Svend Aage Mortensen

Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II).

OBJECTIVES This study investigated the influence of the mechanical blood pump HeartMate II (HMII) (Thoratec Corporation, Pleasanton, California) on blood coagulation and platelet function. BACKGROUND HMII is an implantable left ventricular assist device used for the treatment of heart failure. Patients treated with HMII have increased bleeding tendencies. METHODS We measured agonist-induced platelet aggregation in 16 patients on HMII support. RESULTS The von Willebrand factor (vWF)-dependent ristocetin-induced platelet aggregation was impaired in 11 of the 16 patients, of which 12 had experienced at least 1 minor or major bleeding episode. The impaired ristocetin-induced platelet aggregation was associated both with decreased specific activity of plasma vWF, presumably due to lack of high molecular weight vWF multimers, as well as with attenuated function of the platelets themselves. CONCLUSIONS The results imply that HMII treatment is associated with impaired platelet aggregation, which may contribute to an increased tendency to bleed.

Prevalence and bother of nocturia, and causes of sleep interruption in a Danish population of men and women aged 60–80 years

To study the prevalence and bother of nocturia, and sleep interruptions in an unselected population of Danish men and women aged 60–80 years.

Nocturia and associated morbidity in a Danish population of men and women aged 60–80 years

To evaluate the association between nocturia and medical diseases, medication, urinary incontinence (UI), recurrent cystitis, smoking, alcohol, parity, hysterectomy, pelvic organ prolapse surgery, UI surgery, and prostate surgery.

Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate

BACKGROUND The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (TTx) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. METHODS This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediaminetetraacetic acid clearance. RESULTS In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((ΔmGFR 6.7 ± 9.0 vs -1.6 ± 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (ΔmGFR 5.1 ± 11.1 vs -0.5 ± 8.7 ml/min/1.73 m(2); p < 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CNI reduction during the study period. CONCLUSIONS Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.

Dietary coenzyme Q10 supplementation alters platelet size and inhibits human vitronectin (CD51/CD61) receptor expression.

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed to explain the effects of CoQ10, but a comprehensive explanation of its cardioprotective properties is still lacking. One attractive theory links ubiquinone with the inhibition of platelets. The effect of CoQ10 intake on platelet size and surface antigens was examined in human volunteers. Study participants received 100 mg of CoQ10 twice daily in addition to their usual diet for 20 days. Receptor expression was measured by flow cytometry with monoclonal murine anti-human antibodies CD9 (p24), CD42B (Ib), CD41b (IIb), CD61 (IIIa), CD41a (IIb/IIIa), CD49b (VLA-2), CD62p (P selectin), CD31 (PECAM-1), and CD51/CD61 (vitronectin). An increase of total serum CoQ10 level (from 0.6 +/- 0.1 to 1.8 +/- 0.3 micrograms/ml; p < 0.001) was found at protocol termination. Fluorescence intensity was higher for the large platelets when compared with the whole platelet population. Significant inhibition of vitronectin-receptor expression was observed consistently throughout ubiquinone treatment. Reduction of platelet size was observed at the end of CoQ10 supplementation. Inhibition of the platelet vitronectin receptor and a reduction of the platelet size are direct evidence of a link between dietary CoQ10 intake and platelets. These findings may not be fully explained by the known antioxidant and bioenergetic properties of CoQ10. Diminished vitronectin-receptor expression and reduced platelet size resulting from CoQ10 therapy may contribute to the observed clinical benefits in patients with cardiovascular diseases.

Repeatability of Cystometry and Pressure–Flow Parameters in Female Patients

The repeatability of cystometric and pressure–flow data was studied in 31 female patients. The measured parameters had poor correlation coefficients, and logarithmic transforming of the data was generally not warranted. Previous studies and statistical methods of reliability measurement are reviewed. It is suggested as a subject for future studies, that urodynamic measurements are repeated in each patient so that confidence limits can be established within disease entities.

Cytomegalovirus Infection Rate among Heart Transplant Patients in Relation to Anti-thymocyte Immunoglobulin Induction Therapy

During a 2-year period, 49 patients underwent heart transplantation at Rigshospitalet, Copenhagen. Nine (18%) were females and the mean age for all patients was 44 years (range 14-56 years). Immunosuppressive therapy included cyclosporin, azathioprine and steroids in all patients. 43 patients received in addition short-term (approx. 4 days) induction treatment with antithymocyte immunoglobulin (ATG). 17 patients received ATG Fresenius, 2.5 mg/kg/day or ATGAM, 12.5 mg/kg/day, whereas the remaining 26 patients received ATG Merieux, 2.5 mg/kg/day. Prophylactic antimicrobial chemotherapy included ceftriaxone, acyclovir (1 g daily), nystatin, and pyrimethamine in toxoplasmosis mismatch patients. Serological assays for cytomegalovirus (CMV), Epstein-Barr virus, varicella-zoster virus, herpes simplex virus, legionella and toxoplasmosis as well as CMV and bacterial culturing were carried out before transplantation, at regular intervals and when clinically indicated. Five patients developed septicaemia. Nine had pulmonary bacterial infections, including 2 cases of legionella pneumonia. Two had Clostridium difficile diarrhoea. Three patients had Pneumocystis carinii pneumonitis. 24 patients (49%) had evidence of CMV infection/reactivation. Seven out of 10 CMV mismatch (pos donor/neg recipient) patients and 3 out of 12 CMV match (pos donor/pos recipient) patients developed clinical CMV disease. The rate of CMV infection/reactivation was significantly higher among patients who had CMV-positive donors (p < 0.01) and among patients receiving ATG Merieux induction treatment (p < 0.0001). Logistic regression analysis showed that both positive CMV donor status and ATG Merieux induction treatment were significant independent predictors of CMV infection. Six patients (12%) died. Two out of 4 infection related deaths could be ascribed to CMV disease.

Assessment of lower urinary tract symptoms in women by a self-administered questionnaire: Test-retest reliability

A self-administered questionnaire assessing female lower urinary tract symptoms and their impact on quality of life is described and validated, on 56 females in six participating departments. The patients answered two identical questionnaires on separate occasions before treatment. Test-retest reliability of the questionnaire, correlation between the symptoms and their troublesomeness, and the reproducibility of this correlation were assessed. The percentage of mistakes in answers to each of the questions varied from 1.8% to 49.1%, mainly owing to missing answers in the item groups: appliances, sexual function and social activities. Test-retest showed a repeat frequency of 50.0%–91.0% for symptoms and 44.6%–82.1% for trouble. A highly significant positive correlation was found between symptoms and trouble, which was most pronounced for questions concerning pain and incontinence. This correlation was consistent within time. The primary validation of this questionnaire is good. Its relevance as a basis for medical priority and clinical decision making remains to be investigated.

Effect of Nitroglycerin in Patients with Increased Pulmonary Vascular Resistance Undergoing Cardiac Transplantation

Acute right ventricular failure due to persistent pulmonary hypertension is a risk factor for premature death after cardiac transplantation. The purpose of this study was to follow changes in pulmonary haemodynamics in patients with pulmonary hypertension undergoing heart transplantation, and to examine whether postoperative changes can be predicted from a preoperative nitroglycerin (NTG) challenge. Seventeen consecutive patients with NYHA class IV heart failure and pulmonary hypertension (pulmonal vascular resistance (PVR) > 2.5 Wood units) underwent an NTG infusion before cardiac transplantation and were followed up using measurements of pulmonary haemodynamics before, early (24 h) and late (6 months) after cardiac transplantation. The effect of NTG was measured preoperatively and compared with posttransplantation values. Postoperative (24 h) PVR was reduced in all patients when compared with preoperative findings (PVR from 4.1 +/- 0.2 to 1.9 +/- 0.2 Wood units, Mean +/- SEM, p < 0.05). Mean pulmonary artery pressure (mPAP) was lowered in 16 of out 17 patients (41 +/- 2 to 26 +/- 1 mmHg, p < 0.05). None of the parameters were significantly changed during the subsequent 6 months. Postoperative PVR and mPAP were accurately estimated by preoperative NTG infusion (NTG vs 24 h posttranspl: PVR 2.2 +/- 0.2 vs 1.9 +/- 0.2 Wood units, p > 0.05; mPAP 30 +/- 2 vs 26 +/- 1 mmHg, p > 0.05). Heart transplantation candidates with pulmonary hypertension responsive to NTG can be expected to obtain a postoperative immediate fall in pulmonary pressures and PVR. The magnitude of this circulatory improvement can be predicted from a preoperative NTG infusion and is not different from values measured 6 months after transplantation.

Temporal changes in myocardial endothelial nitric oxide synthase expression following human heart transplantation

BACKGROUND The incidence of cardiac allograft vasculopathy increases with time after heart transplantation. Allograft vasculopathy is associated with endothelial dysfunction and reduced endothelium-dependent nitric oxide-mediated vascular effects. In this study, temporal changes in endothelial nitric oxide synthase (NOS3) expression in human myocardial biopsies were investigated during the first 3 years after heart transplantation. METHODS In each patient (n = 7), the immunohistochemical presence of NOS3 and inducible nitric oxide synthase were examined in serial biopsies taken at 1, 4, and 26 weeks and at 1, 2, and 3 years after transplantation. RESULTS Endothelial nitric oxide synthase was present in vascular endothelial cells in all biopsies at the time of transplantation. A rapid fall within the first months in the number of NOS3-positive biopsies was observed, with a possible difference in the rate of disappearance among the capillaries, the arterial endothelium, and the venous endothelium. After 2 years, very little NOS3 could be detected. Inducible nitric oxide synthase was present in vascular smooth muscle cells throughout the study period and did not change. CONCLUSION Endothelial nitric oxide synthase immunoreactivity is gradually lost after heart transplantation. These changes may be responsible for the coronary endothelial dysfunction often seen after human cardiac transplantation.