on pulmonary and systemic vascular resistances and systemic and right ventricular haemodynamic variables. We conclude that TNG is more than 10 times as potent as ISDN in its acute haemodynamic effects in cardiac surgical patients in the immediate postoperative period. Both nitrates have relatively greater effects on the pulmonary than the systemic vasculature.

Adult↗
PubMed1993

Hydroxyethyl starch as a prime for cardiopulmonary bypass: effects of two different solutions on haemostasis.

Hydroxyethyl starch (HES) is efficacious as a volume expander in cardiac surgical patients, but it may impair the haemostatic mechanisms. However, this latter effect may be less conspicuous with low molecular weight (LMW) solutions than with high molecular weight (HMW) solutions. Therefore, LMW- and HMW-HES solutions were evaluated as priming solutions for cardiopulmonary bypass (CPB) with respect to their effect on haemostasis. Forty-five patients undergoing coronary bypass grafting were prospectively randomised to three groups and received in a double-blind manner as their CPB prime either 20 ml.kg-1 LMW-HES (Mw 120,000), 20 ml.kg-1 HMW-HES (Mw 400,000) or Ringer's acetate 2000 ml. The final volume of the prime was completed to 2000 ml with Ringer's acetate in the HES groups. Anaesthesia and CPB management were standardised. Plasma levels of von Willebrand factor antigen and factor VIII procoagulant activity were significantly more depressed after CPB in both HES-groups as compared with the crystalloid prime group. In addition, APTT was more prolonged and the maximal amplitude of thromboelastographic tracing was more decreased in the HES-groups. It is concluded that it may be advisable to avoid HES solutions in the CPB prime, especially in patients with an increased risk for bleeding after cardiac operations.

Cardiopulmonary Bypass↗
PubMed1992

Vasodilator properties of nitroglycerin and isosorbide dinitrate during cardiopulmonary bypass.

In a placebo-controlled trial, we have studied the vasodilator properties of bolus doses of nitroglycerin (TNG) and isosorbide dinitrate (ISDN) in 32 patients during cardiopulmonary bypass with a constant pump flow. Blood volume of the venous reservoir and mean arterial pressure were recorded for 10 min after drug administration to detect changes in venous capacitance and arteriolar resistance, respectively. The venous capacitance-increasing effects of TNG 200 micrograms and ISDN 1,600 micrograms were initially identical and significant at 2 and 3 min after the bolus. Thereafter, the effect of TNG began to decline, while that of ISDN remained significant until the end of the study. TNG 200 micrograms decreased arterial pressure slightly more than ISDN 1,600 micrograms, but the effect of both drugs lasted for only 1-2 min. TNG and ISDN were equipotent in increasing venous capacitance when administered in a bolus dose ratio of 1:8 during CPB, but the venodilator effect of ISDN lasted longer than that of TNG. The duration of the arteriolar dilator effect was very short with both drugs.

Adult↗
PubMed1992

IV diclofenac in post-thoracotomy pain.

We have studied the efficacy of a continuous i.v. infusion of diclofenac 2 mg kg-1/24 h given for 2 days after major thoracic surgery in 30 patients in a double-blind, placebo-controlled, parallel-group design. The patients were able to obtain additional pain relief as on demand morphine boluses. In the diclofenac group, the consumption of morphine was reduced by 60% during the first and by 76% during the second day after operation compared with the control group. Overall, analgesia was also superior in the diclofenac group. Arterial oxygenation was significantly greater and the arterial PCO2 increased less during the first day after operation in the diclofenac group compared with the control group. Diclofenac had no significant effect compared with placebo on blood loss or on any bleeding or platelet test. Urine output was significantly less during the first day after operation in the diclofenac group compared with the control group, but was normal on the second day after operation; plasma creatinine concentrations were unchanged. I.v. diclofenac infusion combined with opioids delivered via a patient-controlled analgesia device seems a valuable method of pain relief after thoracic surgery in patients in whom more invasive techniques, such as extradural local anaesthetics and opioids, cannot be used. However, non-steroidal anti-inflammatory drugs should be used cautiously, if at all, in patients who are at risk of acute renal failure.

Adult↗