Readmissions Following Endovascular Thoracic and Thoracoabdominal Aortic Repairs in The Vascular Implant Surveillance and Interventional Outcomes Network (VISION).

OBJECTIVES: Investigate readmission rates, diagnoses associated with readmission, and associations with mortality through 90-days post-operatively after elective endovascular thoracic and thoracoabdominal aortic repair overall and by extent of coverage. METHODS: A cohort of index elective non-traumatic endovascular thoracic and thoracoabdominal aortic cases from 2010-2018 was derived from the Vascular Implant Surveillance and Interventional Outcomes Network. Cohort readmissions within 90-days postoperative were examined both overall and by Crawford extent (CE) of aortic coverage. Postoperative mortality was examined by reason for readmission and CE. RESULTS: The cohort consisted of 2,093 patients who underwent endovascular thoracic and thoracoabdominal aortic repair (1,541 CE 0A/0B; 240 CE 1-3; 312 CE 4-5). Cumulative risk for 90-day readmission was 34.3% in CE 0A/0B repairs, 33.4% in CE4-5 repairs and 47.4% in CE 1-3 repairs. Compared to CE 0A/B, patients with CE 1-3 repairs experienced an increased risk of readmission within 90 days postoperatively after adjusting for preoperative factors (aHR 1.27(1.00,1.61) while the readmission risk for CE 4-5 repairs did not differ significantly (aHR 0.83 (0.64,1.06). Significant risk factors for 90-day readmission included COPD, dialysis dependence, limited ambulation, visceral/spinal ischemia, and in-hospital stroke. Discharge to home was protective against readmission (HR 0.65, CI 0.54-0.79). Patients with a readmission within 90-days had a 7.89-fold increase in 90-day mortality (HR 7.84; 5.17, 11.9) compared to those not readmitted. CONCLUSIONS: Increasing extent of endovascular thoracic and thoracoabdominal aortic repair was associated with higher 90-day readmission rates. Readmission for all CE was associated with near 8-fold increased risk of mortality. Risk factors associated with increased risk for readmission included pulmonary insufficiency, renal disease, and poor functional status. These findings can inform stakeholders about investment of resources to improve processes of care that both target prevention and mitigate risk of readmission after elective endovascular thoracic and thoracoabdominal aortic repair.

Evaluation of bone marrow aspirates from multiple sites for staging of canine lymphoma and mast cell tumours.

This prospective study evaluated the utility of bone marrow aspirates (BMAs) obtained from multiple sites for staging of canine lymphoma (LSA) and mast cell tumours (MCTs). Forty dogs (LSA, n = 24; MCTs, n = 16) were enrolled, but only 33 (82.5%) had diagnostic bone marrow (BM) aspirates obtained from two sites for inclusion in the study. Nineteen dogs with LSA were included, and 6 (31.6%) had BM involvement. Neoplastic lymphocytes were present in BM from both sites in all of these dogs. Fourteen dogs with MCTs were included, and 3 (21.4%) had BM involvement. Neoplastic mast cells were present at both sites in two dogs and at only one site in the third. These results indicate that BMAs from multiple sites may not be needed for accurate staging of canine LSA patients, but more studies evaluating the pattern of BM infiltration in dogs with high-grade MCTs are warranted.

The effects of age and lipopolysaccharide (LPS)-mediated peripheral inflammation on numbers of central catecholaminergic neurons.

Parkinson's disease (PD), an age-related movement disorder, is characterized by severe catecholaminergic neuron loss in the substantia nigra pars compacta (SN(PC))-ventral tegmental area (VTA) and locus coeruleus (LC). To assess the stability of these central catecholaminergic neurons following an acute episode of severe inflammation, 6 to 22 month old C57/Bl6 mice received a maximally tolerated dose of lipopolysaccharide (LPS) followed by euthanasia 2 hours later to assay peak levels of peripheral and central cytokines; and, 14 weeks later for computerized stereology of tyrosine hydroxylase-immunopositive (tyrosine hydroxylase-positive [TH+]) neurons in the SN(PC)-VTA and LC. Two hours after LPS, cytokine levels varied in an age-related manner, with the greatest peripheral and central elevations in old and young mice, respectively. Severe inflammation failed to cause loss of TH+ neurons in SN(PC)-VTA or LC; however, there was an age-related decline in these TH+ neurons in LPS-treated and control groups. Thus, unknown mechanisms in the B6 mouse brain appear to protect against catecholaminergic neuron loss following an acute episode of severe inflammation, while catecholaminergic neuron loss occurs during normal aging.

Dissection of corticotropin-releasing factor system involvement in locomotor sensitivity to methamphetamine.

Sensitivity to the euphoric and locomotor-activating effects of drugs of abuse may contribute to risk for excessive use and addiction. Repeated administration of psychostimulants such as methamphetamine (MA) can result in neuroadaptive consequences that manifest behaviorally as a progressive escalation of locomotor activation, termed psychomotor sensitization. The present studies addressed the involvement of specific components of the corticotropin-releasing factor (CRF) system in locomotor activation and psychomotor sensitization induced by MA (1, 2 mg/kg) by utilizing pharmacological approaches, as well as a series of genetic knockout (KO) mice, each deficient for a single component of the CRF system: CRF-R1, CRF-R2, CRF, or the CRF-related peptide Urocortin 1 (Ucn1). CRF-R1 KO mice did not differ from wild-type mice in sensitization to MA, and pharmacological blockade of CRF-R1 with CP-154,526 (15, 30 mg/kg) in DBA/2J mice did not selectively attenuate either the acquisition or expression of MA-induced sensitization. Deletion of either of the endogenous ligands of CRF-R1 (CRF, Ucn1) either enhanced or had no effect on MA-induced sensitization, providing further evidence against a role for CRF-R1 signaling. Interestingly, deletion of CRF-R2 attenuated MA-induced locomotor activation, elucidating a novel contribution of the CRF system to MA sensitivity, and suggesting the participation of the endogenous urocortin peptides Ucn2 and Ucn3. Immunohistochemistry for Fos was used to visualize neural activation underlying CRF-R2-dependent sensitivity to MA, identifying the basolateral and central nuclei of the amygdala as neural substrates involved in this response. Our results support further examination of CRF-R2 involvement in neural processes associated with MA addiction.

Multicentric cutaneous neuroendocrine (Merkel cell) carcinoma in a dog.

Multicentric cutaneous neuroendocrine (Merkel cell) carcinoma was diagnosed in a 5-year-old castrated male Keeshond dog with multiple firm nodular cutaneous masses. The neoplastic tissue locally effaced the periadnexal and deep dermis and consisted of densely cellular confluent clusters of round to polygonal cells supported by a delicate fibrovascular stroma. The cells were moderately immunoreactive with chromogranin A, synaptophysin, and cytokeratin. Ultrastructurally, the cells had characteristic membrane-bound dense-core neuroendocrine granules approximately 120 nm in diameter and randomly dispersed throughout the cytoplasm. Effacement of dermal structures and multicentric distribution suggested low-grade malignant phenotype. These findings contrast with the typical benign behavior of canine cutaneous neuroendocrine tumors.

Differential sensitivity of the perioculomotor urocortin-containing neurons to ethanol, psychostimulants and stress in mice and rats.

The perioculomotor urocortin-containing population of neurons (pIIIu: otherwise known as the non-preganglionic Edinger-Westphal nucleus) is sensitive to alcohol and is involved in the regulation of alcohol intake. A recent study indicated that this brain region is also sensitive to psychostimulants. Since pIIIu has been shown to respond to stress, we investigated how psychostimulant-induced pIIIu activation compares to stress- and ethanol-induced activation, and whether it is independent from a generalized stress response. Several experiments were performed to test how the pIIIu responds to psychostimulants by quantifying the number of Fos immunoreactive nuclei after acute i.p. injections of saline, 10-30 mg/kg cocaine, 5 mg/kg methamphetamine, 5 mg/kg amphetamine, 2.5 g/kg ethanol, 2 h of restraint stress, 10 min of swim stress, or six applications of mild foot shock in male C57BL/6 J mice. We also compared Fos immunoreactivity in pIIIu after acute (20 mg/kg cocaine) and repeated cocaine exposure (7 days of 20 mg/kg cocaine) injections in male C57BL/6 J mice in order to investigate the potential habituation of this response. Finally, we quantified the number of Fos immunoreactive nuclei in pIIIu after administration of saline, 2.5 g/kg ethanol, 20 mg/kg cocaine, or 2 h of restraint stress in male Sprague-Dawley rats. We found that exposure to psychostimulants and ethanol induced significantly higher Fos levels in pIIIu compared to stress in mice. Furthermore, repeated cocaine injections did not decrease Fos immunoreactivity as would be expected if this response were due to stress. In rats, exposure to ethanol, psychostimulant and restraint stress all induced pIIIu Fos immunoreactivity compared to saline-injected controls. In both mice and rats, ethanol- and cocaine-induced Fos immunoreactivity occurred exclusively in urocortin 1-positive, but not in tyrosine hydroxylase-positive, cells. These results provide evidence that the pIIIu Fos-response to psychostimulants is independent of a generalized stress in mice, but not rats. They additionally show that the pIIIu response to stress differs significantly between species.

Efficient copackaging and cotransport yields postsynaptic colocalization of neuromodulators associated with synaptic plasticity.

Recent data suggest that tissue plasminogen activator (tPA) influences long-term plasticity at hippocampal synapses by converting plasminogen into plasmin, which then generates mature brain-derived neurotrophic factor (mBDNF) from its precursor, proBDNF. Motivated by this hypothesis, we used fluorescent chimeras, expressed in hippocampal neurons, to elucidate (1) mechanisms underlying plasminogen secretion from hippocampal neurons, (2) if tPA, plasminogen, and proBDNF are copackaged and cotransported in hippocampal neurons, especially within dendritic spines, and (3) mechanisms mediating the transport of these neuromodulators to sites of release. We find that plasminogen chimeras traffic through the regulated secretory pathway of hippocampal neurons in dense-core granules (DCGs) and that tPA, plasminogen, and proBDNF chimeras are extensively copackaged in DCGs throughout hippocampal neurons. We also find that 80% of spines that contain DCGs contain chimeras of these neuromodulators in the same DCG. Finally, we demonstrate, for the first time, that neuromodulators undergo cotransport along dendrites in rapidly mobile DCGs, indicating that neuromodulators can be efficiently recruited into active spines. These results support the hypothesis that tPA mediates synaptic activation of BDNF by demonstrating that tPA, plasminogen, and proBDNF colocalize in DCGs in spines, where these neuromodulators can undergo activity-dependent release and then interact and/or mediate changes that influence synaptic efficacy. The results also raise the possibility that frequency-dependent changes in extents of neuromodulator release from DCGs influence the direction of plasticity at hippocampal synapses by altering the relative proportions of two proteins, mBDNF and proBDNF, that exert opposing effects on synaptic efficacy.

Association of obesity with tumor characteristics and treatment failure of prostate cancer in African-American and European American men.

PURPOSE: The impact of body mass index on tumor characteristics and treatment failure in prostate cancer is not well understood in diverse ethnic groups. We evaluated the effect of body mass index in African-American and European American patients from a radical prostatectomy cohort between 1995 and 2004 with regard to tumor histopathological characteristics and biochemical relapse-free survival. MATERIALS AND METHODS: A total of 924 patients were studied to evaluate whether obese men (body mass index greater than 30) had different preoperative and postoperative tumor characteristics or biochemical relapse-free survival compared to nonobese men. There were 784 European American and 140 African-American patients analyzed using failure time models, adjusted for age, preoperative prostate specific antigen, tumor stage and race. RESULTS: Mean and median followup was 42 and 36 months, respectively. African-American men were significantly more obese than European American men. Mean body mass index was 29.0 in African-American and 28.1 in European American men (p = 0.003). African-American men (OR 2.30, 95% CI 1.04-5.1) were more likely to have higher tumor stage on final pathology. Obesity was a risk factor for biochemical failure in African-American men (adjusted hazard ratio 5.49, 95% CI 2.16-13.9) but not in European American men (HR 1.41, 95% CI 0.96-2.08), and this difference was statistically significant (p value for interaction 0.036). CONCLUSIONS: Obesity is associated with poorer tumor prognostic characteristics and decreased biochemical relapse-free survival, particularly in African-American men. These data suggest that obesity may in part explain the poorer prostate cancer prognosis seen in African-American men compared to other racial and ethnic groups.

Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors.

Genetic factors may be used not only to assess risk of prostate cancer development but also to evaluate prostate cancer outcomes including clinical prognosis, treatment methods, and treatment response. To assess the role of family history on prostate cancer outcomes, we evaluated tumor characteristics, diagnostic precursors and biochemical (prostate specific antigen) relapse-free survival in men with and without a family history of prostate cancer. A total of 684 prostate cancer cases unselected for family history were identified from an ongoing hospital based prostate cancer case-control study between 1995 and 2002. Self-reported family history was grouped within the following categories: none, any, moderate (one affected first or second degree relative) and high (2 or more affected first or second degree relatives). We further considered groups defined by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor stage was not significantly associated with any (odds ratio [OR] = 1.43 95% confidence interval [CI] = 1.00-2.05) or moderate (OR = 1.48, 95% CI = 1.0-2.19) family histories. Men diagnosed before age 60, however, had higher tumor stages if they had any (OR = 2.19, 95% CI = 1.28-3.75) or moderate (OR = 2.15, 95% CI = 1.2-3.9) family histories. Men diagnosed after age 60 with any family history were significantly more likely to experience biochemical (PSA) failure (Hazard ratio [HR] = 2.60, 95%CI = 1.08-6.25). Men with any and moderate family histories were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI = 1.25-4.95 and HR = 2.46, 95% CI = 1.17-5.16, respectively). Moderate family history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI = 1.06-4.34). Our results suggest that a family history of prostate cancer may be associated with predictors of clinical outcome in prostate cancer cases unselected for a family history of prostate cancer.

Clinical characteristics of prostate cancer in African Americans, American whites, and Senegalese men.

OBJECTIVES: To describe the clinical features of prostate cancer in Senegalese men and compare these features with those found in African-American and white American men. METHODS: We identified an unselected series of 121 patients with prostate cancer diagnosed at two hospitals in Dakar, Senegal between 1997 and 2002. Medical record abstractions were undertaken to evaluate the prostate tumor characteristics, patient age at diagnosis, prostate-specific antigen (PSA) levels, and reason for referral. In addition, these characteristics were compared with a sample of 455 U.S. white men and 60 African-American men with prostate cancer who were studied as part of a prostate cancer case-control study. RESULTS: Senegalese men had a significantly worse tumor stage than Americans (41.3% versus 18.8%, P <0.001), a significantly worse mean PSA level at diagnosis (mean PSA 72.7 ng/mL versus 9.0 ng/mL in Americans; P <0.001), and were diagnosed at a significantly later age than U.S. men (69 years versus 61 years, P <0.001). U.S. men were most likely to be diagnosed with prostate cancer after an elevated PSA test, and Senegalese men were most often diagnosed after presenting for prostate-related symptoms. CONCLUSIONS: These observations are not unexpected given the differences in the patterns of prostate cancer screening and health care in the United States compared with Senegal. However, our data provide descriptive information about the characteristics of prostate cancer diagnosed in Senegal and highlight differences in the characteristics and detection of these tumors across populations with very different healthcare systems.

Ethnic differences in the frequency of prostate cancer susceptibility alleles at SRD5A2 and CYP3A4.

OBJECTIVES: Ethnic differences in prostate cancer incidence are well documented, with African-Americans having among the highest rates in the world. Ethnic differences in genotypes for genes associated with androgen metabolism including SRD5A2 and CYP3A4 also may exist. The aim of this study was to evaluate differences in these genotypes by ethnicity. METHODS: We studied cancer-free controls representative of four groups: 147 African Americans, 410 Caucasian-Americans, 129 Ghanaians, and 178 Senegalese. PCR-based genotype analysis was undertaken to identify two alleles (V89L, A49T) at SRD5A2 and *1B allele at CYP3A4. RESULTS: Differences were observed for V89L (variant frequency of 30% in Caucasians, 27% in African Americans, 19% in Ghanaians, and 18% in Senegalese, p = 0.002) and were observed for CYP3A4*1B (variant frequencies of 8% in Caucasians, 59% in African Americans, 81% in Ghanaians, and 78% in Senegalese, p = 0.0001). Pooled data combining the present data and previously published data from from Asian, Hispanic, and Arab cancer-free controls showed significant ethnic differences for SRD5A2 and CYP3A4 polymorphisms. Overall, Asians were least likely to have alleles associated with increased prostate cancer risk, while Africans were most likely to have those alleles. CONCLUSIONS: These results suggest that ethnicity-specific differences in genotype frequencies exist for SRD5A2 and CYP3A4. Africans and African-Americans have the highest frequency of those alleles that have previously been associated with increased prostate cancer risk. Future studies should address whether allele frequency differences in part explain differences in prostate cancer incidence in these populations.

Estimated prevalence of Aerococcus viridans and Anophryoides haemophila in American lobsters Homarus americanus freshly captured in the waters of Prince Edward Island, Canada.

The Canadian lobster industry holds lobsters Homarus americanus in captivity for various periods to supply markets with live product year-round. Mortality during holding results in considerable losses, estimated at 10 to 15 % yr(-1) by the industry. This study examined the prevalence of Anophryoides haemophila and Aerococcus viridans, causative agents of 'bumper car' disease and gaffkemia, respectively, in lobsters freshly captured in the waters of Prince Edward Island during the spring and fall fishing seasons of 1997. A total of 116 lobsters were sampled in the spring, and 138 in the fall. A. haemophila was not detected in the spring, while the prevalence was 0.72 % in the fall with a 95% confidence interval (CI) of 0.02 to 3.97% and an overall prevalence of 0.39% (95% CI: 0.01 to 2.17%). The prevalence of A. viridans was estimated at 6.9% (95% CI: 3.0 to 13.14%) in the spring, 5.8% in the fall (95% CI: 2.54 to 11.10%), and 6.30% overall (95% CI: 3.64 to 10.03%). Because of the reduced interest in food of diseased lobsters, and compromised metabolism in the case of gaffkemia, these prevalence estimates are likely underestimates of the true prevalence of gaffkemia and 'bumper car' disease in the wild populations of lobster around Prince Edward Island.

Coronary Artery Risk Detection in Appalachian Communities (CARDIAC): preliminary findings.

West Virginia's mortality and morbidity from cardiovascular disease (CVD) is among the highest in the developed world. Appalachia, and West Virginia in particular, could reduce the high prevalence of premature coronary heart disease (CHD) by addressing modifiable independent risk factors such as poor nutrition, sedentary lifestyle, and tobacco use. School-based health promotion programs have been shown to be an effective means of influencing student and parental health behavior. The pilot phase of the Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) project substantiated an alarmingly high incidence of CVD risk factors among 347 fifth grade children from three rural counties, and was also an effective means of identifying parents at risk of developing CHD. Utilization of the innovative Rural Health Education Partnerships (WVRHEP), coupled with a health conscious public school system, offers a unique opportunity to establish the first statewide cardiovascular disease community intervention project in the nation.

Involvement of dopamine D(2) receptors in complex maze learning and acetylcholine release in ventral hippocampus of rats.

In the current study we focus on the involvement of dopamine D(2) receptors in the ventral hippocampus in memory performance and acetylcholine release. Using the aversively motivated 14-unit T-maze (Stone maze) the injection of raclopride, a D(2) receptor antagonist, into the ventral hippocampus (8 microg/kg) was found to impair memory performance. Co-injection of quinpirole, a D(2) receptor agonist (8 microg/kg), overcame the impairment in performance. Microdialysis study revealed that quinpirole infusion (10-500 microM) into the ventral hippocampus stimulated acetylcholine release in a dose-dependent manner, and systemic injection of quinpirole (0.5 mg/kg, i.p.) also stimulated acetylcholine release in the ventral hippocampus. Infusion of eticlopride, another D(2) receptor antagonist, into the ventral hippocampus suppressed acetylcholine release in the hippocampus induced by systemic injection of quinpirole. Taken together, we suggest that D(2) receptors in the ventral hippocampus are involved in memory performance, possibly through the regulation of acetylcholine.

Identification of maze learning-associated genes in rat hippocampus by cDNA microarray.

Long-term memory formation requires de novo RNA and protein synthesis. To assess gene-expression changes associated with learning and memory processes, we used cDNA microarray to analyze hippocampal gene expression in male Fischer-344 rats following training in a multiunit T-maze. Here, we report the identification of 28 clones (18 known genes and 10 ESTs) for which expression increased after the maze learning. Some of the known genes appear to be involved in Ca2+ signaling, Ras activation, kinase cascades, and extracellular matrix (ECM) function, which may regulate neural transmission, synaptic plasticity, and neurogenesis. The gene-expression profile presented here provides the groundwork for future, more focused research to elucidate the contribution of these genes in learning and memory processes.

Hemodynamic changes during aging associated with cerebral blood flow and impaired cognitive function.

This study investigates the age associated changes in hemorheological properties and cerebral blood flow. Partial correlations indicate that part of the age-dependent decrease in flow velocities can be attributed to a hemorheological decrement resulting in part from enhanced oxidative stress in the aged. A possible link with Alzheimer's pathology is suggested by the augmented hemorheological impairment resulting from in vitro incubation of red cells with amyloids. These results suggest that in aging, oxidative stress as well as amyloids may influence the fluid properties of blood, resulting in a potential decrement in blood flow and oxygen delivery to the brain. Animal intervention studies further demonstrate that altered hemorheological properties of blood can actually influence cognitive function. The relationships shown to exist between hemorheology, blood flow, amyloids, oxidative stress, and cognitive function suggest that these factors may be one of the mechanisms operating in the complex etiology of Alzheimer's disease.

Meningoencephalitis secondary to bacterial otitis media/interna in a dog.

Central nervous system (CNS) complications of bacterial otitis media/interna are an infrequent occurrence in human patients and have rarely been reported in the veterinary literature. Early recognition of CNS involvement and the use of appropriate diagnostic tests to characterize the nature of the lesion(s) are crucial in determining the best course of treatment. In this paper, the authors describe a dog with bacterial meningoencephalitis secondary to otitis media/interna.

Telomerase enzyme activity as a diagnostic tool to distinguish effusions of malignant and benign origin.

Telomerase enzyme activity is high in populations of cells that are dividing, and is low or undetectable in quiescent cell populations. Activation of telomerase in tissues that normally lack the capacity for self-renewal is strongly correlated with neoplasia. Telomerase activity can be detected in samples containing very small numbers of cells and studies of human patients suggest that measurement of telomerase activity may be useful for the evaluation of samples that can be obtained in a minimally invasive manner. This study compares the presence or absence of telomerase activity with cytologic evaluation of body cavity effusions, to determine if neoplasia is the underlying cause for the effusion in dogs and cats. Detection of telomerase in effusions was no more sensitive than cytologic evaluation for the identification of underlying neoplasia, and was less specific (telomerase assay: sensitivity = 50%, specificity = 83%; cytology: sensitivity = 50%, specificity = 100%). We conclude that although the telomerase assay may constitute a useful adjunctive test for the diagnosis of neoplasia in some dogs and cats with body cavity effusions, the results of this assay are not sufficiently reliable to be used as a sole diagnostic test.

Maze learning impairment is associated with stress hemopoiesis induced by chronic treatment of aged rats with human recombinant erythropoietin.

Mean cell volume (MCV) of erythrocytes has been reported to increase with age in humans, and to be negatively correlated with memory performance in humans and rats. We evaluated hematological changes in 21-mo old male Fischer 344 rats undergoing a 3-mo twice weekly subcutaneous injection of human recombinant erythropoietin (EPO). A baseline hematocrit (HCT) was obtained initially and repeated at monthly intervals to determine the effectiveness of EPO treatment. At 24-mo of age and after 3 mo EPO treatment, the rats were tested for their ability to learn a 14-unit T maze. Following maze testing, blood was drawn for hematologic analyses, including HCT, MCV, maximum swollen cell volume (MCVS), mean cell transit time (MCTT), and the membrane shear modulus of elasticity (G), the latter a derived measure of the relative elasticity of the red cell membrane. After 1 mo EPO treatment, HCT significantly increased compared to saline-injected controls. After 2 mo treatment, HCT began to decline but remained elevated above baseline levels even after 3 mo treatment. After 3 mo EPO treatment, MCV was significantly lower in EPO-treated rats compared to controls. These changes imply altered hemopoiesis to produce cells which undergo shrinkage associated with accelerated cellular aging. The lower MCV would have predicted a shorter MCTT which instead was unchanged. This observation suggested the presence of an additional factor contributing to the MCTT. The G, which measures the membrane contribution to deformability, very significantly increased with EPO treatment. This finding indicates an increased contribution of membrane properties to the MCTT after EPO treatment, which cancels the expected decrease in MCTT for smaller cells. After 3 mo of EPO treatment, aged rats exhibited significantly impaired maze learning compared to controls. A relationship between, changes in erythrocyte membrane properties and impaired function was indicated by a significant correlation (r=0.67, p <0.04) between G and errors in the 14-unit T-maze. These findings suggest that stress-induced erythropoiesis produces accelerated aging in the red blood cell population that may have functional implications (i.e., impaired learning ability).