Anti-inflammatory effect of β2-agonists: Inhibition of TNF-α release from human mast cells

β₂-Agonists inhibit the release of preformed mediators such as histamine and newly synthesized mediators such as prostaglandin D₂ from mast cells. However, although mast cells have been identified as an important source of several cytokines including tumor necrosis factor-α (TNF-α), there is no information about their regulation by β₂-agonists. Thus given the importance of TNF-α in inflammation and the widespread use of β₂-agonists, we investigated the effect of long-acting (salmeterol) and short-acting (salbutamol) β₂-agonists on the secretion of TNF-α from human skin mast cells. Treatment of mast cells with salmeterol or salbutamol (100 nmol/L) inhibited the IgE-dependent release of TNF-α (82% and 74%, respectively). Moreover, 2-hour treatment with salmeterol, isoproterenol, or salbutamol inhibited mast cell cytotoxicity against a TNF-α–sensitive cell line, WEHI-164, with an IC₅₀ of 71, 50, and 29 nmol/L, respectively. Specificity for β-adrenergic receptors was shown with propranolol. The inhibitory effect of β₂-agonists was observed after only 20 minutes of treatment but was lost by 24 hours after removal of salbutamol and isoproterenol (7% and 11% inhibition remaining, respectively). In contrast, the inhibition of TNF-α release was increased 1 hour after removal of salmeterol and remained significant 24 hours later. Furthermore, β₂-agonists did not show tachyphylaxis for the inhibition of TNF-α release. Thus selective β₂-agonists demonstrate anti-inflammatory activity by inhibiting the release of TNF-α from mast cells stimulated through their IgE receptor or by a tumor target cell. This inhibitory effect of β-agonists may be important in their mode of action in the treatment of allergic diseases. (J Allergy Clin Immunol 1997;100:825-31.)     

Pilomatrix carcinoma. A new case

We present a new case of Pilomatrix Carcinoma after having review the 22 cases previously published. The tumor arisen in a 74 years old male, in the left preauricular region. The lesion was excised with wide margins. A year after there is not any evidence of recurrence or metastases.     

Postoperative Apnea in Former Preterm Infants after Inguinal Herniorrhaphy: A Combined Analysis

Background: Controversy exists as to the risk for postoperative apnea in former preterm infants. The conclusions of published studies are limited by the small number of patients.

Methods: The original data from eight prospective studies were subject to a combined analysis. Only patients having inguinal herniorrhaphy under general anesthesia were included; patients receiving caffeine, regional anesthesia, or undergoing other surgical procedures were excluded. A uniform definition for apnea was used for all patients. Eleven risk factors were examined: gestational age, postconceptual age, birth weight, history of respiratory distress syndrome, bronchopulmonary dysplasia, neonatal apnea, necrotizing enterocolitis, ongoing apnea, anemia, and use of opioids or nondepolarizing muscle relaxants.

Results: Two hundred fifty-five of 384 patients from eight studies at four institutions fulfilled study criteria. There was significant variation in apnea rates and the location of apnea (recovery room and postrecovery room) between institutions (P < 0.001). There was considerable variation in the duration and type of monitoring, definitions of apnea, and availability of historical information. The incidence of detected apnea was greater when continuous recording devices were used compared to standard impedance pneumography with alarms or nursing observations. Despite these limitations, it was determined that: (1) apnea was strongly and inversely related to both gestational age (P = 0.0005) and postconceptual age (P < 0.0001); (2) an associated risk factor was continuing apnea at home; (3) small-for-gestational-age infants seemed to be somewhat protected from apnea compared to appropriate- and large-for-gestational-age infants; (4) anemia was a significant risk factor, particularly for patients > 43 weeks' postconceptual age; (5) a relationship to apnea with history of necrotizing enterocolitis, neonatal apnea, respiratory distress syndrome, bronchopulmonary dysplasia, or operative use of opioids and/or muscle relaxants could not be demonstrated.     

Measurement of Perceived Disruption During Rebuilding Following Hurricane Andrew

The purpose of this study was to develop and evaluate a measure of perceived disruption during rebuilding following a disaster. Two eight-item scales, which measured intensity of disruption during the entire repair phase (Intensity-RP) and intensity of disruption during the past month (Intensity-PM) were developed and administered to 135 survivors of Hurricane Andrew. At 9 to 12 months postdisaster, Intensity-RP and Intensity-PM were both significantly associated with scores on the Global Severity Index of the SCL-90-R, and with scores on the Impact of Event-Intrusion Scale; Intensity-PM alone was significantly associated with PTSD scores. Regression analyses indicated that each scale contributed significant unique variance in predicting mental health symptoms, even after controlling for relevant demographic and initial disaster exposure variables.     

Vagus Nerve Stimulation Induces a Sustained Anticonvulsant Effect

Summary: Purpose: Stimulation of the vagus nerve can effectively abort several types of experimentally induced seizures in animals when administered near the time of seizure onset. Indirect evidence from human trials and animal studies suggests that the anticonvulsant effects of vagus nerve stimulation (VNS) extend beyond the duration of stimulation. We used the pentylenetetrazol model to determine whether VNS exerts a persistent anticonvulsant effect.
Methods: VNS (1 mA, 30 Hz, 500 μs pulse width) was administered continuously for 0, 1, or 60 min, or intermittently (30 s on, 5 min off) for 60 min, to awake and freely moving animals. After the end of stimulation, pentylenetetrazol (50 mg/kg i.p.) was administered to induce seizures. Time-course studies were also performed, consisting of 60 min of VNS followed by pentylenetetrazol injection after 0, 3-, 5-, and 10-min intervals.
Results: The greatest anticonvulsant effect occurred after 60 min of continuous VNS, which prevented convulsions in four of 12 rats and reduced significantly seizure duration, the total number of seizures, and number of tonic seizures. Intermittent VNS was less effective than continuous stimulation for 60 min, but more effective than that for 1 min. The anticonvulsant effect declined in a time-dependent fashion after discontinuation of VNS, with return to nonstimulated control values by 10 min.
Conclusions: The results of this study verify a persistent VNS-induced anticonvulsant effect and indicate that its efficacy is dependent on the cumulative stimulus duration.     

Beneficial Effects of Short-term Vasopressin Infusion during Severe Septic Shock

Background: Septic shock is associated with vasopressin deficiency and a hypersensitivity to its exogenous administration. The goal of the current study was to determine whether short-term vasopressin infusion in patients experiencing severe septic shock has a vasopressor sparing effect while maintaining hemodynamic stability and adequate end-organ perfusion.

Methods: Patients experiencing septic shock that required high-dose vasopressor support were randomized to a double-blinded 4-h infusion of either norepinephrine (n = 11) or vasopressin (n = 13), and open-label vasopressors were titrated to maintain blood pressure. To assess end-organ perfusion, urine output and creatinine clearance, gastric mucosal carbon dioxide tension, and electrocardiogram ST segment position were measured.

Results: Patients randomized to norepinephrine went from a median prestudy norepinephrine infusion of 20.0 [mu]g/min to a blinded infusion of 17.0 [mu]g/min at 4 h, whereas those randomized to vasopressin went from a median prestudy norepinephrine infusion of 25.0 [mu]g/min to 5.3 [mu]g/min at 4 h (P < 0.001). Mean arterial pressure and cardiac index were maintained in both groups. Urine output did not change in the norepinephrine group (median, 25 to 15 ml/h) but increased substantially in the vasopressin group (median, 32.5 to 65 ml/h;P < 0.05). Similarly, creatinine clearance did not change in the norepinephrine group but increased by 75% in the vasopressin group (P < 0.05). Gastric mucosal carbon dioxide tension and electrocardiogram ST segments did not change significantly in either group.     

Laterality, torque and personality

Evidence accumulating from a variety of methodological approaches suggests that unusual laterality is often a concomitant feature of emotional pathology. In the present study both torque and a multifaceted measure of laterality were examined with respect to personality variables measured by the 16 PF in a normal population. Interestingly, a pattern of emotionality for subjects with a more confused laterality was revealed in a normal population which is notably similar to reported aberrant personality factors and laterality in more pathological groups. The existence of a cohesive continuum of emotional expression in relation to confused laterality is suggested. In addition, both torque and the multifactored measure of laterality are critiqued as research measures and for their clinical potential.     

Elevated hypothalamic neuropeptide Y levels in rats with dorsomedial hindbrain lesions

Lesions centered on the area postrema (AP) and adjacent nucleus of the solitary tract (AP/mNTS-lesions) are reported to result in increased consumption of highly palatable diets. Recent studies suggest that neuropeptide Y (NPY) may cause a preference for carbohydrate-rich diets. Thus, it is possible that NPY may play a role in the enhanced intake of highly palatable diets by AP/mNTS-lesioned rats. In the studies reported here, we found that lesions centered on the AP result in increased levels of NPY-immunoreactivity in the paraventricular nucleus of the hypothalamus. Additionally, steady-state NPY mRNA in the basomedial hypothalamus including the arcuate nucleus was elevated. Enhanced NPY was not found throughout the hypothalamus however, as NPY-immunoreactivity was not elevated in the lateral hypothalamus or the tissue bordering the anteroventral third ventricle. These data suggest the possibility that elevated hypothalamic NPY, particularly in the arcuate and paraventricular nuclei, may contribute to the altered food intake and energy balance observed in rats with lesions centered on the AP.