Herbivory regulates the establishment of a native species of submerged aquatic vegetation (SAV) in a tidal estuary of the USA.

Herbivores are a diverse group of fauna that shape the distribution and composition of plant communities. In some cases, herbivory may prevent the re-establishment of submerged aquatic vegetation (SAV), such as Vallisneria americana, into systems. The goal of this study was to investigate the role and nature of herbivory on V. americana transplants with camera and transect surveys of grazing intensity and with field and laboratory grazing experiments using a suspected herbivore, the blue crab, Callinectes sapidus. Camera surveys recorded C. sapidus clipping and consuming shoots of V. americana for the first time. Grazing intensity surveys in low-salinity regions of the lower Chesapeake Bay indicated that the majority of V. americana transplants (50-75%) were clipped off at their base within one week of planting. Field and laboratory experiments demonstrated that C. sapidus clips and consumes V. americana as well as other rapidly colonizing, non-native SAV. Analysis of the gut contents of C. sapidus caught in SAV beds in the Chesapeake Bay revealed that SAV comprised 16% of their stomach contents, suggesting low levels of C. sapidus herbivory occurred over a wide area. Callinectes sapidus is yet another animal documented to consume SAV for some portion of their diet. These results also suggest that herbivores or omnivores, including C. sapidus, can serve as bottlenecks to recovery of SAV, like V. americana, in some areas. Herbivores may not serve as bottlenecks in other environments or to other SAV with more rapid plant growth or higher recruitment levels that may overcome grazing pressure.

Support needs and quality of life in oral cancer: a systematic review.

PURPOSE: This review aims to systematically review the literature describing quality of life (QoL) outcomes and support needs in patients with oral cancer along the cancer trajectory. This is needed to form an evidence base for the design of interventions that enhance outcomes for this group. METHODS: Six electronic databases were searched. The results were screened for eligibility, and articles were included if they described patient-reported QoL outcomes that were translatable to support needs in patients with oral cancer. Data were extracted and synthesized according to the support needs identified and their relative impact on QoL. Methodological quality was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool. RESULTS: Thirty-one articles met the inclusion criteria. Support needs related to coping with the burden of radiotherapy in both psychosocial and physical aspects, swallowing dysfunction, dry mouth and oral functional deficits. Issues of depression, anxiety and malnutrition were identified as having a significant impact on QoL. CONCLUSIONS: Oral cancer support needs are highly subjective and varied in severity across the cancer continuum. Support needs that may warrant further investigation include management of changes to oral health and functioning, swallowing and nutritional compromise and psychological effects of cancer and treatment.

"I have quality of life but ": Exploring support needs important to quality of life in head and neck cancer.

PURPOSE OF RESEARCH: Head and neck cancer (HNC) treatment disrupts quality of life and is associated with individualised supportive care needs. This study aimed to describe the support needs that affected the QoL of HNC patients, and to describe how patients coped with unmet support needs. METHODS: Qualitative, semi-structured interviews were held with 8 participants previously treated for HNC. Participants were identified through snowball and convenience sampling methods. Interview data was analysed using content analysis (CA). Inductive CA was used to describe support needs and directed CA was guided by the stress appraisal and coping model to describe coping with unmet support needs. RESULTS: Support needs that affected QoL related to acute needs while undergoing treatment and support in coping with permanent treatment side effects. Coping with psychological stressors (i.e. depression and anxiety) affected QoL in the first six to twelve months following treatment. Coping was influenced by loss of access to the supportive hospital environment after treatment, and resulted in feelings of isolation post treatment. CONCLUSIONS: HNC patients drew support from professional and personal networks while undergoing treatment and post treatment. Patients described difficulties in coping with the side effects of treatment and accessing supportive care when away from the hospital setting. The transactional model of stress, appraisal and coping is useful in understanding the psychosocial outcomes of head and neck cancer; however conclusions from this study are limited by a small and homogenous sample.

Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON-Recurrent Fracture Trial.

UNLABELLED: This study evaluated the benefits of ZOL versus placebo on health-related quality of life (HRQoL) among patients from HORIZON-RFT. At month 24 and end of the study visit, ZOL significantly improved patients' overall health state compared to placebo as assessed by the EQ-5D VAS. INTRODUCTION: To evaluate the benefits of zoledronic acid (ZOL) versus placebo on health-related quality of life (HRQoL) among patients from The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON-RFT). METHODS: In this randomized, double-blind, placebo-controlled trial, 2,127 patients were randomized to receive annual infusion of ZOL 5 mg (n = 1,065) or placebo (n = 1,062) within 90 days after surgical repair of low-trauma hip fracture. HRQoL was measured using EQ-5D Visual Analogue Scale (VAS) and utility scores (EuroQol instrument) at months 6, 12, 24, 36, and end of the study visit. Analysis of covariance model included baseline EQ-5D value, region, and treatment as explanatory variables. RESULTS: At baseline, patients (mean age 75 years; 24% men and 76% women) were well matched between treatment groups with mean EQ-5D VAS of 65.82 in ZOL and 65.70 in placebo group. At the end of the study, mean change from baseline in EQ-5D VAS was greater for ZOL vs. placebo in all patients (7.67 ± 0.56 vs. 5.42 ± 0.56), and in subgroups of patients experiencing clinical vertebral fractures (8.86 ± 4.91 vs. -1.69 ± 3.42), non-vertebral fractures (5.03 ± 2.48 vs. -1.07 ± 2.16), and clinical fractures (5.19 ± 2.25 vs. -0.72 ± 1.82) with treatment difference significantly in favor of ZOL. EQ-5D utility scores were comparable for ZOL and placebo groups, but more patients on placebo consistently had extreme difficulty in mobility (1.74% for ZOL vs. 2.13% for placebo; p = 0.6238), self-care (4.92% vs. 6.69%; p = 0.1013), and usual activities (10.28% vs. 12.91%; p = 0.0775). CONCLUSION: ZOL significantly improves HRQoL in patients with low-trauma hip fracture.

The prevalence and recognition of major depression among low-level aged care residents with and without cognitive impairment.

Previous research has demonstrated a high level of depression in nursing homes. The current study was designed to determine the prevalence of depression, using a structured diagnostic interview, among older people with and without mild-moderate cognitive impairment residing in low-level care facilities. The results demonstrated that, consistent with previous research in nursing homes, 16.9% of older people were diagnosed with major depressive disorder. Less than half of these cases had been detected or treated. Individuals with moderate cognitive impairment were more likely to be depressed, but cognitive impairment did not appear to act as a strong impediment to the detection of depression by general practitioners. A low awareness of their use of antidepressant medications was demonstrated among older people prescribed this treatment, including those with normal cognitive function. Reasons for the poor recognition of depression among older people are discussed.

Alcohol concentration and the ability to form intent.

The ability to form intent to commit a particular act is often a significant issue in criminal litigation. Often, a complicating factor in the resolution of this issue is the presence of ethanol and drugs in the individual whose motives are to be ascertained. To determine whether an intoxicating blood ethanol concentration (BAC) in the absence of other information is sufficient to establish intent, we reviewed cases investigated by the Office of the Chief Medical Examiner, State of Maryland over a two-year period. Specifically, we identified cases of suicide with a suicide note, the presence of ethanol and the absence of other psychoactive drugs. The BACs ranged from 0.01 to 0.37 g/dL. The average BAC was 0.14 g/dL and the median BAC was 0.13 g/dL. Twenty-five of the 37 cases had a BAC greater than 0.08 g/dL. We conclude that a BAC alone is not sufficient to determine the capability of an individual to form intent to commit a particular act.

Gabapentin-- actions on adult superficial dorsal horn neurons.

Despite identification of GABA(B) receptors with gb1a-gb2 composition and the alpha2delta calcium channel subunit as putative molecular targets for gabapentin (GBP), its cellular mechanism of action has remained elusive. Therefore, we have used an in vitro spinal cord slice preparation to study the effects of GBP on lamina II neurons. The frequency and amplitude of spontaneous EPSCs and IPSCs were unaffected by GBP, suggesting presynaptic neurotransmitter release is not regulated. Direct modulation of postsynaptic membrane excitability is also unlikely since the level of holding current required to maintain neurons at -70, 0 and +45 mV was unaffected by GBP. Effects on excitatory and inhibitory synaptic transmission were variable across the population. Primary afferent-evoked fast glutamatergic EPSCs were unaffected by GBP, while evoked NMDA receptor-mediated EPSCs and IPSCs were variably affected. In contrast, GBP enhanced responses to bath applied NMDA in 71% of neurons. Thus, in adult rat dorsal horn, synaptic and extrasynaptic NMDA receptors may be differentially regulated by GBP perhaps due to differences in subunit composition.

A water-soluble synthetic spicamycin derivative (San-Gly) decreases mechanical allodynia in a rodent model of neuropathic pain.

The goal of this study was to examine the effects of synthetic spicamycin derivative, SAN-Gly, on mechanical allodynia in a spared nerve injury animal model of neuropathic pain. Adult male rats underwent surgical ligation and cutting of the common peroneal and tibial nerves, which produced a mechanical allodynia within 2-4 days. One week after the surgery, SAN-Gly was administered via intravenous injection. Mechanical allodynia was measured using von-Frey hairs. Spicamycin produced a significant reduction in mechanical allodynia for up to 6 weeks. This study demonstrates that SAN-Gly may be of potential use in treating patients with neuropathic pain.

Assessment of the acuteness of heroin deaths from the analysis of multiple blood specimens.

Data was compiled from 126 morphine-involved cases investigated by the Office of the Chief Medical Examiner, State of Maryland, USA. An investigation was conducted into whether comparison of morphine concentrations from a central and peripheral site could be used to determine whether a morphine death was acute or delayed. Fifty cases were identified as 'acute' because the urine free morphine concentration by radioimmunoassay (RIA) was less than 25 ng/mL; 76 cases were classified as 'random' because they had a urine morphine concentration greater than 25 ng/mL by RIA. The average heart blood to peripheral blood morphine concentration ratio in the acute deaths was 1.40. The average heart blood to peripheral blood morphine concentration ratio in the random deaths was 1.18. Because there was considerable overlap between the two groups of data, the authors conclude that it was not possible to predict 'acute' opiate intoxication deaths versus 'delayed' deaths when the only information available is heart and peripheral blood free morphine concentrations.

The AFT024 stromal cell line supports long-term ex vivo maintenance of engrafting multipotent human hematopoietic progenitors.

The immortalized murine stromal cell line AFT024 has been reported to maintain human hematopoietic progenitors in an undifferentiated state in vitro. In the current studies the beige/nude/xid (bnx) mouse in vivo xenograft model was used to examine the engraftment and multilineage generative potential of human hematopoietic progenitors after 2-3 weeks growth on AFT024 stroma, in comparison to primary stromal monolayers derived from post-natal human bone marrow. Eight to 12 months after transplantation of human CD34+CD38- cells from umbilical cord blood, cultured on AFT024 vs human stroma for 2-3 weeks, the murine bone marrow was harvested and analyzed for the presence of human myeloid and lymphoid cells. The mean percent engraftment of total human hematopoietic cells in the murine marrow was significantly higher after co-cultivation on AFT024 than on human stroma. Human myeloid and lymphoid lineage cells were detected in all mice. However, engraftment of myeloid lineage cells (CD33+), B lymphoid (CD19+), and T lymphoid cells (CD4+and CD8+) were significantly higher after co-cultivation of the human cells on AFT024 than on human stroma, prior to transplantation. Interestingly, the length of time in culture did not significantly affect the engraftment of the myeloid and T lymphoid lineage progenitors, but the percentage of B lymphoid lineage engraftment decreased significantly between 2 and 3 weeks of co-cultivation on both types of stroma. Cells with a primitive phenotype (CD45+/CD34-/CD38- and CD45+/CD34-/lin-) and cells with the capacity to generate secondary human CFU after recovery from the bnx bone marrow were maintained at significantly higher levels during culture on AFT024 stroma than on human stroma. The current studies demonstrate that the AFT024 murine stromal cell line supports the ex vivo survival and maintenance of human hematopoietic progenitors that are capable of long-term multilineage reconstitution for 2-3 weeks ex vivo, to levels superior to those that can be obtained using human stromal cells.

Urine concentrations of ketamine and norketamine following illegal consumption.

Ketamine, an anesthetic agent primarily used in veterinary medicine and pediatrics, continues to gain in popularity in the drug abuse scene or 'Rave Wave' of all-night dance clubs. The Division of Forensic Toxicology Laboratory (Office of the Armed Forces Medical Examiner) at the Armed Forces Institute of Pathology, as the primary analytical laboratory for criminal investigative agencies in the Department of Defense (DOD), has seen requests for ketamine analysis rise from 1 in 1997 to 116 in 2000. This increasing abuse has led the DOD Urine Drug Testing Laboratories to consider adding ketamine screening to their random urinalysis program. However, before ketamine testing can be implemented as standard policy, concentrations of ketamine and metabolites in urine need to be evaluated after actual drug use. There is very little information regarding the pharmacokinetics of ketamine, especially concentrations of the drug or its two major metabolites, norketamine and dehydronorketamine, that can be expected in urine. In fact, dehydronorketamine has been believed to be an analytical artifact caused by the high temperatures of gas chromatography. In this paper, we attempt to resolve this issue with the development of a liquid chromatography-mass spectrometry (LC-MS) method. The urine concentrations of ketamine, norketamine and dehydronorketamine (presumptive) detected in 33 "positive" cases received in our laboratory since 1998 are reported. Quantitations were accomplished with LC-MS. Ketamine concentrations ranged from 6 to 7744 ng/mL. Norketamine concentrations ranged from 7 to 7986 ng/mL and dehydronorketamine (presumptive) concentrations ranged from 37 to 23,239 ng/mL.

Community-acquired methicillin-resistant Staphylococcus aureus in a rural American Indian community.

CONTEXT: Until recently, methicillin-resistant Staphylococcus aureus (MRSA) infections have been acquired primarily in nosocomial settings. Four recent deaths due to MRSA infection in previously healthy children in the Midwest suggest that serious MRSA infections can be acquired in the community in rural as well as urban locations. OBJECTIVES: To document the occurrence of community-acquired MRSA infections and evaluate risk factors for community-acquired MRSA infection compared with methicillin-susceptible S aureus (MSSA) infection. DESIGN: Retrospective cohort study with medical record review. SETTING: Indian Health Service facility in a rural midwestern American Indian community. PATIENTS: Patients whose medical records indicated laboratory-confirmed S aureus infection diagnosed during 1997. MAIN OUTCOME MEASURES: Proportion of MRSA infections classified as community acquired based on standardized criteria; risk factors for community-acquired MRSA infection compared with those for community-acquired MSSA infection; and relatedness of MRSA strains, determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Of 112 S aureus isolates, 62 (55%) were MRSA and 50 (45%) were MSSA. Forty-six (74%) of the 62 MRSA infections were classified as community acquired. Risk factors for community-acquired MRSA infections were not significantly different from those for community-acquired MSSA. Pulsed-field gel electrophoresis subtyping indicated that 34 (89%) of 38 community-acquired MRSA isolates were clonally related and distinct from nosocomial MRSA isolates found in the region. CONCLUSIONS: Community-acquired MRSA may have replaced community-acquired MSSA as the dominant strain in this community. Antimicrobial susceptibility patterns and PFGE subtyping support the finding that MRSA is circulating beyond nosocomial settings in this and possibly other rural US communities.

Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota, 1996-1998.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged among patients in the general population who do not have established risk factors for MRSA. Records from 10 Minnesota health facilities were reviewed to identify cases of MRSA infection that occurred during 1996-1998 and to identify which cases were community acquired. Susceptibility testing and pulsed-field gel electrophoresis (PFGE) subtyping were performed on available isolates. A total of 354 patients (median age, 16 years) with community-acquired MRSA (CAMRSA) infection were identified. Most case patients (299 [84%]) had skin infections, and 103 (29%) were hospitalized. More than 90% of isolates were susceptible to all antimicrobial agents tested, with the exception of beta-lactams and erythromycin. Of 334 patients treated with antimicrobial agents, 282 (84%) initially were treated with agents to which their isolates were nonsusceptible. Of 174 Minnesota isolates tested, 150 (86%) belonged to 1 PFGE clonal group. CAMRSA infections were identified throughout Minnesota; although most isolates were genetically related and susceptible to multiple antimicrobials, they were generally nonsusceptible to initial empirical therapy.

Factors associated with self-reported pneumococcal immunization among adults 65 years of age or older in the Minneapolis-St. Paul metropolitan area.

BACKGROUND: As part of a 3-year demonstration project to improve pneumococcal polysaccharide vaccine (PPV) coverage among older adults, the Minnesota Department of Health conducted a baseline evaluation of knowledge, attitudes, and beliefs among the general public regarding PPV. METHODS: A random-digit dialing telephone survey was conducted among community-dwelling adults age 65 years or older in three metropolitan counties in Minnesota during April through June 1998. RESULTS: Three hundred fifty-three interviews were completed; self-reported PPV coverage was 59% (95% CI 54%, 64%). Nearly all (94%) respondents reported at least one medical visit in the past year. Unvaccinated respondents expressed willingness to be vaccinated if they knew about PPV's safety, dosage, and preventive role. In a final multivariate regression model, factors associated with PPV vaccination included awareness of PPV (OR 7.8; CI 2.1, 29.2; P = 0.002), opinion that receiving PPV is "very important" (OR 8.3; CI 3.2, 21.6; P < 0.001), awareness that Medicare covers PPV (OR 5.1; CI 1.9, 13.8; P = 0.001), physician ever offering PPV (OR 21.7; CI 6.2, 76.6; P < 0.001), and physician regularly offering PPV (OR 3.9; CI 1.1, 13.7; P = 0.03). CONCLUSIONS: Respondents were significantly influenced by their physician offering PPV. Therefore, providers' practices are a critical target for improving PPV coverage. Educational efforts to inform patients about PPV and to address misconceptions (e.g., safety, efficacy, Medicare coverage) also may improve vaccination levels.

The detection of psilocin in human urine.

Pharmacokinetic studies of psilocybin in humans have shown the rapid dephosphorylation of psilocybin to psilocin with further conversion to 4-hydroxy-tryptophole (4HT) and 4-hydroxyindole-3-acetic acid (4HIAA) in plasma. Our study shows that psilocin also undergoes conjugation and can be found in the urine as the psilocin-glucuronide conjugate. Recoveries after enzymatic hydrolysis of the urine with beta-glucuronidase (Helix Pomatia or E. Coli) when compared to non-hydrolyzed urine confirmed the presence of the glucuronide. Detection of psilocin from hydrolyzed and extracted samples was optimized for GC/MS by derivatization with MSTFA. The method developed allows for the detection of psilocin in urine with a limit of quantitation of 10 ng/mL, based on 5 mL of spiked urine. Using this method, our laboratory has confirmed the presence of psilocin in 6 out of 8 urine samples, with concentrations ranging from 10 ng/mL to greater than 200 ng/mL. Before implementation of the hydrolysis and derivatization steps, our limit of detection was 200 ng/mL, based on spiked urine standards. No case samples were positive without hydrolysis and derivatization.

Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system.

This report describes stroma-based and stroma-free cultures that maintain long-term engrafting hematopoietic cells for at least 14 days ex vivo. Umbilical cord blood (UCB) CD34(+) cells were cultured in transwells above AFT024 feeders with fetal-liver-tyrosine-kinase (FL) + stem cell factor (SCF) + interleukin 7 (IL-7), or FL + thrombopoietin (Tpo). CD34(+) progeny were transplanted into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice or preimmune fetal sheep. SCID repopulating cells (SRC) with multilineage differentiation potential were maintained in FL-SCF-IL-7 or FL-Tpo containing cultures for up to 28 days. Marrow from mice highly engrafted with uncultured or expanded cells induced multilineage human hematopoiesis in 50% of secondary but not tertiary recipients. Day 7 expanded cells engrafted primary, secondary, and tertiary fetal sheep. Day 14 expanded cells, although engrafting primary and to a lesser degree secondary fetal sheep, failed to engraft tertiary recipients. SRC that can be transferred to secondary recipients were maintained for at least 14 days in medium containing glycosaminoglycans and cytokines found in stromal supernatants. This is the first demonstration that ex vivo culture in stroma-noncontact and stroma-free cultures maintains "long-term" engrafting cells, defined by their capacity to engraft secondary or tertiary hosts. (Blood. 2001;97:3441-3449)

Treatment of endocarditis with valve replacement: the question of tissue versus mechanical prosthesis.

BACKGROUND: It remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis. METHODS: Between 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients. RESULTS: Operative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64). CONCLUSIONS: Mechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity.

Inflammation causes the induction of cyclooxygenase-2 (Cox-2), leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. Peripheral inflammation also generates pain hypersensitivity in neighbouring uninjured tissue (secondary hyperalgesia), because of increased neuronal excitability in the spinal cord (central sensitization), and a syndrome comprising diffuse muscle and joint pain, fever, lethargy and anorexia. Here we show that Cox-2 may be involved in these central nervous system (CNS) responses, by finding a widespread induction of Cox-2 expression in spinal cord neurons and in other regions of the CNS, elevating prostaglandin E2 (PGE2) levels in the cerebrospinal fluid. The major inducer of central Cox-2 upregulation is interleukin-1beta in the CNS, and as basal phospholipase A2 activity in the CNS does not change with peripheral inflammation, Cox-2 levels must regulate central prostanoid production. Intraspinal administration of an interleukin-converting enzyme or Cox-2 inhibitor decreases inflammation-induced central PGE2 levels and mechanical hyperalgesia. Thus, preventing central prostanoid production by inhibiting the interleukin-1beta-mediated induction of Cox-2 in neurons or by inhibiting central Cox-2 activity reduces centrally generated inflammatory pain hypersensitivity.

Direct activation of rat spinal dorsal horn neurons by prostaglandin E2.

Whole-cell patch-clamp and intracellular recording techniques have been used to study the action of prostaglandin E2 (PGE2) on neurons in adult rat transverse spinal cord slices. Bath-applied PGE2 (1-20 microm) induced an inward current or membrane depolarization in the majority of deep dorsal horn neurons (laminas III-VI; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53 cells). PGE2 alone never elicited spontaneous action potentials; however, it did convert subthreshold EPSPs to suprathreshold, leading to action potential generation. PGE2-induced inward currents were unaffected by perfusion with either a Ca(2+)-free/high Mg(2+) (5 mm) solution or tetrodotoxin (1 microm), indicating a direct postsynaptic action. Both 17-phenyl trinor prostaglandin E2 (an EP1 agonist) and sulprostone (an EP3 agonist) had little effect on membrane current, whereas butaprost methyl ester (an EP2 agonist) mimicked the effect of PGE2. Depolarizing responses to PGE2 were associated with a decrease in input resistance, and the amplitude of inward current was decreased as the holding potential was depolarized. PGE2-induced inward currents were reduced by substitution of extracellular Na(+) with N-methyl-d-glucamine and inhibited by flufenamic acid (50-200 microm), which is compatible with activation of a nonselective cation channel. These results suggest that PGE2, acting via an EP2-like receptor, directly depolarizes spinal neurons. Moreover, these findings imply an involvement of spinal cord-generated prostanoids in modulating sensory processing through an alteration in dorsal horn neuronal excitability.