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Jan F Gummert

Publications and source records attributed to Jan F Gummert.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacodynamic monitoring of the immunosuppressive therapy in patients after heart transplantation: whole blood flow cytometric analysis of lymphocyte function.

Despite therapeutic monitoring and daily measurements of blood concentrations (pharmacokinetics) of immunosuppressive medications, immunosuppressive therapy remains still a challenge after heart transplantation (HTx) due to drug interactions, toxicities and individual responses to drug effects. We established whole blood flow cytometric assays of lymphocyte function to assess the pharmacodynamics of immunosuppressive therapy and investigated both pharmacokinetic and pharmacodynamic approaches after HTx. Our results showed that pharmacodynamic measurements provide a more direct assessment of the functional activity of immunosuppressants on immune cells compared to drug level monitoring alone. The information from both pharmacokinetic and pharmacodynamic monitoring has the potential to increase the efficacy and safety of individual immunosuppressive therapy after HTx.

Aged↗
PubMed2006

Affects of immunosuppression on circulating dendritic cells: an adjunct to therapeutic drug monitoring after heart transplantation.

OBJECTIVES: Recent evidence emerges dendritic cells (DCs) as pharmacological targets of immunosuppressive drugs. Therefore, in this study we monitored DCs in peripheral blood to compare the effects of calcineurin inhibitors (CNI: cyclosporine, tacrolimus) and mammalian target of rapamycin inhibitors (sirolimus, SRL, everolimus, ERL) basis-immunosuppressive therapies in human heart transplanted (HTx) recipients. METHODS: We compared HTx recipients which were converted from either CNI to ERL (severe renal dysfunction, n=8), or from SRL to ERL (approval of ERL for HTx, n=8) with 20 healthy human controls. Twenty four after the last CNI or SRL dose recipients were treated with ERL/BID on days 1-3. Peripheral blood was collected at trough in the morning before and on day 4 after conversion. Percentages of positive myeloid and plasmacytoid DC (m and pDC) subsets in peripheral blood were analysed by flow cytometry. The status of maturation was further characterised by flow cytometry analysis of % expression of CD83 and % expression of various intracellular cytokines (IL-1beta, TNF-alpha, IL-8, IL-12), respectively. RESULTS: HTx recipients had higher % positive mDCs regardless the immunosuppressive therapy compared to controls (p<0.05). Whereas, % positive pDCs were only significantly lower in recipients converted from CNI to ERL compared to controls (p<0.05). The data consolidate the finding that the subset ratio pDCs/mDCs was lower in recipients compared to controls. But after conversion from CNI or SRL to ERL the ratio increased towards pDCs. Percentages of expression of CD83 on mDCs were not different among the recipient groups and controls. Recipients with CNI and SRL had higher % expression of IL-12 and lower % expression of IL-1beta compared to controls (p<0.05). However, after conversion to ERL % expression of both IL-12 and IL-1beta returned to control values in both groups. CONCLUSIONS: The results showed that analysis of immunosuppression of circulating DCs in peripheral blood may be an adjunct to therapeutic drug monitoring to optimize immunosuppressive therapy after HTx.

Antigens, CD↗
PubMed2006

The influence of immunosuppressive drugs on T- and B-cell apoptosis via p53-mediated pathway in vitro and in vivo.

BACKGROUND: This study was designed to assess the effects of calcineurin and inosine-5-monophosphate-dehydrogenase inhibitors on p53-mediated-apoptosis in T- and B-cells in vitro and in human heart-transplanted recipients (HTx-R). METHODS: For in vitro experiments, peripheral blood from healthy volunteers was collected and treated either with 1 microM cyclosporin A (CsA; n = 6), 10 microM mycophenolic acid (MPA; n = 6) or 100 nM tacrolimus (TRL; n = 6). For the second part, peripheral blood was collected from HTx-R undergoing CsA-MPA (n = 11) or TRL-MPA (n = 11) therapy before (0 hr) and after (2 hr) acute drug application and from healthy volunteers (n = 11) without drug therapy. Whole blood (part 1+2) was stimulated (24 hr) with eight different concentrations of actinomycin-D (0-800 nM), an apoptosis inductor acting via p53-pathway. Apoptotic lymphocytes were measured by TUNEL and expression of Annexin-V using FACS. Drug effects were calculated by taking the effects of actinomycin-D as baseline values. RESULTS: In vitro drug treatment with CsA, MPA, and TRL significantly (P < 0.05) decreased the apoptotic effect of actinomycin-D in T-cells in a noncompetitive manner. In HTx-R undergoing drug therapy, there was a similar antiapoptotic effect observed in both T- and B-cells (P < 0.05). Differences between 0 hr and 2 hr after acute drug application did not exist. Apoptosis induced by actinomycin-D can be completely blocked by caspase-inhibitor zVAD-FMK. CONCLUSION: Our results suggest that, in vitro and in HTx-R, an inhibition of calcineurin and inosine-5-monophosphate-dehydrogenase by CsA, TRL, or MPA lead to an inhibition of T-and B-cell apoptosis via p53-pathway. This assay may be helpful to provide insights into mechanisms of immunosuppressive drugs in regulation of apoptosis in lymphocytes.

Apoptosis↗
PubMed2006

Patient prosthesis mismatch affects short- and long-term outcomes after aortic valve replacement.

OBJECTIVE: The aim of this study was to evaluate the impact of patient prosthesis mismatch (PPM) and additional risk factors on outcome after aortic valve replacement (AVR). METHODS: Four thousand one hundred and thirty-one patients who were operated between May 1996 and April 2004 were evaluated. One thousand eight hundred and fifty-six patients received bileaflet mechanical AVR and 2275 stented xenograft AVR. PPM was defined as severe if manufacturers effective orifice area (EOA) divided by body surface area (BSA) was <0.65 cm(2)/m(2) and as moderate in the range of 0.65-0.85 cm(2)/m(2). PPM, age, gender, EOA index, emergency indication for surgery (within 24h), EuroSCORE as well as requirement for additional procedures were tested. Univariate (Fisher's exact test) and multivariate logistic regression analysis as well as survival analysis (Kaplan-Meier) were performed. RESULTS: Severe PPM was present in 97 (2.4%) and moderate PPM in 1103 (26.7%) patients. PPM occurs more frequently with xenograft AVR. In-hospital mortality was 5.2% for severe, 10.6% for moderate and 6.9% with no PPM (p=0.018, OR 1.4). Moderate PPM was independently predictive for short- and long-term mortality. Further analysis revealed patient age >70 years (n=1589, p=0.002, OR 1.85), emergency indication (n=374, p<0.001, OR 4.4), EuroSCORE >10 (n=494, p<0.001, OR 4.7) and additional cardiac procedures (n=2049, p<0.001, OR 2.0) as predictors for adverse outcome after AVR. CONCLUSION: Severe PPM is rare; moderate PPM is present in a quarter of patients. PPM has a significant impact on short- and long-term mortality after AVR.

Aged↗
PubMed2006

Cytokine analysis to predict immunosuppression.

BACKGROUND: Recently, it has been realized that TH1/TH2 cytokine production offer the unique possibility to predict drug efficacy. However, there is still an incessant need to explore assay conditions and techniques of analyzing cytokines, which are specific and reliable for monitoring drug efficacy. METHODS: In this study we used the multiplex bead array technique to detect cytokines of TH1/TH2 cells in whole blood of heart transplanted (HTx) recipients. RESULTS: We found significantly different levels of cytokine expression in HTx recipients compared with cytokine levels in patients prior to HTx. Furthermore, particular cytokine levels were significantly decreased 2 h after drug dosing, compared with cytokine levels before dosing in mitogen-stimulated whole blood. CONCLUSIONS: Cytokine analysis with the multiplex array technique in mitogen-stimulated whole blood provides the possibility to predict immunosuppression.

Cyclosporine↗
PubMed2006

Six-month angiographic follow-up of the PAS-Port II clinical trial.

BACKGROUND: The PAS-Port device (Cardica, Redwood City, CA) allows the rapid deployment of a clampless proximal anastomosis between a vein graft and the aorta. METHODS: Fifty-four patients awaiting elective coronary artery bypass graft surgery were enrolled. Outcome variables were intraoperative device performance, early and 6- month angiographic graft patency, and 12-month clinical follow-up. RESULTS: Sixty-three PAS-Port devices were deployed in 54 patients. Two deployments were unsuccessful. There were no reoperations for bleeding. Two patients died of causes unrelated to the device. Patency evaluation at discharge was performed by angiogram on 49 implants and computed tomography in 2 implants (86% follow-up). At discharge, all evaluated grafts were patent (100%) and rated Fitzgibbon A. At 6-month follow-up, there was no additional mortality; 47 implants (88% follow-up) were evaluated by angiography (Fitzgibbon O [n = 1], Fitzgibbon B [n = 1], and Fitzgibbon A [n = 45]) and 5 by computed tomography. All grafts but 1 were patent (98.1%). At 12 months, 2 additional patients died of causes unrelated to the PAS-Port implant. Forty-six of 50 alive patients (95.8%) were followed up without any reports of device-related major adverse cardiac events. CONCLUSIONS: Discharge (100%) and 6-month patency (98%) are excellent; patency and 12 months' clinical follow-up compares favorably with data from historical hand-sewn controls. The PAS-Port system safely allows the clampless creation of a proximal anastomosis.

Aged↗
PubMed2006

Both T-786C and G894T polymorphism of endothelial nitric oxide synthase affect in-vitro endothelium-dependent relaxation of internal mammary artery rings from patients with coronary artery disease.

OBJECTIVES: Polymorphisms of endothelial nitric oxide synthase (eNOS) gene in the promoter (T-786C) and exon 7 (G894T) have been suggested to attenuate endothelial function. As it is unknown whether these polymorphisms, on top of classical risk factors, further deteriorate endothelium-dependent vasomotion, we aimed to elucidate the impact of both polymorphisms on the ex-vivo vasomotor function of left internal mammary artery rings from patients with coronary artery disease (CAD) undergoing coronary bypass surgery (CABG). METHODS: Mammary artery rings from 51 consecutive patients with CAD were obtained during elective CABG. Endothelium-dependent ring relaxation was measured in vitro in an organ chamber using acetylcholine (10 to 3 x 10 mol/l). Polymorphisms were determined by polymerase chain reaction restriction length polymorphism. RESULTS: Thirty-three per cent of patients were positive for the T-786C polymorphism, 25% for the G894T polymorphism, and 18% carried mutated alleles in both loci. Maximal acetylcholine-induced ring relaxation was 46.7+/-3.2% in T-786C, 59.6+/-4.2% in G894T, and 66.7+/-7.4% in T-786C/G894T compared with 94.9+/-2.0% in wild-type subjects (P<0.05 versus T-786C, G894T, T-786C/G894T). Patients positive for an eNOS polymorphism with more than three cardiovascular risk factors displayed a further attenuation of acetylcholine-mediated relaxation (45+/-6 %) compared with having up to three risk factors (59+/-3%, P<0.05). CONCLUSION: In patients with CAD, in-vitro assessed endothelium-dependent relaxation of mammary arteries was significantly impaired in those positive for the T-786C or the G894T eNOS polymorphism. These results suggest that the presence of either one of the eNOS polymorphisms deteriorated endothelium-dependent vasodilatory capacity of large conduit vessels on top of classical risk factors in patients with CAD.

Aged↗
PubMed2005

Comparison of bare-metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery: a 5-year follow-up.

BACKGROUND: Randomized trials comparing stenting with minimally invasive direct coronary artery bypass surgery in patients with isolated proximal left anterior descending lesions have shown a significantly higher reintervention rate for stenting and similar results for mortality and reinfarction at short-term follow-up. Long-term follow-up data are sparse. METHODS AND RESULTS: Patients with isolated proximal left anterior descending stenosis were randomized to either surgery (n=110) or bare-metal stenting (n=110). At 5 years, follow-up data were obtained with respect to the primary end point of death, reinfarction, or repeated target vessel revascularization. Clinical symptoms were assessed by the Canadian Cardiovascular Society (CCS) classification. Follow-up information was completed for 216 patients (98.2%), and mean follow-up was 5.6+/-1.2 years. With respect to mortality (surgery, 12%; stenting, 10%; P=0.54) and reinfarctions (surgery, 7%; stenting, 5%; P=0.46), there were no differences between treatment strategies. The need for repeated target vessel revascularization was significantly higher after stenting (32%) compared with surgery (10%; P<0.001). Clinical symptoms improved significantly in both treatment groups compared with baseline; however, there was a favorable trend for surgery (stenting: CCS, 2.6+/-0.9 to 0.5+/-0.8, P<0.001; surgery: CCS, 2.6+/-0.9 to 0.3+/-0.6, P<0.001; P=0.05, stenting versus surgery). CONCLUSIONS: At the 5-year follow-up, minimally invasive bypass surgery and bare-metal stenting showed similar results for the end points of mortality and reinfarctions. However, the reintervention rate is higher after stenting, and the relief in clinical symptoms is slightly better after surgery.

Aged↗
PubMed2005

The Cardica C-Port System: clinical and angiographic evaluation of a new device for automated, compliant distal anastomoses in coronary artery bypass grafting surgery--a multicenter prospective clinical trial.

OBJECTIVES: The C-Port System (Cardica, Inc, Redwood City, Calif) integrates in one tool all functions necessary to enable rapid automated distal coronary anastomoses. The goal of this prospective, nonrandomized, and multicenter study is to determine the safety and efficacy of this novel anastomotic system. METHODS: Five centers enrolled 133 patients awaiting elective coronary artery bypass grafting surgery. Outcome variables were intraoperative device performance, incidence of device-related adverse events, predischarge and 6-month angiographic graft patency, and 12-month clinical outcome. Independent core laboratories performed qualitative and quantitative angiographic and computed tomographic assessments. RESULTS: The C-Port was used to perform a vein-to-coronary anastomosis in 130 patients. Intraoperative conversion to a hand-sewn anastomosis was necessary in 11 patients because of inadequate target site preparation, inappropriate target vessel selection, or both. Inadequate blood flow related to poor runoff required conversion in 3 additional patients. Three patients died before discharge of causes unrelated to the device. At discharge, 113 patients had a C-Port implant in place, and 104 C-Port anastomoses were studied by means of angiography, resulting in 100 FitzGibbon A, 3 FitzGibbon B, and 1 FitzGibbon 0 classifications. At 6 months, one additional patient died of a device-unrelated cause, and 98 patients were evaluated by means of angiography (n = 89). Overall patency (FitzGibbon A) was 92.1%. Three C-Port anastomoses were rated FitzGibbon B, and 4 were rated FitzGibbon 0. At 12 months, 107 (98.2%) of 109 alive patients were followed up, without any reports of device-related major adverse cardiac events. CONCLUSIONS: The C-Port System allows for a rapid, reliable, and compliant distal anastomosis and yields favorable 6-month angiographic and 12-month clinical results when compared with published studies.

Aged↗
PubMed2005

Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease.

BACKGROUND: In patients with stable coronary artery disease, physical exercise training (ET) improves endothelial dysfunction. A potential mechanism mediating the enhanced vasomotor function is a reduced breakdown of endothelium-derived nitric oxide by reactive oxygen species (ROS). The aim of the present study was to analyze the impact of ET on sources of ROS generation in the left internal mammary artery of patients with symptomatic coronary artery disease. METHODS AND RESULTS: In left internal mammary artery rings sampled during bypass surgery from 45 patients randomized to either a training (n=22) or an inactive control (n=23) group, the mRNA expression of NAD(P)H oxidase subunits, NAD(P)H oxidase activity, and ROS production were assessed. In addition, endothelial function, expression of angiotensin II (Ang II) receptor type 1 and 2 (AT1-R and AT2-R), and Ang II-mediated vasoconstriction were determined. ET resulted in a significant lower expression of gp91phox (23.1+/-0.5 versus 69.1+/-18.1 arbitrary units, training versus control), p22phox (0.7+/-0.3 versus 2.0+/-0.5 arbitrary units), and Nox4 (2.7+/-1.2 versus 5.4+/-1.0 arbitrary units). Enzymatic activity (2.1+/-0.3 versus 4.9+/-0.4 mU/mg) and ROS generation (0.02+/-0.01 versus 0.06+/-0.02 arbitrary units) were significantly lower in the training compared with the control group. On a functional level, ET resulted in improved acetylcholine-mediated vasodilatation and a 49% reduction in Ang II-induced vasoconstriction, accompanied by lower AT1-R (3.7+/-0.8 versus 16.6+/-5.7 arbitrary units, training versus control) and higher AT2-R (7.8+/-2.5 versus 1.6+/-0.7 arbitrary units) mRNA expression. CONCLUSIONS: ET reduces vascular expression of NAD(P)H oxidase and AT1-R, resulting in decreased local ROS generation. These molecular effects converge in a reduced Ang II-mediated vasoconstriction.

Aged↗
PubMed2005

Anomalous origin of the right coronary artery from the pulmonary artery combined with aortic valve stenosis.

We report the case of a 41-year-old patient presenting with anomalous of origin of the right coronary artery from the pulmonary artery (ARCAPA) and severe aortic valve stenosis. Surgical correction was performed by partial (T-shaped) sternotomy. After replacing the bicuspid aortic valve, the right coronary artery ostium was directly reimplanted into the aortic root. The main pulmonary artery was reconstructed using an autologous pericardial patch. Postoperative recovery was uneventful. Four cases involving an association of the bicuspid aortic valve and ARCAPA have been reported in the literature. This potential relationship should be considered whenever diagnosing a bicuspid aortic valve.

Abnormalities, Multiple↗
PubMed2005

Successful management of two heart transplant recipients with mycobacterial pulmonary infections.

We report two cases of pulmonary tuberculosis in heart transplant recipients: a 46-year-old man with pulmonary tuberculosis due to Mycobacterium tuberculosis and a 64-year-old man with nontuberculous mycobacterial infection with pulmonary infiltrates due to Mycobacterium xenopi. The time intervals from transplantation to diagnosis were 3 and 4 years, respectively. The patient with tuberculosis underwent standard treatment with isoniazid, rifampin, ethambutol, and pyrazinamide. The patient with the nontuberculous mycobacterial infection received treatment with clarithromycin and ciprofloxacin for 18 months in addition to rifampin for the first 3 months. Both patients responded well to treatment. No recurrences were observed during follow-up. The interactions between antibiotic treatment and cyclosporine therapy should be observed closely in organ transplant recipients, requiring frequent level determinations and dosing changes.

Anti-Infective Agents↗
PubMed2005

Facilitated minimally invasive left ventricular epicardial lead placement.

PURPOSE: Atrial-synchronized biventricular pacing is an effective treatment option in patients with heart failure and interventricular conduction delay. Owing to a failed transvenous implantation in some patients, the left ventricular (LV) lead has to be placed surgically, usually by an anterolateral thoracotomy. We used a novel malleable epicardial lead placement tool (Epicardial Lead Implant Tool, Model 10626; Medtronic, Minneapolis, MN) that facilitates lead placement on the posterior aspect of the LV through an anterolateral minithoracotomy. DESCRIPTION: The tool consists of a malleable steel shaft with distal gripping tongs for the epicardial lead. Proximally, a thumbwheel and an actuator button allow fixation and release of the lead on the myocardium. EVALUATION: We used this tool in 7 patients through an anterolateral minithoracotomy. All patients had a safe, successful, and rather short procedure. No scopes were required. CONCLUSIONS: Epicardial LV lead placement through an anterolateral minithoracotomy is facilitated by using the Lead Implant Tool. Lead placement is achieved by the malleable shaft design, which enables perpendicular implantation of the lead pad on the posterior LV surface with an anterolateral approach.

Defibrillators, Implantable↗
PubMed2005

Impact of off-pump coronary bypass grafting on the prevalence of adverse perioperative outcome in women undergoing coronary artery bypass grafting surgery.

BACKGROUND: Female gender has been associated with a high prevalence of perioperative morbidity and mortality in coronary artery bypass grafting surgery (CABG). We attempted to determine a potential benefit of off-pump CABG as compared with on-pump CABG (OPCAB) with regard to perioperative outcome in female patients. METHODS: Data were prospectively gathered on 2,182 consecutive female patients undergoing CABG either with or without cardiopulmonary bypass from 1996 to 2001. The associations between OPCAB surgery in addition with 22 further preoperative patient-related or treatment-related variables and 26 perioperative outcome variables were assessed with multivariable logistic regression analysis. RESULTS: One hundred fifty-two (7.0%) female patients underwent OPCAB surgery during the study period. Women undergoing OPCAB had higher ejection fractions and received fewer coronary artery bypass grafts than CABG patients. Surgery using OPCAB was associated with shorter hospital stays, less bleeding, less transfusion requirements, and lower mortality than CABG. Furthermore, OPCAB surgery was independently associated with a lower prevalence of high perioperative transfusion requirement, postoperative respiratory insufficiency, postoperative renal insufficiency, and dialysis. Prevalence of postoperative blood loss of at least 500 mL was significantly higher after OPCAB surgery. CONCLUSIONS: OPCAB in female patients undergoing coronary artery bypass surgery is safe and seems to be beneficial with regard to perioperative outcome as compared with conventional on-pump CABG. For that reason, off-pump surgery may be an effective method of lowering morbidity and mortality in these relatively high-risk patients.

Aged↗
PubMed2005

Significant value of autopsy for quality management in cardiac surgery.

OBJECTIVE: With recent advances in diagnostic imaging, the value of autopsy has been called into question. The aim of our study was to assess the current impact of autopsy for early postoperative quality management in cardiac surgery. METHODS: Between 2000 and 2003, a total of 14,313 patients underwent cardiac surgery at our center. Of these, 898 patients (6.3%) died, and autopsy was performed in 468 cases (52.1%). Data from clinical and postmortem examination were prospectively analyzed regarding causes of death, postoperative complications, concomitant diseases, and surgery-associated pathologic findings. RESULTS: Mean age was 68.7 years. Mean survival was 13.9 postoperative days. On autopsy, causes of death were cardiac in 49.8% of cases (n = 233), respiratory in 8.3% (n = 39), cerebral in 6.4% (n = 30), abdominal in 4.7% (n = 22), multiorgan failure or sepsis in 14.9% (n = 70), pulmonary embolism in 6.6% (n = 31), procedure associated in 8.3% (n = 39), and others in 0.9% (n = 4). Discrepancies between clinical and postmortem determinations of cause of death were found in 108 cases (23.1%). These were acute myocardial infarction (n = 38), low cardiac output (n = 9), respiratory (n = 8), cerebral (n = 5), abdominal (n = 7), multiorgan failure or sepsis (n = 12), pulmonary embolism (n = 18), and procedure associated (11). Clinically unrecognized postoperative complications were found in 364 cases (77.8%). Unknown concomitant diseases were found in 464 cases (99.1%), with potential therapeutic relevance in 90 cases (19.2%). In 85 cases (18.2%), autopsy examination revealed 96 premortem unrecognized surgery-associated pathologic findings. CONCLUSION: A high overall discrepancy rate between premortem and autopsy diagnoses was recognized. Autopsy revealed clinically relevant information in a significant number of cases. Therefore autopsy remains essential for quality assessment in perioperative treatment.

Aged↗
PubMed2005

Mycophenolic acid interaction with cyclosporine and tacrolimus in vitro and in vivo: evaluation of additive effects on rat blood lymphocyte function.

The effect of mycophenolic acid (MPA) in combination with either cyclosporine (CsA) or tacrolimus (TRL) on whole-blood lymphocyte function was assessed in vitro as well as in vivo. For the in vitro studies, rat whole blood was incubated with different concentrations of MPA together with CsA or TRL. In vivo, rats (n = 6 per group) were orally treated with 2.5 or 5 mg/kg of mycophenolate mofetil (MMF), either alone or in combination with 5 mg/kg CsA or 4 mg/kg TRL. Blood was obtained before and at different times after dosing. For both in vitro and in vivo studies, mitogen-stimulated whole blood was analyzed by flow cytometry to determine inhibition of expression of lymphocyte proliferation (proliferating cell nuclear antigen, PCNA) and T-cell activation (eg, CD25). Plasma MPA concentrations were measured by HPLC, and whole-blood CsA and TRL concentrations were quantified using LC-MS/MS. In vitro, low concentrations of 250 and 500 nM MPA acted additively with CsA and overadditively with TRL to suppress lymphocyte function, whereas higher MPA concentrations (1000 nM) in these combinations did not further increase inhibition compared with monotherapy with CsA or TRL alone. In vivo, the MPA AUC0-24 showed a dose-dependent increase. CsA and TRL AUC0-24 were not influenced by the MMF dose. Combination therapy increased inhibition of lymphocyte function compared with MMF monotherapy with a pronounced effect on PCNA compared with CD25. Significant differences between 2.5 and 5 mg/kg MMF in the combination groups were observed at 2 or 6 hours after dosing because of the maximal inhibitory effect on PCNA and CD25 expression (P < 0.05, ANOVA). However, in combination with TRL no different effects on the inhibition of CD25 expression were found between the 2 MMF doses. These novel data indicate that measurement of pharmacodynamic parameters of lymphocyte function in whole blood may help to monitor drug combination therapy and provide a rationale for drug reduction to minimize toxicity without compromising efficacy.

Administration, Oral↗
PubMed2005

Anastomotic devices for coronary artery bypass grafting.

With the advent of off-pump and minimally invasive coronary artery bypass grafting, efforts to facilitate construction of the graft to coronary anastomosis have increased. As a result, a number of anastomotic devices have been developed. While the ideal anastomotic device should be easy to use, produce a geometrically optimal anastomosis with minimal endothelial damage and minimal blood-exposed nonintimal surface, a number of design constraints apply. This review collects the available preclinical and clinical data for some of the devices, with special regard as to surgical outcome, patency rate and the need for additional perioperative anticoagulation treatment.

Anastomosis, Surgical↗