Feasibility Cues during a Sexual Encounter Impact the Strength of Heterosexual Women's Orgasm Goal Pursuit.

The "orgasm gap" for women who have sex with men remains a pressing gender equity issue. Recent research found that women who pursued orgasm as a goal were more likely to have one. The current research replicated this relationship between orgasm goal pursuit and orgasm frequency for heterosexual women, and found that this relationship did not exist for heterosexual men (Study 1). Then, across two experimental studies, we examined how heterosexual women vary their orgasm goal pursuit across sexual encounters. In Study 2, women who read that a hypothetical sexual encounter would be "quick" reported less intent to pursue orgasm than women who were told they could "take their time" or received no time information. In Study 3, women who read that their hypothetical sexual partner seemed selfish reported less intent to pursue orgasm than women who were given a non-selfish partner or no partner information. Importantly, these effects were mediated by women's perceived orgasm likelihood in the scenario. These results suggest that women shift their pursuit of orgasm depending on cues which signal whether orgasm will be feasible. This research used self-regulation theory to understand women's motivations for pursuing orgasm during sexual encounters with men, with implications for reducing the orgasm gap.

Myeloid knockout of HIF-1 α does not markedly affect hemorrhage/resuscitation-induced inflammation and hepatic injury.

BACKGROUND: Hypoxia-inducible factor-1 α (HIF-1 α ) and NF- κ B play important roles in the inflammatory response after hemorrhagic shock and resuscitation (H/R). Here, the role of myeloid HIF-1 α in liver hypoxia, injury, and inflammation after H/R with special regard to NF- κ B activation was studied. METHODS: Mice with a conditional HIF-1 α knockout (KO) in myeloid cell-line and wild-type (WT) controls were hemorrhaged for 90 min (30 ± 2 mm Hg) and resuscitated. Controls underwent only surgical procedures. RESULTS: After six hours, H/R enhanced the expression of HIF-1 α -induced genes vascular endothelial growth factor (VEGF) and adrenomedullin (ADM). In KO mice, this was not observed. H/R-induced liver injury in HIF-1 α KO was comparable to WT. Elevated plasma interleukin-6 (IL-6) levels after H/R were not reduced by HIF-1 α KO. Local hepatic hypoxia was not significantly reduced in HIF-1 α KO compared to controls after H/R. H/R-induced NF- κB phosphorylation in liver did not significantly differ between WT and KO. CONCLUSIONS: Here, deleting HIF-1 α in myeloid cells and thereby in Kupffer cells was not protective after H/R. This data indicates that other factors, such as NF- κB, due to its upregulated phosphorylation in WT and KO mice, contrary to HIF-1 α, are rather key modulators of inflammation after H/R in our model.

Albuterol increases lean body mass in ambulatory boys with Duchenne or Becker muscular dystrophy.

BACKGROUND: Albuterol is a beta-2 agonist that has been demonstrated to increase muscle strength in studies in animals and humans. Based on a pilot study of extended-release albuterol Repetabs in children with dystrophinopathies, the authors conducted a randomized, double-blind, placebo-controlled study with a crossover design. METHODS: Fourteen boys with Duchenne or Becker muscular dystrophy, 6 to 11 years old, completed two treatment periods (albuterol and placebo), 12 weeks each, separated by a 12-week washout period. As the albuterol Repetab formulation was no longer available, an alternate extended release albuterol was used (Volmax, 12 mg per day). Outcome measurements included 1) lean body mass, 2) fat mass, 3) isometric knee extensor and flexor moments, 4) manual muscle testing, and 5) timed functional tests. RESULTS: Lean body mass was significantly higher for subjects following albuterol treatment compared to placebo treatment, while fat mass was significantly lower. No differences were found in isometric knee moments or manual muscle tests. Time to run/walk 30 feet was improved following albuterol. CONCLUSIONS: Short-term treatment with extended release albuterol may increase lean body mass, decrease fat mass, and improve functional measures in patients with dystrophinopathies. However, the significant change in strength of specific muscle groups found in the pilot study was not observed in the present study. These findings may be attributed to differences in the drug release and kinetics between Repetab and Volmax formulations as they affect the concentration of available beta-2 receptors on the muscle cell surface differently.

Predictors of graft longevity in pediatric heart transplantation.

Given the volume of pediatric orthotopic heart transplants (OHTs) at several centers, it is now possible to generate pediatric-specific, single-center OHT survival data. The transplant experience for 152 pediatric OHT patients at our institution was reviewed. The following were noted for each patient: graft survival; immunosuppressant therapy; initial diagnosis; cause of graft failure; clinical status at time of transplant; donor and recipient blood type, sex, weight, and age; ischemic time; previous cardiac surgery; race; and immune status. A series of Kaplan-Meier survival curves were constructed. Univariate comparisons of survival curves were performed with the Breslow test to determine equality of each pair of curves. Only immunosuppression with tacrolimus and an initial diagnosis of noncongenital heart disease positively influenced survival in pediatric OHT patients (p < or = 0.021 and p < or = 0.03, respectively). The more recently transplanted patients, managed with tacrolimus, had less mortality early after OHT (acute rejection) and less mortality during the period 2 or 3 years after OHT. No other factors, including prior cardiothoracic surgery, sex matching, and race matching, significantly influenced survival. Recently transplanted patients managed with tacrolimus-based immunosuppression and patients with noncongenital cardiomyopathy have significantly superior graft survival.

Pilot trial of albuterol in Duchenne and Becker muscular dystrophy.

The authors conducted a randomized, crossover, double-blind, placebo-controlled pilot study of albuterol in nine boys with dystrophinopathies. Primary outcomes were 1) isometric knee extensor and flexor strength; and 2) manual muscle testing (MMT). Isometric knee extensor strength and MMT scores were significantly higher in patients taking albuterol vs placebo. Therefore, 12-week treatment with extended-release albuterol may increase strength in patients with dystrophinopathies. A larger, double-blind, randomized study is necessary to confirm these results.

Inhibition of L-type Ca2+ channel current in Xenopus oocytes by amiodarone.

BACKGROUND: Although amiodarone has been referred to as a class III antiarrhythmic agent, it also possesses electrophysiologic characteristics of the three other classes (classes I and IV and minor class II effects). Previous studies have demonstrated that amiodarone inhibits Ca2+ channel current in intact cardiac myocytes. However, it is not clear whether this response reflects a pure class IV effect (direct Ca2+ channel inhibition) or a class II effect (beta-adrenergic receptor blockade) of amiodarone. METHODS: In the current study, the effects of amiodarone on Ca2+ current were studied in the absence of sympathetic regulation using a Xenopus oocyte expression system. The L-type Ca2+ channel alpha1C subunit was coexpressed with the alpha2delta and beta2a subunits in enzymatically digested Xenopus oocytes. Ca2+ currents were recorded using the cut-open oocyte preparation. RESULTS: We found that perfusion of 10 microM isoproterenol produced no significant change in peak Ca2+ current (from 223+/-33 to 210+/-29 nA, mean+/-SEM, n=5, P=not significant), indicating the absence of a functional stimulatory sympathetic signal pathway in these oocytes. After 10 minutes of exposure to 10 microM amiodarone, Ca2+ current amplitude was significantly decreased from 174+/-33 to 100+/-26 nA (n=8, P<0.01; control group: 220+/-33 to 212+/-29 nA, n=5, P=not significant). These effects were similar to those of 10 microM nifedipine (201+/-48 to 108+/-48 nA, n=6, P<0.05), a typical Ca2+ channel blocker. On the other hand, neither amiodarone nor nifedipine significantly altered the Ca2+ current activation or inactivation kinetics. CONCLUSIONS: These results demonstrate that amiodarone inhibits Ca2+ current in the absence of a functional intrinsic beta-adrenergic stimulatory system and, therefore, represents a true class IV effect.

Lack of muscarinic regulation of Ca(2+) channels in G(i2)alpha gene knockout mouse hearts.

The purpose of the present study was to examine the role of G(i2)alpha in Ca(2+) channel regulation using G(i2)alpha gene knockout mouse ventricular myocytes. The whole cell voltage-clamp technique was used to study the effects of the muscarinic agonist carbachol (CCh) and the beta-adrenergic agonist isoproterenol (Iso) on cardiac L-type Ca(2+) currents in both 129Sv wild-type (WT) and G(i2)alpha gene knockout (G(i2)alpha-/-) mice. Perfusion with CCh significantly inhibited the Ca(2+) current in WT cells, and this effect was reversed by adding atropine to the CCh-containing solution. In contrast, CCh did not affect Ca(2+) currents in G(i2)alpha-/- ventricular myocytes. Addition of CCh to Iso-containing solutions attenuated the Iso-stimulated Ca(2+) current in WT cardiomyocytes but not in G(i2)alpha-/- cells. These findings demonstrate that, whereas the Iso-G(s)alpha signal pathway is intact in G(i2)alpha gene knockout mouse hearts, these cells lack the inhibitory regulation of Ca(2+) channels by CCh. Therefore, G(i2)alpha is necessary for the muscarinic regulation of Ca(2+) channels in the mouse heart. Further studies are needed to delineate the possible interaction of G(i) and other cell signaling proteins and to clarify the level of interaction of G protein-coupled regulation of L-type Ca(2+) current in the heart.

Sarcoplasmic reticulum Ca(2+)ATPase and cell contraction in developing rabbit heart.

The purpose of the present study was to determine whether age-related changes in the expression and function of the cardiac isoform of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) play a role in SR Ca(2+)release and cell contraction. SERCA2a protein levels and subcellular localization were compared between fetal, neonatal, juvenile and adult New Zealand White rabbits. Studies of SERCA function in isolated myocytes were performed in situ by examining the rate of reloading of the SR Ca(2+)stores following caffeine-induced depletion. We found that significant quantities of SERCA2a were present early in immature heart and that SERCA2a expression reached adult levels within 15-30 days after birth. Furthermore, SERCA2a protein is present as a series of transverse striations within the cell as early as 1 day of age. In contrast to previous studies of SERCA in vitro, the SERCA protein function in situ was found to be comparable between neonatal and adult myocytes in maintaining SR Ca(2+)stores. These results indicate that the paucity of SR Ca(2+)release in immature ventricular cardiac myocytes is not the result of immaturity in SERCA2a expression.

Molecular cloning of junctin from human and developing rabbit heart.

Canine junctin is a 26-kDa transmembrane protein found in the sarcoplasmic reticulum (SR) membrane in cardiac and skeletal muscle. Junctin has recently been shown to bind directly to calsequestrin, the ryanodine receptor, and triadin. Junctin is thought to play a role in facilitating (and perhaps regulating) Ca(2+) release from the SR. Immature heart exhibits decreased utilization of SR Ca(2+) stores for cell contraction. We have cloned human and rabbit cardiac junctin and investigated the expression of junctin in developing rabbit heart. Human junctin was cloned from an adult cardiac cDNA library. Rabbit junctin was cloned by RT-PCR. Northern blot analysis demonstrates a single primary mRNA transcript of approximately 2.8 kb in hearts from both species. Sequence analysis demonstrates greater than 97% homology between the predicted amino acid sequences of human, rabbit, and canine junctin in the putative transmembrane domain and subsequent initial 61 amino acid portion of the putative luminal domain. These domains also exhibit sequence homology with triadin. The C-terminal region shows much lower (72 to 75%) sequence homology among the three species. In addition, Northern blot analysis demonstrates that the expression of junctin increases markedly in postnatal rabbit myocardium. These findings suggest that the putative transmembrane domain and subsequent initial portion of the putative luminal domain of junctin play an important role in the binding of junctin to calsequestrin, the ryanodine receptor, and triadin in the postnatal heart. Furthermore, the previously described increase in SR Ca(2+) release with development is associated with the increased expression of junctin.

Arctic ozone loss due to denitrification

Measurements from the winter of 1994-95 indicating removal of total reactive nitrogen from the Arctic stratosphere by particle sedimentation were used to constrain a microphysical model. The model suggests that denitrification is caused predominantly by nitric acid trihydrate particles in small number densities. The denitrification is shown to increase Arctic ozone loss substantially. Sensitivity studies indicate that the Arctic stratosphere is currently at a threshold of denitrification. This implies that future stratospheric cooling, induced by an increase in the anthropogenic carbon dioxide burden, is likely to enhance denitrification and to delay until late in the next century the return of Arctic stratospheric ozone to preindustrial values.

Red flags in common pediatric symptoms.

The purpose of this article is to alert nurse practitioners to elements of the pediatric history or physical examination that could herald urgent/emergent conditions. Five common symptoms along with suggested key questions and physical examination parameters for evaluation of these possible "red flags" are presented.

The relationship between temperature and calcium in acute cell damage after exposure to radiofrequency or thermal energy in isolated neonatal and adult rabbit cardiac myocytes.

Radiofrequency (RF) ablation is a nonsurgical technique using catheter-directed RF energy for treating cardiac arrhythmias in children and adults. Previous reports have suggested that sequestration of calcium (Ca2+) by the sarcoplasmic reticulum may partially protect mature cardiac myocytes from the effects of RF energy. The purposes of this study were to determine whether differences exist between neonatal and adult myocyte responses to RF energy and if myocyte damage is a Ca2+-dependent process. Because immature myocardium is functionally deficient in sarcoplasmic reticulum, we hypothesized that immature myocytes would be more susceptible to damage induced by RF energy. Isolated ventricular myocytes were obtained from neonatal and adult New Zealand White rabbits by enzymatic dissociation, then placed in a perfusion chamber designed to deliver RF energy or a heated perfusate solution. Measurements of bath temperature, cell morphology, and contractile response to electrical stimuli were recorded. RF energy application associated with increased perfusate temperature resulted in cell death, but not when the temperature rise was inhibited. Thus, the acute damage to cells exposed to RF energy appears to be mediated by thermal energy. After exposure to thermal energy, neonatal cells underwent contracture at lower temperatures than did adult cells. Perfusion with solutions containing low Ca2+ concentrations, comparable to intracellular diastolic Ca2+ levels, had a protective effect for both neonatal and adult myocytes. These findings indicate that acute cell damage after exposure to RF energy is mediated by a Ca2+-dependent process. Furthermore, immature myocardium is particularly susceptible to RF-mediated cell damage, possibly secondary to reduced Ca2+ sequestration by the sarcoplasmic reticulum.

Caffeine-induced contractions in developing rabbit heart.

Mature myocardium utilizes calcium released by the sarcoplasmic reticulum (SR) for cell contraction. Transient exposure of mature myocytes to caffeine is known to directly trigger Ca2+ release from the SR. In contrast, neonatal rabbit heart cells rely on transsarcolemmal Ca2+ influx for tension generation. SR function is decreased in immature heart and appears to play a minimal role as a calcium source. Accordingly, we hypothesized that neonatal rabbit myocytes would not respond to a caffeine pulse. Isolated neonatal and adult myocytes were paced to load the SR with calcium and then exposed to a 1-s pulse of 10 mM caffeine. As previously described, adult myocytes exhibited a brisk contraction in response to caffeine. Unexpectedly, neonatal myocytes also exhibited a similar, brisk response. These caffeine-induced contractions were not dependent on extracellular Ca2+ but were dependent upon the loading of SR Ca2+ stores. When SR Ca2+ stores were depleted by exposure to caffeine, mature myocytes exhibited only small, slow contractions in response to electrical field stimulation. Replenishing the SR Ca2+ stores resulted in normal, brisk contractions. In contrast, electrically stimulated contractions in immature myocytes were largely unaffected by caffeine-induced SR depletion. Thus, although neonatal myocytes are capable of loading and releasing calcium from the SR, such SR calcium release is not normally required for contraction in the developing heart. The minor role of SR Ca2+ release in immature rabbit heart may not result from immaturity of the SR, but rather from an inadequate mechanism to trigger SR calcium release.

Synergy between anti-CD40 MAb and Epstein-Barr virus in activation and transformation of human B lymphocytes.

For human B lymphocytes, Epstein-Barr virus (EBV) is a polyclonal activator, inducing both proliferation and Ig secretion. It is also a transforming virus capable of generating immortalized B cell lines. These early and late functions of EBV are not apparently connected. The receptor for EBV, CD21, also serves as a receptor for some complement components and is called CR2. This molecule associates with CD19 and TAPA-1 on the surface of B cells. This complex is involved in signaling B cells and participates in many responses. We have observed that simultaneous ligation of CD40 and the CD21 complex, by exposure to anti-CD40 MAbs and EBV, enhances both the short-term proliferation as well as the long-term transformation rate of human B lymphocytes. B cell proliferation shows synergy between anti-CD40 MAb and EBV. CD19 also appears to be involved in the synergistic activation of B cells through CD40 and CD21, since ligation of CD19 with anti-CD19 MAbs, either prior to or concomitant with exposure to anti-CD40 and EBV, markedly inhibits both proliferation and subsequent B cell transformation. These observations do not elucidate the mechanisms of B cell transformation employed by EBV but the do suggest a relationship between early proliferation and later transformation induced by the virus. Anti-CD40 enhances both these effects and anti-CD19 is capable of inhibiting both.

Mechanisms of amiodarone-induced inhibition of Ca2+ current in isolated neonatal rabbit ventricular myocytes.

BACKGROUND: Amiodarone is an effective antiarrhythmic drug used to treat a wide variety of ventricular and supraventricular tachyarrhythmias. Recent voltage clamp studies indicate that amiodarone may possess a variety of antiarrhythmic effects. METHODS: The tight-seal, whole-cell voltage clamp technique was used to investigate the acute effects of amiodarone on L-type Ca2+ channel kinetics in isolated neonatal ventricular myocytes. RESULTS: We found that acute perfusion with 1 mumol/L amiodarone inhibited peak inward Ca2+ current by 39.1% (4.85 +/- 0.42 to 2.95 +/- 0.6 pA/pF, n = 10, p < 0.001) without changing the shape of the current-voltage relation. In addition, amiodarone shifted Ca2+ channel steady-state inactivation to more negative membrane potentials. In the absence of amiodarone, half inactivation of the Ca2+ current occurred at a membrane potential of -23.8 +/- 0.2 mV compared to -34.2 +/- 0.6 mV after addition of amiodarone (n = 11, p < 0.01). Furthermore, amiodarone significantly delayed Ca2+ current recovery from previous inactivation. CONCLUSIONS: These results provide evidence that amiodarone blocks voltage-dependent Ca2+ current in isolated neonatal rabbit ventricular myocytes by a variety of different mechanisms. The inhibitory effect of amiodarone on L-type Ca2+ current may represent an important facet of amiodarone's acute antiarrhythmic activity in the immature heart.

Effects of isoflurane on electrophysiological measurements in children with the Wolff-Parkinson-White syndrome.

This study was designed to assess the effects of isoflurane (ISO) on the electrophysiological properties of the accessory pathway, atrium, ventricle, and AV node in children with the Wolff-Parkinson-White (WPW) syndrome. The results of programmed electrical stimulation were analyzed in 51 patients (4 months to 17 years of age) with WPW. The study population was divided into two groups. Twenty-seven patients received local anesthesia and intramuscular injection of meperidine, promethazine, and chlorpromazine (MPC group). Twenty-four patients received general anesthesia with ISO inhalation (ISO group). We compared the antegrade effective refractory period of the accessory pathway (antegrade APERP), ventricular effective refractory period (VERP), atrial effective refractory period (AERP), AH interval, and cycle length of circus movement tachycardia (CMT-CL) in 12 pairs of age and sex matched patients selected from the MPC and ISO groups. Of the 12 pairs of age and sex matched patients, antegrade APERP in patients who received ISO (299 +/- 17 ms, mean +/- SEM) was significantly longer as compared with matched patients in the MPC group (262 +/- 5 ms, P < 0.025). The VERP and AERP in patients from the ISO group were significantly prolonged compared with the MPC patients (239 +/- 7 vs 210 +/- 8 ms, P < 0.025, and 228 +/- 11 vs 180 +/- 6 ms, P < 0.01, respectively). There was no significant difference in the AH interval or CMT-CL between the two subgroups. Thus, ISO prolongs the antegrade APERPs as well as the effective refractory periods of atrial and ventricular muscle in children with WPW, while the AH interval and CMT-CL appear to be unaffected. Care must be taken in interpreting measurements of the antegrade APERP made in patients under general anesthesia for RF ablation of accessory pathways.