Effects of the IGF-I/IGFBP-3 complex on GH and ghrelin nocturnal concentrations in low birth weight children

OBJECTIVE: There is limited information regarding the effects of IGF-I and/or IGFBP-3 on circulating ghrelin concentrations. To determine the effects of IGF-I on GH and ghrelin concentrations, we examined the GH and ghrelin nocturnal profiles before and after the administration of the IGF-I/-IGFBP-3 complex (Iplex) to low birth weight children. DESIGN: The children were studied on two separate occasions, the first under basal conditions, and the second time after the sc administration of 1 mg/kg of Iplex at 2100 h. Blood samples for determination of GH and ghrelin were obtained every 20 min between 2300 h and 0700 h, while the children were sleeping. In each patient, we calculated the mean GH and ghrelin area under the curve (GH AUC and GHR AUC), both under basal conditions and after the administration of the IGF-I/IGFBP-3 complex. SETTING: The study was performed at a University Research Centre located at a General Hospital in Santiago, Chile. PATIENTS: Twenty prepubertal children (11 boys and 9 girls), born after a full-term pregnancy with a birth weight below 2.8 kg were studied at a mean +/- SEM age of 7.3 +/- 0.5 years (range 4-11 years). Their mean height was -1.8 +/- 0.3 standard deviation score (SDS) and their mean BMI was 0.1 +/- 0.2 SDS at the time of the study. MAIN OUTCOME AND RESULTS: Mean nocturnal GH AUC exhibited a significant decrease (2903 +/- 185 vs 1860 +/- 122 ng/ml min, P < 0.01), whereas mean GHR AUC showed a significant increase after administration of the IGF-I/IGFBP-3 complex (68 +/- 16 vs 288 +/- 36 ng/ml min, P < 0.01). CONCLUSIONS: These findings indicate that the IGF-I/IGFBP-3 complex appears to have opposite effects on circulating GH and ghrelin concentrations in low birth weight children, suggesting that, in addition to its known negative feed-back effect on GH, IGF-I and/or IGFBP-3 may have a positive feed-back effect on ghrelin.     

Dose-intensified treatment of advanced-stage diffuse large B-cell lymphomas

The introduction of the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen 30 years ago was the great breakthrough in the treatment of advanced-stage aggressive lymphomas. About 50% of all patients treated with CHOP achieved complete remission, and about one third experienced long-term disease-free survival and cure. Attempts to improve results by modifications of CHOP using escalated doses, additional drugs, or the alternative use of putatively non-cross-resistant chemotherapy regimens were not confirmed in randomized trials. With the availability of granulocyte colony-stimulating factor (G-CSF) and the tool of autologous stem cell support in the 1990s, dose escalation, dose densification (by interval reduction), or combinations thereof were pursued to increase dose intensity. While dose-escalation strategies, including high-dose approaches necessitating stem cell support, have not been demonstrated unequivocally yet to be superior to a baseline CHOP-21, dose-dense (biweekly) modifications improved the outcome of young and elderly patients with aggressive lymphomas compared to baseline CHOP-21. The challenges in the era of the monoclonal antibody rituximab are the identification of the ideal chemotherapy partner for rituximab both with respect to potential synergistic effects and to the lack of interference with its effector mechanisms. Finally, the issue of intensifying rituximab within such approaches must be addressed by appropriately designed randomized trials.     

CARP编码蛋白的相互作用蛋白筛选

目的 :筛选与CARP编码蛋白相互作用的蛋白 ,为其功能研究奠定基础。方法 :将编码全长CARP的DNA序列插入到pGBKT7 BD载体中 ,转化AH1 0 9酵母 ,然后与含有已克隆到pACT2载体上的人心脏cDNA文库的Y1 87酵母融合。CARP与相应的人心脏cDNA片段编码的蛋白发生相互作用后 ,可激活报告基因的表达。阳性克隆的质粒进行测序分析。同源性检索搜寻GenBank中与之相同或相似的序列。结果 :共筛选约 3× 1 0 7个cDNA ,筛选出 9个阳性克隆 ,其中包括FLNa (actin bindingprotein 2 80 )。结论 :CARP编码蛋白在酵母中可以特异性的结合FLNa ,提示CARP可能通过与FLNa相互作用参与调控细胞增殖     

早发冠心病患者的G蛋白β3亚单位基因多态性分析

目的: 探讨G蛋白β3亚单位(GNB3)基因C825T多态性在早发冠心病患者中的分布情况及特点,分析其与疾病的关系.方法: 采用聚合酶链反应和限制性片段内切酶的方法检测了342例经冠状动脉造影证实的早发冠心病患者(冠心病组,男性275例,年龄<55岁;女性67例,年龄<65岁)及133例经冠状动脉造影排除冠心病者(对照组)的GNB3基因C825T多态性.结果: GNB3基因C825T多态性在两组人群中的分布有显著性差异,冠心病组T等位基因和TT基因型频率显著高于对照组(P<0.05～0.01),C等位基因和CT、CC基因型频率两组比较均无显著性差异(P>0.05).逻辑回归分析结果显示:在调整了其他危险因素后,825T等位基因携带者和具有825TT基因型者早发冠心病的相对危险度增加(825T等位基因携带:相对危险度=1.8,95%可信区间为1.117～3.040,P=0.017;825TT基因型:相对危险度=2.4,95%可信区间为1.312～4.254,P=0.004),C等位基因和CC、CT基因型频率与早发冠心病的关系没有统计学意义(P>0.05). 结论: GNB3基因C825T多态性的825T等位基因和TT基因型可能是冠心病早期发病的遗传因素之一.     

Use of drug-eluting stents for the treatment of in-stent restenosis in routine clinical practice

BACKGROUND: Although target lesion revascularization (TLR) has been dramatically decreased by using drug-eluting stents (DESs) in de-novo lesions, their efficacy for in-stent restenosis (ISR) has not yet been well established. METHODS: We retrospectively analysed patients treated for ISR with DESs from three referral hospitals. RESULTS: Eighty-seven consecutive patients, from June 2002 to April 2004, were included, with a mean age of 64+/-11 years; 83% were men, 32% had diabetes, 47% had had a previous myocardial infarction and 16% had low left ventricular ejection fraction. Angiographic characteristics were as follows: mean vessel diameter, 3.05+/-0.4 mm; lesion length, 17.8+/-7.7 mm; diameter stenosis, 84.0+/-10.7%; and complex lesion, 81%. The restenosis was focal in 45%, diffuse/proliferative in 51.3% and total occlusion in 3.7% of the cases. Sirolimus- and paclitaxel-eluting stents were used in 42 and 58% of the patients, respectively. Stent diameter was 3.1+/-0.3 mm and the length was 26.1+/-5.8 mm. Angiographic success was achieved in all patients, with one patient experiencing a post-procedural non-Q-wave myocardial infarction. At 6-month clinical follow-up, two patients had died from non-cardiac deaths, five had experienced a new TLR (5.7%, four percutaneous and one coronary artery bypass graft) and eight (9.2%) had had major adverse cardiac events. A stress test was performed in 60% of the population; target vessel ischemia was observed in one patient (3.3%). CONCLUSION: In this non-select cohort of patients, the use of DESs is a safe and effective strategy for ISR lesions.     

Body plethysmography--its principles and clinical use

Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airway resistance (sRaw) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance (Raw) is calculated as the ratio of sRaw to FRC(pleth). Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s(-1). In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the same, mirror image-like shift volume as the lung. This shift volume can be measured via the variation of box pressure. The relationship between shift volume and alveolar pressure is assessed in a shutter maneuver, by identifying mouth and alveolar pressure under zero-flow conditions. These variables are combined to obtain FRC(pleth), sRaw and Raw. This presentation aims at providing the reader with a thorough and precise but non-technical understanding of the working principle of body plethysmography. It also aims at showing that this method yields significant additional information compared to spirometry and even bears a potential for further development.     

Oral N-acetylcysteine attenuates elastase-induced pulmonary emphysema in rats

STUDY OBJECTIVE: To study the effect of the antioxidant N-acetylcysteine (NAC) in the development of elastase-induced emphysema in rats. MATERIALS AND METHODS: Wistar rats (n = 72) were orotracheally instilled with 75 IU elastase or saline solution. Eighteen rats from each group received the antioxidant NAC from 2 days before induction of the lesion until they were killed 2, 8, and 28 days after instillation. The effects of treatment were assessed by measuring collagen content for the left lung, a histopathology evaluation (ie, mean alveolar internal surface area (AIA) and mean linear intercept measurement), and lung function. RESULTS: Twenty-eight days after elastase instillation, rats treated with NAC showed significant attenuation of the lesion in comparison with rats treated only with elastase, including the following: normalization of mean (+/- SEM) collagen content (1.23 +/- 0.09 vs 1.51 +/- 0.10 mg per left lung, respectively; p < 0.05); partial inhibition of mean AIA (14,860 +/- 1,135 vs 19,622 +/- 1,294 micro m(2), respectively; p < 0.05) and mean linear intercept (108.8 +/- 3.7 vs 123.0 +/- 4.2 micro m, respectively; p < 0.05); and increases and improvement in expiratory flows (27.8 +/- 1.2 vs 23.4 +/- 1.3 mL/s, respectively; p < 0.05). NAC was not able to avoid the compliance increase in the elastase-plus-NAC group. CONCLUSION: Consistent with the results of anatomic, pathologic, and functional studies, NAC is able to attenuate the lesions induced by elastase in rats, which is in accordance with previous data supporting the idea that oxidant injury could contribute to the development of elastase-induced emphysema.     

Efficacy of lincomycin versus penicillin and clarithromycin in patients with acute pharyngitis/tonsillitis caused by group a beta-hemolytic streptococci and a clinical history of recurrence

This open-label, prospective, randomized, comparative, single-masked study was performed at eight centers in the Philippines and Latin America (Chile, Colombia, Peru, Brazil, and Venezuela). The purpose of this study was to assess the efficacy and tolerability of three different antibiotic regimens for the treatment of acute pharyngitis/tonsillitis as a result of group A beta-hemolytic streptococci (GABHS), and to assess the rate of recurrences. Children (aged 3 to 15 years) and adults with a recent history of tonsillitis associated with a positive rapid diagnostic test for group A streptococcus, later confirmed by positive cultures for GABHS, were randomized to one of the following antibiotic regimens (according to patient age) for 10 days: (1) lincomycin hydrochloride capsules or suspension: adults—two 500-mg capsules two times a day (BID) for 10 days; children—60 mg/kg per day divided BID for 10 days (maximum dose, 1000 mg/d); (2) phenoxymethylpenicillin capsules or suspension: adults—one 500-mg capsule three times a day (TID) for 10 days; children—50 mg/kg per day divided TID for 10 days (maximum dose, 1500 mg/d); (3) clarithromycin capsules or suspension: adults—one 250-mg capsule BID for 10 days; children—7.5 mg/kg per day divided BID for 10 days (maximum dose, 500 mg/d). After the initiation of treatment (12 to 14 days) and 3 months after completion, patients were evaluated to assess clinical and microbiologic recurrences. Our results indicate that all drugs had statistically similar clinical and bacteriologic efficacy as well as tolerability for the treatment of acute GABHS pharyngitis/tonsillitis with a clinical history of recurrence.     

Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group

Conventional chemotherapy has failed to substantially prolong survival for patients with advanced follicular lymphoma. To improve outcomes, the German Low-Grade Lymphoma Study Group (GLSG) initiated a randomized trial to compare the effect of potentially curative myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) with interferon-alpha (IFN-alpha) maintenance therapy in first remission. Three hundred seven patients (younger than 60 years) with follicular lymphoma were recruited into the trial from 130 institutions. After 2 cycles of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or mitoxantrone-chlorambucil-prednisone (MCP) induction chemotherapy, patients were randomly assigned to either the ASCT or the IFN-alpha group. The respective therapy was started when patients achieved complete or partial remission after induction chemotherapy. Two hundred forty patients with follicular lymphoma are evaluable for the comparison of ASCT and IFN-alpha. In patients who underwent ASCT, the 5-year progression-free survival (PFS) rate was 64.7%, and in the IFN-alpha arm it was 33.3% (P < .0001). As expected, acute toxicity was higher in the ASCT group, but early mortality was below 2.5% in both study arms. In this randomized, multicenter trial, high-dose radiochemotherapy followed by ASCT significantly improved PFS compared with IFN-alpha in patients with follicular lymphoma when applied as consolidation in first remission. Longer follow-up is necessary to determine the effect of ASCT on overall survival.     

Guidelines for the sociomedical assessment of performance in patients suffering from inflammatory bowel disease

The following guidelines were developed for the medical assessment services of the German Federal Insurance Institute for Salaried Employees (BfA). Starting from day-to-day practice, criteria and attributes to guide decisions for a systemization of the sociomedical assessment of performance in inflammatory bowel disease (Crohn's disease, ulcerative colitis) were compiled. The guidelines aim at standardising the sociomedical assessment of performance and help to make the decision-making process more transparent -- e. g. for the assessment of applications for decreased earning capacity benefits. The guidelines summarise typical manifestations of inflammatory bowel disease and describe the necessary medical information for the sociomedical assessment of performance. Relevant assessment criteria for the medical history, clinical examination, and for diagnostic tests are illustrated. The assessment of the individual's capacity is outlined, taking occupational factors into account. Following the determination of dysfunctions the remaining abilities and disabilities, respectively, are deduced and compared with occupational demands. Finally, inferences are drawn regarding the occupational capacity of the individual.