Dynamic endocrine testing. The Mayo Clinic model

An endocrine testing center (ETC) is a universal requirement for the practice of endocrinology. Modifications of the Mayo Clinic model for an ETC should be applicable to most endocrine practices. Key components of an ETC include a centralized testing area, registered nurse-physician team, detailed testing protocols, and patient education programs.     

Tyrosine hydroxylase expression in primary cultures of olfactory bulb: role of L-type calcium channels

Sensory activity mediates regulation of tyrosine hydroxylase (TH), the first enzyme in the dopamine biosynthetic pathway, in the rodent olfactory bulb. The current studies established for the first time primary cultures of neonatal mouse olfactory bulb expressing TH and tested whether L-type calcium channels mediate the activity-dependent regulation of the dopamine phenotype. After 1 d in vitro (DIV), a small population of TH-immunostained neurons that lacked extensive processes could be demonstrated. After an additional 2 DIV in serum-free medium, the number of TH neurons had doubled, and they exhibited long interdigitating processes. Membrane depolarization for 48 hr with 50 mM KCl produced a further 2.4-fold increase in the number of TH-immunoreactive neurons compared with control cultures. Increased TH neuron number required at least 36 hr of exposure to KCl. Forskolin, which increases intracellular cAMP levels, induced a 1.5- to 1.6-fold increase in the number of TH-immunostained neurons. Combined treatment with KCl and forskolin was not additive. Nifedipine, an L-type calcium channel blocker, completely prevented the depolarization-mediated increase in TH expression but did not block the response to forskolin. Treatment with Bay K8644, an L-type calcium channel agonist, also significantly increased the number of TH-expressing neurons. Depolarization also induced alterations in neuritic outgrowth, resulting in a stellate versus an elongate morphology that, in contrast, was not prevented by nifedipine. These results are the first demonstration that in vitro, as in vivo, depolarization increases TH expression in olfactory bulb and that L-type calcium channels mediate this activity-dependent regulation of the dopamine phenotype.     

Formulation for Reliable Analysis of Structural Frames

Structural engineers use design codes formulated to consider uncertainty for both reinforced concrete and structural steel design. For a simple one-bay structural steel frame, we survey typical uncertainties and compute an interval solution for displacements and forces. The naive solutions have large over-estimations, so we explore the Mullen-Muhanna assembly strategy, scaling, and constraint propagation to achieve tight enclosures of the true ranges for displacements and forces in a fraction of the CPU time typically used for simulations. That we compute tight enclosures, even for large parameter uncertainties used in practice, suggests the promise of interval methods for much larger structures.     

Epidemiology of Trauma and Posttraumatic Stress Disorder in Mexico.

Prevalence rates of trauma and posttraumatic stress disorder (PTSD) were estimated from a probability sample of 2,509 adults from 4 cities in Mexico. PTSD was assessed according to Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) criteria using the Composite International Diagnostic Interview (CIDI; WHO, 1997). Lifetime prevalence of exposure and PTSD were 76% and 11.2%, respectively. Risk for PTSD was highest in Oaxaca (the poorest city), persons of lower socioeconomic status, and women. Conditional risk for PTSD was highest following sexual violence, but nonsexual violence and traumatic bereavement had greater overall impact because of their frequency. Of lifetime cases, 62% became chronic; only 42% received medical or professional care. The research demonstrates the importance of expanding the epidemiologic research base on trauma to include developing countries around the world. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physical and chemical characteristics of butterfat fractions obtained by crystallization from molten fat

Both summer and winter butterfats were fractionated using a laboratory procedure which was designed to simulate a commercial fractionation process. The process is based on a slow, controlled cooling of the melted fat, a short stabilization time at the fractionation temperature, and separation of the crystals from the liquid oil by vacuum filtration using a stainless steel perforated disc. Fractionation temperatures of 29, 26, 23 and 19 C for winter butterfat and 29 and 19 C for summer butterfat were used to obtain solid and liquid fractions at each temperature. Three replications at each temperature showed good reproducibility of results. The fractions were characterized by their fatty acid and triglyceride compositions, melting and crystallization behavior, iodine value, peroxide value and melting point. Presented at the AOCS meeting in Philadelphia in May 1985.     

Netted radar sensitivity and ambiguity

The performance of netted radar is evaluated in terms of a netted version of the radar equation and the ambiguity function. A software simulation has been developed to allow assessment of netted radar sensitivity and ambiguity properties in both two-and three-dimensional space. Simulation results demonstrate that coherent netted radar sensitivity depends not only on the radar parameters, but also on the numbers, locations and specification of transmit and receive nodes. The netted radar ambiguity function is affected by a combination of many factors. In addition to those that determine the form of the monostatic ambiguity function, the locations of transmit and receive nodes as well as the position and velocity of the target all are shown to play an important role in evaluating system performance. As a result of these dependencies, it is shown that there is severe degradation of range and Doppler resolution when a target crosses sufficiently close to a transmit-receive baseline.     

Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.     

Pharmacokinetics of dolasetron after oral and intravenous administration of dolasetron mesylate in healthy volunteers and patients with hepatic dysfunction

In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III). Single 150-mg doses of dolasetron mesylate were administered intravenously and orally, with a 7-day washout period separating treatments. After intravenous administration, no differences were observed between healthy volunteers and patients with hepatic impairment in maximum plasma concentration (Cmax), areas under the plasma concentration-time curve (AUC), or elimination half-life (t1/2) of intact dolasetron. No significant differences were found in Cmax, AUC, or apparent clearance (C(lapp)) of hydrodolasetron, the primary metabolite of dolasetron. The mean t1/2 increased from 6.87 hours in group I to 11.69 hours in group III. After oral administration, C(lapp) of hydrodolasetron decreased by 42%, and Cmax increased by 18% in patients with moderate to severe hepatic impairment. There were less changes in patients with mildly hepatic impairment. Total percentage of dose excreted as metabolites was similar for healthy volunteers and patients with hepatic impairment, although urinary metabolite profiles differed slightly. Dolasetron was well tolerated and there were no apparent differences in adverse effects between groups or treatments. Because hepatic impairment did not influence Cl(app) of hydrodolasetron after intravenous administration, and the range of plasma concentrations of hydrodolasetron after oral administration was not different from those observed in healthy volunteers, dosage adjustments are not recommended for patients with hepatic disease and normal renal function.