bluuebunny/crossref_metadata_2025 huggingface dataset:
The Croatian profit tax: an ACE in practice
Authors: Keen Michael , King John
Published: August 2010

This paper discusses the experience of Croatia in applying, from 1994 to the beginning of 2001, a profit tax that was charged only on equity income in excess of an imputed normal return ‐ and was thus, in essence, an ‘Allowance for Corporate Equity’ (ACE) scheme of the kind advocated by the IFS Capital Taxes Group and others. The computation of taxable profit under this system is summarised, and the theoretical attractions of the system are described. The paper then discusses a variety of criticisms that were made of the system in Croatia, including an alleged bias in favour of capital‐intensive enterprises (and, in particular, large State‐owned enterprises with overvalued assets), international complications, the complexity of the computations of taxable profit, the possibility that the rate of protective interest was set at an inappropriate level, and excessive revenue cost.
The restructuring and privatisation of British Rail: was it really that bad?
Authors: Pollitt Michael G. , Smith Andrew S. J.
Published: August 2010

This paper uses a social cost‐benefit analysis (SCBA) framework to assess whether rail privatisation in Britain has produced savings in operating costs. The paper shows that major efficiencies have been achieved and consumers have benefited through lower prices, whilst the increased government subsidy has been largely recouped through privatisation proceeds. We also find that output quality is no lower (and is probably better) than under the counterfactual scenario of public ownership (pre‐Hatfield). The achievement of further savings is key to delivering improved rail services in the future. This paper finds that a privatised structure, where shareholders demand a return on their investment, has led to significant improvements in operating efficiency. It remains to be seen whether the new regime, with a not‐for‐profit infrastructure owner, will deliver the same efficiency improvements.
Citizenship and Social Security
Authors: Plant Raymond
Published: August 2010

The aim of this paper is to elucidate the idea of citizenship that lies behind the Labour government's welfare reforms. There has been no proper statement about this from the government, so the paper is an attempt to make explicit what is latent in the reforms. It does this partly historically by looking at ideas of citizenship that have been presupposed in the development of the British Welfare State. It is claimed that there are two rather different approaches to be discerned: one sees citizenship as a basic status, which in turn is the basis of entitlement; the other view is that citizenship is something that has to be developed or achieved, typically by participation in the labour market and by discharging obligations. This distinction is then used more analytically to assess some of the welfare reforms and to indicate possible sources of future difficulty and tension in so far as the government embraces the obligation‐oriented view of citizenship.
Data Governance and Stewardship: Designing Data Stewardship Entities and Advancing Data Access
Authors: Rosenbaum Sara
Published: August 2010

U.S. health policy is engaged in a struggle over access to health information, in particular, the conditions under which information should be accessible for research when appropriate privacy protections and security safeguards are in place. The expanded use of health information—an inevitable step in an information age—is widely considered be essential to health system reform. Models exist for the creation of data‐sharing arrangements that promote proper use of information in a safe and secure environment and with attention to ethical standards. Data stewardship is a concept with deep roots in the science and practice of data collection, sharing, and analysis. Reflecting the values of fair information practice, data stewardship denotes an approach to the management of data, particularly data that can identify individuals. The concept of a data steward is intended to convey a fiduciary (or trust) level of responsibility toward the data. Data governance is the process by which responsibilities of stewardship are conceptualized and carried out. As the concept of health information data stewardship advances in a technology‐enabled environment, the question is whether legal barriers to data access and use will begin to give way. One possible answer may lie in defining the public interest in certain data uses, tying provider participation in federal health programs to the release of all‐payer data to recognized data stewardship entities for aggregation and management, and enabling such entities to foster and enable the creation of knowledge through research.
Balancing Access to Health Data and Privacy: A Review of the Issues and Approaches for the Future
Authors: Lane Julia , Schur Claudia
Published: August 2010

Background. There has been a dramatic increase in the types of microdata, and this holds great promise for health services research. However, legislative efforts to protect individual privacy have reduced the flow of health care data for research purposes and increased costs and delays, affecting the quality of analysis.

Aim. This paper provides an overview of the challenges raised by concerns about data confidentiality in the context of health services research, the current methodologies used to ensure data security, and a description of one successful approach to balancing access and privacy.

Materials and Methods. We analyze the issues of access and privacy using a conceptual framework based on balancing the risk of reidentification with the utility associated with data analysis. The guiding principle should be to generate released data that are as close to the maximum acceptable risk as possible. HIPAA and other privacy measures can perhaps be seen as having had the effect of lowering the “maximum acceptable risk” level and rendering some data unreleasable.

Results. We discuss the levels of risk and utility associated with different types of data used in health services research and the ability to link data from multiple sources as well as current models of data sharing and their limitations.

Discussion. One particularly compelling approach is to establish a remote access “data enclave,” where statistical protections are applied to the data, technical protections ensure compliance with data‐sharing requirements, and operational controls limit researchers' access to the data they need for their specific research questions.

Conclusion. We recommend reducing delays in access to data for research, increasing the use of remote access data enclaves, and disseminating knowledge and promulgating standards for best practices related to data protection.
Health Services Research and Data Linkages: Issues, Methods, and Directions for the Future
Authors: Bradley Cathy J. , Penberthy Lynne , Devers Kelly J. , Holden Debra J.
Published: August 2010

Background. Research on pressing health services and policy issues requires access to complete, accurate, and timely patient and organizational data.

Aim. This paper describes how administrative and health records (including electronic medical records) can be linked for comparative effectiveness and health services research.

Materials and Methods. We categorize the major agents (i.e., who owns and controls data and who carries out the data linkage) into three areas: (1) individual investigators; (2) government sponsored linked data bases; and (3) public–private partnerships that facilitate linkage of data owned by private organizations. We describe challenges that may be encountered in the linkage process, and the benefits of combining secondary databases with primary qualitative and quantitative sources. We use cancer care research to illustrate our points.

Results. To fill the gaps in the existing data infrastructure, additional steps are required to foster collaboration among institutions, researchers, and public and private components of the health care sector. Without such effort, independent researchers, governmental agencies, and nonprofit organizations are likely to continue building upon a fragmented and costly system with limited access.

Discussion. Without the development and support for emerging information technologies across multiple health care settings, the potential for data collected for clinical and transactional purposes to benefit the research community and, ultimately, the patient population may go unrealized.

Conclusion. The current environment is characterized by budget and technical challenges, but investments in data infrastructure are arguably cost‐effective given the need to reform our health care system and to monitor the impact of health reform initiatives.
Viewing Health Care Delivery as Science: Challenges, Benefits, and Policy Implications
Authors: Pronovost Peter J. , Goeschel Christine A.
Published: August 2010

The need for health services research is likely to rise rapidly as the population ages, health care costs soar, and therapeutic and diagnostic choices proliferate. Building an effective and efficient health care delivery system is a national priority. Yet the national health care quality report concludes that we lack the ability to monitor progress toward even basic quality and patient safety goals effectively.

The gap between the need to improve and our ability to do so exists in part because we fail to view the delivery of health care as science, we lack national improvement priorities, and we lack a national infrastructure to achieve our stated goals.

We discuss key challenges implicit in correcting these failures and recommend actions to expedite progress.
Modeling Health Care Policy Alternatives
Authors: Ringel Jeanne S. , Eibner Christine , Girosi Federico , Cordova Amado , McGlynn Elizabeth A.
Published: August 2010

Background. Computer models played an important role in the health care reform debate, and they will continue to be used during implementation. However, current models are limited by inputs, including available data.

Aim. We review microsimulation and cell‐based models. For each type of model, we discuss data requirements and other factors that may affect its scope. We also discuss how to improve models by changing data collection and data access procedures.

Materials and Methods. We review the modeling literature, documentation on existing models, and data resources available to modelers.

Results. Even with limitations, models can be a useful resource. However, limitations must be clearly communicated. Modeling approaches could be improved by enhancing existing longitudinal data, improving access to linked data, and developing data focused on health care providers.

Discussion. Longitudinal datasets could be improved by standardizing questions across surveys or by fielding supplemental panels. Funding could be provided to identify causal parameters and to clarify ranges of effects reported in the literature. Finally, a forum for routine communication between modelers and policy makers could be established.

Conclusion. Modeling can provide useful information for health care policy makers. Thus, investing in tools to improve modeling capabilities should be a high priority.
The Safety and Efficacy of Varenicline in Cocaine Using Smokers Maintained on Methadone: A Pilot Study
Authors: Poling James , Rounsaville Bruce , Gonsai Kishorchandra , Severino Kevin , Sofuoglu Mehmet
Published: August 2010

In this double‐blind, placebo‐controlled trial, we compared varenicline (2 mg) to placebo for treatment for cocaine and tobacco dependence in 31 methadone‐maintained subjects. Subjects received weekly counseling during the 12‐week study participation. Our results indicate that varenicline is safe to give to this subject population, as there were no adverse events related to medication during this study. Varenicline was no more effective than placebo for abstinence from cocaine. Treatment with varenicline was associated with a reduced number of cigarettes smoked per day, even though subjects received only a brief education for smoking cessation. The self‐report reduction in smoking was corroborated by CO levels and the Fagerström Test of Nicotine Dependence. However, self‐ratings of positive mood on the Positive Affect Negative Affect Schedule did significantly decrease in the varenicline group as compared to the placebo group, although this appears to be due to randomization differences related to lifetime depression diagnosis. These preliminary findings may point to potential therapeutic value of varenicline for smoking cessation in cocaine users maintained on methadone. (Am J Addict 2010;19:401–408)
Time's Arrow: Violence and Ethnohistorical Surrealism in the Lost Colony
Authors: HARKIN MICHAEL E.
Published: August 2010

Standard ethnohistorical accounts of colonial encounters downplay violence and genocide in the interest of holistic ethnographic accounts. In particular, “upstreaming” is a technique that attempts to sublimate violence into interpretations of ethnological understanding. An argument is made for “ethnohistorical surrealism” as a methodology for preserving the ruptures of colonial contact. The principle of incommensurability is an important driver for the transformation of contact zone exchange systems into structures of violence. Drawing on Bataille's reading of the potlatch, exchange systems based on unreturnable gifts produce abjection in the recipient, which results in cycles of violence and ultimately subjection.
Violence and Recreation: Vacationing in the Realm of Dark Tourism
Authors: ROBB ERIKA M.
Published: August 2010

Tourist destinations are typically conceptualized as sites of leisure. However, in recent years places associated with human misery and death have become the focus of sizable touristic interest. This practice, called dark tourism (Lennon and Foley 2000), involves visiting destinations at which violence is the main attraction. Dark tourism includes both places with violent legacies and those at which violence is an ongoing reality. It encompasses a wide variety of visitor motivations—educational, memorial, or recreational. In this article, I take a cross‐regional approach to a diverse group of dark tourism sites, from Rwanda and Argentina to the United States and Brazil, considering their aesthetics and the experiences of visitors to contribute to the theoretical exploration of the relationship between tourism and violence.
Two cases of tongue cancer treated with intra‐ and peri‐tumoral injection of recombinant interleukin‐2 alone: immunohistochemical considerations to clinical tumor response
Authors: Hiratsuka H , Noguchi M , Kinjo H , Odajima T , Kohama G
Published: August 2010

SUBJECTS AND METHODS: Two cases with stage II tongue cancer who exhibited different responses to intra‐and peri‐tumoral administration of rlL‐2 alone are presented. Special consideration is given to the relationship between tumor responses to rlL‐2 and clinicopatholog‐ical and immunohistopathological findings.

RESULTS: The patient who responded completely to treatment showed an exophytic tumor growth pattern, low‐grade cancer invasion, and predominant infiltration of CD8+ lymphocytes over CD4+ lymphocytes in cancer cell nests. The non‐responder showed endophytic tumor growth, high‐grade cancer invasion, and uniform distribution of both CD4+ and CD8+ lymphocytes in cancer cell nests.

CONCLUSIONS: Distribution of adequate amounts of T lymphocytes subsets may be necessary in order for good tumor response to biotherapy with rlL‐2; other clinical and histopathological variables predicting the effect for cancer chemotherapy remain to be identified.
Origins and functions of cells essential for periodontal repair: the role of fibroblasts in tissue homeostasis
Authors: McCulloch CAG
Published: August 2010

OBJECTIVE: A review is undertaken of redent model systems and cell culture studies that address the role of periodontal fibroblasts in tissue homeostasis in both normal function and after wound healing.

RATIONALE: Fibroblasts are the predominant cells of the periodontal ligament (PL) and of healthy gingiva and have important roles in the development, function and regeneration of the tooth support apparatus.

REVIEW: In normally functioning periodontal tissues cell turnover involves generation of new cells by proliferation which in turn is balanced by apoptotic cell death. Consequently PL fibroblasts comprise a renewal cell system in steady‐state. PL cell progenitors can generate multiple types of more differentiated, specialized cells including latge numbers of fibroblastic cells and more limited numbers of osteogenic or cementogenic cells. However PL fibroblasts constitutively block osteogenesis and thereby maintain the PL width. Proliferating progenitor cell populations of the PL are enriched in locations adjacent to blood vessels and in contiguous endosteal spaces from where they migrate to the body of the PL. Large increases of cell formation and cell differentiation occur after wounding but surprisingly, the cells that repopulate the PL adjacent to the root surface are largely post‐mitotic. As PL cell populations comprise multiple lineages, it is likely that after wounding, the separate phenotypes repopulating the wound site will be selected by environmental factors. Further, the specific repopulating lineages will strongly influence the form and function of the nascent tissue. To illustrate the specificity of fibroblast functions, examples of migratory and contractile fibroblast phenotypes are provided which exhibit constitutively different levels of gelsolin and α‐smooth muscle actin respectively, cytoskeletal proteins which are markers for these cell types.

CONCLUSION: Fibroblasts contribute to PL homeostasis by their abilities to remodel tissues, to repopulate wounds, to influence the metabolism of other cell types and to create a new fibrous attachment.
Desmoplastic and non‐desmoplastic ameloblastoma: a comparative clinicopathological analysis
Authors: Keszler A , Paparella ML , Dominguez FV
Published: August 2010

OBJECTIVES: The aim of this study was to review a large series of ameloblastomas, accessioned during a period of 35 years in a single Oral Pathology Diagnostic Center, for the incidence of desmoplastic ameloblastoma (DA) and in order to analyze the clinical features of this unusual variant.

MATERIALS AND METHODS: All cases diagnosed as ameloblastoma were reviewed and 14 were rediagnosed as DA. These cases were analyzed in terms of gender, patient age, location, clinical diagnosis, radiographic features and recurrence following treatment. Data from DA and non‐desmoplastic ameloblastoma (NDA) were compared.

RESULTS: The incidence of DA in this series was 8.8%. The mean age of NDA and DA were 39.1 and 38.8 years respectively, and a higher female prevalence was observed in the latter. The mandible was the most affected bone in both groups of tumors, but with a different regional distribution. Most NDA arose in the angle and ramus of the mandible, but the premolar/molar region was the preferential location for DA. The most common radiographic feature in DA was the osteolytic type, either monolocular or multilocular. Most of these cases were clinically diagnosed as ameloblastoma. According to follow‐up data available, 21.4% of DA and 10.1% of NDA recurred.

CONCLUSIONS: The results of this study do not support the hypothesis that DA should be a separate clinicopathological entity. It seems most likely that DA is another his‐tologic variant of ameloblastoma.
Chemokines and chemokine receptors: the key to understanding AIDS
Authors: Thornhill MH , Li J.
Published: August 2010

This article reviews the recent rapid developments in research that have demonstrated the importance of chemokines and their receptors in HIV infection and the progression to AIDS. These discoveries have transformed our understanding of how the virus may infect cells and why certain individuals may be resistant to HIV infection, and for the first time have opened up the very real prospect of developing strategies to prevent and treat this disease.
Analysis of oral manifestations of leukemia: a retrospective study
Authors: Hou G‐L , Huang J‐S , Tsai C‐C
Published: August 2010

OBJECTIVE: To evaluate in detail the oral complications of leukemia at initial presentation. Associations between oral manifestations and laboratory data were also investigated.

STUDY DESIGN: A retrospective study of 230 cases was conducted to investigate the nature and incidence of oral manifestations at initial presentation. The following data were determined for each patient: age, sex, haemogram at diagnosis (which included haemoglobin, red blood cell counts, differential white blood cell counts, platelet counts), classification of the type of leukemia's systemic symptoms and oral manifestations at the initial physical examination including the dental consultation.

RESULTS: It was revealed that the type of leukemia diagnosed, except with CML, is related to the age prediliction of patients. The incidence of leukemia is higher in males than in females. The most common manifestations of leukemia are lymphadenopathy (71.4% in ALL; 45% in AML), laryngeal pain (52.7% in ALL; 37.3% in AML), gingival bleeding (43.2% in AML; 28.6% in ALL), oral ulceration, and gingival enlargement. Fever (92.2%) was the most common symptom in patients with all types of leukemia. Platelet counts from 25000 mm‐3 to 60000 mm‐3 are at sufficiently low levels to result in spontaneous bleeding. Most of the patients had WBC counts of greater than 10000 mm‐3.Only 12.6% of patients had normal WBC counts.

CONCLUSIONS: It was concluded that the age predilic‐tion and prevalence of oral manifestations are closely related to the type of leukemia.
Extracts of Prevotella intermedia and Actinobacillus actinomycetemcomitans inhibit alkaline phosphatase activity in osteoblastic cells in vitro
Authors: Murata T. , Ansai T. , Takehara T. , Kobayashi S. , Haneji T.
Published: August 2010

In order to study the effects of sonicated extracts from Prevotella intermedia, Actinobacillus actinomycetemcomit‐ans, Porphyromonas gingivalis, and other oral‐related bacteria, as well as Escherichia coli on bone formation, clone MC3T3‐E1 cells, which have retained osteoblastic activity, were cultured with various bacterial extracts.

The addition of the sonicated extracts from Prevotella intermedia and Actinobacillus actinomycetemcomitans decreased the alkaline phosphatase activity in a dose‐dependent fashion over the concentration range of 1– 1000 ng ml‐1 compared with the control. By contrast, the sonicated extracts from other oral bacteria including Porphyromonas gingivalis, Capnocytophaga ochracea, Streptococcus milleri and Streptococcus sanguis, and Escherichia coli did not decrease the alkaline phosphatase activity even in the presence of 100 ng ml‐1 protein.

The addition of Prevotella intermedia and Actinobacillus actinomycetemcomitans extracts that had been treated with heat and trypsin to the cell cultures also inhibited alkaline phosphatase activity in the cells, suggesting that inhibitory factors are not proteinaceouS. Polymyxin B did not change the alkaline phosphatase activity in the cells treated with the extracts from Prevotella intermedia and Actinobacillus actinomycetemcomitans, suggesting that the inhibitory activity of the extracts is not lipopolysaccha‐ride.

The inhibitory effect of both extracts was observed in the molecular mass over 290 kDa eluted from Sephadex G‐200 column. The inhibitory substances of Prevotella intermedia were partially purified and showed broad band with estimated molecular weight of 170–190 kDa by sodium dodecyl sulfate‐polyacrylamide gel electro‐phoresis.

These results indicate that Prevotella intermedia and Actinobacillus actinomycetemcomitans may play an important role in inhibiting bone formation as well as in stimulating bone resorption.
Granulomatous cheilitis: a study of six cases
Authors: Kolokotronis A. , Antoniades D. , Trigonidis G. , Papanagiotou P.
Published: August 2010

OBJECTIVE: Granulomatous cheilitis (GC) is a very rare disorder of unknown etiology. Clinically, GC is characterised by recurrent swelling of the labial tissues, which may be followed by a permanent enlargement. Histologically, the typical form of GC is characterised by the formation of scattered aggregates of non‐caseating granulomaS. GC is the most frequent sign of orofacial granulomatosis, a disorder under which also encompasses sarcoidosis, Crohn's disease, atypical tuberculosis, Anderson‐Fabry disease, possibly some allergic reactions, and Melkersson‐Rosenthal syndrome (MRS).Some consider GC as an oli‐gosymptomatic or monosymptomatic form of MRS.

SUBJECTS AND METHODS: In this study we examined the clinical records of six patients presenting with GC which were examined and treated in the Department of Oral Medicine and Pathology of the Dental School of Aristotle University of Thessaloniki (Greece) during a 16‐year period. In five of six patients a persistent swelling of the lower lip was recorded, one of whom also developed swelling in the upper lip. In one case the swelling was present in both lips and in another the GC was the only clinical finding, while in the other five cases it was accompanied by at least one other feature of MRS. In five cases, the histological picture revealed non‐caseating granulomas.

RESULTS: The treatment with the intralesional infusion of corticosteroids in three cases and the oral administration of corticosteroids in two cases was successful. One of the patients refused to be treated. This patient also presented later with permanent swelling of the upper lip.
Intranodal injection of anticancer drugs into fixed cervical metastatic lymph nodes
Authors: Osaki T. , Ueta E. , Yoneda K. , Yamamoto T.
Published: August 2010

OBJECTIVE: In patients with head and neck carcinoma, fixed enlarged metastatic lymph nodes (LNs) are sometimes inoperable and carry an increased risk of mortality. To control metastatic LNs, we attempted intranodal injection of anticancer agents.

SUBJECTS AND METHODS: Fifteen patients with squamous cell carcinoma arising in the gingiva (8), tongue (3), floor of the mouth (1), or maxillary sinus (3) were enrolled. These patients consisted of two groups, those in the early era in which the fixed LNs of six patients were treated with 60Co (RA group) and those in the late era in which both radiation and intranodal injection of anticancer agents were administered to nine patients (IN group). Intranodal injection consisted of peplomycin, 5‐fiuorouracil, and cis‐diamminedichloroplatinum.

RESULTS: In the IN group, LNs regressed from about 40% to nearly 100%, although two patients showed no appreciable response. The LNs treated by combination therapy regressed considerably while LNs in the same patients treated with 60Co alone showed a minor response or grew gradually. In three patients, the LNs regressed sufficiently to be extirpated safely. The good clinical response in the locally injected LNs was histologically associated with distinct evidence of tumor cell degeneration. In the RA group, none of the LNs responded to radiation with 60Co; one LN exhibited slight regression, but the others enlarged during and soon after the radiation. Compatible with the clinical effects, many patients in the IN group demonstrated a good prognosis; three are alive without disease, and four survived for prolonged periodS. However, all patients in the RA group died due to progression of the positive LNs or pulmonary complication within 10 months.

CONCLUSION: These results indicate that intranodal injection of anticancer drugs is useful for the management of fixed enlarged LNs.
The role of IL‐6 in the pathogenesis of periodontal disease
Authors: Irwin CR , Myrillas TT
Published: August 2010

The mechanisms underlying periodontal disease involve complex interactions between bacterial products, host cells and locally produced, biologically active factors. The umbrella term cytokine has been used to include a variety of such factors, including the interleukin family. The role of one cytokine, IL‐β, in periodontal disease pathogenesis has been widely reported. More recent studies have focused on a potential role for IL‐6 in driving the destructive processes. Most of these reports have suggested a pro‐inflammatory role for IL‐6 alongside IL‐I and TNF‐α. This manuscript reviews the biological functions of IL‐6, specifically related to tissue destruction at the periodontal site. We would suggest that the activity of IL‐6 in periodontal disease differs from IL‐I and TNF‐α, and may, in part, play a protective role.
Snuff use and smoking among senior high school students: effects of a snuff sales ban
Authors: Merne MET , Tiekso JT , Syrjänen SM
Published: August 2010

OBJECTIVES: The popularity of snuff especially among adolescents is rising. The association between long‐term snuff use and oral cancer discovered in epidemiological studies has prompted a variety of preventive measures to be taken to reduce snuff use and prevent adoption of the habit. In this study, the effect of a recent (I March, 1995) snuff sales ban introduced in Finland was investigated. Further, the rates of smoking, snuff use, alcohol use and drug experimenting were investigated before the introduction of the ban to characterize the study population.

DESIGN AND SUBJECTS: Two questionnaire studies were carried out. The first was carried out 3 months prior to the ban in 1994 and the second 9 months after the ban in 1995 in a senior high school population in southwestern Finland. The participants were 793 students (aged 15–22 years) in the first survey and 545 students (aged 16–23) in the second. Associations between variables were analyzed using cross‐tabulation and stepwise logistic regression. The effects of the ban were determined on the basis of direct questions in the second questionnaire relating to the snuff sales ban.

RESULTS: Snuff was used by 9% of the students participating in the first study. The results of the second questionnaire indicate that the implementation of the snuff sales ban reduced the rate of snuff use by 1% in the study population. The majority of the snuff users (76%) reported that they had maintained their snuff habit. Of those reporting that they were snuff users before implementation of the snuff sales ban, 12% had switched to smoking and 5% to drugs.

CONCLUSIONS: The results of the present study suggest that the snuff sales ban in this population with a high rate of snuff use had little effect on snuff use rates and may have some short‐term negative consequences as some snuff users switch to other substitutes, such as smoking, with known adverse health effects.
The postantifungal effect (PAFE) of antimycotics on oral C. albicans isolates and its impact on candidal adhesion
Authors: Ellepola ANB , Samaranayake LP
Published: August 2010

OBJECTIVE:

Postantifungal effect (PAFE) is defined as the suppression of growth that persists following limited exposure of yeasts to antimycotics and subsequent removal of the drug. As there are no data on the PAFE of oral C albicans isolates the main aim of this investigation was to measure the PAFE of 10 oral isolates of C albicans following limited exposure (I h) to five antifungal drugs, including nystatin which has not been previously used in PAFE assays. A secondary aim of the study was to evaluate the biological significance of PAFE, using a nystatin pre‐exposed isolate of C albicans and observing its adherence to denture acrylic surfaces, during the PAFE period.

DESIGN:

A total of 10 oral isolates of C albicans were examined for the presence of the PAFE after I h exposure to five antifungal drugs, nystatin, amphotericin B, 5‐fluorocytosine, ketoconazole and fluconazole. PAFE was automatically assessed with the help of a Spectramax machine which utilizes the principle of periodic turbidometric assessment of growth rates at a given temperature over a given period. The data thus collected are automatically processed in a graphic format as a computer printout. The PAFE was determined as the difference in time (h) required for growth of the drug‐free control and the drug‐exposed test cultures to increase to 0.05 absorbance level following removal of the antifungal agent (by repeated washing). The adhesion of the single isolate to denture acrylic following limited exposure to nystatin was assessed by a previously described in vitro adhesion assay.

RESULTS:

Significant PAFE were observed for nystatin, amphotericin‐B and 5‐fluorocytosine. A marginal PAFE was observed for ketoconazole and little or none for fluconazole. The mean duration of the PAFE of nystatin, amphotericin‐B, 5‐fluorocytosine, ketoconazole and fluconazole were 2.89 (±0.27) h, 2.83 (±0.23) h, 3.18 (±0.31) h, 0.65 (±0.11) h and 0.16 (±0.06) h, respectively. The mean percentage reduction of adhesion of oral C albicans BU47204 to denture acrylic during the PAFE period following exposure to nystatin for 10, 30, 50, 70 and 90 min was 9.12%, 61.73%, 65.99%, 82.16% and 83.14%, respectively.

CONCLUSIONS:

These in vitro findings imply that even a short period of exposure to antifungals may result in modulation of the growth and the virulent attributes of C albicans, which however is largely dictated by the anti‐mycotic agent in question. Whether such mechanisms operate in vivo needs to be clarified by further studies.
Xylitol in caries prevention: what is the evidence for clinical efficacy?
Authors: Scheie AAa , Fejerskov OB
Published: August 2010

Xylitol has attracted much attention as an alternative sweetener. Essentially all clinical studies concerning the effect of xylitol on caries development consent to its non‐cariogenicity and to the beneficial effect of substituting sucrose with xylitol in chewing gums and sweets. However, claims of anti‐caries or therapeutic effects, and superiority of xylitol over other polyols are still to be confirmed by well designed and conducted studies from independent research groups.
The epidemiology of mouth cancer: a review of global incidence
Authors: Moore SR , Johnson NW , Pierce AM , Wilson DF
Published: August 2010

Mouth cancer (143–145 ICD‐9) is a major health problem in many parts of the world. While its incidence is relatively low in most western countries there are some important exceptions to this trend: on the Indian subcontinent and in other parts of Asia it remains one of the most common forms of cancer. This review article summarises the global incidence of mouth cancer using cancer mapS. Data have been compiled from the latest edition of Cancer Incidence in Five Continents and recent studies from various locations around the world. Significant geographic variation is noted in the incidence of mouth cancer, with high rates reported for the Indian subcontinent and parts of Asia (male incidence rates in excess of 10 per 100 000 per annum). It is also noted that as with other forms of oral cancer, the majority of population‐based data for mouth cancer comes from the Western world with a paucity of reliable data from the so‐called developing countrieS. Mouth cancer remains a serious health problem in many parts of the world with many regions reporting increasing incidence rates particularly in maleS. Ongoing research into the aetiologic risk factors associated with this disease must remain a very high priority if the causes of mouth cancer are to be established and disease control protocols introduced widely.
The epidemiology of tongue cancer: a review of global incidence
Authors: Moore SR , Johnson NW , Pierce AM , Wilson DF
Published: August 2010

The tongue (141 ICD‐9) is the most common intraoral site for cancer in most countries, however its global epidemiology shows significant geographic variation. This review paper summarises the global incidence of cancer of the tongue using cancer maps and references to recent studies from various locations. Tongue cancer remains a serious health problem in many countries including India (male incidence rates up to 6.5 per 100 000 per annum) and parts of Europe (male incidence rates in France up to 8.0 per 100 000 per annum). It is noted that as with other forms of oral cancer the majority of population‐based data for tongue cancer comes from the Western world with a paucity of reliable data from the so‐called developing countries. The tongue remains the most common intraoral site for oral cancer worldwide and in a number of countries it is a serious public health problem with significant morbidity and mortality. While the incidence of tongue cancer appears to be stable or falling in some regions of the world, in other areas it is rising, particularly among younger people.
Occurrence of oral lesions in relation to clinical and immunological status among HIV‐infected adult Tanzanians
Authors: Matee MI , Scheutz F. , Moshy J.
Published: August 2010

OBJECTIVE: To determine the association, if any, between the presence of oral lesions and clinical and immunological status of untreated HIV‐infected adults in Tanzania.

DESIGN: A cross‐sectional study.

SETTING: AIDS Clinical Trial Clinic (ATCC) at Muhimbili Medical Centre in Dar‐es‐Salaam, Tanzania. SUBJECTS: 192 HIV‐infected individuals not receiving treatment; 156 individuals confirmed to be HIV‐sero‐negative acted as a control group.

METHODS: Examination of oral structures, determination of HIV serostatus, clinical status, and peripheral CD4+ T cell and total lymphocyte counts.

MAIN OUTCOME MEASURE: Presence of oral lesionS. RESULTS: Intra‐oral lesions were seen among 7.7% of the HIV‐seronegative, 10.4% of the HIV‐seropositive and 36.8% of the AIDS groups, respectively. Enlarged parotid glands were seen in 20% of the AIDS patients, 11.9% of the HIV‐seropositives, and 5.1% of the HIV seronegativeS. Enlargement of submandibular salivary glands was seen in 29.6% of the AIDS patients, 31.3% of the HIV‐seropositives compared with 14.7% among the HIV‐seronegativeS. Multiple regression analysis was used to calculate adjusted odds ratio (OR) for presence of oral lesionS. OR for an intra‐oral lesion was 1.6 (95% CI = 0.5; 5.0) among the HIV‐seropositives and 8.2 (95% CI = 3.5; 19.7) among the AIDS patients using the HIV‐seronegatives as reference. OR for an intra‐oral lesion was 0.9 (95% CI = 0.3; 2.9) in HIV‐infected patients with peripheral CD4+ T cell count of between 200–500 cells mm‐3 and 2.7 (95% CI = 0.9; 7.7) in patients with less than 200 cells mm‐3.OR for an intra‐oral lesion was 0.4 (95% CI = 0.2; 0.9) for patients with peripheral total lymphocyte counts of between 1000–2000 cells mm‐3 and 0.9 (95 CI = 0.4; 2.0) for patients with less than 1000 cells mm‐3.

CONCLUSION: The association of oral lesions with the clinical stage of HIV infection and to a lesser extent peripheral CD4+ T cell count does suggest that these lesions could be used as additional markers of immunosuppression and AIDS.
Human immunodeficiency virus‐positive individuals with oral hairy leukoplakia are able to mount cytotoxic T lymphocyte responses to Epstein‐Barr virus
Authors: de Jong A , Palefsky JM , Stites DP , Nakagawa M
Published: August 2010

OBJECTIVE: Oral hairy leukoplakia (OHL) is a white lesion of the tongue that is caused by Epstein‐Barr virus (EBV) and occurs mainly in people infected with human immunodeficiency virus (HIV). The aim of this study was to determine whether the presence of OHL reflects the absence of EBV‐specific cytotoxic T lymphocyte (CTL) activity.

SUBJECTS AND METHODS: EBV‐specific CTL responses were measured in HIV‐positive homosexual men with OHL, HIV‐positive homosexual men without OHL, and HIV‐negative homosexual men. Also, the phenotypes of cells responsible for EBV‐specific responses were studied.

RESULTS: Eighty percent (8/10) of HIV‐positive subjects with OHL, 52% (12/23) of HIV‐positive subjects without OHL, and 83% (15/18) HIV‐negative subjects had a positive anti‐EBV CTL response (P= 0.004, Kruskal‐Wallis test). Two HIV‐positive subjects showed a greater anti‐EBV CTL response after developing OHL than before the appearance of OHL. Additional experiments showed that CD8‐positive T cells and CD4‐positive T cells were responsible for the EBV‐specific CTL responses.

CONCLUSION: Our data show more EBV‐specific CTL activities in HIV‐positive individuals with OHL than in HIV‐positive individuals without OHL. Whether the presence of EBV‐specific CTL contributes to resolution of OHL remains to be clarified.
OPTIONS FOR DENTIN/ENAMEL BONDING: PART IV
Authors: Swift Edward J.
Published: August 2010

Four categories of resin‐based dentin/enamel adhesives are currently available. These include the three‐step etch‐&‐rinse, “one‐bottle” etch‐&‐rinse, two‐step self‐etch primer systems, and “all‐in‐one” self‐etch adhesives. In consecutive issues of the Journal, the Critical Appraisal series is presenting salient publications on research in each of the categories. This final installment of the series focuses on the all‐in‐one self‐etch adhesives.
Meeting Trips Commitments in Ukraine
Authors: Antonyuk Olena V. , Kerr William A.
Published: August 2010

“America and Europe have been actively encouraging Mr. Yushchenko, and assisting civil‐society groups in Ukraine… But they should also consider offering more concrete inducements to Ukraine… cuts in Europe's high tariffs on steel and farm goods, for example, or progress with Ukraine's bid for membership of the World Trade Organisation…”1
Predicting pituitary iron and endocrine dysfunction
Authors: Wood John C. , Noetzl Leila , Hyderi Aleya , Joukar Mehrdad , Coates Thomas , Mittelman Steven
Published: August 2010

Patients with thalassemia major (TM) require lifelong transfusion therapy to survive, leading to toxic iron overload in the endocrine glands and heart. The pituitary gland is one of the most vulnerable targets, leading to irreversible hypogonadotropic hypogonadism in approximately half of patients. Improvements in magnetic resonance imaging (MRI) technology and understanding have allowed earlier recognition of preclinical iron deposition in the heart, pancreas, and liver; prior work also supports a similar role for the pituitary. The purpose of this study is threefold, (1) to develop age‐specific nomograms for pituitary iron and volume metrics; (2) to determine the prevalence, severity, and age of onset of pituitary iron deposition and volume loss in TM patients, and (3) to determine whether deferasirox monotherapy can modify the trajectory of pituitary iron accumulation and damage over a two‐year period. This article outlines relevant background studies and methodological details as well as providing preliminary results from our first two aims.
Ninth Cooley's Anemia Symposium: summary and perspective
Authors: Nienhuis Arthur W.
Published: August 2010

The Ninth Cooley's Symposium provided an outstanding summary of progress in the field. Highlights of the conference included the report of clinical benefit in one of two patients treated in a gene therapy trial. Another major breakthrough was the report that the transcriptional factor, BCL11A, is a key molecular component of the γ‐globin silencing mechanism that results in the fetal to adult perinatal switch. The ability to evaluate tissue iron is becoming increasingly more sophisticated, with results presented at this conference indicating that independent measurement of cardiac ferritin and hemosiderin can be achieved with specific MRI sequences. The three available iron chelators, deferoxamine, deferiprone, and deferasirox, provide a potent therapeutic armamentarium so that effective chelation regimens can be devised for most individual patients. Unfortunately, compliance remains a significant issue despite the availability of oral chelators. Modification of conditioning regimens and the use of alternative donor sources have made stem cell transplantation available to an increasing number of patients with progressive improvement in outcome. Despite many advances, the global burden of disease for the thalassemias remains very high, with many challenges that still need to be addressed in order to optimize treatment for the majority of patients.
The natural history of thalassemia intermedia
Authors: Borgna‐Pignatti Caterina , Marsella Maria , Zanforlin Nicolò
Published: August 2010

The severity of thalassemia intermedia depends on the degree of imbalance between alpha and non‐alpha chains as well as other genetic and environmental factors that modify the natural history of the disease. By definition, the patients spontaneously maintain hemoglobin at or above 7 g/dL, sometimes at the price of intense hyperplasia of the bone marrow that is in turn responsible for bone deformities, osteoporosis, and extramedullary erythropoietic masses that often characterize thalassemia intermedia. Transfusion may become necessary with advancing age, during infection and pregnancy, and when hypersplenism develops. Splenectomy is often needed. Iron overload in nontransfused patients is due to increased gastrointestinal absorption and involves mainly the liver. Complications affecting the lives of patients with thalassemia intermedia include pulmonary hypertension, leg ulcers, pseudoxanthoma elasticum, gallstones, hepatocellular carcinoma, and thromboembolic events.
Transcriptional silencing of fetal hemoglobin by BCL11A
Authors: Sankaran Vijay G. , Xu Jian , Orkin Stuart H.
Published: August 2010

The β‐thalassemia syndromes are a major global health problem. Increased levels of fetal hemoglobin (HbF) ameliorate the clinical symptoms seen in this disease. By taking advantage of the natural variation in the level of HbF in various populations, we and others identified several common genetic variants in three major loci that regulate HbF levels. One of these variants resides in the gene BCL11A. We have studied the role of this gene product and established that BCL11A maintains silencing of γ‐globin expression in adult erythroid cells and functions as a direct transcriptional regulator of the fetal to adult hemoglobin switch in humans. Moreover, we found that BCL11A plays a central role in the evolutionarily divergent globin gene switches of mammals. As a factor critical for γ‐globin gene silencing, BCL11A should be considered as a therapeutic target to increase HbF in a directed manner in β‐thalassemia patients.
The role of antioxidants and iron chelators in the treatment of oxidative stress in thalassemia
Authors: Fibach Eitan , Rachmilewitz Eliezer A.
Published: August 2010

On the basis of all the presented data, one can conclude that oxidative stress plays a major role in the pathophysiology of thalassemia and other congenital and acquired hemolytic anemias. Free extracellular (labile plasma iron, LPI) and intracellular (labile iron pool, LIP) iron species that have been identified in thalassemic blood cells are responsible for generation of oxidative stress by catalyzing formation of oxygen radicals over the antioxidant capacity of the cell. Consequently, there is a rationale for iron chelation to eliminate the free‐iron species, which in this respect, act like antioxidants. In addition, antioxidants such as vitamin E and polyphenols are also capable of ameliorating increased oxidative stress parameters and, given together with iron chelators, may provide a substantial improvement in the pathophysiology of hemolytic anemias and particularly in thalassemia.