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Biomedical subjects

M Koskinen

Publications and source records attributed to M Koskinen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Tamoxifen-induced DNA adducts in leucocytes of breast cancer patients.

Tamoxifen-induced DNA adducts were searched in leucocyte DNA from breast cancer patients. Total white blood cell DNA from tamoxifen-treated and control patients was analysed by 32P-postlabelling using HPLC-radioactivity detection. Rat liver DNA was used as a positive standard. In blinded analysis four of the six treated patients showed DNA adducts; none of the five controls were positive. The identity of fraction as a tamoxifen adduct was confirmed by using different chromatographic systems, each with spiked rat liver samples. The level of adducts in the treated patients was 5.5 adducts/10(9) nucleotides as compared to an apparent level of 1.9/10(9) in the controls.

Adult↗
PubMed1996

Determination of the antileukemic drug mitoguazone and seven other closely related bis(amidinohydrazones) in human blood serum by high-performance liquid chromatography.

A reversed-phase (C18) HPLC method with diode-array detection was developed for the separation and determination of methylglyoxal bis(amidinohydrazone) (mitoguazone) and seven closely related aliphatic analogs thereof, namely the bis(amidinohydrazones) of glyoxal, dimethylglyoxal, ethylmethylglyoxal, methylpropylglyoxal, butylmethylglyoxal, diethylglyoxal and dipropylglyoxal. The mobile phase consisted of a non-linear binary gradient of methanol and 0.03 M aqueous sodium acetate buffer (pH 4.3). Good separation of the eight congeners was achieved. On increasing the methanol content of the eluent, the bis(amidinohydrazones) eluted in the order of increasing number of carbon atoms in the side-chains. The method was also applied to the quantitative analysis of the compounds in aqueous solution and, combined with ultrafiltration, for the separation of the eight congeners in spiked human blood serum. A separate simplified method for the quantitative determination of each of the compounds in spiked human blood serum samples was also developed. The methods developed made for the first time possible the simultaneous HPLC analysis of more than one bis(amidinohydrazones). The results obtained indicate that the bis(amidinohydrazones) studied obviously have a distinct tendency to form ion associates with acetate ions and probably also other carboxylate ions in aqueous solution. This aspect may be of biochemical significance, especially concerning the intracellular binding of the compounds. Each one of the compounds studied invariably gave rise to one peak only, this result supporting the theory that the conventional synthesis of each of the compounds gives rise to one geometrical isomer only. This result is completely in agreement with the results of previous proton and carbon NMR spectroscopic as well as X-ray diffraction studies.

Adult↗
PubMed1996

Scatter correction for first-pass radiocardiography.

The effect of the dual window scatter subtraction method was tested for first-pass radiocardiography using 99Tcm. The photopeak window of 126-154 keV (20%) and Compton window of 93-125 keV (30%) were used. The set of scattered images was multiplied by a factor of 0.4 and subtracted from the primary images. The size of the correction was tested by recalculation among a group of 16 patients sent for cardiac output studies for various reasons. The average of the percentage increase following correction was 4.0% (range -1.1 to 11.7%). The size of scatter correction was rather small in individual patients, but consistent for the group of patients as a whole. There was a statistically significant difference between the raw and corrected cardiac output values.

Aged↗
PubMed1996

Biochemical and chemical characterization of phenylglyoxal bis(guanylhydrazone), an aromatic analogue of mitoguazone.

Since little has been known about the properties of aromatic analogues of the antineoplastic agent methylglyoxal bis(guanylhydrazone) (MGBG), an investigation was performed on phenylglyoxal bis(guanylhydrazone) (PhGBG). PhGBG competitively inhibited yeast adenosylmethionine decarboxylase (AdoMetDC) with a Ki of 65 microM. As compared to MGBG (Ki 0.23 microM), PhGBG is a much weaker inhibitor, being even weaker than the unsubstituted congener glyoxal bis(guanylhydrazone) (GBG, Ki 18 microM). PhGBG inhibited porcine kidney diamine oxidase (DAO) non-competitively, being a more potent inhibitor (Ki 0.12 microM) than GBG (Ki 0.17 microM) or MGBG (Ki 0.33 microM). Thus, PhGBG has an unfavourably high ratio of Ki(AdoMetDC)/Ki(DAO) for potential use for selectively inhibiting polyamine biosynthesis. This does not exclude the possibility that PhGBG or other aromatic congeners might have therapeutic value since the corresponding ratio of the antileukaemic congeners GBG and MGBG is also high as compared to many aliphatic non-antileukaemic analogues. The pKa1 and pKa2 values of PhGBG dication were found to be 6.39 +/- 0.02 and 8.64 +/- 0.02 respectively, their difference being distinctly larger than in the case of GBG or its C-alkylated analogues. This may result from decreased stability of the dication form, caused by the resonance effect or possibly by the inductive effect of the phenyl group. The species distribution of PhGBG (proportion of free base 5.5%, predominant species the monocation) at 37 degrees C resembles that of GBG and MGBG but is clearly different from that of non-antileukaemic C-alkylated analogues. These similarities suggest that PhGBG and its derivatives may be worth antitumour screening. Depending on the conditions used in the crystallization, three different types of crystals of PhGBG sulphate were obtained. Crystallography indicated that, in two of the types, the crystal consisted exclusively of the anti-anti isomer, i.e. the same isomer as has been observed in the case of GBG and its C-alkylated congeners. One crystal type, however, consisted of a different geometrical isomer (anti-syn), suggesting that PhGBG may isomerize more easily than its aliphatic analogues. Previous concepts on the isomerism of GBG and C-alkylated bis(guanylhydrazones) thus cannot be generalized to aromatic congeners. A theory based on resonance, inductive and hyperconjugative effects and electron transfers is presented that is capable of explaining the formation of the two geometrical isomers of PhGBG that were experimentally observed. A similar theory, based on hyperconjugation of C-F bonds, is presented that is capable of explaining the previous finding of the formation of the anti-syn isomer of trifluoromethylglyoxal bis(guanylhydrazone) (CF3GBG). Like that of CF3GBG, the anti-syn isomer of the PhGBG dication is stabilized by an internal hydrogen bond. The lack of structural rigidity may affect the biological properties of PhGBG, e.g. its ability to inhibit AdoMetDC.

Animals↗
PubMed1995

Two antireflux operations: floppy versus standard Nissen fundoplication.

The effects of fundic mobilization in Nissen fundoplication on belching ability, abdominal gas volume, bloating and flatus were assessed in a prospective, randomized study of 25 patients with refractory gastro-oesophageal reflux disease. Reflux was cured regardless of fundic mobilization. Subjective ability to belch was restored to preoperative in 73% of the patients with fundic mobilization, compared to 50% without. About 10% in both groups totally lost their ability to belch. Disturbance from flatus increased postoperatively slightly in both groups, but from bloating it remained the same or even diminished. The residual intra-abdominal radioactivity (median (interquartile range)) after provoked belching was preoperatively 8.9% (4.4-12.0) with and 13.2% (6.8-15.2) without fundic mobilization, compared to 36.7% (31.1-40.9) of the controls (P < 0.05). After fundoplication this residual activity was normalized in both study groups. Disturbance from postoperative bloating or flatus were not related to the ability of belching. Preoperatively symptomatic patients tended to have more complaints postoperatively. In conclusion, fundic mobilization restored belching ability slightly more effectively without compromising antireflux efficacy, but there did not seem to be any advantage regarding flatus or bloating.

Adult↗
PubMed1994

Patency of the infarct-related coronary artery--a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy?

The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarct-related coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-123I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (< 70% of maximum) fatty acid uptake was initially 20.2 +/- 4.7 (mean +/- SD) and was reduced to 11.3 +/- 6.1 during the follow-up (95% confidence interval of the decrease 16.0-1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7 +/- 13.1, initial test, and 21.3 +/- 13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗
PubMed1994

Inhomogeneous exercise uptake and accelerated washout of a radioiodinated fatty acid analogue in syndrome X. A SPECT study of the left ventricle.

Myocardial metabolism in exercise was determined by studying 21 syndrome X patients and 14 healthy volunteers with an aromatic fatty acid analogue IPPA and a gamma camera. We developed criteria for visual semiquantitative assessment of relative segmental radiotracer uptake and washout, and tested a new computer program for quantitative evaluation. One volunteer (7%) and 12 patients (57%) showed visually inhomogeneous uptake (p = 0.006, chi 2-test) in SPECT polar tomograms after a maximal ergometry test. Images in none of the volunteers and seven patients (33%) gave the impression of a slowed regional washout (p = 0.057). Only six patients (29%) had a normal radial polarogram. Patients with irregular coronary angiograms (showing 'slow flow' or minor sclerosis) and those with chest pain during the IPPA exercise test had a very low frequency of normalcy, but this was not significant. Total washout was higher in patients than in the reference population, as the exercise to rest activity ratio was 1.36 SD 0.13 versus 1.25 SD 0.11 in computerized quantitation (p = 0.015, t-test). Washout did not correlate with age, sex or exercise heart rate. Regarding computerized analysis of uptake and slow washout, the number of deviant segments was not significantly higher in patients than in reference population. Semiquantitative and quantitative analysis correlated in the assessment of uptake, but not in the assessment of washout. Possible reasons for the discrepancy are discussed. Conclusions of this study are not straightforward. Syndrome X was associated with inhomogeneous IPPA uptake, which is not at variance with the theory of microvascular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Fatty acid exercise scintigraphy after percutaneous transluminal coronary angioplasty.

We performed a sequential fatty acid exercise-rest scintigraphy in 18 patients with an initially successful percutaneous transluminal coronary angioplasty (PTCA) to study the concordance of trends in symptoms, exercise tolerance and myocardial metabolism. Eleven patients stopped the exercise because of angina pectoris in the preoperative test; 2 days after PTCA this number decreased to two, but again increased to eight 3 months later. Exercise time (9.7 +/- 0.6 min, mean +/- SEM) and maximum exercise heart rate (128 +/- 4 beats min-1) were at least as good immediately after the operation as originally (8.8 +/- 0.6 min and 121 +/- 4 beats min-1, respectively). After 3 months both parameters were significantly (P < 0.05) better (10.3 +/- 0.6 min and 136 +/- 4 beats min-1, respectively) than originally. Some relative improvement in washout was noticed in 61% 2 days and in 56% of cases 3 months after PTCA. Fatty acid exercise uptake was more homogeneous in 72% of cases immediately after angioplasty and in 44% 3 months later. The trend in fatty acid uptake, exercise characteristics, and also in symptoms was most favourable among the eight patients with a dilatated left anterior descending coronary artery. Although the gamma camera technique possibly underestimated the effects of angioplasty, the impaired fatty acid metabolism could be linked with persistent symptoms after the operation. We conclude that most patients can safely participate in a symptom-limited (maximal) ergometry test already 2 days after PTCA, and that postoperatively myocardial perfusion and metabolism improve rapidly. However, this advantage is eventually lost to some degree, even if exercise tolerance continues to improve.

Adult↗
PubMed1993

Diagnostic value of 123I-phenylpentadecanoic acid (IPPA) metabolic and thallium 201 perfusion imaging in stable coronary artery disease.

The diagnostic value of 123I-phenylpentadecanoic acid (IPPA) metabolic cardiac imaging was studied in a group (n = 29) of patients with angiographically confirmed CAD using single photon emission computed tomography (SPECT). A symptom-limited exercise test was first done with IPPA, and 2 days later with thallium. Medications were not withheld during testing. Fourteen healthy control subjects participated in parallel IPPA and 15 in thallium tests. Data acquisition and output were comparable in the two imaging modalities. By testing various relatively simple criteria for abnormality we found that the semiquantitative interpretation was more accurate than the visual readings. The best compromise of accuracy with the scored criteria consisted of a sensitivity of 86% and a specificity of 86%, obtained with IPPA polar tomograms (mild exercise defect) and a sensitivity of 86% and a specificity of 80% obtained with thallium (regionally decreased washout). With visual interpretation alone, a sensitivity of 83% and a specificity of 71% was detected with IPPA (mild exercise defect) and 72% and 73%, respectively, with thallium (partial reversibility). The sensitivity of the exercise ECG alone was 62%. The results of this study imply that IPPA imaging could be a rational, uncomplicated clinical method for non-invasive diagnosis of CAD. The diagnostic ability of IPPA is at least as good as that of thallium, and it is possible to use them in succession.

Adult↗
PubMed1993

Fate of Nissen fundoplication after 20 years. A clinical, endoscopical, and functional analysis.

Of 46 patients who had Nissen fundoplication for proved gastro-oesophageal reflux, 25 were available for follow up after a median of 20 years, 15 had died of unrelated causes, and six could not be traced. All 25 patients in the follow up study were personally interviewed: 21 consented to an endoscopy, 14 to 24 hour recording of oesophageal pH and manometry, and 15 to radionuclide transit test. Repeat fundoplication for recurrent reflux was performed in two cases during the study. Heartburn and regurgitation were significantly lessened (p < 0.005), but the incidence of dysphagia was slightly increased. Endoscopy showed six of 21 fundic wraps to be defective. Erosive oesophagitis was seen in two patients, and Barrett's oesophagus (histologically confirmed) in one of them and six other patients. Total reflux time was abnormal in four of 14 patients. No patient with an intact fundic wrap seen on endoscopy, only two of seven with Barrett's oesophagus, and one of four with abnormal reflux had oesophagitis. Fundoplication in itself did not affect oesophageal motility or transit, provided that the wrap was intact. It is concluded that Nissen fundoplication gave a reasonably good longterm effect in chronic reflux disease, with the stage of the fundic wrap as the main determinant of outcome.

Adult↗
PubMed1993

Nifedipine for suspected type II sphincter of Oddi dyskinesia.

Endoscopic sphincterotomy may be the treatment of choice in type I sphincter of Oddi dyskinesia, but in type II dyskinesia the results are controversial, the complication rate may be high, and technically endoscopic sphincterotomy is not always possible. Nifedipine has been observed to relax the sphincter of Oddi and to enhance biliary drainage, especially in patients suffering from sphincter of Oddi dyskinesia. Therefore, nifedipine (10 mg, three times a day) was compared with placebo in treating suspected type II sphincter of Oddi dyskinesia in 13 cholecystectomized patients in a 16-wk study period in a double-blind "cross-over" manner. Daily, the patients completed a diary of the pains, need of pain medication, and headache. Clinical examinations and blood tests for liver chemistry were performed at 4-wk intervals. Nifedipine diminished the number of days on which the patients experienced biliary-type pains (10.5 +/- 8.6 vs. 5.8 +/- 4.1, p = 0.042), and the number of days when pain medication was needed was slightly reduced (5.2 +/- 3.9 vs. 3.6 +/- 3.2, p = 0.066). After the study, one patient preferred to undergo endoscopic sphincterotomy, eight patients preferred to continue with nifedipine, and four patients preferred analgesics only. Liver chemistry remained unchanged in this study. Also heart rate, blood pressure, and the number of days of headache were not different between the nifedipine and placebo periods. We conclude that nifedipine is well tolerated in patients with type II sphincter of Oddi dyskinesia, and nifedipine may be tried for reducing the number of painful days and need for analgesics in patients with this disorder.

Adult↗
PubMed1988

Double blind study on the need for vitamin D supplementation in prepubertal children.

Fifty-one healthy prepubertal schoolchildren were followed for 13 months in a double blind study. Twenty-four of them were supplemented with 400 IU of vitamin D2 5-7 times weekly, while 27 received a placebo. The children were examined in winter both at the beginning and at the end of the study, and in the middle of the study in autumn. Mean 25-hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter, when the study ended. The vitamin D supplementation did not, however, affect other vitamin D metabolites, serum calcium, albumin, inorganic phosphorus, parathyroid hormone concentrations or alkaline phosphatase activity. Moreover, the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children, and thus subclinical rickets could not be shown.

Bone and Bones↗
PubMed1987

Thallium-201 washout in coronary artery disease using SPECT--a comparison with coronary angiography.

In this study, tomographic 201Tl washout analysis and coronary angiography were compared in 100 subjects. Seventeen subjects with healthy coronary arteries were used as reference material, on the basis of which the reference ranges for both the total washout of the heart muscle and the regional washout were determined. With angiography as the standard, this material yielded the following sensitivity values for total myocardial washout: 80% for three vessel proximal disease (n = 30), 64% for peripheral three vessel disease (n = 14), 66% for two vessel disease (n = 29) and 71% for single vessel disease (n = 17). Specificity in the reference group was 94%. Sensitivity values for regional washout were 83%, 93%, 59% and 71%, respectively. Stress ECG gave about 10% lower sensitivities. As far as sensitivity is concerned, however, visual assessment of tomographic images proved to be the best single method. In three patients, washout analysis was necessary to reveal evenly distributed ischemia and in seven cases it was essential in order to confirm an uncertain diagnosis; in other words, washout analysis had diagnostic value in 10 of the 100 patients.

Coronary Angiography↗
PubMed1987

Visual evoked potentials in high-risk infants.

Flash VEPs were recorded in 109 high-risk infants, and the result were compared with the clinical outcome of the infants at the age of one year. 87 of the infants (80%) had a normal outcome and also seemed to have normal VEP maturation. This material was used as a reference for infants with abnormal outcome. Altogether, 20 infants (18%) had abnormal VEPs. In most of these repeated VEPs were recorded. In 70 cases the first VEP was recorded at an age of less than three months. Among these 57 children had normal outcome, with abnormal VEPs in 8 cases (14%). 13 infants who had an abnormal outcome had abnormal VEPs in 7 cases (54%). 7 infants of them had poor outcome, and they had abnormal VEPs in 6 cases (86%). The difference between normal and abnormal outcome was statistically significant. The present results indicate that it is possible to predict the poor outcome but not the moderate abnormality by VEP. The absence of VEP or its abnormal wave form were the most important parameters to predict the prognosis. Our present opinion is that VEPs should be recorded selectively, e.g. according to the findings in ultrasound examination, at least twice, the first time as soon as possible after birth and the second time at the age of two months.

Asphyxia Neonatorum↗
PubMed1987

Intravenous streptokinase treatment and serum C-reactive protein in patients with acute myocardial infarction.

Serum concentrations of C-reactive protein were studied in 23 patients with acute myocardial infarction. In 14 patients who did not receive thrombolytic treatment there was a linear relation between infarct size (determined by serial creatine kinase-MB determinations and thallium-201 isotope emission tomography) and the C-reactive protein response. The correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.96. The correlation coefficient between the creatine kinase-MB concentration-time integral and the peak serum value of C-reactive protein was 0.93. In the nine patients who received intravenous streptokinase treatment there was also a positive correlation between the concentration-time integrals of creatine kinase-MB and C-reactive protein. The relation, however, depended on the success of the treatment. In patients with successful reperfusion the C-reactive protein response was only approximately 20% of that in patients in whom reperfusion failed or who received no thrombolytic treatment and who were matched by infarct size. When thrombolysis was successful the correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.86. Daily measurement of serum C-reactive protein is useful in evaluating infarct size in patients with acute myocardial infarction who do not receive thrombolytic treatment. In patients treated with streptokinase C-reactive protein concentrations may be used to assess the success of thrombolysis.

Aged↗
PubMed1986

Renal perfusion in experimental coarctation of the aorta during antihypertensive therapy.

Renal perfusion and the effectiveness of antihypertensive therapy were evaluated in experimental coarctation. A sham operation was performed at the age of two months on one group of dogs (n = 5); coarctation of the thoracic aorta was produced at the same age in a second group (n = 7) which was not treated with antihypertensive drugs; and coarctation was similarly produced in a third group (n = 6) which was treated with antihypertensive drugs; the drug treatment was begun one month after the coarctation operation. After operation, all dogs were observed for seven months under similar circumstances. With high doses of antihypertensive agents (hydrochlorothiazide 25 mg/day, propranolol 80 mg/day, and prazosin 20 mg/day), the blood pressure decreased significantly in the coarctation with treatment group compared with the coarctation without treatment group. Renal perfusion, when measured by xenon-133 washout at the age of five months, was similar in the coarctation without drug treatment and control groups but significantly lower (23% decrease, p less than 0.01) in the coarctation with drug treatment group; renal perfusion was similar in all three groups when measured at the ages of eight and nine months. The observed temporary decrease suggests a need to evaluate renal perfusion during antihypertensive treatment in coarctation in man.

Animals↗