Recurrence of pericardial effusion after different procedure modalities in patients with non-small-cell lung cancer.

BACKGROUND: Lung cancer with related pericardial effusion is not rare. Intervention is a crucial step for symptomatic effusion. It is unknown, however, whether the different invasive interventions for pericardial effusion result in different survival outcomes. This study analyzed the clinical characteristics and prognostic factors for patients with non-small-cell lung cancer (NSCLC) who have undergone different procedures. METHODS: From January 2006 to June 2018, we collected data from patients with NSCLC who have received invasive intervention for pericardial effusions. The patients were divided into three categories: simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy. Kaplan-Meier curve and log-rank test were used to analyze the pericardial effusion recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 244 patients were enrolled. Adenocarcinoma (83.6%) was the major NSCLC subtype. Invasive intervention, including simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy, had been carried out on 52, 170, and 22 patients, respectively. The 1-year RFS rates in simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy were 19.2%, 31.2%, and 31.8%, respectively (P = 0.128), and the median RFS was 1.67, 5.03, and 8.32 months, respectively (P = 0.008). There was no significant difference in OS, however, with the median OS at 1.67, 6.43, and 8.32 months, respectively (P = 0.064). According to the multivariable analysis, the gravity in pericardial fluid analysis, receiving systemic therapy after pericardial effusion, and the time period from stage IV lung cancer to the presence of pericardial effusion were independent prognostic factors for pericardial effusion RFS and OS. CONCLUSIONS: Patients who have undergone simple pericardiocentesis alone for the management of NSCLC-related pericardial effusion have lower 1-year RFS rates than those who have undergone balloon pericardiotomy and surgical pericardiectomy. Therefore, balloon pericardiotomy and surgical pericardiectomy should be carried out for patients with NSCLC-related pericardial effusion if tolerable.

The impact of herbal medicines on dermatologic surgery.

BACKGROUND: In recent years herbal medicines and supplements have become increasingly popular. With their increased popularity, more publications are warning about the potential harmful effects of some of these products. OBJECTIVE: To present scientific evidence of the benefits and surgical risks of herbal products. METHODS: A Medline search and review of the literature was performed. RESULTS: Many herbal medicines are relevant in dermatologic surgery since Ginkgo biloba, garlic, ginger, ginseng, feverfew, and vitamin E may increase the risk of bleeding, and ephedra may potentiate the side effects of epinephrine. CONCLUSION: Dermatologists should be aware of these herbal products and their uses. Many of these products prescribed by alternative medicine physicians or purchased over the counter should be discontinued prior to dermatologic surgery to minimize the risk of surgical complications.

Activation of the BRLF1 promoter and lytic cycle of Epstein-Barr virus by histone acetylation.

Histone acetylation alters the chromatin structure and activates the genes that are repressed by histone deacetylation. This investigation demonstrates that treating P3HR1 cells with trichostatin A (TSA) activates the Epstein-Barr virus (EBV) lytic cycle, allowing the virus to synthesize three viral lytic proteins-Rta, Zta and EA-D. Experimental results indicate that TSA and 12-O:-tetradecanoylphorbol-13-acetate synergistically activate the transcription of BRLF1, an immediate-early gene of EBV. Chromatin immunoprecipitation assay reveals that histone H4 at the BRLF1 promoter is acetylated after P3HR1 cells are treated with TSA, suggesting that histone acetylation activates BRLF1 transcription. Furthermore, results in this study demonstrate that mutation of a YY1-binding site in the BRLF1 promoter activates BRLF1 transcription 1.6- and 2.3-fold in P3HR1 cells and C33A cells, respectively. Real time PCR analysis reveals that the mutation also increases the histone acetylation level of the nucleosomes at the BRLF1 promoter 1. 64- and 3.08-fold in P3HR1 and C33A cells, respectively. Results presented herein suggest that histone deacetylation plays an important role in maintaining the viral latency and histone acetylation at the BRLF1 promoter allows the virus to express Rta and to activate the viral lytic cycle.

Nitric oxide synthase inhibition negates bombesin-induced gastroprotection.

BACKGROUND: Bombesin prevents gastric injury primarily by the release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase inhibition, which implicates a role for nitric oxide as a protective mediator. Because both endothelial and inducible isoforms of this enzyme can play a role in mucosal defense, this study was done to examine the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-induced gastroprotection. METHODS: Rats were given subcutaneous saline or bombesin (10-100 microg/kg) 30 minutes before they received a 1-mL orogastric bolus of acidified ethanol (150 mmol/L of hydrochloric acid/50% ethanol) and rats were killed 5 minutes later for assessment of macroscopic injury (mm(2)). Gastric mucosal blood flow was measured by laser Doppler. Endothelial, neural, and inducible nitric oxide synthase were assessed by using Western immunoblot. RESULTS: Bombesin decreased gastric mucosal damage, and dose-dependently increased blood flow when compared with saline-treated rats. Endothelial but not neural or inducible nitric oxide synthase immunoreactivity was increased by bombesin. In additional studies, intraperitoneal administration of N(G)-nitro-l-arginine methyl ester (l-NAME, 5-10 mg/kg), a nonselective nitric oxide synthase inhibitor, negated bombesin-induced gastroprotection and hyperemia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg) did not. Subcutaneous (SC) l-arginine (300 mg/kg), but not d-arginine, abolished the effects of l-NAME. CONCLUSIONS: Taken together, these data suggest that nitric oxide produced by the endothelial isoform of nitric oxide synthase plays an important role in mediating the gastroprotective and hyperemic actions associated with bombesin.

Injectability and tissue compatibility of poly-(N-vinyl-2-pyrrolidone) in the skin of rats: a pilot study.

BACKGROUND: Filling substances have been used in dermatologic surgery for decades, but an ideal agent has yet to be discovered. Poly-(N-vinyl-2-pyrrolidone) is a hydrogel that has been used in medical settings for more than 50 years, but not as a cutaneous filling agent. OBJECTIVE: We investigated the intracutaneous injectability and tissue compatibility of this hydrogel in a rat model. Particular attention was paid to ease of injection through small needles, volume retention of the implant, clinical course, and histocompatibility. METHODS: The shaved backs of 12 anesthetized Sprague-Dawley rats were injected with the sterilized hydrogel and the rats closely observed. The rats were sacrificed in groups of four at 2, 4, and 12 weeks after implantation. Implant size was measured, volume calculated, and biopsies taken at each time interval. RESULTS: Poly-(N-vinyl-2-pyrrolidone) is easily injected through 30-gauge needles. All rats tolerated the implants well clinically. Histopathology revealed well-circumscribed implants with pseudoencapsulation, neoangiogenesis, and mixed inflammatory cells predominating at the periphery. Volume calculations revealed an average of 33% reduction at 4 weeks and 35% reduction at 12 weeks. CONCLUSION: Poly-(N-vinyl-2-pyrrolidone) is easy to inject intracutaneously and is well tolerated in the rat model. Short-term volume retention is good. Histopathology suggests a subclinical inflammatory reaction expected with implantation of a synthetic substance into the skin. Additional studies are necessary to investigate the continued persistence of the hydrogel and its long-term effects on surrounding tissue.

Analysis of a novel mechanism of neuronal toxicity produced by an apolipoprotein E-derived peptide.

The apolipoprotein E (apoE)-derived peptide (141-155)2 has a neurotoxic effect, implying that apoE itself could be a source of toxicity in Alzheimer's disease brain. We characterized the toxicity of this peptide on superior cervical ganglion (SCG) neurons and compared the death with the apoptotic death that occurs after nerve growth factor (NGF) deprivation in these cells. A dose of 10 microM apoE (141-155)2 resulted in the death of approximately 50% of the neurons within 24 h. Nuclear condensation and DNA fragmentation preceded the death. However, most inhibitors of NGF deprivation-induced death, including the caspase inhibitor Boc-aspartyl(O-methyl)fluoromethyl ketone and genetic deletion of bax-/-, had no effect on the toxicity. Inclusion of depolarizing levels of potassium did block the toxicity. Receptor-associated peptide (RAP), an antagonist for apoE receptors, did not protect cells in either SCG or hippocampal cultures. In addition, RAP had no effect on internalization of the apoE peptide. These data support the observation that apoE (141-155)2 is neurotoxic but suggest that the neurotoxicity is distinct from classical apoptosis or necrosis. Furthermore, these results indicate that the toxic effect may occur independently of members of the low-density lipoprotein receptor gene family.

Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses.

Cannabinoid receptors couple to both Gs and Gi proteins and can consequently stimulate or inhibit the formation of cAMP. To test whether there is specificity among cannabinoid receptor agonists in activating Gs- or Gi-coupled pathways, the potency and intrinsic activity of various cannabinoid receptor ligands in stimulating or inhibiting cAMP accumulation were quantified. The rank order of potencies of cannabinoid receptor agonists in increasing or inhibiting forskolin-stimulated cAMP accumulation, in CHO cells expressing hCB1 receptors, was identical (HU-210 > CP-55,940 > THC > WIN-55212-2 > anandamide). However, the activities of these agonists were different in the two assays with anandamide and CP-55,940 being markedly less efficacious in stimulating the accumulation of cAMP than in inhibiting its formation. Studies examining the effects of forskolin on cannabinoid receptor mediated stimulation of adenyly cyclase also revealed differences among agonists in as much as forskolin enhanced the potency of HU-210 and CP-55,940 by approximately 100-fold but, by contrast, had no effect on the potency of WIN-55212-2 or anandamide. Taken together these findings demonstrate marked differences among cannabinoid receptor agonists in their activation of intracellular transduction pathways. This provides support for the emerging concept of agonist-specific trafficking of cellular responses and further suggests strategies for developing receptor agonists with increased therapeutic utility.

Delayed repair of congenital diaphragmatic hernia with early high-frequency oscillatory ventilation during preoperative stabilization.

PURPOSE: The authors reviewed their experience in the management of CDH after the introduction of early high-frequency oscillatory ventilation (HFOV) during the preoperative stabilization period and delayed CDH repair. METHODS: This is a retrospective analysis of 24 consecutive infants with CDH treated at University of California, Irvine Medical Center (UCIMC) during a 36-month period from January 1993 to December 1996. RESULTS: Two patients were excluded from the study: one fetus with a prenatal diagnosis was referred for fetal surgery; one infant received CDH repair at another institution 2 weeks before transfer to UCIMC. Eight (36%) infants were inborn, and nine (41%) had a prenatal diagnosis of CDH. Median gestational age was 40 weeks (range, 29 to 42 weeks). Median birth weight was 3,019 g (range, 1,205 to 4,337 g). The defect was left sided in 18 infants (86%). Twenty-one infants were intubated within 5 hours of life, 15 had an AaDO2 greater than 610, 11 had an oxygenation index greater than 40, and 11 had a pH of less than 7.2. The median ratio of pulmonary artery pressure to systemic blood pressure was 0.93 (range, 0.51 to 1.15) in 12 infants. Eighteen infants were placed on HFOV within a median of 1 hour of life. Nitric oxide was given to six infants and surfactant to eight. Four infants were referred for extracorporeal membrane oxygenation (ECMO). Repair of CDH was performed on infants at a median age of 33.5 hours (range, 5.5 to 322). Six (30%) received a prosthetic patch. Overall 18 of 22 infants survived (81%); three survivors received ECMO. Two infants of the survivor group had congenital heart anomalies: one ventricular septal defect (VSD) and one double-outlet right ventricle with a VSD. Of the four nonsurvivors, one had lethal cardiac anomalies and bilateral CDH, two had severe bilateral pulmonary hypoplasia (one received ECMO), and one infant was a 29-week premature baby who did not qualify for ECMO. CONCLUSION: We report a survival rate of 81% (18 of 22) with the management of CDH by delayed surgical repair, early postnatal HFOV, and selective referral for ECMO.

Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding.

Alpha-2 adrenergic receptors (alpha2 AR) mediate incorporation of guanosine 5'-O-(gamma-thio)triphosphate ([35S]GTPgammaS) into isolated membranes via receptor-catalyzed exchange of [35S]GTPgammaS for GDP. In the current study, we used [35S]GTPgammaS incorporation to characterize the intrinsic activity and potency of agonists and antagonists at the cloned mouse alpha2a/d and human alpha2a, alpha2b, and alpha2c ARs. Full agonists increased [35S]GTPgammaS binding to membranes by 2- to 3-fold. Antagonists did not increase [35S]GTPgammaS binding but competitively inhibited agonist-stimulated [35S]GTPgammaS binding. Compounds with intrinsic activities less than that of the full agonists norepinephrine (NE) or epinephrine (EPI) were capable of antagonizing agonist-stimulated [35S]GTPgammaS binding. The agonistic properties of a number of alpha2 AR ligands were characterized at each alpha2 AR subtype. The rank order of agonist potency for selected compounds at the human receptors (with intrinsic activity compared with NE, defined as 1.0) was: alpha2a: Dexmedetomidine (0.73) > guanabenz (0.38) > UK-14304 (1.02) > clonidine (0.32) > ST-91 (0.63) > NE (1.00). alpha2b: Dexmedetomidine (1.10) > clonidine (0.18) > guanabenz (0.71) > NE (1.00) > ST-91 (0.44) > UK-14304 (0.59). alpha2c: Dexmedetomidine (1.03) > NE (1.00) > UK-14304 (0.75) > ST-91 (0.32) > or = clonidine (0.23) >> guanabenz (0). This report provides a functional characterization of adrenergic receptor ligands at human and mouse alpha2a/d AR. It also illustrates the utility of [35S]GTPgammaS incorporation as a functional marker of receptor activation.

Transposon mutagenesis and cloning of the genes encoding the enzymes of fengycin biosynthesis in Bacillus subtilis.

A total of 20 Bacillus subtilis F29-3 mutants defective in fengycin biosynthesis was obtained by Tn917 mutagenesis. Cloning and mapping results showed that the transposon in these mutants was inserted in eleven different locations on the chromosome. We were able to use the chromosomal sequence adjacent to the transposon as a probe to screen for cosmid clones containing the fengycin biosynthesis genes. One of the clones obtained, pFC660, was 46 kb long. Eight transposon insertion sites were mapped within this plasmid. Among the eleven different mutants analyzed, four mutants had Tn917 inserted in regions which encoded peptide sequences similar to part of gramicidin S synthetase, surfactin synthetase, and tyrocidine synthetase. Our results suggest that fengycin is synthesized nonribosomally by the multienzyme thiotemplate mechanism.

Usefulness and limitations of transesophageal echocardiography in the assessment of proximal coronary artery stenosis.

To assess the usefulness of transesophageal echocardiography in the evaluation of proximal coronary artery stenosis, 111 consecutive patients (mean age 61 years) who had intraoperative transesophageal echocardiography and coronary angiography within 1 week of surgery were studied. Transesophageal echocardiography visualized the entire length of the left main artery (0.2 to 2.2 cm, mean 0.93), 0.2 to 2.2 cm of the proximal left anterior descending artery and 0.1 to 3.4 cm of the proximal left circumflex artery in 103 patients (93%) and 0.1 to 4.6 cm of the proximal right coronary artery in 55 patients (49%). In the coronary artery segments visualized by echocardiography and compared with the corresponding angiographic segments, transesophageal echocardiography correctly identified 23 (96%) of 24 left main stenoses, 11 (78%) of 14 stenoses involving the left anterior descending artery, 6 (75%) of 8 left circumflex stenoses and all 7 stenoses (100%) of the right coronary artery. In all seven patients with ostial stenosis (left main artery in five and right coronary artery in two), the condition was correctly diagnosed by this technique. The sensitivity and specificity of transesophageal echocardiography in the overall evaluation of proximal coronary artery stenosis as customarily defined by angiography were 96% and 99% for the left main artery, 48% and 99% for the left anterior descending artery, 67% and 100% for the left circumflex artery and 37% and 100% for the right coronary artery, respectively. The distance of the stenotic lesion from the origin of the vessel by transesophageal echocardiography also correlated well with that measured by angiography (r = 0.63 to 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)

Rat gastric mucosal adenylyl cyclase.

Prostaglandin E1, epinephrine, secretin, and glucagon are known inhibitors of gastric acid secretion, and each agent stimulated mucosal membrane (600 X g pellet) adenylyl cyclase activity from the corpus of the rat stomach. This adenylyl cyclase activity was also stimulated by 5'-guanylyl-imidodiphosphate and sodium fluoride but not by guanosine-5'-triphosphate. By contrast, the gastric acid secretagogues, pentagastrin, histamine, and carbachol, had no effect on basal or prostaglandin E1-stimulated mucosal adenylyl cyclase activity. Most of the sodium fluoride- and hormone-stimulated adenylyl cyclase of the corpus mucosa was contained in the 600 X g membrane fraction. The enzyme exhibited Michaelis-Menten kinetics with respect to the concentration of ATP, with an apparent Km of 0.25 mM. Histamine did not stimulate rat mucosal adenylyl cyclase activity under a variety of conditions, but did stimulate the same enzyme in guinea pig gastric fundic mucosa, an enzyme also activated by prostaglandin E1. These studies do not support the hypothesis that cyclic AMP mediates the actions of gastric acid secretagogues on the parietal cell in the rat.

Activation of rat gastric mucosal adenylyl cyclase by secretory inhibitors.

Prostaglandin (PG) E1, E2, A1, and A2 stimulated rat gastric corpus mucosal membrane adenylyl cyclase activity. PGE1 (Kalpha congruent to 8 muM) affected the maximum velocity but not the affinity of the enzyme for ATP and maximum PGE1 activation was not affected by histamine H1 or H2 receptor antagonists. 5'-Guanylyl-diphosphoimide (Gpp(NH)p), but not GTP, stimulated both the basal and PGE1-stimulated adenylyl cyclase activities, although the percentage stimulation by maximal PGE was the same with or without Gpp(NH)p. NaF stimulation was also additive to that of PGE1. Secretin also stimulated gastric mucosal adenylyl cyclase activity (Kalpha congruent to 30 nM). Maximal secretin activation was not additive to that of PGE1, suggesting a coupling to the same adenylyl cyclase catalytic site. These studies suggest that mucosal membranes may contain beta-adrenergic receptors. The adenylyl cyclase activating agents used in this study, PGE1, secretin, and the catecholamines, are all known inhibitors of gastric acid secretion, suggesting a possible involvement of cyclic AMP in the inhibition of acid secretion in the rat stomach.