bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased prevalence of iron‐overload associated endocrinopathy in thalassaemia versus sickle‐cell disease
Authors: Fung Ellen B. , Harmatz Paul R. , Lee Phillip D.K. , Milet Meredith , Bellevue Rita , Jeng Michael R. , Kalinyak Karen A. , Hudes Mark , Bhatia Suruchi , Vichinsky Elliott P. ,   the Multi‐Centre Study of Iron Overload Research Group.
Published: October 2006

Iron‐overload associated endocrinopathy is the most frequently reported complication of chronic transfusion therapy in patients with thalassaemia (Thal). This study compared iron‐overloaded subjects with Thal (n = 142; 54%M; age 25·8 ± 8·1 years) and transfused sickle‐cell disease (Tx‐SCD; n = 199; 43%M, 24·9 ± 13·2 years) to non‐transfused SCD subjects (non‐Tx‐SCD; n = 64, 50%M, 25·3 ± 11·3 years), to explore whether the underlying haemoglobinopathy influences the development of endocrinopathy. Subjects were recruited from 31 centres in the USA, Canada and the UK. Subjects with Thal had more evidence of diabetes (13% vs. 2%, P < 0·001), hypogonadism (40% vs. 4%, P < 0·001), hypothyroidism (10% vs. 2%, P = <0·001) and growth failure (33% vs. 7%, P < 0·001), versus Tx‐SCD. Fifty‐six per cent of Thal had more than one endocrinopathy compared with only 13% of Tx‐SCD (P < 0·001). In contrast, Tx‐SCD was not different from non‐Tx‐SCD. Multivariate analysis indicated that endocrinopathy was more likely in Thal than SCD [Odds Ratio (OR) = 9·4, P < 0·001], with duration of chronic transfusion a significant predictor (OR = 1·4 per 10 years of transfusion, P = 0·04). Despite iron overload, endocrinopathy was not increased in Tx‐SCD versus non‐Tx‐SCD, suggesting that the underlying disease may modulate iron‐related endocrine injury. However, because transfusion duration remained a significant predictor of endocrinopathy, these data should be confirmed in SCD subjects that have been chronically transfused for longer periods of time.
Down syndrome and acute lymphoblastic leukaemia
Authors: Whitlock James A.
Published: October 2006

Acute lymphoblastic leukaemia in children with Down syndrome (ALL‐DS) is characterised by unique clinical and biological features. Notable among these are an absence of ALL in DS patients <1 year of age; a lower incidence of favourable and unfavourable chromosomal translocations; heightened sensitivity to methotrexate; and an increased propensity to infections. Although children with ALL‐DS have historically fared less well than their non‐DS counterparts (ALL‐NDS), recent data indicate that outcomes in ALL‐DS are now comparable with ALL‐NDS with risk‐adapted therapies, after adjusting for biological differences between the ALL‐DS and ALL‐NDS populations. Given the increased risk of ALL‐DS patients for treatment‐related toxicities, further intensification of therapy may not yield continued improvements in survival. Future investigations in the ALL‐DS population should focus on maintaining excellent outcomes while reducing treatment‐related complications through novel treatment strategies, such as the integration of targeted noncytotoxic agents.
Microbial contamination of nebulizers in the home treatment of cystic fibrosis
Authors: Blau H. , Mussaffi H. , Mei Zahav M. , Prais D. , Livne M. , Czitron B. M. , Cohen H. A.
Published: October 2006

Background Home nebulizers are in widespread use in cystic fibrosis (CF) and other chronic pulmonary diseases. Bacterial contamination may be a source of respiratory tract colonization.

Objectives To investigate microbial contamination of home nebulizers in CF patients, compare with sputum cultures and relate to cleaning practices.

Methods A total of 29 home nebulizers of CF patients were cultured. Families were interviewed regarding cleaning routines and patients had sputum cultures for bacteria and fungi.

Results In total, 19/29 (65%) nebulizers were contaminated: 18 reservoir cups, 14 mouthpieces and five filters. Pseudomonas spp. were isolated from 10 nebulizers (35%) and all 10 had Pseudomonas aeruginosa airway infection although without genetic typing we could not be sure this was the same bacteria as that from their nebulizer unit. An additional 7/29 had Pseudomonas aeruginosa airway infection without a contaminated nebulizer (P = 0.001). No nebulizers were contaminated with Aspergillus. Only 4/19 contaminated nebulizers (22%) had been cleaned after every use, compared with seven of the 10 (70%) uncontaminated nebulizers (P = 0.017). Only 7/19 patients with contaminated nebulizers (37%) and 5/10 with clean nebulizers (50%) recalled receiving cleaning instructions (not significant).

Conclusions Home nebulizers are frequently contaminated, particularly when cleaning instructions are inadequate, and may be a source of airway infection or reinfection especially following contamination from a patient chronically colonized with P. aeruginosa. Simple oral and written cleaning instructions should be offered.
Social perception of the development of disabled children
Authors: Castañeto M. V. , Willemsen E. W.
Published: October 2006

Background  This experiment extends our study of perception of the disabled from the realm of personality into child development to determine if our results, which reveal prejudice against disabled adults, apply to perceptions of a toddler’s development.

Methods  Participants watched a video of either a disabled or a non‐disabled toddler in sessions conducted by either a disabled or a non‐disabled experimenter. Participants rated the target using the Achenbach Caregiver‐Teacher Report Form for ages 1.5–5 years twice: first, each participant imagined being the caregiver of the toddler at age 4 years (self‐rating), and then the participant envisioned how a typical childcare provider would rate the target (other‐rating).

Results  Data revealed an interaction between the experimenter’s disability and the source of ratings. For the disabled experimenter, participants thought that ‘others’ would perceive more behavioural problems than they themselves do. For the non‐disabled experimenter, participants rated the disabled target more pessimistically in both the self‐ and other‐ratings.

Conclusion  As we found in our first study of disabled adults, our current results reveal subtle prejudice against disabled children.
Mechanisms of osteoporosis in spinal cord injury
Authors: Jiang Sheng‐Dan , Jiang Lei‐Sheng , Dai Li‐Yang
Published: October 2006

Osteoporosis is a known complication of spinal cord injury (SCI), but its mechanism remains unknown. The pathogenesis of osteoporosis after SCI is generally considered disuse. However, although unloading is an important factor in the pathogenesis of osteoporosis after SCI, neural lesion and hormonal changes also seem to be involved in this process. Innervation and neuropeptides play an important role in normal bone remodelling. SCI results in denervation of the sublesional bones and the neural lesion itself may play a pivotal role in the development of osteoporosis after SCI. Although upper limbs are normally loaded and innervated, bone loss also occurs in the upper extremities in patients with paraplegia, indicating that hormonal changes may be associated with osteoporosis after SCI. SCI‐mediated hormonal changes may contribute to osteoporosis after SCI by different mechanisms: (1) increased renal elimination and reduced intestinal absorption of calcium leading to a negative calcium balance; (2) vitamin D deficiency plays a role in the pathogenesis of SCI‐induced osteoporosis; (3) SCI antagonizes gonadal function and inhibits the osteoanabolic action of sex steroids; (4) hyperleptinaemia after SCI may contribute to the development of osteoporosis; (5) pituitary suppression of TSH may be another contributory factor to bone loss after SCI; and (6) bone loss after SCI may be caused directly, at least in part, by insulin resistance and IGFs. Thus, oversupply of osteoclasts relative to the requirement for bone resorption and/or undersupply of osteoblasts relative to the requirement for cavity repair results in bone loss after SCI. Mechanisms for the osteoporosis following SCI include a range of systems, and osteoporosis after SCI should not be simply considered as disuse osteoporosis. Unloading, neural lesion and hormonal changes after SCI result in severe bone loss. The aim of this review is to improve understanding with regard to the mechanisms of osteoporosis after SCI. The understanding of the pathogenesis of osteoporosis after SCI can help in the consideration of new treatment strategies. Because bone resorption after SCI is very high, intravenous bisphosphonates and denosumab should be considered for the treatment of osteoporosis after SCI.
Workshop cluster 1+γδ T‐cell receptor+ T cells from calves express high levels of interferon‐γ in response to stimulation with interleukin‐12 and ‐18
Authors: Price Sally J. , Sopp Paul , Howard Christopher J. , Hope Jayne C.
Published: October 2006

γδ T‐cell receptor+ T lymphocytes are an important element of the innate immune system. Early production of interferon (IFN)‐γ by γδ T cells may have a role in linking innate and adaptive immune responses and contribute to T helper‐1 bias. We investigated the role of cytokines in the activation and induction of IFN‐γ secretion by bovine workshop cluster 1+ (WC1+) γδ T cells. The effects of culture with interleukin (IL)‐12, IL‐18, IL‐15 and IL‐2 were investigated; these cytokines are known to influence murine and human γδ T cells. We report that bovine WC1+γδ T cells are synergistically stimulated by IL‐12 and IL‐18 to secrete large quantities of IFN‐γ. Neonatal calves were shown to have significantly higher numbers of circulating WC1+γδ T cells than adult animals. In addition, the response of peripheral blood WC1+γδ T cells was significantly higher in neonatal calves compared with adult animals. However, in adult animals the response of lymph node WC1+γδ T cells to IL‐12/IL‐18 was more pronounced than that of peripheral blood WC1+γδ T cells. We hypothesize that the induction of IFN‐γ secretion from WC1+γδ T cells by IL‐12 and IL‐18 is likely to be an important element of the innate response to pathogens such as Mycobacterium bovis. The high numbers of WC1+γδ T cells in neonatal calves, and their inherent ability to respond to inflammatory cytokines, could be a key factor in the enhanced responses seen in calves to BCG vaccination.
Toll‐like receptor interactions: tolerance of MyD88‐dependent cytokines but enhancement of MyD88‐independent interferon‐β production
Authors: Broad Andrea , Kirby John A. , Jones David E. J. ,   Applied Immunology and Transplantation Research Group
Published: October 2006

Toll‐like receptors (TLRs) signal through two main pathways: a myeloid differentiation factor (MyD)88‐dependent pathway that acts via nuclear factor κB (NF‐κB) to induce proinflammatory cytokines such as tumour necrosis factor‐α (TNF‐α) and a MyD88‐independent pathway that acts via type I interferons to increase the expression of interferon‐inducible genes. Repeated signalling through TLR4 and a number of other TLRs has been reported to result in a reduction in the subsequent proinflammatory cytokine response, a phenomenon known as TLR tolerance. In this study we have shown that, whilst NF‐κB activation and production of TNF‐α and interleukin‐12 by murine RAW264.7 and J774.2 cells in response to stimulation by TLR4, ‐5, ‐7 or ‐9, was reduced by prior stimulation with TLR4, ‐5, ‐7 or ‐9 ligands, the primary stimulation of TLR3, which does not use the MyD88 pathway, did not reduce the TNF‐α or interleukin‐12 responses to subsequent TLR stimulation. The response to TLR3 stimulation was not diminished by prior TLR ligand exposure. Furthermore, the production of interferon‐β (IFN‐β) following stimulation of TLR3 or ‐4, which is MyD88‐independent, was increased by prior activation of TLR4, ‐5, ‐7 or ‐9. In contrast, TLR9 ligand‐induced IFN‐β production, which is MyD88‐dependent, was tolerized by prior TLR stimulation. These results are consistent with differential regulation of MyD88‐dependent and MyD88‐independent cytokine production following serial activation of TLRs.
Avoidance of solid food in weight losing older patients with Parkinson's disease
Authors: Lorefält Birgitta , Granérus Ann‐Katherine , Unosson Mitra
Published: October 2006

Aim.  The aim of this paper was to investigate to what extent parkinsonian symptoms, including mild dysphagia and other eating problems, could influence the choice of consistency and the amount of food intake and if this could be related to weight loss as an expression of the underlying neurodegenerative process.

Background.  Previous studies show that patients with Parkinson's disease tend to lose body weight even early during the disease.

Design.  The design was a longitudinal prospective study.

Methods.  Twenty‐six free‐living Parkinson's disease patients and 26 age‐ and sex‐matched controls were investigated twice, with one‐year apart, with focus on Parkinson's disease symptoms, as well as swallowing function. Intake of food items and food consistency were assessed by food records, completed over three consecutive days at each investigation.

Results.  In patients with weight loss, motor symptoms, problems with activities of daily living and problems with eating, related to motor symptoms, increased and they had more dysphagia compared with their controls. They consumed lower amounts of fluid and solid food on both investigated occasions, compared with their controls. Multiple regression analysis showed that weight loss was associated with female gender, eating difficulties related to activities of daily living and preference towards soft food, but negatively correlated with age.

Conclusion.  Parkinson's disease patients with weight loss seemed to avoid solid food, partly because of eating difficulties. Eating problems, as well as weight loss, could be because of the underlying disease, even when it is not at an advanced stage.

Relevance to clinical practice.  Caring for patients with Parkinson's disease should not only include medical treatment, but also support for adequate food intake to prevent weight loss.
Calcineurin inhibitor‐free immunosuppression in dual kidney transplantation from elderly donors
Authors: Furian Lucrezia , Baldan Nicola , Margani Giuseppe , Ekser Burcin , Silvestre Cristina , Marchini Francesco , Bonfante Luciana , Rossi Barbara , Valente Maria Luisa , Rigotti Paolo
Published: October 2006

Abstract:  Background:  Kidneys from expanded‐criteria donors may be particularly susceptible to calcineurin inhibitor (CI)‐mediated vasoconstriction and nephrotoxicity. In the early post‐transplant phase, using CI may prolong ischemic injury and, in the long term, chronic CI nephrotoxicity is an even greater concern. To avoid the acute and chronic consequences of CI in kidneys from marginal donors, CI‐free protocols have been introduced for maintenance immunosuppressive therapy. A CI‐free protocol of anti‐thymocyte globulin (ATG) induction, sirolimus, mycophenolate mofetil (MMF) and steroids has been adopted at our center in recipients of dual kidney transplantation (DKT) from elderly donors (EDs).

Methods:  Dual kidney transplantations performed since April 2003 on CI‐free immunosuppression (group 1 = 31) were compared with earlier DKTs in recipients treated with CI‐based therapy (group 2 = 25), retrospectively analyzing patient and graft survival, surgical and medical complications, rejection episodes and renal function.

Results:  No deaths occurred after a mean follow‐up of 10.1 ± 7.6 (group 1) and 48.2 ± 17.4 months (group 2). Graft loss occurred in one patient in group 1 (bilateral renal vein thrombosis) and in three patients in group 2 (one primary non‐function [PNF], one chronic rejection, one Kaposi's sarcoma). The incidence of acute rejection was 19% in group 1 and 16% in group 2. Delayed graft function (DGF) was recorded in 16% and 48%, respectively. Renal function was better in group 1, with a mean S‐Cr of 135 ± 48 vs. 210 ± 141 μmol/L at one month and 116 ± 30 vs. 149 ± 49 μmol/L at six months.

Conclusions:  After DKT from EDs, a CI‐free immunosuppressive regimen including ATG induction, sirolimus, MMF and steroids affords excellent results, with a lower DGF rate and a better renal function.
Non‐Hodgkin lymphoma and skin cancer: A dangerous combination
Authors: Otley Clark C
Published: October 2006

There is a significant association between non‐Hodgkin lymphoma, including chronic lymphocytic leukaemia, and both melanoma and non‐melanoma skin cancer. This review highlights the existing data on the phenomenon of accelerated skin cancer in patients with non‐Hodgkin lymphoma and specifically chronic lymphocytic leukaemia. The outcomes of patients with non‐Hodgkin lymphoma (including chronic lymphocytic leukaemia) and non‐melanoma skin cancer are worse than in patients without concomitant lymphoreticular malignancy, as shown by increased rates of local recurrence, regional metastasis and death. Pathogenic factors may be common between non‐Hodgkin lymphoma and chronic lymphocytic leukaemia and skin cancer. The treatment of skin cancer in patients with non‐Hodgkin lymphoma must factor in the worse prognosis and adapt standard therapeutic approaches to minimize the risk of metastasis and death. Preventive strategies and early detection are paramount in this high‐risk population.
Muir–Torre syndrome: Diagnostic and screening guidelines
Authors: Jones Brad , Oh Carol , Mangold Elisabeth , Egan Conleth A
Published: October 2006

A 65‐year‐old man presented with a history of multiple skin coloured papules on his face that were asymptomatic. He had an adenocarcinoma resected from his proximal colon 12 years prior to presentation as well as a family history of colon cancer on the maternal side. Diagnostic biopsies showed the lesions to be sebaceous adenomas and epitheliomas and the diagnosis of Muir–Torre syndrome was made. The sebaceous tumour tissue showed microsatellite instability and immunohistochemical staining indicated diminished expression in the DNA mismatch–repair protein complex MSH2/MSH6. Genetic analysis showed a germline mutation in the MSH2 gene confirming the diagnosis of Muir–Torre syndrome. The patient and his first‐degree relatives have been referred for genetic counselling and screening. We review the diagnostic criteria in this syndrome and review the recommended screening guidelines.
Primary cutaneous diffuse leiomyosarcoma with desmoplasia
Authors: Choy Carolyn , Cooper Alan , Kossard Steven
Published: October 2006

A 65‐year‐old man presented with an indurated plaque over his left cheek and left neck. An initial punch biopsy of skin showing increased smooth muscle bundles was consistent with a diagnosis of smooth muscle hamartoma. A second incisional skin biopsy revealed a well‐differentiated smooth muscle proliferation invading into the dermis and subcutaneous fat in a diffusely infiltrative pattern and with a desmoplastic component, suggesting a diagnosis of desmoplastic leiomyosarcoma. Resection of the tumour confirmed the presence of a cytologically low grade leiomyosarcoma with an insidious infiltrative growth pattern. This rare pattern of diffuse leiomyosarcoma is important to recognize as the histological features are subtle and may potentially constitute a pitfall in histological diagnosis in a small biopsy specimen. In addition, our case illustrates overlapping morphology between diffuse and desmoplastic types of leiomyosarcoma.
A comparative study between electron microscopy and immunofluorescence mapping in the diagnosis of epidermolysis bullosa
Authors: Yiasemides Eleni , Walton Judie , Marr Penelope , Villanueva Elmer V. , Murrell Dédée F.
Published: October 2006

INTRODUCTION: The classification of epidermolysis bullosa (EB) into 3 main subtypes has been based on electron microscopy (EM) that is able to directly visualize and quantify specific ultrastructural features. Immunofluorescence antigenic mapping (IFM) is a technique that determines the precise level of skin cleavage by determining the site of binding of a series of antibodies. To date, no study has compared the accuracy of these two techniques in diagnosing the major types of EB.

METHODS: A prospective cohort of 33 patients thought to have EB on clinical grounds had both EM and IFM. The sensitivity and specificity of EM and IFM were calculated using the genetic results as the ‘gold standard’. Statistical analysis involved the determination of positive and negative predictive values, accuracies, positive and negative likelihood ratios and post‐test probabilities of the IFM and EM diagnosis being correct compared to genetic diagnosis.

RESULTS: 30/33 cases had a positive EB diagnosis. TEM subclassified EB into its three major forms in 24/30 cases (80%) and IFM in 29/30 cases (97%). Overall, TEM sensitivities and specificities when compared to genetic results were 71% and 81%, respectively. IFM sensitivities and specificities when compared to genetic results were 97% and 100% respectively. If a patient tested positive for EB by IFM, the likelihood ratio of having a particular type of EB was consistently greater than 20 against the reference standard (compared to a likelihood ratio less than 10 for TEM).

CONCLUSION: These findings dispute the contention that EM and IFM are equally accurate and sensitive as diagnostic tests for the classification of the major types of EB. The results indicate that the diagnosis of EB is improved (sometimes substantially) by the use of IFM compared to TEM.
A molecular phylogeny of Planorboidea (Gastropoda, Pulmonata): insights from enhanced taxon sampling
Authors: Albrecht Christian , Kuhn Kerstin , Streit Bruno
Published: October 2006

Planorbid gastropods are the most diverse group of limnic pulmonates, with both discoidal and highspired taxa. Phylogenetic relationships among these genera are confused and controversial. In particular, the monophyly of the limpet‐like taxa (traditionally Ancylidae) is disputed. Even recent molecular studies have concluded that substantially more work is necessary to solve the remaining issues concerning intergeneric phylogenetic relationships and higher taxa systematics. Planorbid snails are of great significance for humans as several members of this group are intermediate hosts of blood flukes (schistosomes) causing a chronic disease, schistosomiasis. We used the two independent molecular markers COI and 18S (concatenated dataset of 2837 nucleotide bp) to infer phylogenetic relationships of 26 genera (27 species) of Planorboidea, represented mostly by type species from mainly topotypical populations. With the majority of the taxa discussed not having been studied previously, this study attempted to test several hypotheses on planorbid phylogenetic relationships using Bayesian inference techniques. The monophyly of Planorboidea (= ‘Ancyloplanorbidae’) is strongly suggested on the basis of our extensive molecular analysis. Besides a distinct Burnupia clade, two major clades were recovered that correspond to family level taxa (traditional Bulinidae and Planorbidae). Considerable rearrangements of suprageneric taxa are evident from the phylogeny inferred. Therefore, the only clades recognized by current classifications and supported by our analysis are Planorbini and Segmentinini. The present study found that Ancylidae as traditionally understood, i.e. covering most freshwater limpet gastropods, is paraphyletic, as the genera of Burnupia and Protancylus have been shown to lie phylogenetically outside the Ancylini. Chromosome numbers and levels of polyploidy are discussed in the light of the new phylogeny. An earlier theory of shell shape evolution, i.e. that of patelliform taxa being most advanced, was not supported by this study; a limpet‐shaped taxon is most basal within Planorboidea. Although many taxa still remain to be studied, our results will hopefully contribute towards a better understanding of this very important group of freshwater organisms. Some taxonomic implications are discussed.
Outpatient dermatology major surgery: a 1‐year experience in a Spanish tertiary hospital
Authors: Fernández‐Jorge B , Peña‐Penabad C , Vieira V , Paradela S , Rodríguez‐Lozano J , Fernández‐Entralgo A , García‐Silva J , Fonseca E
Published: October 2006

Introduction  The constant increase in the incidence of skin cancer together with the requirement for maximum exploitation of available medical resources has meant that dermatological major surgery on an outpatient basis has greatly increased in recent years.

Objective  This article reviews the practice of dermatological surgery in an outpatient setting over a 1‐year period. Its purpose is to analyse the number of surgical procedures, the type of cutaneous processes treated and the kind of surgical intervention and anaesthesia used. We also assessed the percentage of cancellations, postsurgical hospital admission and postsurgical complications. Clinicopathological correlation and complete tumour removal were also evaluated.

Material and methods  Our clinical experience of major surgery of outpatients at the dermatology department of the Hospital Juan Canalejo in A Coruña (Spain), analysing 565 patients in a non‐randomized pilot study running from January to December 2003, is presented.

Results  Six hundred and forty‐four surgical procedures were performed on a total of 565 patients. The three main cutaneous processes treated were basal cell carcinoma (240), squamous cell carcinoma (117) and melanoma (77). The most frequent type of procedure was direct closure (346), followed by exeresis and flap (133) and partial‐ or full‐thickness skin graft (29), nail apparatus surgery (56) and lip surgery (33). Twelve patients were admitted to hospital after surgery owing to the complexity of their operations or to complications arising during surgery. Five hundred and fifty‐three patients were discharged after being kept under observation for a few hours. Seventeen patients (3%) suffered complications following surgery, which consisted of partial implant failure (six cases), infection of the surgical wound (six cases), intense pain (four cases) and haemorrhage (one case). There was a good clinicopathological correlation in 90.78% of non‐melanoma skin cancers, of which 92.03% were completely removed.

Conclusions  Medium and high complexity operations for dermatological processes, traditionally performed on hospitalized patients, can be conducted on an outpatient basis. This allows hospitalization costs and waiting lists to be reduced and affords the possibility of achieving better morbidity rates and medical care than in the standard hospital setting.
Immunoglobulin Enhancer HS1,2 polymorphism: a new powerful anthropogenetic marker
Authors: Giambra V. , Martínez‐Labarga C. , Giufre' M. , Modiano D. , Simpore' J. , Gisladottir B. K. , Francavilla R. , Zhelezova G. , Kilic S. S. , Crawford M. , Biondi G. , Rickards O. , Frezza D.
Published: October 2006

The human HS1,2 enhancer of the immunoglobulin (Ig) heavy chain 3′ enhancer complex plays a central role in the regulation of Ig maturation and production. Four common alleles HS1,2‐A*1, *2, *3, *4 are directly implicated with the transcription level and at least one of them, HS1, 2‐A*2, seems to be related to immune disorders, such as coeliac disease, herpetiform dermatitis and Berger syndrome. Given their clinical significance it is of interest to know the distribution of HS1,2‐A variants in populations from different continents, as well as to determine whether the polymorphism is associated to specific evolutionary factors. In this paper we report the distribution of the HS1,2‐A polymorphism in 1098 individuals from various African, Asian and European populations. HS1,2‐A*3 and HS1,2‐A*4 alleles are at their highest frequencies among Africans, and HS1,2‐A*2 is significantly lower in Africans in comparison with both Europeans and, to a lesser extent, Asians. Analysis of molecular variance of the allele frequencies indicates that the HS1,2‐A polymorphism can be considered as a reliable anthropogenetic marker.
Estimating the Effects of Prescription Drug Coverage for Medicare Beneficiaries
Authors: Shea Dennis G. , Terza Joseph V. , Stuart Bruce C. , Briesacher Becky
Published: October 2006

Objective. To identify the effect of insurance coverage on prescription utilization by Medicare beneficiaries.

Data Sources/Study Setting. Secondary data from the 1999 Medicare Current Beneficiary Survey (MCBS) Cost and Use files, a nationally representative survey of Medicare enrollees.

Study Design. The paper uses a cross‐sectional design with (1) a standard regression framework to estimate the impact of prescription coverage on utilization controlling for potential selection bias with covariate control based on the Diagnostic Cost Group/Hierarchical Condition Category (DCG/HCC) risk adjuster, and (2) a multistage residual inclusion method using instrumental variables to control for selection bias and identify the insurance coverage effect.

Data Collection/Extraction Methods. Data were extracted from the 1999 MCBS. Study inclusion criteria are community‐dwelling MCBS respondents with full‐year Medicare enrollment and supplemental medical insurance with or without full‐year drug benefits. The final sample totaled 5,270 Medicare beneficiaries.

Principal Findings. Both the model using the DCG/HCC risk adjuster and the model using the residual inclusion method produced similar results. The estimated price elasticity of demand for prescription drugs for the Medicare beneficiaries in our sample was −0.54.

Conclusions. Our results confirm that selection into prescription coverage is predictable based on observable health. Our results further confirm prior estimates of price sensitivity of prescription drug demand for Medicare beneficiaries, though our estimate is slightly above prior results.
Interictal EEG and the Diagnosis of Epilepsy
Authors: Pillai Jyoti , Sperling Michael R.
Published: October 2006

Summary:  The interictal EEG provides information that aids in diagnosis and management of epilepsy. One must remember that the EEG is merely a tool, and its usefulness depends largely upon the skill of the individual who wields it. Like all diagnostic tests, it has significant limitations and cannot substitute for a careful history and exercise of good judgment. Nonetheless, in skilled hands, it provides unique and vital information in many patients, and enhances our understanding of their condition.
Starting and Stopping Treatment for Seizures and Epilepsy
Authors: Chadwick David
Published: October 2006

Summary:  Decisions about when to start or to stop antiepileptic drug (AED) treatment must be informed by reliable information of the natural history of epilepsy, the effect of treatment, and the social context of the individual. Ultimately the patient will be the decision maker, the clinician or health‐care professional, the provider and interpreter of information. While observational studies will provide information on natural history, the most reliable information on the effect of intervention will come from randomised controlled trials in relevant populations of patients. However, these need to be large enough to allow interpretation not just of the average effect across the recruited patients, but also some estimate of the effects for an individual based on the prognostic effects that most effect outcomes. When trials are of sufficient size they can allow the development of predictive models that assist decision making. The Medical Research Council studies of AED withdrawal and early epilepsy and single seizures provide examples of such trials.
Epilepsy in the Elderly
Authors: Leppik Ilo E.
Published: October 2006

Summary:  The elderly are the most rapidly growing segment of the population and the incidence of epilepsy is higher in the elderly than in any other age group. They have been subdivided into the “young old,” 65–74 years, “middle old” 75–84 years, and the “old old,” 85 years or older. But further subdivisions are needed: persons with only epilepsy, those with epilepsy and multiple medical problems, and the frail elderly. Thus, when considering therapy, one must tailor the interventions to nine categories: young old healthy, young old with medical problems, frail young old, old healthy, old with medical problems, frail old, old old healthy, old old with medical problems, and frail old old. The prevalence of antiepileptic drug (AED) use in community dwelling elderly is 1.5%; in the nursing home population it is 10%. Surprisingly, 3% have an AED newly prescribed after admission. Overall, 6.2% were using phenytoin, 1.8% carbamazepine, 0.9% valproic acid, 1.7% phenobarbital, and others combined, 1.2%. AEDs rank fifth among all drug categories as a cause of adverse reactions. There are very few data regarding the clinical use of AEDs in the elderly. The paucity of information makes it very difficult to recommend specific AEDs with any confidence that the outcomes will be optimal. An appropriate for elderly healthy may not be appropriate for elderly with multiple medical problems, and in frail elderly variable absorption may be a major problem. One of the major advantages of some newer AEDs is lack of drug interactions. Cost is an advantage of the older AEDs. Regardless of the AED chosen, one must use doses appropriate to the clearance of the drug, and AED levels, especially unbound (free) levels, must be monitored. The elderly nursing home resident may be more frail, be taking many medications, and have several concomitant illnesses, making them difficult to treat. The most commonly used AED, phenytoin, may not be the easiest or safest AED to prescribe in the elderly with multiple medical problems or the frail elderly.
Identification of Ethanol Responsive Domains of Adenylyl Cyclase
Authors: Yoshimura Masami , Pearson Susan , Kadota Yoichi , Gonzalez Cristina E.
Published: October 2006

Background: The activity of adenylyl cyclase (AC) is enhanced by pharmacologically relevant concentrations of ethanol. The enhancing effect of ethanol on AC activity is AC isoform‐specific. Therefore, we hypothesized that within a cyclic AMP–generating system, AC is the target of ethanol's action and that ethanol‐sensitive AC molecules contain structural elements modulated by ethanol. The structural elements are designated as “ethanol responsive domains.”

Methods: By using a series of chimeric mutants, we searched regions of the AC molecule that are important for the ethanol effect. These chimeric mutants were derived from 3 isoforms of AC: AC7 (type 7), the most ethanol responsive isoform; AC3 (type 3), an isoform that is far less responsive to ethanol; and AC2 (type 2), an isoform that is homologous to AC7 but less responsive to ethanol.

Results: We identified 2 discrete regions of the AC molecule that are important for the enhancement of AC activity by ethanol. The first is the N‐terminal 28‐amino‐acid (aa) region of the C1a domain. The second is the C‐terminal region (∼140 aa) of the AC molecule. Sequence differences in the N‐terminal tail, 2 putative transmembrane domains, and the C1b domain are not important for ethanol's effect.

Conclusions: The current study with mammalian ACs provides a new class of alcohol‐responsive protein and possibly a new mechanism of alcohol action on cellular function. The identification of ethanol responsive domains will facilitate the elucidation of the mechanisms by which ethanol enhances the activity of AC.
Ontogeny of Acute Tolerance to Ethanol‐Induced Social Inhibition in Sprague–Dawley Rats
Authors: Varlinskaya Elena I. , Spear Linda P.
Published: October 2006

Background:Adolescent rats are less sensitive than adults to a number of acute effects of ethanol, including ethanol‐induced social inhibition. Adolescent insensitivity to the suppressing effects of ethanol on social interactions could be related in part to age differences in compensatory responses, including acute tolerance, that serve to counteract these inhibitory effects of ethanol. The present study explored ontogenetic development of acute tolerance within 30 minutes after administration of a relatively low ethanol dose, using ethanol‐induced social impairment as the target response measure.

Methods:Overall social activity was examined following challenge with 1 g/kg ethanol (intraperitoneally) at 2 postinjection intervals (5 or 30 minutes) in early [postnatal day (P) 28], mid (P35), or late (P42) adolescent or adult (P70) group‐housed male and female Sprague–Dawley rats (Experiment 1). Blood and brain ethanol concentrations (BECs and BrECs) were assessed in separate groups of animals 5 or 30 minutes after ethanol administration (Experiment 2). Expression of acute tolerance was examined by assessing the relationship between BrECs and the degree of social impairment in individual animals at P28, P35, P42, and P70 during early recovery period (up to 30 minutes) following acute ethanol challenge (Experiment 3).

Results:Effects of ethanol on overall social activity were age‐dependent and time‐dependent. Whereas all age groups showed equivalent ethanol‐induced social inhibition 5 minutes after injection, testing at 30 minutes revealed marked age differences. Social inhibition was still pronounced at this time in adults, but was diminished in an age‐related manner at younger ages (Experiment 1). In contrast to the ontogenetic differences in rates of decline in social impairment across time, decreases in brain and blood ethanol levels over time were similar across age (Experiment 2). Only P28 and P35 adolescents showed acute tolerance to ethanol‐induced social inhibition, as indexed by an increasing time‐dependent dissociation between BrECs and ethanol‐induced social impairment, with social impairment declining faster than BrECs (Experiment 3).

Conclusions:This is the first study to document enhanced acute tolerance in adolescent rats relative to adult animals at nonhypnotic doses of ethanol. The greater expression of acute tolerance in young animals may reflect an enhanced predisposition of their nervous systems to respond rapidly to even modest doses of ethanol with compensatory adaptations. A greater propensity of early adolescents to develop acute tolerance may contribute to their resistance to adverse effects of ethanol, thereby permitting heavy drinking at this age and placing early adolescents at higher risk for extensive alcohol use.
How Should Nations Measure the Quality of End‐of‐Life Care for Older Adults? Recommendations for an International Minimum Data Set
Authors: Casarett David J. , Teno Joan , Higginson Irene
Published: October 2006

Nations face numerous challenges in providing high‐quality end‐of‐life care for their citizens, and an aging population that has a prolonged trajectory of decline and substantial needs for care magnifies these challenges. As nations begin to address these challenges, it will be essential to determine whether their responses are effective, but current national data collection efforts are sporadic, and data are often collected only for patients who receive care through certain funding programs or provider organizations or in selected sites of care. Therefore, governments do not know whether their citizens are receiving adequate care, whether current programs are improving care, or how their outcomes compare with those of other countries. This article describes the importance of developing national minimum data sets that can be used to assess the quality of end‐of‐life care that older adults receive and recommends key variables that these data sets should include.
Oral health in Florida nursing homes
Authors: Murray PE , Ede‐Nichols D , Garcia‐Godoy F
Published: October 2006

Abstract:  Objectives: The purpose of this study was to measure the oral health and hygiene status among 265 South Florida nursing home residents aged between 45 and 98 years. Methods: The oral health and hygiene status of the residents were assessed by noting the presence of calculus, caries, gingivitis, cheilitis, apthous ulcer, dry mouth and red or white lesions. Results: The incidence of nursing home residents with calculus was 79.6% and the remaining 20.4% were edentulous. More than half of residents had oral problems (50.6%) the commonest was gingivitis (36.6%), followed by caries (26%) and tooth fracture (15.9%). Almost half the residents wore dentures (47.2%). Statistical analysis was conducted using analysis of variance (P‐values). Ageing of the residents was statistically correlated to a worsening of oral hygiene status (P < 0.0066), absence and presence of one or two dentures (P < 0.0034) and a loss of teeth (P < 0.0001). Conclusions: The ageing of residents is correlated to increasing oral health problems and the loss of teeth. Oral health neglect affects almost all of the nursing home residents. Care providers should receive education and training from dental hygienists to improve the standard of oral hygiene and health of the elderly.
Sexual Function in Women with Urinary Incontinence Treated by Pelvic Floor Transvaginal Electrical Stimulation
Authors: Giuseppe Paradiso Galatioto , Pace Gianna , Vicentini Carlo
Published: October 2006

Introduction

Women’s sexual dysfunctions (WSD) have been commonly associated with urinary incontinence (UI). Women with UI and who scored low on the Female Sexual Function Index (FSFI) showed an improvement in urinary leakage and also in their sexual life following treatment by transvaginal electrical stimulation (TES).

Aims

To determine the effects of TES in 37 women complaining of UI, of whom 23 also had WSD, and to compare the FSFI scores of women with UI and 43 women not affected by UI who underwent routine urologic evaluation.

Methods

Thirty-seven women complaining of UI were evaluated by voiding diary and with FSFI before and after 3 months of TES. All had a urogynecologic evaluation and urodynamic study.

Main Outcome Measures

In the voiding diary the women reported the types of liquid they ingested, urinary frequency, and episodes of urgency and urine leakage. The domain scores of the FSFI, including desire, arousal, lubrication, orgasm, satisfaction, and pain, were calculated. TES was conducted for 15–30 minutes, twice a week for 3 months, using biphasic intermittent current with a frequency of 50 Hz for stress UI (SUI) and 20 Hz for urge UI (UUI), and the most tolerable intensity of stimulation.

Results

After TES, only two of the 10 women with UUI experienced a few leakage incidents; patients with SUI were completely dry during TES; and only three reported a few episodes of UI during intense activities. The five patients with mixed UI improved mainly as regards urgency. The FSFI scores of patients complaining of UI showed significantly lower desire and sexual satisfaction, and higher sexual pain than controls. After 3 months, the 23 women affected by WSD, of the 37 participants with UI, reported a remarkable improvement in their sexual life.

Conclusion

TES was found to be a safe and effective therapy for selected patients affected by mild to moderate UI. Because women with UI also complain of WSD compared with the general female population, an investigation of female sexuality is suggested for these patients.
Thermal Degradation of Acylated and Nonacylated Anthocyanins
Authors: Sadilova E. , Stintzing F. C. , Carle R.
Published: October 2006

ABSTRACT:  The thermal degradation pathways of acylated and nonacylated anthocyanins from 3 commercial sources have been investigated. Strawberry, elderberry, and black carrot concentrates were purified on XAD‐16‐HP and Sephadex‐LH‐20 columns to remove sugars, amino acids, salts, and phenolic compounds, respectively. The so obtained anthocyanin isolates were heated at 95 °C at pH 1, the optimum stability condition for the flavylium cation. During 7 h of thermal exposure, the samples were monitored by HPLC‐DAD‐MS3 at 280, 320, and 520 nm, respectively, together with spectrophotometric color and anthocyanin assessment. Total anthocyanin content lightness, and chroma, but not hue angle, were appropriate parameters to monitor anthocyanin loss on a statistically significant level. Anthocyanin glycosides were generally cleaved by successive loss of sugar moieties and pentoses were more readily split off than hexoses. Anthocyanin aglycones were further degraded by scission into phloroglucinaldehyde (cyanidin, pelargonidin), 4‐hydroxybenzoic acid (pelargonidin), and protocatechuic acid (cyanidin), the residues of the A‐ and B‐rings, respectively. Most interestingly, acylated cyanidin‐triglycosides from black carrot were degraded into their corresponding diglycoside derivatives, which are not genuine carrot pigments. Moreover, hydroxycinnamic acid glycosides were generated. It is therefore assumed that the thermal burden during processing of anthocyanic food can be deduced by monitoring the colored and colorless compound profiles.
Stability of α‐, γ‐, or δ‐Tocopherol during Soybean Oil Oxidation
Authors: Player M.E. , Kim H.J. , Lee H.O. , Min D.B.
Published: October 2006

ABSTRACT:  The decomposition of α‐, γ‐, or δ‐tocopherol in soybean oil during 24 d of storage at 50 °C was determined by high performance liquid chromatography (HPLC). The initial contents of α‐, γ‐, and δ‐tocopherol in soybean oil were 53, 750, and 268 ppm, respectively. The degradation rates of α‐, γ‐, and δ‐tocopherol for the first 10 d were 5.6%, 1.2, and 0.5% per day, respectively. The α‐tocopherol was completely destroyed in 16 d. The destructions of γ‐ and δ‐tocopherol were 28% and 17% after 24 d. The induction period of soybean oil determined by headspace oxygen, conjugated diene, and peroxide value was 8 d. As the degradations of α‐, γ‐, and δ‐tocopherol increased, the headspace oxygen disappearance, conjugated diene formation, and peroxide value of soybean oil increased. The correlation coefficient between the degradation of tocopherols and the oxidation of soybean oil was about 0.95. The degradation of tocopherols in soybean oil during storage was due to the oxidation.
Determination of mRNA half-lives inCandida albicansusing thiolutin as a transcription inhibitor
Authors: Kebaara Bessie W , Nielsen Lindsey E , Nickerson Kenneth W , Atkin Audrey L
Published: October 2006

A method for determining mRNA half-lives in the polymorphic fungus Candida albicans is described. It employs growth in a defined medium, the inhibition of transcription with thiolutin (10–20 µg/mL), and quantitative Northern blotting. The method is effective for the A72, SC5314, and CAI-4 strains of C. albicans, and for mRNAs that have a wide variety of decay rates and steady-state abundances. The range of half-lives detected (from 4–168 min) shows that this method is effective for mRNAs with widely varying half-lives. The mRNA decay rates obtained are compared with those for orthologous mRNAs from Saccharomyces cerevisiae. This procedure should work for a broad range of C. albicans strains and can be adapted to other fungal species.Key words: comparative mRNA stability, ACT1, ADH1, EFG1, PGK1, 18S rRNA, mRNA decay.
A SUFFICIENT AND NECESSARY CONDITION FOR CREDIBILITY MEASURES
Authors: LI XIANG , LIU BAODING
Published: October 2006

Possibility measures and credibility measures are widely used in fuzzy set theory. Compared with possibility measures, the advantage of credibility measures is the self-duality property. This paper gives a relation between possibility measures and credibility measures, and proves a sufficient and necessary condition for credibility measures. Finally, the credibility extension theorem is shown.
UTILIZING DISTRIBUTED LEARNING AUTOMATA TO SOLVE STOCHASTIC SHORTEST PATH PROBLEMS
Authors: BEIGY HAMID , MEYBODI M. R.
Published: October 2006

In this paper, we first introduce a network of learning automata, which we call it as distributed learning automata and then propose some iterative algorithms for solving stochastic shortest path problem. These algorithms use distributed learning automata to find a policy that determines a path from a source node to a destination node with minimal expected cost (length). In these algorithms, at each stage distributed learning automata determines which edges to be sampled. This sampling method may result in decreasing unnecessary samples and hence decreasing the running time of algorithms. It is shown that the shortest path is found with a probability as close as to unity by proper choice of the parameters of the proposed algorithms.