Pathophysiology of congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH.

Exogenous surfactant therapy (EST) in surfactant-deficient premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Reports have demonstrated that newborns with congenital diaphragmatic hernia (CDH) have lung compliance, pressure-volume curves, and hyaline membrane formation resembling those changes seen in surfactant deficient premature newborns. We hypothesize that EST may also benefit infants with CDH. All high risk cases of prenatally diagnosed CDH at Children's Hospital of Buffalo from November 1988 to February 1991 were prospectively evaluated for EST. In those families who chose to participate, the surfactant preparation, Infasurf (100 mg/kg), was instilled into the newborn's lungs prior to the first breath. The remainder of the perinatal, neonatal, and surgical care was performed in a routine manner. Three high-risk prenatally diagnosed newborns with left CDH were treated with EST. All showed signs of decreased pulmonary compliance, but could still be adequately oxygenated and ventilated. Surgical correction was performed after stabilization and all required patch closures. Two of the three infants suffered no life-threatening episodes of pulmonary hypertension and all survived. These infants had many known indicators for poor outcome in CDH with an expected survival of less than 20%. We believe that EST in these neonates with CDH contributed to their survival with minimum morbidity. These results suggest that surfactant replacement for the high-risk neonate with CDH warrants further consideration and a randomized clinical trial is being planned.     

Cyclooxygenase 2 expression in serous tumors of the ovary.

This study was designed to investigate the expression of cyclooxygenase (COX)-2 in ovarian serous tumors (benign, borderline tumors, and carcinomas) and primary peritoneal serous carcinomas. Cases diagnosed between 1995 and 2001 were reviewed; 47 benign tumors, 6 borderline tumors, and 39 carcinomas were examined, as well as 12 normal ovaries that served as controls. Blocks were stained with anti COX-2 polyclonal antibody and staining was graded qualitatively. The staining intensity was assessed as weak (score of 1), moderate (score of 2), or strong (score of 3). Normal ovarian and tubal epithelium, inclusion cysts, benign serous tumors, and borderline tumors had a uniform score 3 staining pattern. Serous ovarian carcinomas had variable staining scores, tending to correlate with the level of tumor differentiation. Well-differentiated carcinomas had more intense COX-2 staining than poorly differentiated carcinomas, which had only weak COX-2 staining. The degree of COX-2 staining was not significantly related to overall survival. In conclusion, COX-2 expression is present in serous tumors, including benign tumors, borderline tumors, and carcinomas. Similar to the findings in other neoplasms, COX-2 expression is strongest in well-differentiated tumors and is much less evident in those that are poorly differentiated. The clinical utility of these findings is related to the potential role of nonsteroidal anti-inflammatory drugs, which are COX-2 inhibitors, in treating and/or preventing some forms of ovarian carcinoma.     

Apoptosis incidence and protein expression of p53, TGF-beta receptor II, p27Kip1, and Smad4 in benign, premalignant, and malignant human prostate

Deregulation of apoptosis is involved in prostate cancer development and progression. This study involved an immunohistochemical "profiling" of prostate tissue specimens from patients who underwent prostatectomy for localized prostate cancer, to identify apoptosis-specific alterations associated with premalignant precursor lesions. Prostate tissue was pathologically evaluated, and areas of benign acini, high-grade prostate intraepithelial neoplasia (HGPIN), and prostate cancer were identified. Immunohistochemical analysis was performed to determine the expression of p27Kip1, a key cell cycle regulator, transforming growth factor (TGF)-beta receptor II (TbetaRII), a critical signaling effector of TGF-beta; Smad4, a downstream intracellular effector of TGF-beta signaling; p53, a key apoptosis regulator; and prostate-specific antigen (PSA), a clinical marker of prostate cancer. The apoptotic index of the same cell populations was determined using the transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end labeling assay. Our findings indicate a significant reduction in p27Kip1 immunoreactivity in HGPIN (P<0.0001) and prostate cancer (P<0.0001) compared with the benign tissue. A significant down-regulation was detected in TbetaRII expression in HGPIN and prostate cancer compared with benign prostatic hyperplasia (BPH)(P<0.001). A significant decrease was also observed in Smad4 levels in HGPIN and prostate cancer compared with BPH (P<0.001). Evaluation of the incidence of apoptosis revealed a significant decrease in the apoptotic index among the epithelial cell populations in HGPIN and a further decrease in prostate carcinoma (P<0.01). This reduced apoptotic index correlated with a significant increase in p53 immunoreactivity in the prostatic carcinoma foci. Prostate cancer cells exhibited strong nuclear staining for p53 compared with adjacent HGPIN (P<0.05) and the benign lesions of the same prostate specimens (P<0.05). A significant reduction in PSA immunostaining was detected in HGPIN and prostate carcinoma foci compared with the benign glandular epithelia (P<0.001). These results further define deregulation of TGF-beta signaling effectors as a molecular basis for loss of apoptotic control contributing to the development of prostate tumors. Identification of apoptotic regulators in precursor premalignant lesions may have prognostic significance in disease progression as well as therapeutic value for targeting prostate cancer.     

Hydrophobically Modified Poly(acrylic acid) Using 3‐Pentadecylcyclohexylamine: Synthesis and Rheology

Summary: Hydrophobically modified poly(acrylic acid) was synthesized using 3‐pentadecylcyclohexylamine (3‐PDCA), which was in turn synthesized from 3‐pentadecylphenol, one of the components of cashew‐nut shell liquid (CNSL), a renewable resource material. ¹H NMR spectra confirmed the incorporation of 3‐PDCA onto PAA and a series of HMPs with three different molar concentrations, viz ? 3, 5 and 7 mol‐% of 3‐PDCA, were synthesized. An increase in viscosity with increasing hydrophobic content was observed by rheological measurements. The critical association concentrations were determined using an Ubbelohde viscometer and a controlled stress rheometer. The stability of HMPs towards temperature and shear was studied. Rheological measurements showed that there was a steady increase in viscosity with increase in hydrophobe content due to the formation of reversible networks. These polymers exhibited gel‐like behavior at low concentrations (≥2 wt.‐%) with an apparent yield stress (ca. 10 Pa) and showed shear thinning properties (non‐Newtonian). However, below a critical concentration, c [η], they showed Newtonian behavior.

η_sp of unmodified and modified PAA‐Na at various polymer concentrations.     

Evaluation of the nephrotoxicity of iproplatin (CHIP) in comparison to cisplatin by the measurement of urinary enzymes

Summary Levels of three enzymes, leucine aminopeptidase (LAP), N-acetyl--D-glucosaminidase (NAG), and -glucuronidase (BGA) were measured in the urine of patients receiving hematologically toxic doses of iproplatin (a) with or (b) without pretreatment hydration. The maximum post-treatment increases in the levels of each of the enzymes were compared between these two groups of patients. In addition, the maximum increases in urinary enzyme levels in iproplatin-treated patients were compared with those in patients treated with 40 mg/m² cisplatin, a known nephrotoxic agent.Increases in LAP levels after cisplatin treatment in the periods studied are significantly higher than those after iproplatin treatment (P0.05). No differences were found in the increases in BGA and NAG levels between iproplatin treatment and cisplatin treatment. No differences were found in the increases in levels of any of the enzymes between patients receiving iproplatin with pretreatment hydration and no prior hydration.The work reported in this paper was supported in part by grant CA-21071 from USPHS NCI and by Bristol Myers Co.     

利益传导视角下医疗服务价格改革对医务人员薪酬水平的影响*

目的：医疗服务价格改革对完善医疗服务合理定价,合理体现医务人员劳务价值,提高医务人员薪酬水平具有重要意义。方法：基于利益传导的视角,以医务人员劳务价值的体现为中介,采用定量研究方法,实证检验医疗服务价格对医务人员薪酬水平的影响。结果：医疗费用规模对医务人员薪酬水平有着显著的正向影响,但在门诊医疗和住院医疗二者间存在异质性,主要体现在劳务价值在医疗费用中的差异方面。结论：应持续深化医疗服务价格改革,提高医务人员薪酬水平。     

曲马多缓释片用于拔牙镇痛的效果观察

近年来随着各种新镇痛药的问世 ,牙科治疗中的疼痛问题有了新的解决办法。本研究采用随机双盲法观察了拔牙术前应用曲马多缓释片 (下称曲马多 )的镇痛效果 ,并对拔牙术后疼痛的相关因素作多元回归分析。对象与方法1.对象 :10 4例门诊需拔牙的患者 ,其中男性 46例、女性 5 8例 ;年龄 18～ 86岁。根据随机双盲原则分为曲马多组 42例、索米痛组 30例和安慰剂组32例 (用葡萄糖酸钙片 )。2 .方法 :由专门一位医生 (不知患者已用何种药物 )按常规方法拔牙 ,以减少技术上的差异 ,并告诉患者拔牙前使用了止痛药以避免干扰性心理因素的作用。各组在术…     

Correlation between Extreme Drug Resistance Assay and Response to Primary Paclitaxel and Cisplatin in Patients with Epithelial Ovarian Cancer

Objective.The extreme drug resistance (EDR) assay has been correlated with failure of response to chemotherapy in greater than 99% of patients. The goal of this study is to correlate the results of the EDR assay to response to first-line paclitaxel/cisplatin among patients with epithelial ovarian cancer.Methods.Seventy-five of 100 patients with epithelial ovarian cancer for whom EDR assay was performed were treated with weekly induction cisplatin (1 mg/kg body wt) × 4, followed by monthly paclitaxel (135 mg/m²) and cisplatin (75 mg/m²) × 6 and were evaluable for correlation of response to chemotherapy and EDR assay. Specimens for EDR assay were obtained at primary surgery and the EDR assay was performed by Oncotech, Inc. Response to chemotherapy was correlated to EDR assay results regarding paclitaxel and cisplatin.Results.Among 75 evaluable patients, the prevalence of EDR to paclitaxel was 20.0% (n= 15) and to cisplatin it was 2.7% (n= 2). Only 1 patient (1.3%) exhibited EDR to both paclitaxel and cisplatin. Surgical assessment of response was performed in 42 patients; 33 patients were clinically evaluable. The overall response rate was 85.3%. The overall response rate for patients whose tumors demonstrated no EDR to either paclitaxel or cisplatin did not differ significantly from that for patients whose tumors demonstrated EDR to at least one of these two drugs (86.4% versus 81.3%, respectively,P= 0.692). Similarly, the complete surgical response rate for both groups did not differ significantly (25.4% versus 12.5%, respectively,P= 0.34). A single patient whose tumor exhibited EDR to both paclitaxel and cisplatin had tumor progression. The sensitivity, specificity, positive predictive value, and negative predictive value of the EDR assay were 79.6, 27.0, 86.0, and 19.0%, respectively.Conclusions.EDR to paclitaxel does not preclude response to the combination of paclitaxel and cisplatin as primary therapy for patients with epithelial ovarian cancer. The role of the EDR assay in the primary management of patients with epithelial ovarian cancer remains to be determined.     

Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15×10^?5, OR=5.07), rs16861329 on 3q27.3 (P=2.02×10^?4, OR=0.87) and rs849135 on 7p15.1 (P=6.59×10^?9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T‐cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes.     

中药灌肠对大肠湿热型UC患者血浆MMP-1及TIMP-1的影响

目的应用中药灌肠,探讨清热利湿中药对溃疡性结肠炎(UC)患者血浆MMP-1及TIMP-1的影响。方法观察我院自拟中药保留灌肠治疗溃疡性结肠炎的疗效。将60例患者随机分为两组:西药灌肠组30例给予柳氮磺胺吡啶保留灌肠,疗程4周;中药灌肠组30例给予我院自拟中药汤剂保留灌肠。另选择30例来自门诊健康体检者作为健康对照组。结果 UC患者血浆MMP-1、TIMP-1水平明显高于对照组,中药灌肠组MMP-1及TIMP-1下降水平明显高于对照组。结论中药灌肠治疗UC与西药柳氮磺胺吡啶对比,可明显降低血浆MMP-1及TIMP-1,是治疗UC可能的作用机制之一。