Prostatic MR imaging in the dark.
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Diagnosis, Differential↗
Biomedical subjects
H J Smith
Publications and source records attributed to H J Smith.
Contrast-enhanced MR imaging in the diagnosis and preservation of cardiac viability.
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Animals↗
Effects of transmyocardial revascularization on myocardial perfusion and systolic function assessed by nuclear and magnetic resonance imaging methods.
OBJECTIVE: There is no obvious explanation, except placebo, to the symptomatic effect of transmyocardial laser revascularization (TMR) in patients with refractory angina. Whether TMR improves myocardial perfusion or relieves symptoms without altering cardiac function is not clarified. METHODS: One hundred patients with refractory angina were randomized 1:1 to TMR (CO2 laser) and medical treatment, or medical treatment alone. Technetium 99m (99mTc)-tetrofosmin myocardial perfusion tomography (SPECT), quantitative myocardial perfusion gated SPECT (QGSPECT), technetium 99m (99mTc) multiple gated acquisition radionuclide ventriculografi (MUGA) and cine-magnetic resonance imaging (cine-MRI) were performed at baseline and after 3 and 12 months. RESULTS: Following TMR, a slight reduction in left ventricular ejection fraction (LVEF) (p < 0.05) was observed (MUGA and QGSPECT) compared to baseline. Inclusion of incomplete studies (QGSPECT) revealed a significant reduction in LVEF and increase in left ventricular end-diastolic volume (LVEDV) (p < 0.05) compared to a control group. Otherwise, no between-group comparisons showed statistically significant differences. CONCLUSION: TMR did not improve myocardial perfusion, but led to a reduction in LVEF and increase in LVEDV, however not significantly different from the control group.
Aged↗
Inhibitors of human and rat testes microsomal 17beta-hydroxysteroid dehydrogenase (17beta-HSD) as potential agents for prostatic cancer.
In a screening programme for inhibitors of human testis 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 3), as potential agents for the treatment of hormone-dependent prostatic cancer, we have used crude human testis microsomal 17beta-hydroxysteroid dehydrogenase as a convenient source of the enzyme. Crude human enzyme was shown to have a similar substrate profile to recombinant Type 3 17beta-HSD from the same source as determined by the low Km/Vmax ratio for the reduction of androstenedione compared to the oxidation of testosterone, and a low level of activity in reduction of oestrone. Screening of a wide range of compounds of different structural types as potential inhibitors of the microsomal enzyme in the reduction step revealed that certain p-benzoquinones and flavones/isoflavones were potent inhibitors of the enzyme, diphenyl-p-benzoquinone (2.7 microM), phenyl-p-benzoquinone (5.7 microM), 7-hydroxyflavone (9.0 microM), baicalein (9.3 microM) and biochanin A (10.8 microM). Some structure-activity relationships within the flavone/isoflavone series are discussed. Studies with rat testis microsomal 17beta-HSD showed that it differed from the human enzyme mainly in its greater ability to accept oestrone as substrate and the pH-optimum for oxidation of testosterone. It was found to be much less sensitive to inhibition by the compounds studied so negating it use as a more readily available tissue for the screening of potential inhibitors.
17-Hydroxysteroid Dehydrogenases↗
Enantioselectivity of some 1-[(benzofuran-2-yl) phenylmethyl] imidazoles as aromatase (P450AROM) inhibitors.
The enantioselectivity ratio ((+)-:(-)-forms) of three substituted 1-[(benzofuran-2-yl) phenylmethyl] imidazoles as inhibitors of aromatase (P450AROM) was 2.16, 12.3 and 1.0 for the 4-methyl-, 4-fluoro- and 4-chloro-substituted compounds, respectively. The (+/-)-compounds were all >1000 times more potent than (+/-)-aminoglutethimide (IC50 = 12 x 10(3) nM). High potency (5.3-65.0 nM) for all the enantiomers studied is unusual since activity usually resides in one form for chiral inhibitors of P450AROM. The 4-methyl derivative was fitted into the model [Furet, P., Batzl, C., Bhatnager, A.S., Francotte, E., Rihs, G. and Lang, M. (1993) J. Med. Chem. 36, pp. 1393-1400] for binding of S-(-)-fadrazole to the active site and the (R)- and (S)- forms both gave a good fitting pattern with (S)-(-)-fadrazole so accounting for their close activity. Docking of both forms into the active site model for P450AROM [Laughton, C.A., Zvelebil, M.J.J.M. and Neidel, S. (1993) J. Steroid Biochem. Mol. Biol. 44, pp. 399-407], using the orientation of (S)-(-)-fadrazole, gave similar strong binding along the position of the C and D rings of the steroid substrate and in the hydrophobic cavity below the A/B rings. The site was probed for group size accommodation using the less potent 4-phenyl analogue (IC50(+/-) = 242 nM): the (S)-form showed restricted access to the region under the A ring due to the extended bulk of the biphenyl group.
Animals↗
Graft control by transit time flow measurement and intraoperative angiography in coronary artery bypass surgery.
BACKGROUND: The aim of this study was to compare the relationship between intraoperative transit time flow measurements and angiographic findings with long-term graft patency in 72 patients who underwent coronary artery bypass surgery. METHODS: Transit time flow measurements with recording of mean flow and pulsatility indexes were performed after completion of the anastomoses. Coronary angiography was performed on-table while the patients were still in general anesthesia, and then at follow-up three months and 12 months after surgery. Based on angiography, the grafts were graded as type A (fully patent), type B (having more than 50% diameter reduction), or type O (occluded). RESULTS: Of the 67 left internal mammary artery (LIMA) grafts, 51 (76%) were type A on-table, 14 (21%) were type B, and two (3%) were type O. Of the 57 saphenous vein grafts, 49 (86%) were type A, 7 (12%) were type B, and one (2%) was type O. For both LIMA and vein grafts, there were no differences in flow (p = 0.69 and 0.47, respectively) or pulsatility index (p = 0.79 and 0.83) between type A and B. There were also no differences in flow (p = 0.37 and 0.7) or pulsatility index (p = 0.37 and 0.24) between type B on-table that either normalized or persisted occluded at the follow-up. Transit time flow measurement failed to detect an occluded LIMA graft as shown by intraoperative angiography. CONCLUSIONS: Blood flow measurements performed intraoperatively could not identify significant lesions in arterial or vein grafts, and could not predict graft patency. We have become cautious in interpreting flow measurements alone and combine blood flow recordings with intraoperative angiography in the assessment of graft quality.
Aged↗
[Magnetic tomography--new imaging techniques and future perspectives].
BACKGROUND: From the very introduction of MRI into medicine, the modality has presented the user a long list of theoretical tissue contrast parameters. The development of MRI has been aimed at turning these theoretical possibilities into practical options. MATERIAL AND METHODS: We give an overview of the new MRI techniques and perspectives for the future based on a literature search and our own experience. RESULTS: Today, the modality offers state-of-the-art anatomical details as well as visualisation of several functional parameters such as perfusion, diffusion, blood oxygen saturation, and tissue temperature. In the near future, MRI may provide absolute quantification of regional perfusion and rate of oxygen consumption in a clinical setting. New vascular and gastrointestinal contrast media will further increase the sensitivity and specificity of MRI. A continuous increase in imaging speed has made MRI capable of providing adequate "fluoroscopic" guidance during interventional procedures, and real-time diagnostic imaging is only few years ahead. INTERPRETATION: The spread of MRI installations will increase as a result of increasing demand for the best and least harmful diagnostic procedure. The main challenge to the MRI community will be to exploit the vast diagnostic possibilities.
Blood Circulation↗
[Magnetic resonance angiography].
INTRODUCTION: MR angiography (MRA) is a group of MRI techniques capable of producing projectional images of arteries and veins without the use of ionising radiation or catheters. MATERIAL AND METHODS: This review describes two of the main techniques, time-of-flight (TOF) MRA and phase contrast MRA, that provide high signal-intensity vessels due to flow phenomena, and a third main technique, contrast-enhanced MRA, which relies on intravenous injection of contrast media. Contrary to the iodine-containing x-ray contrast media, the contrast media for MRA are not nephrotoxic, making contrast-enhanced MRA a good alternative for patients with reduced renal function. MRA is indicated in several vascular areas, especially head and neck arteries and veins, the large thoracic and abdominal arteries and veins, and the lower extremity arteries. INTERPRETATION: For several indications, the sensitivity and specificity of MRA is approaching those of the gold standard, x-ray angiography. There are reasons to believe that most diagnostic angiographic procedures will soon be performed as MRA.
Aortography↗
[Magnetic resonance tomography of the heart].
Magnetic resonance imaging is a rarely performed procedure in cardiac disease, mainly due to easily available alternative techniques, especially echocardiography. MR imaging may, however, provide unique anatomical and functional information and represents a valuable supplement to the alternative invasive and non-invasive modalities. Clinical indications for MR imaging of the heart include congenital heart disease, acute and chronic ischaemic heart disease, valvular heart disease, cardiomyopathy, right ventricular dysplasia, pericardial disease, and cardiac tumours. In the near future, MR imaging may provide a complete "one-stop" evaluation of cardiac disease.
Cardiomyopathies↗
[Magnetic resonance--historical and theoretical basis].
Magnetic resonance (MR) imaging is a fast developing modality that has become an indispensable diagnostic tool at numerous disease states. The first MR imager in Norway was installed in 1986; by the end of 1999 Norway will have a total of 39 units, approximately one unit per 114,000 inhabitants. MR technique uses radiowaves and magnetic fields, and no ionising radiation is involved. Imaging is based on the fact that all biological tissues are magnetized when placed in a strong, static magnetic field. Short radiofrequency pulses set the tissue magnetic vector into rotation, and the vector induces electric currents in a receiver coil. The electric signals are spatially encoded by means of magnetic field gradients, thus enabling image reconstruction by means of Fourier transformation. The signal intensities can be made dependent on several tissue parameters, thus creating several unique image contrast possibilities.
Brain↗
[Magnetic resonance angiography].
INTRODUCTION: MR angiography (MRA) is a group of MRI techniques capable of producing projectional images of arteries and veins without the use of ionising radiation or catheters. MATERIAL AND METHODS: This review describes two of the main techniques, time-of-flight (TOF) MRA and phase contrast MRA, that provide high signal-intensity vessels due to flow phenomena, and a third main technique, contrast-enhanced MRA, which relies on intravenous injection of contrast media. Contrary to the iodine-containing x-ray contrast media, the contrast media for MRA are not nephrotoxic, making contrast-enhanced MRA a good alternative for patients with reduced renal function. MRA is indicated in several vascular areas, especially head and neck arteries and veins, the large thoracic and abdominal arteries and veins, and the lower extremity arteries. INTERPRETATION: For several indications, the sensitivity and specificity of MRA is approaching those of the gold standard, x-ray angiography. There are reasons to believe that most diagnostic angiographic procedures will soon be performed as MRA.
Aortography↗
Iron chelating agents for treating malaria.
BACKGROUND: Mortality from Plasmodium falciparum malaria remains high; death and sequelae occur in even in patients treated with antimalarial drugs. Researchers are exploring the effects of adding treatments to the main antimalarial regimens in an attempt to reduce mortality. Iron chelation is one potential chemotherapeutic adjuvant treatment. Before advocating adjunctive therapy, the effects of iron chelators in improving patient outcomes needs to be examined. OBJECTIVES: To assess the effects of iron-chelating agents combined with antimalarial drugs, or iron chelators alone, for treating Plasmodium falciparum malaria in adults and children, in relation to mortality, coma recovery time, parasite clearance, and adverse effects. SEARCH STRATEGY: Electronic searches of the Cochrane Library, MEDLINE, and EMBASE, using the standard Cochrane search strategy. Bibliographies of retrieved studies were scrutinized in order to identify further relevant trials. Organisations, experts and other individuals in malaria research were contacted for unpublished studies. SELECTION CRITERIA: All randomised controlled trials of adults or children with P.falciparum malaria. DATA COLLECTION AND ANALYSIS: Trials were identified and extracted by a single reviewer (HS) and checked by a second (MM). Inclusion criteria were applied, and data were extracted independently by both reviewers. Authors were contacted for missing and additional data. Meta-analysis used Relative Risk (RR) and 95% Confidence Intervals. MAIN RESULTS: No evidence of benefit or harm were shown in relation to mortality, but studies were small, and one trial was tending towards more deaths with the intervention when it was stopped. The risk of experiencing persistent seizures was significantly lower with desferrioxamine compared to placebo treatment (RR 0.80, 95% CI 0.67 to 0.95). Many adverse effects were more common in participants treated with desferrioxamine. REVIEWER'S CONCLUSIONS: Trends suggestive of both harm (death) and potential benefit (fewer seizures) are demonstrated in this review. It is not possible to comment on time to event outcomes that include coma recovery or parasitaemia as we are clarifying data with the trialists. Whether to conduct further trials will depend on a judgement about potential benefit.
Adult↗
Blood transfusion for treating malarial anaemia.
BACKGROUND: Blood transfusion is used in patients with severe malarial anaemia, but risks adverse reactions, transmission of disease, and is complicated to organise in developing countries. OBJECTIVES: This review evaluates the effects of routine blood transfusion for severe anaemia on death and adverse outcomes in malarious areas. SEARCH STRATEGY: The Cochrane Controlled Trials Register, African Index Medicus, LILACS, EMBASE and reference lists of relevant articles, and contact with researchers and organizations working in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of blood transfusion compared with conservative management in malaria-associated severe anaemia. DATA COLLECTION AND ANALYSIS: Trials were identified and extracted by a single reviewer (MM) and checked by a second (HS). Inclusion criteria were applied and data were extracted independendtly by both reviewers. MAIN RESULTS: Two randomised trials of 230 children were included. In the transfusion group, there was a non-significant tendency towards fewer deaths (RR 0.41, 95% CI 0.06 to 2.70), but significantly more severe adverse events (RR 8.60, 95% CI 1.11 to 66. 43). In one trial by Bojang (1997a) respiratory distress was less common and hospital stay was shorter in the transfusion group (WMD 1.9 days, 95% CI 2.4 to 1.3). Subsequent need for urgent blood transfusion was less common in the transfusion group (RR 0.11, 95% CI 0.02 to 0.62). Day 28 packed cell volume was less in the transfusion group (WMD -1.34, 95% CI -2.57 to -0.11). There was no information on HIV or Hepatitis B virus transmission. REVIEWER'S CONCLUSIONS: There is insufficient data to be sure whether routinely giving blood to clinically stable children with severe anaemia in endemic malarious areas reduces death, or results in higher haematocrit measured at one month.
Adult↗
Dynamic MR-imaging in the diagnosis of pigmented villonodular synovitis of the knee.
The aim of this report was to study the rate of contrast enhancement at MRI in pigmented villonodular synovitis (PVNS). Dynamic MRI was performed in a patient with PVNS just before and 1 week and 3 years following synovectomy of the knee. As opposed to patients with rheumatic disease the patient with PVNS showed a slower enhancement rate before synovectomy than 1 week after. At 3 years follow-up the patient with PVNS showed an enhancement rate just above that of the normal controls. The results indicate that PVNS has features more common to hyperplastic or neoplastic lesions than to inflammatory ones. The results at 3 years follow-up also suggest that dynamic MRI may indicate the efficacy of arthroscopic synovectomy.
Adolescent↗
A comparison of four quality of life instruments in cardiac patients: SF-36, QLI, QLMI, and SEIQoL.
BACKGROUND: With the increasing use of quality of life measures in evaluations of cardiac interventions, criteria are needed for selecting appropriate quality of life measures. An important criterion is the sensitivity of a measure for detecting clinically important changes. OBJECTIVES: To compare the sensitivity of four measures when used in a group of cardiac patients undergoing the same intervention. METHODS: The short form 36 (SF-36), the quality of life index-cardiac version (QLI), the quality of life after myocardial infarction questionnaire (QLMI), and the schedule for the evaluation of individual quality of life (SEIQoL) were used to evaluate quality of life in a group of 22 patients after myocardial infarction or coronary artery bypass graft (CABG), at the beginning of rehabilitation and six weeks later. Analysable data were obtained from 16 patients. RESULTS: A significant improvement over time was only observed for the SF-36 subscale, vitality (p < 0.05). Five of the eight SF-36 subscales and one of the four QLMI subscales showed modest sensitivity (index: > 0.2 and < 0.5), while all other subscales showed poor sensitivity (index: < 0.2). Using SEIQoL, family was most often nominated as an area of importance to quality of life (n = 13), followed by health (n = 10), leisure/hobbies (n = 8), marriage (n = 8), and work (n = 6). CONCLUSIONS: All four QOL measures used in this study were found to lack sensitivity to change. Further research is needed using other cardiac populations and interventions in order to verify these findings, with a view to developing more sensitive quality of life scales.
Coronary Artery Bypass↗
Effect of P450 isozyme-selective inhibitors on in-vitro metabolism of retinoic acid by rat hepatic microsomes.
Cytochrome P450-mediated 4-hydroxylation of retinoic acid is an important pathway in the termination of its biological action and the activity of certain P450 isozymes has been studied in non-induced male rat hepatic microsomes using isozyme-selective inhibitors. The importance of the activity of the isozyme to retinoic acid metabolism was, 2A6 (diethyl dithiocarbamate as selective inhibitor) > 1A1/1A2 (7,8-benzoflavone) >> 1A1 (ellipticine) > 3A4 (naringenin, ketoconazole) as shown by the respective apparent IC50 values of 0.12, 0.34, 2.7, 9.25 and 13.5 microM with 2C8-10, 2D6 and 2E1 having little effect on metabolism. It is concluded that although the P450 3A family normally constitutes half the total rat hepatic P450 activity, other hepatic isozymes (1A1, 1A2 and 2A6) are also involved in retinoic acid metabolism. This suggests that the horizons for the design of potential anticancer agents acting through inhibition of retinoic acid metabolism may be widened to include structures which do not resemble the established hetereocyclic base P450 3A4 inhibitors.
Animals↗
In-vitro metabolism of retinoic acid by different tissues from male rats.
Significant differences between the metabolism of retinoic acid by different tissues might be an important determinant of the effectiveness of a systemically administered inhibitor at a particular tissue site. Here the metabolism of retinoic acid has been studied in microsomal fractions from different tissues (liver, kidney, intestinal mucosa, lung, skin, brain) of the male rat to determine their relative metabolic activity. Kinetic analysis revealed major differences between the activity of different tissue microsomes. This is shown by the Vmax values for the metabolism of retinoic acid-liver (102+/-39.0 pmol (mg protein)(-1) min(-1)) was 100 times more active than the lung (1+/-0.03 pmol (mg protein)(-1) min(-1)), which was the least active. The range of Km values for microsomes from the different tissues was narrow (0.48-1.40 microM). Taking into account the mass of the tissue, the gross activity ranking for metabolism of retinoic acid was liver >> skin = kidney > brain > intestinal mucosa >> lung. It is concluded that metabolism of administered retinoic acid occurs mainly in the liver but that cellular retinoic acid levels in some other tissues (skin, kidney, brain) could be reduced (metabolized) to such an extent that higher levels might be observed after the use of inhibitors of retinoic acid metabolism.
Animals↗
Dynamic MR imaging of mandibular osteoradionecrosis.
PURPOSE: Osteoradionecrotic bone has been characterised as hypovascular and metabolically inactive tissue with impaired perfusion. The present study was conducted to determine if dynamic contrast-enhanced MR imaging could provide additional information about the vascularity of radionecrotic mandibular bone. MATERIAL AND METHODS: Dynamic contrast-enhanced MR imaging was performed on 10 patients with mandibular osteoradionecrosis (ORN), and on 6 patients, irradiated for oropharyngeal tumours, without symptoms or signs of ORN. Nine patients in the ORN group received a series of 20 hyperbaric oxygen (HBO) treatments, after which the dynamic MR investigation was repeated. RESULTS AND CONCLUSION: Radiation per se did not lead to increased contrast enhancement, whereas all patients with ORN showed marked contrast enhancement of the osteoradionecrotic bone marrow. After HBO treatment, pathological contrast enhancement of the abnormal bone marrow could still be seen, but the rate of enhancement was less than before in 7 of 9 patients. Two patients had an increase in the enhancement rate. The findings suggest the existence of an increased and patent microvasculature.
Adult↗