Acute myocardial infarction occurring in versus out of the hospital: patient characteristics and clinical outcome

OBJECTIVES

We describe the baseline characteristics and clinical course of patients who had an acute myocardial infarction (AMI) during their hospital stay.

BACKGROUND

In comparison with patients who had an AMI outside of the hospital (prehospital AMI), the data on patients who had an AMI in the hospital are poorly described.

METHODS

Patients with an in-hospital AMI were prospectively registered in the Southwest German Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and compared with patients with prehospital AMI.

RESULTS

Of 5,888 patients with AMI, 403 patients (6.8%) had an in-hospital AMI. These patients were older, more often male and sicker as compared with the patients with a prehospital AMI. They also showed a higher prevalence of concomitant diseases, such as arterial hypertension, diabetes mellitus, renal insufficiency and contraindications for thrombolysis. There was no significant difference regarding the use of reperfusion therapy, either thrombolysis (in-hospital AMI 44.2% vs. prehospital AMI 49.1%; odds ratio [OR] 0.86, 95% confidence interval [CI] 0.70 to 1.05) or primary angioplasty (9.9% vs. 8.2%; OR 1.23, 95% CI 0.88 to 1.73), or a combination of both, between the two groups. The interval from symptom onset to the start of treatment in patients receiving reperfusion therapy was 55 min for patients with an in-hospital AMI versus 180 min for patients with a prehospital AMI (p = 0.001). In-hospital death occurred in 110 (27.3%) of 403 patients with an in-hospital versus 762 (13.9%) of 5,485 patients with a prehospital AMI (OR 2.33, 95% CI 1.85 to 2.94). This was confirmed by logistic regression analysis after adjusting for other confounding variables (OR 1.67, 95% CI 1.23 to 2.24).

CONCLUSIONS

In-hospital AMI occurred in 6.8% of patients. Time to intervention was shorter; however, the use of reperfusion therapy for in-hospital AMI was not different from that for prehospital AMI. In particular, primary angioplasty seems to be underused in these patients. This, as well as the selection of patients, may result in the high hospital mortality rate of 27.3%.     

Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial

CONTEXT: Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth. OBJECTIVE: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort. DESIGN: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003). SETTING: The study was conducted at 11 U.S. pediatric endocrine centers. SUBJECTS: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled. INTERVENTIONS: Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr. MAIN OUTCOME MEASURE: The main outcome measure was baseline-to-2-yr change in height SDS. RESULTS: Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected. CONCLUSION: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.     

吡格列酮对脂质诱导胰岛素抵抗大鼠的影响及其机制研究

目的探讨吡格列酮(Pio)对脂质诱导的胰岛素抵抗(IR)大鼠糖代谢、血浆脂联素和抵抗素浓度及组织抵抗素水平的影响。方法采用清醒状态大鼠进行扩展高胰岛素-正糖钳夹术,检测4h脂质灌注升高血浆游离脂肪酸(FFA)引起的IR状态下,肝糖及外周组织糖代谢,血浆脂联素和抵抗素浓度,肝、肌肉、脂肪组织抵抗素水平的变化,以及经Pio处理后的影响。结果在钳夹稳态期,脂质灌注组(L组)和Pio处理+脂质灌注组(P/L组)FFA水平明显较对照组升高。P/L组葡萄糖输注率(GIR)较对照组降低[(20.6±0.9vs 33.6±1.5)mg·kg~(-1)·min~(-1),JP＜0.01],而L组又低于P/L组[(12.6±1.7)vs (20.6±0.9)mg·kg~(-1)·min~(-1),P＜0.01]；对照组和P/L组肝糖输出(HGP)与基础值相比被抑制85%,在L组胰岛素对HGP的抑制作用明显障碍。L组和P/L组葡萄糖清除率(G_(Rd))低于对照组(P＜0.01)。P/L组基础血浆抵抗素水平低于对照组[(7.8±1.3vs 29.1±3.1)μL,P＜0.01]。脂质灌注后P/L组抵抗素浓度明显升高,但仍低于L组[(18.1±3.8vs 47.0±2.2)μg/L,P＜0.01]。P/L组基础血浆脂联素水平明显高于对照组和L组[(3.9±0.2vs 2.8±0.1和2.6±0.2)mg/L,P＜0.01]。但在钳夹结束后,L和P/L组血浆脂联素水平降低(均P＜0.05)。P/L组肝脏抵抗素水平低于对照组和L组(均P＜0.05)；L组骨骼肌抵抗素水平高于对照组和P/L组(均P＜0.05)；各组脂肪组织抵抗素水平差异无统计学意义。结论脂质灌注在体内诱导了一种急性IR。Pio干预部分阻断了脂质诱导的IR。抵抗素和脂联素的变化在IR的发生和发展中可能发挥了一定的作用。     

A randomized, double-blind, comparative trial of a new oral combination of artemether and benflumetol (CGP 56697) with mefloquine in the treatment of acute Plasmodium falciparum malaria in Thailand

CGP 56697, a new oral fixed combination of artemether and benflumetol, was tested in a double-blinded, randomized trial in 252 adult patients treated either with CGP 56697 (4 x 4 tablets each containing 20 mg of artemether and 120 mg of benflumetol, given at 0, 8, 24, and 48 hr), or with mefloquine (three tablets of 250 mg at initial diagnosis, followed by two tablets of 250 mg at 8 hr). Baseline data of the two groups were comparable. The 28-day cure rate with CGP 56697 was lower than with mefloquine (69.3% versus 82.4%; P = 0.002). However, CGP 56697 was more effective than mefloquine in parasite clearance time (43 hr versus 66 hr; P < 0.001) fever clearance time (32 hr versus 54 hr; P < 0.005), and gametocyte clearance time (152 hr versus 331 hr; P < 0.001). This study revealed that CGP 56697 is effective against multidrug-resistant Plasmodium falciparum malaria in Thailand, but higher doses will probably be needed to improve the cure rate.     

Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease

Chronic left ventricular failure causes pulmonary congestion with increased lung weight and type 2 pulmonary hypertension. Understanding the molecular mechanisms for type 2 pulmonary hypertension and the development of novel treatments for this condition requires a robust experimental animal model and a good understanding of the nature of the resultant pulmonary remodeling. Here we demonstrate that chronic transverse aortic constriction causes massive pulmonary fibrosis and remodeling, as well as type 2 pulmonary hypertension, in mice. Thus, aortic constriction-induced left ventricular dysfunction and increased left ventricular end-diastolic pressure are associated with a ≤5.3-fold increase in lung wet weight and dry weight, pulmonary hypertension, and right ventricular hypertrophy. Interestingly, the aortic constriction-induced increase in lung weight was not associated with pulmonary edema but resulted from profound pulmonary remodeling with a dramatic increase in the percentage of fully muscularized lung vessels, marked vascular and lung fibrosis, myofibroblast proliferation, and leukocyte infiltration. The aortic constriction-induced left ventricular dysfunction was also associated with right ventricular hypertrophy, increased right ventricular end-diastolic pressure, and right atrial hypertrophy. The massive lung fibrosis, leukocyte infiltration, and pulmonary hypertension in mice after transverse aortic constriction clearly indicate that congestive heart failure also causes severe lung disease. The lung fibrosis and leukocyte infiltration may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. Thus, the effective treatment of left ventricular failure may require additional efforts to reduce lung fibrosis and the inflammatory response.     

Effect of direct cold atmospheric plasma (diCAP) on microcirculation of intact skin in a controlled mechanical environment

Objective

The microcirculatory response of intact human skin to exposure with diCAP for different durations with a focus on the effect of implied mechanical pressure during plasma treatment was investigated.

Methods

Local relative hemoglobin, blood flow velocity, tissue oxygen saturation, and blood flow were monitored noninvasively for up to 1 hour in 1‐2 mm depth by optical techniques, as well as temperature, pH values, and moisture before and after skin stimulation. The experimental protocol (N = 10) was set up to differentiate between pressure‐ and plasma‐induced effects.

Results

Significant increases in microcirculation were only observed after plasma stimulation but not after pressure stimulus alone. For a period of 1 h after stimulation, local relative hemoglobin was increased by 5.1% after 270 seconds diCAP treatment. Tissue oxygen saturation increased by up to 9.4%, whereas blood flow was doubled (+106%). Skin pH decreased by 0.3 after 180 seconds and 270 seconds diCAP treatment, whereas skin temperature and moisture were not affected.

Conclusions

diCAP treatment of intact skin notably enhances microcirculation for a therapeutically relevant period. This effect is specific to the plasma treatment and not an effect of the applied pressure. Prolonged treatment durations lead to more pronounced effects.     

Effect of oral captopril on premature ventricular complexes in patients with preserved left ventricular systolic function: A randomized clinical trial

Some studies have suggested that angiotensin-converting enzyme (ACE) inhibition in patients with heart failure is associated with a decrease in frequency of spontaneous premature ventricular complexes (PVCs). It is not clear whether such a finding represents a primary effect of ACE inhibition or, instead, a secondary result of treatment of heart failure. For a primary drug effect to be present, PVC suppression during ACE inhibition should also occur in patients with preserved left ventricular systolic function. We therefore undertook a randomized double-blind placebo-controlled crossover clinical trial to assess the effect of oral captopril (50 mg. b. i. d.) on ventricular arrhythmia frequency in 11 patients with > 30 PVCs/h (during a 48-h ambulatory recording) and a left ventricular ejection fraction of ≥ 45% (measured by radionuclide multigated acquisition scan). Pharmacologic activity of the administered drug was evidenced by an increase in median plasma renin activity to 2. 4 ng/AI/ml/h from a value of 1.1 ng/AI/ml/h during placebo (p = 0.001) and an 8.5 ± 10.3 drop in mean diastolic blood pressure during captopril versus placebo (p < 0.03). During captopril treatment, a mean of 491 ± 378 PVCs/h were observed compared with 389 ± 169 PVCs/h during placebo, a nonsignificant difference. There was also no significant change in left ventricular ejection fraction, plasma catecholamines, or serum potassium during captopril treatment. Thus, ACE inhibition in patients with preserved left ventricular systolic function fails to suppress ventricular ectopic activity. Extrapolated to patients with heart failure, our observations argue against a primary PVC suppressive action of ACE inhibitors but do not rule out possible secondary antiarrhythmic effects of these agents.     

Efficacy of artemisinin and mefloquine combinations against Plasmodium falciparum. In vitro simulation of in vivo pharmacokinetics

The activity of artemisinin in combination with mefloquine was tested in vitro against a chloroquine‐sensitive (F32) strain of Plasmodium falciparum . A method of repetitive dosing and extending the culture observation period to 28–30 days was used to mimic the in vivo pharmacokinetic situation. Plasmodium falciparum was exposed to artemisinin from 10⁻⁸ to 10⁻⁵  m , mefloquine from 3×10⁻⁹ to 10⁻⁵  m and their combinations. The exposure time for artemisinin was 3 hours twice daily and for mefloquine 24 hours. The drug‐dosing duration was 3 days.
Neither artemisinin nor mefloquine alone provided radical clearance of P. falciparum , even when maximum concentrations (10⁻⁵  m ) were applied. The antiparasitic activity of artemisinin and mefloquine were significantly higher when dosed alone. Effective concentrations for different degrees of inhibition (EC 50, 90 and 99) of both artemisinin and mefloquine respectively were significantly lower when used in combination. At concentrations normally reached in vivo , this effect was clearly synergistic ( P =0.016)
Our in vitro model of intermittent dosing of artemisinin and mefloquine combinations for 3 days provides significant evidence of positive interaction between the two compounds. Lower combination concentrations around the MIC‐values for the individual compounds showed synergistic effect, and high concentrations showed additive effect. This indicates that such drug combinations may provide radical clearance at concentrations lower than those required for single‐drug treatment.     

Surfactant replacement for ventilator-associated pneumonia: a preliminary report

BACKGROUND: Surfactant abnormalities have been described in bacterial pneumonia. OBJECTIVE: To determine the safety and effect of exogenous surfactant replacement in patients with ventilator-associated pneumonia (VAP). METHODS: Patients with VAP were randomized in a double-blind study to receive either an artificial surfactant (Exosurf) consisting mostly of disaturated phospholipids (DSPL) or saline via a continuous nebulizer system for 5 days. Patients underwent bronchoscopy and bronchoalveolar lavage (BAL) prior to and after 4 days of therapy. RESULTS: Twenty-two patients were randomized, with 8 receiving Exosurf. There was no detected difference in outcome between the saline- and Exosurf-treated patients in terms of days on ventilator, 30-day or hospital mortality. At the follow-up lavage, the patients treated with Exosurf had a significant rise in the level of DSPL (p < 0.05), while the saline group did not, suggesting delivery of drug. Also at the follow-up lavage, the percentage of neutrophils in the BAL fell in the Exosurf patients (p < 0.01), but not in the saline group. CONCLUSION: Exogenous surfactant replacement given to patients with VAP increased the amount of DSPL retrieved by BAL. This treatment was associated with a fall in the neutrophil response to pneumonia.