Plasminogen activator system in smokers and non-smokers with and without periodontal disease

BACKGROUND: The present study assessed levels of plasminogen activator (PA) system proteins in gingival crevicular fluid (GCF) and serum of chronic gingivitis, chronic periodontitis patients and periodontally healthy subjects and evaluated how smoking influenced these levels. METHODS: Twenty chronic gingivitis; 20 chronic periodontitis patients and 20 periodontally healthy volunteers were consecutively recruited according to the inclusion criteria so that exactly half of the subjects in each category were smokers. GCF samples from four sites together with serum samples were obtained from each subject. GCF levels of tissue type PA (t-PA), urokinase type PA (u-PA), PA inhibitor-1 (PAI-1) and PA inhibitor-2 (PAI-2) and serum concentrations of cotinine, u-PA and PAI-1 were analysed by enzyme-linked immunosorbent assay. RESULTS: The only statistically significant difference between smokers and non-smokers was a lower GCF PAI-2 concentrations in healthy smokers compared with healthy non-smokers (p<0.01). Gingivitis and periodontitis patients had higher GCF concentrations of PAI-2 than healthy subjects (p<0.002 and p<0.02 respectively). The ratio of u-PA:PAI-1 and t-PA:PAI-1 were significantly higher in GCF of smokers with periodontitis compared with "healthy" smokers, whereas the ratio of t-PA:PAI-2 was significantly lower in smokers with periodontal disease (p<0.05). CONCLUSIONS: GCF levels of the PA system proteins are increased in chronic gingivitis and periodontitis compared with healthy gingiva. Smoking had only subtle effects on the GCF PA system proteins with the exception of PAI-2, and the balance of activators and inhibitors. These findings suggest one mechanism whereby smoking may exert detrimental effects on the periodontal tissues.     

选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

MGB1 Poor Adherence to Hypertension Treatment Guidelines: An Analysis of Therapeutic Choices

The recent Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) reiterated long-standing recommendations that Stage 1 hypertension (BP ≥ 140/90 mm Hg) without comorbidity should be treated initially with diuretics (DI) or beta blockers (BB). Yet market research suggests that many physicians prefer to use other drug classes, such as calcium channel blockers and ACE inhibitors.
OBJECTIVES: To explore the determinants of therapeutic choice in hypertension.
METHODS: We surveyed by mail a stratified random sample of 10,000 U.S. cardiologists, internists, and family/general practitioners. Physicians were queried about their practice environment and their knowledge, attitudes, and practices regarding antihypertensive therapy, including their choice of drugs to treat patients with specified clinical profiles. The probability that physicians would follow JNC guidelines Stage 1 hypertension was analyzed using multiple logistic regression with stepwise backward elimination to select variable with p < 0.001.
RESULTS: Completed surveys were received from 1,023 physicians. 86.7% prescribe drug therapy for Stage 1 hypertension, and 19.5% (22.5% of drug prescribers) limit their choices to DI and BB. Guideline conformity was higher among physicians who: practice in academic medical centrers; are older; are general practitioners (versus general internists); have smaller caseloads; have fewer hypertensive patients; have higher proportions of HMO, Medicaid, and uninsured patients; and experience more formulary restrictions. Cardiologists and family practitioners were less likely than internists to follow guidelines.
CONCLUSION: JNC guidelines are better accepted by academic physicians, older physicians who have more expenence using DI and BB, physicians with smaller caseloads and hence more time for follow-up and therapy adjustment, and physicians who face drug reimbursement constraints.     

An Audit of the Activities of the Pediatric Dermatology Nurse Specialist (PDNS)

Abstract:   In the current financial climate where resources in the National Health Service are becoming increasingly limited, it is essential that the role of the pediatric dermatology nurse specialist remains appreciated and supported. Our pediatric dermatology nurse specialist was first employed in September 2002 having had 6 years experience nursing children with a wide variety of dermatologic conditions prior to her employment. She achieved her pediatric community nursing degree in 2003 undertaking the nurse prescribing extended formulary course in 2006, her training history representative of many nurse specialists. We present the results of an audit highlighting how the employment of our pediatric dermatology nurse specialist has led to a decrease in hospital admissions as well as providing a significant positive impact on waiting lists.     

New agents for treatment of advanced transitional cell carcinoma

The prognosis for any patient with progressive or recurrentinvasive transitional cell carcinoma remains poor. In this context,the focus of clinical research in these invasive cancers concentrateson identifying systemic treatment options and new agents inorder to improve survival of patients. Cisplatin-based chemotherapyis standard treatment of patients with metastatic urothelialcancer; however, despite regimens as the cisplatin–gemcitabinecombination, the overall response rates vary between 40% and65%, with complete response in 15%–25% with survivalsup to 16 months. This survival is frequently achieved with severeand life-threatening side effects. None the less, almost allresponding patients relapse within the first year; therefore,the need for development of new and tolerable agents is urgent.This review highlights some new active chemotherapeutic as newplatinum compounds (oxaliplatin, lobaplatin), gallium nitrate,ifosfamide, the antifolates piritrexim and pemetrexed (Alimta®,LY231514), vinflunine and molecular targeting agents such asfarnesyltransferase inhibitors (lonafarnib, R115777, SCH66336),ribozyme (RPI.4610), histone deacetylase inhibitor (CI-994)and monoclonal antibodies (epidermal growth factor receptor,Her 2/neu). Key words: transitional cell carcinoma, gallium nitrate, vinflunine, platinum compounds, antifolates, molecular targeting agents Received for publication February 8, 2006. Revision received August 4, 2006. Accepted for publication August 10, 2006.     

Activated human monocytes inhibit the intracellular multiplication of legionnaires’ disease bacteria

We have examined the interaction between virulent egg yolk-grown L. pneumophila, Philadelphia 1 strain, and in vitro-activated human monocytes, under antibiotic-free conditions. Freshly explanted human monocytes activated by incubation with concanavalin A (Con A) and human lymphocytes inhibited the intracellular multiplication of L. pneumophila. Both Con A and lymphocytes were required for activation. Con A was consistently maximally effective at greater than or equal to 4 μg/ml. Monocytes activated by incubation with cell-free filtered supernatant from Con A-sensitized mononuclear cell cultures also inhibited the intracellular multiplication of L. pneumophil a. The most potent supernatant was obtained from mononuclear cell cultures incubated with greater than or equal to 15 μg/ml Con A for 48 h. The degree of monocyte inhibition of L. pneumophila multiplication was proportional to the length of time monocytes were preincubated with supernatant (48 {greater than} 24 {greater than} 12 h) and to the concentration of supernatant added (40 percent {greater than} 20 percent {greater than} 10 percent {greater than} 5 percent). Monocytes treated with supernatant daily were more inhibitory than monocytes treated initially only. With time in culture, monocytes progressively lost a limited degree of spontaneous inhibitory capacity and also lost their capacity to respond to supernatant with inhibition of L. pneumophila multiplication. Supernatant-activated monocytes inhibited L. pneumophila multiplication in two ways. They phagocytosed fewer bacteria, and they slowed the rate of intracellular multiplication of bacteria that were internalized. As was the case with nonactivated monocytes, antibody had no effect on the rate of intracellular multiplication in supernatant-activated monocytes. Neither supernatant-activated nor nonactivated monocytes killed L. pneumophila in the absence of antibody. Both killed a limited proportion of these bacteria in the presence of antibody and complement. We have previously reported that anti-L, pneumophila antibody and complement neither promote effective killing of L. pneumophila by human polymorphonuclear leukocytes and monocytes nor inhibit the rate of L. pneumophila multiplication in monocytes. These findings and our present report that activated monocytes do inhibit L. pneumophila multiplication indicate that cell-mediated immunity plays a major role in host defense against Legionnaires’ disease.