Papers by Mechthild Westhoff-bleck
British Journal of Clinical Pharmacology, Jun 1, 1996
Six male and six female stable renal allograft recipients under cyclosporine immunosuppression an... more Six male and six female stable renal allograft recipients under cyclosporine immunosuppression and without concomitant therapy with drugs known either to induce or inhibit CYP3A enzymes were included in the study and received 180 mg day−1 diltiazem for 1 week in a two-period cross-over fashion. Cyclosporine (352±56 mg day−1) was given in two daily oral doses. The daily doses were not changed during the study. Blood samples were collected for 12 h after receiving cyclosporine alone and after receiving diltiazem in addition for 1 week. Cyclosporine and nine of its metabolites were quantified using h.p.l.c. 2 Co-administration of diltiazem caused a 1.6 fold increase of the AUC(0,12 h) of cyclosporine and a 1.7 fold increase of the AUC(0, 12 h) of its metabolites. Analysis of the metabolite patterns showed an over-proportional increase of the AUC(0, 12 h) of the cyclized metabolites AM1c (2.6 fold) and AM1c9 (2.2 fold). The AUC(0, 12 h) values of cyclosporine and the hydroxylated metabolites increased less than two fold. 3 Differences of the AUC(0, 12 h) values of cyclosporine with and without diltiazem were significantly higher in female than in male patients (P<0.02). The differences in the AUC(0, 12 h) values of the metabolites, especially AM1c, tended to be higher in female patients as well. 4 It is concluded that coadministration of diltiazem not only increases the blood concentration of cyclosporine but also those of its metabolites, leads to a shift of the metabolite pattern towards cyclized metabolites, and that the pharmacokinetic changes under diltiazem administration are more prominent in female than in male patients.
Journal of Magnetic Resonance Imaging, Dec 6, 2021
BackgroundPhase‐resolved functional lung (PREFUL) magnetic resonance imaging (MRI) pulmonary puls... more BackgroundPhase‐resolved functional lung (PREFUL) magnetic resonance imaging (MRI) pulmonary pulse wave transit time (pPTT) is a contrast agent free, vascular imaging biomarker, but has not been validated in chronic obstructive pulmonary disease (COPD).PurposeTo validate PREFUL with echocardiographic pPTT as a reference standard and to compare arterial/venous pPTT mapping with spirometry and clinical parameters.Study typeProspective.PopulationTwenty‐one patients (62% female) with COPD and 44 healthy participants (50% female).Field Strength/Sequence1.5 T; 2D‐spoiled gradient‐echo sequence.AssessmentThree coronal PREFUL MRI slices, echocardiography, and spirometry including forced expiratory volume in 1 second (FEV1, liter) and predicted defined as FEV1 in% divided by the population average FEV1%, were performed. Pulmonary pulse transit time from the main artery to the microvasculature (PREFUL pPTT), to the right upper lobe vein (PREFUL pPTTav, echo pPTTav), from microvasculature to right upper lobe vein (PREFULvein) and the ratio of PREFUL pPTT to PREFUL pPTTvein were calculated. Body mass index (BMI), Global Initiative for COPD (GOLD) stage 1–4, disease duration, and cigarette packs smoked per day multiplied by the smoked years (pack years) were computed.Statistical TestsShapiro–Wilk‐test, paired‐two‐sided‐t‐tests, Bland–Altman‐analysis, coefficient of variation, Pearson ρ were applied, pPTT data were compared between 21 subjects from the 44 healthy subjects who were age‐ and sex‐matched to the COPD cohort, P &lt; 0.05 was considered statistically significant.ResultsPREFUL pPTTav significantly correlated with echo pPTTav (ρ = 0.95) with 1.85 msec bias, 95% limits of agreement: 55.94 msec, −52.23 msec in all participants (P = 0.59). In the healthy participants, PREFUL and echo pPTTav significantly correlated with age (ρ = 0.81, ρ = 0.78), FEV1 (ρ = −0.47, ρ = −0.34) and BMI (ρ = 0.56, ρ = 0.51). In COPD patients, PREFUL pPTT significantly correlated with FEV1 predicted (ρ = −0.59), GOLD (ρ = 0.53), disease duration (ρ = 0.54), and pack years (ρ = 0.49).Data ConclusionArteriovenous PTT measured by PREFUL MRI corresponds precisely to echocardiography and appears to be feasible even in severe COPD.Evidence Level1Technical EfficacyStage 2
PubMed, Nov 1, 1988
In patients suffering from an immunosuppressive state pneumonia is a common manifestation of infe... more In patients suffering from an immunosuppressive state pneumonia is a common manifestation of infection. In these patients the radiological appearance of pneumonia is influenced by the still existing immunocompetent reaction and not by the germ itself. Basic defense mechanisms in known underlying disease, clinical condition and the influence of epidemiology on the occurrence of pneumonia are discussed briefly.
The Annals of Thoracic Surgery, Apr 1, 2007
We read with interest the case series by Pirundini and colleagues [1], reporting their surgical e... more We read with interest the case series by Pirundini and colleagues [1], reporting their surgical experience with quadricuspid aortic valves (QAV). The authors state that the most common anatomic variant of QAV is consisting of three equal cusps and one smaller cusp. However, according to the most comprehensive review of this topic available to date, the most common type of QAV is the type with four equal cusps [2]. While this is probably only of academic interest, dysfunction of the valve can be found in approximately 80%-90% of cases in both types, there is one pitfall facing the surgeon operating on a case with a quadricuspid aortic valve not mentioned by the authors: QAVs are often associated with other congenital heart defects [2]. In approximately 18% of the cases reviewed, an additional malformation was found. As was previously mentioned by us [3], it is of special importance to the surgeon that anomalies of the coronary arteries are the most frequent cardiac defects associated with a QAV. They can be found in approximately 10% of the cases [2, 3]. Single coronary ostium [4] and displacement of the coronary orifices [5, 6] have all been reported in association with a QAV. Aoyagi and colleagues [7] remarked that from the surgical standpoint it is important to recognize any displacement of the coronary ostia to prevent ostial obstruction of the coronary arteries during fixation of the prosthetic valve ring. Therefore, a careful evaluation of the cardiac anatomy in cases with a QAV prior to surgery is of utmost importance [3].
Journal of Thoracic Disease, Jun 1, 2018
Background: Grown-up patients with surgically corrected dextro-transposition of the great arterie... more Background: Grown-up patients with surgically corrected dextro-transposition of the great arteries (dTGA) as well as patients with congenitally corrected transposition of the great arteries (ccTGA) carry a high risk of ventricular arrhythmias. Data regarding implantable cardioverter defibrillator (ICD) therapy and efficacy of anti-tachycardia pacing in these patients is limited. Methods: Clinical data from a contemporary cohort of ICD carriers with atrial switch-corrected dTGA and burdened right ventricle or with ccTGA were obtained retrospectively from hospital records and patients were followed for additional 25 months prospectively. Clinical characteristics and ICD episode data were analyzed. Results: Fourteen ICD carriers (8 male) with dTGA or ccTGA were included in the analysis. Four patients received the ICD for primary prevention based on severely reduced systemic ventricular function. The remaining patients had an ICD indication for secondary prevention. Cumulative follow-up added up to 113.5 patient-years. One patient died suddenly due to massive pulmonary embolism. One patient received a ventricular assist device. There were no arrhythmic deaths during the prospective follow-up period. Nine patients (64%) experienced a total of 177 ventricular tachyarrhythmias. Anti-tachycardia pacing was highly effective with 80% success rate in termination of arrhythmias. Five patients (36%) suffered from a total of 28 inappropriate ICD shocks for supraventricular tachycardia. Conclusions: In a contemporary cohort of ICD carriers with dTGA and ccTGA we observed a high proportion of appropriate ICD therapies for ventricular tachyarrhythmias. Over a period of up to 15 years almost two thirds of the patients received appropriate therapies. ATP was highly effective in our cohort and should therefore be programmed whenever possible.
Scientific Reports, May 10, 2022
Major depressive disorder (MDD) is frequently associated with poor response to treatment. Common ... more Major depressive disorder (MDD) is frequently associated with poor response to treatment. Common antidepressants target neurotransmission and neuronal plasticity, which require adequate energy supply. As imaging studies indicate disturbances in central energy metabolism, and caloric restriction improves neuroplasticity and impacts mood and cognition, correction of energy status might increase the effectiveness of antidepressant treatments and reduce the psychopathological symptoms of depression. Metabolic parameters, stress hormones, and brain-derived neurotrophic factor (BDNF) levels were assessed in serum of depressed inpatients (MDD, N = 21) and healthy volunteers (Ctrl, N = 28) before and after a 72 h fasting period during which only water was consumed. Depression severity was assessed by Beck's Depression Inventory (BDI)-2 sum-score and cognitive-affective and somatic sub-scores. Fasting similarly impacted metabolic parameters and stress systems in both groups. Fasting elevated BDI-2 sum-scores and somatic sub-scores in Ctrl. In MDD, fasting increased somatic-, but decreased cognitive-affective symptoms. Subgroup analyses based on BDI-2 sumscores pre-fasting showed that cognitive-affective symptoms decreased in patients with moderate/ severe but not in those with mild symptoms. This was associated with differential changes in BDNF levels. In conclusion, fasting improved cognitive-affective sub-scores in MDD patients with moderate/ severe symptoms that had not responded to prior therapy. Interventions that modulate energy metabolism might directly improve cognitive-affective symptoms and/or augment therapeutic efficacy in moderate-to-severely depressed patients. Major depressive disorder (MDD) is a severe mental disease predicted by the World Health Organization to be the leading cause of disease burden by 2030 1. Due to its multifactorial nature and heterogeneous symptomatology, determination of the precise etiology of MDD remains challenging. An early hypothesis, based on the proposed cause of action of antidepressant drugs, suggested a depletion of monoamines in the central nervous system as the underlying pathomechanism of MDD 2. However, despite the availability of a variety of different antidepressants that primarily target neurotransmission, these treatment options often fail to produce adequate results concerning response and remission 3-5. In fact, up to 50% of all patients diagnosed with MDD display a therapy-resistant form of the disease 3,5 , indicating that alternative pathomechanisms, which are not directly targeted by classical antidepressant treatment, are likely to contribute to MDD development and progression, and that alternative treatment options are needed. Imaging studies and subsequent meta-analyses proposed changes in neuronal plasticity to be critically involved in the pathology of MDD 6 and decreased levels of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), were previously reported 7. Importantly, maintenance of neuroplasticity requires an adequate energy supply and multiple studies have indicated that caloric restriction augments function and structure in the hippocampal region while high calorie
Springer Reference Medizin, 2023
Congenital Heart Disease, Oct 20, 2011
Anomalies of the coronary arteries are commonly associated with congenital heart disease (CHD). A... more Anomalies of the coronary arteries are commonly associated with congenital heart disease (CHD). Anomalies include variations in number, shape, and location of the origin, as well as the course of the coronary artery. An intramural course of one of the coronary arteries is a rather rare condition. Most cases of anomalies are of no clinical relevance and are found incidentally during evaluation for other cardiac conditions. However, they become of importance when cardiac surgery/intervention, especially valve replacement, needs to be performed. We conducted a literature review for coronary anomalies with an intramural course in patients with CHD and include three cases from our own clinic. Note that transposition of the great arteries seems to be the condition most frequently associated with an intramural course of one of the coronary arteries. In case of a suspected anomaly, transesophageal echocardiography presents a valuable tool to visualize the origin and course of the coronary artery, as well as the relationship to important anatomical structures like the aortic or pulmonary valve. Alternatively, cardiac magnetic resonance imaging can be used. Although rare, both cardiologists and surgeons need to be aware of intramural courses of coronary arteries to prevent accidental trauma to them and thereby, reducing the risk for the patient.
Kidney & Blood Pressure Research, Dec 16, 2010
slightly weaker correlation (r = 0.439, p ! 0.001). The Cockcroft-Gault formula showed no correla... more slightly weaker correlation (r = 0.439, p ! 0.001). The Cockcroft-Gault formula showed no correlation at all to the cystatin C-based eGFR (r = 0.144, p = 0.17). The strongest correlation was observed for SDMA and cystatin C-based eGFR (r =-0.552, p ! 0.001). Conclusion: GFR in adults with congenital heart disease should be estimated using the original MDRD or the CKD-EPI formula. SDMA seems to be a promising marker of renal function for this patient group.
Deutsches Ärzteblatt, Jun 23, 2023
Frontiers in Psychiatry, Mar 17, 2022
Introduction: In March 2020, the World Health organization declared COVID-19 a global pandemic. O... more Introduction: In March 2020, the World Health organization declared COVID-19 a global pandemic. One year later, the direct and indirect burden of the COVID-19 pandemic become more visible. In this context, there is concern about the allocation of medical resources and medical treatment of other diseases than COVID-19. Particularly, patients with chronic diseases need constant medical and pharmacological treatment. Therefore, we evaluated a large cohort of patients with adult congenital heart disease (ACHD) regarding postponed medical appointments and their possibilities to receive medical treatment during the COVID-19 pandemic. Methods: This cross-sectional study included 559 patients with ACHD (mean age 37.32 ± 11.98; 47% female). Clinical characteristics, answers to questionnaires concerning lifestyle, psychological well-being, addictive behavior and adherence were related to postponed medical appointments and limited access to medical care. Results: One hundred and nine patients (19.5%) reported problems getting necessary medical treatment or visiting a physician. Higher anxiety levels (p = 0.004) emerged as the main factor associated with medical undertreatment. The main risk factors for postponement of least one medical appointment (n = 91) were higher depression (p = 0.013) and anxiety (p = 0.05) symptoms as well as female sex (p ≤ 0.0001) and documented arrhythmias (p = 0.007) indicating a particular risk group of cardiovascular complications. In contrast, frequent physical activity identified patients at lower risk. Conclusion: In ACHD anxiety and depressive symptoms handicap patients to receive medical care. Postponement of medical appointments additionally relates to female sex and documented arrhythmias. The latter indicates that patients at high risk of adverse cardiac outcome avoid routine medical care. Our data may lead policy makers to develop strategies for the provision of medical services to particular vulnerable patient groups, and to optimize management of both future pandemics and daily routine.
PubMed, Oct 1, 1987
The clinical and radiological features of viral pneumonias are summarized and discussed. Although... more The clinical and radiological features of viral pneumonias are summarized and discussed. Although viral infections of the lung belong to atypical pneumonias they do not demonstrate always the radiographic pattern of an interstitial pneumonia. Characteristic radiographic findings are quite rare. In most cases the microbial etiology cannot be predicted from chest radiographs. The appearance varies depending on the virulence of the organism and the resistance of the host. In this regard knowledge of epidemiological data as well as patient condition and underlying disease is of utmost importance. Differentiation between community- and hospital-acquired infections may be very helpful.
PubMed, Nov 1, 1988
Advances in the area of tumour therapy and transplantation medicine as well as increasing numbers... more Advances in the area of tumour therapy and transplantation medicine as well as increasing numbers of immunodeficiency syndromes have resulted into growing importance of opportunistic infections. The radiological diagnosis and differential diagnosis become more difficult due to the broad spectrum of possible pathogenic organisms, pulmonary complications as part of the underlying disease and finally through possible side effects of therapy. An assignment of these changes to certain radiographic patterns seems useful. However, very few infections present with a characteristic pattern. In the majority of cases the radiography by itself cannot lead to the correct diagnosis. Here, more than in other areas, additional information and wide experience are of great importance to the radiologist.
AhCt In ubraeollic imagea of the liver umvcntid two dimcnkmal texture parametcm (CTP) WCTe compad... more AhCt In ubraeollic imagea of the liver umvcntid two dimcnkmal texture parametcm (CTP) WCTe compad with paramctefl derived from a new stochasiic mudcl, it. periodic random field models (AF'RFM). By fitiing the model to a given textual paUcm, the esdimated model pammctm arc suitable texture features to disringuish between images of the liver with and without nticrofd lesions. The APRFM approach produce classificrtion rteul$ equivalent or ewn bettcr than those obtained by usagc of CTP parameters. Taking advantage of Mt plinciplc of adyilis by qnth~ the poesibility of camping vieuafly the re-qmth* image with the orighal ultrasollic imagc is important for clinical acceptance.
QJM: An International Journal of Medicine, Nov 2, 2010
Congenital Heart Disease, Sep 4, 2013
Cardiopulmonary exercise capacity is often reduced in patients with transposition of the great ar... more Cardiopulmonary exercise capacity is often reduced in patients with transposition of the great arteries after atrial switch operation. Reduced exercise capacity may be caused by deterioration of systemic right ventricular function over time. This study analyzed serial changes in systemic right ventricular function and cardiopulmonary exercise capacity in young adults with transposition of the great arteries after atrial redirection surgery. Twenty-one patients (37% female, mean age 23.2 ± 3.3, mean age at surgery 12.8 ± 14 years) with transposition of the great arteries after atrial switch operation were included in this study. Patients were followed up for a mean period of 39.6 ± 13.1 months. Exercise capacity expressed as peak VO2 max, systemic right ventricular function and subpulmonary left ventricular function assessed by cardiac magnetic resonance imaging and NT-proBNP levels were obtained at baseline and follow-up. Changes in peak VO2 max were correlated to changes in cardiac magnetic resonance imaging and NT-proBNP levels. Baseline peak VO2 max decreased significantly (28.31 ± 5.80 mL/kg/min vs. 25.17 ± 5.71 mL/kg/min, P = .005) on follow-up. Cardiac magnetic resonance imaging parameters of systemic right ventricular ejection fraction as well as subpulmonary left ventricular ejection fraction remained unchanged (44.68 ± 6.59% vs. 45.65 ± 9.60%, P = .54, 60.18 ± 6.29% vs. 61.52 ± 5.30%, P = .35). NT-proBNP levels did not increase (211.7 ± 85.7 ng/mL vs. 261.2 ± 182.2 ng/mL, P = .16). After atrial switch operation for transposition of the great arteries we observed a declining functional exercise capacity. This was not associated with worsening systemic right ventricular function, suggesting that other factors are contributing to the decline in physical exercise capacity.
Drug Safety, 1991
I. Chemical Structure and Physicochemical Properties of Contrast Media 2. Reactions to Contrast M... more I. Chemical Structure and Physicochemical Properties of Contrast Media 2. Reactions to Contrast Media 2.1 Incidence 2.2 Allergic and Pseudoallergic Reactions 2.3 Effect on Thyroid Function 2.4 Cardiovascular Side Effects 2.5 Nephrotoxicity 2.6 Neurotoxicity 3. Drug Interactions 4. Choice of Contrast Medium Radiographic procedures which require the intravascular administration of watersoluble radiocontrast media are performed with increasing frequency. Each examination carries risks that are related either to the technique itself or to the opaque medium chosen. The pathogenesis of radiocontrast media-related adverse effects cannot be explained by a unique theory. The major factors implicated are direct chemotoxic effects and the physicochemical properties of contrast media, the latter being the basis for development of new contrast agents. With nonionic opaque media cardiovascular adverse effects, heat sensation and local pain are observed less frequently. However, it remains unclear whether the incidence of organ dysfunction or anaphylactic reactions with non ionic contrast media currently used can be reduced. This review compares ionic and non ionic contrast media, and current thoughts on the pathophysiology and treatment of adverse reactions are presented.
Since a growing number of patients after surgical repair of transposition of the great arteries (... more Since a growing number of patients after surgical repair of transposition of the great arteries (TGA) survive until adulthood the focus of attention has shifted to the management of associated long-term morbidity and quality of life (QoL). Therefore, we reviewed all patients that underwent surgical repair of TGA at our institution and compared long-term results after atrial and arterial switch operation. Between 1973 and 2000, a total of 302 patients underwent either atrial switch operation (ns222) or arterial switch operation (ns80). Mean followup was 14.5"10.1 years. The arterial switch repair was associated with a higher early mortality whereas long-term survival was comparable between both groups. Postoperative arrhythmias including loss of sinus rhythm and pacemaker implantation occurred significantly more often after atrial switch repair. There was a trend towards a more favourable outcome of the arterial switch group concerning freedom from re-interventions, severe systemic ventricular dysfunction and need for heart failure medication. However, also the arterial switch operation was associated with an increased incidence of loss of sinus rhythm and neo-aortic valve regurgitation during late follow-up. Health related QoL according to the SF-36 questionnaire was not significantly different between both groups and comparable to a healthy population.
International Journal of Cardiology, Oct 1, 2013
Purpose: Asymmetrical dimethylarginine (ADMA) and its structural isomer symmetrical dimethylargin... more Purpose: Asymmetrical dimethylarginine (ADMA) and its structural isomer symmetrical dimethylarginine (SDMA) were identified as biomarkers for left ventricular heart failure. It has been reported that ADMA is more sensitive than NT-proBNP in diagnosing heart failure in general adult congenital heart disease patients. The role of both biomarkers in patients with a systemic right ventricle after atrial repair for transposition of the great arteries (D-TGA) has not been evaluated Methods: In 45 patients (mean age 29.4±3.5 years, female 17 (37.8%)) SDMA, ADMA and NT-proBNP levels were measured and correlated to clinical parameters, cardiac functional parameters assessed by magnetic resonance imaging, and cardiopulmonary exercise testing. Results: SDMA correlated significantly with systemic ventricular ejection fraction (RVEF): r=-0.40, p=0.007. In contrast, ADMA (r=0.09, p=0.54) and NT-proBNP (ρ=-0.28, p=0.06) showed no correlation with RVEF. Additionally, SDMA distinguished between patients with a severely reduced, moderately reduced and normal RVEF. SDMA showed a strong correlation with QRS duration (ρ=0.51, p=0.0004), while ADMA (ρ=0.14, p=0.35) and NT-proBNP (ρ=0.27, p=0.07) did not. Furthermore, SDMA was elevated in patients with a broad QRS complex (≥ 120 ms) compared to patients with a QRS complex < 120 ms. Conclusions: In the current study SDMA emerged as a superior biomarker of systemic ventricular dysfunction in patients after atrial repair for D-TGA compared to NT-proBNP. The promising role of SDMA as a biomarker in this selected patient population needs to be confirmed in larger studies.
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Papers by Mechthild Westhoff-bleck