Electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic ischemic heart disease

BACKGROUND: Bone marrow cell injection has been introduced to treat patients with ischemic heart disease. However, focal application of bone marrow cells may generate an arrhythmogenic substrate. OBJECTIVES: To assess the electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. METHODS: Bone marrow was aspirated in 20 patients (65+/-11 years, 19 male) with drug-refractory angina and myocardial ischemia. Electroanatomical mapping (NOGA, Biosense-Webster, Waterloo, Belgium) was performed during mononuclear cell isolation. Areas for cell injection were selected based on the localization of ischemia on SPECT. These areas were mapped in detail to evaluate local bipolar electrogram duration, amplitude and fragmentation. Mononuclear cells were injected in the ischemic area with the NOGA system. SPECT and electroanatomical mapping were repeated at 3 months. Holter monitoring was repeated at 3 and 6 months. RESULTS: SPECT revealed a decrease in the number of segments with ischemia (3.5+/-2.5 vs. 1.1+/-1.0 at 3 months; P<0.01) and an increased left ventricular ejection fraction (44+/-13% vs. 49+/-17% at 3 months; P=0.02). The number of ventricular premature beats remained unchanged (10+/-24x10(2)/24h vs. 8+/-23x10(2)/24h at 3 months (P=NS) and 12+/-30x10(2)/24h at 6 months (P=NS)). At 3 months follow-up, bone marrow cell injection did not prolong electrogram duration (15.9+/-4.6 ms vs. 15.6+/-4.0 ms; P=NS), decrease electrogram amplitude (3.8+/-1.5 mV vs. 3.8+/-1.5 mV; P=NS), or increase fragmentation (2.0+/-0.5 vs. 1.9+/-0.4; P=NS). CONCLUSION: Intramyocardial bone marrow cell injection does not increase the incidence of ventricular arrhythmias and does not alter the electrophysiological properties of the injected myocardium.     

Clinical implications of airway inflammation in mild intermittent asthma.

OBJECTIVE: To determine whether inhaled corticosteroids should be prescribed to patients with milder forms of asthma and whether markers of airway inflammation should be considered when making therapy decisions. DATA SOURCES: A PubMed search was performed of the English-language literature published in the preceding 10 years (January 1, 1993, through December 31, 2003) concerning epidemiology, pathophysiology, therapy, and prognosis of mild intermittent asthma, with asthma, mild, and intermittent as indexing terms. STUDY SELECTION: All relevant studies including author's expert opinions were selected. RESULTS: Several studies have addressed the question of a possible benefit of maintenance therapy (ie, inhaled steroids) in patients with mild intermittent asthma. Although a diminishing effect on airway inflammation has been widely demonstrated, even in patients with mild disease, the impact of inhaled steroids on the long-term prognosis is much less clear. For patients with mild disease who are long-term inhaled steroid users, alternative therapy strategies, including low-dose inhaled steroids and leukotriene receptor antagonists, have been advocated. CONCLUSIONS: Mild intermittent asthma is a disease characterized not only by infrequent symptoms and normal lung function but also by chronic airway inflammation, possibly resulting in irreversible airflow limitation if left unattended. Therefore, maintenance therapy, such as (low-dose) inhaled steroids or leukotriene receptor antagonists, should be considered in patients with mild disease. Future studies should give more insight into the impact of prolonged anti-inflammatory therapy on the long-term prognosis of mild intermittent asthma patients. Whether results from these studies will justify a more aggressive treatment for these patients remains to be answered.     

Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

Berufsbedingte Latexallergie

Trauma und Berufskrankheit - Die Vermeidung gepuderter Latexhandschuhe gilt als wichtige Maßnahme zur Prävention von latexbedingten Haut- und Atemwegsallergien bei Beschäftigten im...     

Intracardiac transplantation of a mixed population of bone marrow cells improves both regional systolic contractility and diastolic relaxation.

BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction.     

Contributions of ovarian failure and aging to blood pressure in normotensive perimenopausal women: a mixed longitudinal study

Epidemiologic studies have shown that blood pressure increases more rapidly in middle-aged women than in middle-aged men. Whether or not ovarian failure contributes to this rapid rise is still not clear. In a follow-up study begun in 1979 and to continue for 10 years, the blood pressure of 193 healthy normotensive perimenopausal women, who lived in the mixed rural/industrial community of Ede, the Netherlands and who were initially aged between 49 and 56 years, was measured annually. During the course of the study, the onset of menopause of each participant could be established. Because of the mixed longitudinal design of the study, it was possible to evaluate the effects of both chronologic aging and time pre- or postmenopause on blood pressure. After the first seven years of follow-up, it was demonstrated that blood pressure did not increase in 168 women whose body weight was relatively stable. After multivariate analyses, systolic as well as diastolic pressure showed a significant negative relation (slope, 1.34 mmHg per year and 0.63 mmHg per year, respectively) with the years since menopause. On the other hand, the observed positive relation (slope, 0.81 mmHg per year) of systolic pressure with chronologic aging was not significant. No consistent association was found between diastolic pressure and chronologic aging. It is concluded that menopause cannot be regarded as a cause of hypertension; on the contrary, ovarian failure appears to have a protective effect on the increase in blood pressure as a result of chronologic aging. on the increase in blood pressure as a result of chronologic aging.     

Small proportions: what to report for confidence intervals?

The original article to which this Erratum refers was published in Pharmacoepidemiology and Drug Safety 2005; 14: 239–247.