bluuebunny/crossref_metadata_2025 huggingface dataset:
Histologic Lesions in Cynomolgus Monkeys (Macaca fascicularis) Naturally Infected with Simian Retrovirus Type D: Comparison of Seropositive, Virus-Positive, and Uninfected Animals
Authors: Guzman Roberto E. , Kerlin Roy L. , Zimmerman Thomas E.
Published: February 2008

Simian retrovirus (SRV) type D is a common cause of simian acquired immunodeficiency syndrome (SAIDS), a usually fatal immunosuppressive disease of macaques. Associated gross and histologic lesions have been well described for the rhesus macaque (Macaca mulatta) in experimental and natural infections. However, morphologic changes induced by this virus at the gross and light-microscopic level have not been documented in the cynomolgus macaque (Macaca fascicularis). In 1996, sporadic cases of anemia, weight loss, and diarrhea were noted in a colony of cynomolgus macaques in our research facility. Out of 28 animals, 24 tested positive for SRV by serology or virus isolation. Animals could mainly be classified into 1 of 2 categories: 1) positive for virus isolation but negative for SRV antibody and 2) negative for virus isolation but antibody positive. During the process of eliminating the virus from the colony, a complete postmortem examination was performed on the 24 infected animals that had to be culled. Twelve SRVnegative animals were available as controls. Minimal to mild follicular lymphoid infiltrates were seen in various organ systems in 75% of the negative animals, compared with moderate to marked infiltrates in 83% of infected animals. Lymphoid infiltrates were more common in the brain, bone marrow, and salivary gland of viremic animals and were rare to nonexistent in seropositive or negative animals. Lymphoid hyperplasia was present in 38% of the infected animals, whereas lymphoid depletion was seen in 47% of the infected animals. Overall, lesions were of greater severity in viremic animals than in virus-negative or seropositive animals. Overall, infected animals had lower, statistically significant hematocrit and lymphocyte values. Viremic animals had significantly lower hematocrit, white blood cell, lymphocyte, and neutrophil values than did controls. Only 1 out of 24 infected animals had clinical signs that were consistent with the definition of SAIDS, and none had evidence of opportunistic infections. Lesions were similar to those already reported in other species of macaques, but the absence of severe illness that was consistent with SAIDS in most viremic animals suggests that there may be a different manifestation of disease in the cynomolgus.
The Role of the Toxicologic Pathologist in the Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals
Authors: Pilling Andrew M.
Published: February 2008

Biotechnology-derived pharmaceuticals, or biopharmaceuticals, represent a special class of complex, high-molecular weight products, such as monoclonal antibodies, recombinant proteins, and nucleic acids. With these compounds, it is not appropriate to follow conventional safety testing programs, and the preclinical "package" for each biopharmaceutical needs to be individually designed. In addition to standard histopathology, the use of molecular pathology techniques is often required either in conventional animal studies or in in vitro tests. In this review, the safety evaluation of biopharmaceuticals is discussed from the perspective of the toxicologic pathologist, and appropriate examples are given of the use of molecular pathology procedures. Examples include the use of in situ hybridization to localize gene therapy vectors, the assessment of vector integration into genomic DNA by the polymerase chain reaction (PCR), and the use of immunohistochemistry to evaluate the potential cross-reactivity of monoclonal antibodies. In situ PCR techniques may allow for confirmation of the germ cell localization of nucleic acids and may therefore facilitate the risk assessment of germline transmission. Increased involvement with biopharmaceuticals will present challenging opportunities for the toxicologic pathologist and will allow for much greater use of molecular techniques, which have a critical role in the preclinical development of these compounds.
Exploring Variations in Contracting for Services Among American Local Governments
Authors: Fernandez Sergio , Ryu Jay Eungha , Brudney Jeffrey L.
Published: February 2008

During the previous two decades, researchers have conducted an array of empirical studies of local government contracting for services. Some of the more recent findings have suggested that this form of privatization has become less politically controversial and more accepted as a service delivery approach. Do politics still matter when it comes to explaining patterns in local government contracting? The findings from this study indicate that the influence of political factors, such as demand for smaller government and public employee opposition to privatization, still help to account for variations in local government contracting, as they did during the 1980s and early 1990s. Contract management capacity is an important determinant of local government contracting.
Nonprofit Governance, Management, and Organizational Learning
Authors: Stephenson Max O. , Schnitzer Marcy H. , Arroyave Verónica M.
Published: February 2008

Little scholarly attention has focused on understanding the impact of large gifts for small nonprofit organizations or on the mechanisms by which those institutions respond to such events. The authors studied the organizational and governance stresses mega-gifts create by examining the case of the $175 million Ruth Lilly gift to the Modern Poetry Association. The association's governing board successfully adapted to its changed circumstances by self-consciously learning and realigning its responsibilities relative to those of the organization's executive, which required individual and organizational learning. The authors chart the changes and actions that prompted that self-education and draw on the nonprofit organization governance, organizational learning, sense making, and adaptive change literatures to contend that nonprofit organization leaders must recognize that large-scale change will demand adaptive organizational work and require concomitant shifts in the routines of governance, management, and leadership so as to encourage and capture the learning necessary for successful organizational adjustment.
Why do Some Boundary Organizations Result in New Ideas and Practices and Others only Meet Resistance?
Authors: Schneider Anne L.
Published: February 2008

This study compares two federal grants, both from the same agency and both utilizing a national “boundary organization,” to assess how and why one was better able than the other to integrate divergent perspectives and produce new approaches to juvenile justice in multiple local jurisdictions. Results confirm the utility of boundary organizations but also show that not all organizations that bring together divergent perspectives necessarily result in anything new or better. Four factors stand out: (a) a different philosophy of evaluation research, (b) the grass-roots emergence of an inclusive rationale for the program that was orthogonal to the traditional “treatment versus punishment” ideology, (c) management strategies and agenda-setting arrangements at meetings that facilitated horizontal, upward, and downward information exchange, and (d) a different approach to knowledge and knowledge production that emphasized user-defined knowledge needs and diverse research methods. The case studies provide a wide range of insights for collaborative management practices, research—practitioner relationships, and implementation success.
Male Rape Myths
Authors: Chapleau Kristine M. , Oswald Debra L. , Russell Brenda L.
Published: February 2008

This study investigates the structure of Struckman-Johnson and Struckman-Johnson's Male Rape Myth Scale, examines gender differences in rape myth acceptance, and explores the underlying ideologies that facilitate male rape myth acceptance. A three-factor model, with rape myths regarding Trauma, Blame, and Denial as separate subscales, is the best fitting solution. However, the results indicate that additional scale development and validity tests are necessary. In exploratory analyses, men are more accepting of male rape myths than are women. Benevolent sexism toward men and acceptance of interpersonal violence are strong predictors of male rape myth acceptance for both men and women. Thus, the attitudes that facilitate rape myth acceptance against men appear to be similar to those that facilitate rape myth acceptance against women. Suggestions for future scale development are outlined and theoretical implications of the findings are discussed.
A 16-Year Examination of Domestic Violence Among Asians and Asian Americans in the Empirical Knowledge Base
Authors: Yick Alice G. , Oomen-Early Jody
Published: February 2008

Until recently, research studies have implied that domestic violence does not affect Asian American and immigrant communities, or even Asians abroad, because ethnicity or culture has not been addressed. In this content analysis, the authors examined trends in publications in leading scholarly journals on violence relating to Asian women and domestic violence. A coding schema was developed, with two raters coding the data with high interrater reliability. Sixty articles were published over the 16 years studied, most atheoretical and focusing on individual levels of analysis. The terms used in discussing domestic violence reflected a feminist perspective. Three quarters of the studies were empirical, with most guided by logical positivism using quantitative designs. Most targeted specific Asian subgroups (almost a third focused on Asian Indians) rather than categorizing Asians as a general ethnic category. The concept of “Asian culture” was most often assessed by discussing Asian family structure. Future research is discussed in light of the findings.
Testing and Developing the Health Promotion Model in Low-Income, Korean Elderly Women
Authors: Kyung Rim Shin  , Kang Younhee , Hyo Jung Park  , Myoung Ok Cho  , Heitkemper Margaret
Published: February 2008

This study was conducted to test Pender's health promotion model in low-income, Korean elderly women. A total of 389 low-income, Korean elderly women completed the interviews focused on the concepts in health promotion model. Seventy-three percent of the variance in health-promoting behaviors was accounted for by prior health-related behavior, biological, psychological, and sociocultural factors, behavior-specific cognitions and affect, environmental influences, commitment to a plan of action, and health-promoting behavior variables in a modified health promotion model. Findings from this study may support the conceptual framework for future nursing practice and research studies in this vulnerable population.
Religion
Authors: Benjamins Maureen R. , Buck Anna Campbell
Published: February 2008

Objective: Tobacco, alcohol, and physical inactivity are now among the top 10 risk factors for mortality in the Americas region. Subsequently, a more complete understanding of the various cultural factors that influence health behaviors such as these is needed. Method: This study investigates how religion influences the use of alcohol and cigarettes within a large, nationally representative sample of older adults in Mexico (Mexican Health and Aging Study, N = 10,399). Results: Religious salience and participation in religious activities are both significantly associated with smoking status, but not alcohol use. Discussion: This is one of the first studies to examine these associations in a developing country. Despite cultural differences, the negative relationship between religion and smoking in Mexico corresponds to associations seen in the United States and other Western countries. This type of information may be useful to health researchers, providers, and policy makers attempting to reduce deaths due to preventable causes.
The Effects of September 11 on Arab American Nurses in Metropolitan Detroit
Authors: Kulwicki Anahid , Khalifa Rose , Moore Gary
Published: February 2008

The purpose of this article is to determine the effects of 9/11 on Arab American nurses' workplace discrimination in the Detroit metropolitan area. Thirty-four Arab American nurses completed a survey about perceptions and experiences related to discrimination before and after the terror attacks on 9/11. Most participants did not experience demotion, but some experienced intimidation and patient rejection more often or with the same frequency following 9/11. September 11 continues to negatively affect Arab Americans in the work environment. Studies are needed to further examine the workplace discrimination relationship with specific health indicators for Arab Americans.
Psychological Acculturation: A Concept Analysis With Implications for Nursing Practice
Authors: Al-Omari Hasan , Pallikkathayil Leonie
Published: February 2008

Psychological acculturation is a complex process that has been widely discussed in the literature of anthropology, psychology, and sociology. The purpose of this article is to analyze the concept of psychological acculturation using Walker and Avant's strategy for concept analysis. The authors bring greater clarity to this process of acculturation to help nurses understand individuals'health behaviors. Definitions of acculturation are examined using different resources including dictionaries and scholarly literature. Antecedents, defining attributes, and consequences are identified, discussed, and summarized. A model case and contrary case are presented. Measurement of psychological acculturation is discussed in the context of defining attributes. Direction for future research and implications for nursing practice are presented.
Gastric Signet-Ring Cell Adenocarcinoma Presenting With Left Arm Deep-Vein Thrombosis and Bilateral Chylothorax
Authors: Kayacan Oya , Karnak Demet , Ayşe Can Berna , Dizbay Sak Serpil , Beder Sumru
Published: February 2008

A 28-year-old housewife, a life-long nonsmoker, presented with 3 weeks of pleuritic chest pain along with swollen right leg, left arm, and left breast. Six months previously she had left subclavian vein thrombosis. On admission, bilateral supraclavicular lymphedema on right leg and left arm and breast was observed and bilateral pleural fluid, chylous exudates, was detected. Abdomen computed tomography revealed abundant ascites and right ovarian enlargement. Whole body bone scintigraphy showed bone metastases on left humerus, right femur, and pelvis. Bronchial biopsy, obtained from edematous, hyperemic-irregular mucosa, revealed a carcinoma composed of signet-ring cells with intracytoplasmic mucin. Breast biopsy also showed signet-ring cells within the lymphatics. Pleural fluid cytology showed similar malignant cells. The patient was diagnosed as gastric signet-ring cell adenocarcinoma with endobronchial, mammary, ovarian, pleural, pericardial, peritoneal, and osteal metastases. The authors recommend that deep-vein thrombosis in unusual sites deserves further evaluation for an occult malignancy.
Use of Recombinant Factor VIIa in Inherited and Acquired von Willebrand Disease
Authors: Sucker Christoph , Scharf Rüdiger E. , Zotz Rainer B.
Published: February 2008

Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for the treatment of life-threatening bleeding episodes after failure of respective standard therapy. In this article, the authors focus on the use of the agent in patients with inherited or acquired von Willebrand disease (vWD). Although the current experience is sparse, published cases indicate the high efficacy of rFVIIa for the treatment of patients refractory to conventional treatment. The agent may be used in patients with congenital vWD complicated by alloantibodies directed against substituted von Willebrand factor or in the presence of concomitant hemostatic defects as well as acquired vWD with hitherto limited therapeutic options. Controlled clinical studies are necessary to define the use of rFVIIa in this clinical setting.
Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium
Authors: Ekström Smedby Karin , Vajdic Claire M. , Falster Michael , Engels Eric A. , Martínez-Maza Otoniel , Turner Jennifer , Hjalgrim Henrik , Vineis Paolo , Seniori Costantini Adele , Bracci Paige M. , Holly Elizabeth A. , Willett Eleanor , Spinelli John J. , La Vecchia Carlo , Zheng Tongzhang , Becker Nikolaus , De Sanjosé Silvia , Chiu Brian C.-H. , Dal Maso Luigino , Cocco Pierluigi , Maynadié Marc , Foretova Lenka , Staines Anthony , Brennan Paul , Davis Scott , Severson Richard , Cerhan James R. , Breen Elizabeth C. , Birmann Brenda , Grulich Andrew E. , Cozen Wendy
Published: February 2008

Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.
Expression of the "stem cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas
Authors: Immervoll Heike , Hoem Dag , Sakariassen Per Øystein , Steffensen Ole Johnny , Molven Anders
Published: February 2008

Background

It has been suggested that a small population of cells with unique self-renewal properties and malignant potential exists in solid tumors. Such "cancer stem cells" have been isolated by flow cytometry, followed by xenograft studies of their tumor-initiating properties. A frequently used sorting marker in these experiments is the cell surface protein CD133 (prominin-1). The aim of this work was to examine the distribution of CD133 in pancreatic exocrine cancer.

Methods

Fifty-one cases of pancreatic ductal adenocarcinomas were clinically and histopathologically evaluated, and immunohistochemically investigated for expression of CD133, cytokeratin 19 and chromogranin A. The results were interpreted on the background of CD133 expression in normal pancreas and other normal and malignant human tissues.

Results

CD133 positivity could not be related to a specific embryonic layer of organ origin and was seen mainly at the apical/endoluminal surface of non-squamous, glandular epithelia and of malignant cells in ductal arrangement. Cytoplasmic CD133 staining was observed in some non-epithelial malignancies. In the pancreas, we found CD133 expressed on the apical membrane of ductal cells. In a small subset of ductal cells and in cells in centroacinar position, we also observed expression in the cytoplasm. Pancreatic ductal adenocarcinomas showed a varying degree of apical cell surface CD133 expression, and cytoplasmic staining in a few tumor cells was noted. There was no correlation between the level of CD133 expression and patient survival.

Conclusion

Neither in the pancreas nor in the other investigated organs can CD133 membrane expression alone be a criterion for "stemness". However, there was an interesting difference in subcellular localization with a minor cell population in normal and malignant pancreatic tissue showing cytoplasmic expression. Moreover, since CD133 was expressed in shed ductal cells of pancreatic tumors and was found on the surface of tumor cells in vessels, this molecule may have a potential as clinical marker in patients suffering from pancreatic cancer.
Activation of cyclic-AMP response element binding protein contributes to adiponectin-stimulated interleukin-10 expression in raw 264.7 macrophages
Authors: Park Pil-hoon , Huang Honglian , McMullen Megan R , Bryan Kathryn , Nagy Laura E
Published: February 2008

Adiponectin, an adipokine predominantly secreted from adipose tissue, has potent anti-inflammatory properties. Although the mechanisms for the anti-inflammatory properties of adiponectin are not well understood, recent evidence suggests that increased production of interleukin-10 (IL-10), a potent immunomodulatory cytokine, is involved in the anti-inflammatory actions of adiponectin. Globular adiponectin (gAcrp) increased IL-10 promoter activity and IL-10 mRNA accumulation in RAW 264.7 macrophages. Deletion of the sequences from −416 and −369 in the IL-10 promoter, containing a cyclic AMP-response element (CRE), decreased gAcrp-induced IL-10 promoter activation. Treatment of RAW 264.7 macrophages with gAcrp increased the phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133, as well as enhanced the DNA binding activity of CREB. Further, overexpression of a dominant negative form of CREB suppressed gAcrp-induced transcriptional activation of IL-10. gAcrp-stimulated CREB phosphorylation was mediated by the activation of both ERK1/2- and cAMP-dependent protein kinase (PKA)-dependent pathways. Inhibition of either ERK1/2 or PKA activity prevented gAcrp-stimulated CREB phosphorylation, as well as gAcrp-stimulated IL-10 promoter activation. Taken together, these data identify gAcrp-stimulated phospho-CREB as a key transcription factor responsible for gAcrp-induced IL-10 promoter activation.
Natural killer cells from protein kinase C θ−/− mice stimulated with interleukin-12 are deficient in production of interferon-γ
Authors: Page Karen M , Chaudhary Divya , Goldman Samuel J , Kasaian Marion T
Published: February 2008

Protein kinase C θ (PKCθ) is expressed in NK cells, but its functional role has not been defined. Here, we demonstrate involvement of PKCθ in IL-12-induced NK cell IFN-γ production. NK cells from PKCθ−/− mice produced less IFN-γ in response to IL-12 than those from wild-type (WT) mice. IL-12-induced NK cell cytotoxicity was unaffected, and NK cells from PKCθ−/− mice did not display reduced IFN-γ production in response to IL-18, indicating a specific role for PKCθ in IL-12-induced IFN-γ production. Under the conditions tested, T cells did not produce IFN-γ in response to IL-12 or affect the ability of NK cells to produce the cytokine. PKCθ deficiency did not affect NK cell numbers, granularity, viability, or cytotoxic activity in response to polyinosinic:polycytydylic acid. NK cells from PKCθ−/− mice exhibited normal expression of IL-12Rβ1 and STAT4 proteins and normal induction of STAT4 phosphorylation in response to IL-12. Phosphorylation of threonine 538 within the catalytic domain of PKCθ was detectable in NK cells from WT mice but was not enhanced by IL-12. Transcription of IFN-γ increased similarly in NK cells from WT and PKCθ−/− mice in response to IL-12, and there was no difference in IFN-γ mRNA stability. Taken together, these findings indicate a role for PKCθ in the post-transcriptional regulation of IL-12-induced IFN-γ production.
Quantification of lamivudine-resistant hepatitis B virus mutants by type-specific TaqMan minor groove binder probe assay in patients with chronic hepatitis B
Authors: Yoshida Shigeru , Hige Shuhei , Yoshida Miyuki , Yamashita Naoki , Fujisawa Shin-ichi , Sato Kaori , Kitamura Tadashiro , Nishimura Masaharu , Chuma Makoto , Asaka Masahiro , Chiba Hitoshi
Published: February 2008

Background

Lamivudine (LAM)-resistant hepatitis B virus (HBV) with mutations in the polymerase region frequently appears after long-term use of LAM. Several methods allowing detection of mutant strains (YIDD, YVDD) have been reported, but they have no quantitative characteristics. In this study, we explored a unique approach for quantification of each mutant strain.

Methods

A method for detection and quantification of wild and mutant strains was developed using realtime polymerase chain reaction and type-specific minor groove binder (MGB) probes, and tested in patients with chronic hepatitis B before and after additive treatment with adefovir dipivoxil (ADV).

Results

A good correlation was confirmed in HBV DNA quantity obtained between the YMDD-specific MBG probe assay and Amplicor HBV Monitor assay results ( P < 0.001), linear between 3 and 9 log copies/mL serum. Of 109 samples from patients with chronic hepatitis B tested by both these assays and conventional direct sequencing, 90 (88.2%) showed identical results. The assays successfully detected and quantified a single type of mutant in three of four patients with additive ADV treatment, and also two coexisting mutant types (YIDD and YVDD) in the remaining patient.

Conclusions

Our specific and sensitive method for detection and quantification of HBV DNA with the wild-type YMDD motif and its two mutant forms (YIDD and YVDD) appears to be clinically useful, especially in patients with multiple mutant HBV infections.
Multifocal fibrosclerosis: a new case report
Authors: Sommerfield A J , Lockman K A , Bathgate A J , Patrick A W
Published: February 2008

We describe the case of a gentleman who initially presented with isolated cranial diabetes insipidus and has subsequently developed progressive anterior pituitary failure. In addition, he has been found to have evidence of mesenteric fibrosis and primary sclerosing cholangitis. We suggest that his pituitary disease may also be caused by progressive fibrosis and that these separate pathological entities may be linked by the unifying diagnosis of progressive multifocal fibrosclerosis, a rare fibro-inflammatory process involving multiple organ systems.
Clinical biochemistry guidelines in Wales: their impact on laboratory services
Authors: Griffiths K D , Duffy E J , Oleesky D A
Published: February 2008

Background

Evidence of significant variations in clinical biochemistry practice in Wales led to the formation of the All Wales Clinical Biochemistry Audit Group (AWCBAG) in 1993, with the aim of auditing laboratory services to ensure that they are optimally used. As part of this process, clinical guidelines are produced and circulated to all clinical biochemistry departments in Wales. The current aim of the AWCBAG is to assess the extent and impact of adoption of these guidelines across Wales.

Methods

Three surveys were despatched at intervals over a decade to all clinical biochemistry departments in Wales to investigate practice in: (1) urine albumin testing to screen for diabetic nephropathy; (2) biochemical investigation of menopausal status and the monitoring of hormone replacement therapy; (3) screening for Cushing's syndrome.

Results

The results show that laboratories across Wales are generally following guideline criteria and are adapting their practice in-line with changing recommendations.

Conclusion

The introduction of AWCBAG guidelines has been widely accepted by clinical biochemistry departments in Wales. These guidelines have led to a more efficient and effective use of laboratory services.
Supraphysiological doses of intravenous PYY3-36 cause nausea, but no additional reduction in food intake
Authors: le Roux Carel W , Borg Cynthia M , Murphy Kevin G , Vincent Royce P , Ghatei Mohammad A , Bloom Stephen R
Published: February 2008

Background

Peptide YY (PYY3-36) infused to levels within the physiological range reduces appetite and food intake in humans without nausea. However, PYY3-36 has previously been shown to cause nausea at higher doses.

Methods

We studied the relationship of PYY3-36, nausea and food intake in six volunteers, using three different PYY3-36 preparations infused to achieve supraphysiological PYY plasma levels.

Results

Supraphysiological levels of PYY caused nausea in five subjects ( P < 0.05). Although PYY3-36 increased satiety ( P < 0.05) and reduced food intake ( P < 0.05), no greater enhancement of satiety or inhibition of food intake was observed compared with previous reports.

Conclusions

This study cautions against the use of supraphysiological doses of PYY3-36 as it may increase nausea with no benefit in food reduction.
Self-prescribed high-dose vitamin D3: effects on biochemical parameters in two men
Authors: Kimball Samantha , Vieth Reinhold
Published: February 2008

The lowest observed adverse effect level for vitamin D, said to cause hypercalcaemia in normal adults, is officially 95 µg/day. Serum 25-hydroxyvitamin D (25[OH]D) concentrations associated with hypervitaminosis D remain undefined. Reported 25(OH)D concentrations resulting from prolonged excessive vitamin D3 intakes have exceeded 700 nmol/L. We report self-prescribed high dose of vitamin D3 over 5–6 years by two men. Subject 1 had been taking 100 μg/day for 3 years followed by 3 years of 200 μg/day. Serum 25(OH)D concentrations averaged 130 nmol/L while taking 100 μg/day of vitamin D3. While taking 200 μg/day of vitamin D3, mean serum 25(OH)D concentrations were 260 nmol/L with no hypercalcaemia or hypercalcuria over the 6 years of vitamin D3 intake. Subject 2 was a 39-year-old man diagnosed with multiple sclerosis. He initiated his own dose-escalation schedule. His vitamin D3 intake increased from 200 to 2200 μg/day over 4 years. The first evidence of a potential adverse effect was that urinary calcium:creatinine ratios showed an increasing trend, which preceded serum calcium concentrations above the reference range (2.2–2.6 mmol/L). His serum 25(OH)D concentration was 1126 nmol/L when total serum calcium reached 2.63 mmol/L. He stopped vitamin D3 supplementation at this point. Two months later, all biochemistry values were within reference ranges; serum 25(OH)D concentrations fell by about one-half, to 656 nmol/L. These results help to clarify the human response to higher intakes of vitamin D3. Close monitoring of biochemical responses confirmed that an increase in urinary calcium:creatinine ratio precedes hypercalcaemia as serum 25(OH)D concentrations rise.
Extent of bilirubin interference with Beckman creatinine methods
Authors: Dimeski Goce , McWhinney Brett , Jones Brock , Mason Rebecca , Carter Andrew
Published: February 2008

Background

The aim of the study was to determine the extent of bilirubin interference on two different Beckman–Coulter creatinine methods used on the CX5 PRO/DxC 600 and the DxC 800 systems, respectively.

Methods

The Beckman methods were compared with a high-performance liquid chromatography (HPLC) method using 104 patient samples with creatinine concentrations <133 μmol/L and bilirubin concentrations of between 30 and 802 μmol/L.

Results

The linear regression analysis calculations expressing the relationship between bilirubin concentration and the observed difference between the Beckman and HPLC creatinine methods are: DxC800 creatinine M (modular or cup) method: r2 0.217, slope −0.023 and intercept 6.43; and DxC600 method: r2 0.7324, slope −0.0882 and intercept 12.01.

Conclusions

There is significantly greater interference by bilirubin on the CX5 PRO/DxC 600 method, which can lead to inaccuracy in the calculation of the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation.
Diagnosing unsuspected hypopituitarism in adults from suggestive thyroid function test results
Authors: Preiss David , Todd Louise , Panarelli Maurizio
Published: February 2008

Background

The typical pattern of thyroid function tests (TFTs) associated with hypopituitarism consists of subnormal free T4 (fT4) or total T4 and normal or marginally elevated thyroid-stimulating hormone (TSH). A previous study calculated an incidence of hypopituitarism of 3.2 cases/100,000/year by following up abnormal TFTs. The aim of this study was to verify the incidence of unsuspected hypopituitarism diagnosed by reflective testing on such samples in a Scottish population.

Methods

Prospective audit of TFT results over 15 months. Individuals with suitable results (fT4 < 9 pmol/L, TSH < 10 mU/L) were identified by the laboratory information system at the Biochemistry Department, Glasgow Royal Infirmary, serving a population of 200,000. fT4 (repeat analysis following assay recalibration), total T3, testosterone (males), luteinizing hormone, follicle-stimulating hormone, prolactin and cortisol were analysed on appropriate samples.

Results

Three hundred and eleven suitable results from 266 adult individuals were identified from a total of 73,650 TFT results, leading to the diagnosis of 10 new cases (age range 28–90 years) of hypopituitarism (approximately 4 cases/100,000/year). Nine patients now attend endocrine clinics. Pituitary imaging was abnormal in five cases (2 large pituitary tumours, one macroadenoma, 2 empty sellae), normal in three cases and two patients were not scanned.

Conclusions

A significant number of cases of unsuspected hypopituitarism can be diagnosed by reflective testing on appropriate samples. fT4 should be an integral part of frontline TFTs as TSH alone cannot assist in the identification of possible hypopituitarism. Laboratories are in an excellent position to assist in early identification of hypopituitarism, which may lead to improved outcomes in such patients.
Delay in separating blood samples affects creatinine measurement using the Roche kinetic Jaffe method
Authors: Ford Loretta , Berg Jonathan
Published: February 2008

Background

We have examined the effect of delayed sample separation on serum creatinine measurement using the kinetic Jaffe method and estimated glomerular filtration rate (eGFR), and the impact this can have on chronic kidney disease (CKD) staging.

Methods

In a preliminary study clotted samples were left at room temperature for up to 48 h prior to centrifugation and serum creatinine measurement on a Roche modular analyser. A larger study then used paired clotted samples separated at baseline (30 min) and after 24 h at room temperature. To determine the effect on CKD staging, eGFR was calculated using the simplified [4-v] Modification of Diet in Renal Disease formula.

Results

Preliminary study. A significant increase in creatinine concentration ( P < 0.001) occurred after a 16 h delay in sample separation. By 48 h the mean increase in creatinine was 29% (range 21–63%). Twenty-four hour delay study. The mean increase in creatinine for 113 outpatient samples after delaying sample separation by 24 h was 11%, and exhibited considerable individual variation (range 2–87%). CKD staging for 32% of the group changed, 26% from stage 1 to 2 and 6% from stage 2 to 3.

Conclusions

Delay in sample separation affects the creatinine measurement using the Roche kinetic Jaffe reaction, and can result in the misclassification of CKD staging. Laboratories using the kinetic Jaffe method should not report creatinine results where there has been a delay in separation. This advice should also be reflected in practice guidelines.
Biochemical detection of phaeochromocytoma: why are we continuing to ignore the evidence?
Authors: Peaston Robert T , Ball Stephen
Published: February 2008

Phaeochromocytomas are rare tumours that require consideration among large numbers of patients with hypertension. If not diagnosed, the excessive secretion of catecholamines by these tumours can cause considerable morbidity and mortality. With a wide clinical variability in presentation, diagnosis can be difficult and invariably requires the biochemical confirmation of excessive catecholamine production by the tumour. At the First International Symposium on Phaeochromocytoma in October 2005, a panel of experts recommended that initial biochemical testing for phaeochromocytoma should include measurements of plasma and urinary metadrenalines. The accumulated evidence clearly indicates that measurement of fractionated metadrenalines in urine or plasma provides superior diagnostic sensitivity over plasma or urine measurements of catecholamines and metabolites. The low prevalence of phaeochromocytoma and paraganglioma (PGL) emphasizes the need to use biochemical tests of the highest sensitivity. To achieve this, it is recommended that the initial biochemical testing for phaeochromocytoma and secreting PGL should always include the measurements of metadrenalines in plasma or urine or both.
Learning needs in clinical biochemistry for doctors in foundation years
Authors: Khromova Victoria , Gray Trevor A
Published: February 2008

Background

Most medical school curricula have reduced the amount of time available for teaching in pathology despite the fact that junior staff in the early stages of their training were responsible for requesting the majority of pathology tests on acutely ill hospital patients. So, the lack of specific training in this area means that test requesting may be poorly performed and the results ill understood by these staff. This paper describes a questionnaire, which was designed to assist laboratory staff providing targeted teaching in this area.

Methods

Doctors in Foundation year 1 (F1) and Foundation year 2 (F2) in Sheffield teaching hospitals were given a questionnaire to ascertain how confident they were in requesting and interpreting the results of clinical biochemistry tests. The doctors were also asked about which areas of laboratory medicine they would like to be taught.

Results

Responses were received from 82 doctors, about half those in F1 and F2. The survey revealed areas where juniors are less confident in requesting tests and interpreting results. Despite lack of confidence in interpreting the result, 18% were confident about requesting tests. Doctors were also unsure of the effects of common problems like haemolysis on the interpretation of results. More than 70% of the doctors requested specific teaching in these areas.

Conclusions

Foundation doctors have learning needs in clinical biochemistry, addressing which would assist them in patient care. While better training in medical school may help in future, there are specific needs for those on the wards now that require targeted teaching.
Newborn bloodspot screening in the UK – past, present and future
Authors: Downing Melanie , Pollitt Rodney
Published: February 2008

Screening newborn babies for inherited metabolic disease began in the UK in the late 1950s with the ‘nappy test’ for phenylketonuria. In 1969 the Department of Health recommended changing to bloodspot screening using the techniques developed in the USA by Robert Guthrie and his associates. Bloodspot screening for various other disorders (galactosaemia, maple syrup urine disease, homocystinuria, cystic fibrosis and others) was introduced on a patchy local basis but, until 2000, the only additional disorder officially recommended was congenital hypothyroidism. Screening for haemoglobinopathies received official support in 2000 and for cystic fibrosis in 2001 though implementation was slow, particularly for the latter. Both these screens have raised difficult issues relating to genetic privacy and the detection of carrier status in children. During the last decade screening has become increasingly subject to central control. Though a more consistent and systematic approach was clearly needed, this has undoubtedly slowed the rate of innovation. In particular the UK has lagged behind many other European countries in the application of tandem mass spectrometry (MS-MS) though, following a major pilot study, screening for medium-chain acyl-CoA dehydrogenase deficiency is now in the process of introduction. Attempts to codify clinical and laboratory procedures have also proved controversial, highlighting marked differences in practice in various parts of the country and the difficulty of rationalizing these within a practicable and scientifically justified framework. Notwithstanding this, there are many positive developments and newborn screening remains a stimulating and rewarding field in which to work.
Are biochemistry interpretative comments helpful? Results of a general practitioner and nurse practitioner survey
Authors: Barlow Ian M
Published: February 2008

Background

Adding or incorporating clinical interpretative comments on biochemistry results is widespread in UK laboratories; although this consumes considerable human resource, there is still little evidence to suggest that it is either effective or appreciated by our clinical colleagues. I therefore decided to survey our local general practitioners (GPs) and nurse practitioners to analyse whether they found biochemistry comments on reports helpful.

Methods

A simple questionnaire was designed and sent to 159 GPs and 81 nurse practitioners asking them whether they found this activity useful for the limited range of test groups that we routinely comment on and also whether they would like to see commenting on more groups of tests.

Results

Overall, 49.6% of questionnaires were returned. Of these, there was overwhelming support for commenting on reports and 77% would like to see comments on a greater range of tests.

Conclusions

Although adding clinical interpretative comments is very time-consuming for senior laboratory staff, there is overwhelming support of this activity among our GPs and nurse practitioner users; therefore, our local policy of routinely adding clinical comments will remain for the foreseeable future.
Association of leprosy with HLA-DRB1 in an Argentinean population
Authors: Borrás Silvia García , Cotorruelo Carlos , Racca Liliana , Recarte Mónica , Garcías Celeste , Biondi Claudia , Bottasso Oscar , Racca Amelia
Published: February 2008

Background

Previous studies have suggested an influence of HLA molecules on the regulation of the anti Mycobacterium leprae immune response.

Methods

DNA typing of HLA-DRB1 alleles in 71 leprosy patients and 81 healthy controls was performed. Genomic DNA was extracted from peripheral blood and used as a template to amplify the polymorphic second exon of the HLA-DRBl by the ploymerase chain reaction (PCR). PCR products were hybridized separately with sequence-specific oligonucleotides.

Results

DRB1*1401 and DRB1*1406 alleles were significantly more prevalent in leprosy patients, whereas a decreased frequency of DRB1*0808 and DRB1*1103 alleles was found, by comparison with the group control.

Conclusions

The HLA-DRB1 alleles could act alone or in combination with other genes to confer differential susceptibility and also protection to leprosy disease in endemic areas of the American continent.
Too close for comfort: Accidental burn following subcutaneous mastectomy and immediate implant reconstruction
Authors: Seth R , Lamyman Mj , Athanassopoulos A , Tyler M
Published: February 2008

We report a case of an accidental burn from a self-applied heat pack following subcutaneous mastectomy and implant reconstruction. Such patients are at increased risk of accidental burns not only due to loss of protective sensation, but also because of the thinner, less vascular overlying skin. We have changed our practice so that all patients undergoing breast reconstructive surgery are warned postoperatively to protect the skin from externally applied heat sources.
Gender and variation in activity rates of hospital consultants
Authors: Bloor Karen , Freemantle Nick , Maynard Alan
Published: February 2008

Objective

To explore whether or not gender predicts consultant activity rates.

Design

Using data from the Hospital Episode Statistics for England 2004/2005, we explored inpatient activity rates of male and female hospital consultants, with and without adjustment for case-mix differences. As a sensitivity analysis we also explored outpatient attendances for male and female hospital consultants.

Setting

Data from the Hospital Episode Statistics for England.

Main outcome measures

Finished consultant episodes per year, with and without adjustment for case-mix differences, age and gender of consultant, contract held, hospital trust, specialty of practice, and clinical excellence awards, discretionary points and distinction awards.

Results

Including only consultants on full-time or maximum part-time contracts, men have significantly higher activity rates than women, after accounting for age, specialty and hospital trust.

Conclusions

The reasons for the different activity rates of male and female consultatns are unclear, but the implications of these results for the planning of the medical workforce are important.
Shooting Decisions by Police Firearms Officers
Authors: Mitchell Lucy , Flin Rhona
Published: February 2008

This study is an investigation into whether briefing information, which was heard prior to seeing a firearms incident in a firearms training simulator, affected British police officers' decisions to shoot, as measured by their shooting behavior. Police authorized firearms officers (AFOs) heard either threat or neutral briefing information and then saw a “shoot” (suspect shot at AFO) or “no-shoot” (suspect surrendered without shooting) scenario. AFOs were tested in one of four conditions: threat briefing with shoot scenario, threat briefing with no-shoot scenario, neutral briefing with shoot scenario, or neutral briefing with no-shoot scenario. A postevent questionnaire and the General Decision Making Style (GDMS) questionnaire were completed by the AFOs. Those who had heard the neutral briefing felt more surprised when they saw the suspects than did those who had heard the threat briefing, regardless of which scenario they had seen. However, the briefing type did not affect the time taken to draw and aim the gun at the screen. No shots were fired in the no-shoot scenario, regardless of which briefing the AFOs had received. Differences in preferred decision style were not related to shooting decisions. The results suggest that the briefing information did not influence the AFOs'decisions to shoot, but they attended to cues in the scenario (not identified) and responded accordingly.
Augmenting Context-Dependent Memory
Authors: Stefanucci Jeanine K. , O'Hargan Shawn P. , Proffitt Dennis R.
Published: February 2008

The goal of this study was to design a human-computer interface that would increase the memorability of information presented by providing context as compared with memory with no context. Our focus was in augmenting context-dependent memory because it is a powerful and often unexploited characteristic of human cognition. To amplify this cognitive strength, we built the InfoCockpit, which included a large screen containing projected images of places, a three-dimensional surround-sound system that played ambient noises congruent with the projected images, and a flat-panel monitor that served as the focal display for the presentation of the to-be-remembered information. Participants in our study learned and recalled information in either the InfoCockpit or a standard desktop environment. The InfoCockpit group demonstrated a 131% memory advantage. Contextual factors that were previously found to be effective in isolation created a large effect when presented in combination.