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Large cutaneous burns are clearly recognized to produce acute myocardial contractile dysfunction. This study used a model of burn serum challenge in either primary cardiomyocyte cultures or isolated perfused hearts to examine several aspects of burn-serum-related contractile dysfunction as well as myocardial inflammatory responses. Despite the absence of detectable LPS in burn serum, pretreating isolated cells or perfused hearts with recombinant bactericidal permeability-increasing protein (rBPI21) prevented both the inflammatory cytokine cascade and the cardiac contractile dysfunction induced by burn serum treatment of myocytes or ventricular muscle preparations. Our finding that anti-TNF strategies applied to isolated myocytes or hearts before burn serum challenge prevented myocardial inflammation and contractile dysfunction suggested that LPS or LPS-like factors may require the action of second messengers such as TNF-alpha and IL-1beta to mediate LPS-related myocardial depressant effects. Our finding that experimental approaches neutralizing circulating LPS provided cardioprotection suggested that bacterial endotoxin or LPS-like molecules contribute, in part, to burn-related myocardial contractile dysfunction.

Background: It is generally accepted that an initial injury such as burn trauma alters immune function such that a second insult increases the morbidity and mortality over that observed with each individual insult. We have shown previously that either burn trauma or sepsis promotes cardiomyocyte secretion of TNF-alpha and IL-1beta, cytokines that have been shown to produce myocardial contractile dysfunction. This study determined whether a previous burn injury (given eight days prior to sepsis) (1) provides a preconditioning phenomenon, decreasing inflammatory responses to a second insult or (2) exacerbates inflammatory response observed with either injury alone., Methods: Anesthetized Sprague-Dawley rats were given either burn injury over 40% total body surface area, sepsis alone (intratracheal S. pneumoniae, 4 x 10(6) colony forming units) or sepsis eight days after burn; all rats received lactated Ringer's solution. Hearts harvested 24 h after onset of sepsis alone or sepsis plus eight-day burn were used to (1) isolate cardiomyocytes (collagenase) or (2) assess contractile function (Langendorff). Cardiomyocytes loaded with 2 microg/mL Fura-2AM or sodium-binding benzofuran isophthalate were used to measure intracellular calcium and sodium concentrations (Nikon inverted microscope, Grooney optics, InCyt Im2 Fluorescence Imaging System). Additional cardiomyocytes were used to measure myocyte-secreted TNFalpha, IL-1, IL-6, IL-10 (pg/ml, ELISA)., Results: Either burn trauma alone or sepsis alone promoted TNF-alpha, IL-1beta, nitric oxide, IL6 and IL-10 secretion by cardiomyocytes (p < 0.05). Producing aspiration-related pneumonia eight days postburn produced myocardial pro- and anti-inflammatory responses and increased myocyte Ca2+/Na+ concentrations to a significantly greater degree than the responses observed after either insult alone., Conclusions: A previous burn injury alters myocardial inflammatory responses, predisposing the burn-injured subject to exaggerated inflammation, which correlates with greater myocardial dysfunction.

Whereas controversial, several studies have suggested that nitric oxide (NO) alters cardiac contractility via cGMP, peroxynitrite, or poly(ADP ribose) synthetase (PARS) activation. This study determined whether burn-related upregulation of myocardial inducible NO synthase (iNOS) and NO generation contributes to burn-mediated cardiac contractile dysfunction. Mice homozygous null for the iNOS gene (iNOS knockouts) were obtained from Jackson Laboratory. iNOS knockouts (KO) as well as wild-type mice were given a cutaneous burn over 40% of the total body surface area by the application of brass probes (1 x 2 x 0.3 cm) heated to 100 degrees C to the animals' sides and back for 5 s (iNOS/KO burn and wild-type burn). Additional groups of iNOS KO and wild-type mice served as appropriate sham burn groups (iNOS/KO sham and wild-type sham). Cardiac function was assessed 24 h postburn by perfusing hearts (n = 7-10 mice/group). Burn trauma in wild-type mice impaired cardiac function as indicated by the lower left ventricular pressure (LVP, 67 +/- 2 mmHg) compared with that measured in wild-type shams (94 +/- 2 mmHg, P < 0.001), a lower rate of LVP rise (+dP/dtmax, 1,620 +/- 94 vs. 2,240 +/- 58 mmHg/s, P < 0.001), and a lower rate of LVP fall (-dP/dtmax, 1,200 +/- 84 vs. 1,800 +/- 42 mmHg/s, P < 0.001). Ventricular function curves confirmed significant contractile dysfunction after burn trauma in wild-type mice. Burn trauma in iNOS KO mice produced fewer cardiac derangements compared with those observed in wild-type burns (LVP: 78 +/- 5 mmHg; +dP/dt: 1,889 +/- 160 mmHg/s; -dP/dt: 1,480 +/- 154 mmHg/s). The use of a pharmacological approach to inhibit iNOS (aminoguanidine, given ip) in additional wild-type shams and burns confirmed the iNOS KO data. Whereas the absence of iNOS attenuated burn-mediated cardiac contractile dysfunction, these experiments did not determine the contribution of cardiac-derived NO versus NO generated by immune cells. However, our data indicate a role for NO in cardiac dysfunction after major trauma.

Background: Initial reports from observational and randomized trials of uterine endometrial thermal balloon therapy (UBT) suggested good results as judged by return to eumenorrhoea or less and patient satisfaction. Long-term follow-up data remained limited by the small numbers of patients and duration of follow-up. We present long-term (4-6 years) follow-up data from a cohort of women previously treated with UBT for menorrhagia., Methods: Of the 260 questionnaires sent to women eligible for long-term follow-up from 10 centres, 188 (72%) replies were received. The primary outcome measure was avoidance of hysterectomy., Results: In women who responded to the questionnaire, 25 had undergone hysterectomy and 21 had had repeat ablation. At 4-6 years after UBT, the probability of avoiding hysterectomy was 86% of all women, and of avoiding re-ablation was 88% of non-hysterectomized women. Overall, the probability of avoiding any surgery was 75%. Women with an axial or retroverted uterus were at greater risk of hysterectomy or re-ablation. Among the participants, 47% of the non-hysterectomized women were amenorrhoeic, 30% were hypomenorrhoeic, 13.6% were eumenorrhoeic and 8.5% had heavy periods., Conclusions: This is the first long-term follow-up report of a second-generation endometrial ablation procedure and confirms our initial experience. The high rate of hysterectomy avoidance over 5 years or more is very encouraging for this technology.

Purpose: The purpose of this study was the assessment of the long-term safety and effectiveness of the Techmedica (Camarillo, CA) CAD/CAM Total Temporomandibular Joint Reconstruction System (now called the TMJ Concepts Patient Fitted Total Temporomandibular Joint Reconstruction System, Ventura, CA)., Patients and Methods: A survey was mailed to the available addresses of 170 (79%) of the 215 patients who had been implanted with the Techmedica System devices between 1990 and 1994. Seventy-nine (46%) surveys were returned by the US Postal Service as undeliverable. Three patients (1.4%) were reported as deceased in returns from relatives. Therefore, of the remaining 91 possible responses, 60 (65.9%) were returned. Fifty-eight (58) surveys, considered complete and valid (96.7%), representing 97 (39 bilateral, 19 unilateral) devices with a mean follow-up of 107.4 +/- 15.5 months (range, 60 to 120 months) were analyzed. Subjective data related to pain, mandibular function, diet consistency, and present quality of life were collected using visual analog scales. Objective measures of mandibular interincisal opening and lateral excursions were obtained from direct measurements using the Therabite (Therabite, Philadelphia, PA) measuring scale provided in the survey with instructions as to its use., Results: Analysis of the subjective data at 10 years revealed a 76% reduction in mean pain scores and a 68% increase in mean mandibular function and diet consistency scores (P <.0001). Analysis of objective data revealed a 30% improvement in mandibular range of motion after 10 years (P =.0009). Long-term quality of life improvement scores were statistically related to the number of prior temporomandibular joint operations the patients had undergone., Conclusion: These data indicate that the CAD/CAM Patient Fitted Total Temporomandibular Joint Reconstruction System has proved to be a safe and effective long-term management modality in the patient population surveyed for this study., (Copyright 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:1440-1448, 2002)

We introduce a quantum key distribution scheme based on four-photon coincidence measurements. This scheme offers a much higher degree of security than current quantum key distribution methods and minimizes problems due to photon losses and dark counts.

Objectives: To examine the prevalence rates of household smoking and ownership of a furred or feathered pet, the intercorrelation of these home environment measures, and their association with sociodemographic, family, and child asthma variables., Study Design: Children with asthma (n = 152, aged 7-18 years) with asthma and their primary parent were evaluated through the use of reliable and valid questionnaires focusing on exposure to household smoke and furred or feathered pets as well as sociodemographic, family, and asthma variables., Results: Prevalence of household smoking and pet ownership were high and comparable to normal levels in the US population. Smoking and pet ownership were not correlated with each other or with asthma medication adherence. Sociodemographic, family, and asthma variables showed distinct patterns of correlation with smoking and pet status. Household smoking was associated with poorer family resources and greater stress; pet ownership was associated with greater resources., Conclusions: Smoke exposure and pet ownership are not related to one another in children with asthma and will require independent counseling strategies because they relate in different and opposite ways to socioeconomic status.

The purpose of this study was to determine the effect on mechanical properties and antimicrobial activity of the addition of chlorhexidine (CHX) to a resin modified glass-ionomer (Photac-fil, ESPE, Norristown, PA, USA). Chlorhexidine diacetate was combined with a resin modified glass-ionomer material at a concentration of 5%. The samples were tested for hardness, tensile strength and erosion at 24 h and 6-week intervals and for elution of CHX and antimicrobial activity weekly for 6 weeks. At 24 h there was no significant difference in hardness between the two groups, but at 6 weeks the resin modified glass-ionomer group was significantly harder than the CHX groups (P < 0.05). The diametral tensile strength test indicated no difference between the control and CHX groups at 24 h or at 6 weeks. The jet erosion test demonstrated significantly less erosion with the CHX group at 24 h but at 6 weeks the CHX group showed significantly more erosion than the control group. The chemical assay data demonstrated a peak elution of CHX at week 1 with residual amounts at weeks 2 and 3. The microbial data demonstrated that the CHX group had a significant reduction in Streptococcus mutans numbers for weeks 1-3, but after week 4 there was no difference between the glass-ionomer with and without CHX. The addition of CHX to resin modified glass-ionomer altered hardness and erosion of the resin-modified glass-ionomer, but because there are no material specifications, it is difficult to determine clinical implications. Chlorhexidine did significantly improve the antimicrobial effect of the glass-ionomer which was consistent with the chemical assay data. The results indicated that the addition of CHX to resin modified glass-ionomer material (Photac-fil) did not seriously degrade the physical properties during the time period tested and that the addition of CHX resulted in a greater reduction in S. mutans when compared with glass-ionomer alone.

Objectives: Although previous studies have examined the electrosurgical pulpotomy technique for primary teeth, no well-controlled, clinical human trials have been published. The purpose of this study was to prospectively compare electrosurgical pulpotomies vs. formocresol pulpotomies in human vital primary molar teeth., Design: Fifty children were randomly divided into two groups, 25 receiving an electrosurgical pulpotomy and 25 receiving a formocresol pulpotomy., Results: After at least 5 months postoperative observation time, the clinical and radiographic success rates for the electrosurgical groups were 96 and 84%, respectively; and for the formocresol group, 100 and 92%, respectively., Conclusion: There were no statistically significant differences between the success rates for the two groups at the P < 0.05 level as tested by Fisher's exact test. This study failed to demonstrate a difference in the success rate between the electrosurgical and formocresol pulpotomy techniques.

Objective: To examine the effects of pharmacologic agents designed to limit burn-mediated calcium overload on cardiomyocyte [Ca2+] and cardiac contractile function., Design: Experimental, comparative study., Setting: Cellular biology and physiology laboratory., Subjects: Adult Sprague Dawley rats., Interventions: Rats were given third-degree burn injury over 40% of the total body surface area, were fluid resuscitated, and then were divided randomly to receive one of five treatments: vehicle (normal saline); amiloride (50 mg/kg) to inhibit H+-Na+ exchange and subsequent Na+-Ca2+ exchange; dantrolene (10 mg/kg, 30 mins, 6 and 22 hrs postburn) to inhibit sarcoplasmic reticulum Ca2+ release; diltiazem (10 mg/kg given over first 6 hrs postburn); or amlodipine (0.07 mg/kg, 24 hrs preburn and 30 mins postburn) to block calcium slow channels. Appropriate controls (sham burns given the appropriate pharmacologic agent) were included in each group. Twenty-four hrs postburn, left ventricular function (Langendorff), cardiomyocyte [Ca2+]i and [Na+]i measured by fura-2-AM or sodium-binding benzofurzan isophthalate loading of cardiomyocytes, and myocyte secretion of tumor necrosis factor-alpha (enzyme-linked immunosorbent assay) were assessed in shams and burns from each experimental group. This time point was selected based on our previous work confirming maximal ventricular contractile defects and maximal cytokine secretion 24 hrs postburn., Measurements and Main Results: Burn trauma increased myocyte [Ca2+]i and [Na+]i, promoted tumor necrosis factor-alpha secretion by cardiomyocytes, and impaired left ventricular function. All pharmacologic agents reduced the burn-mediated Ca2+/Na+ accumulation in cardiomyocytes and ablated burn-mediated tumor necrosis factor-alpha secretion by myocytes; in contrast, dantrolene and amiloride provided significantly greater cardioprotection than pharmacologic agents that specifically targeted Ca2+ slow channels (diltiazem and amlodipine)., Conclusion: Our data suggest that the calcium antagonists used in this study provide cardioprotection by modulating several aspects of the overall inflammatory cascade rather than solely limiting cardiomyocyte accumulation of calcium.

RRR-alpha-Tocopheryl succinate (vitamin E succinate, VES) is a potent antitumor agent, inducing DNA synthesis arrest, differentiation, and apoptosis. Because little is known about VES-induced differentiation, studies reported here characterize VES effects on the differentiation status of human breast cancer cell lines and investigate possible molecular mechanisms involved. VES-induced differentiation of human MCF-7 and MDA-MB-435 breast cancer cells was characterized by morphological changes, induction of lipid droplets, induction of beta-casein mRNA expression, and down-regulation of Her2/neu protein. In contrast, VES treatment of normal human mammary epithelial cells, MCF-10A cells, and T-47D cells did not induce differentiation. Studies addressing mechanisms showed that neither antibody neutralization of the transforming growth factor-beta signaling pathway nor expression of a dominant-negative mutant of c-Jun N-terminal kinase blocked the ability of VES to induce differentiation; however, treatment of cells with PD 98059, a chemical inhibitor of mitogen-activated protein kinase kinase (MEK1/2), blocked the ability of VES to induce differentiation.

RRR-alpha-tocopherol succinate (vitamin E succinate, VES) is a potent, selective apoptotic agent for cancer cells but not normal cells. VES has been shown to inhibit the growth of a wide variety of tumor cells in cell culture and animal models. Studies addressing mechanisms of action of VES-induced apoptosis have identified transforming growth factor-beta, Fas/CD95-APO-1, and mitogen-activated protein kinase (MAPK) signaling pathway involvement. Here we show that MAPKs, the extracellular signal-regulated kinases (ERK), and the stress-activated protein kinases, c-Jun NH2-terminal kinases (JNK), but not p38, are critical mediators in VES-induced apoptosis of human breast cancer MDA-MB-435 cells. VES activates ERK1/2 and JNK both in level and duration of kinase activity. Expression of dominant negative mutants of ERK1, MAPK/ERK activator-1, or JNK1 but not p38 blocked phosphorylation of the substrate glutathione S-transferase-c-Jun and inhibited VES-induced apoptosis. Increased phosphorylation and transactivation activity of nuclear transcription factors c-Jun, ATF-2, and Elk-1 are observed after VES treatments; however, only c-Jun and ATF-2 appear to be involved in VES-induced apoptosis based on antisense blockage experiments. Collectively, these results imply a critical role for ERK1 and JNK1 but not p38 in VES-induced apoptosis of human MDA-MB-435 breast cancer cells.

We show that the sender and the receiver each require coherent devices in order to achieve unconditional continuous variable quantum teleportation (CVQT), and this requirement cannot be achieved with conventional laser sources, linear optics, ideal photon detectors, and perfect Fock state sources. The appearance of successful CVQT in recent experiments is due to interpreting the measurement record fallaciously in terms of one preferred ensemble (or decomposition) of the correct density matrix describing the state. Our analysis is unrelated to technical problems such as laser phase drift or finite squeezing bandwidth.

Elevated levels of enterococci bacteria, an indicator of fecal pollution, are routinely detected in the surf zone at Huntington State and City Beaches in southern California. A multidisciplinary study was carried out to identify sources of enterococci bacteria landward of the coastline. We find that enterococci bacteria are present at high concentrations in urban runoff, bird feces, marsh sediments, and on marine vegetation. Surprisingly, urban runoff appears to have relatively little impact on surf zone water quality because of the long time required for this water to travel from its source to the ocean. On the other hand, enterococci bacteria generated in a tidal saltwater marsh located near the beach significantly impact surf zone water quality. This study identifies a potential tradeoff between restoring coastal wetlands and protecting beach water quality and calls into question the use of ocean bathing water standards based on enterococci at locations near coastal wetlands.

In the study presented here, we examined the affects of a close to complete replacement of sweat water and Na+ losses on fluid shifts during exercise. Six cyclists performed three 4-h rides at 55% of their peak oxygen uptake in a 20 degrees C environment while consuming 3.85 l of an 8% carbohydrate solution containing 5, 50 or 100 mEq.l-1 of Na+. Increases in Na+ intake reduced renal free water clearance from around 40 ml.h-1 to -8 and -121 ml.h-1 and led to a decrease in urine volume from approximately equal to 1.0 to 0.5 l (P < 0.05). In contrast, the 3.5-3.9 l fluid and 150-190 mEq Na+ losses in sweat were similar in each trial, as were the approximately equal to 80 mEq K+ losses in sweat and urine and the 282-288 mosmol.kg-1 plasma osmolalities. During the low-Na+ trial, plasma osmolality was maintained by a approximately equal to 1.3 l contraction of extracellular fluid (ECF) with the loss of approximately equal to 200 mEq Na+. However, in the other trials, approximately equal to 1.3 l of water was lost from the intracellular fluid. During the medium-Na+ trial, a loss of only approximately equal to 40 mEq Na+ maintained ECF volume, and during the high-Na+ trial, a gain of approximately equal to 160 mEq Na+ expanded the ECF by approximately equal to 0.8 l. However, corresponding changes in plasma volumes from -0.20 to 0.15 l had no effect on cardiovascular drift or thermoregulation. These data suggest that during prolonged exercise of moderate intensity under mild environmental conditions when sweat rates are approximately equal to 0.9 l.h-1, complete Na+ replacement maintains plasma volume and reduces dehydration, but when fluid intake matches sweat rate, has little effect on plasma osmolality.

Whereas hypertonic saline-dextran (HSD, 7.5% NaCl in 6% D70) improves cardiac contractile function after burn trauma, the mechanisms of HSD-related cardioprotection remain unclear. We recently showed that cardiomyocytes secrete tumor necrosis factor-alpha (TNF-alpha), a response that was enhanced by burn trauma. This study addressed the question: does HSD modulate cardiac contraction/relaxation by altering cardiomyocyte TNF-alpha secretion? Wistar-Furth rats (325 g) were given a burn injury over 40% of the total body surface area and were then randomized to receive a bolus of either isotonic saline or HSD (4 ml/kg, n = 14 rats/group). Sham burn rats were given either isotonic saline or HSD (n = 14 rats/group) to provide appropriate controls for the two burn groups. Hearts were isolated 24 h postburn for either Langendorff perfusion (n = 8 hearts/group) or to prepare cardiomyocytes (n = 6 hearts/group). Myocytes were stimulated with lipopolysaccharide (LPS) (0, 10, 25, or 50 microg for 18 h) to measure cytokine secretion. Burn trauma increased myocyte TNF-alpha and interleukin-1 beta and -6 secretion, exacerbated cytokine response to LPS stimulus, and impaired cardiac contraction. HSD treatment of burns decreased cardiomyocyte cytokine secretion, decreased responsiveness to LPS challenge with regard to cytokine secretion, and improved ventricular function. These data suggest that HSD mediates cardioprotection after burn trauma, in part, by downregulating cardiomyocyte secretion of inflammatory cytokines.

We present the first scheme for producing and measuring an Abelian geometric phase shift in a three-level system where states are invariant under a non-Abelian group. In contrast to existing experiments and proposals for experiments, based on U(1)-invariant states, our scheme geodesically evolves U(2)-invariant states in a four-dimensional SU(3)/U(2) space and is physically realized via a three-channel optical interferometer.

Background/purpose: Initially described in 1937, inflammatory pseudotumor (IPT) inflammatory myofibroblastic tumor (IMT) or plasma cell granulomas are synonymous for an inflammatory solid tumor that contains spindle cells, myofibroblasts, plasma cells, and histocytes. Common sites of presentation include lung, mesentary, liver, and spleen; intestinal presentations are rare, and the etiology remains obscure. This report details the clinical and surgical experiences in 4 children with alimentary tract IPT at a single institution., Methods: A retrospective chart review was conducted of pediatric patients with the pathologic diagnosis of IPT., Results: Between 1990 and 1999, 4 patients (4 girls, ages 5 to 15 years) were identified with gastrointestinal tract origins of IPT. Symptoms at presentation included anemia (n = 4), intermittent abdominal pain (n = 3), fever (n = 3), weight loss (n = 2), diarrhea (n = 2), dysphagia (n = 1). Two patients had comorbid conditions of juvenile rheumatoid arthritis and mature B cell lymphoma. Three of 4 patients had elevated sedimentation rates. The sites of origin were the gastroesophageal junction, the colon, the rectum, and the appendix, with the referral diagnosis achalasia, perforated appendix, inflammatory bowel disease, and recurrent lymphoma, respectively. All were treated with aggressive surgical resection, and 3 girls have had no recurrences since the initial surgery. One patient had 3 recurrences within 8 months of presentation; she remains disease free 8 years later., Conclusions: IPT, although rare in the gastrointestinal tract, mimics more common problems. Successful surgical management is possible even in cases of multiple recurrences.

Munchausen syndrome is a rare psychiatric disorder. Patients with Munchausen syndrome insist on and repeatedly undergo unnecessary investigations and operative treatments. No organic pathosis is demonstrated, and treatment consistently fails to alleviate the symptoms. This article presents a case report and a brief discussion to facilitate recognition and management techniques.

There is evidence of a substantial increase in teen use of both cigars and marijuana over the last decade. The theoretical concept of sensation seeking suggests a conceptual relationship between teen use of the substances. The hypothesis was that a relationship existed between the use of cigars and marijuana. Data for this study were gathered during the evaluation in a local school district of a teen tobacco-use reduction program. Questionnaire data and focus group results supported the study hypothesis and provided the direction for peer tobacco education to include an emphasis on this significant relationship. Identified associations between use of different substances supplies cues for the school nurse and other health providers to pursue specific areas of substance use practices when assessing students.

Temporomandibular disorders are only one of a host of different conditions that may result in orofacial pain. Hence, due to this multifactorial etiology, it is imperative to adopt a multidisciplinary approach when treating these patients. Listed in Table 3 are some of the conditions that must be considered when a dentist faces the dilemma of orofacial pain of unknown etiology in clinical practice.

Whereas previous studies suggest that tumor necrosis factor-alpha (TNF-alpha) induces cardiac contraction-relaxation deficits, the mechanisms remain unclear. Our recent studies have implicated cardiac-derived nitric oxide (NO). This study examined the detrimental and protective effects of NO donors S-nitroso-N-acetyl-penicillamine (SNAP) or (Z)-1- [N-(3-ammonio-propyl)-N-(n-propyl)amino]diazen-1-ium- 1,2diolate (PAPA/NO) on TNF-alpha-related changes in cardiac contractile function (Langendorff), cellular injury, and intracellular myocyte Ca(2+) concentration ([Ca(2+)](i)). Myocytes were incubated in the presence/absence of TNF-alpha (200-500 pg/ml x 10(5) cells) for 3 h; subsets of myocytes were incubated with one of several concentrations of SNAP or PAPA/NO (0.1, 0.3, 0.5, and 1.5 mM) for 15 min before TNF-alpha challenge. Supernatant creatine kinase (CK), cell viability (Trypan blue dye exclusion), and myocyte [Ca(2+)](i) (fura 2-acetoxymethyl ester) were measured. In parallel experiments, cardiac function (Langendorff) was examined after TNF-alpha challenge in the presence or absence of SNAP or PAPA/NO (0.1 and 1.5 mM). TNF-alpha in the absence of an NO donor impaired cardiac contraction and relaxation and produced cardiomyocyte injury. Pretreating perfused hearts or isolated cardiomyocytes with a low concentration of either SNAP or PAPA/NO decreased TNF-alpha-mediated cardiac injury and improved contractile dysfunction, whereas high concentrations of NO donor exacerbated TNF-alpha-mediated cardiac effects. These data provide one explanation for the conflicting reports of beneficial versus detrimental effects of NO in the face of inflammation and suggest that the effects of NO on organ function are concentration dependent; low concentrations of NO are cardioprotective, whereas high concentrations of NO are deleterious.

The apoptosis-triggering properties of vitamin E succinate (VES, RRR-alpha-tocopheryl succinate) for human LNCaP and PC-3 prostate carcinoma cells and normal PrEC human prostate epithelial cells were investigated. LNCaP and PC-3 cells were sensitive to VES-induced apoptosis, with 100% and 60% of cells undergoing apoptosis after three days of treatment with 10 micrograms of VES/ml, respectively. PrEC cells were resistant to VES-induced apoptosis. Treatment of prostate cells with agonistic anti-Fas antibody triggered apoptosis in approximately 50% of PC-3 cells within 48 hours, whereas LNCaP and PrEC cells were resistant. Prostate cells simultaneously treated with VES and agonistic anti-Fas antibodies revealed 1) no effect on PrEC cells, 2) an additive effect on Fas-sensitive PC-3 cells, and 3) a synergistic effect on LNCaP cells. VES treatment of LNCaP cells caused depletion of cytosolic 43-kDa Fas, enhanced membrane levels of 43-kDa Fas, and induced Fas sensitivity. PC-3 cells expressed high levels of membrane 43-kDa Fas that were enhanced by VES treatments. Fas ligand expression by LNCaP cells was enhanced by VES treatments. In summary, VES triggers apoptosis in human prostate carcinoma cells but not normal prostate cells in vitro, and VES modulates Fas signaling.

Burn trauma initiates a pathophysiologic cascade, which includes cardiac dysfunction and intramyocyte calcium accumulation. This study examined the hypothesis that therapeutic interventions which limit intracellular cardiac Ca(2+) accumulation after burn trauma will improve cardiac function. Guinea pigs were anesthetized (methoxyflurane), burned over 43% of total body surface area, and fluid resuscitated (FR) for 24 h. Burn guinea pigs were randomly divided into three groups: Group 1, FR alone, Group 2, FR plus dantrolene (10 mg/kg body wt, IV, 30 min, 8 and 22 h postburn), a drug which inhibits the Ca(2+) release channel (ryanodine receptor) of the cardiac sarcoplasmic reticulum, and Group 3, FR plus diltiazem (0.20-0.22 mg/kg given IV as a slow infusion over 6 h postburn), a drug which specifically blocks Ca(2+) slow channels; sham burn guinea pigs were given vehicle (Group 4), dantrolene (Group 5), or diltiazem (Group 6) as described above (respective controls). Cardiac dysfunction was impaired in fluid-treated burns (Group 1) compared to sham burns (Group 4) as indicated by reduced developed left ventricular pressure (LVP) (86 +/- 2 vs 52 +/- 3 mm Hg, P < 0.05), rate of LVP rise, (+dP/dt max, 1379 +/- 64 vs 909 +/- 44 mm Hg/s, P < 0.05), and LVP fall (-dP/dt max, 1184 +/- 31 vs 881 +/- 40 mm Hg/s, P < 0.05), and time to peak pressure (110 +/- 2 vs 102 +/- 2 ms, P < 0.05). In addition, [Ca(2+)](i) rose in cardiomyocytes harvested from fluid-treated burns (Group 1, 307 +/- 29 nM) compared to vehicle-treated controls (Group 4, 152 +/- 6 nM, P < 0.05). Neither calcium antagonist altered ventricular function or [Ca(2+)](i) in sham burns (Groups 5 and 6). In contrast, antagonists given after burn injury reduced cardiomyocyte [Ca(2+)](i) (Group 2, dantrolene-treated burns: 196 +/- 8 nM, and Group 3, diltiazem treated burns: 216 +/- 8 nM) and improved cardiac performance compared to that measured in burns given FR alone. Our data suggest that calcium antagonists given after burn trauma restored intracellular Ca(2+) homeostasis, decreased cardiac cell injury, and improved cardiac contractile function., (Copyright 1999 Academic Press.)

Background: Tamoxifen has been linked to an increased risk for the development of endometrial adenocarcinoma. The majority of these carcinomas present with postmenopausal bleeding. The current standard is to undertake sampling only after the onset of bleeding., Cases: Two cases illustrate the utility of transvaginal saline infusion sonohysterography (TVS/SIS) in the detection of endometrial carcinoma prior to the onset of bleeding., Conclusion: Annual TVS/SIS may be useful for screening asymptomatic, tamoxifen-exposed patients with a uterus in situ and is likely to be more acceptable to such patients than annual biopsies.

In this study, we examined whether athletes, who typically replace only approximately 50% of their fluid losses during moderate-duration endurance exercise, should attempt to replace their Na+ losses to maintain extracellular fluid volume. Six male cyclists performed three 90-min rides at 65% of peak O2 uptake in a 32 degrees C environment and ingested either no fluid (NF), 1.21 of water (W), or saline (S) containing 100 mmol of NaCl x l(-1) to replace their electrolyte losses. Both W and S conditions decreased final heart rates by approximately 10 betas min(-1) (P<0.005) and reduced falls in plasma volume (PV) by approximately 4% (P<0.05). Maintenance of PV after 10 min in the W trial prevented further rises in plasma concentrations of Na+ [Na+], Cl- and protein but in the S and NF trials, plasma [Na+] continued to increase by approximately 4 mEq x l(-1). Differences in plasma [Na+] had little effect on the approximately 2.4 l fluid, approximately 120 mEq Na+ and approximately 50 mEq K+ losses in sweat and urine in the three trials. The main effects of W and S were on body fluid shifts. During the NF trial, PV and interstitial fluid (ISF) and intracellular fluid (ICF) volumes decreased by approximately 0.1, 1.2 and 1.0 l, respectively. In the W trial, the approximately 1.2 l fluid and approximately 120 mEq Na+ losses contracted the ISF volume, and in the S trial, ISF volume was maintained by the movement of water from the ICF. Since the W and S trials were equally effective in maintaining PV, Na+ ingestion may not be of much advantage to athletes who typically replace only approximately 50% of their fluid losses during competitive endurance exercise.

Background and Purpose: Clinical instructors (CIs) observe behavior to determine whether students have the skills assumed necessary for safe and effective delivery of physical therapy services. Studies have examined assumptions about necessary skills, but few studies have identified the types of student behaviors that are "red flags" for CIs. This study examined the student behaviors that negatively affect students' clinical performance, which can alert CIs to inadequate performance., Subjects: Twenty-eight female and 5 male CIs discussed the performance of 23 female and 17 male students who were anonymous., Methods: Using questionnaires and semistructured interviews that were taped and transcribed, CIs described demographics and incidents of unsafe and ineffective physical therapy. After reading the transcripts, investigators identified and classified the behaviors into categories and checked their classification for reliability (kappa=.60-.75)., Results: Behaviors in 3 categories emerged as red flags for CIs: 1 cognitive category--inadequate knowledge and psychomotor skill (43% of 134 behaviors)--and 2 noncognitive categories--unprofessional behavior (29.1%) and poor communication (27.6%). The CIs noticed and valued noncognitive behaviors but addressed cognitive behaviors more often with students. Students who did not receive feedback about their performance were unlikely to change their behavior. The CIs used cognitive behaviors often as reasons to recommend negative outcomes., Conclusion and Discussion: Clinical instructors need to identify unacceptable cognitive and noncognitive behaviors as early as possible in clinical experiences. Evidence suggests that they should discuss their concerns with students and expect students to change.

Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In contrast, no enhancement of anti-Fas agonistic antibody-triggered apoptosis was observed following VES pretreatment or cotreatment with Fas-sensitive primary cultures of human mammary epithelial cells, immortalized MCF-10A cells, or T47D human breast cancer cells. Although VES is itself a potent apoptotic triggering agent, the 6-h pretreatment procedure for Fas sensitization did not initiate VES-mediated apoptosis. The combination of VES plus anti-Fas in pretreatment protocols was synergistic, inducing 2.8-, 3.0-, and 6.3-fold enhanced apoptosis in Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells, respectively. Likewise, cotreatment of Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells with VES plus anti-Fas enhanced apoptosis 1.9-, 2.0-, and 2.6-fold, respectively. Functional knockout of Fas-mediated signaling with either Fas-neutralizing antibody (MCF-7-, MDA-MB-231-, and MDA-MB-435-treated cells) or Fas antisense oligomers (MDA-MB-435-treated cells only), reduced VES-triggered apoptosis by approximately 50%. Analyses of whole cell extracts from Fas-sensitive cells revealed high constitutive expression of Mr 43,000 Fas, whereas Fas-resistant cells expressed low levels that were confined to the cytosolic fraction. VES treatment of the Fas-resistant cells caused a depletion of cytosolic Mr 43,000 Fas with a concomitant increase in Mr 43,000 membrane Fas. These data show that VES can convert Fas-resistant human breast cancer cells to a Fas-sensitive phenotype, perhaps by translocation of cytosolic Mr 43,000 Fas to the membrane and show that VES-mediated apoptosis involves Mr 43,000 Fas signaling.

N-(4 hydroxyphenyl)retinamide (4-HPR), a synthetic derivative of all-trans-retinoic acid, induces DNA synthesis arrest and apoptosis in human breast cancer cells in a dose- and time-dependent manner. MDA-MB-435 cells treated with 3 microM 4-HPR exhibited 58% and 75% DNA synthesis arrest after 1 and 2 days of treatment and 31%, 39%, 48%, and 56% apoptosis after 3, 4, 5, and 6 days of treatment, respectively. Conditioned media from 4-HPR-treated MDA-MB-435 cells contained 63 and 57 pg of active transforming growth factor-beta (TGF-beta) per 10(6) cells after 1 and 2 days of treatment, whereas conditioned media from control cells contained only 9 pg/10(6) cells. TGF-beta involvement in 4-HPR-induced apoptosis, but not DNA synthesis arrest, in MDA-MB-435 cells was demonstrated by 1) blockage of 4-HPR-induced apoptosis by 66-75% after treatment of cells with neutralizing antibodies to TGF-beta s, 2) blockage of 4-HPR-induced apoptosis by 64-67% after transient transfection of cells with antisense oligomers to TGF-beta 1 or TGF-beta type II receptor, 3) blockage of 4-HPR-induced apoptosis by approximately 50% after inhibition of latent TGF-beta activation, and 4) demonstration that human breast cancer cells (T47D) defective in TGF-beta signaling were refractive to 4-HPR-induced apoptosis. These data indicate that 4-HPR is a potent activator of TGF-beta and that TGF-beta participates in 4-HPR-induced apoptosis of human breast cancer cells.

The apoptosis-inducing properties of RRR-alpha-, beta-, gamma-, and delta-tocopherols, alpha-, gamma-, and delta-tocotrienols, RRR-alpha-tocopheryl acetate (vitamin E acetate), and RRR-alpha-tocopheryl succinate (vitamin E succinate) were investigated in estrogen-responsive MCF7 and estrogen-nonresponsive MDA-MB-435 human breast cancer cell lines in culture. Apoptosis was characterized by two criteria: 1) morphology of 4,6-diamidino-2-phenylindole-stained cells and oligonucleosomal DNA laddering. Vitamin E succinate, a known inducer of apoptosis in several cell lines, including human breast cancer cells, served as a positive control. The estrogen-responsive MCF7 cells were more susceptible than the estrogen-nonresponsive MDA-MB-435 cells, with concentrations for half-maximal response for tocotrienols (alpha, gamma, and delta) and RRR-delta-tocopherol of 14, 15, 7, and 97 micrograms/ml, respectively. The tocotrienols (alpha, gamma, and delta) and RRR-delta-tocopherol induced MDA-MB-435 cells to undergo apoptosis, with concentrations for half-maximal response of 176, 28, 13, and 145 micrograms/ml, respectively. With the exception of RRR-delta-tocopherol, the tocopherols (alpha, beta, and gamma) and the acetate derivative of RRR-alpha-tocopherol (RRR-alpha-tocopheryl acetate) were ineffective in induction of apoptosis in both cell lines when tested within the range of their solubility, i.e., 10-200 micrograms/ml. In summary, these studies demonstrate that naturally occurring tocotrienols and RRR-delta-tocopherol are effective apoptotic inducers for human breast cancer cells.

Objective: To describe the value of concurrent interventional radiology with hysteroscopy for the management of complex intrauterine abnormalities., Design: A new descriptive technique., Setting: Tertiary care center., Patient(s): Three case reports., Intervention(s): Interventional radiology with the placement of guidewires and/or dilatation of resistant structures may assist with hysteroscopic management of complex intrauterine abnormalities or may be a primary therapeutic option., Main Outcome Measure(s): Resolution of dysmenorrhea and restoration of fertility., Result(s): The placement of a guidewire into an occluded portion of the intrauterine cavity provides direction and safety for hysteroscopic resolution of the underlying problem. In the last case, placement of the guidewire and passing dilators over the guidewire provided complete treatment., Conclusion(s): The uterine cavity or a smaller segment of it may be blocked by occlusive fibrous tissue that is not amenable to standard hysteroscopic dissection. Combining radiologic imaging with hysteroscopic surgery allows visual access to instrumentation and the hidden structures or organs throughout the entire procedure. It adds complexity to the surgery but may allow restoration of function to an organ or structure that is otherwise inaccessible.