Oral health-related quality of life of patients after solid organ transplantation is not affected by oral conditions: results of a multicentre cross-sectional study.

BACKGROUND: This multicentre cross-sectional study aimed in examination of oral health-related quality of life (OHRQoL) of patients after solid organ transplantation (SOT). MATERIAL AND METHODS: Patients after SOT (liver, lung and heart) at one out of three German centers (Goettingen, Essen, Leipzig) were included. For comparison, a healthy control (HC) was recruited. OHRQoL was assessed by German short form of oral health impact profile (OHIP G14). Oral examination comprised: decayed-, missing- and filled-teeth index (DMF-T), remaining teeth and periodontitis severity. RESULTS: In total, 196 patients after SOT and 130 HC with comparable age, gender and smoking habits were included (p>0.05). DMF-T and number of remaining teeth was worse in SOT group (p<0.01). OHIP G14 sum score was significantly higher in SOT (3.49 ± 5.73 vs. 1.33 ± 2.63, p<0.01). In contrast to HC, in SOT no associations between OHIP G14 and oral health parameters were found (pi>0.05). Number of remaining teeth was not an independent predictor of OHIP G14 sum score in SOT (ß -0.082, CI95 -0.156 - 0.045, p=0.28). CONCLUSIONS: OHRQoL of SOT recipients is not affected by their oral condition, leading to the assumption that the individual perception of patients physical oral health is not in line with the clinical situation.

Fate of patients with extracorporeal lung assist as a bridge to lung transplantation versus patients without--a single-center experience.

OBJECTIVES: Mechanical lung assist (MLA; extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA)) is increasingly used as a temporary bridge to lung transplantation (LTx). This study was designed to evaluate the impact of preoperative MLA on the operative outcome, including longer-term survival, in comparison to patients undergoing LTx without preoperative MLA. METHODS: A total of 143 patients underwent LTx at our institution from 2002 to 2011. Forty-three percent (n=62) of patients presented with idiopathic pulmonary fibrosis and 71% (n=102) presented with severely elevated pulmonary artery pressure. RESULTS: Thirteen patients (9.1%) required pre-LTx MLA support (age 44 ±13 years, double LTx 73.3%, female gender 53%) whereas 130 patients did not (age 52 ±11 years, double LTx 41.5%, female gender 36.9%). In one patient, MLA was successfully weaned and the patient underwent subsequent LTx. All patients in the MLA group were intraoperatively supported with continuous ECMO. One patient had to be supported with MLA after LTx for a period of 8 days. The short-term and mid-term postoperative survival of the MLA patient group was not significantly different from the non-MLA group (LogRank p=0.28). The 30-day, 90-day and 1-year survivals were 95%, 90% and 71%, respectively, in the patients without MLA compared to 85%, 77% and 68% in the MLA group. CONCLUSIONS: MLA has no impact on long-term survival rate in LTx patients, but has an influence in postoperative survival. MLA support is a valuable tool to bridge unstable patients to LTx.

[Pericardial effusion. Differential diagnostics, surveillance and treatment]. / Perikarderguss. Differenzierte Diagnostik, Überwachung und Therapie.

Cardiac tamponade can be a life-threatening condition due to the high variability of clinical symptoms and the associated risk of rapid hemodynamic deterioration. Therefore, accurate diagnosis followed by immediate intervention is necessary. Common clinical features of cardiac tamponade are pulsus paradoxus, tachycardia, elevated jugular venous pressure and hypotension; however, although these can be indicative of cardiac tamponade they are non-specific. Instant confirmation of the clinical diagnosis of cardiac tamponade can be pursued with echocardiography which also enables a clear estimation of the current hemodynamic situation. Thus in contemporary clinical practice echocardiography plays a key role in the management of cardiac tamponade and must be consulted with regards to final treatment decisions. Common practice includes pericardial puncture under echocardiographic and/or X-ray guidance but only in cases of significantly sized pericardial effusions. Whenever there is a limited sized but hemodynamically significant effusion, inferior pericardiotomy should be the preferred treatment strategy. In cases of cardiac tamponade following chest trauma a full median sternotomy can be a suitable approach for surgical treatment.

Activation of cardiomyocytes depending on their proximity to human bone marrow stem cells.

Our study aimed to elucidate whether bone marrow stem cell (BMC) treatment might result in a cellular response in cardiomyocytes IN VITRO. Subconfluent neonatal rat cardiomyocyte cultures were cocultured for three days with Vybrant CM-DiI labeled BMC from human sternal bone marrow and underwent immunohistological staining for the proto-oncogene c-Myc and the cell cycle proteins CDK2, CDK4 and ATF-3. ß-adrenoceptor density was analyzed using [125I]-iodocyanopindolol (ICYP) histoautoradiography. Quantitative analysis of immunohistochemical images revealed significantly increased expression and upregulation of c-Myc, and its downstream targets ATF-3, CDK2 and CDK4 in neighboring cardiomyocytes to BMC, depending on their distance to the BMC compared to cardiomyocytes far from the BMC. Histoautoradiography revealed a significantly higher ß-adrenoceptor density in cardiomyocytes in the immediate vicinity to the BMC. With increasing distance to the BMC, ß-adrenoceptor density in cardiomyocytes declined. Thus, a small number of BMC can affect a larger number of cardiomyocytes by activating an intracellular signaling cascade and enhancing ß-adrenoceptor density.

Postoperative development of aspirin resistance following coronary artery bypass.

BACKGROUND: Aspirin therapy is known to substantially reduce mortality and the rate of ischaemic complications after coronary artery bypass grafting (CABG). Rates of perioperative aspirin resistance cited in the literature are up to 50% and could be influenced by extracorporeal circulation. Thus, aspirin resistance after CABG may have a significant clinical relevance. MATERIALS AND METHODS: In 59 patients undergoing CABG (on-pump, off-pump and combined procedures) aspirin resistance was investigated by arachidonic acid induced platelet aggregometry. Clinical relevance was assessed with 12-month follow up. RESULTS: Two types of resistance were observed: A preoperative resistance (despite oral aspirin or in vitro addition) was present in 29% and a postoperative developing type was seen in 49% resulting in only 22% of patients with a 'normal' reaction to aspirin. If patients were already on oral aspirin at admission, the rate of resistance was significantly reduced. Off-pump surgery or pump-times exceeding 120 min had no significant impact on resistance. During the 12-month follow up (98.3%), there were three deaths (one stroke, one intestinal ischaemia, one mediastinitis after postoperative delirium) in patients with the perioperative resistance and none in other patients (P = 0.345). In none of those patients who presented with perioperative aspirin resistance, could this aspirin resistance be demonstrated when tested again after 12 months? CONCLUSIONS: Aspirin resistance is a transient phenomenon present in the majority of patients undergoing CABG. The three deaths in the resistant group may - although not statistically significant - indicate the possibility of a worse outcome for patients with aspirin resistance.

Effects of autologous stem cells on immunohistochemical patterns and gene expression of metalloproteinases and their tissue inhibitors in doxorubicin cardiomyopathy in a rabbit model.

This study aims to investigate the expression of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in chronic doxorubicin cardiomyopathy in a rabbit model and to evaluate the effects of bone marrow-derived mesenchymal stem cell (MSC) transplantation in this disease. Thirty-nine 3-month-old New Zealand rabbits were divided into 4 groups: group 1 (n = 9) was the untreated control. Groups 2-4 were treated with 6 weeks of doxorubicin (3 mg/kg). Group 2 (n = 6) received no further treatment. In group 3 (n = 9), animals were treated with culture medium (CM) alone. In group 4 (n = 15), autologous MSCs (1.5-2.0 x 10(6)/ml) were injected in the left ventricular (LV) wall. Hearts were stained with HE and picrosirius red. MMP-1, -2, -3 and -9 and TIMP-2 and -3 were detected immunohistochemically. The mRNA levels were determined by real-time polymerase chain reaction. The results confirmed that doxorubicin treatment resulted in minimal myocardial fibrosis and showed that expression of MMPs increased and TIMP-3 decreased. The injection procedure resulted in increased myocardial fibrosis in groups 3 and 4. After MSC injection, MMP-1, MMP-2, and TIMP-3 expression was higher than that in group 2. CM injection led to more fibrosis, elevated TIMP-3, but diminished MMP-1 and MMP-2 expression compared with MSC injection. The mRNA levels of MMPs and TIMPs were not significantly different among all groups. In conclusion, chronic doxorubicin cardiomyopathy was characterized by increased MMP and decreased TIMP-3 expression. MSCs injection into the LV resulted in marked differences of collagen content and MMP/TIMP expression in the whole heart, although significant numbers of living MSCs were not detected after 4 weeks.

Ultrastructural findings in porcine hearts after extracorporeal long-term preservation with a modified Langendorff perfusion system.

Preserved ultrastructure is an important precondition for functional regeneration after heart transplantation. We investigated the effectiveness of a newly developed modified Langendorff system in extracorporeal heart perfusion. (Experiment I) Cardioplegia and cold ischaemia were performed in six pigs. Hearts were connected to a modified Langendorff system, and perfused with leucocyte depleted autologous blood. (Experiment II) The untreated hearts of three healthy pigs served as controls. Forty-seven myocardial biopsies at different timepoints (I: n = 29, II: n = 18) were investigated by transmission electronmicroscopy. Cardioplegia/hypothermia (I) induced mild-to-moderate mitochondrial swelling, mild myofibrillar degeneration in cardiomyocytes and moderate endothelial oedema. After 4 h reperfusion cardiomyocytes showed moderate myofibrillar and mild sarcolemmal damage. Moderate endothelial degeneration, mild interstitial oedema and haemorrhages appeared. Untreated hearts (II) showed severely damaged mitochondria and nuclei after 30 min while the myofibrillar structure remained unaffected until 4 h later. This is a promising model for extracorporeal heart perfusion. However, ultrastructural findings indicated that some necessary modifications to prevent cellular damages during reperfusion were needed.

Pharmacodynamics of T-cell function for monitoring immunosuppression.

OBJECTIVES: Recent studies show that measuring pharmacodynamic (PD) effects offers a unique possibility to predict immunosuppression. Thus, in this study we have monitored the PD properties of immunosuppressants on diverse T-cell functions in heart transplant (HTx) recipients. MATERIALS: PDs and blood concentrations (PK) of three different basis-immunosuppressive drugs were studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T-cell function was analysed by expression of proliferating cell nuclear antigen (PCNA) labelling, expression of cytokines (IL-2, IFN-gamma) and surface antigen (for example, CD25) by FACS analysis. RESULTS: In group I, at time points C0 and C2, increased CsA-PK significantly inhibited expression of IL-2, IFN-gamma, PCNA and CD25 (P < 0.05). Correlations (r(2)) at C2 between inhibition of T-cell functions (PD) with PK and with drug doses were: CsA-PK: 0.71-0.91 and CsA-dose: 0.73-0.87. In group II, increased TRL-PK over time did not further inhibit expression of CD25, but inhibited PCNA expression more on day 3, and IL-2 and IFN-gamma expression was significantly higher on days 2 and 3 compared to PD effects of CsA (P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL-PK category, whereas expression of CD25 was higher and expression of cytokines was lower than PD effects of CsA. CONCLUSIONS: Our results show that PD effects on T-cell function can be used to monitor immunosuppression bringing potential to increase the efficacy and safety of immunosuppressive therapy after HTx.

ACE-inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation.

OBJECTIVE: Chronic atrial fibrillation (AF) is characterized by a remodeling process which involves the development of fibrosis. Since angiotensin II has been suspected to be involved in this process, the aim of our study was to investigate a possible influence of an ACE-I therapy in patients with chronic AF regarding the occurrence of left atrial structural remodeling. METHODS: Atrial tissue samples were obtained from patients with lone chronic AF or sinus rhythm (SR). Collagen I, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expression were measured by quantitative Western Blotting techniques and calculated as mean +/- SEM. Histological tissue samples were used for calculating microvessel density (microvessel/mm(2) +/- SEM). RESULTS: In AF, the collagen amount was higher (1.78 +/- 0.21; p = 0.01) vs. SR (0.37 +/- 0.07) accompanied by declining microcapillary density (AF: 145 +/- 13 vs. SR: 202 +/- 9; p = 0.01). Additionally, a negative correlation (p = 0.01) between collagen content and microcapillary density was observed. To investigate the influence of an ACE-I therapy on this remodeling process, patient groups were divided into AF and SR both with or without ACE-I. Interestingly, there was a significantly lower expression of collagen I in AF with ACE-I (1.04 +/- 0.26) vs. AF without ACE-I treatment (2.07 +/- 0.24, p = 0.02). The microcapillaries were not diminished in AF with ACE-I (180 +/- 15) vs. SR with ACE-I (196 +/- 9), but there was a significant rarification in AF without ACE-I (123 +/- 18; p = 0.03). The expression of VEGF and bFGF did not reveal any significant differences. CONCLUSION: In patients undergoing ACE-I treatment: atrial structural remodeling was attenuated and the loss of atrial microcapillaries was prevented.

Foreign body in the airway: unusual cause of acute dyspnoe after cardiac surgery.

We report on a 68-year-old male who presented with acute onset of dyspnoea and cough. After coronary artery bypass grafting and mitral valve repair with an annuloplasty ring, postoperative recovery was initially uneventful. On the 6th postoperative day, he came back to intensive care unit due to acute dyspnoea. Fig. 1 demonstrates chest x-ray. We identified the foreign body as a dental prosthesis (Fig. 2). Removal from the right bronchial tree was successful using a flexible bronchoscope under local anesthesia; intubation was not required. This procedure was safe and well tolerated by the patient. Clinical presentation of adult foreign body aspiration are often nonspecific. Chest x-ray is very helpful for identification and localization of foreign bodies in the airway. Extraction can be performed with flexible or rigid bronchoscopy. For the removal, biopsy forceps, Fogarty balloon catheter, alligator forceps or wire baskets are effective.

C0h/C2h monitoring of the pharmacodynamics of cyclosporin plus mycophenolate mofetil in human heart transplant recipients.

UNLABELLED: Pharmacokinetic (PK) parameters like C2h have improved efficacy of immunosuppressive therapy. However, drug interactions, toxicities, and individual differences to drug effects still remain challenging. Therefore, this study was designed to assess pharmacodynamic (PD) effects of the combination cyclosporin (CsA) plus mycophenolate mofetil (MMF) on lymphocyte functions in peripheral blood of stable heart transplant recipients (HTx) using our established FACS assays. METHODS: Blood from 25 HTx patients was drawn before (C0h) and 2 hours after dosing (C2h). CsA and mycophenolic acid (MPA) concentrations were measured by EMIT. FACS assessed expression of cytokine production (IL-2, TNF-alpha), lymphocyte proliferation (PCNA), and T-cell activation (CD25, CD95). RESULTS: Evening doses of CsA (25/50/75 or 100 mg) and MMF (250/500 or 1000 mg) produced C0h levels as follows: CsA, 162 +/- 12 ng/mL; MPA, 1.7 +/- 0.2 mg/L. Morning doses of CsA (50/75 or 100 mg) and MMF (250/500/1000 or 1500 mg) produced C2h-levels as follows: CsA, 589 +/- 56 ng/mL and MPA, 7.4 +/- 1.3 mg/L. PD effects at C0h/C2h (% expression +/- SEM, all P < .05) were IL-2, 18 +/- 3/10 +/- 2; TNF-alpha, 12 +/- 2/7 +/- 1; PCNA, 8 +/- 1/5 +/- 1; CD25, 26 +/- 4/13 +/- 2; CD95, 23 +/- 4/11 +/- 2). Correlations (r2) at time point C2h between inhibition of lymphocyte functions (PD) with drug concentrations (PK) and with drug doses were CsA-PK, 0.71 to 0.91; MMF-PK, 0.55 to 0.76; CsA-dose, 0.73 to 0.87; MMF-dose, 0.61 to 0.80. CONCLUSION: For the first time, the immunosuppressive effects of the combination CsA plus MMF were quantified in whole blood of human HTx at different time points. PD assays may offer the opportunity to optimize clinical immunosuppressive drug therapy.

Pharmacodynamic monitoring of the conversion of cyclosporine to tacrolimus in heart and lung transplant recipients.

OBJECTIVE: Conversion from cyclosporine (CsA) to tacrolimus (TRL) remains challenging in the daily routine due to individual variations in blood concentrations (pharmacokinetics, PK), pharmacodynamics (PD) and in interactions on plasma mycophenolic acid (MPA) concentrations. Therefore, we used our PD assays of lymphocyte function to monitor the conversion of CsA to TRL in heart (HTx) and lung (LTx) transplant recipients. METHODS: Patients (six HTx, two LTx) were converted from CsA to TRL because of gingival hyperplasia. All patients were treated with 6 mg BID TRL 24 hours after the last CsA dose and received mycophenolate mofetil BID cotherapy. PK measurements of CsA, TRL, and MPA were done by EMIT. Expression of cytokine production (IL-2, TNF-alpha), lymphocyte proliferation (PCNA), and activation (CD25) was assessed by FACS. RESULTS: TRL concentrations increased from day 1 to 3, but did not alter MPA concentrations, which were comparably high to MPA concentrations in combination with CsA (day 0). Compared to CsA therapy, increased TRL concentrations did not further inhibit PCNA expression, inhibited CD25 expression less on days 1 and 2 and equally high on day 3, but inhibited expression of IL-2 and TNF-alpha significantly higher on days 2 and 3 (P < .05). CONCLUSION: This study shows that monitoring PD of lymphocyte functions after conversion from CsA to TRL in HTx and LTx recipients revealed differences of inhibition of lymphocyte functions. Monitoring PD of lymphocyte function may provide insights in drug interactions of immunosuppressive combination therapy and may help to tailor immunosuppression to avoid toxicity and to enhance efficacy.

Early angiographic control of perioperative ischemia after coronary artery bypass grafting.

OBJECTIVE: To assess the impact of immediate angiography in patients with defined clinical and laboratory criteria of perioperative myocardial infarction after coronary artery bypass operation. PATIENTS AND METHODS: Between January 1999 and December 1999 2052 patients underwent coronary artery bypass grafting in our institution. Out of this cohort 131 (6.4%) patients met the criteria of perioperative myocardial ischemia, which was defined as: (a) increase in the isoenzyme ratio of creatinine phosphokinase (CK/CK-MB] above 10%; (b) ischemic electrocardiographic episodes (defined as a new onset of elevated ST-segment change lasting at least 1 min and involving a shift from baseline of greater than or equal to 0.1 mV of ST-depression and a new association of a postoperative Q; (c) recurrent episodes of, or sustained ventricular tachyarrhythmia as well as ventricular fibrillation; (d) hemodynamic deterioration despite adequate inotropic support. RESULTS: Angiography was performed in 108 patients (5.3%, group A) whereas 23 patients (1.1%, group B) were immediately re-operated due to severely compromised hemodynamics. Angiographic results in group A showed regular grafts in 45 patients (2.2%); 63 patients (3.1%) had either an occlusion (n=41), incorrect anastomosis (n=29), graft stenosis (n=14), graft spasm (n=6), displaced graft (n=6), poor distal run-off (n=5) or incomplete revascularization (n=2). In group A 43 patients underwent a re-operation (34 patients) or an early angioplasty (nine patients). Due to poor coronary artery status no intervention was performed in the remaining 20 patients with angiographic findings. Operative findings in group B showed graft occlusion in ten patients (43.5%), incorrect anastomosis in five patients (21.7%), bleeding, stretched graft, venous graft spasm and displaced graft in one patient (4.3%) each, and no patho-morphological finding in 4 patients (17.4%). Thirty-day mortality rate was ten patients in group A (9.3%), all of them with angiographic findings, as opposed to nine patients (39.1%) in group B. CONCLUSION: ST-change and elevated CK/CK-MB enzyme ratio is highly indicative for possible graft failure and should be followed early angiographic control to assess the need for reintervention.