Cyclooxygenase inhibitors use is associated with reduced risk of esophageal adenocarcinoma in patients with Barrett's esophagus: a meta-analysis.

BACKGROUND: Esophageal adenocarcinoma (EAC) has high mortality and is increasing in incidence. Barrett's esophagus (BE) increases the risk for EAC. Studies have reported inconsistent findings on the association between use of cyclooxygenase (COX) inhibitors and the risk of neoplastic progression in BE patients. Therefore, we performed a meta-analysis to investigate this association. METHODS: A meta-analysis was undertaken among a total of 9 observational studies using fixed- and random-effects models, comprising 5446 participants; 605 had EAC or high-grade dysplasia (HGD). RESULTS: Overall, COX inhibitors use was associated with a reduced risk of EAC/HGD among BE patients (relative risk (RR)=0.64, 95% confidence interval (CI)=0.53-0.77). Aspirin use also reduced the risk of EAC/HGD (RR=0.63, 95% CI=0.43-0.94), as well as non-aspirin COX inhibitors (RR=0.50, 95% CI=0.32-0.78). The chemopreventive effect seemed to be independent of duration response. CONCLUSIONS: Cyclooxygenase inhibitors use is associated with a reduced risk of developing EAC in patients with BE. Both low-dose aspirin and non-aspirin COX inhibitors are associated with a reduced risk of neoplasia. More well-designed randomised controlled trials are needed to increase our understanding of the chemopreventive effect of COX inhibitors.

Corticotrophin-releasing hormone (CRH) facilitates axon outgrowth.

OBJECTIVE: To evaluate the role of corticotrophin-releasing hormone (CRH) in facilitating axon outgrowth. BACKGROUND: Injured neural tissue is difficult to regenerate; the mechanism has not been fully understood. METHODS: A rat model of spinal cord transection injury was developed. Levels of BDNF, CRH and oligodendrocyte glycoprotein (OMgp) in injured spinal cord were monitored dynamically after surgery. Cellular interaction among rat dorsal root ganglia (DRG) cells, oligocondrocytes and microglial cells was observed with a coculture model. The axon outgrowth from DRG cells was examined by confocal microscopy. RESULTS: After spinal cord transection, levels of BDNF and CRH increased the next day and decreased afterward, whereas OMgp levels increased from day 3. Administration with BDNF suppressed the levels of OMgp in vitro. The results from a coculture model showed that CRH increased microglial cells to release BDNF; BDNF inhibited OMgp levels in oligodendrocytes and enhanced the axon outgrowth from DRG cells. CONCLUSIONS: This study shows that CRH has the ability to facilitate the outgrowth of axon in spinal neurons, which has therapeutic potential in the treatment of spinal cord injury.

Improving bone marrow biopsy quality through peer discussion and data comparisons: A single institution experience.

INTRODUCTION: Bone marrow biopsy (BMB) is crucial for the diagnosis, staging, and monitoring of a variety of hematologic diseases. Obtaining an adequate BMB can be challenging given the need to balance patient comfort with acquisition of high quality specimens. We had observed variable BMB quality at our institution with poor quality specimens sometimes affecting diagnosis. We thus undertook this quality improvement (QI) project to improve the quality of diagnostic BMB specimens. METHODS: We used an A3 QI process to identify factors possibly influencing BMB quality. We collected baseline data on 211 BMB, with short and long-term follow-up data on a further 382 cases. We used clinical conferences to discuss data, perform peer comparisons and identify strategies to create a sustainable improvement in BMB quality. RESULTS: Baseline data showed that BMB length was influenced most by the individual performer, with some influence of needle gauge. Other factors such as sedation, BMB indication were noncontributory. BMB lengths improved following performer education and individual performer data comparisons (15.2 mm post vs 12.8 mm baseline, P < .0001) and with use of an 8- rather than 11-gauge needle (18.3 mm 8-gauge vs 13.3 mm 11-gauge P < .0001), and were sustained over the long term. CONCLUSIONS: Education on BMB standards, sharing of performer data, and changing needle gauge are relatively straightforward methods to improve BMB quality, leading to easier pathology diagnosis.

Relationship between 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in saliva and plasma of healthy volunteers.

Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels may reflect changes in central noradrenergic and dopaminergic activity, respectively. The relationship between MHPG and HVA in saliva and plasma was investigated to evaluate the utility of salivary metabolite measurement as a relatively noninvasive and useful alternative to plasma analysis. MHPG and HVA in saliva and plasma, collected concurrently, from 12 healthy volunteers, were measured by high-performance liquid chromatography. Concentration of free MHPG in saliva correlated significantly with plasma free MHPG. Salivary free MHPG was significantly higher than in plasma. Enzymatic hydrolysis of conjugated MHPG corroborated other work that plasma free MHPG, MHPG-glucuronide, and MHPG-sulfate were in roughly equal proportions. Unpredictably, in saliva, free MHPG was greater than 80% of the total. Salivary and plasma free HVA concentrations also correlated significantly, but salivary HVA levels were significantly lower than in plasma. Conjugated HVA was consistently less than 10% of total both in saliva and plasma. These findings suggest that salivary MHPG and HVA can reflect plasma metabolite levels. Although local factors may influence their formation and concentration in saliva, large changes in plasma free MHPG or HVA could be reflected by parallel changes in saliva.

Predictors of cortisol and 3-methoxy-4-hydroxyphenylglycol responses in the acute aftermath of rape.

BACKGROUND: Prospective studies of trauma survivors can provide information about the relationship between rape characteristics and the development of subsequent symptoms. METHODS: The present study examined the relationship of prior assault, rape severity, posttraumatic stress disorder (PTSD) symptoms following rape, and subsequent PTSD diagnosis, to the acute cortisol and 3-methoxy-4-hydroxyphenylglycol (MHPG) response to this traumatic event in 20 women. RESULTS: Women with a history of prior physical or sexual assault showed a significantly attenuated cortisol response to the acute stress of rape compared to women without such a history. MHPG appeared to be associated with injury-related rape characteristics, and symptoms of active avoidance, but not prior history. PTSD status at the 3-month follow-up was predicted by both a prior history of assault and high injury rape, but was not directly predicted by either cortisol or MHPG levels. MHPG and cortisol were not correlated in the sample as a whole, but were correlated among individuals who did not subsequently develop PTSD (p = .04) CONCLUSIONS: The results suggest that different neuroendocrine systems may mediate different components of the response to traumatic stress.

Plasma norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations and severity of depression in combat posttraumatic stress disorder and major depressive disorder.

BACKGROUND: Catecholamines are thought to play a significant role in the pathophysiology of posttraumatic stress disorder (PTSD), but findings in PTSD have been discrepant. METHODS: To obtain more information about catecholamine activity in PTSD, we sampled plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations over a 24-hour period in men with PTSD (n = 15) and major depressive disorder (MDD) (n = 12), and nonpsychiatric comparison subjects (n = 13), under unstimulated conditions. Chronobiological analyses were performed to determine possible changes in the circadian and ultradian release of these hormones. RESULTS: Significant group differences were present for mean plasma NE levels (p = .03), but not MHPG. NE levels were significantly associated with severity of depression in the PTSD group (p = .002). Therefore, PTSD subjects were further subdivided into those with and without a comorbid secondary depression. Increased NE levels were only present in PTSD subjects who did not have a secondary depression. This study also found no significant group differences on any of the chronobiological parameters. CONCLUSIONS: The results clarify that increased NE levels in PTSD may be confined to the subgroup of subjects who do not have comorbid depression, and as such, may help resolve some of the discrepancies in the literature regarding basal catecholamine activity.

Basal cortisol, dexamethasone suppression of cortisol, and MHPG in adolescents after the 1988 earthquake in Armenia.

OBJECTIVE: This study evaluated basal salivary cortisol, 3-methoxy-4-hydroxyphenylglycol (MHPG), and cortisol suppression following dexamethasone administration in adolescents exposed to two levels of earthquake-related trauma. METHOD: Five years after the 1988 earthquake, saliva samples were obtained from 37 adolescents from two cities in Armenia at different distances from the epicenter. Baseline saliva samples were obtained at 8:00 a.m., 4:00 p.m., and 11:00 p.m., following which 0.5 mg of dexamethasone was administered. Nine and 17 hours later, saliva samples were again obtained. Subjects were evaluated for posttraumatic stress and depressive reactions through use of self-report instruments. RESULTS: Significantly lower mean baseline 8:00 a.m. cortisol levels and greater day 24:00 p.m. cortisol suppression following dexamethasone were observed in the more symptomatic adolescents living in the city closer to the epicenter. Of the three symptom categories of posttraumatic stress disorder (PTSD), only intrusion (category B) symptoms were significantly correlated with basal morning cortisol levels and percent suppression by dexamethasone. The more highly exposed adolescents also exhibited a more rapid decline in MHPG levels over the course of day 1. CONCLUSIONS: The findings indicate that chronic posttraumatic stress reactions among adolescents exposed to catastrophic disaster are associated with hypothalamic-pituitary-adrenal (HPA) axis alterations. The findings are congruent with those previously described in adults with chronic PTSD. Persistent intrusion (category B) symptoms may constitute continued episodes of distress and evoke repeated physiological stress responses, which, over time, alter HPA axis function. The MHPG findings suggest that there may be diurnal changes associated with severity of posttraumatic stress symptoms.

Noradrenergic responses to clonidine in acute and remitted depressed male patients.

To investigate noradrenergic function in depression, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma norepinephrine (NE), mean arterial pressure (MAP), and heart rate responses to intravenous clonidine (2 micrograms/kg), an alpha 2-adrenergic agonist, were measured in 27 acutely depressed patients, 18 remitted depressed patients, and 27 normal control subjects; a placebo infusion was administered to a subgroup. Clonidine compared with placebo, over a 150-minute time course, decreased plasma NE, MAP, and heart rate, but not plasma MHPG, in the control subjects. Plasma MHPG, plasma NE, MAP, and heart rate at baseline or in response to clonidine and placebo over 150 minutes did not indicate any group differences. The only significant plasma MHPG response to clonidine in the normal control subjects occurred 60 minutes after the infusion. A significantly diminished plasma MHPG response to clonidine at 60 minutes was found in the acutely depressed group compared with the normal control subjects. These results suggest that peripheral inhibitory noradrenergic responses to clonidine are normal in depressed patients, while plasma MHPG responses to clonidine, which have a limited central contribution, appear to be a weak reflection of central noradrenergic function and appear insufficiently robust for a meaningful evaluation of hypothetical group differences in central inhibitory alpha 2-adrenergic activity in this population.

Clinical correlates of DHEA associated with post-traumatic stress disorder.

OBJECTIVE: Increased plasma dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) have been demonstrated in post-traumatic stress disorder (PTSD), but the documented beneficial effects of these steroids in enhancing mood and cognition, as well as neuroprotection, suggest their presence in PTSD may be associated with defensive rather than maladaptive effects. METHOD: We, therefore, examined plasma DHEA, DHEAS, cortisol, and the DHEA/cortisol ratio in 40 male veterans with or without PTSD, and determined their relationships to PTSD symptom severity and symptom improvement. RESULTS: The PTSD group showed significantly higher plasma DHEA and non-significantly higher DHEAS levels as well as a significantly lower cortisol/DHEA ratio, controlling for age. Regression analyses demonstrated that DHEA and DHEAS levels could be predicted by symptom improvement and coping, whereas the cortisol/DHEA ratio was predicted by severity of childhood trauma and current symptom severity. CONCLUSION: That greater symptom improvement was related to DHEA levels may suggest for a role for these hormones in modulating recovery from PTSD.

A critique of "obstetrical pain-relieving drugs as predictors of infant behavior variability".

Aleksandrowicz and Aleksandrowicz (1974) concluded that "the use of obstetrical drugs is related to a considerable degree, to infantile behavior over the first month of life" (p. 944). Questions are raised about the adequacy of a number of their procedures. These questions are serious enough to disturb the foundation for any conclusions.

A study of the "inversion of intensity" between newborn and preschool-age behavior.

To test the inversion of intensity interpretation based on negative relations between newborn and preschool intensity behaviors (Bell, Weller, & Waldrop 1971), 106 normal children were examined at the neonatal and preschool periods. Data analyses were carried out in 2 parts: Part I was an attempt to reconstruct the same measures of intensity Bell et al. used at both periods, and Part II was a broader factor analytic analysis using all measures conceptually related to intensity in the neonatal and preschool periods. In Part I, several correlations were in the direction consistent with inversion, but only 1 of 20 correlations reached significance. In Part II, several significant correlations between intensity behavior at newborn and preschool periods were obtained, indicating intense newborn behavior to be related to low levels of socially negative behaviors. Interpretations of intensity behaviors at both periods and their longitudinal relations are discussed.

Perception of child, child-rearing values, and emotional distress as mediating links between environmental stressors and observed maternal behavior.

This observational study of 74 families investigated 3 areas of maternal psychological functioning (emotional distress, authoritarian child-rearing values, negative perceptions of children) that might mediate the relationship between 3 separate dimensions of family demographic characteristics, conceptualized as chronic environmental stressors (i.e., financial, structural, and historical circumstances), and the emotionally affective behavior of mothers. Demographic conditions accounted for 52.9% of the variance in mothers' psychological characteristics and as much as 36.6% of the variance in positive and negative behaviors to children. The psychological characteristics explained as much as 15.1% of the variance in maternal behavior. Both chronic stress and the psychological variables had an independent influence on the general emotional tone of maternal behavior. The findings provide tentative support for the conclusion that the psychological characteristics examined here partially mediate the influence of some demographic or stressful life conditions on the positive and negative behaviors of mothers.

Secretin responses to feeding and acid load.

Secretin can be readily concentrated from 10 ml of plasma by adsorption to and elution from octadecylsilyl silica columns (C18 Sep-Pak cartridges). This method of concentration is more expedient than either ethanol extraction or adsorption to and elution from precipitated silica (QUSO G32) and permits detection of secretin in plasma at concentrations of 1 pg/ml or greater. Basal secretin in normal subjects was found to be less than 4 pg/ml of plasma. In response to an STM, plasma secretin increased on the average to twice the fasting level, but in response to an oral SAL, it generally increased about 10-fold.

The influence of the wider use of surfactant therapy on neonatal mortality among blacks and whites.

BACKGROUND: Surfactant therapy reduces morbidity and mortality among premature infants with the respiratory distress syndrome (RDS). Fetal pulmonary surfactant matures more slowly in white than in black fetuses, and therefore RDS is more prevalent among whites than among blacks. We reasoned that the increased use of surfactant after its approval by the Food and Drug Administration (FDA) in 1990 might have reduced neonatal mortality more among whites than among blacks. METHODS: We merged vital-statistics information for all 1563 infants with very low birth weights (500 to 1500 g) born from 1987 through 1989 or in 1991 and 1992 to residents of St. Louis with clinical data from the four neonatal intensive care units in the St. Louis area; we then compared neonatal mortality during two periods, one before and one after the FDA's approval of surfactant for clinical use (1987 through 1989 and 1991 through 1992). RESULTS: The use of surfactant increased by a factor of 10 between 1987 through 1989 and 1991 through 1992. The neonatal mortality rate among all very-low-birth-weight infants decreased 17 percent, from 220.3 deaths per 1000 very-low-birth-weight babies born alive (in 1987 through 1989) to 183.9 per 1000 (in 1991 through 1992; P = 0.07). This decrease was due to a 41 percent reduction in the mortality rate among white newborns with very low birth weights (from 261.5 per 1000 to 155.5 per 1000; P = 0.003). In contrast, among black infants, the mortality rate for very-low-birth-weight infants did not change significantly (195.6 per 1000 and 196.8 per 1000). The relative risk of death among black newborns with very low birth weights as compared with white newborns with similar weights was 0.7 from 1987 through 1989 and 1.3 from 1991 through 1992 (P = 0.02). The differences in mortality were not explained by differences in access to surfactant therapy, by differences in mortality between black and white infants who received surfactant, or by differences in the use of antenatal corticosteroid therapy. CONCLUSIONS: After surfactant therapy for RDS became generally available, neonatal mortality improved more for white than for black infants with very low birth weights.