bluuebunny/crossref_metadata_2025 huggingface dataset:
No association between a 3’ untranslated region polymorphism in the neprilysin gene and Alzheimer's disease in the Japanese population
Authors: LI Guoyan , SHIBATA Nobuto , NAKAMURA Shinji , TAKAHASHI Tadashi , UEKI Akira , ARAI Heii
Published: October 2005

Background:  Alzheimer's disease (AD) is caused by neuronal cell death with aggregation of amyloid‐β (Aβ) in the brain cortex and hippocampus. Neprilysin (NEP) plays an important role mainly in the degradation of Aβ. The NEP‐knockout mouse shows low degradation of Aβ and is confirmed to have AD. The frequency of the C/C genotype of NEP159 C/T polymorphism in the 3’ untranslated region (UTR) of the NEP gene Apolipoprotein E (Apo E) ɛ4 group has been reported to be higher than that of the control group. In the present study, we screened for the polymorphism in our Japanese AD and control subjects. Furthermore, we searched for a new polymorphism in exon 1 and exon 24 in the NEP gene.

Methods:  121 sporadic AD (SAD) patients were recruited from among the inpatients and outpatients of the hospital the authors work in. The 101 age‐matched control subjects were recruited from healthy volunteers with no history of dementia or other neuropsychiatric diseases. The NEP159 C/T polymorphism and Apo E were genotyped by the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method and a new polymorphism was detected by the polymerase chain reaction–single strand conformation polymorphism (PCR–SSCP) method.

Results:  We confirmed that the frequency of the Apo E ɛ4‐allele was higher in the SAD group than in the control group. There was no significant difference in genotypic distribution of the NEP159 C/T polymorphism between the control and SAD groups.

Conclusion:  Our studies suggest that there is no genetic association between the NEP159 C/T polymorphism and the risk of Japanese SAD. Our results indicate that further genetic studies of the NEP gene should be performed in other ethnic groups.
Current concept and future research directions of mild cognitive impairment
Authors: ARAI Hiroyuki
Published: October 2005

Alzheimer's disease (AD) generally begins with mild memory problems which occur in an insidious manner and progresses to the development of multiple cognitive impairments. There is a ‘gray’ area between what is classified as ‘normal’ and what is classified as ‘dementia’, currently called mild cognitive impairment (MCI). In this article, a case of MCI is described, and the diagnosis, assessment, subclassification (pre‐Alzheimer type and white matter lesion type) and future therapeutic plans for MCI are reviewed.
Studies on diagnostic markers for Alzheimer's disease
Authors: URAKAMI Katsuya , TANIGUCHI Miyako , INOUE Masashi , WADA‐ISOE Kenji , WAKUTANI Yosuke , NAKASHIMA Kenji
Published: October 2005

In recent years, Alzheimer's disease (AD) has increased in incidence in Japan and elsewhere, and the marketing of donepezil hydrochloride (Aricept®) has allowed for the treatment of AD. These circumstances have encouraged the development of and research in markers for the early diagnosis of AD. Currently, the measurement of phosphorylated tau protein in the cerebrospinal fluid is considered to provide the most reliable and useful diagnostic marker for AD. For this purpose, a screening test using a touch panel computer can be recommended. The results of our study also suggest that the analysis of acetylcholine receptor α7 genetic polymorphism may be useful as a marker in the treatment with acetylcholine esterase inhibitors.
Successful risperidone therapy for a first episode of musical auditory hallucinations in elderly patients
Authors: OKUMURA Kazuo
Published: October 2005

Although musical auditory hallucinations (MH) occur mostly in women with a history of hearing disorders, brain tumors or epilepsy, there has been insufficient symptomatological discussion to date. We present two cases in which MH occurring in old age were successfully treated with risperidone (RIS). Case 1 involved a 74‐year‐old woman who complained chiefly of insomnia and abrupt onset of MH without any other symptoms. Case 2 involved an 85‐year‐old woman with a 10‐year history of symptomatic hearing loss who had abrupt onset of MH accompanied by tinnitus. Neither patient had a history of mental illness before their initial examination and they were both treated with RIS in the outpatient clinic. The dose range of 0.2–0.5 mg daily seemed effective, with a therapeutic response appearing in 2–4 weeks. Low‐dose RIS therapy may therefore be effective pharmacotherapy for MH.
Prevalence, incidence, and residual risk of human immunodeficiency virus among community and replacement first‐time blood donors in São Paulo, Brazil
Authors: Barreto Claudia C. , Sabino Ester C. , Gonçalez Thelma T. , Laycock Megan E. , Pappalardo Brandee L. , Salles Nanci A. , Wright David J. , Chamone Dalton F. , Busch Michael P.
Published: October 2005

BACKGROUND:  Concerted efforts have been directed toward recruitment of community rather than replacement donors in Brazil. Time trends and demographic correlates of human immunodeficiency (HIV) prevalence and incidence among first‐time (FT) donors in Brazil were examined by donation type. HIV residual risk from FT‐donor transfusions, and projected yield of p24 antigen and nucleic acid test (NAT) screening were estimated.

STUDY DESIGN AND METHODS:  HIV prevalence data and seroreactive specimens were obtained at Fundação Pró‐Sangue/Hemocentro‐de‐São Paulo from 1995 to 2001. To estimate incidence, confirmed‐positive samples from July 1998 through December 2001 were tested with a less‐sensitive (detuned) enzyme immunoassay to detect recent seroconversions. Incidence data were used to estimate residual risk and p24 and NAT yield based on published window periods (WPs).

RESULTS:  HIV prevalence was 22 percent higher among the FT community donors than replacement donors (19.6 vs. 16.1 per 10,000; p < 0.01) and 48 percent higher among men than women (19.1 vs. 12.9; p < 0.01). In the multivariable logistic regression, both variables remained significant predictors of HIV prevalence. HIV prevalence decreased from 20.4 (1995) to 13.1 per 10,000 FT donations (2001). HIV incidence was 2.7 per 10,000 person‐years. The estimated rate of infected antibody‐negative donations was 14.9 per 1,000,000 units (95% confidence interval, 9.8‐20.0). It was estimated that addition of p24 antigen, minipool NAT, and individual‐donation NAT assays would detect 3.9 (2.0‐5.8), 8.3 (5.3‐11.3), and 10.8 (7.1‐14.5) WP units per 1,000,000 FT donations, respectively.

CONCLUSION:  HIV incidence and residual transfusion risk estimates are approximately 10 times higher in Brazil FT donors compared to US and European FT donors. Community FT donors had higher HIV prevalence than replacement FT donors. The yield of p24 antigen or RNA screening will be low in Brazilian donors, but substantially higher than in US donors.
Platelet glycolytic flux increases stimulated by ultraviolet‐induced stress is not the direct cause of platelet morphology and activation changes: possible implications for the role of glucose in platelet storage
Authors: Li Junzhi , Goodrich Laura , Hansen Eric , Edrich Rick , Gampp Deanna , Goodrich Raymond P.
Published: October 2005

BACKGROUND:  Stress‐enhanced platelet (PLT) storage lesions include increased glycolysis, discoid‐to‐sphere morphology change, and spontaneous PLT activation. It is not clear if reduction in glycolysis can alleviate storage lesion development.

STUDY DESIGN AND METHODS:  Apheresis PLT concentrates were exposed to 17.2 J/mL UV light and 50 µM riboflavin, followed by storage with various concentrations of 2‐deoxyglucose (2‐DOG) for 5 days. The control had no UV or 2‐DOG exposure.

RESULTS:  Lactate production and glucose consumption were increased significantly to 0.1371 ± 0.0281 and 0.0724 ± 0.0151 mmol per 1012 cells per hour for UV‐treated PLTs, respectively, when compared to control samples. UV treatment induced a decline in pH to 6.55 ± 0.26 for treated PLTs on Day 5, hypotonic shock response (HSR) 33 ± 25 percent, extent of shape change (ESC) to 3.8 ± 3.6 percent, swirl 1.0 ± 1.0 and increased P‐selectin expression 85.2 ± 9.4 percent. Addition of 2‐DOG up to 20 mmol per L significantly reduced lactate production to 0.0515 ± 0.0045 mmol per 1012 cells per hour (p < 0.05) and glucose consumption to 0.0293 ± 0.0060 mmol per 1012 cells per hour and increased pH to 7.35 ± 0.09 in a dose‐dependent manner. 2‐DOG, however, had no effects on HSR, ESC, swirl, and P‐selectin expression. Furthermore, an exaggeration of UV‐stressed PLT aggregation by addition of 2‐DOG was also observed.

CONCLUSIONS:  Increased glycolytic flux is not a direct cause for PLT morphology change and spontaneous activation during storage lesion development. Reduction of glucose utilization may increase PLT loss during storage.
Therapeutic efficacy and safety of red blood cells treated with a chemical process (S‐303) for pathogen inactivation: a Phase III clinical trial in cardiac surgery patients
Authors: Benjamin Richard J. , McCullough Jeffrey , Mintz Paul D. , Snyder Edward , Spotnitz William D. , Rizzo Robert J. , Wages David , Lin Jin‐Sying , Wood Lindsey , Corash Laurence , Conlan Maureen G.
Published: October 2005

BACKGROUND: A randomized, double‐blind trial is reported of the clinical efficacy of red blood cells (RBCs) treated for pathogen inactivation with S‐303, a synthetic labile alkylating agent.

STUDY DESIGN AND METHODS: Patients undergoing complex cardiac surgeries were randomly assigned to receive either S‐303–treated (test) or conventional (control) RBC transfusion during surgery and for 6 days thereafter. Efficacy was evaluated by comparing the occurrence of a composite primary endpoint of treatment‐related morbidity (myocardial infarction and renal failure) and mortality.

RESULTS: Two‐hundred twenty‐three patients were randomly assigned and 148 patients who received transfusions (74 with S‐303–treated RBCs and 74 with control RBCs) were evaluable. The incidence of the primary endpoint was equivalent between the two groups (22 and 21% in the S‐303–treated and control RBC groups, respectively). Secondary endpoints, including hemoglobin increment (mean, 1.4 vs. 1.5 g/dL), number of RBC transfusions (mean, 4.4 vs. 3.8 units), and other blood product support, were also comparable. The adverse event profile was similar between groups; however, patients who received S‐303 RBCs were significantly more likely to develop constipation and less likely to suffer supraventricular extrasystoles. Four patients (2 test and 2 control) demonstrated positive indirect antiglobulin tests with reactivity for S‐303 RBCs at one or more time points before or after transfusion, without evidence of hemolysis.

CONCLUSION: S‐303–treated and conventional RBCs were equivalent with respect to clinical efficacy and safety in supporting the transfusion needs of cardiac surgery patients. Investigations are under way to ascertain the significance of S‐303 RBC antibodies and to prevent their occurrence.
Forecasting Spanish Natural Life Expectancy
Authors: Guillen Montserrat , Vidiella‐i‐Anguera Antoni
Published: October 2005

Knowledge of trends in life expectancy is of major importance for policy planning. It is also a key indicator for assessing future development of life insurance products, substantiality of existing retirement schemes, and long‐term care for the elderly. This article examines the feasibility of decomposing age‐gender‐specific accidental and natural mortality rates. We study this decomposition by using the Lee and Carter model. In particular, we fit the Poisson log‐bilinear version of this model proposed by Wilmoth and Brouhns et al. to historical (1975–1998) Spanish mortality rates. In addition, by using the model introduced by Wilmoth and Valkonen we analyze mortality‐gender differentials for accidental and natural rates. We present aggregated life expectancy forecasts compared with those constructed using nondecomposed mortality rates.
Sensitivity Analysis for Computer Model Projections of Hurricane Losses
Authors: Iman Ronald L. , Johnson Mark E. , Watson Charles C.
Published: October 2005

Projecting losses associated with hurricanes is a complex and difficult undertaking that is fraught with uncertainties. Hurricane Charley, which struck southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting damages from these storms. Due to shifts in the track and the rapid intensification of the storm, real‐time estimates grew from $2 billion to $3 billion in losses late on the 12th to a peak of $50 billion for a brief time as the storm appeared to be headed for the Tampa Bay area. The storm struck the resort areas of Charlotte Harbor and moved across the densely populated central part of the state, with early poststorm estimates in the $28 to $31 billion range, and final estimates converging at $15 billion as the actual intensity at landfall became apparent. The Florida Commission on Hurricane Loss Projection Methodology (FCHLPM) has a great appreciation for the role of computer models in projecting losses from hurricanes. The FCHLPM contracts with a professional team to perform onsite (confidential) audits of computer models developed by several different companies in the United States that seek to have their models approved for use in insurance rate filings in Florida. The team's members represent the fields of actuarial science, computer science, meteorology, statistics, and wind and structural engineering. An important part of the auditing process requires uncertainty and sensitivity analyses to be performed with the applicant's proprietary model. To influence future such analyses, an uncertainty and sensitivity analysis has been completed for loss projections arising from use of a sophisticated computer model based on the Holland wind field. Sensitivity analyses presented in this article utilize standardized regression coefficients to quantify the contribution of the computer input variables to the magnitude of the wind speed.
Uncertainty Analysis for Computer Model Projections of Hurricane Losses
Authors: Iman Ronald L. , Johnson Mark E. , Watson Charles C.
Published: October 2005

Projecting losses associated with hurricanes is a complex and difficult undertaking that is wrought with uncertainties. Hurricane Charley, which struck southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting damages from these storms. Due to shifts in the track and the rapid intensification of the storm, real‐time estimates grew from $2 to $3 billion in losses late on August 12 to a peak of $50 billion for a brief time as the storm appeared to be headed for the Tampa Bay area. The storm hit the resort areas of Charlotte Harbor near Punta Gorda and then went on to Orlando in the central part of the state, with early poststorm estimates converging on a damage estimate in the $28 to $31 billion range. Comparable damage to central Florida had not been seen since Hurricane Donna in 1960. The Florida Commission on Hurricane Loss Projection Methodology (FCHLPM) has recognized the role of computer models in projecting losses from hurricanes. The FCHLPM established a professional team to perform onsite (confidential) audits of computer models developed by several different companies in the United States that seek to have their models approved for use in insurance rate filings in Florida. The team's members represent the fields of actuarial science, computer science, meteorology, statistics, and wind and structural engineering. An important part of the auditing process requires uncertainty and sensitivity analyses to be performed with the applicant's proprietary model. To influence future such analyses, an uncertainty and sensitivity analysis has been completed for loss projections arising from use of a Holland B parameter hurricane wind field model. Uncertainty analysis quantifies the expected percentage reduction in the uncertainty of wind speed and loss that is attributable to each of the input variables.
Feeling at Risk Matters: Water Managers and the Decision to Use Forecasts
Authors: O'Connor Robert E. , Yarnal Brent , Dow Kirstin , Jocoy Christine L. , Carbone Gregory J.
Published: October 2005

Experts contend that weather and climate forecasts could have an important role in risk management strategies for community water systems. Yet, most water managers make minimal use of these forecasts. This research explores the determinants of the use of weather and climate forecasts by surveying managers of community water systems in two eastern American states (South Carolina and the Susquehanna River Basin of Pennsylvania). Assessments of the reliability of weather and climate forecasts are not driving their use as water managers who find forecasts reliable are no more likely to use them than are managers who find them unreliable. Although larger systems and those depending on surface water are more likely to use forecasts for some (but not all) purposes, the strongest determinant of forecast use is risk perceptions. Water managers who expect to face problems from weather events in the next decade are much more likely to use forecasts than are water managers who expect few problems. Their expectations of future problems are closely linked with past experience: water managers who have had problems with specific types of weather events (e.g., flood emergencies) in the last 5 years are likely to expect to experience problems in the next decade. Feeling at risk, regardless of the specific source of that weather‐related risk, stimulates a decision to use weather and climate forecasts.
Model Averaging Using the Kullback Information Criterion in Estimating Effective Doses for Microbial Infection and Illness
Authors: Moon Hojin , Kim Hyun‐Joo , Chen James J. , Kodell Ralph L.
Published: October 2005

Since the National Food Safety Initiative of 1997, risk assessment has been an important issue in food safety areas. Microbial risk assessment is a systematic process for describing and quantifying a potential to cause adverse health effects associated with exposure to microorganisms. Various dose‐response models for estimating microbial risks have been investigated. We have considered four two‐parameter models and four three‐parameter models in order to evaluate variability among the models for microbial risk assessment using infectivity and illness data from studies with human volunteers exposed to a variety of microbial pathogens. Model variability is measured in terms of estimated ED01s and ED10s, with the view that these effective dose levels correspond to the lower and upper limits of the 1% to 10% risk range generally recommended for establishing benchmark doses in risk assessment. Parameters of the statistical models are estimated using the maximum likelihood method. In this article a weighted average of effective dose estimates from eight two‐ and three‐parameter dose‐response models, with weights determined by the Kullback information criterion, is proposed to address model uncertainties in microbial risk assessment. The proposed procedures for incorporating model uncertainties and making inferences are illustrated with human infection/illness dose‐response data sets.
Prediction of change in level of problem behavior among children of bipolar parents
Authors: Wals M. , Reichart C. G. , Hillegers M. H. J. , Nolen W. A. , Van Os J. , Ormel J. , Verhulst F. C.
Published: October 2005

Objective:  To determine the effects of familial loading, birth weight, and family problems on change in parent‐reported problems across a 14‐month period among children of bipolar parents.

Method:  Emotional and behavioral problems in a sample of 140 offspring of bipolar parents and familial loading in first‐ and second‐degree relatives were assessed at two measurements. Parents reported the birth weight of their offspring and completed a questionnaire on family problems. Multiple linear regression analyses were performed to assess associations of the three predictors with change in problem scores at follow‐up.

Results:  Familial loading of unipolar disorder was a unique predictor for an increase in problem scores from the first to the second measurement with β‐coefficients ranging from 0.17 to 0.25. Birth weight and family problems were not associated with change in problem scores across the two measurements.

Conclusion:  Familial loading of unipolar disorder predicted an increase in behavioral and emotional problems across the 14‐month follow‐up.
New excavations at the Barbar Temple, Bahrain
Authors: Højlund Flemming , Bangsgaard Pernille , Hansen Jesper , Haue Niels , Kjærum Poul , Lund Dorthe Danner
Published: October 2005

In 2004 excavations at the Barbar Temple dating to c. 2000 BC established that the function of the southeastern subterranean channel connected to the temple pool was to supply the pool with water and not to divert water away from the pool. North and west of the temple the oval terrace wall of its third phase was located. In the centre of the Northeast Temple the remains of a shaft‐stairway leading down to a well‐chamber was uncovered and shown to be furnished with two subterranean channels leading water into the chamber. South of the Northeast Temple a house with late pottery was excavated. Two stamp seals and two seal‐impressed tokens were found.
Some thoughts on ibex on plinths in early South Arabian art
Authors: Avanzini Alessandra
Published: October 2005

Ibex are an important iconographic element in the art of South Arabia. The origins, geographical distribution, chronology and divine affinities of ibex are considered, drawing on both archaeological and epigraphic sources.
Composite bows at ed‐Dur (Umm al‐Qaiwain, U.A.E.)
Authors: Waele An De
Published: October 2005

This article discusses seven bone fragments excavated during the second Belgian archaeological campaign at ed‐Dur (tomb G.3831, area N). Rather than weaving implements, these objects are identified as the reinforcing bone laths of composite bows. Information on the composite bow in general—origins, structural composition and technical advantages—will be given. Additionally, the question of which types of composite bows could have been present at ed‐Dur and what role these weapons could have played at the site are discussed.
Tombstones bearing Hebrew inscriptions in Aden
Authors: Klein‐Franke A.
Published: October 2005

Inscriptions on tombstones provide us with information about the family and society of the deceased. Through a reading of these inscriptions the individual is no longer anonymous. In addition to names, grave inscriptions often contain information on an individual's status and profession, offering us insights into the life of a community which include different classes and professions. The information emphasised in grave inscriptions reveals the values of a society and its traditions. This study investigates the corpus of Hebrew inscriptions on tombstones in Aden.
Surgical treatment of multilevel cervical radiculomyelopathy caused by the concomitant ossification of the ligamentum flavum and the posterior longitudinal ligament
Authors: Yang Jiao‐Chiao , Lin Chien‐Pang , Chan Jun‐Yeen , Liu Yuan‐Kai , Huang Jing‐Shan
Published: October 2005

Objectives:  A two‐stage operation is essential for patients with cervical spine myelopathy that is the result of concomitant ligamentum flavum and posterior longitudinal ligament ossification.

Methods:  Modified open door laminoplasty with a miniplate and screw from the posterior approach was carried out first. Then anterior decompression and fusion with a Casper plate and Surgibone at the C5‐6 intervertebral space were carried out 1 week after the first operation.

Results:  One week after the second procedure, the postoperative Nurick score improved from four to two. The patient withstood the whole procedure well and within one week was noted to have improved muscle strength.

Conclusions:  The two‐stage operation is a safe and effective choice for treating concomitant OPLL and OLF in the cervical spine with radiculomyelopathy.
Gastrosplenic fistula: A rare complication of splenic abscess
Authors: Ballas Konstantinos , Rafailidis Savvas , Demertzidis Charalambos , Eugenidis Nikolaos , Alatsakis Michael , Zafiriadou Eythymia , Sakadamis Athanassios
Published: October 2005

Gastrosplenic fistulas are rare complications of malignant gastric or splenic diseases and, less frequently, are the result of benign diseases such as gastric ulcers and Crohn's disease. Spontaneous gastrosplenic fistula as a result of splenic abcess has not been reported in the literature so far. A 70‐year‐old man presented with a splenic abscess which had spontaneously developed a gastrosplenic fistula. The fistula was diagnosed by computed tomography scan and upper gastrointestinal endoscopy and was successfully managed by splenectomy with en bloc resection of part of the greater curvature of the stomach. Although gastrosplenic fistulas are a relatively rare complication of gastric or splenic diseases, an awareness might lead the clinician to early recognition and surgery can be offered earlier as the treatment of choice.
Developments in trauma management: From the field to the intensive care unit
Authors: Young Karl Kang
Published: October 2005

There have not been dramatic changes in trauma management in recent years. Nevertheless, there are noteworthy developments that might eventually change both paradigms of trauma systems and clinical management. In the present study, organizational aspects of mass casualty scenarios and what we have learned from the experiences of military doctors are examined. Then, the perennial theme of fluid resuscitation; when, what and how much to give, is examined. The management of bleeding and minimization of allogeneic blood transfusions raise the topics of recombinant factor VIIa and oxygen carrying blood substitutes. Finally, an aspect of intensive care management that is very topical, that of immunonutrition and the modulation of sepsis in intensive care, is examined.
Bleeding duodenal choriocarcinoma: An unusual cause of positive urine pregnancy test
Authors: Li Jimmy Chak‐Man , Kan Amanda Nim‐Chi , Wan Suk‐King , Chan Angus Chi‐Wai
Published: October 2005

Primary choriocarcinoma of the duodenum is exceedingly rare. Only a few cases have been reported previously. A case of extragenital choriocarcinoma of the duodenum in a 43‐year‐old Chinese woman is described. Her presenting symptoms were abdominal pain, anaemia and melaena. Her urine pregnancy test was positive, which made ectopic pregnancy one of the differential diagnoses. An urgent ultrasound scan and computed tomography scan of the abdomen showed no evidence of an ectopic pregnancy. Upper endoscopy found a bleeding ulcer at the second part of the duodenum. A duodenal ulcer biopsy showed choriocarcinoma. The positive urine pregnancy test represents a useful marker in early diagnosis.
Isolated spontaneous breast haemorrhage in a patient on anticoagulation therapy: Breast biopsy or not?
Authors: Dutta Roy Subhajit , Scally John , Troop Anne , Selvachandran Sithamparapillai
Published: October 2005

A 62‐year‐old woman presented with a hard, well circumscribed, painless breast lump of 2 weeks duration. Past history showed an episode of deep vein thrombosis 6 weeks earlier, for which she was on warfarin. Mammogram, ultrasound and needle biopsy confirmed spontaneous haemorrhagic necrosis of breast tissue, a rare site for spontaneous bleeding for patients on anticoagulants. Though concurrent use of warfarin or heparin is generally considered a contraindication to carrying out core breast biopsy, recent evidence suggests it is unnecessary to discontinue anticoagulants in patients undergoing such procedures, which is crucial in ruling out incidental malignancy, especially in elderly patients.
What's new in burns trauma?
Authors: Burd Andrew , Noronha Frederick V.
Published: October 2005

Objectives:  To review advances in burns care in Hong Kong over the past five years and compare these with global advances.

Methods:  Global advances have been summarized from literature reviews and current practices detailed from published and ongoing local studies.

Results:  Hong Kong is providing a world class burns service and makes a significant contribution to evolving clinical practice on a global scale.

Conclusions:  Burns care is continually evolving and survival per se is not the significant challenge it was in previous decades. The emphasis remains on burns prevention but in the event of injuries occurring, quality of survival is the key issue which involves prompt and appropriate acute care, effective reconstruction and holistic rehabilitation.
Penetrating injuries to the aerodigestive tract
Authors: Weigelt John A.
Published: October 2005

Although not all penetrating injuries to the neck need operative intervention, most patients with an aerodigestive tract injury should undergo operative repair. After initial stabilization of airway, breathing and circulation, a simple diagnostic approach should identify most patients with injuries. Most patients require simple repairs of injuries to the cervical oesophagus or trachea. Basic principles of proper exposure, debridement and tension free closures should provide the best outcomes and lowest complication rates.
Interleukin‐6 gene polymorphism is an age‐dependent risk factor for myocardial infarction in men
Authors: Chiappelli M. , Tampieri C. , Tumini E. , Porcellini E. , Caldarera C. M. , Nanni S. , Branzi A. , Lio D. , Caruso M. , Hoffmann E. , Caruso C. , Licastro F.
Published: October 2005

Several studies show that inflammatory components may contribute to atherosclerosis and increase the risk for myocardial infarction (MI). Interleukin‐6 (IL‐6) is a key pro‐inflammatory and immune‐modulatory cytokine of relevance for cardiovascular diseases. In this case‐control study, 200 patients with MI and 257 healthy controls were genotyped for the polymorphism present in −174 promoter region of the IL‐6 gene. Plasma concentrations of IL‐6 and C‐reactive protein (CRP) in a group of patients and controls were measured. The −174 C allele was associated with an increased risk of developing MI (OR = 2.886, c.i. = 1.801–4.624, P = 0.0001) in older patients, while no association was found in younger ones. The IL‐6 plasma levels were higher in patients with MI carrying the CC genotype than in GG patients (CC carriers, IL‐6 = 2.97 pg mL−1 vs. GG carriers = 1.81 pg mL−1, P = 0.016). A positive correlation of IL‐6 levels with those of CRP in serum from patients with MI was also found. Data from this study suggest that the C allele of the promoter polymorphism in the IL‐6 gene is a risk factor for MI in the elderly, and the production of the IL‐6 is differentially affected by different genotypes of the IL‐6 −174 promoter polymorphism.
HLA‐C locus alleles distribution in patients from northern Poland with psoriatic arthritis — preliminary report
Authors: Szczerkowska Dobosz A. , Rebała K. , Szczerkowska Z. , Nedoszytko B.
Published: October 2005

The aim of the study was to compare the frequency of human leucocyte antigen‐C (HLA‐C) locus alleles in patients with psoriatic arthritis and in healthy controls in the same ethnic group in Poland, and to correlate them with age of onset of psoriatic skin changes and joints symptoms. HLA‐C locus alleles of 41 patients and 80 controls were determined by a polymerase chain reaction (PCR) low‐resolution method. The Cw*06 allele occurred more frequently (P adjusted for multiple comparison = 0.004) in patients with psoriatic arthritis than in controls. Patients who carried the HLA‐Cw*06 allele had a significantly earlier mean age of onset of both psoriasis (P = 0.01) and arthritis (P = 0.008) compared with Cw*06‐negative patients. Our results confirm the association between Cw*06 allele and psoriatic arthritis in the northern Poland population and suggest that the HLA‐Cw*06 may determine not only the disease susceptibility, but also the age of onset of psoriatic arthritis.
Automation of analysis of cardiovascular autonomic function from chronic measurements of arterial pressure in conscious rats
Authors: Waki Hidefumi , Katahira Kiyoaki , Polson Jaimie W. , Kasparov Sergey , Murphy David , Paton Julian F. R.
Published: October 2005

At present, there is no single software package that provides a comprehensive power spectral analysis of pulse interval (PI) and arterial blood pressure (BP), spontaneous cardiac baroreceptor reflex gain (sBRG) and respiratory rate. Furthermore, scientific validation of the software that is currently commercially available and employed has not been published. We introduce ‘Hey‐Presto’ software, which fully evaluates cardiovascular autonomic function from the BP signal obtained from rats. The program performs power spectral analysis of HR and BP variability, respiratory rate and, based on a time‐series method, spontaneous cardiac baroreceptor (sBRG). We have validated Hey‐Presto with conventional pharmacological agents to block cardiac vagal and cardiac sympathetic transmission in conscious rats fitted with a radio‐telemetery BP transducer. Following administration of atropine (1 mg kg−1, i.v.), high‐frequency (HF) power of the PI decreased (P < 0.01) and was associated with the expected increase in HR. Subsequent cardiac sympathetic blockade (atenolol, 1 mg kg−1, i.v.) reduced the low frequency (LF) to HF ratio (LF:HF) of the PI (P < 0.01), which was consistent with the observed reduction in HR. We also found that alterations in sBRG after blockade of cardiac autonomic transmission were highly comparable to values computed manually using vasoactive drugs administered intravenously. The software also detected circadian rhythms in sBRG, HF component of the PI, LF:HF of the PI and LF component of the BP as well as BP and HR during continuous 24 h recording. By demonstrating its application to humans, we found appropriate changes in the power of PI and the LF power of the BP during postural changes. These results demonstrate that Hey‐Presto allows a fully automated, reliable, fast and comprehensive evaluation of cardiovascular autonomic function based on chronic measurements of BP in rats. Moreover, we have confirmed its versatility by demonstrating its application to man.
Inhibitory neurotransmission in the nucleus tractus solitarii: implications for baroreflex resetting during exercise
Authors: Potts Jeffrey T.
Published: October 2005

Inhibitory neurotransmission plays a crucial role in the processing of sensory afferent signals in the nucleus of the solitary tract (NTS). The aim of this review is to provide a critical overview of inhibitory mechanisms that may be responsible for altering arterial baroreflex function during physical activity or exercise. Over a decade ago, the view of reflex control of cardiovascular function during exercise was revised because of the finding that the arterial baroreflex is reset in humans, enabling continuous beat‐to‐beat reflex regulation of blood pressure and heart rate. During the ensuing decade, many investigators proposed that resetting was mediated by central neural mechanisms that were intrinsic to the brain. Recent experimental data suggest that rapid and reversible changes in γ‐aminobutyric acid (GABA) inhibitory neurotransmission within the NTS play a fundamental role in this process. The hypothesis will be presented that baroreflex resetting by somatosensory input is mediated by: (1) selective inhibition of barosensitive NTS neurones; and (2) excitation of sympathoexcitatory neurones in the rostral ventrolateral medulla. Current research findings will be discussed that support an interaction between GABA and substance P (SP) signalling mechanisms in the NTS. An understanding of these mechanisms may prove to be essential for future detailed analysis of the cellular and molecular mechanisms underlying sensory integration in the NTS.
Intraspinal microstimulation preferentially recruits fatigue‐resistant muscle fibres and generates gradual force in rat
Authors: Bamford J. A. , Putman C. T. , Mushahwar V. K.
Published: October 2005

Intraspinal microstimulation (ISMS), a novel rehabilitative therapy consisting of stimulation through fine, hair‐like microwires targeted at the ventral spinal cord, has been proposed for restoring standing and walking following spinal cord injury. This study compared muscle recruitment characteristics of ISMS with those produced by peripheral nerve cuff stimulation (NCS). Thirty‐three minutes of either ISMS or NCS at 1, 20 or 50 s−1 and 1.2 × threshold (T) amplitude depleted glycogen from muscle fibres of vastus lateralis and rectus femoris. ISMS and NCS were also carried out at 20 s−1 and 3.0T. Muscle serial sections were stained for glycogen and for myosin heavy chain (MHC)‐based fibre types using a panel of monoclonal antibodies. The results of this study show that ISMS recruited fatigue‐resistant (FR) fibres at 2.9, 1.9, 1.7 and 2.5 times their relative MHC content at 1, 20 and 50 s−1 1.2T and 20 s−1 3.0T, respectively. In contrast, NCS recruited FR fibres at 1.2, 1.0, 2.1 and 0.0 times their MHC content at 1, 20 and 50 s−1 1.2T and 20 s−1 3.0T, respectively. The proportion of FR fibres recruited by ISMS and NCS was significantly different in the 20 s−1 3.0T condition (P < 0.0001). We also report that force recruitment curves were 4.9‐fold less steep (P < 0.019) for ISMS than NCS. The findings of this study provide evidence for the efficacy of ISMS and further our understanding of muscle recruitment properties of this novel rehabilitative therapy.
Retracted: Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats
Authors: Gao Jun , Wu Xiaoyin , Owyang Chung , Li Ying
Published: October 2005

The anterior cingulate cortex (ACC) is critically involved in processing the affective component of pain sensation. Visceral hypersensitivity is a characteristic of irritable bowel syndrome. Electrophysiological activity of the ACC with regard to visceral sensitization has not been characterized. Single ACC neuronal activities in response to colorectal distension (CRD) were recorded in control, sham‐treated rats and viscerally hypersensitive (EA) rats (induced by chicken egg albumin injection,i.p). The ACC neurones of controls failed to respond to 10 or 30 mmHg CRD; only 22% were activated by 50 mmHg CRD. Among the latter, 16.4% exhibited an excitatory response to CRD and were labelled ‘CRD‐excited’ neurones. In contrast, CRD (10, 30 and 50 mmHg) markedly increased ACC neuronal responses of EA rats (10%, 28% and 47%, respectively). CRD produced greater pressure‐dependent increases in ACC spike firing rates in EA rats compared with controls. Splanchnicectomy combined with pelvic nerve section abolished ACC responses to CRD in EA rats. Spontaneous activity in CRD‐excited ACC neurones was significantly higher in EA rats than in controls. CRD‐excited ACC neurones in control and EA rats (7 of 16 (42%) and 8 of 20 (40%), respectively) were activated by transcutaneous electrical and thermal stimuli. However, ACC neuronal activity evoked by noxious cutaneous stimuli did not change significantly in EA rats. This study identifies CRD‐responsive neurones in the ACC and establishes for the first time that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization, characterized by increased spontaneous activity of CRD‐excited neurones, decreased CRD pressure threshold, and increased response magnitude. Enhanced ACC nociceptive transmission in viscerally hypersensitive rats is restricted to visceral afferent input.
Activity‐dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus
Authors: Di Shi , Boudaba Cherif , Popescu Ion R. , Weng Feng‐Ju , Harris Christina , Marcheselli Victor L. , Bazan Nicolas G. , Tasker Jeffrey G.
Published: October 2005

Exogenous cannabinoids have been shown to significantly alter neuroendocrine output, presaging the emergence of endogenous cannabinoids as important signalling molecules in the neuroendocrine control of homeostatic and reproductive functions, including the stress response, energy metabolism and gonadal regulation. We showed recently that magnocellular and parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus and supraoptic nucleus (SON) respond to glucocorticoids by releasing endocannabinoids as retrograde messengers to modulate the synaptic release of glutamate. Here we show directly for the first time that both of the main endocannabinoids, anandamide (AEA) and 2‐arachidonoyl glycerol (2‐AG), are released in an activity‐dependent fashion from the soma/dendrites of SON magnocellular neurones and suppress synaptic glutamate release and postsynaptic spiking. Cannabinoid reuptake blockade increases activity‐dependent endocannabinoid levels in the region of the SON, and results in the inhibition of synaptically driven spiking activity in magnocellular neurones. Together, these findings demonstrate an activity‐dependent release of AEA and 2‐AG that leads to the suppression of glutamate release and that is capable of shaping spiking activity in magnocellular neurones. This activity‐dependent regulation of excitatory synaptic input by endocannabinoids may play a role in determining spiking patterns characteristic of magnocellular neurones under stimulated conditions.
Synaptic fatigue at the naive perforant path–dentate granule cell synapse in the rat
Authors: Abrahamsson Therése , Gustafsson Bengt , Hanse Eric
Published: October 2005

Synaptic activation at low frequency is often used to probe synaptic function and synaptic plasticity, but little is known about how such low‐frequency activation itself affects synaptic transmission. In the present study, we have examined how the perforant path–dentate granule cell (PP–GC) synapse adapts to low‐frequency activation from a previously non‐activated (naive) state. Stimulation at 0.2 Hz in acute slices from developing rats (7–12 days old) caused a gradual depression of the AMPA EPSC (at −80 mV) to about half within 50 stimuli. This synaptic fatigue was unaffected by the NMDA and metabotropic glutamate (mGlu) receptor antagonists d‐AP5 and LY‐341495. A smaller component of this synaptic fatigue was readily reversible when switching to very low‐frequency stimulation (0.033–0.017 Hz) and is attributed to a reversible decrease in release probability, which is probably due to depletion of readily releasable vesicles. Thus, it was expressed to the same extent by AMPA and NMDA EPSCs, and was associated with a decrease in quantal content (measured as 1/CV2) with no change in the paired‐pulse ratio. The larger component of the synaptic fatigue was not readily reversible, was selective for AMPA EPSCs and was associated with a decrease in 1/CV2, thus probably representing silencing of AMPA signalling in a subset of synapses. In adult rats (> 30 days old), the AMPA silencing had disappeared while the low‐frequency depression remained unaltered. The present study has thus identified two forms of synaptic plasticity that contribute to fatigue of synaptic transmission at low frequencies at the developing PP–GC synapse; AMPA silencing and a low‐frequency depression of release probability.
Prostaglandin H2 synthase‐1 and ‐2 expression in guinea pig gestational tissues during late pregnancy and parturition
Authors: Welsh Toni , Mitchell Carolyn M. , Walters William A. , Mesiano Sam , Zakar Tamas
Published: October 2005

Increased intrauterine prostaglandin (PG) production is crucial for the initiation of parturition. To investigate the mechanisms controlling intrauterine PG synthesis, we examined the expression of the key PG biosynthetic isoenzymes, PG‐H2 synthase (PTGS)‐1 and ‐2, in the amnion, visceral yolk sac (VYS), placenta and myo‐endometrium of pregnant guinea pigs. This animal model was chosen because the hormonal milieu of pregnancy and the role of PGs in the hormonal control of parturition are similar to those in the human. PTGS1 mRNA abundance, measured by real‐time RT‐PCR, increased in the amnion and the placenta during the last third of gestation. During labour, PTGS1 mRNA levels decreased precipitously in all four tissues. PTGS1 protein abundance, assessed by immunoblotting, increased to high levels in the amnion and the placenta by the end of pregnancy and remained high during labour. PTGS2 mRNA expression was higher in the placenta than in the other tissues, but did not change before and during labour. PTGS2 protein expression decreased in the placenta and remained low in the other tissues during labour. Immunohistochemistry showed pervasive PTGS1 protein expression in the amnion and strong expression in the parietal yolk sac membrane (PYS) covering the placenta. PTGS2 was expressed in the PYS and the endometrium. The PTGS inhibitor piroxicam, administered in doses that inhibited PTGS1 but not PTGS2, significantly prolonged gestation. These data suggest that PGs generated by intrauterine PTGS1 are involved in the timing of birth in guinea pigs. The induction of PTGS1 in the amnion and the PYS is a critical event leading to labour in guinea pigs and models analogous changes in the human gestational tissues before labour.
Origin of spontaneous rhythmicity in smooth muscle
Authors: McHale Noel , Hollywood Mark , Sergeant Gerard , Thornbury Keith
Published: October 2005

Rhythmic electrical activity is a feature of most smooth muscles but the mechanical consequences can vary from regular rapid phasic contractions to sustained contracture. For many years it was thought that spontaneous electrical activity originated in smooth muscle cells but recently it has become apparent that there are specialized pacemaker cells in many organs that are morphologically and functionally distinct from smooth muscle and that the former cells are the source of spontaneous electrical activity. Such a pacemaker function is well documented for the ICC of the gastrointestinal tract but evidence is accumulating that ICC‐like cells play a similar role in other types of smooth muscle. We have recently shown that there are specialized pacemaking cells in the rabbit urethra which are spontaneously active when freshly isolated, readily distinguishable from smooth muscle cells under bright field illumination and relatively easy to study using patch‐clamp and confocal imaging techniques. Recent results suggest that calcium oscillations in isolated rabbit urethral interstitial cells are initiated by calcium release from ryanodine sensitive intracellular stores, that oscillation frequency is very sensitive to the external calcium concentration and that conversion of the primary oscillation to a propagated calcium wave depends upon IP3‐induced calcium release.
Lipid rafts, the sarcoplasmic reticulum and uterine calcium signalling: an integrated approach
Authors: Noble Karen , Zhang Jie , Wray Susan
Published: October 2005

The pathways involved in Ca2+ signalling in the uterus remain incompletely understood, impairing our ability to prevent preterm and difficult labours. In this review we focus on two elements in the pathway of Ca2+ signalling that have recently emerged as playing important roles: membrane lipid rafts and the sarcoplasmic reticulum. We examine the evidence for lipid rafts in the uterus and discuss their functional role. We suggest that the increases in cytosolic [Ca2+] and contractility that occur with raft disruption are due, at least in part, to effects on large conductance Ca2+‐activated K+ (BK) channels that are localized to rafts. The role of the SR in contributing to subsarcolemmal cytosolic microdomains in uterus is evaluated, along with its interactions with ion channels on the plasma membrane. Thus, signalling microdomains play an important, but incompletely understood, role in the uterus, and integrating them into other Ca2+ signalling pathways is a challenge for further research. We suggest that the role of the SR changes in pregnancy, from promoting quiescence via BK channels or SR Ca2+ uptake, to promoting Ca2+ entry and contractility at term, and relate data on lipid rafts to clinical outcome in obese pregnant women.