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Biomedical subjects

J Gummert

Publications and source records attributed to J Gummert.

At least 19 recordsLinked to original sources

Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease.

OBJECTIVE: To examine the hypothesis that major extracellular matrix (ECM) proteins are expressed differently in the left atrial tissue of patients in sinus rhythm (SR), lone atrial fibrillation (AF), and AF with underlying mitral valve disease (MVD). DESIGN: Case-control study. PATIENTS: 118 patients with lone AF, MVD+AF, and SR. MAIN OUTCOME MEASURES: Collagen I, collagen III, and fibronectin protein expression measured by quantitative western blotting techniques and immunohistochemical methods. RESULTS: Protein concentrations increased in patients with AF (all forms) compared with those in SR (all forms): collagen I (1.15 (0.11) v 0.45 (0.28), respectively; p = 0.002), collagen III (0.74 (0.05) v 0.46 (0.11); p = 0.002, and fibronectin (0.88 (0.06) v 0.62 (0.13); p = 0.08). Especially, collagen I was similarly enhanced in both lone AF (1.49 (0.15) and MVD+AF (1.53 (0.16) compared with SR (0.56 (0.28); both p = 0.01). Collagen III was not significantly increased in lone AF but was significantly increased in AF combined with MVD (0.84 (0.07) both compared with SR (0.46 (0.11); p = 0.01). The concentration of fibronectin was not significantly increased in lone AF and MVD+AF (both compared with SR). Furthermore, there was a similar degree of enhanced collagen expression in paroxysmal AF and chronic AF. CONCLUSIONS: AF is associated with fibrosis. Forms of AF differ from each other in collagen III expression. However, there was no systematic difference in ECM expression between paroxysmal AF and chronic AF. Enhanced concentrations of ECM proteins may have a role in structural remodelling and the pathogenesis of AF as a result of separation of the cells by fibrotic depositions.

Atrial Fibrillation↗

Cardiac malformations associated with the Holt-Oram syndrome--report on a family and review of the literature.

The Holt-Oram syndrome (HOS) is characterized by mild-to-severe congenital cardiac defects and skeletal abnormalities of the upper limb. The most common cardiac disorder is an ostium secundum atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. Electrocardiographic abnormalities, such as various degrees of atrioventricular block, have also been reported. In addition, hypoplastic peripheral vessels of the upper limbs have been observed. Here, we will report about a family with three sons having HOS, and we will detail the cardiac spectrum of HOS as reported in the literature.

Adult↗

Humoral immune response during coronary artery bypass grafting: A comparison of limited approach, "off-pump" technique, and conventional cardiopulmonary bypass.

BACKGROUND: The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques. METHODS AND RESULTS: Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-alpha receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (P:<0.05). TNF-alpha receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach. CONCLUSIONS: There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma. The release of immune mediators is enhanced by the use of CPB during various perioperative and postoperative phases. The type of operative approach did not influence this immune response.

Aged↗

Prevention of acute allograft rejection in nonhuman primate lung transplant recipients: induction with chimeric anti-interleukin-2 receptor monoclonal antibody improves the tolerability and potentiates the immunosuppressive activity of a regimen using low doses of both microemulsion cyclosporine and 40-O-(2-hydroxyethyl)-rapamycin.

BACKGROUND: In previous studies of cynomolgus monkey lung allograft recipients, we demonstrated significant immunosuppressive efficacy but reduced tolerability after combined treatment with high doses of microemulsion cyclosporine (CsA) and SDZ RAD (40-O-(2-hydroxyethyl)-rapamycin). The current study was designed to compare efficacy and tolerability of a combination of low-dose CsA and high-dose SDZ RAD (CTL group) to triple therapy using the chimeric anti-interleukin-2 (IL-2) receptor (CD25) monoclonal antibody (mAb) basiliximab (anti-IL-2 receptor mAb) for induction therapy (basiliximab: 5 mg intravenously on days 0 and 4) plus low-dose CsA and low-dose SDZ RAD for maintenance immunosuppression (CD25 group). CsA and anti-IL-2 receptor mAb are drugs that reduce cytokine synthesis and block IL-2-mediated lymphocyte stimulation, respectively. SDZ RAD blocks lymphocyte stimulation by other cytokines (e.g., IL-15) that are not inhibited by anti-IL-2 receptor mAb. METHODS: Twelve unilateral lung transplants were performed. Recipients were observed for 49 days by daily weight assessment, hemograms, blood chemistries, radiographs, and lung biopsies. Monkeys were euthanized before day 49 in the event of excessive weight loss (>25%) or organ failure. Target CsA trough levels were 100-200 ng/ml. Target SDZ RAD trough levels in the CTL group (no mAb) were 20-40 ng/ml, and 10-20 ng/ml in the CD25 group. RESULTS: None of the monkeys in the CD25 group needed to be euthanized early due to signs of drug toxicity. In contrast, four monkeys in the CTL group were sacrificed on days 28-35 as a result of excessive weight loss (n=3) and renal functional impairment (n=1). Three recipients in the CD25 group were euthanized on days 36, 38, and 46 as a result of persistent high fever associated with severe rejection. The median animal survival in the CTL group was 32 vs. 46 days in the CD25 group (P<0.04). The only two long-term survivors in the CTL group showed moderate rejection at day 49. The median rejection scores at day 14 (A0) and day 28 (A2) were identical in the two groups, despite the fact that the mean SDZ RAD trough level was significantly lower in the CD25 group (CTL: 38+/-3 ng/ml, CD25: 18+/-2 ng/ml, P<0.0001). After basiliximab levels fell below the minimum therapeutic level (1 mg/ml) on day 28, the median rejection score at day 49 increased to A4 in the CD25 group. CONCLUSION: This is the first study to combine an anti-IL-2 receptor mAb with a drug from the rapamycin class plus CsA. Our study shows that induction therapy with basiliximab enabled SDZ RAD blood levels to be significantly reduced, which led to improved tolerability without the penalty of increased rejection.

Animals↗

Prospectively randomized evaluation of stentless versus conventional biological aortic valves: impact on early regression of left ventricular hypertrophy.

BACKGROUND: The aim of this prospectively randomized study was to evaluate left ventricular hypertrophy and its regression after stentless versus conventional biological aortic valve replacement. METHODS AND RESULTS: From March 1996 through April 1998, 180 patients were prospectively selected; 106 patients received a stentless aortic valve (SAV), and 74 received a conventional stented bioprosthesis (CSB). Of these patients, 95% and 96%, respectively, had aortic stenosis. Their mean age was 72.3 and 74.8 years, and there were no significant differences in left ventricular function, preoperative pressure gradients, and NYHA functional status. Aortic annulus diameter indexes were comparable at 13.46 (SAV) versus 13.55 (CSB) mm (P=NS). Larger SAVs were implanted because of the oversizing technique. In-hospital mortality (n=3 and 1 for SAV and CSB) was not valve related. At follow-up, all patients were in NYHA class 1 or 2. Baseline end-diastolic left ventricular posterior wall thickness was 15.6 (SAV) and 14.8(CSB) mm (P=NS) and decreased to 11. 8 (SAV) and 13.2 (CSB) mm (P<0.05) at 6 months. Left ventricular mass index was 213 and 202 g/m(2) at baseline (P=NS), whereas after 6 months, it was 141 (SAV) and 170 (CSB) g/m(2) (P<0.05). CONCLUSIONS: Regression of left ventricular hypertrophy occurs in all patients after aortic valve replacement but is significantly enhanced after SAV implantation. This possibly is due to improved transvalvular hemodynamics.

Aged↗

Effectiveness of different anticalcification treatments for stentless aortic bioprostheses.

BACKGROUND: New anticalcification treatments for stentless bioprostheses have not yet been compared independently. MATERIAL AND METHODS: The No-reacts (Biocor), AOA (Medtronic Freestyle), and BiLinx (SJM Toronto SPV II) methods were studied and compared with a control group. Aortic valve leaflet and aortic root tissue was subcutaneously implanted in 60 male, 21-days-old Sprague-Dawley rats. Calcium content was quantified using inductively coupled plasma spectrophotometry. RESULTS: No infections occurred. Low levels of calcium were measured in aortic valve leaflet tissue for all methods (0.4 to 1.5 mg/g dry weight) in comparison to the control group (225 mg/g), p < 0.01. Calcification of aortic root tissue was low in the Bilinx group (2.4 mg/g, p < 0.01), whereas calcium levels were high in all other groups (104 to 127 mg/g). CONCLUSIONS: Calcification of aortic valve leaflets was significantly reduced by all new anticalcification treatments, whereas aortic root calcification was only reduced by inhibition of cellular calcification (BiLinx). Maximum anticalcification properties of both leaflet and aortic root are important, as these are considered a functional unit in stentless bioprostheses.

Aluminum Chloride↗

Regression of left ventricular hypertrophy after stentless versus conventional aortic valve replacement.

The goal of this study was to analyze regression of left ventricular hypertrophy after randomization to conventional biological versus stentless aortic valve replacement. Stentless (Freestyle, Toronto, n = 106) or conventional biological aortic valves (Carpentier-Edwards, n = 74) were evaluated prospectively. Preoperatively there were no differences with regard to aortic valve pathology, left ventricular function, and pressure gradients between the two patient groups. The patient annulus index (13.55 vs. 13.46 mm; NS) measured intraoperatively was used as baseline for further comparison. Postoperatively, left ventricular mass index was 213+/-77 g/m2 (stentless) compared with 202+/-72 (conventional group) g/m2 (NS), whereas after 6 months it was 141+/-41 g/m2 in the stentless and 170+/-43 g/m2 in the conventional group (P<.05). Regression of left ventricular hypertrophy occurs in all patients after aortic valve replacement. Nevertheless, the use of stentless bioprostheses leads to a significant enhancement, which may result in a reduction of the cardiac risk profile for the patient.

Aged↗

Sensing lead insulation defect resulting in a damage of the ICD pulse generator case.

Eight months after ICD implantation with an electrically active case the patient presented with ICD system sensing failure. Upon reoperation, we found an insulation defect of the proximal sensing lead and the generator case showed arc marks suggesting a short circuit between the sensing lead and case. The generator was replaced, the original sensing lead insulated, and a new sensing lead inserted. Bench testing of the explanted generator showed a damaged internal circuitry. Proximal lead insulation defects combined with electrically active cases may result in damage of the case. The potential damage of internal circuitry warrants generator replacement.

Defibrillators, Implantable↗

Stentless valve replacement in the small aortic root.

Despite the variety of different artificial heart valves available, no ideal prosthesis for the small aortic root has yet been identified. The aim of this study was to evaluate the haemodynamic performance and clinical outcome after stentless aortic valve replacement. A total of 70 patients with a small aortic root underwent Toronto (n = 61) or Freestyle (n = 9) stentless aortic valve replacement. All but three patients had aortic stenosis. Mean (s.d.) age at operation was 71.2(7.9) years. The mean annular diameter was 21.4(1.2) mm. Using controlled oversizing adjusting valve size to the sinotubular junction diameter, a 23-mm prosthesis was implanted in 23 patients and a 25-mm prosthesis in 47 patients. The maximum pressure gradient was 19.1(6.8) mmHg and effective valve orifice area was 1.47(0.27) cm2. At discharge and at follow-up, all patients were in New York Heart Association class I or II. At follow-up there was a significant reduction in pressure gradients, an increase in effective valve orifice areas, and decrease of pre-existing left ventricular hypertrophy. In conclusion, with controlled oversizing a gain in prosthesis size of 2 to 4 mm can be achieved. Implantation of oversized stentless valves leads to improved haemodynamics and to left ventricular remodelling in patients with a small aortic root.

Aged↗

Should 6-thioguanine nucleotides be monitored in heart transplant recipients given azathioprine?

The commonly used immunosuppressive regimen after orthotopic heart transplantation consists of cyclosporine (CsA), azathioprine (AZA), and steroids. Although AZA therapy is generally regarded as unproblematic, its use can be associated with severe side effects, particularly myelosuppression. Since AZA is a prodrug, which must first be metabolized to its active metabolites, AZA therapy, in contrast to CsA therapy, cannot be controlled by measuring blood levels of this drug. Because of the myelosuppressive properties of the AZA metabolites, the 6-thioguanine nucleotides (6-TGN), the white blood cell count is usually monitored in patients on AZA therapy, and AZA is discontinued if neutropenia appears. In a group of 20 consecutive heart recipients, 6-TGN concentrations ranged from < 30 to 2,211 pmol/8 x 10(8) red blood cells (RBCs); levels < or = 450 pmol/8 x 10(8) RBCs were not associated with AZA-induced myelosuppression. Three cases of neutropenia were experienced, two of them with a fatal outcome. One patient died in septicemia owing to total myelosuppression. In this case an excessively high erythrocyte 6-TGN concentration (2,211 pmol/8 x 10(8) RBCs) was associated with a complete deficiency of thiopurine methyltransferase (TPMT), one of the main AZA detoxifying enzymes. The second patient, who had high RBC TPMT activity, developed neutropenia during rehabilitation, and AZA was withdrawn. Coincidentally, in this case the CsA blood level was only 132 g/L, and the RBC 6-TGN level was very low (maximum 46 pmol/8 x 10(8) RBCs). This patient rapidly developed cardiogenic shock with clinical signs of acute rejection and was given a second transplant on an emergency basis, but finally died from rejection of the second graft. Retrospectively, it was determined that neutropenia in this patient was not related to AZA toxicity. A high 6-TGN level (698 pmol/8 x 10(8) RBCs) was also seen in a third patient with mild neutropenia, who required allopurinol, an inhibitor of xanthine oxidase, the other major detoxifying enzyme for AZA. In this patient AZA therapy could be individually adapted by RBC 6-TGN monitoring. Based on our experience, we suggest that RBC 6-TGN monitoring allows for better individualization of treatment with AZA and may help avoid fatal complications.

Adolescent↗

Azathioprine pharmacogenetics: the relationship between 6-thioguanine nucleotides and thiopurine methyltransferase in patients after heart and kidney transplantation.

The commonly used immunosuppressive regimen after solid organ transplantation consists of cyclosporine A, azathioprine and steroids. Azathioprine, which is known to carry the risk of severe myelosuppression, is catabolized in vivo by xanthine oxidase and thiopurine methyltransferase, an enzyme which exhibits a common genetic polymorphism; 11% of Caucasians are heterozygous and 0.3% are homozygous with respect to thiopurine methyltransferase deficiency. Toxicity and immunosuppressive effects have been attributed to the 6-thioguanine nucleotides generated from azathioprine. We have studied thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations in erythrocytes from 39 heart and kidney recipients. Erythrocyte thiopurine methyl-transferase was determined by a radioenzymatic assay and erythrocyte 6-thioguanine nucleotide concentration with HPLC. Thiopurine methyltransferase activity [median (range, 10th-90th percentile)] was significantly (p < 0.05) higher in patients (n = 39) receiving azathioprine [285 (218-362) vs. 262 (160-352) mU/I erythrocytes] than in healthy blood donors as controls (n = 120). When stratified according to thiopurine methyltransferase phenotype, one patient homozygous for the low allele exhibited an excessive erythrocyte 6-thioguanine nucleotide concentration (2210 pmol/0.8 x 10(9) erythrocytes). Heterozygous patients had significantly higher 6-thioguanine nucleotide concentrations median: 435 pmol/0.8 x 10(9) erythrocytes) compared with concentrations in patients homozygous for the high allele (median: 86 pmol/0.8 x 10(9) erythrocytes; p < 0.01), although the azathioprine dosage did not differ (p = 0.66). Erythrocyte thiopurine methyltransferase determination therefore identifies patients at high risk of accumulating 6-thioguanine nucleotides. The monitoring of this enzyme may contribute to the safer management of immunosuppressive therapy with azathioprine. Alternative regimens such as cyclosporin A/mycophenolate mofetil or tacrolimus should also be considered for this patient group.

Azathioprine↗

Stentless bioprostheses for the small aortic root.

BACKGROUND AND AIMS OF THE STUDY: Despite a variety of different artificial heart valves no ideal prosthesis for the small aortic root is yet available. Conventional stented valves are hemodynamically disadvantageous because of higher transvalvular pressure gradients. Stentless bioprostheses were implanted in such patients to evaluate their performance as an alternative to homografts and to conventional mechanical prostheses. MATERIALS AND METHODS: We analyzed 57 patients with small aortic roots who underwent stentless aortic valve replacement (Toronto SPV) from March 1993 to November 1995. All but two patients had aortic stenosis. The mean age at operation was 70.9 (+/-8.2) years. The annular diameter was 18-23 mm (mean 21.4 +/- 1.1 mm) in all patients. Of the 57 patients, 17 received a 23 mm and 40 patients a 25 mm prosthesis. RESULTS: Using the oversizing technique, valve size was adjusted according to the sinotubular junction diameter, allowing a gain in prosthesis size of 2-4 mm to be achieved in all patients. On pre-discharge echocardiography maximum flow velocity was 2.3 +/- 0.4 m/s, maximum pressure gradient was 19.1 +/- 6.8 mmHg, and effective valve orifice area was 1.46 +/- 0.27 cm2. All patients were in NYHA class I or II at discharge. One patient was reoperated due to a folded annulus caused by too much oversizing. At six months follow up there was a significant reduction in pressure gradients and an increase in effective valve orifice areas in relation to a decrease in pre-existing left ventricular hypertrophy. CONCLUSIONS: Stentless bioprostheses show excellent hemodynamics due to their comparably large internal diameter and flexibility. Controlled oversizing is a safe technique without additional complications. As larger valve sizes can be implanted, aortic root enlargement is not necessary. The superior hemodynamic profile of stentless aortic valves is especially advantageous in patients with small aortic roots.

Aged↗

One-stage surgery of coronary arteries and abdominal aorta in patients with impaired left ventricular function.

BACKGROUND: Coronary artery disease (CAD) is common in patients with abdominal aortic aneurysms (AAA). Some patients will present with the combination of unstable angina, impaired left ventricular function, and a large symptomatic (ie, leaking, expanding) AAA. In this subgroup of high-risk patients, aortic cross-clamping may have a deleterious effect on cardiac function, whereas coronary artery bypass graft surgery before aneurysmectomy (staged operation) carries the risk of perioperative aneurysm rupture. One-stage surgery, ie, myocardial revascularization and simultaneous aortic aneurysm repair, has been proposed in this situation. This article summarizes our results with the combined one-stage approach in patients with symptomatic CAD, impaired left ventricular function, and large symptomatic aortic aneurysms or severe aortic occlusive disease. As yet, this cohort is the largest reported in the English literature. METHODS AND RESULTS: In 25 patients (24 men) with a mean age of 69.4 years (range, 55 to 80 years), we performed combined open heart and intra-abdominal aortic surgery. Eighteen patients had severe three-vessel disease and impaired left ventricular function (ejection fraction, < 35%). In addition, 3 of these patients had severe aortic valvular stenosis and/or insufficiency. Seven patients had one- or two-vessel disease with a low left ventricular ejection fraction in the range of 15% to 30%. All patients were in New York Heart Association functional class III or IV. Twenty-one of 25 patients had symptomatic infrarenal AAA (perianeurysm hematoma was present in 9 patients, and 12 patients had signs of beginning perforation). Four patients with aortoiliac occlusive disease and limb ischemia were simultaneously operated on. The surgical procedure started with the performance of coronary artery bypass graft surgery. After completion of myocardial revascularization, aortic aneurysm repair was performed while extracorporeal circulation was continued for mechanical cardiac assist until aortic surgery was fully accomplished. An average of 3.3 (3 to 5) coronary bypass grafts were placed, including 17 internal thoracic artery grafts. In addition, three aortic valves were replaced. In the abdominal aortic position, 12 straight tube grafts and 13 bifurcation grafts were implanted, and three renal and two carotid arteries were simultaneously repaired. The total time of surgery varied from 2.3 to 8.5 hours, with a mean time of 3.9 +/- 1.4 hours. One intraoperative myocardial infarction occurred despite open grafts. Intensive care unit treatment lasted 1 to 13 days, with a mean of 3.6 +/- 2.5 days. Three patients (12%) died after surgery--1 because of acute renal failure induced by an adverse reaction to heparin, 1 because of myocardial infarction, and 1 because of multiorgan failure. One-year actuarial survival rate was 88%, which compares favorably with survival after isolated AAA surgery in this high-risk patient subgroup and equals survival in patients with severe CAD and severely depressed myocardial function. CONCLUSIONS: One-stage surgery is a possible approach to highly symptomatic patients with severe multivascular disease and has acceptable early morbidity and mortality. Patients with severely impaired left ventricular function and unstable CAD carry a high risk of left heart failure and/or myocardial infarction during abdominal aortic surgery. Extracorporeal circulation protects the heart from the hemodynamic changes after aortic clamping or declamping during abdominal aortic surgery. The present study demonstrates that one-stage procedure is a reasonable option for this patient subgroup.

Aged↗

Open heart surgery in the octogenarians--a study on long-term survival and quality of life.

This retrospective study analyzes the perioperative and long-term survival rate as well as the long-term quality of life of 54 patients (23 f/31 m), aged 80 years or older (80 to 87, mean 82.2, SD +/- 1.79 years), who underwent open heart surgery between January 1986 and December 1993. There were 23 patients with coronary bypass, 21 with aortic valve replacement, 1 with mitral valve replacement, 8 with combined aortic valve replacement and coronary bypass, and 1 with double valve replacement. Preoperatively, 26 of the patients were in New York Heart Association (NYHA) class IV, 28 patients in class III. The in-hospital mortality was 9.3% (5/54) over all and 6.1% (3/49) for elective procedures. Follow-up time ranged from 6 to 91 months (mean 26.2 +/- 16.5). Of 49 discharged patients, 6 (12.2%) died during the follow-up period. At the time of re-evaluation 21 patients were in NYHA class I, 24 patients in class II, and 4 in class III. There was a significant long-term benefit from the surgical intervention in 39 or the 54 patients. Of 43 survivors 41 were able to live on their own and 38 were able to handle their daily routine without help. Two patients were cared for in a nursing home. This long-term analysis demonstrates the benefits of cardiovascular surgery in octogenarians in terms of social integration and quality of life.

Aged↗