病重特护患者压疮的发生率、预防和治疗

研究背景压疮普遍发生于急性和慢性患者.然而危重疾病患者通常是压疮发生的高风险因素.目标这个研究的主导是评估重症护理患者的压疮发生率,个体进入到病重护理状态下时,影响压疮发生率的因素和压疮过程.设计纵向设计.     

Insulin resistance in early untreated rheumatoid arthritis patients

ObjectivesTo assess insulin resistance in early untreated rheumatoid arthritis patients and its relation to the clinical, inflammatory and biochemical characteristics of these patients.Patients and methodsSixty-six untreated rheumatoid arthritis (RA) patients with disease duration less than 1 year along with age and sex matched controls were studied. Disease activity score (DAS28) was used to assess disease activity. Plasma levels of C- reactive protein (CRP), glucose, insulin and complete lipid profile were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment for insulin resistance (HOMA-IR).ResultsRA patients revealed high grade systemic inflammation compared to control group p < 0.0001. Patients with high disease activity were more insulin resistant than patients with moderate disease activity P < 0.0001.ConclusionThe findings of the present study showed that early untreated RA patients are characterized by a severe insulin resistant state that is driven primarily by disease activity and systemic inflammation.     

The preclinical pharmacology of roflumilast – A selective,oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease

After more than two decades of research into phosphodiesterase 4 (PDE4) inhibitors, roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) may become the first agent in this class to be approved for patient treatment worldwide. Within the PDE family of 11 known isoenzymes, roflumilast is selective for PDE4, showing balanced selectivity for subtypes A–D, and is of high subnanomolar potency. The active principle of roflumilast in man is its dichloropyridyl N-oxide metabolite, which has similar potency as a PDE4 inhibitor as the parent compound. The long half-life and high potency of this metabolite allows for once-daily, oral administration of a single, 500-μg tablet of roflumilast.The molecular mode of action of roflumilast – PDE4 inhibition and subsequent enhancement of cAMP levels – is well established. To further understand its functional mode of action in chronic obstructive pulmonary disease (COPD), for which roflumilast is being developed, a series of in vitro and in vivo preclinical studies has been performed.COPD is a progressive, devastating condition of the lung associated with an abnormal inflammatory response to noxious particles and gases, particularly tobacco smoke. In addition, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), significant extrapulmonary effects, including comorbidities, may add to the severity of the disease in individual patients, and which may be addressed preferentially by orally administered remedies. COPD shows an increasing prevalence and mortality, and its treatment remains a high, unmet medical need.In vivo, roflumilast mitigates key COPD-related disease mechanisms such as tobacco smoke-induced lung inflammation, mucociliary malfunction, lung fibrotic and emphysematous remodelling, oxidative stress, pulmonary vascular remodelling and pulmonary hypertension. In vitro, roflumilast N-oxide has been demonstrated to affect the functions of many cell types, including neutrophils, monocytes/macrophages, CD4+ and CD8+ T-cells, endothelial cells, epithelial cells, smooth muscle cells and fibroblasts. These cellular effects are thought to be responsible for the beneficial effects of roflumilast on the disease mechanisms of COPD, which translate into reduced exacerbations and improved lung function. As a multicomponent disease, COPD requires a broad therapeutic approach that might be achieved by PDE4 inhibition. However, as a PDE4 inhibitor, roflumilast is not a direct bronchodilator.In summary, roflumilast may be the first-in-class PDE4 inhibitor for COPD therapy. In addition to being a non-steroid, anti-inflammatory drug designed to target pulmonary inflammation, the preclinical pharmacology described in this review points to a broad functional mode of action of roflumilast that putatively addresses additional COPD mechanisms. This enables roflumilast to offer effective, oral maintenance treatment for COPD, with an acceptable tolerability profile and the potential to favourably affect the extrapulmonary effects of the disease.     

Detection of gastric contents in tracheal fluid of infants by lactose assay

We designed an in vitro assay to detect the presence of lactose in the tracheal aspirates of premature, ventilator-dependent infants. This method was employed to identify recurrent, unrecognized aspiration, which could prolong the requirements for ventilator support and contribute to the development of chronic lung disease. One hundred five determinations of lactose were performed on the tracheal fluid obtained from 42 ventilator-dependent infants who were receiving enteral feedings. There was a wide range of lactose levels (0 to 3,270 nmol lactose/ml tracheal aspirate). Six infants had samples that were highly suggestive of aspiration (greater than 200 nmol lactose/ml tracheal aspirate). Twenty infants had questionably positive samples (25 to 200 nmol lactose/ml tracheal aspirate), and 16 infants had samples that were considered negative for aspiration (less than 25 nmol lactose/ml tracheal aspirate).     

Ciprofloxacin resistance in Neisseria gonorrhoeae in England and Wales in 2002

The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) monitors trends in antimicrobial resistance in consecutive gonococcal isolates from 26 genitourinary medicine clinics in England and Wales. In 2002, 2204 gonococcal isolates were tested, and the overall prevalence of ciprofloxacin resistance (minimum inhibitory concentration > or =1 mg/L) was 9.8%, compared with 3.1% in 2001 and 2.1% in 2000. Between 2001 and 2002, prevalence of ciprofloxacin resistance increased two to three-fold, irrespective of recent sexual contact overseas, sex, or residence within or outside of London. These findings suggest that national and local treatment guidelines need to be reviewed urgently.     

A phase I/II trial of rAd/p53 (SCH 58500) gene replacement in recurrent ovarian cancer

PURPOSE: To determine the safety, gene transfer, host immune response, and pharmacokinetics of a replication-deficient adenovirus encoding human, recombinant, wild-type p53 (SCH 58500) delivered into the peritoneal cavity (i.p.) alone and sequentially in combination with platinum-based chemotherapy, of patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer containing aberrant or mutant p53. METHODS: SCH 58500 was administered i.p. to three groups of patients with heavily pretreated recurrent disease. Group 1 (n=17) received a single dose of SCH 58500 escalated from 7.5 x 10(10) to 7.5 x 10(12) particles. Group 2 (n=9) received two or three doses of SCH 58500 given alone for one cycle, and then with chemotherapy for two cycles. The SCH 58500 dose was further escalated to 2.5 x 10(13) particles/dose in group 2. A third group (n=15) received a 5-day regimen of SCH 58500 given at 7.5 x 10(13) particles/dose per day i.p. alone for cycle 1 and then with intravenous carboplatin/paclitaxel chemotherapy for cycles 2 and 3. RESULTS: No dose-limiting toxicity resulted from the delivery of 236/287 (82.2%) planned doses of SCH 58500. Fever, hypotension abdominal complaints, nausea, and vomiting were the most common adverse events. Vector-specific transgene expression in tumor was documented by RT-PCR in cells from both ascitic fluid and tissue biopsies. Despite marked increases in serum adenoviral antibody titers, transgene expression was measurable in 17 of 20 samples obtained after two or three cycles of SCH 58500. Vector was detectable in peritoneal fluid by 24 hours and persisted for as long as 7 days whereas none was detected in urine or stool. There was poor correlation between CT scans and CA125 responses. CA125 responses, defined as a greater than 50% decrement in serum CA125 from baseline, were documented in 8 of 16 women who completed three cycles of the multidose regimen. CONCLUSION: CT scans are not a valid measure of response to i.p. SCH 58500 due to extensive adenoviral-induced inflammatory changes. Intraperitoneal SCH 58500 is safe, well tolerated, and combined with platinum-based chemotherapy can be associated with a significant reduction of serum CA125 in heavily pretreated patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.     

G-protein alpha(olf) subunit promotes cellular invasion,survival, and neuroendocrine differentiation in digestive and urogenital epithelial cells

The heterotrimeric G-protein subunits Galpha and Gbetagamma are involved in cellular transformation and tumor development. Here, we report the expression of Galpha(olf) in human digestive and urogenital epithelial cells using RT-PCR and Western blot. When the constitutively activated form of Galpha(olf)Q214L (AGalpha(olf)) was stably transfected in canine kidney MDCKts.src and human colonic HCT-8/S11 epithelial cells, it induced cellular invasion in collagen gels. AGalpha(olf)-mediated invasion was abrogated by agonists of platelet activating factor receptors (PAF-R) and protease-activated receptors -1 (PAR-1), pharmacological inhibitors of PI3'-Kinase (wortmannin), protein kinase C (G?6976 and GF109203X), Rho GTPase (C3T exoenzyme), but was independent of protein kinase A. Accordingly, the invasive phenotype induced by AGalpha(olf) in HCT-8/S11 cells was reversed by the RhoA antagonist RhoD (G26V). Although AGalpha(olf) protected MDCKts.src cells against serum starvation-mediated apoptosis via a Rho-independent pathway, both AGalpha(olf) and Rho inhibition by C3T induced neuroendocrine-like differentiation linked to extensive neurite outgrowth and parathyroid hormone-related protein expression in human prostatic LNCaP-AGalpha(olf) cells. Since prostate tumors with a larger neuroendocrine cell population display increased invasiveness, persistent activation of the G-protein alpha(olf) may exert convergent adverse effects on cellular invasion and survival in solid tumors during the neoplastic progression towards metastasis. doi:10.1038/sj.onc.1205498     

Iodine-131 MIBG scintigraphy in small cell lung cancer

There is a well documented relationship between small cell carcinoma of the lung and the amine precursor uptake and decarboxylation system of endocrine cells (APUD). We attempted to exploit this association by employing the unique radiopharmaceutical,¹³¹I-MIBG, which is recognized and taken up by the APUD system to monitor disease activity in patients with small cell carcinoma of the lung. A total of eight patients with biopsy proven, metastatic small cell carcinoma of the lung were studied.¹³¹I-MIBG was synthesized in our laboratory by reacting metaiodobenzylamine synthesized in our laboratory by reacting metaiodobenzylamine hydrochloride with cyanamide with subsequent solid phase radioiodination. A dose of 0.5 mCi radiopharmaceutical was injected and images obtained on a large field of view gamma camera with a high energy parallel hole collimator at 2, 24, and either 48 or 72 h. Images were compared with known focal areas of metastatic disease demonstrable on computed tomographic scan, chest roentgenogram or bone scan. We were unable to detect reproducible correlations between the images produced by conventional radiographic techniques and the images produced by our radiopharmaceutical. We conclude that this agent will probably not be useful for localization of metastatic small cell lung carcinoma.This work was supported by a Pilot Research Grant from the Education and Research Foundation of the Society of Nuclear Medicine