The relationship between jaw posture and muscular strength in sports dentistry: a reappraisal

In a previous report, we observed by light microscopy the extracellular matrix in 51 vulvar squamous carcinomas and found that some tumors has a prominent stromal response in the form of a regional or diffuse zone of extracellular myxoid matrix containing immature collagen and fibroblasts at the tumor-stromal junction. These tumors were associated with clitoral involvement, ulcerative nonexophytic growth pattern, older age groups, poorer survival rate, and more extensive lymph node metastases than when prominent fibromyxoid stromal response (PFSR) was absent. This behavior was demonstrated despite the fact that these tumors were not larger, more deeply invasive, or of higher grade than when PFSR was absent. In the current immunohistochemical study, we examined cytokine, cell adhesion receptor, and tumor suppressor gene expression in 50 vulvar squamous carcinomas using a panel of antibodies to identify any potential role of these proteins in the development of a PFSR. Semiquantification of expression into none, focal (< 25% of cells showing expression), regional (25-50%), and diffuse (> 50%) patterns revealed PFSR to be statistically associated with high CD44, transforming growth factor (TGF) beta 3, and p53 protein expression, but not with fibroblast growth factor, epidermal growth factor, epidermal growth factor receptor, or E-cadherin expression. When expression of CD44 and either stromal or tumor TGF-beta 3 expression was high, i.e., regional or diffuse in distribution, 15 (50%) of 30 cases were associated with PFSR. In contrast, only 1 (7%) of 14 cases was associated with PFSR when expression was high for only one of these two proteins and none of 3 cases was associated with response when expression was low for both proteins (p = 0.005). Furthermore, in cases showing high expression for both TGF-beta 3 and CD44, PFSR was found in 13 (72%) of 18 cases when p53 expression was diffuse compared with 2 (17%) of 12 cases when expression was less (p = 0.01). Since TGF-beta acts mitogenically for fibroblasts and has been shown to be an inhibitor of epithelial cell growth, its high expression in a carcinoma with PFSR would suggest loss of effect on the epithelial component but an intact effect on the stroma. Since CD44 is known to act as a receptor for hyaluronic acid, which is a prominent stromal component and known to play an important role in cell mobility and tumor aggressiveness, its high expression in association with PFSR would suggest a role of CD44 overexpression in altered hyaluronate metabolism with accelerated tumor cell migration and subsequent distal spread. The current study demonstrates that alterations in cytokine and cell adhesion receptor status variably occur in vulvar squamous carcinoma and that such alterations may affect tumor morphology and behavior.     

Profile of a clinical practice: Thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: a national survey of endocrine surgeons

A 1991 NIH Consensus Development Conference statement provided recommendations for the management of patients with asymptomatic and minimally symptomatic primary hyperparathyroidism (primary HPT), but adherence to these guidelines has not been documented. We conducted a cross-sectional survey of North American members of the American Association of Endocrine Surgeons inquiring about surgeon and primary HPT patient characteristics, thresholds for surgery, and clinical outcomes. Multivariate regression was used to assess the relationship of physician characteristics to practice patterns and outcomes. Of 190 surgeons surveyed, 147 (77%) responded; 109 provided complete responses (57%). These surgeons spend 66% of their time in patient care and perform an average of 33 (range, 1-130) parathyroidectomies/yr. More than 72% of primary HPT patients who underwent surgery were asymptomatic or minimally symptomatic. High volume surgeons (>50 cases/yr) had significantly lower thresholds for surgery with respect to abnormalities in preoperative creatinine clearance, bone densitometry changes, and levels of intact PTH and urinary calcium compared to their low volume colleagues (1-15 cases/yr). Overall reported surgical cure rates were 95.2% after primary operation and 82.7% after reoperation. Compared to high volume surgeons, low volume endocrine surgeons had significantly higher complication rates after primary operation (1.9% vs. 1.0% respectively; P < 0.01) and reoperation (3.8% vs. 1.5%; P < 0.001) as well as higher in-hospital mortality rates (1.0% vs. 0.04%; P < 0.05). Endocrine surgeons operate on a large number of asymptomatic or minimally symptomatic primary HPT patients. Even among a group of highly experienced surgeons who typically see patients after referral from endocrinologists, clinical outcomes and criteria for surgery vary widely and appear to be associated with surgeon experience. Their criteria for surgery diverge from NIH guidelines. These results implore the endocrine community to examine the evidential basis for decisions made in the management of primary HPT.     

The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities

The role of beta3- and other putative atypical beta-adrenoceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine beta3-adrenoceptor (beta3AR) agonists with varying intrinsic activities and selectivities for human cloned betaAR subtypes. The ability to demonstrate beta1/2AR antagonist-insensitive (beta3 or other atypical betaAR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective beta3AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited beta1/2AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full beta3AR agonist elicited full lipolytic and inotropic responses that were sensitive to beta1/2AR antagonism, despite it having very low efficacies at cloned beta1- and beta2ARs. A component of the response to another phenylethanolamine selective beta3AR agonist (SB-215691) was insensitive to beta1/2AR antagonism in some experiments. Because no [corrected] novel aryloxypropanolamine had a beta1/2AR antagonist-insensitive inotropic effect, these results establish more firmly that beta3ARs mediate lipolysis in human white adipocytes, and suggest that putative 'beta4ARs' mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned betaARs which betaARs will mediate responses to agonists in tissues that have a high number of beta1- and beta2ARs or a low number of beta3ARs.     

A comparison of thrombolytic therapy with primary coronary angioplasty for acute myocardial infarction. Myocardial Infarction Triage and Intervention Investigators

BACKGROUND: Several relatively small randomized trials have shown that primary angioplasty results in a better short-term outcome than thrombolytic therapy in patients with acute myocardial infarction. These results, however, have not been duplicated other than in investigational trials. METHODS: We compared mortality during hospitalization and long-term mortality, as well as the use of resources, among 1050 patients in a primary-angioplasty group and 2095 patients in a thrombolytic-therapy group. Patients were selected from the Myocardial Infarction Triage and Intervention Project Registry cohort of 12,331 consecutive patients admitted with acute myocardial infarction to 19 Seattle hospitals between 1988 and 1994. Because of the potential for selection bias, several subgroup analyses were performed that included patients eligible for thrombolysis, high-risk patients, and patients in the primary-angioplasty group who were treated at hospitals with high volumes of angioplasty. RESULTS: There was no significant difference in mortality during hospitalization or long-term follow-up between patients in the thrombolytic-therapy group and those in the primary-angioplasty group (mortality during hospitalization, 5.6 percent and 5.5 percent, respectively; P=0.93; adjusted hazard ratio for the risk of death within three years after primary angioplasty, 0.95; 95 percent confidence interval, 0.8 to 1.2). There was also no significant difference in mortality between high-risk subgroups of patients in the two treatment groups. The rates of procedures and costs were lower among patients in the thrombolytic-therapy group both at the time of hospital discharge and after three years of follow-up (30 percent fewer coronary angiograms, 15 percent fewer coronary angioplasties, and 13 percent lower costs after three years of follow-up). CONCLUSIONS: In a community setting, we observed no benefit in terms of either mortality or the use of resources with a strategy of primary angioplasty rather than thrombolytic therapy in a large cohort of patients with acute myocardial infarction.     

Predicting harmonic problems resulting from customer capacitoradditions for demand-side management

The use of capacitors to correct for poor power factor is a well-established and cost-effective means of reducing demand and system losses. Utilities routinely apply capacitors on transmission and distribution systems. Additional gains may be made by installing capacitors in customer facilities and many utilities are encouraging such installations for demand-side management (DSM) purposes. Unfortunately, many industrial customers have serious problems with capacitor installations because of interactions with harmonic distortion from plant loads. Capacitors may cause one or more harmonics to be accentuated through resonance. The capacitors themselves may be damaged or the resulting voltage distortion may make it impossible to operate some process equipment. It is often difficult to predict which capacitor installations will be troublesome, particularly when there are numerous capacitors and harmonic-producing loads scattered over a plant's power system. A simplified approach that depends on less input data is described. The method is based on the voltage distortion at the main bus and the currents in the capacitors. Two test cases are presented     

Efficacy and acceptability of two monophasic oral contraceptives containing ethinylestradiol and either desogestrel or gestodene

In this study, we have examined the effects of authentic nitric oxide (NO), NO+ (NOBF4), glutathione (GSH), glutathione disulphide (GSSG), and S-nitrosoglutathione (GSNO) in the presence and absence of Cu2+, which thermally releases NO from S-nitrosothiols on the transport of L-arginine into the human platelet. The K(M,apparent) was unaffected by NO, NO+, GSH, and GSNO. However, Cu2+ lowered K(M,apparent) by approximately 2.85-fold. Cu2+-dependent lowering of K(M,apparent) was also observed, albeit to a smaller extent when this ion was mixed with GSH (approximately 1.9-fold lower) and GSNO (approximately 2.0-fold). GSSG also lowered K(M,apparent) by approximately 1.5-fold. The Vmax,apparent of L-arginine uptake was unaffected by NO, NO+, GSH, and Cu2+. Vmax,apparent was stimulated by to the largest extent by GSNO (approximately 2.28-fold) and GSNO plus Cu2+ (approximately 2.7-fold). GSSG and GSH plus Cu2+ also increased Vmax,apparent by approximately 1.9-fold. When these parameters are expressed in terms of transport efficiency (Vmax/K(M)) the largest effect of nearly 4.7-fold (over controls) was obtained by a combination of GSNO plus Cu2+. These results suggest that platelet L-Arg transport is not affected either by NO or NO+ but by a thiol-disulphide exchange reactions on the platelet L-Arg transporter, brought about by GSNO and GSSG. Based on these results, a GSNO/GSSG/Cu2+ dependent regulatory mechanism for the uptake of L-arginine in human platelets has been proposed.     

Rational design of novel antimicrobials: blocking purine salvage in a parasitic protozoan

All parasitic protozoa obtain purine nucleotides solely by salvaging purine bases and/or nucleosides from their host. This observation suggests that inhibiting purine salvage may be a good way of killing these organisms. To explore this idea, we attempted to block the purine salvage pathway of the parasitic protozoan Tritrichomonas foetus. T. foetus is a good organism to study because its purine salvage depends primarily on a single enzyme, hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase), and could provide a good model for rational drug design through specific enzyme inhibition. Guided by the crystal structure of T. foetus HGXPRTase, we used structure-based drug design to identify several non-purine compounds that inhibited this enzyme without any detectable effect on human HGPRTase. One of these compounds, 4-[N-(3, 4-dichlorophenyl)carbamoyl]phthalic anhydride (referred to as TF1), was selected for further characterization. TF1 was shown to be a competitive inhibitor of T. foetus HGXPRTase with respect to both guanine (in the forward reaction; Ki = 13 microM) and GMP (in the reverse reaction; Ki = 10 microM), but showed no effect on the homologous human enzyme at concentrations of up to 1 mM. TF1 inhibited the in vitro growth of T. foetus with an EC50 of approximately 40 microM. This inhibitory effect was associated with a decrease in the incorporation of exogenous guanine into nucleic acids, and could be reversed by supplementing the growth medium with excess exogenous hypoxanthine or guanine. Thus, rationally targeting an essential enzyme in a parasitic organism has yielded specific enzyme inhibitors capable of suppressing that parasite's growth.     

BDD-based reliability analysis of phased-mission systems with multimode failures

This paper proposes a new algorithm (DEP-BDD) based on binary decision diagram (BDD) for reliability analysis of phased-mission systems (PMS) with multimode failures. DEP-BDD is a BDD-based combinatorial model which can be used to deal with more than one kind of dependences by applying dependence algebra, which is a generalization of phase algebra that handles more complex dependences. The nature of the BDD contributes the efficiency and low computational complexity of this algorithm. Two examples are analysed to illustrate the applications and advantages of our approach.