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Hartmut Hecker

Publications and source records attributed to Hartmut Hecker.

At least 19 recordsLinked to original sources

Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: A single center study.

OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with varying severity and progression. This study describes the natural history of PSC patients and evaluates the prognostic significance of clinical, biochemical, and cholangiographic findings constructing a novel prognostic model. METHODS: A population of 273 German PSC patients was studied with a median follow-up time of 76 months (range 1-280 months). Survival curves were analyzed by the Kaplan-Meier method, and prognostic significance of clinical, biochemical, and cholangiographic features recorded at the time of diagnosis was evaluated by multivariate analysis using Cox proportional-hazards regression models. RESULTS: The estimated median survival from the time of diagnosis to death or time of liver transplantation was 9.6 yr. One hundred eight (39.6%) patients underwent liver transplantation. Hepatobiliary malignancies were found in 39 (14.3%) patients of the entire PSC population. Age, low albumin, persistent bilirubin elevation longer than 3 months, hepatomegaly, splenomegaly, dominant bile duct stenosis, and intra- and extrahepatic ductal changes at the time of diagnosis were found to be independent risk factors correlating with poor prognosis and were used to construct a new prognostic model. CONCLUSIONS: A persistent bilirubin elevation for longer than 3 months from the time of diagnosis could be identified as a novel marker correlating with a poor outcome. A new prognostic model was developed to predict progression of PSC, which may be useful in timing of liver transplantation.

Adolescent↗

Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels.

Lidocaine-like sodium channel blocking drugs provide pain relief either by interrupting impulse conduction in neurons when applied locally in high concentrations or, when given systemically, by suppressing high-frequency ectopic discharges due to preferential drug binding to inactivated channel states. Lidocaine-like actions of opioids have frequently been demonstrated clinically. However, drug binding to resting and inactivated channel conformations has been studied systematically only in the case of meperidine. The aim of this in vitro study was to investigate the effects of four currently used opioids on heterologously expressed neuronal (NaV(1.2)) voltage-gated sodium channels. Block of sodium currents was studied at hyperpolarized holding potentials and at depolarized potentials inducing either fast- or slow-inactivation. Sufentanil, fentanyl and tramadol but not morphine reversibly suppressed sodium inward currents at high concentrations (half-maximum blocking concentrations (IC50) 49+/-4, 141+/-6 and 103+/-8 microM) when depolarizations were started from hyperpolarized holding potentials. Short depolarizations inducing fast-inactivation and long prepulses inducing slow-inactivation significantly (*p < or = 0.001) increased the blocking potency for these opioids. 15% slow inactivated channels reduced the respective IC50 values to 5+/-3, 12+/-2 and 21+/-2 microM. These results show that: (1) Sufentanil, fentanyl and tramadol block voltage-gated sodium channels with half-maximum inhibitory concentrations similar to the IC50 reported for meperidine. (2) Slow inactivation--a physiological mechanism to suppress ectopic activity in response to slow shifts in membrane potential--increases binding affinity for sufentanil, fentanyl and tramadol. (3) Morphine has no such effects.

Analgesics, Opioid↗

Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial.

BACKGROUND: Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered. METHODS AND RESULTS: After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8+/-1.3 days after PCI. Cardiac MRI was performed 3.5+/-1.5 days, 6+/-1 months, and 18+/-6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001). CONCLUSIONS: In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.

Adult↗

Serial analysis of troponin I levels in patients with ischemic and nonischemic dilated cardiomyopathy.

BACKGROUND: Ongoing myocardial cell damage forms the basis for progression of chronic heart failure. Evidence is accumulating that progressive loss of cardiac myocytes is associated with the release of cardiac troponin I (cTnI). HYPOTHESIS: This study sought to determine whether levels of cTnI are of prognostic value for risk stratification of patients with chronic heart failure. METHODS: Release of cTnI was measured by conventional enzyme immunoassay following serum ultrafiltration in 58 consecutive patients hospitalized for chronic heart failure and 31 healthy volunteers serving as control group. Determination of serum levels was performed every 2 weeks over a time interval of 3 months. According to the results of coronary angiography, patients were divided into Group D showing normal coronary arteries (n=33, ejection fraction 27 +/- 6.1%) and Group I showing severe coronary heart disease (n=25, ejection fraction 28.8 +/- 7.8%). Survival of patients was evaluated after a mean time interval of 3 years. RESULTS: The mean cTnI serum level over all measurements was 0.66 +/- 1.8 ng/ml in patients versus 0.11 +/- 0.48 ng/ml in volunteers. At all six points of analysis, the mean cTnI serum level was significantly different (p < 0.001) between patients and volunteers. There was no significant difference between patients with and without coronary heart disease following hospital discharge, however, troponin release was significantly different between survivors and nonsurvivors (n=27) (0.56 ng/ml vs. 0.84 ng/ml; p < 0.05). CONCLUSION: Permanent cTnI release is a common finding in patients with chronic heart failure and a strong prognosticator. In this setting, coronary morphology seems to play a minor role for disease progression.

Adult↗

Characterization and clinical course of hepatobiliary carcinoma in patients with primary sclerosing cholangitis.

OBJECTIVE: Primary sclerosing cholangitis (PSC) confers a high risk of development of hepatobiliary carcinoma (HBC). The aim of the study was to identify indicators and risk factors for developing HBC in PSC patients. MATERIAL AND METHODS: Thirty-nine PSC patients with HBC at time of HBC diagnosis were compared with 101 PSC patients without HBC at time of acceptance for liver transplantation. RESULTS: Eighteen of these patients (46.2%) developed HBC within one year after diagnosis of PSC. In PSC patients with HBC male gender, nicotine abuse, long duration of inflammatory bowl disease (IBD), clinical symptoms, elevation of CA 19-9, as well as dominant bile duct stenosis were significantly more frequent (p<0.05) compared with the PSC control group. A cross-validated sensitivity and specificity of 85% and 97%, respectively, for the detection of HBC was obtained using the following parameters: weight loss, elevation of CA 19-9 >or= 200 kU/l, and dominant bile duct stenosis. CONCLUSIONS: HBC is not necessarily a late complication of end-stage PSC. A long history of IBD, male gender, and nicotine abuse are risk factors for the development of HBC. In particular, CA 19-9, body-weight and dominant bile duct stenosis are valuable indicators in detecting HBC in PSC patients.

Adolescent↗

Correlation of oxygen delivery with central venous oxygen saturation, mean arterial pressure and heart rate in piglets.

BACKGROUND: Accurate assessment and monitoring of the cardiocirculatory function is essential during major pediatric and pediatric cardiac surgery. Invasive monitoring of cardiac output and oxygen delivery (DO(2)) is expensive and sometimes associated with adverse events. Measurement of central venous oxygen saturation (ScvO(2)) is less invasive and may reflect the DO(2). Therefore, we investigated the correlation of ScvO(2) with cardiac index (CI) and DO(2) and in comparison the more common monitored parameters heart rate (HR) and mean arterial pressure (MAP) with DO(2) in an animal experimental setting. METHODS: In five fasted, anesthetized and mechanically ventilated piglets CI (transpulmonary thermodilution), venous and arterial blood gases, HR and MAP was measured during normal conditions, volume loading, inotropic support, and exsanguination. RESULTS: In the five piglets 168 measurements could be performed. In a wide hemodynamic range (CI 22-335 ml x kg(-1) min(-1)) we found significant correlations of ScvO(2) with DO(2)) (r(2) = 0.91, P < 0.0001) and CI (r(2) = 0.88, P < 0.0001) and also between DO(2) and MAP (r = 0.86, P < 0.0001) and HR (r = 0.19, P < 0.05). CONCLUSIONS: ScvO(2) is a better parameter for indirect estimation of DO(2) than MAP and heart rate. Measurement of ScvO(2) is simple and does not necessitate additional invasive techniques. In the clinical setting ScvO(2) should be used in combination with other standard vital parameters, i.e. MAP, central venous pressure, lactate, base excess, and urine output.

Animals↗

Does the way that women experience the onset of labour influence the duration of labour?

OBJECTIVE: To assess whether the way in which women experience the onset of their labour influences the duration of their labour. DESIGN: Longitudinal study on a convenient sample of women in spontaneous labour with a singleton pregnancy in cephalic presentation at term. SETTING: University hospital in Germany. POPULATION/SAMPLE: Six hundred and fifty-one women (347 primiparae and 304 parae). METHODS: Women recorded how and when labour had started. Responses were subjected to structured content analysis. Two investigators independently subdivided women's reported signs and symptoms into eight predefined categories. These data were related to maternal characteristics and to the course and outcome of labour as documented in the perinatal record. MAIN OUTCOME MEASURES: Women's perception of how labour had started, interval between onset of labour and rupture of the membranes and duration of first stage labour and overall duration of labour. RESULTS: Only 60% of women reported contractions as a sign of the onset of their labour. These women had a longer interval between the onset of labour and rupture of the membranes but a similar duration of labour when compared with women who did not report contractions as a sign of the onset of labour. Self-reported loss of amniotic fluid was the only sign that showed a consistent relationship with the duration of labour. Other patterns of labour onset had no effect on the duration of labour. CONCLUSION: Irrespective of whether they have given birth before, women experience their onset of labour in a variety of ways. A large proportion of these experiences bear no resemblance to the classical diagnosis of labour and most are unrelated to the duration of labour.

Adult↗

Clinical and prognostic role of plasma coagulation factor XIII activity for bleeding disorders and 6-year survival in patients with chronic liver disease.

BACKGROUND/AIMS: Alterations of plasma coagulation factor XIII may contribute to bleeding disorders in patients with liver cirrhosis. As standard clotting tests such as prothrombin time or activated thromboplastin time (aPTT) cannot detect factor XIII deficiency, this may often be overlooked in clinical practice. We aimed to define factor XIII's clinical and prognostic role in chronic liver disease. PATIENTS AND METHODS: Factor XIII activities were assessed among various other parameters in 111 patients with chronic liver diseases during evaluation for liver transplantation in a prospective study. RESULTS: Unlike coagulation factors II, V or VII, factor XIII activity was maintained in the majority of patients with liver cirrhosis. However, although rarely, factor XIII deficiencies (<50%) occurred, especially in Child C cirrhosis. Factor XIII levels correlated with liver's biosynthetic capacity (cholinesterase activity, albumin, total protein) as well as with platelet count, global coagulation tests and other single coagulation factors. Patients reporting a current systemic bleeding tendency at study entry had significantly reduced factor XIII. In a 6-year follow-up, patients with factor XIII<50% had a significantly increased risk of severe upper gastrointestinal bleed, and reduced factor XIII (<50%, 50-75% vs. normal) was associated with increased mortality. CONCLUSIONS: Factor XIII deficiency is rare in patients with liver cirrhosis, but is associated with a clinical bleeding tendency and an unfavorable prognosis for future hemorrhages and survival.

Adolescent↗

Hemolysis, high-intensity transient signals (HITS) and hemodynamic results after aortic valve replacement with the Medtronic Hall Easy-Fit heart valve prosthesis.

BACKGROUND AND AIM OF THE STUDY: Previous studies have shown a correlation between type, orientation and valve size of mechanical heart valve prostheses and the incidence of high-intensity transient signals (HITS). The study aim was to investigate the presence of HITS and hemolysis and the impact of valve size and hemodynamic parameters following aortic valve replacement (AVR) using the new Medtronic Hall Easy-Fit prosthesis. METHODS: A total of 150 patients (120 males, 30 females; mean age 62 +/- 8 years; range: 32-78 years) underwent AVR (n = 94; 63% concomitant procedures) with the Easy-Fit valve in its optimal orientation. Patients were investigated at between three and 36 months after AVR using transcranial Doppler examination of the right and left middle cerebral artery, and the incidence of HITS was determined. For evaluation of hemolysis, serum lactate dehydrogenase (LDH), hemoglobin and bilirubin were measured. These parameters were related to valve size. Transthoracic echocardiography was performed in all patients. RESULTS: Among the patients, 112 (75%) showed no or low HITS (34% none, 41% < 30/h), while only 38 (25%) had elevated HITS (range 31-100/h, 14%; range > 100/h, 11%). Statistical analysis showed a linear association between the HITS count and valve size. A positive correlation between valve size and LDH was observed; hemoglobin and bilirubin showed normal values. CONCLUSION: The valve size-dependent increase in LDH after AVR corresponds with the observation that the presence of HITS increases with valve size. In light of these findings, the surgical approach to implant the largest size Easy-Fit valve possible should be discussed, given the excellent hemodynamic results provided by the valve, even in smaller sizes.

Adult↗

Mid term course after pediatric right ventricular outflow tract reconstruction: a comparison of homografts, porcine xenografts and Contegras.

OBJECTIVE: Homografts and porcine xenografts are valved conduits for pediatric RVOT reconstruction. They lack availability and durability. The Contegra, a glutaraldehyde fixed bovine jugular vein, was developed as an alternative. In this article, we compare single center results of 190 RVOT conduit implantations. METHODS: 52 homografts, 30 porcine xenografts, 108 Contegras were implanted since 1992. Since 1999, data collection was prospective, for Contegras within a controlled clinical trial. Follow-up is complete for all evaluated items. We stratified reoperations by problem zone (sub-, intra-, and supravalvular) and analyzed the role of patient age, diagnosis, graft type, graft size, previous operations and year of operation on freedom from explantation or reoperation related to supravalvular reasons. RESULTS: Porcine xenografts were inferior concerning freedom from explantation and reoperation (P<0.0001). They gave erlier reason for explantation in each zone (P<0.001). At 4 years, homograft valve related reoperation need reached 20%, Contegras 0% (P=0.002). Supravalvlar reoperation reasons developed about equally in homografts and Contegras. Multivariable Cox' regression analysis showed porcine xenografts and age <1 year as independent risk factors for explantation due to supravalvular reasons. We found no reason to assume that supravalvular reoperation reasons occured more frequently after Contegra than after homograft implantation. CONCLUSION: After 12 years RVOT reconstruction with 190 valved conduits, Contegras remain our device of choice. At 4 years, they show no subvalvular or valvular reason for explantation or reoperation. Contegras have the advantages of easy handling and availability, and they compare well with homografts regarding freedom from explantation and freedom from reoperation.

Adolescent↗

Structural features of phenol derivatives determining potency for activation of chloride currents via alpha(1) homomeric and alpha(1)beta heteromeric glycine receptors.

Phenol derivatives constitute a family of neuroactive compounds. The aim of our study was to identify structural features that determine their modulatory effects at glycine receptors. We investigated the effects of four methylated phenol derivatives and two halogenated analogues on chloride inward currents via rat alpha(1) and alpha(1)beta glycine receptors, heterologously expressed in HEK 293. All compounds potentiated the effect of a submaximal glycine concentration in both alpha(1) homomeric and alpha(1)beta glycine receptors. While the degree of maximum potentiation of the glycine 10 microM effect in alpha(1)beta receptors was not different between the compounds, the halogenated compounds achieved half-maximum potentiating effects in the low microM range -- at more than 20-fold lower concentrations compared with their nonhalogenated analogues (P<0.0001). The coactivating effect was over-ridden by inhibitory effects at concentrations >300 microM in the halogenated compounds. Neither the number nor the position of the methyl groups significantly affected the EC(50) for coactivation. Only the bimethylated compounds 2,6 and 3,5 dimethylphenol (at concentrations >1000 microM) directly activated both alpha(1) and alpha(1)beta receptors up to 30% of the maximum response evoked by 1000 microM glycine. These results show that halogenation in the para position is a crucial structural feature for the potency of a phenolic compound to positively modulate glycine receptor function, while direct activation is only seen with high concentrations of compounds that carry at least two methyl groups. The presence of the beta subunit is not required for both effects.

Cells, Cultured↗

Effectiveness and safety of internal rectilinear biphasic versus monophasic defibrillation in patients undergoing cardiac surgery.

BACKGROUND: Recently it has been shown that biphasic external shocks are more effective in the treatment of ventricular fibrillation (VF) compared with monophasic external shocks in terms of number of defibrillation attempts and maximal energy used for termination of VF. Biphasic defibrillators apply different biphasic impulse forms, depending on technology. To the authors' knowledge, there are no existing data concerning the effects of rectilinear biphasic internal shocks in patients undergoing cardiac surgery. The purpose of this study was to compare monophasic with rectilinear biphasic internal shock waveforms for termination of VF in patients undergoing cardiac surgery. METHODS: One hundred thirty-four patients scheduled for elective cardiac surgery were prospectively randomized either to monophasic (group A) or biphasic (group B) internal defibrillation. Defibrillation was started with 7 J and increased stepwise to 30 J in each group until successful termination of VF after aortic declamping. The number of defibrillations, as well as the cumulative and maximal energy for termination of VF, were determined. Preoperatively, intraoperatively, and postoperatively troponin T, total creatine phosphokinase (CPK), and CPK- MB isoenzymes were measured. RESULTS: In 64 patients (47%) VF occurred. The groups consisted of 32 patients each. The number of defibrillations (1.3 +/- 0.6 v 1.9+/- 1.2; p = 0.013), maximal energy per patient (7.9 +/- 2.5 v 11.6 +/- 7.32; p = 0.006), and cumulative energy (10.1 +/-6.1 v 21.3 +/- 24.1; p = 0.016) for successful termination of VF were significantly reduced in group B. Troponin T, CPK, and CPK-MB did not differ between groups. CONCLUSIONS: Results of this study indicate that rectilinear biphasic internal defibrillation is more effective in the treatment of VF during cardiac surgery than is monophasic defibrillation. However, no significant difference in myocardial damage could be detected between groups.

Adolescent↗

An evaluation of pain and "fitness" during labor and its acceptability to women.

BACKGROUND: Labor experiences involve many dimensions that change during labor but are rarely measured contemporaneously and longitudinally. We examined pain and "fitness" aspects of women's labor experience and assessed the acceptability to participants. METHODS: Thirty nulliparas and 20 multiparas in term labor indicated pain and fitness every 45 minutes in contraction-free intervals on visual analog scales from 0 to 10. Fitness implied both physical and psychological strength. Data were analyzed cross-sectionally and longitudinally, with adjustment for analgesia and time dependency. Women received feedback and evaluated their participation on the first day postpartum. RESULTS: Measurements of pain and fitness ranged from 2 to 22 per woman (mean +/- SD: 7.4 +/- 4.4). Pain scores showed various patterns, mostly increasing from 1.4 (+/- 1.9) at the first to 6.6 (+/- 3.8) at the last measurement in nulliparas and from 1.3 (+/- 2.1) to 6.2 (+/- 4.0) in multiparas. One half of the women declined steadily in fitness throughout labor, occasionally after a slight increase early on. Multiparas entered labor more fit (5.9 +/- 3.0) than nulliparas (3.9 +/- 2.7), but showed a sharper decline so that the difference leveled out just before birth. Although fitness at any one time did not reflect pain levels, fitness and pain were inversely related, especially in nulliparas (p = 0.003). Analgesia affected pain scores but affected fitness only a little. Women's responses were mainly positive, especially in appreciating the feedback. Nevertheless, 32 percent of women skipped one or more measurements, often toward the end or when too close to a contraction. CONCLUSIONS: Pain and "fitness" are two distinctly different dimensions of labor experience. Repeated longitudinal measurements of elements of well-being are clearly feasible and acceptable to laboring women. They may be useful to assess how labor events and interventions affect women's well-being.

Cross-Sectional Studies↗

Effects of 1-week and 6-week exposure to GSM/DCS radiofrequency radiation on micronucleus formation in B6C3F1 mice.

The aim of this study was to examine the possible induction of micronuclei in erythrocytes of the peripheral blood and bone marrow and in keratinocytes and spleen lymphocytes of mice exposed to radiofrequency (RF) radiation for 2 h per day over periods of 1 and 6 weeks, respectively. The applied signal simulated the exposure from GSM900 and DCS1800 handsets, including the low-frequency amplitude-modulation components as they occur during speaking (GSM Basic), listening (DTX) and moving within the environment (handovers, power control). The carrier frequency was set to the center of the system's uplink band, i.e., 902 MHz for GSM and 1747 MHz for DCS. Uniform whole-body exposure was achieved by restraining the mice in tubes at fixed positions in the exposure setup. Mice were exposed to slot-averaged whole-body SARs of 33.2, 11.0, 3.7 and 0 mW/g during the 1-week study and 24.9, 8.3, 2.8 and 0 mW/g during the 6-week study. Exposure levels for the 1- and 6-week studies were determined in a pretest to confirm that no thermal effect was present that could influence the genotoxic end points. During both experiments and for both frequencies, no clinical abnormalities were detected in the animals. Cells of the bone marrow from the femur (1-week study), erythrocytes of the peripheral blood (6-week study), keratinocytes from the tail root, and lymphocytes from the spleen (both studies) were isolated on slides and stained for micronucleus analysis. Two thousand cells per animal were scored in erythrocyte and keratinocyte samples. In spleen lymphocytes, 1000 binucleated lymphocytes were scored for each animal. The RF-field exposure had no influence on the formation of red blood cells. After 1 week of exposure, the ratio of polychromatic to normochromatic erythrocytes was unchanged in the treated groups compared to the sham-exposed groups. Furthermore, the RF-field exposure of mice did not induce an increase in the number of micronuclei in erythrocytes of the bone marrow or peripheral blood, in keratinocytes, or in spleen lymphocytes compared to the sham-treated control.

Animals↗

Regional differences in cerebral blood flow and cerebral ammonia metabolism in patients with cirrhosis.

Clinical and histopathological findings hint at regional differences in the brain's sensitivity to metabolic changes in cirrhosis. The aim of the present study was to examine regional differences in cerebral ammonia metabolism in patients with cirrhosis and grade 0-to-I hepatic encephalopathy (HE). (13)N-ammonia, (15)O-water positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed. Quantitative values of cerebral blood flow (CBF) and the initial cerebral ammonia uptake rate (K1) were derived for several regions of interest from images of the desired parameters after interactive coregistration with the patients' MRI-studies. CBF (mL/mL/min), K1 (mL/mL/min), and the ammonia extraction fraction (K1/CBF) showed marked regional variance with the highest levels in the thalamus, the lenticular nucleus, and the cerebellum. In conclusion, the regional differences in cerebral ammonia uptake correspond to the distribution of histopathological changes in the brain of patients with cirrhosis as well as clinical features of HE, characterized by signs of basal ganglia and cerebellar dysfunction with corresponding signs of functional impairment, especially of the frontal cortex and cingulate gyrus.

Adult↗

Transthoracic Doppler validation in mammary artery grafts after minimal invasive direct coronary artery bypass operation.

OBJECTIVE: This study was performed to validate noninvasive transthoracic Doppler ultrasound (TTD) with simultaneous invasive Doppler guidewire measurements in patients after minimal invasive direct coronary artery bypass operation. METHODS: A total of 14 patients were examined 3 to 8 days after minimal invasive direct coronary artery bypass operation. TTD was performed to measure systolic and diastolic peak velocities of the left internal mammary artery (LIMA) at rest and during adenosine-induced hyperemia. Simultaneous Doppler guidewire measurements were performed. RESULTS: LIMA flow was detected in 12 of 14 patients (86%). There was high agreement between TTD and Doppler guidewire measurements of LIMA flow velocities (systolic peak velocity: r = 0.86, y = 11.3 + 0.82x +/- 7.9; diastolic peak velocity: r = 0.95, y = 5.7 + 1.02x +/- 7.5; average peak velocity: r = 0.95, y = 5.2 + 0.94x +/- 5.4; and flow velocity reserve: r = 0.97, y = 5.2 + 0.99x +/- 4.5). CONCLUSION: TTD represents an accurate method to evaluate flow velocities and flow velocity reserve of LIMA bypass grafts even in the early phase after minimal invasive direct coronary artery bypass operation.

Adult↗

Hepatitis C virus infection affects the brain-evidence from psychometric studies and magnetic resonance spectroscopy.

BACKGROUND/AIMS: Up to 50% of patients infected with the hepatitis C virus (HCV) complain of chronic fatigue and difficulties in concentration and memory. The aim of the present study was to seek evidence for the presence of central nervous system involvement in HCV infected patients with only mild liver disease. METHODS: Thirty HCV infected patients with normal liver function, 15 of whom were identified as having mild and 15 moderate to severe fatigue using the fatigue impact scale, underwent neurological and neuropsychological examination, electroencephalography (EEG) and cerebral proton magnetic resonance imaging (MRI) and spectroscopy (MRS). Fifteen healthy volunteers, matched for age and educational attainment, served as controls. RESULTS: In comparison to the healthy controls the patients with HCV infection showed evidence of cognitive impairment, primarily attention and higher executive functions, higher levels of anxiety and depression and impairment of quality of life. In addition they showed a significant decrease of the N-acetyl-aspartate/creatine ratio in the cerebral cortex on 1H MRS while the EEG was slowed in 25%. In general the deficits were more marked in the patients with moderate rather than mild fatigue. CONCLUSIONS: The data provide evidence of central nervous system involvement in patients with HCV infection.

Adult↗

Novel NKX2-5 mutations in diseased heart tissues of patients with cardiac malformations.

NKX2-5 is a homeodomain-containing transcription factor important in cardiac development. Familial mutations in the NKX2-5 gene are associated with cardiac abnormalities, but mutations are rare in sporadic cases. We studied the pathology and molecular genetics of NKX2-5 in diseased heart tissues of 68 patients with complex congenital heart disease (CHD), particularly atrial (ASD), ventricular (VSD), and atrioventricular septal defects (AVSD). We also studied DNA extracted from 16 normal hearts, as well as lymphocytic DNA from 50 healthy volunteers, 7 families, and 4 unrelated individuals with CHD. Direct sequencing revealed 53 NKX2-5 mutations in the diseased heart tissues, including nonsynonymous substitutions in the homeodomain of NKX2-5. We found common mutations among unrelated patients, but certain mutations were specific to VSDs and AVSDs. Many patients had multiple NKX2-5 mutations, up to 14 nonsynonymous mutations per patient in VSDs. Importantly, these nonsynonymous mutations were mainly absent in normal heart tissues of the same CHD patients, thus indicating somatic origin and mosaicism of mutations. Further, observed mutations were completely absent in normal hearts and lymphocytic DNA of healthy individuals. Our findings provide new insights for somatic NKX2-5 mutations to be of importance in congenital heart disease.

Base Sequence↗