Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart

Postischemic cardiomyopathy remains one of the disorders in urgent need of effective noninvasive therapy. It is currently accepted that the isolation, expansion and application of resident cardiac stem cells may hold therapeutic promise for the future. Recently, it has been demonstrated that shock waves (SW) could enhance the expression of vascular endothelial growth factor (VEGF) and its receptor, Flt-1. As the development of angiogenic noninvasive therapy is very important for future therapeutic strategies in cardiovascular diseases, we examined in vitro, the effects of SW treatment on adult resident cardiac primitive cells isolated from bioptic fragments of normal human hearts and from explanted pathologic hearts with postischemic cardiomyopathy. This study demonstrates that SW have positive influence on both the proliferation and the differentiation of cardiomyocytes, smooth muscle and endothelial cells precursors, with a more obvious effect being evident in the cells from normal heart than in those taken from pathologic hearts. Our results suggest that SW treatment could inhibit or retard the pathologic remodeling and functional degradation of the heart if applied during the early stages of heart failure.     

Autonomic nervous system abnormalities in spinocerebellar ataxia type 2: a cardiovascular neurophysiologic study

Autonomic nervous system dysfunction is part of the spinocerebellar ataxia (SCA) clinical picture, but few data are available on this topic. The present study is aimed to report a detailed investigation of autonomic nervous system in patients with molecular diagnosis of SCA type 2, one of the most frequent forms and the commonest in Italy. Nine patients with a mild to moderate form of SCA2 underwent a questionnaire about dysautonomic symptoms and a complete cardiovascular neurophysiologic evaluation of both sympathetic and parasympathetic system, comprising head-up tilt, standing, isometric hand grip, cold pressure, mental arithmetic, Valsalva manoeuvre, deep breathing, and hyperventilation tests. An echocardiographic study and Holter-ECG recording were also performed. All patients complained dysautonomic problems regarding urinary tract, cardiovascular system, or gastrointestinal dysfunction. The neurophysiologic study showed both sympathetic and parasympathetic involvement, with highly variable degree and pattern of dysautonomia. The present study results show that the autonomic dysfunction is common in SCA2 representing a significant component of the complex picture of the disease. We found a wide spectrum of cardiovascular autonomic abnormalities, without a typical pattern of dysfunction and without correlation with clinical variables.     

Clinical Outcome in Patients with Intermediate Stenosis of Left Anterior Descending Coronary Artery after Deferral of Revascularization on the Basis of Noninvasive Coronary Flow Reserve Measurement

Background: Several reports suggest that noninvasive measurements of coronary flow reserve (CFR) by use of echocardiography may support decision making in intermediate stenosis of the left anterior descending coronary artery (LAD). The aim of the present study was therefore to analyze the clinical outcome in patients with intermediate stenosis of LAD after deferral of coronary revascularization on the basis of noninvasive CFR measurement. Methods: the study population included 280 patients with intermediate LAD stenosis (50–70% by angiography) (62.2 ± 9.6 years). All the patients underwent transthoracic CFR assessment of LAD (after dipyridamole infusion) within 2 weeks from coronary angiography. If CFR of LAD was ≤ 2, PTCA was recommended; if CFR was > 2, medical treatment was chosen. Primary end points were cardiac death, myocardial infarction, coronary revascularization procedure, and unstable angina. Results: mean follow-up was 43 ± 11 months (range 12–52 months). In 150 patients (53.6%) (CFR ≤ 2), coronary artery revascularization was performed (PTCA group); the remaining 130 patients (46.4%) (CFR > 2) were medically treated (medical group). Survival from cardiac death was 94% in the PTCA group and 92.4% in the medical group (P = 0.56). As for all cardiac events, the Kaplan–Meier percentage survival from cardiac events was 88.3% in the PTCA group and 86.4% in the medical group (P = 0.36). Conclusions: even if CFR as a "stand-alone" diagnostic criterion suffers from several structural limitations, a combined strategy including also other clinical and instrumental measurements before undergoing interventional procedures could improve the cost–benefit practice, in particular, for the management of patients with intermediate LAD stenosis.     

A comparison of 5-day courses of dirithromycin and azithromycin in the treatment of acute exacerbations of chronic obstructive pulmonary disease

BACKGROUND: Short-term use of antibiotics has become a common component of the management of acute exacerbations of chronic bronchitis (AECB), particularly in complex cases with productive cough or purulent phlegm. The macrolide antibiotics, particularly second-generation agents such as dirithromycin and azithromycin, are among the antibiotic classes frequently recommended and used to treat upper and lower respiratory infections, including AECB. OBJECTIVE: This study compared the clinical efficacy and tolerability of 5-day courses of dirithromycin and azithromycin given once daily for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: This randomized, investigator-blinded, parallel-group clinical trial was conducted at 5 centers in the United States. Eligible patients were adult (age >35 years) smokers or ex-smokers (smoking history of at least 10 pack-years) with chronic bronchitis and an acute exacerbation, defined by the occurrence of increased dyspnea and/or productive cough and feverishness within 48 hours of enrollment. Before randomization, an attempt was made to obtain a sputum specimen from each patient for Gram's staining and culture. Patients were randomized to receive dirithromycin 500 mg QD for 5 days or azithromycin 500 mg QD on day 1 and 250 mg QD on days 2 to 5. Clinical efficacy was assessed separately by patients and physicians at early (days 7-10) and late (days 25-35) posttreatment visits. RESULTS: Eighty-six patients (48 women, 38 men; mean age, 55 years) with a mean smoking history of 31 pack-years were included in the intent-to-treat analysis. Forty-six (54%) patients were randomized to dirithromycin and 40 (47%) patients to azithromycin. Clinical efficacy was reported in a high proportion of patients in both treatment groups, both at the early posttreatment visit (84.8% dirithromycin, 75.7% azithromycin; difference dirithromycin - azithromycin, 9.1%; 95% CI, -8.2 to 26.4) and the late posttreatment visit (95.5% and 86.5%, respectively; difference dirithromycin - azithromycin, 9.0%; 95% CI, -3.7 to 21.6). A similar proportion of patients required a second course of antibiotics over the study period (20.5% dirithromycin, 27.0% azithromycin; difference dirithromycin - azithromycin, -6.6%; 95% CI, -25.2 to 12.1). Only 42 (48.8%) patients were able to produce a sputum sample before receiving study treatment, and of these, only 20 (47.6%) demonstrated a preponderance of neutrophils on Gram's staining. Both treatments were well tolerated. CONCLUSIONS: The results of this study suggest comparable clinical efficacy between 5-day courses of once-daily dirithromycin and azithromycin in acute exacerbations of COPD. There were insufficient data to permit meaningful comparison of the bacteriologic efficacy of these macrolide antibiotics.     

Butyrate as an effective treatment of congenital chloride diarrhea

BACKGROUND & AIMS: Many therapeutic attempts have demonstrated to be ineffective in reducing the severity of congenital chloride diarrhea and its long-term complications. The short-chain fatty acid butyrate stimulates intestinal water and ion absorption through a variety of mechanisms, including the activation of a parallel Cl-/butyrate and Na+/H+ exchanger. In this case report, we report the therapeutic efficacy of butyrate on an 11-year-old patient affected by congenital chloride diarrhea. METHODS: The efficacy of increasing doses of oral butyrate (from 50 to 100 mg/kg/day) was investigated through the daily evaluation of stool volume, bowel movements, fecal incontinence, serum, and stool electrolytes concentrations. The modifications in transepithelial intestinal ion transport elicited by butyrate were examined by rectal dialysis study. RESULTS: A butyrate dose of 100 mg/kg/day induced a normalization of stool pattern and of serum and fecal electrolytes concentration. The rectal dialysis study demonstrated a proabsorptive effect induced by butyrate on Na+, Cl-, and K+ intestinal transport. Butyrate therapy was well tolerated during the entire 12-month observation period, and the stool pattern and fecal and serum ion concentrations remained stable within the normal ranges. No clinical adverse events or episodes of dehydration requiring hospital care were observed. CONCLUSIONS: Butyrate could be effective in treating congenital chloride diarrhea. It is easily administered, useful in preventing severe dehydration episodes, and may be a promising therapeutic approach for a long-term treatment in this rare and severe condition.     

Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function

The purpose of this study was to determine whether the heart in large mammals contains cardiac progenitor cells that regulate organ homeostasis and regenerate dead myocardium after infarction. We report that the dog heart possesses a cardiac stem cell pool characterized by undifferentiated cells that are self-renewing, clonogenic, and multipotent. These clonogenic cells and early committed progeny possess a hepatocyte growth factor (HGF)-c-Met and an insulin-like growth factor 1 (IGF-1)-IGF-1 receptor system that can be activated to induce their migration, proliferation, and survival. Therefore, myocardial infarction was induced in chronically instrumented dogs implanted with sonomicrometric crystals in the region of the left ventricular wall supplied by the occluded left anterior descending coronary artery. After infarction, HGF and IGF-1 were injected intramyocardially to stimulate resident cardiac progenitor cells. This intervention led to the formation of myocytes and coronary vessels within the infarct. Newly generated myocytes expressed nuclear and cytoplasmic proteins specific of cardiomyocytes: MEF2C was detected in the nucleus, whereas alpha-sarcomeric actin, cardiac myosin heavy chain, troponin I, and alpha-actinin were identified in the cytoplasm. Connexin 43 and N-cadherin were also present. Myocardial reconstitution resulted in a marked recovery of contractile performance of the infarcted heart. In conclusion, the activation of resident primitive cells in the damaged dog heart can promote a significant restoration of dead tissue, which is paralleled by a progressive improvement in cardiac function. These results suggest that strategies capable of activating the growth reserve of the myocardium may be important in cardiac repair after ischemic injury.