bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Specialty Care Versus Standard Retail Pharmacies for Treatment of Hepatitis C
Authors: Cohen Stanley Martin , Kwasny Mary J , Ahn Joseph
Published: February 2009

Background:

Treatment for hepatitis C virus (HCV) is associated with significant adverse events. Improved adherence increases the probability of achieving sustained virologic response (SVR). Despite a lack of supporting literature, the use of specialty care pharmacies has increased in recent years in an attempt to improve HCV treatment outcomes.

Objective:

To compare specialty care versus standard retail pharmacies in HCV treatment outcomes, utilization of office resources, and the use of supplemental medications.

Methods:

A retrospective chart review was performed at a single academic institution for adults with HCV infection treated between 2001 and 2006. SVR was the primary endpoint. Secondary endpoints included therapy completion rates, HCV treatment dose reductions, additional phone calls and clinic visits, and the use of supplemental medications.

Results:

One hundred ninety-seven patients were identified (102 standard and 95 specialty care pharmacy). There were no differences in baseline demographics between the groups, except for a higher proportion of African Americans using specialty care pharmacies. Overall SVR was 103/197 (52%). SVR was 57/102 (56%) in the standard pharmacy group and 46/95 (48%) in the specialty care pharmacy group. There were no statistically significant differences with regard to SVR (even after accounting for differences in ethnicity), the use of supplemental medications, additional clinic phone calls and visits required, and the reasons for HCV therapy discontinuation. There was a statistically significantly higher incidence of HCV medication dose reductions in the standard retail pharmacy group (45% vs 28%; p = 0.016).

Conclusions:

The use of specialty care pharmacies for the treatment of HCV was not associated with higher SVR rates. Patients using specialty care pharmacies had a lower incidence of interferon and/or ribavirin dose reductions, but there was no difference between the groups in therapy completion rates, use of additional office resources, or use of supplemental medications.
Racial/Ethnic Disparities in Medication Use Among Veterans with Hypertension and Dementia: A National Cohort Study
Authors: Poon Ivy , Lal Lincy S , Ford Marvella E , Braun Ursula K
Published: February 2009

Background:

Hypertension and comorbid dementia are common illnesses affecting older adults disproportionally. Medication adherence is vital in achieving therapeutic outcomes. Use of antihypertensive and dementia medications may vary by race/ethnicity and has not been well explored.

Objective:

To evaluate the utilization of antihypertensive and dementia drugs and adherence in a national cohort of veterans aged 65 years or older with a diagnosis of both hypertension and dementia across different racial/ethnic groups.

Methods:

This was a retrospective cohort study that used 2 national databases of the Veterans Health Administration to estimate medication utilization and adherence rates among whites, African Americans, and Hispanics from 2000 to 2005. A medication possession ratio of 0.8 or greater defined adherence. The association between race/ethnicity and adherence was analyzed using multivariate logistic regression analysis.

Results:

A total of 56,561 patients (70.5% white, 15.6% African American, 6.6% Hispanic) aged 65 years or older had diagnoses of dementia and hypertension. African Americans were less likely than whites to receive angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers, acetylcholinesterase inhibitors, and memantine (p < 0.05). Hispanics were more likely than whites to be prescribed an ACE inhibitor and less likely to be prescribed an ARB, β-blocker, nondihydropyridine calcium-channel blocker (CCB), loop diuretic, β-agonist, or potassium-sparing diuretic (PSD) (p < 0.05). Medication adherence was significantly lower in African Americans than whites in all classes except for ARBs, loop diuretics, and PSDs (p < 0.05). Being Hispanic was associated with significantly lower adherence rates than whites for dihydropyridine CCBs and acetylcholinesterase inhibitors (p <0.05).

Conclusions:

Racial/ethnic differences exist in antihypertensive and dementia medication use in a cohort of older adults with hypertension and dementia. Adherence rates for a number of antihypertensive and dementia drugs are lower for minorities compared with whites. Healthcare providers should make special efforts to improve medication adherence among minorities.
Oncology: Treatment of Multiple Myeloma in the Targeted Therapy Era
Authors: Saad Ayman A , Sharma Manish , Higa Gerald M
Published: February 2009

Objective:

To review the clinical trials that have impacted treatment standards of multiple myeloma (MM).

Data Source:

A PubMed search (1980–June 2008) restricted to English-language publications was conducted using the key words multiple myeloma, clinical trials, targeted therapy, thalidomide, lenalidomide, bortezomib, dexamethasone, melphalan, autologous stem-cell transplantation, and tumor biology. Abstracts emanating from the meetings of the American Society of Clinical Oncology and American Society of Hematology from June 2002 to June 2008 were also reviewed.

Data Synthesis:

Although hematopoietic stem-cell transplantation has improved the response rate and duration of overall survival, MM remains an incurable disease. However, focused research aimed at the molecular basis of the disease has led to a number of new treatment strategies. Evidence from clinical trials indicates that each of the 3 novel agents, thalidomide, lenalidomide, and bortezomib, is remarkably effective as first-line therapy. The data also suggest that clinicians may need to reevaluate the role of stem-cell transplantation in the disease.

Conclusions:

Thalidomide, lenalidomide, or bortezomib in combination with dexamethasone have replaced traditional chemotherapy such as melphalan, doxorubicin, and vincristine as initial therapy of patients with MM who are eligible for stem-cell transplantation. Furthermore, these novel drugs can be incorporated into regimens used to treat transplant-ineligible patients or those with relapsing disease.
Serum Sickness–Like Reaction Associated with Efalizumab
Authors: Ashraf-Benson Sadia , Wall Geoffrey C , Veach Lisa A
Published: February 2009

Objective:

To report a case of serum sickness–like reaction (SSLR) possibly induced by efalizumab, a recombinant humanized immunoglobulin G1 κ isotype monoclonal antibody approved for treatment of moderate-to-severe plaque psoriasis.

Case Summary:

A 37-year-old woman with plaque psoriasis who had been treated with efalizumab for 2 months developed a fever, erythematous rash, and progressive joint swelling and pain that required hospitalization. An exhaustive workup for infectious and rheumatologic causes of the patient's symptoms was negative. Given the relative temporal relationship between efalizumab therapy and the patient's signs and symptoms, a diagnosis of serum sickness was made. Systemic corticosteroids were initiated, which resulted in rapid resolution of the patient's signs and symptoms. Use of an objective causality assessment suggests that the patient's SSLR was possibly related to efalizumab.

Discussion:

Like many therapeutic monoclonal antibodies, efalizumab is associated with several adverse events, including allergic reactions. SSLR, a nonimmediate hypersensitivity syndrome, can occur with a variety of drugs including monoclonal antibodies. However, a MEDLINE search (1964–July 2008) identified only one other possible case of SSLR related to efalizumab.

Conclusions:

Clinicians using efalizumab should be aware of this possible adverse reaction.
Cost-Effectiveness of Trastuzumab as Adjuvant Therapy for Early Breast Cancer: A Systematic Review
Authors: Chan Agnes LF , Leung Henry WC , Lu Chin-Li , Lin Shun Jin
Published: February 2009

Objective:

To identify published, original, cost-effectiveness analyses presenting cost/quality-adjusted life year (QALY) ratios for trastuzumab used as an adjuvant treatment for HER2-positive early breast cancer and to evaluate the quality of reporting the favorable cost-effectiveness ratios.

Data Sources:

The terms trastuzumab adjuvant therapy, cost-effectiveness, quality-adjusted, QALY, and early breast cancer were searched in MEDLINE, PubMed, Embase, and CancerLit, as well as in Cochrane economic evaluation and reference lists from 1998 to June 2008. Only English-language publications were eligible.

Study Selection and Data Extraction:

All published studies examining cost-effectiveness outcomes on the basis of modeling or clinical trials were included. Cost-effectiveness analysis that measured health effects in units other than QALY, life year gained, neoadjuvant data, reviews, and comments were excluded. Each study was assessed independently by 2 trained reviewers.

Data Synthesis:

Thirteen of the 239 articles identified met the inclusion criteria, with 23 cost-effectiveness ratios pertaining to treatment of early breast cancer. These ratios ranged from $5020/QALY to $134,610/QALY. Most studies reported favorable cost-effectiveness values (ie, below $50,000/QALY). About 84.6% were conducted using a Markov model based on data from clinical trials and 15.3% were analyzed by other economic or cost models; 84.6% reported sensitivity analysis, 11 studies (84.6%) clearly described a justification of selecting study design, and only 15.3% noted study limitations. All studies mentioned their perspective; 92.3% did not show the funding source. Methods of reporting costs, effectiveness, and time-horizons for disease states varied significantly. Nine (69.2%) studies used a discount rate of 3%, 3 studies used a discount rate of 5%, and 1 study used 3.5%. The mean quality of the studies was 4.43.

Conclusions:

Most studies presenting the frequently proposed threshold of QALY suggest that trastuzumab may be cost-effective for treatment of early breast cancer in a 1-year treatment regimen.
The marine algal (seaweed) flora of the Azores: additions and amendments 3
Authors: Tittley Ian , Neto Ana I. , Parente Manuela I.
Published: February 2009

Thirteen species of benthic marine algae are reported as new to the mid Atlantic Azores archipelago, and the status is confirmed for five other species. Some of the new records fall within their overall distributional range. The discovery of seven species (Codium taylorii,Digenea simplex,Gelidiella tinerfensis,Gelidiopsis intricata,Laurencia microcladia,Papenfussiella kuromo,Phyllophora gelidioides) represents a northern extension in their Atlantic distributional range. The archipelago is the western limit ofPapenfussiella kuromoandPhyllophora gelidioidesin the Atlantic Ocean.Ascophyllum nodosum, common as drift, was found for the first time attached to rocks on Graciosa Island andCaulerpa webbianais confirmed as a recent immigrant to the archipelago. Four species are removed from the flora.
First record of Contarinia squamariae (Rhizophyllidaceae, Rhodophyta) from Portugal: description of morphological and reproductive structures
Authors: Berecibar Estibaliz , Wynne Michael J. , Santos Rui
Published: February 2009

The red algal species Contarinia squamariae (Rhizophyllidaceae, Gigartinales) is newly reported from the European Atlantic coast off southern and southwestern Portugal. Tetrasporangiate, spermatangial, and female/cystocarpic specimens were found growing closely attached to Peyssonnelia squamaria, and a non-reproductive specimen was found attached to Sphaerococcus coronopifolius.
Gyrosigma orbitum sp. nov. (Bacillariophyta) from a salt marsh in the Bay of Fundy, eastern Canada
Authors: Thaler Mary , Kaczmarska Irena
Published: February 2009

An undescribed species of tube-dwelling sigmoid diatoms, Gyrosigma orbitum sp. nov., was found in the surface sediments of a salt marsh in Peck's Cove, Bay of Fundy, Atlantic Canada. The specimens belong to the section Strigiles
sensu H. Peragallo and they are characterized by very fine longitudinal striation (34–45 in 10 μm), isomorphic proximal raphe endings and two large oval pits within the central area. While recorded in adjacent tidal mudflats, this species reached its highest abundances in the salt marsh, particularly within the cordgrass Spartina patens where it occurred in association with other epipelic taxa, including Diploneis cf. smithii, Surirella spp., Gyrosigma limosum, Nitzschia epithemioides, N. ligowskii, N. sigma, and a number of small sigmoid Nitzschia species. Gyrosigma orbitum is found mainly at sites with high sediment temperature and water content, but a shallow anoxic layer.
β-Phenylethylamine content in marine algae around Turkish coasts
Authors: Percot Aline , Yalçın Ahmet , Aysel Veysel , Erdugan Hüseyin , Dural Berrin , Güven Kasım Cemal
Published: February 2009

β-Phenylethylamine content was investigated in two green, five brown, and ten red marine algae by gas chromatography/mass spectrometry. β-Phenylethylamine was found in six red algae but was not detected in the brown and green algae studied. The highest amount of β-phenylethylamine was determined in Gelidium crinale (30.42 μg g-1). This is the first report of β-phenylethylamine in the algae tested and also the first to quantify β-phenylethylamine in marine algae.
Preheparin serum lipoprotein lipase mass interacts with gender, gene polymorphism and, positively, with smoking
Authors: Onat Altan , Hergenç Gülay , Agırbaşlı Mehmet , Kaya Zekeriya , Can Günay , Ünaltuna Nihan E.
Published: February 2009

: Correlates of preheparin serum lipoprotein lipase (LPL) mass and its associations with the likelihood of metabolic syndrome (MS) and coronary heart disease (CHD) were investigated.

: A cross-sectional study was carried out in a population sample (n=352, median age 55). MS was defined according to modified Adult Treatment Panel III criteria.

: Age-adjusted geometric mean preheparin LPL concentrations were 58.6±1.04 ng/mL in men and 66.9±1.03 ng/mL in women (p<0.004). A positive interaction with both the

:

Clin Chem Lab Med 2009;47:208–15.
Methodology for monitoring cytomegalovirus infection after renal transplantation
Authors: Xue Wujun , Liu Hua , Yan Hang , Tian Puxun , Ding Xiaoming , Pan Xiaoming , Feng Xinshun , Xiang Heli , Hou Jun , He Xiaoli
Published: February 2009

: The aim of this study was to evaluate the diagnostic value of different detection methods for cytomegalovirus (CMV) infection after renal transplantation and also to establish a system to monitor therapy for CMV infection.

: We retrospectively studied 1516 renal transplant recipients from June 1994 to December 2006. All patients were screened for CMV-DNA. A total of 1402 patients had received CMV-IgG/IgM detection since June 1996 and 660 had received CMV antigen detection since June 2000.

: A total of 664 (43.8%) recipients developed CMV infection. The sensitivity, specificity and Youden index of the three methods, respectively, were 18.84%, 100% and 0.1884 for ELISA, 91.86%, 82.98% and 0.7484 for PCR, and 88.06%, 96.95% and 0.8501 for the CMV-pp65 antigenemia test. The sensitivity and specificity of the two combined detection methods (CMV-DNA and CMV-pp65) for post-operation CMV infection were 93.49% and 99.06%; the two detection methods had significant dependability (p<0.05) in diagnosis of CMV infection and in evaluation of therapeutic effect of antiviral drugs.

: Only ELISA can be used as a screening index in order to distinguish whether the donors or recipients are infected with CMV or not. CMV-pp65 antigenemia can help guide clinical therapy for CMV infection. CMV-pp65 and CMV-PCR combined together provide a more effective method to monitor CMV infection and predict its outcome.

Clin Chem Lab Med 2009;47:177–81.
Polymorphisms and plasma soluble levels of E-selectin in patients with chronic hepatitis B virus infection
Authors: Wu Shimin , Zhou Xin , Yang Huafen , Yin Jidong , Cai Chunlin , Zheng Fang
Published: February 2009

: Infections with hepatitis B virus (HBV) may lead to a distinct clinical outcome which is partially related to host genetic variability. Our aim was to investigate the relationships between the polymorphisms of the E-selectin gene and disease progression in a HBV-infected Chinese Han population, and also to determine the plasma soluble E-selectin (sE-selectin) levels in this population.

: Genomic DNA was extracted from the peripheral blood of 367 HBV carriers and 281 healthy controls. Two polymorphisms (

: The frequency of the C allele (AC or CC) of the

: This is the first report describing the association between E-selectin polymorphisms and HBV-related chronic liver diseases. Our data suggest that the

Clin Chem Lab Med 2009;47:159–64.
Comparison of calcium, magnesium, sodium, potassium, zinc, and creatinine concentration in 24-h and spot urine samples in women
Authors: Ilich Jasminka Z. , Blanuša Maja , Orlić Željka Crnčević , Orct Tatjana , Kostial Krista
Published: February 2009

: The 24-h urine sample is considered as the most reliable material for testing many but not necessarily all constituents in urine. However, its collection is tedious for both patients and research participants. The aim of this study was to compare concentrations of essential elements calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), and zinc (Zn) in 24-h and spot urine samples.

: Urine samples were collected from 143 generally healthy women, aged 30–79 years. Fasting spot urine was collected immediately after the end of the 24-h collection, therefore being of the same content as the first morning urine which ended the 24-h collection. Elements were analyzed by flame atomic absorption/emission spectrometry and expressed as mg/g and/or mmol/mol of creatinine (Cr). Spearman rank order correlations between 24-h and spot urine were carried out for each element. Ratios of elements in 24-h to spot urine samples were calculated to estimate the element-proportion of spot in the 24-h sample.

: All coefficients of correlation between 24-h and spot urine of measured elements and Cr were significant (p<0.05): Zn (0.637), Mg (0.623), Ca (0.603), Na (0.452), K (0.396), and Cr (0.217). Ratios of 24-h to spot urine samples for each element (except K) were similar and close to 2, indicating uniform proportion of elements from spot urine sample in the 24-h sample. In addition, a high correlation between various pairs of elements was obtained in both 24-h and spot urine; the highest being between Na/Ca (0.435) and (0.578), respectively. This is in accordance with theoretical presumptions and previous findings regarding those relationships.

: Although replacing burdensome 24-h urine collection with spot urine sampling might not provide the solution in all cases, our results show that for the elements analyzed, spot urine could be a reliable alternative.

Clin Chem Lab Med 2009;47:216–21.
Effect of high levels of human chorionic gonadotropin and estradiol on the severity of hyperemesis gravidarum
Authors: Tan Peng Chiong , Tan Nugroho C. , Omar Siti Z.
Published: February 2009

: Serum human chorionic gonadotropin (hCG) and estradiol levels are higher in women with hyperemesis gravidarum (HG) than in unaffected pregnant controls. We postulated that higher levels of these hormones may be associated with clinically more severe HG. The aim of this study was to evaluate the effect of maternal hCG and estradiol levels on the severity of HG.

: A prospective study was performed on 167 first trimester women hospitalized for HG. Venous blood was taken for hCG and estradiol levels. Scattergrams were plotted for hCG or estradiol levels vs. gestational age. A curve of best fit was drawn. Women were categorized into two groups according to their position above or below the curve. Prolonged hospital stay (≥4 days) was used as a marker for HG severity. Multivariable logistic regression analysis was used to control for differences in characteristics, laboratory results on admission, and treatment received.

: After adjustment, high hCG level adjusted odds ratio (AOR) (2.2, 95% CI 1.0–4.9, p=0.04) and hyponatremia AOR (2.8, 95% CI 1.2–6.6, p=0.02) were independently associated with prolonged hospital stay. With bivariate analysis, high estradiol level was not associated with prolonged stay.

: High hCG but not estradiol is associated with more severe HG.

Clin Chem Lab Med 2009;47:165–71.
Performance of free β-human chorionic gonadotrophin (free β-hCG) and pregnancy associated plasma protein-A (PAPP-A) analysis between Delfia Xpress and AutoDelfia systems in The Netherlands
Authors: Linskens Ingeborg H. , Levitus Marieke , Frans Anneke , Schielen Peter C.J.I. , van Vugt John M.G. , Blankenstein Marinus A. , Dijstelbloem Hilde M.
Published: February 2009

: The VU University Medical Center (VUmc) was the first hospital in the Netherlands to introduce the Delfia Xpress for the analysis of free β-human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester screening program for Down syndrome. Since then, others have implemented this system. In this study, we tested the equality of measurements for free β-hCG and PAPP-A between Delfia Xpress systems and one AutoDelfia system.

: A total of 40 serum samples were aliquoted and stored at –20°C. Samples were analyzed by six Delfia Xpress systems and one AutoDelfia system over a time period of 2 years.

: The relationships between free β-hCG and PAPP-A were excellent for the different Delfia Xpress systems (r>0.99, p<0.0001). For PAPP-A, the agreement between the main system at VUmc and five other systems was linear with slopes between 0.99 and 1.06. Similarly, agreement for free β-hCG was linear with slopes between 0.99 and 1.09. Likewise, agreement for PAPP-A and free β-hCG was excellent for the AutoDelfia vs. the main Delfia Xpress at the VUmc (r>0.99, p<0.0001). For both PAPP-A and free β-hCG, the relationships were linear with slopes of 1.08 and 1.07.

: We demonstrate an excellent agreement for the analysis of PAPP-A and free β-hCG between Delfia Xpress systems and one AutoDelfia system.

Clin Chem Lab Med 2009;47:222–6.
Vitamin B12 deficiency is associated with coronary artery disease in an Indian population
Authors: Kumar Jitender , Garg Gaurav , Sundaramoorthy Elayanambi , Prasad P. Veerendra , Karthikeyan Ganesan , Ramakrishnan Lakshmy , Ghosh Saurabh , Sengupta Shantanu
Published: February 2009

: The incidence of coronary artery disease (CAD) is increasing at an alarming rate, especially in developing countries, such as India. It is often advocated that a vegetarian lifestyle could reduce the burden of CAD. However, in spite of a majority of Indians being vegetarians, the incidence of CAD is highest in this population. This may be due to deficiency of vitamin B12, a micronutrient, sourced only from animal products.

: Herein, we assessed the effect of vitamin B12 with respect to CAD in 816 individuals (368 CAD patients and 448 controls) recruited from a tertiary care center in New Delhi, India.

: We found that vitamin B12 levels were significantly lower in CAD patients than in controls (p<0.0001). Also, vegetarians were found to have significantly lower vitamin B12 concentrations (p=0.0001) and higher incidence of CAD (p=0.01). Interestingly, elevated homocysteine levels, a hallmark of vitamin B12 deficiency, was not associated with CAD. In contrast, cysteine levels were significantly higher in CAD patients than in controls (p=0.004).

: We believe that, when vitamin B12 is deficient, homocysteine is rapidly metabolized via the transsulfuration pathway leading to increased cysteine levels.

Clin Chem Lab Med 2009;47:334–8.
The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: Code of Conduct, Version 2 – 2008
Authors: McMurray Janet , Zerah Simone , Hallworth Michael , Koeller Ursula , Blaton Victor , Tzatchev Kamen , Charilaou Charis , Racek Jaroslav , Johnsen Anders , Tomberg Karel , Harmoinen Aimo , Baum Hannsjörg , Rizos Demetrios , Kappelmayer Janos , O'Mullane John , Nubile Giuseppe , Pupure Silvija , Kucinskiene Zita , Opp Matthias , Huisman Wim , Solnica Bogdan , Reguengo Henrique , Grigore Camelia , Špaňár Július , Štrakl Greta , Queralto Josep , Wallinder Hans , Schuff-Werner Peter
Published: February 2009

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 10 years, more than 2000 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Federation of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). A Code of Conduct was adopted in 2003 and a revised and updated version, taking account particularly of the guidelines of the Conseil Européen des Professions Libérales (CEPLIS) of which EFCC is a member, is presented in this article. The revised version was approved by the EC4 Register Commission and by the EFCC Executive Board in Paris on 6 November, 2008.

Clin Chem Lab Med 2009;47:372–5.
The GABAB1aIsoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses
Authors: Guetg Nicole , Seddik Riad , Vigot Réjan , Turecek Rostislav , Gassmann Martin , Vogt Kaspar E. , Bräuner-Osborne Hans , Shigemoto Ryuichi , Kretz Oliver , Frotscher Michael , Kulik Ákos , Bettler Bernhard
Published: February 2009

GABABreceptor subtypes are based on the subunit isoforms GABAB1aand GABAB1b, which associate with GABAB2subunits to form pharmacologically indistinguishable GABAB(1a,2)and GABAB(1b,2)receptors. Studies with mice selectively expressing GABAB1aor GABAB1bsubunits revealed that GABAB(1a,2)receptors are more abundant than GABAB(1b,2)receptors at glutamatergic terminals. Accordingly, it was found that GABAB(1a,2)receptors are more efficient than GABAB(1b,2)receptors in inhibiting glutamate release when maximally activated by exogenous application of the agonist baclofen. Here, we used a combination of genetic, ultrastructural and electrophysiological approaches to analyze to what extent GABAB(1a,2)and GABAB(1b,2)receptors inhibit glutamate release in response to physiological activation. We first show that at hippocampal mossy fiber (MF)-CA3 pyramidal neuron synapses more GABAB1athan GABAB1bprotein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations ≥1 μm, both GABAB(1a,2)and GABAB(1b,2)receptors contribute to presynaptic inhibition of glutamate release. However, at lower concentrations of baclofen, selectively GABAB(1a,2)receptors contribute to presynaptic inhibition. Remarkably, exclusively GABAB(1a,2)receptors inhibit glutamate release in response to synaptically released GABA. Specifically, we demonstrate that selectively GABAB(1a,2)receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABABreceptors. Our data demonstrate that the difference in GABAB1aand GABAB1bprotein levels at MF terminals is sufficient to produce a strictly GABAB1a-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABAB1aand GABAB1bproteins is of regulatory relevance.
Coagonist Release Modulates NMDA Receptor Subtype Contributions at Synaptic Inputs to Retinal Ganglion Cells
Authors: Kalbaugh Trisha L. , Zhang Jun , Diamond Jeffrey S.
Published: February 2009

NMDA receptors (NMDARs) are tetrameric protein complexes usually comprising two NR1 and two NR2 subunits. Different combinations of four potential NR2 subunits (NR2A-D) confer diversity in developmental expression, subsynaptic localization, and functional characteristics, including affinity for neurotransmitter. NR2B-containing NMDARs, for example, exhibit relatively high affinity both for glutamate and the coagonist glycine. Although multiple NMDAR subtypes can colocalize at individual synapses, particular subtypes often mediate inputs from distinct functional pathways. In retinal ganglion cells (RGCs), NMDARs contribute to synaptic responses elicited by light stimulus onset (“ON”) and offset (“OFF”), but roles for particular NMDAR subtypes, and potential segregation between the ON and OFF pathways, have not been explored. Moreover, elements in the retinal circuitry release two different NMDAR coagonists, glycine andd-serine, but the effects of endogenous coagonist release on the relative contribution of different NMDAR subtypes are unclear. Here, we show that coagonist release within the retina modulates the relative contribution of different NMDARs in the ON pathway of the rat retina. By pharmacologically stimulating functional pathways independently in acute slices and recording synaptic responses in RGCs, we show that ON inputs, but not OFF inputs, are mediated in part by NMDARs exhibiting NR2B-like pharmacology. Furthermore, suppressing release of NMDAR coagonist reduces NMDAR activation at ON synapses and increases the relative contribution of these putative NR2B-containing receptors. These results demonstrate direct evidence for evoked coagonist release onto NMDARs and indicate that modulating coagonist release may regulate the relative activation of different NMDAR subtypes in the ON pathway.
Striatal Dopamine Predicts Outcome-Specific Reversal Learning and Its Sensitivity to Dopaminergic Drug Administration
Authors: Cools Roshan , Frank Michael J. , Gibbs Sasha E. , Miyakawa Asako , Jagust William , D'Esposito Mark
Published: February 2009

Individual variability in reward-based learning has been ascribed to quantitative variation in baseline levels of striatal dopamine. However, direct evidence for this pervasive hypothesis has hitherto been unavailable. We demonstrate that individual differences in reward-based reversal learning reflect variation in baseline striatal dopamine synthesis capacity, as measured with neurochemical positron emission tomography. Subjects with high baseline dopamine synthesis in the striatum showed relatively better reversal learning from unexpected rewards than from unexpected punishments, whereas subjects with low baseline dopamine synthesis in the striatum showed the reverse pattern. In addition, baseline dopamine synthesis predicted the direction of dopaminergic drug effects. The D2receptor agonist bromocriptine improved reward-based relative to punishment-based reversal learning in subjects with low baseline dopamine synthesis capacity, while impairing it in subjects with high baseline dopamine synthesis capacity in the striatum. Finally, this pattern of drug effects was outcome-specific, and driven primarily by drug effects on punishment-, but not reward-based reversal learning. These data demonstrate that the effects of D2receptor stimulation on reversal learning in humans depend on task demands and baseline striatal dopamine synthesis capacity.
Neuroendocrine Proopiomelanocortin Neurons Are Excited by Hypocretin/Orexin
Authors: Acuna-Goycolea Claudio , van den Pol Anthony N.
Published: February 2009

Hypocretin/orexin, produced by a group of neurons in the lateral hypothalamus/perifornical area, enhances cognitive arousal and also may play a crucial role in modulating the neuroendocrine system. How hypocretin modulates the endocrine system remains an open question. Hypocretin cells innervate the mediobasal hypothalamus where they can potentially influence the activity of specific cell populations within the arcuate nucleus. Here, we examine whether hypocretin modulates the median eminence-projecting proopiomelanocortin (POMC) neurons identified by selective green fluorescent protein expression and antidromic stimulation or retrograde Evans blue dye tracing in transgenic mice. We find that POMC neurons, in general, and, in addition, those that project their axons to the median eminence, were robustly activated by hypocretin in a dose-dependent manner. These excitatory actions included a threefold increase in spike frequency and direct membrane depolarization of up to 22 mV (mean, 17.9 ± 7.2 mV). Direct postsynaptic depolarization was decreased at more positive membrane potentials, inhibited by the sodium–calcium exchanger antagonist KB-R7943, and reduced by lowering the bath temperature, or by buffering the postsynaptic calcium with BAPTA, suggesting that the primary mechanism for hypocretin-mediated excitation is the activation of the sodium–calcium exchanger. Hypocretin also enhanced excitatory inputs to POMC cells via a presynaptic mechanism and indirectly increased the release of GABA onto these cells in a spike-dependent manner. However, these synaptic actions were not necessary to cause postsynaptic membrane depolarization and spiking. Thus, in contrast to previous suggestions that hypocretin inhibited POMC cells, our results demonstrate robust direct excitation of POMC neurons by hypocretin.
Activity of Pontine Neurons during Sleep and Cataplexy in Hypocretin Knock-Out Mice
Authors: Thankachan Stephen , Kaur Satvinder , Shiromani Priyattam J.
Published: February 2009

Narcolepsy is a human sleep disorder resulting from the loss of neurons containing the neuropeptide orexin, also known as hypocretin. Cataplexy, which is a sudden loss of muscle tone during waking, is an important diagnostic symptom of narcolepsy. In humans and canines with narcolepsy, cataplexy is considered to be a separate and distinct behavioral state. However, in the mouse model of the disease this issue is not resolved. The present study monitored the activity of forty four neurons in the rostral pons in hypocretin knock-out mice. Majority of the neurons were active during wake and REM sleep, while four neurons were selectively active during REM sleep. All of these neurons were less active during cataplexy compared with REM sleep. Thus, although cataplexy and REM sleep share many common features, including the muscle atonia, cataplexy is a distinct state in mice.
Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor
Authors: Lambertsen Kate Lykke , Clausen Bettina Hjelm , Babcock Alicia Anne , Gregersen Rikke , Fenger Christina , Nielsen Helle Hvilsted , Haugaard Laila Skov , Wirenfeldt Martin , Nielsen Marianne , Dagnaes-Hansen Frederik , Bluethmann Horst , Færgeman Nils Joakim , Meldgaard Michael , Deierborg Tomas , Finsen Bente
Published: February 2009

Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical infarction and behavioral deficit are significantly exacerbated in TNF-knock-out (KO) mice compared with wild-type mice. By usingin situhybridization, immunohistochemistry, and green fluorescent protein bone marrow (BM)-chimeric mice, TNF was shown to be produced by microglia and infiltrating leukocytes. Additional analysis demonstrating that BM-chimeric TNF-KO mice grafted with wild-type BM cells developed larger infarcts than BM-chimeric wild-type mice grafted with TNF-KO BM cells provided evidence that the neuroprotective effect of TNF was attributable to microglial- not leukocyte-derived TNF. In addition, observation of increased infarction in TNF-p55 receptor (TNF-p55R)-KO mice compared with TNF-p75R and wild-type mice suggested that microglial-derived TNF exerts neuroprotective effects through TNF-p55R. We finally report that TNF deficiency is associated with reduced microglial population size and Toll-like receptor 2 expression in unmanipulated brain, which might also influence the neuronal response to injury. Our results identify microglia and microglial-derived TNF as playing a key role in determining the survival of endangered neurons in cerebral ischemia.
Surgery or invasive endoscopy for the treatment of chronic pancreatitis?
Authors: Kelemen Dezső
Published: February 2009

A krónikus pancreatitis elsődlegesen belgyógyászati betegség. Az esetek egy részében azonban a konzervatív kezelés nem szünteti meg a panaszokat, és valamilyen intervencióra van szükség. Ennek lehetőségeit vizsgálja a közlemény. Műtéti indikáció az erős fájdalom, a pseudocysta, a környező képletek kompressziója miatti tünetek és a tumorgyanú. Az invazív endoszkópia is teret nyert a krónikus pancreatitis terápiájában, elsőként választandó eljárásként jön szóba bizonyos esetekben, mint például pseudocysta esetében, továbbá rossz általános állapotú betegeknél az epe- és a pancreasvezeték szűkületének megoldására, valamint részleges Wirsung-vezeték-rupturánál. A nyitott kérdések megválaszolásához azonban további tanulmányok szükségesek. Összefoglalva megállapítható, hogy mind a műtéti, mind az endoszkópos kezelésnek létjogosultsága van a krónikus pancreatitis terápiájában, a megfelelő kritériumok alapján.
Frequent occurance of level burnout among general practitioners and residents
Authors: Ádám Szilvia , Torzsa Péter , Győrffy Zsuzsa , Vörös Krisztián , Kalabay László
Published: February 2009

A családorvosok szerepe a betegellátásban központi jelentőségű. A nagyszámú orvos-beteg találkozás, a fizikai és érzelmi megterhelés munkahelyi stresszhez és kiégéshez vezethet. Tudomásunk szerint eddig nem folyt olyan vizsgálat Magyarországon, amely a családorvosok kiégéssel kapcsolatos mutatóit térképezte volna fel.
Célkitűzés:
A kiégés prevalenciájának feltárása magyarországi családorvosok és családorvosi rezidensek körében.
Módszerek:
Feltáró/leíró jellegű keresztmetszeti vizsgálat önkitöltős kérdőíves felméréssel 453 háziorvos és 43 háziorvosi rezidens részvételével. A kiégés mérésére a Maslach Burnout Inventory-t (MBI-GS) használtuk. A kiégés szintjének megállapításához az emocionális kimerülés, a cinizmus/deperszonalizáció és a teljesítménycsökkenés átlagát (SD) számoltuk ki férfiak és nők, valamint orvosok és rezidensek között. A kiégés szintjének, illetve fokának (alacsony, közepes, illetve magas fokú kiégés) nemek és foglalkozási csoportok (orvos vs. rezidens) közötti összehasonlítását a kiégés összes dimenziójában független mintás
t
-teszttel, illetve χ
2
-teszttel végeztük. A kiégés szociodemográfiai stresszorait lineáris regressziós analízissel vizsgáltuk.
Eredmények:
A rezidensek szignifikánsan kisebb szintű cinizmusról/deperszonalizációról [
t
(df): 2,8 (476);
p
< 0,01)] és teljesítménycsökkenésről [
t
(df): 2,0 (485);
p
< 0,05] számoltak be, mint a családorvosok. A kiégés szintjében szignifikáns nemi különbséget nem találtunk. Szignifikánsan több háziorvos számolt be magas [χ
2
(df) = 5,9 (1);
p
< 0,05] és közepes [χ
2
 (df) = 4,6 (1);
p
< 0,05] fokú deperszonalizációról, mint rezidens. Az orvosok közel harmada számolt be magas fokú emocionális kimerülésről, közel 60%-uk magas fokú deperszonalizációról, és közel 100%-uk magas fokú teljesítménycsökkenésről. A foglalkozás jellege, vagyis a rezidencia bizonyult a deperszonalizáció legerősebb negatív prediktorának (β = –0,09, 95%-os CI –0,22 – –0,002).
Következtetések:
A magyar családorvosok körében a kiégés prevalenciája kiemelkedően magas, a magas fokú teljesítménycsökkenés pedig majdnem minden háziorvost érint. A rezidensi munka szignifikáns védő kapcsolatot mutatott a deperszonalizációval. Eredményeink új adatokat szolgáltatnak a kiégés magyarországi és nemzetközi kutatásához.
Absence of mutations in Pax6 gene in three cases of Morning Glory syndrome associated with isolated growth hormone deficiency
Authors: Guerra-Junior Gil , Spinola-Castro Angela Maria , Siviero-Miachon Adriana A. , Nogueira Roberto Gomes , Lemos-Marini Sofia Helena V. , D'Souza-Li Lilia Freire Rodrigues , Silva Priscila Cristina da , França Emerson Salvador S. , Soardi Fernanda Caroline , Mello Maricilda Palandi de
Published: February 2009

Morning glory syndrome (MGS) is a congenital optic disc dysplasia often associated with craniofacial anomalies, especially basal encephalocele and hypopituitarism. Clinical signs are varied and often occult. The PAX6 gene is involved in ocular morphogenesis and is expressed in numerous ocular tissues during development especially in the developing central nervous system. The aim of the present study is to evaluate PAX6 in MGS associated with isolated growth hormone deficiency. Three pre-pubertal males (A, B and C) with MGS and short stature due to growth hormone deficiency, treated with recombinant human growth hormone with limited response, were reported. Two of them had basal encephalocele. Coding and non-coding sequences corresponding of PAX6 different transcripts were analyzed by direct sequencing. Nucleotide variations causing putative aminoacid change were not observed. Patient A presented the new IVS2+9G>A transition, whereas patients A and C were heterozygous for known single nucleotide polymorphisms (SNP) within the intron 4. In addition, two SNP heterozygoses were observed for patient C in both intron 9 and 13. Sequencing also revealed several nucleotide variations in patient B. Two heterozygoses for known polymorphisms were identified along with a novel C>A nucleotide change in intron 4. This patient also presented a low number on the TG repeat in intron 9 and a new IVS11+33A>T transversion. Gene regulation and transcription of PAX6 are complex processes; there are two major protein isoforms, PAX6(-5a) and PAX6(+5a), and nine transcripts described. Furthermore, extra transcription regulatory elements have been postulated within PAX6 introns. Considering that neither population distributions on PAX6 polymorphism nor their linkeages with diseases have been reported, a functional effect due to alterations described here cannot be discarded.
Novos aspectos da genética e dos mecanismos moleculares da morfogênese da tiróide para o entendimento da disgenesia tiroidiana
Authors: Ramos Helton E. , Nesi-França Suzana , Maciel Rui M. B.
Published: February 2009

A organogênese da tiróide ainda não está completamente elucidada, assim como também não se conhece o mecanismo patogenético da maioria dos casos de disgenesias tiroidianas. Vários genes têm sido identificados como importantes para a sobrevivência, a proliferação e a migração dos precursores das células tiroidianas e tem-se demonstrado que eles atuam de modo integrado. Além disso, por meio da geração de camundongos geneticamente modificados, diversos estudos têm trazido melhor entendimento para o papel destes genes na morfogênese tiroidiana. Finalmente, tem-se também evidenciado que mutações em alguns destes genes são responsáveis pelo desenvolvimento de disgenesias tiroidianas em crianças com hipotiroidismo congênito. O objetivo desta revisão é sumarizar os aspectos moleculares do desenvolvimento tiroidiano, descrever os modelos animais e respectivos fenótipos e oferecer novas informações sobre a ontogenia e a patogênese das disgenesias tiroidianas humanas.
Laboratory diagnosis of late-onset male hypogonadism andropause
Authors: Clapauch Ruth , Carmo Aline Machado , Marinheiro Lizanka , Buksman Salo , Pessoa Isabel
Published: February 2009

OBJECTIVES: To evaluate which factors influence the laboratorial diagnosis of late-onset male hypogonadism (LOH). METHODS: Total testosterone (TT), SHBG and albumin were measured in 216 men aged 52-84 years. The laboratorial definition of LOH was two values of calculated free testosterone (cFT) <6.5 ng/dl, according to Vermeulen's formula. RESULTS: At the first blood test, cFT was <6.5 ng/dl in 27% of the men. Laboratorial LOH (confirmed by two tests) was present in 19%, but TT levels were low in only 4.1%. Age influenced TT (p=0.0051) as well as BMI; 23.5% of patients > 70 years and 38.9% of the obese men who had TT within the reference range were, in fact, hypogonadal. CONCLUSION: Especially in obese men and in those > 70 years old, SHBG dosage is important to calculate FT levels and diagnose hypogonadism.
Risk of late-onset hypogonadism (andropause) in Brazilian men over 50 years of age with osteoporosis: usefulness of screening questionnaires
Authors: Clapauch Ruth , Braga Daniel Jorge de Castro , Marinheiro Lizanka Paola , Buksman Salo , Schrank Yolanda
Published: February 2009

OBJECTIVE: To analyze the relative risk of late-onset hypogonadism in men with osteoporosis and the usefulness of screening questionnaires. METHODS: We correlated the Aging Male's Symptoms (AMS), Androgen Deficiency in Aging Male (ADAM) and International Index of Erectile Function (IIEF-5) questionnaires and the laboratory diagnosis of hypogonadism in 216 men aged 50-84 years (110 with osteoporosis and 106 with normal bone density, paired by age and ethnicity). RESULTS: Hypogonadism presented in 25% of the osteoporotic and in 12.2 % of normal bone density men (OR 2.08; IC95%: 1.14-3.79) and was associated with ADAM first question (low libido, p=0.013). Levels of TT below 400 ng/dl correlated with an AMS score above 26 (p=0.0278). IIEF-5 showed no correlation with testosterone levels. CONCLUSION: Hypogonadism was 2.08 times more prevalent in osteoporotic men. The symptom that best correlated with late-onset hypogonadism was low libido (ADAM 1 positive).
Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years
Authors: Rosario Pedro Weslley
Published: February 2009

The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged < 65 years. Forty-eight women with SCH were evaluated. The control group consisted of 48 euthyroid volunteers. The mean symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women with SCH showed a significant increase in serum markers of bone formation and resorption. In addition, bone mineral density (BMD) was lower in the femoral neck but not in the lumbar spine in patients before menopause, whereas a lower BMD was observed at both sites in postmenopausal patients. SCH is not completely asymptomatic in women aged < 65 years, and is associated with heart abnormalities and with increased bone turnover and reduced BMD even before menopause.
Cost-effectiveness analysis of somatostatin analogues in the treatment of acromegaly in Brazil
Authors: Valentim Joice , Passos Vanessa , Mataveli Fabio , Calabró Alessandra
Published: February 2009

This study aims to compare economic and patient impacts of the treatment of acromegaly with two different somatostatin analogues (octreotide LAR and lanreotide SR) in Brazil. A cost-effectiveness analysis was carried out under the Brazilian Public Health Care System (SUS) perspective. A decision analytical model was developed based on the Brazilian Public Health Care System Clinical Guideline for Acromegaly. A hypothetical cohort of 276 patients was followed for two years. Data were extracted from literature and administrative databases. Based on the analytical model, treatment with octreotide LAR would avoid 12 and 17 cases of GH and IGF-I elevated serum levels, respectively. Octreotide LAR was a cost-saving strategy, with net savings of R$10,448,324 (US$4,465,096) to SUS. Annual net savings per patient were R$ 18,928 (US$8,089). Treatment of acromegaly with octreotide LAR is a dominant strategy when compared to the treatment with lanreotide SR in Brazil. Sensitivity analysis did not alter the cost-saving status.