Evaluation of low-dose endotoxin administration during pregnancy as a model of preeclampsia

BACKGROUND: Recent evidence implicates nitric oxide (*NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that *NO and *NO-derived species play a role in that animal model. METHODS: Endotoxin was infused at doses of 1, 2 and 10 microg/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2- + NO3-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine methyl ester (L-NAME) was administered in drinking water at a dose of 3 mg x kg(-1) x d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 microg/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine. RESULTS: Endotoxin administration at doses of 2 and 10 microg/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2- + NO3- concentration, reflective of tissue *NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 microg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 microg/kg, and a combination of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity. CONCLUSION: Nitric oxide either directly or through secondary species plays a significant role in the biochemical and physiologic changes that occur in a rodent model of endotoxin-induced injury.     

Cost consequences of induced abortion as an attributable risk for preterm birth and impact on informed consent

OBJECTIVE: To investigate the human and monetary cost consequences of preterm delivery as related to induced abortion (IA), with its impact on informed consent and medical malpractice. STUDY DESIGN: A review of the literature in English was performed to assess the effect of IA on preterm delivery rates from 24 to 31 6/7 weeks to assess the risk for preterm birth attributable to IA. After calculating preterm birth risk, the increased initial neonatal hospital costs and cerebral palsy (CP) risks related to IA were calculated. RESULTS: IA increased the early preterm delivery rate by 31.5%, with a yearly increase in initial neonatal hospital costs related to IA of > $1.2 billion. The yearly human cost includes 22,917 excess early preterm births (EPB) (< 32 weeks) and 1096 excess CP cases in very-low-birth-weight newborns, <1500 g. CONCLUSION: IA contributes to significantly increased neonatal health costs by causing 31.5% of EPB. Providers of obstetric care and abortion should be aware of the risk of preterm birth attributable to induced abortion, with its significant increase in initial neonatal hospital costs and CP cases.     

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial

Context  Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. Objective  To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Design and Setting  Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. Patients  Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. Intervention  Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). Main Outcome Measures  Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. Results  Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). Conclusion  Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.      

腺病毒载体介导的PML生长抑制因子对前列腺癌细胞生长和致瘤能力的抑制效果

为探讨用腺病毒载体携带ＰＭＬ（ＰｒｏｍｙｅｌｏｃｙｔｉｃＬｅｕｋｅｍｉａ）基因作为前列腺癌基因治疗的可能性，应用重组人携带ＰＭＬ基因腺病毒（ＡｄＰＭＬ）感染培养的前列腺癌细胞，观察表达ＰＭＬ蛋白的癌细胞与对照组癌细胞的体外生长和裸鼠体内致瘤能力变化，对荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ，观察治疗组和对照组肿瘤生长的变化。结果显示，感染ＡｄＰＭＬ的前列腺癌细胞体外生长和裸鼠体内致瘤能力明显下降，荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ后肿瘤生长速度明显减慢。证实了ＰＭＬ是一种生长抑制因子，提示其可能被应用于前列腺癌的基因治疗研究     

Perceived causes of psychological problems: An exploratory study

This study explored the major categories of causal explanations used by naive observers to account for psychological problems. A pool of items describing potential causes psychological problems was generated using psychiatric and psychological theory and research and pilot work. Three hundred and ninety-four subjects rated each cause. The results were factor analyzed and five interpretable factors resulted: Factor I, Personal Characteristics: Factor II, Organic Causes; Factor III, Natural Disasters; Factor IV, Marital Crises; and Factor V, Childhood Family Conditions. It was suggested that these five dimensions can be useful in further study of the perceived causes of psychological disorders.     

Impact of bariatric surgery and weight loss medications in adults with type 1 diabetes in the T1D Exchange Clinic Registry

AimTo investigate the impact of bariatric surgery and weight loss medications in adults with type 1 diabetes.Materials and methodsSubjects enrolled in the T1D Exchange (T1DX) Clinic Registry age ≥ 18 years with a diabetes duration of ≥1 year were included in the analysis (n = 13,501). Data for participants (n = 37) with bariatric surgery after diabetes onset were assessed before and after surgery and also compared to a matched control group. Data for participants who reported the use of FDA-approved weight loss medications (n = 483) were assessed before starting, during use, and after stopping the medications and also compared to a matched control group. Variables of interest included BMI, HbA1c, blood pressure, lipid profile, rates of acute complications. Data were analyzed using linear mixed models.ResultsBariatric surgery resulted in BMI reduction from 38.8 ± 9.1 kg/m² to 33.3 ± 6.7 kg/m² (P = 0.006) and HbA1c reduction from 8.8 ± 1.3% (73 ± 14.2 mmol/mol) to 8.1 ± 1.1% (65 ± 12.0 mmol/mol) (P = 0.05). Weight loss medications were not associated with weight loss or better glycemic control although stopping liraglutide favored weight gain. Both interventions were not associated with a significant change in blood pressure or lipid profile. There were no adverse events associated with the use of weight loss medications.ConclusionsBariatric surgery is effective for weight loss and may improve glycemic control in selected patients. Weight loss medications are not associated with diabetes improvement. A trial with liraglutide may be attempted for weight control, but weight loss medications in general do not show a significant effect.     

Tracheal diameter as a predictor of pulmonary function

Tracheal diameter (TD) was measured from standard posterior-anterior (PA) roentgenograms and evaluated as a predictor of pulmonary function. A population of 222 non-smokers with normal chest roentgenograms was analyzed. A subset of the population with the trachea indented two or more mm by the aorta (on PA film), as well as males and females, were analyzed separately. In males without aortic indentation of the trachea, tracheal diameter alone accounted for 28% of the variation in peak expiratory flow rate (PEFR). Age and height accounted for an additional 19% of the variation. Tracheal diameter was second to age as a predictor for forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC), accounting for an additional 10% of the variation in each. However, tracheal diameter did not explain significant variability in the female group. This study supports an upper airway effect on flow at large lung volumes. It also demonstrates that a tracheal diameter, measured from a PA chest film, is a useful predictor of pulmonary function that can be easily applied in population surveys.     

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry

OBJECTIVES: This study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation. BACKGROUND: Magnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo. METHODS: Circumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites. RESULTS: Paired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001). CONCLUSIONS: Magnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.