Effects of B-type natriuretic peptide on cardiovascular biomarkers in healthy volunteers.

Cardiovascular biomarkers provide independent prognostic information in the assessment of mortality and cardiovascular complications. However, little is known about possible interactions between these biomarkers. In the present study, we evaluated the influence of B-type natriuretic peptide (BNP) on midregional-proadrenomedullin (MR-proADM), C-terminal-proendothelin-1 (CT-proET-1), growth differentiation factor-15 (GDF-15), midregional-proatrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin in healthy volunteers. Ten healthy male subjects (mean age 24 yr) participating in a randomized, placebo-controlled, single-blinded crossover study received placebo or 3.0 pmol·kg(-1)·min(-1) human BNP 32 during a continuous infusion lasting for 4 h. Effects of BNP on other cardiovascular biomarkers were assessed. BNP did not change concentrations of MR-proADM, copeptin, CT-proET1, GDF-15, or procalcitonin. In contrast, MR-proANP was significantly decreased during BNP infusion. BNP as an established cardiovascular biomarker did not affect plasma concentrations of other cardiovascular biomarkers in a model of healthy volunteers.

Observation of a reflected shock in an indirectly driven spherical implosion at the national ignition facility.

A 200 µm radius hot spot at more than 2 keV temperature, 1 g/cm^{3} density has been achieved on the National Ignition Facility using a near vacuum hohlraum. The implosion exhibits ideal one-dimensional behavior and 99% laser-to-hohlraum coupling. The low opacity of the remaining shell at bang time allows for a measurement of the x-ray emission of the reflected central shock in a deuterium plasma. Comparison with 1D hydrodynamic simulations puts constraints on electron-ion collisions and heat conduction. Results are consistent with classical (Spitzer-Harm) heat flux.

A severe case of haemodynamic instability during anidulafungin administration.

WHAT IS KNOWN AND OBJECTIVE: Anidulafugin is an echinocandin used for the treatment of candida infections in non-neutropenic adults. Echinocandins show few drug-drug interactions and are usually well tolerated. We report a case of acute hypotension, bradycardia and haemodynamic instability with consecutive cardiopulmonary resuscitation during anidulafungin administration. CASE SUMMARY: A 41-year-old man ICU patient received anidulafungin for a suspected Candida glabrata infection. During the first administration of the drug, he developed acute haemodynamic instability with hypotension and bradycardia. The infusion was discontinued immediately and cardiopulmonary resuscitation was performed successfully. The patient regained haemodynamic stability. WHAT IS NEW AND CONCLUSION: To the authors' knowledge, this is the first report of a life-threatening adverse event due to haemodynamic instability during anidulafungin administration. Cardiac toxicity associated with echinocandins has been described. Further studies seem to be mandatory to investigate this potential risk.

Sex differences in the association between albumin and all-cause and vascular mortality.

BACKGROUND: Low serum albumin levels are associated with cardiovascular disease and mortality risk. This study evaluated the predictive value of low serum albumin for all-cause-mortality in a large Viennese patient cohort and investigated sex differences in the association between serum albumin and mortality. MATERIALS AND METHODS: Serum albumin concentrations of 285 930 patients, who attended the General Hospital Vienna between 1992 and 2002, were evaluated and linked with the Austrian Death Registry. The median observation period was 7.4 +/- 4.0 years and the death rate was 16.8%. For Cox regression analysis, albumin levels were divided into deciles, the highest category served as reference value. To analyse associations between albumin and mortality independent of liver function, results were adjusted for cholinesterase, which indicates protein synthesis capacity of the liver. RESULTS: Hazard ratios for all-cause-mortality increased linearly with decreasing albumin levels from 1.05 in the 9th to 2.98 in the 1st decile. Adjusted for cholinesterase, the relative risk for mortality was still 1.91 in the lowest category. Compared with women, men had an average 50% increased risk of death in almost every decile, adjusting for cholinesterase reduced the sex difference to a 10-20% higher mortality risk for men. In critically ill patients, hazard ratios for all-cause-mortality ranged from 4.5 in the 9th decile to 9.5 in the lowest albumin category. CONCLUSION: This study demonstrates a strong inverse association between serum albumin and mortality in a large patient cohort. The predictive value of low albumin was remarkably higher in men than in women.

A quantitative-genetic analysis of hippocampal variation in the mouse.

This report analyses the genetic underpinnings of the proportions of the hippocampal terminal fields in the mouse at the midseptotemporal level. We used 5 inbred strains and all possible F(1) crosses between them (diallel cross). Broad heritabilities ranged from 11 to 53%. Additive genetic variation was present for all phenotypes analyzed. Directional dominance was found for the relative size of the suprapyramidal mossy fiber terminal field only. For the stratum lacunosum-moleculare, ambidirectional dominance emerged. These findings suggest that, in evolutionary history, directional selection has operated for a proportionally large suprapyramidal terminal field. For all other hippocampal variables (viz. the relative sizes for the strata oriens, pyramidale, radiatum, lacunosum-moleculare, CA4, intra- and infrapyramidal mossy fiber terminal field and the absolute size of the regio inferior) past stabilizing selection was inferred.

The evolution of dioecy, heterodichogamy, and labile sex expression in Acer.

The northern hemisphere tree genus Acer comprises 124 species, most of them monoecious, but 13 dioecious. The monoecious species flower dichogamously, duodichogamously (male, female, male), or in some species heterodichogamously (two morphs that each produce male and female flowers but at reciprocal times). Dioecious species cannot engage in these temporal strategies. Using a phylogeny for 66 species and subspecies obtained from 6600 nucleotides of chloroplast introns, spacers, and a protein-coding gene, we address the hypothesis (Pannell and Verdú, Evolution 60: 660-673. 2006) that dioecy evolved from heterodichogamy. This hypothesis was based on phylogenetic analyses (Gleiser and Verdú, New Phytol. 165: 633-640. 2005) that included 29-39 species of Acer coded for five sexual strategies (duodichogamous monoecy, heterodichogamous androdioecy, heterodichogamous trioecy, dichogamous subdioecy, and dioecy) treated as ordered states or as a single continuous variable. When reviewing the basis for these scorings, we found errors that together with the small taxon sample, cast doubt on the earlier inferences. Based on published studies, we coded 56 species of Acer for four sexual strategies, dioecy, monoecy with dichogamous or duodichogamous flowering, monoecy with heterodichogamous flowering, or labile sex expression, in which individuals reverse their sex allocation depending on environment-phenotype interactions. Using Bayesian character mapping, we infer an average of 15 transformations, a third of them involving changes from monoecy-cum-duodichogamy to dioecy; less frequent were changes from this strategy to heterodichogamy; dioecy rarely reverts to other sexual systems. Contra the earlier inferences, we found no switches between heterodichogamy and dioecy. Unexpectedly, most of the species with labile sex expression are grouped together, suggesting that phenotypic plasticity in Acer may be a heritable sexual strategy. Because of the complex flowering phenologies, however, a concern remains that monoecy in Acer might not always be distinguishable from labile sex expression, which needs to be addressed by long-term monitoring of monoecious trees. The 13 dioecious species occur in phylogenetically disparate clades that date back to the Late Eocene and Oligocene, judging from a fossil-calibrated relaxed molecular clock.

Receptor activator of nuclear factor kappaB ligand and osteoprotegerin in men with thyroid cancer.

BACKGROUND: Suppressive thyroid hormone therapy is generally a lifelong treatment for patients with differentiated thyroid cancer (DTC). However, long-standing thyrotropin (TSH) suppression is a risk factor for osteoporosis. Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are central regulators of bone turnover. The aim was to analyze the effects of a suppressive thyroid hormone therapy in males with DTC on the OPG/RANKL system and on bone metabolism. PATIENTS AND METHODS: The OPG and soluble RANKL (sRANKL) were determined in 40 men (mean age, 53.2 years) with DTC on suppressive thyroid hormone therapy (TSH; 0.053 +/- 0.037 mU L(-1), duration 5.7 +/- 4.4 years) and 120 healthy controls matched for age. The markers of bone metabolism were C-terminal telopeptide of type I collagen in serum (sCTx) and osteocalcin (OC). RESULTS: The control group had OPG values (mean +/- SD) of 1.9 +/- 1.0 pmol L(-1) and sRANKL values of 0.40 +/- 0.62 pmol L(-1). In patients with DTC, results for OPG were 3.03 +/- 1.04 pmol L(-1) (P < 0.05) and for sRANKL were 0.13 +/- 0.16 pmol L(-1) (P < 0.05). The control group presented values for sCTx of 2669 +/- 1132 pmol L(-1) and for OC of 17.89 +/- 6.5 ng mL(-1). Patients with DTC on suppressive thyroid hormone therapy had increased sCTx values of 3810 +/- 2020 pmol L(-1) (P = 0.03) but comparable OC values of 19.21 +/- 7.67 ng mL(-1) (NS). CONCLUSIONS: Suppressive thyroid hormone therapy in men with DTC increased bone degradation and induced significant changes in the OPG/RANKL system. These changes include, besides the risk of osteoporosis, possible negative effects on the vascular function and an increased risk of cardiovascular disease.

[Three-dimensional vectorcardiography to predict CRT-responder]. / Dreidimensionale Vektorkardiographie zur CRT-Responderbestimmung.

Cardiac resynchronization therapy (CRT) is an accepted treatment for congestive heart failure (NYHA III-IV), but a substantial number of patients show no response to therapy. LBB, QRS width and echocardiographic measurements are parameters for indication, but they are not valid to predict hemodynamic response. A new method based on vector ECG analysis can deliver additional information, such as: parts or areas with late excitation, and with slow or fast depolarization speed. Electrical excitation is a prerequisite for contraction; this leads to the hypothesis that areas with late electrical activation will contract later. Algorithms for analysis of the vector ECG (determination of the vector -- time, area and speed) may help to identify responders and non-responders.

Design and simple routes of synthesis of oligonucleotide conjugates for studies of DNA triple helix formation.

A series of oligonucleotides conjugated to intercalators, as well as fluorescent and lipophilic substances, minor groove binders and photoactive molecules were synthesized for studies of their ability to form a stable triple helix. Purine-rich short double stranded DNA fragments from HIV-1 genome and pyrimidine 16-mer oligodeoxyribonucleotide were used as models. A conjugate of a dipyrido[3,2-a:2',3'-c]phenazine-ruthenium (II) complex and a triple helix-forming oligonucleotide was constructed. Upon sequence-specific duplex and triplex formation of the conjugate, the ruthenium complex becomes highly fluorescent. The attached ruthenium complex induces a stabilization of the DNA triple helix and a significant increase of the time of residence of the third strand on the duplex.

[Stabilization of DNA triple helix using conjugates of oligonucleotides and synthetic ligands]. / Stabilizatsiia troinykh spiralei DNK s pomoshch'iu kon"iugatov oligonukleotidov i sinteticheskikh ligandov.

Possibility of stabilization of DNA triple helix is discussed using a covalent conjugation to the third strand (through its terminal phosphate) of ligands that have affinity to double and triple helices. Two types of stabilizers are considered: minor groove binders based on oligopyrroles and triplex-specific interacalators. As a target, a synthetic 29-mer duplex containing a natural polypurinic sequence of the human immunodeficiency provirus was employed. The stabilization with minor groove binders requires several conditions to be respected: a sufficiently long linker capable of reaching out the minor groove from the major one, a specific double-stranded structure of the oligopyrrole fragment and its in-phase fitness to the target sequence. The best stabilizers of a triplex turned out to be novel conjugates in which two parallel molecules containing six pyrrole units each are linked to the same 5'-phosphate of a 16-mer triplex-forming oligonucleotide. The stabilizing properties of these derivatives were comparable with those of benzoindoloquinoline (BIQ) intercalators attached to the terminal phosphate of triple-helix forming oligonucleotides.

tert-Butoxyl radicals generate mainly 7,8-dihydro-8-oxoguanine in DNA.

Like hydroxyl radicals, alkoxyl radicals have been implicated in the generation of cellular oxidative DNA damage under physiological conditions; however, their genotoxic potential has not yet been established. We have analyzed the DNA damage induced by a photochemical source of tert-butoxyl radicals, the water soluble peroxy ester [4-(tert-butyldioxycarbonyl)benzyl]triethylammonium chloride (BCBT), using various repair endonucleases as probes. The irradiation (UV(360)) of BCBT in the presence of bacteriophage PM2 DNA was found to generate a DNA damage profile that consisted mostly of base modifications sensitive to the repair endonuclease Fpg protein. Approximately 90% of the modifications were identified as 7,8-dihydro-8-oxoguanine (8-oxoGua) residues by HPLC/ECD analysis. Oxidative pyrimidine modifications (sensitive to endonuclease III), sites of base loss (AP sites) and single-strand breaks were only minor modifications. Experiments with various scavengers and quenchers indicated that the DNA damage by BCBT+UV(360) was caused by tert-butoxyl radicals as the ultimate reactive species. The mutagenicity associated with the induced damage was analyzed in the gpt gene of plasmid pSV2gpt, which was exposed to BCBT+UV(360) and subsequently transfected into Escherichia coli. The results were in agreement with the specific generation of 8-oxoGua. Nearly all point mutations (20 out of 21) were found to be GC-->TA transversions known to be characteristic for 8-oxoGua. In conclusion, alkoxyl radicals generated from BCBT+UV(360) induce 8-oxoGua in DNA with a higher selectivity than any other reactive oxygen species analyzed so far.

Metabolic encephalopathy in critically ill patients suffering from septic or nonseptic multiple organ failure.

OBJECTIVE: Evaluation of changes in the peak latencies of sensory evoked potentials in different patient groups, to evaluate differences in metabolic encephalopathy of critically ill patients with multiple organ failure as a result of septic or nonseptic conditions. DESIGN: Prospective cohort study. SETTING: Intensive care units of the university hospital, Vienna. PATIENTS: Patients (n = 103) treated on an intensive care unit because of multiple organ failure with additional metabolic encephalopathy. Multiple organ failure was induced by sepsis (group A; n = 56), surgery (group B; n = 29), or both (group C; n = 18). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Metabolic encephalopathy was determined by measuring median nerve-stimulated short-latency and long-latency sensory evoked potentials. No differences in the peak latencies of the sensory evoked potentials were detected among the groups. Septic patients had a N70 peak latency of 131+/-21 msecs, nonseptic postsurgical patients of 132+/-17 msecs, and septic postsurgical patients of 134+/-17 msecs. The cervicomedullary N13 to cortical N20 conduction times were 6.4+/-1 msec, 6.4+/-1.4 msecs, and 6.8+/-1.2 msecs, respectively. All measured peak latencies were significantly prolonged compared with peak latencies of healthy controls. The severity of illness assessed by the Acute Physiology and Chronic Health Evaluation III score was not different between the three groups. An increase of the delay of N70 peak latencies was significantly correlated with the severity of illness (r2 = .15; p < .00005). CONCLUSION: There was no difference in sensory evoked potential measurements detectable among septic patients with multiple organ failure, nonseptic postsurgical patients with multiple organ failure, and septic postsurgical patients with multiple organ failure. The N70 peak latency was significantly correlated with the severity of illness but not with the presence or absence of sepsis. In postsurgical patients with multiple organ failure and superimposed sepsis, the N70 peak latencies were not further prolonged compared with postsurgical patients without sepsis.

Improved outcome prediction in unconscious cardiac arrest survivors with sensory evoked potentials compared with clinical assessment.

OBJECTIVE: To compare the prognostic ability of sensory evoked potentials in cardiac arrest survivors with the outcome predicted by a panel of experienced emergency physicians based on detailed prehospital, clinical, and laboratory data. DESIGN: Inception cohort study. SETTING: Medical intensive care unit and department of emergency medicine at a university hospital. PATIENTS: A total of 162 unconscious, mechanically ventilated patients who survived > or =24 hrs after resuscitation from cardiac arrest. INTERVENTIONS: Recording of sensory evoked potentials and outcome prediction after review of detailed clinical and laboratory data by emergency physicians within 24 hrs after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: At 6 months, the outcome of 36 patients was classified as favorable and 126 patients were rated as poor. After review of prehospital data, emergency physicians predicted favorable vs. poor outcome with a sensitivity of 70% and a specificity of 65%. After additional assessment of data 1 hr after cardiac arrest, the sensitivity of emergency physician predictions increased to 80%, whereas the specificity decreased to 48%. Outcome prediction by emergency physicians was most accurate after obtaining detailed patient data 24 hrs after cardiac arrest (sensitivity, 81%; specificity, 58%). In 35 of 36 patients with favorable outcomes, the cortical evoked potential N70 peak was detected between 72 and 128 msec. Of 113 patients with an N70 peak latency >130 msec or an absent N70 peak, all except one had a poor outcome. By using a cutoff of 130 msec, the N70 peak latency alone had a sensitivity of 94% and a specificity of 97%. The predictive accuracy of the N70 peak latency was significantly higher than the clinical assessment 24 hrs after cardiac arrest (91% vs. 76%, p = .0003). CONCLUSION: In unconscious cardiac arrest survivors, a recording of long-latency sensory evoked potentials is more accurate in predicting individual outcome than an emergency physician review of clinical data.

Rapid routes of synthesis of oligonucleotide conjugates from non-protected oligonucleotides and ligands possessing different nucleophilic or electrophilic functional groups.

Optimized methods are described for post-synthetic conjugation of non-protected oligodeoxyribonucleotides to different ligands. Methods for the terminal functionalization of oligonucleotides by amino, sulfhydryl, thiophosphate or carboxyl groups using different chemical reactions and linkers in both organic and aqueous media are described and compared. Experimental conditions for subsequent coupling of ligands containing aliphatic and aromatic amines, aromatic alcohols, carboxylic, sulfhydryl, alkylating, aldehydic and other reactive nucleophilic and electrophilic groups to oligonucleotides were established, including covalent linkage to other oligonucleotides.

[A simple method for AV-delay determination in dual chamber pacemakers]. / Eine einfache Methode zur Bestimmung des AV-Intervalls bei Zweikammerschrittmachern.

The individual adjustment of the AV intervals is a prerequisite for the hemodynamic advantages of dual-chamber pacing. The methods for the optimization of the AV-Delay (AVD) applied so far are time intensive. A simple and fast method is the approximate adjustment of the AVD with the surface-ECG. The aim of this work is the conception and validation of this new method. The optimal AVD is given if at the end of the atrial contraction the mitral valve is closed by the ventricular increase of pressure. In order to achieve this with pacemaker patients, the individually different atrial and ventricular conduction times must be considered. The different conduction times can be determined from the surface-ECG. Intra- and interatrial conduction times can be defined by the beginning of the atrial spike up to the end of the p-wave. The beginning of ventricular pressure increase corresponds to the peak of the stimulated QRS complex (beginning of the Iso-Volumetric Contraction time, ISVC) and depends on the interventricular conduction time.¶ In the case of 100 patients, who did not receive a cardiac pacemaker, the interval at the end of the p-wave (left atrial excitation, EP) up to the peak of the r-wave (ISVC) during rest and exercise was measured and an age referred average value of 100ms determined; this serves as standard value if no AV-conduction is available. The approximated optimized AVD is given if the interval of the end at the p-wave to the peak of the QRS-Complex amounts to 100ms. By means of a simple algorithm, the optimized AVD can, thus, be calculated:¶ After programming a long AVD, the interval at the end of the native or paced p-wave up to the peak of the stimulated QRS-Complex (EP/ISVC) is determined. This value EP/ISVC is then taken from the long AVD, the 100ms standard value is added and one receives the approximately optimized AVD.¶ In order to validate the described method, 13 consecutive patients (2 female, 11 male, average age 67±7.8 years) were included, and received for different indication (7 sick sinus syndrome, 4 AV block III, 2 binode disease) a DDD pacemaker (Affinity, St. Jude Medical).¶ About 8 weeks after implantation all patients underwent a PA catheter investigation, in order to optimize the AV-/PV-Delay of the pacemaker regarding the maximum cardiac output (CO). For CO measurement the thermo dilution method was applied. Altogether 17 complete hemodynamic measurements (9 times with different PVDs, 8 times with different AVDs) were executed. The patients 10-13 could be examined both in the VDD and in the DDD mode.¶ The minimum determined CO amounted to 3.5 l/min, the maximal CO 7.1 l/min and the average value was 5.62±0.98 l/min. In all patients not only one optimal AVD was found but, moreover, a varied interval of AVDs with which optimal CO results could be obtained. The comparison of surface ECG optimized AVD with the PA catheter optimized AVD showed a statistically significant correlation (0.825PV, 0.982 AV, P<0.01). Sixteen out of seventeen measurements were at an interval which enables hemodynamic optimal CO or stroke volume. Only one AVD determined from the surface ECG was situated slightly (10 ms) outside of a hemodynamic optimal determined AVD. Despite the encouraging test results represented here, further studies should examine the value of the new algorithm in comparison with the other techniques for AVD optimization.

[Secondary prevention following coronary intervention. Survey of 13 intervention centers in Austria]. / Sekundärprävention nach Koronarintervention. Vorgangsweise an 13 Interventionellen Zentren in Osterreich.

Risk factor control has been shown to reduce the incidence of coronary events in patients with or without preceding infarction. Secondary prevention should therefore be borne in mind by every cardiologist. In order to test this concept and/or to promote secondary prevention in our country, the following survey was conducted by our working group for epidemiology and prevention. All interventional centres of the country (7 million inhabitants) were asked to report relevant data of 50 consecutive patients with PTCA in a structured questionnaire. Thirteen centres responded and we report the data of 650 patients. The mean proportion of women was 28%, the mean age 61.1 years and the mean stent rate 49.8%. The indications for PTCA varied widely: stable angina 10-74%, unstable angina 10-86%, primary PTCA 0-22%. The risk factor history was distributed as follows: diabetes 12-46% (mean 22.3%), hypertension 32-68% (mean 54.2%), current smoking 6-56% (mean 21.9%), and total cholesterol (TChol) > 200 mg/dl: 30-78% (mean 60.3%). Current lipid values were available for T chol. in 44-100% (mean 84.5%) and for LDL in 4-100% (mean 67.1%). Dietary counselling by a dietician was done in 4-100% of patients (mean 35.6%) Information concerning the hazards of smoking was given to 25-100% (mean 83.6%) of current smokers. Drug treatment at hospital discharge was as follows: 84-100% (mean 93.1%) received ASA, 24-74% (mean 49.8%) ticlopidine, 6-84% (mean 53.3%) nitrates, 34-82% (mean 60.2%) beta blockers, 10-70% (mean 39.5%) ACE inhibitors, 4-74% (mean 4 7.2%) lipid lowering drugs, 7-48% (mean 17.8%) calcium antagonists, 0-12% (mean 6.1%) digitalis and 0-28% (mean 13.6%) diuretics. Follow-up data were collected in 4 centres at 6 months post discharge and were available for 174 patients. Here we found an increase in the prescription of calcium antagonists, digitalis and statins. The following conclusions were drawn at a conference in which all centres participated: lipid values should be available for each patient at PTCA, dietary counselling should be initiated for every patient during hospitalisation (and continued by the family physician) and the national cardiac society should promote guidelines for the use of drugs in which the variation in use is too wide at present. It should be ensured that these guidelines are implemented not only in patients after AMI but also in those after PTCA.

Attenuation correction improves the detection of viable myocardium by thallium-201 cardiac tomography in patients with previous myocardial infarction and left ventricular dysfunction.

The aim of this study was to determine the influence of attenuation-corrected thallium-201 stress/redistribution/reinjection single-photon emission tomography (SPET) on the number of viable segments in patients with previous myocardial infarction and dysfunctional myocardium. Fifty-one patients with previous myocardial infarction and left ventricular dysfunction were included in the study. In all patients, 201Tl non-corrected (NC) and attenuation-corrected (AC) SPET was performed using a stress/redistribution/reinjection protocol followed by coronary angiography. A semiquantitative analysis was performed using polar maps for NC and AC stress, redistribution and reinjection short-axis and vertical long-axis (apex) slices. Severe (perfusion defect below 50%/maximal count rate: PD < 50), mild and moderate persistent defects for redistribution and reinjection were evaluated for both NC and AC studies. A total of 1581 segments were evaluated by semiquantitative segmental analysis for both NC and AC studies for each redistribution and reinjection map. In the redistribution maps, NC revealed a total of 352 segments and AC a total of 222 segments with impaired perfusion below 50% of the maximal count rate (PD < 50). The mean number of affected segments was 6.9 +/- 5.5 in the case of NC and 4.4 +/- 4.8 in the case of AC (P < 0.001). In the reinjection maps, NC revealed a total of 263 non-viable segments (PD < 50) and AC a total of 169 non-viable segments. The mean number of affected segments was 5.2 +/- 5.3 in the case of NC and 3.3 +/- 4.2 in the case of AC (P < 0.001). Recovery of function was better predicted by AC than by NC in 20% of patients in the follow-up group. Therefore, the use of attenuation correction influences the extent of viable segments by showing more viable segments in either redistribution or reinjection maps. 201Tl imaging without attenuation correction may underestimate the extent of tissue viability, which may contribute to the lower sensitivity compared to fluorine-18-fluorodeoxyglucose positron emission tomography, where attenuation correction is a routinely performed procedure.

Previous episodes of hypoglycemic coma are not associated with permanent cognitive brain dysfunction in IDDM patients on intensive insulin treatment.

Intensive insulin treatment of IDDM is associated with increased frequency of hypoglycemic coma. The extent of possible cerebral sequelae after recovery is still unknown. We studied the impact of previous hypoglycemic coma on neurophysiological measures of cognitive brain function in 108 patients with adult-onset IDDM receiving intensive insulin treatment. In the study, 55 IDDM patients (age 38 +/- 14 years, mean +/- SD) who had a history of > or =1 (median 3, range 1-35) comatose hypoglycemic event were compared with 53 IDDM patients (age 34 +/- 12 years) with no history of hypoglycemic events using P300 event-related potentials and psychometric tests (the Mini-Mental State Exam and trailmaking test, part A). Findings on these patients were compared with those from 108 matched healthy control subjects. No difference was observed in P300 latencies and psychometric tests between patients with and without a history of hypoglycemic coma (P300 latency, 346 vs. 342 ms; trailmaking test, 31 vs. 30 s; Mini-Mental State Exam, 29.5 vs. 29.6; NS). In diabetic patients, however, P300 latencies were delayed compared with those of healthy control subjects (344 vs. 332 ms; P < 0.001) and were correlated to diabetes duration but not to total hypoglycemic episodes. Scores on the Mini-Mental State Exam (29.5 vs. 29.6; P = 0.59) and trailmaking test (31 vs. 28 s; P = 0.10) were not different between patients and control subjects. In conclusion, previous episodes of hypoglycemic coma are not associated with permanent impairment of cognitive brain function in patients with adult-onset IDDM receiving intensive insulin treatment compared with patients without such episodes. Cognitive brain function, however, is subclinically impaired in relation to duration of diabetes.

4-tert-butylperoxymethyl-9-methoxypsoralen as intercalating photochemical alkoxyl-radical source for oxidative DNA damage.

We describe the synthesis of a novel psoralen peroxide 1 that generates on irradiation (350 nm) alkoxyl radicals, namely tert-butoxyl radicals, as confirmed by electron spin resonance studies with the spin trap 5,5-dimethyl-pyrroline-N-oxide. The radical source intercalates into the DNA, which has been demonstrated by linear-flow-dichroism measurements. Thus, the alkoxyl radicals are formed advantageously directly in the DNA matrix. In supercoiled pBR322 DNA, the generation of strand breaks by the photochemically or metal-catalyzed generated alkoxyl radicals is demonstrated. Photosensitization by the psoralen chromophore was excluded because similar substances that do not release radicals caused no DNA damage, nor were the photoproducts of the peroxide 1 active. With calf thymus DNA, 8-oxoGua and small amounts of guanidine-releasing products, e.g. oxazolone, were observed. However, in these reactions the photoproduct also displayed some DNA-oxidizing capacity.