Estrogen-induced increase in the magnitude of long-term potentiation occurs only when the ratio of NMDA transmission to AMPA transmission is increased.

Elevated levels of estradiol enhance learning in mammals, including humans, likely a result of hormone-induced heightened plasticity at CA3-CA1 synapses. The increase in long-term potentiation (LTP) magnitude is considered to be a consequence of the estradiol-induced increase in dendritic spine density and NMDA receptor (NMDAR)-mediated transmission; however, direct evidence linking these changes together is lacking. Alternatively, alterations in GABAergic inhibition or presynaptic release probability could contribute.

Skilled care requirements for elderly patients after coronary artery bypass grafting.

Objectives: To examine the extent to which elderly individuals use various skilled care facilities after coronary artery bypass grafting (CABG).

Design: Retrospective cohort study.

Setting: State of Michigan from 1997 to 1998.

Is breast cancer sentinel lymph node mapping valuable for patients in their seventies and beyond?

Background: Axillary lymph node dissection (ALND) is performed less commonly for the axillary staging of elderly patients because it is felt to uncommonly alter therapy. Sentinel lymph node (SLN) dissection can accomplish axillary staging with less morbidity, but it is unclear if it alters subsequent therapy.

Methods: Review of a prospectively collected breast cancer SLN mapping database.

Negative GABA(A) modulators attenuate the discriminative stimulus effects of benzodiazepines and the neuroactive steroid pregnanolone in rhesus monkeys.

Rationale: Negative GABA(A) modulators (i.e., inverse agonists) might be useful for identifying mechanisms at the GABA(A) receptor complex that mediate the effects of positive GABA(A) modulators, especially those for which there are no available competitive antagonists.

Cross-tolerance and mu agonist efficacy in pigeons treated with LAAM or buprenorphine.

The mechanism responsible for decreased opioid use during opioid substitution therapy is not fully understood. To examine whether l-alpha-acetylmethadol (LAAM) or buprenorphine attenuate behavioral effects of opioids through cross-tolerance, discriminative stimulus effects of high and low efficacy mu agonists were examined following 3- or 7-day treatment with LAAM or buprenorphine in pigeons discriminating between saline and heroin or between saline and buprenorphine, respectively. Heroin, buprenorphine and nalbuphine occasioned high levels of drug-appropriate responding in both groups; kappa opioids and non-opioids occasioned predominantly saline-appropriate responding.

Combined discriminative stimulus effects of midazolam with other positive GABAA modulators and GABAA receptor agonists in rhesus monkeys.

Rationale: Interactions among compounds at GABA(A) receptors might have important implications for the therapeutic and other effects of positive GABA(A) modulators (e.g. benzodiazepines).

Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70.

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.

Monoaminergic drugs and directly observable signs of LAAM withdrawal in rhesus monkeys.

Monoaminergic ligands modified a naltrexone discriminative stimulus in rhesus monkeys dependent on 2 mg/kg per day of the mu opioid L-alpha-acetylmethadol (LAAM). This study examined a role for monoamines in the directly observable and physiologic manifestations of LAAM withdrawal induced by naltrexone in the same monkeys. The effects of saline, clonidine (0.

Lymphoma creating colojejunal fistula: report of a case and review of the literature.

Malignant fistula of the colon to the small bowel is rare and is most often due to adenocarcinoma. Colonic lymphoma is unusual, representing only 0.5 percent of all colonic malignancies.

Inez Beverly Prosser and the education of African Americans.

Inez Beverly Prosser (ca. 1895-1934) was arguably the first African American woman to earn a doctorate in psychology. Her dissertation, completed in 1933, examined personality differences in black children attending either voluntarily segregated or integrated schools and concluded that black children were better served in segregated schools.

Systematic review: effects of resident work hours on patient safety.

Background: The Accreditation Council for Graduate Medical Education (ACGME) mandated new work hours rules for all residency programs in July 2003.

Purpose: To critically evaluate the evidence that adhering to the ACGME standards will improve patient safety.

Data Sources: Searches of electronic databases (MEDLINE, EMBASE, PREMEDLINE, and Current Contents) and other methods to identify the English-language literature for studies on resident work hours for the years 1966 to 2004.

A novel sickle hemoglobin: hemoglobin S-south end.

Sickle hemoglobin (Hb S; beta Glu6Val) is due to an A View Article and Find Full Text PDF

Farnesylthiosalicylic acid inhibits mammalian target of rapamycin (mTOR) activity both in cells and in vitro by promoting dissociation of the mTOR-raptor complex.

The mammalian target of rapamycin (mTOR) functions with raptor and mLST8 in a signaling complex that controls rates of cell growth and proliferation. Recent results indicate that an inhibitor of the Ras signaling pathway, farnesylthiosalicylic acid (FTS), decreased phosphorylation of the mTOR effectors, PHAS-I and S6K1, in breast cancer cells. Here we show that incubating 293T cells with FTS produced a stable change in mTOR activity that could be measured in immune complex kinase assays using purified PHAS-I as substrate.

Wegener's granulomatosis in pregnancy: a novel approach to management.

Wegener's granulomatosis rarely is diagnosed in women of childbearing age and is, thus, uncommonly encountered in pregnancy. Although conventional treatment with steroids and cyclophosphamide controls disease activity in 90% of patients, the associated teratogenicity of such a regimen warrants careful consideration in pregnancy. We describe successful remission induction with the use of intravenous immunoglobulin and steroids alone in a woman diagnosed with de novo Wegener's granulomatosis during the first trimester of pregnancy.

Effects of different dialysis membranes on serum concentrations of epoetin alfa, darbepoetin alfa, enoxaparin, and iron sucrose during dialysis.

Background: Numerous substances are administered during dialysis for anticoagulation and the treatment of anemia and iron deficiency. The availability of current dialysis membranes is diverse, but assessment of the effects of different membranes on these routinely administered substances is lacking. This prospective study appraises specific effects of 7 dialysis membranes (4 low-flux membranes, 3 high-flux membranes) on the handling of 4 commonly administered agents (epoetin alfa, darbepoetin alfa, enoxaparin, and iron sucrose) during dialysis.

Novel approaches to models of Alzheimer's disease pathology for drug screening and development.

Development of therapeutics for Alzheimer's disease (AD) requires appropriate cell culture models that reflect the errant biochemical pathways and animal models that reflect the pathological hallmarks of the disease as well as the clinical manifestations. In the past two decades AD research has benefited significantly from the use of genetically engineered cell lines expressing components of the amyloid-generating pathway, as well as from the study of transgenic mice that develop the pathological hallmarks of the disease, mainly neuritic plaques. The choice of certain cell types and the choice of mouse as the model organism have been mandated by the feasibility of introduction and expression of foreign genes into these model systems.

Haemoglobin response to subcutaneous versus intravenous epoetin alfa administration in iron-replete haemodialysis patients.

Background: Numerous prior studies have reported that a substantially higher dose of epoetin is required to maintain haemoglobin (Hb) concentration when patients are switched from a subcutaneous (s.c.) to intravenous (i.

mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways.

Loss of PTEN function leads to activation of phosphoinositide 3-kinase (PI3K) signaling and Akt. Clinical trials are now testing whether mammalian target of rapamycin (mTOR) inhibition is useful in treating PTEN-null cancers. Here, we report that mTOR inhibition induced apoptosis of epithelial cells and the complete reversal of a neoplastic phenotype in the prostate of mice expressing human AKT1 in the ventral prostate.

Development, prevention, and potential reversal of left ventricular hypertrophy in chronic kidney disease.

Although a high prevalence of left ventricular (LV) hypertrophy is recognized with increasing severity of chronic kidney disease (CKD), previously neither its progression nor its potential for prevention or reversal has been addressed adequately in this population group. A nested analysis of a 2-yr study involving 155 patients with stage 3/4 CKD, examining effects of hemoglobin change (range, 90 to 130 g/L) on LV mass in patients with (n = 46; 30%) and without (n = 105; 70%) initial LV hypertrophy, is reported. At baseline, the group with LV hypertrophy was older (P < 0.

What effect does inpatient physician specialty and experience have on clinical outcomes and resource utilization on a general medical service?

Objective: To examine the effects of internal medicine specialty and physician experience on inpatient resource use and clinical outcomes on an academic general medicine service.

Design: A 1-year retrospective cohort study.

Setting: The University of Michigan Hospitals, Ann Arbor, Michigan.