Behavioral and neurochemical responses to cocaine in periadolescent and adult rats.

Although recreational drug use by human adolescents is a well-known and long-standing problem, relatively little is known regarding differences in behavioral and physiological responses to abused substances in adolescent vs adult animals. The present study compared effects of the psychomotor stimulant, cocaine, in periadolescent (postnatal days 37-52) and adult (postnatal days 75-90) male Wistar rats. Locomotion and motor stereotypy were recorded after acute and repeated cocaine injections (0, 10, or 20 mg/kg cocaine, intraperitoneal (i.p.), four injections spaced 5 days apart). Spontaneous acquisition of intravenous (i.v.) cocaine self-administration was investigated in two dose groups ( approximately 0.37 or 0.74 mg/kg/infusion) over 14 days. Dopamine levels in the nucleus accumbens were recorded under basal conditions (no net flux method) and after cocaine administration ( approximately 0.37, 0.74, and 2.92 mg/kg/i.v. infusion or 20 mg/kg i.p.) using in vivo microdialysis. The locomotor data are in partial agreement with previous reports of hyposensitivity to acute cocaine in periadolescent vs adult rats; periadolescents were less active overall than adults. Moreover, adult rats exhibited significant locomotor sensitization after repeated injection of 10 mg/kg cocaine, whereas periadolescents required the high dose of 20 mg/kg cocaine to demonstrate sensitization. Neither age group showed sensitization of motor stereotypies. No age-related difference was observed in acquisition of cocaine self-administration, or in basal or cocaine-stimulated nucleus accumbens dopamine. These experiments imply a developmental dissociation between the motor activating and reinforcing effects of cocaine. Similarities in dopamine levels across age groups suggest that age-specific motor responses to cocaine are not mediated by dopamine in the nucleus accumbens.     

Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome

To determine whether multiple doses of bovine surfactant would improve neonatal mortality in very premature neonates, we conducted two multicenter controlled trials under identical protocols; the results were combined for analysis. Four hundred and thirty neonates born between 23 and 29 weeks gestation and weighing 600 to 1250 g at birth were assigned randomly at birth to receive either 100 mg of phospholipids/kg of Survanta, a modified bovine surfactant (n = 210), or a sham air placebo (n = 220) within 15 minutes of birth. Neonates who developed respiratory distress syndrome and required mechanical ventilation with at least 30% oxygen could be given up to three more doses in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Cause of death was determined by a panel of three independent, board-certified neonatologists after blindly reviewing case report forms and autopsy reports. Fewer Survanta-treated neonates died of any cause (11.4% vs 18.8%, P = .031), died of respiratory distress syndrome (1.9% vs 15.6%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (39.5% vs 49.1%, P = .044). The incidence of respiratory distress syndrome was also lower in Survanta-treated neonates (28.0% vs 56.9%, P less than .001), and the Survanta-treated neonates' oxygenation and ventilatory status were improved significantly at 72 hours. Survanta-treated neonates were also at lowered risk of developing pulmonary interstitial emphysema (23.3% vs 36.9%, P = .002) and other forms of pulmonary air leaks (9.6% vs 20.8%, P .002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Stage IV-N: a favorable subset of children with metastatic neuroblastoma

Among children over 1 year of age with Evans Stage IV neuroblastoma, there appears to be a small group with a relatively favorable prognosis. These patients have extensive lymph node metastases (cervical/axillary/thoracic/abdominal/pelvic), but no extranodal metastases. Three of six such patients (50%) are long-term disease-free survivors, compared with none of 40 patients with extranodal metastatic disease (p less than 0.0002). Patients with only lymph node metastases (Stage "IV-N") may have a biologically more favorable tumor that is curable with conventional, intensive multimodality therapy.     

Hemodynamic response to high-frequency ventilation in infants following cardiac surgery

The hemodynamic response to high-frequency ventilation was compared with conventional ventilation in six infants following cardiac surgery. While undergoing high-frequency ventilation, adequate gas exchange was maintained in all infants. High frequency ventilation allowed a reduction of peak ventilatory pressure at the airway opening by 19%, and peak tracheal pressure by 42%. No clinically important changes in heart rate, systemic and pulmonary arterial pressure, cardiac index, or systemic and pulmonary vascular resistance were noted when high-frequency ventilation was compared with conventional ventilation.     

Schizophrenia as a temporal mode of being: an existential "ante-festum" impatience.

We suggest in a phenomenological perspective to consider schizophrenia as a special form of human temporality. From this perspective, we view the symptoms of schizophrenia as actions undertaken by subjects to stabilize themselves in existence. From this vantage, we describe the clinical expression of the disorder as a type of "existential impatience", characterized by a painful and elusive "now". This present time posits the prime moment of the constitution of the person. Existential impatience reflects from our patients the persistence of excessive efforts towards individuation. Schizophrenia. In human life in general, individuation consists in an unceasing dynamic process of building up of the self. This process starts with the non-self and particularly with the other. Therefore, the emergence of any relation within the self is grounded in the relation with the other and is based on the relation the other establishes with himself. Schizophrenia distinctly displays the two constitutive moments of "being oneself." These moments are generally linked for all of us: an "unending coming to oneself" (difference of identity), and a "continuous maintenance of being a self" (identity of difference). Existential impatience is not only an irritability of a formal order. Existence itself is impatient in the schizophrenic experience as it hastens to reach human goals while trampling on an "ante-festum" temporal mode. This "before-the-feast" temporal structure is dominated by the shiver before an unknown future, a sign of a basic quest for a task. Schizophrenic "ante-festum" is both a constant fear of being unable to come to oneself and a desperate effort to reach this unknown future. If psychopathology claims to settle [establish] that "order" and "measure" would constitute the two fundamental anthropological bases of human being, impatience of existence draws the emblematic figure of the disorder of measure as a referential motion of the birth of any temporalisation. Such considerations suggest the value, in treatment and rehabilitation, of praising patience and focusing on building, or re-building, the past. The main objective is to reach a maieutics of the self based on relationships in the community and with care-givers, all within an accompanying structured, daily framework.     

A sebaceous tumor in a patient with acquired immunodeficiency syndrome

The prevalence of cutaneous malignancies is higher in immunosuppressed patients. Here, we describe a case with a rapid growing and unusually large sebaceous tumor in a patient with acquired immunodeficiency syndrome. Sebaceous adenomas are commonly rare, benign tumors of sebaceous glands. An association of AIDS and a solitary, large sebaceous adenoma has not been described yet. This emphasizes the role of an intact immune system in the suppression of benign and malignant tumors. tubular adenoma; tumor; AIDS     

Pilocarpine-induced seizure-like activity with increased BNDF and neuropeptide Y expression in organotypic hippocampal slice cultures

Organotypic hippocampal slice cultures were treated with the muscarinic agonist pilocarpine to study induced seizure-like activity and changes in neurotrophin and neuropeptide expression. For establishment of a seizure-inducing protocol, 2-week-old cultures derived from 6–8-day-old rats were exposed to 0.1 mM to 5 mM of pilocarpine for 4 h to 7 days. Other cultures were treated with pilocarpine for 7 days and left for 7–14 days in normal medium. Age-matched, non-treated cultures served as controls. Intracellular recordings from CA1 pyramidal cells revealed increased spontaneous activity in 31 of 35 cultures superfused with 0.1 or 5 mM pilocarpine. Epileptiform discharges were recorded in 17 of the 31 cultures, and 19 displayed frequencies specifically in the 6–12-Hz (Theta rhythm) range when superfused with pilocarpine. The pilocarpine effect was blocked by simultaneous superfusion with the muscarinic receptor antagonist atropine (100 μM). Regardless of dose and exposure time, the pilocarpine treatment induced very limited neuronal cell death, recorded as cellular propidium iodide uptake. Cultures exposed to 5 mM pilocarpine for up to 7 days displayed increased BDNF expression when analyzed by Western blot and ELISA. This BDNF increase correlated with increased neuropeptide Y immunoreactivity, known to accompany seizure activity. Addition of BDNF (200 ng/ml) to otherwise untreated cultures also upregulated NPY expression. The pilocarpine-induced seizure-like activity in hippocampal slice cultures, with concomitant increase in BDNF and NPY expression, is compared with in vivo observations and discussed in terms of the potential use of the easily accessible slice cultures in experimental seizure research.     

Tumor-driven paracrine platelet-derived growth factor receptor alpha signaling is a key determinant of stromal cell recruitment in a model of human lung carcinoma.

Activated fibroblasts are thought to play important roles in the progression of many solid tumors, but little is known about the mechanisms responsible for the recruitment of fibroblasts in tumors. Using several methods, we identified platelet-derived growth factor A (PDGFA) as the major fibroblast chemoattractant and mitogen from conditioned medium generated by the Calu-6 lung carcinoma cell line. In addition, we showed that Calu-6 tumors express significant levels of PDGFC, and that the levels of expression of these two PDGFRalpha ligands correlate strongly with the degree of stromal fibroblast infiltration into the tumor mass. The most intense expression of PDGFRalpha was observed in fibroblasts in the tumor outer rim. We subsequently showed that disrupting PDGFRalpha-mediated signaling results in significant inhibition of tumor growth in vivo. Furthermore, analysis of a compendium of microarray data revealed significant expression of PDGFA, PDGFC, and PDGFRalpha in human lung tumors. We propose that therapies targeting this stromal cell type may be effective in treating certain types of solid tumors.     

Effect of IL-1 on experimental bone/bone-marrow metastases.

Bone metastasis is a common event and a major cause of morbidity in cancer patients. The hematopoietic marrow of the bones, rather than the bone tissue per se, is the target organ in bone metastasis. In the bone marrow, IL-1 induces the release of hematopoietic growth factors that may affect tumor-cell growth. We treated groups of mice with rhuIL-1 alpha to examine its role in the establishment of experimental bone/bone-marrow metastasis. We found that injection of 2 micrograms of rhuIL-1 alpha 24 hr prior to, simultaneously with or 24 hr after the injection of 10(4) B16 melanoma cells into the left cardiac ventricle of mice resulted in a 2-fold increase in the average number of colonized bones per mouse. GM-CSF is produced by bone-marrow stromal cells in response to IL-1, and its receptor has been found on tumor cells, including melanoma cells. However, the administration of rmuGM-CSF to mice by either multiple injections or continuous infusion did not affect the number of colonized bones. Many of the biologic effects of IL-1 are mediated by prostaglandins. Treatment of mice with 100 micrograms of indomethacin, a potent inhibitor of prostaglandin synthesis, prior to the injection of rhuIL-1 alpha, prevented the increase in number of bone metastases. To determine whether constitutive productions of IL-1 and/or prostaglandins are involved in the pathogenesis of bone/bone marrow metastasis, we treated mice with antimouse IL-1 alpha neutralizing antibodies, rhuIRAP (an inhibitor of IL-1 activity) or indomethacin. We found no difference in the average number of colonized bones per mouse between treated and control mice. We conclude that exogenous administration of IL-1 enhances experimental bone/bone-marrow metastases, and that this phenomenon is mediated through prostaglandins. However, neither the constitutive production of IL-1 nor that of prostaglandins appear to play a role in the pathogenesis of bone/bone-marrow metastasis in our murine model system.