bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperbaric oxygen therapy reduces neuroinflammation and expression of matrix metalloproteinase‐9 in the rat model of traumatic brain injury
Authors: Vlodavsky E. , Palzur E. , Soustiel J. F.
Published: October 2005

The acute inflammatory response plays an important role in secondary brain damage after traumatic brain injury (TBI). Neutrophils provide the main source of matrix metalloproteinases (MMPs) which also play a deleterious role in TBI. Numerous preclinical studies have suggested that hyperbaric oxygen therapy (HBOT) may by beneficial in various noncerebral and cerebral inflammatory diseases. The goal of this study was to evaluate the effects of HBOT on inflammatory infiltration and the expression of MMPs in correlation with secondary cell death in the rat model of dynamic cortical deformation (DCD). Twenty animals underwent DCD with subsequent HBOT (2.8 ATA, two sessions of 45 min each); 10 animals: DCD and normobaric oxygenation (1 ATA), 10 animals: not treated after DCD. Cell death was evaluated by TUNEL. Neutrophils were revealed by myeloperoxidase staining. Immunohistochemical staining for MMP‐2 and ‐9 and tissue inhibitors of MMP‐1 (TIMP‐1) and ‐2 was also performed and the results were quantitatively evaluated by image analysis. In the animals treated by HBOT, a significant decrease in the number of TUNEL‐positive cells and neutrophilic inflammatory infiltration was seen in comparison with nontreated animals and those treated by normobaric oxygen. The expression of MMP‐9 was also significantly lower in the treated group. Staining for MMP‐2 and TIMP‐2 did not change significantly. Our results demonstrate that HBOT decreased the extent of secondary cell death and reactive neuroinflammation in the TBI model. The decline of MMP‐9 expression after HBOT may also contribute to protection of brain tissue in the perilesional area. Further research should be centred on the evaluation of long‐term functional and morphological results of HBOT.
Age‐related changes in striatal nitric oxide synthase‐immunoreactive interneurones in the dystonic dt sz mutant hamster
Authors: Sander S. E. , Hamann M. , Richter A.
Published: October 2005

The dt sz mutant hamster represents a model of paroxysmal dyskinesia in which dystonic episodes can be age‐dependently induced by stress. GABAergic interneurones which co‐express calcium binding proteins were found to be reduced in the striatum of the dtsz mutant. Other types of striatal interneurones have so far not been examined. In the present study, we therefore determined the density of nitric oxide synthase (NOS)‐immunoreactive interneurones in the striatum of the dtsz mutant in comparison with nondystonic control hamsters. At the age of most marked expression of dystonia (30–40 days of life), the density of NOS‐positive interneurones was decreased in the striatum of dtsz hamsters (−21%) in comparison with age‐matched nondystonic control hamsters. Spontaneous remission of dystonia (age >90 days) coincided with a normalization of the density of NOS‐reactive interneurones within the whole striatum of dtsz hamsters, but there remained a reduced density in distinct subregions. Together with previous findings the present data indicate that the development of striatal interneurones is retarded in mutant hamsters. The age‐related deficit of NOS‐reactive interneurones may at least in part contribute to an abnormal activity of striatal GABAergic projection neurones and thereby to the age–dependent dystonic syndrome in the dtsz mutant.
Protection Against Neonatal Escherichia coli Diarrhoea in Pigs by Vaccination of Sows with a New Vaccine that Contains Purified Enterotoxic E. coli Virulence Factors F4ac, F4ab, F5 and F6 Fimbrial Antigens and Heat‐Labile E. coli Enterotoxin (LT) Toxoid
Authors: Riising H.‐J. , Murmans M. , Witvliet M.
Published: October 2005

The efficacy of a new vaccine against neonatal Escherichia coli diarrhoea in piglets containing purified F4ab, F4ac, F5 and F6 fimbriae and detoxified heat‐labile toxin (LT) was tested in challenge experiments by the method described by the European Pharmacopoeia (3rd edn, EDQM, Council of Europe, Strasbourg, France). A group of 11 young sows from a herd without E. coli problems was vaccinated 6–8 and 2–4 weeks prior to expected farrowing and another group of nine young sows were non‐vaccinated controls. Escherichia coli antibody titres were determined in serum samples taken from the sows before first vaccination and before farrowing and in colostrum samples. The newborn piglets were allowed to suckle colostrum from their mother immediately after birth. The piglets were marked with individually numbered ear tags. Approximately 12 h after birth, 118 piglets from vaccinated sows and 79 piglets from non‐vaccinated control sows were challenged by oral instillation of 5 ml of a freshly prepared culture of one of the challenge strains [O8:K87:F4ab (LT+) or O149:K91:F4ac (LT+) or O9:K30:F5 or O9:K103:F6 respectively]. The challenge cultures contained as a mean 6.8 × 109 CFU/ml. After challenge the piglets were observed for 7 days and mortality and morbidity were recorded. Vaccinated sows developed significant levels of antibody titres in colostrum and serum. Control sows stayed at a low/seronegative level. The protective efficacy was excellent because 66.7–87.5% of the piglets from vaccinated sows remained without clinical signs after challenge. Only 0.0–28.0% of the piglets from non‐vaccinated sows remained healthy and more than 47.1% of the piglets in this group died after challenge. It is concluded that the new vaccine is very effective in protection of piglets against neonatal E. coli diarrhoea.
Detection of Bovine Viral Diarrhoea Virus Infected Cattle – Testing Tissue Samples Derived from Ear Tagging Using an ErnsCapture ELISA
Authors: Kuhne S. , Schroeder C. , Holmquist G. , Wolf G. , Horner S. , Brem G. , Ballagi A.
Published: October 2005

A new diagnostic approach testing tissue samples derived from cattle ear tagging for bovine viral diarrhoea virus (BVDV) antigen in a commercially available antigen capture enzyme‐linked immunosorbent assay (ACE) was developed. To validate this method, 99 positive and 469 negative samples were tested. With those samples the assay yielded a sensitivity of 100% and specificity of ≥99.6%. Serum and ear tissue samples from 11 persistently infected (PI) BVDV calves were tested. While serum samples were negative after intake of colostrum, the ear tissue samples could be detected positive for BVDV all the time. Testing multiple samples derived from the same ear from PI cattle yielded positive results and low variation. Using cattle ear tags combining the ear tag application with sampling of a small ear tissue plug and testing those tissue samples with an ACE could be a reliable and economic way of BVDV testing.
Diagnostic Procedures in Tularaemia with Special Focus on Molecular and Immunological Techniques
Authors: Splettstoesser W. D. , Tomaso H. , Al Dahouk S. , Neubauer H. , Schuff‐Werner P.
Published: October 2005

Tularaemia is a severe bacterial zoonosis caused by the highly infectious agent Francisella tularensis. It is endemic in countries of the northern hemisphere ranging from North America to Europe, Asia and Japan. Very recently, Francisella‐like strains causing disease in humans were described from tropical northern Australia. In the last decade, efforts have been made to develop sensitive and specific immunological and molecular techniques for the laboratory diagnosis of tularaemia and also for the definite identification of members of the species F. tularensis and its four subspecies. Screening for the keyword ‘Francisella’ a Medline search over the last decade was performed and articles describing diagnostic methods for tularaemia and its causative agent were selected. Besides classical microbiological techniques (cultivation, biochemical profiling, susceptibility testing) several new immunological and molecular approaches to identify F. tularensis have been introduced employing highly specific antibodies and various polymerase chain reaction (PCR)‐based methods. Whereas direct antigen detection by enzyme‐linked immunosorbent assay (ELISA) or immunofluorescence might allow early presumptive diagnosis of tularaemia, these methods – like all PCR techniques – still await further evaluation. Therefore, diagnosis of tularaemia still relies mainly on the demonstration of specific antibodies in the host. ELISA and immunoblot methods started to replace the standard tube or micro‐agglutination assays. However, the diagnostic value of antibody detection in the very early clinical phase of tularaemia is limited. Francisella tularensis is regarded as a ‘highest priority’ biological agent (category ‘A’ according to the CDC, Atlanta, GA, USA), thus rapid and reliable diagnosis of tularaemia is required not only for a timely onset of therapy, the handling of outbreak investigations but also for the surveillance of endemic foci. Only very recently, evaluated test kits for serological diagnosis of human tularaemia became available, while the introduction of standardized molecular techniques for detection and typing is still missing.
Mortality risk factors of Acinetobacter baumannii bacteraemia
Authors: Choi J. Y. , Park Y. S. , Kim C. O. , Park Y. S. , Yoon H. J. , Shin S. Y. , Kim Y.‐A. , Song Y. G. , Yong D. , Lee K. , Kim J. M.
Published: October 2005

Abstract

Background:  Acinetobacter baumannii is one of the most important nosocomial pathogens, and its multiple antibiotic resistance has emerged as an obstacle in the treatment of these infections worldwide.

Aims:  To identify risk factors of mortality for A. baumannii bacteraemia.

Methods:  A retrospective cohort study of 72 patients with significant A. baumannii bacteraemia was conducted to evaluate risk factors for mortality.

Results:  The median age of the 72 enrolled patients was 48 years, 96% of the cases were hospital‐acquired, and the bacteraemia‐related mortality rate was 29% (21 of 72 patients). Univariate analysis revealed that the risk factors for mortality included: an elevated acute physiology and chronic health evaluation (APACHE II) score, receipt of in vitro ineffective definitive antimicrobial therapy, in vitro A. baumannii resistance to cefoperazone/ sulbactam, neutropenia, and presentation with septic shock. Multivariate analysis reveals that the independent risk factors for mortality are neutropenia and elevated APACHE II scores.

Conclusion:  Risk factors such as neutropenia and elevated APACHE II scores are found to be associated with higher mortality rates of A. baumannii bacteraemia. Further study is necessary for the determination of optimal strategies for both the prevention and treatment of these infections. (Intern Med J 2005; 35: 599–603)
Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus
Authors: Seed C. R. , Kiely P. , Keller A. J.
Published: October 2005

Abstract

Background:  The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived.

Methods:  Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia.

Results:  Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1 339 000 for HBV, 1 in 1 in 7 299 000 for HIV, and 1 in 3 636 000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1 000 000 using a separate method.

Conclusions:   The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies. (Intern Med J 2005; 35: 592–598)
Cautionary tales in the clinical interpretation of therapeutic trial reports
Authors: Scott I. A. , Greenberg P. B.
Published: October 2005

Abstract

Practising clinicians are assailed daily with reports of new therapeutic clinical trials. The evidence‐based medicine movement has developed critical appraisal methods for assessing the validity and impact of such studies. However, challenges persist in regards to the appropriate interpretation and application of trial results within everyday clinical settings. Using selected examples from recently published literature, we illustrate 15 cautionary themes for translating research evidence from therapeutic trials into clinical practice. (Intern Med J 2005; 35: 611–621)
Orbital decompression in Graves’ orbitopathy: efficacy and safety
Authors: Goh M. S. Y. , McNab A. A.
Published: October 2005

Abstract

Background:   Vision‐threatening compressive optic neuropathy occurs in a minority of patients with Graves’ orbitopathy. Surgical orbital decompression, systemic glucocorticoids and orbital irradiation are treatment options. Orbital decompression is being performed on an increasing number of patients for other indications such as corneal exposure and disfiguring proptosis.

Aims:  To examine the outcomes of surgical orbital decompression for Graves’ orbitopathy by one surgeon.

Methods:  An analysis of a retrospective case series of 88 consecutive patients (151 orbits) who underwent orbital decompression for Graves’ orbitopathy between April 1991 and November 2002.

Results:  The indication for surgery was compressive optic neuropathy for 57 orbits; 94 orbits had an indication other than optic neuropathy. Of those with optic neuropathy, 94% had improvement or maintenance of visual acuity and 93% had improvement in colour vision after decompression. The overall mean reduction in proptosis was 4.7 mm. Of all patients, 30% had new or worsened diplopia postdecompression. Patients with optic neuropathy were more likely to develop new or worsened diplopia than those without optic neuropathy.

Conclusions:  Orbital decompression is a safe procedure and effective in improving vision in compressive optic neuropathy. It is effective in reducing proptosis, therefore improving exposure keratopathy and cosmesis. However, new or worsened diplopia is a significant postoperative complication, and subsequent strabismus surgery might be required. This is an important consideration, especially for patients undergoing surgery for non‐optic neuropathy indications. (Intern Med J 2005; 35: 586–591)
Role of skeletal muscle‐fibre type in regulation of glucose metabolism in middle‐aged subjects with impaired glucose tolerance during a long‐term exercise and dietary intervention
Authors: Venojärvi M. , Puhke R. , Hämäläinen H. , Marniemi J. , Rastas M. , Rusko H. , Nuutila P. , Hänninen O. , Aunola S.
Published: October 2005

Aim:  The aim of this study was to investigate the role of skeletal muscle fibre type in the regulation of glucose metabolism in middle‐aged obese subjects with impaired glucose tolerance (IGT) during a 2‐year exercise and dietary intervention.

Methods:  Muscle biopsies (musculus vastus lateralis) were taken from 22 subjects belonging to the intervention group of the Finnish Diabetes Prevention Study [1]. According to their myosin heavy chain (MHC) profile at the baseline, the subjects were divided into two groups: IGTslow (n = 10) with a high proportion of MHC I isoforms and IGTfast (n = 12) with a high proportion of MHC II isoforms in the vastus lateralis muscle. The intervention consisted of dietary counselling, strength and power training and/or aerobic exercise. The amount of exercise was the same in both groups; the exercise frequency was 5.1 ± 2.7 h/week in the IGTslow and 5.1 ± 2.8 h/week in the IGTfast group.

Results:  Fasting glucose (p < 0.05), 2‐h glucose (p < 0.05), fasting insulin (p < 0.05), haemoglobin A1c (HbA1c) (p < 0.01) and insulin resistance (p < 0.05) [homeostasis model assessment for insulin resistance (HOMA‐IR)] decreased in the IGTfast group, whereas only the 2‐h glucose and HbA1c concentrations decreased in the IGTslow group. The amount of the glycogen synthase kinase‐3‐αβ (GSK‐3‐αβ) decreased in the IGTfast group (p < 0.05). Exercise training increased the lactate dehydrogenase (LDH) (p < 0.01), LDH‐1 (p < 0.05) and citrate synthase (CS) (p < 0.05) activities in the vastus lateralis muscle in the IGTslow group, but only the CS activity (p < 0.05) in the IGTfast group.

Conclusions:  The glucose metabolism improved both in the IGTslow and IGTfast group during the 2‐year exercise and dietary intervention. The change was more prominent in the IGTfast group than in the IGTslow group, associated with the decrease of the GSK‐αβ protein expression in skeletal muscle. The exercise training improved both glycolytic and oxidative capacity in the vastus lateralis muscle. The glycolytic capacity improved in the IGTslow group and the oxidative capacity in both groups.
Preventing type 2 diabetes using combination therapy: design and methods of the CAnadian Normoglycaemia Outcomes Evaluation (CANOE) trial
Authors: Zinman B. , Harris S. B. , Gerstein H. C. , Young T. K. , Raboud J. M. , Neuman J. , Hanley A. J. G.
Published: October 2005

Several studies have demonstrated that type 2 diabetes mellitus (DM) can be prevented/delayed in subjects with impaired glucose tolerance (IGT) by using pharmacologic agents and/or lifestyle interventions. However, a number of challenges remain, including the translation of lifestyle programmes to the general population and the need to achieve greater risk reductions by using pharmacologic approaches. IGT, like DM, is characterized by insulin resistance, β‐cell dysfunction and increased hepatic glucose production. We believe that the use of combination diabetes therapy would be a particularly effective diabetes prevention strategy. In this context, we initiated the Canadian Normoglycemia Outcomes Evaluation (CANOE) study, a moderately sized, randomized, double‐blind, controlled trial. The primary objective of CANOE is to determine whether treatment with metformin plus rosiglitazone, in addition to a healthy living lifestyle programme, will prevent the development of DM. The secondary objective of CANOE is to determine whether this treatment approach will improve cardiovascular risk factors associated with IGT. A total of 200 patients will be recruited in Toronto and London, Ontario, and followed for an average of 4 years (range 3–5 years). Active treatment with metformin (500 mg) plus rosiglitazone (2 mg), administered as one capsule twice daily, will be compared to matched placebo. Subjects will be eligible for randomization if they have IGT and are between the ages of 30–75 years. The primary outcome will be the development of new‐onset DM, diagnosed by either two fasting plasma glucose values of ≥7 mmol/l or one positive oral glucose tolerance test with a 2‐h plasma glucose value of >11.0 mmol/l during the active drug phase of the trial. With a sample size of 100 participants per group, we will be able to detect a relative risk reduction of 45%, with a two‐sided log‐rank test with a significance level of 0.05 and 80% power, assuming that the median time to progression is 8 years in the control group and that participants will be recruited over 2 years and followed for an average of 4 years. In conclusion, the CANOE study will determine whether combination pharmacological therapy combined with a lifestyle intervention programme can significantly modify the development of diabetes in high‐risk Canadians.
Simplified method of hepatic fibrosis quantification: design of a new morphometric analysis application
Authors: Friedenberg Marc A. , Miller Larry , Chung Chan Y. , Fleszler Frederick , Banson Felice L. , Thomas Rebecca , Swartz Kenneth P. , Friedenberg Frank K.
Published: October 2005

Abstract: Introduction: Semiquantitative evaluation of liver specimens is considered the standard method for measuring fibrosis; however, these systems lack the precision of a quantitative technique.

Methods: We developed an image analysis application (FibroXact) that automates and simplifies color segmentation. Trichrome slides were scanned and the program was used to evaluate each pixel based upon hue, lightness, and saturation values. Percent fibrosis was automatically calculated after thresholding.

Results: Linear regression demonstrated a strong relationship between the FibroXact result and the semiquantitative result (P<0.001).

Conclusion: We have developed an image analysis application to quantify liver fibrosis. Correlation between our results and a standard semiquantitative system was demonstrated.
Promoter methylation and loss of coding exons of the fragile histidine triad (FHIT) gene in intrahepatic cholangiocarcinomas
Authors: Foja S. , Goldberg M. , Schagdarsurengin U. , Dammann R. , Tannapfel A. , Ballhausen W. G.
Published: October 2005

Abstract: Aims: About 10–30% of primary liver cancers represent intrahepatic cholangiocarcinomas (IHCC). Since chromosomal losses of 3p are detectable in about 40% of cholangiocarcinomas our study aimed at the identification of mechanisms leading to functional deletion of tumor suppressor genes in this region. Our efforts focussed on genomic losses and epigenetic inactivation of two tumor suppressor genes, the fragile histidine triad (FHIT) and the ras association domain family 1 (RASSF1A) genes, both located on the short arm of chromosome 3.

Methods: Methylation‐specific PCR (MSP) and combined bisulfite‐dependent restriction analysis (COBRA) were applied to detect epigenetic silencing of gene promoters. Genomic duplex PCR was used to identify exon losses of the FHIT gene. Nineteen paraffin‐embedded samples of intrahepatic cholangiocarcinomas were studied.

Results: Here we report for the first time that in addition to frequent losses of the exons 5 and 6, hypermethylation of the FHIT promoter occured in a significant portion of IHCC. Methylation specific PCR (MSP) detected epigenetic inactivation of the FHIT/FRA3B locus in 8 of 19 (42%) cases. Combined bisulfite restriction analysis (COBRA) revealed that high levels of methylated FHIT promoter sequences were present in 6 of the 8 methylation positive samples. In agreement with previous reports MSP identified hypermethylation of the RASSF1A gene in 13 of 19 (68%) IHCC specimens examined.

Conclusions: Epigenetic silencing of the FHIT tumor suppressor gene is a novel inactivation mechanism to be considered in the development of intrahepatic cholangiocarcinomas. However, a statistically significant inverse correlation between K‐Ras activation and RASSF1A inactivation was not found.
Effect of platelet‐activating factor (PAF) receptor antagonist (BN52021) on acetaminophen‐induced acute liver injury and regeneration in rats
Authors: Grypioti A. D. , Theocharis S. E. , Demopoulos C. A. , Papadopoulou‐Daifoti Z. , Basayiannis A. C. , Mykoniatis M G.
Published: October 2005

Abstract:
Background: Platelet‐activating factor (PAF) is an endogenous lipid mediator that plays a key role in catalyzing various pro‐inflammatory processes associated with acute liver injury. In the present study, the possible influence of PAF‐R antagonist (BN52021) on the protection of liver injury after 4‐hydroxyacetanilide, N‐acetyl‐p‐aminophenol, paracetamol (APAP) intoxication was investigated.

Methods: Thereby, one group of rats was treated with a toxic dose of APAP (3.5 g/kg body weight (b.w.). The animals were killed at 56, 66, 72, 84 and 96 h after treatment.

Results: APAP was found to cause an acute hepatic injury, evident by alterations of biochemical (serum enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase) and liver histopathological (degree of necrosis and apoptosis) indices, which was followed by liver regeneration, evident by three independent indices ([3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index). The protective effects of BN52021 were qualified during post‐treatment time by: (1) significant reduction of hepatic injury as showed by all biochemical and histological parameters, (2) high decrease of regenerating activity showed by three regenerative markers and (3) remarkable increase of PAF‐acetylhydrolase (PAF‐AH) activity.

Conclusion: These results suggest that PAF may play an important role in APAP‐induced liver injury and regeneration, and PAF‐R antagonist (BN52021) attenuates liver damage.
The Elderly People of Post‐Soviet Ukraine: Medical, Social, and Economic Challenges
Authors: Lipsitz Lewis A.
Published: October 2005

Over the past 14 years, since Ukraine became an independent nation, the country has made major strides toward achieving political and economic reforms, exemplified by the recent populist uprising for fair and free elections. Despite these successes, many challenges still lie ahead, particularly in the area of health care for older people. The average life expectancy in Ukraine is only 67 years, and those who achieve old age often live in poverty. Women are expected to retire from their professions at age 55 and men at 60. Pensions are so low that retirees are often forced to take laborious jobs on the streets. Because of deficiencies in medical education, deteriorating hospital facilities, a lack of modern medications and supplies, and inadequate physician payment mechanisms that breed corruption, many elderly people mistrust the medical system and often turn to folk medicines and Eastern medical practices to treat their illnesses. By understanding the expectations and former medical practices of elderly patients who have emigrated from Ukraine, Western physicians will be better able to meet their emotional and medical needs.
Increased Use of Hip Protectors in Nursing Homes: Economic Analysis of a Cluster Randomized, Controlled Trial
Authors: Meyer Gabriele , Wegscheider Karl , Kersten Jan F. , Icks Andrea , Mühlhauser Ingrid
Published: October 2005

Objectives: To assess the cost‐efficacy of an intervention program aimed at reducing hip fractures.

Design: Economic evaluation within an 18‐month cluster randomized trial.

Setting: Forty‐nine nursing homes in Hamburg, Germany.

Participants: Residents with a high risk of falling (intervention group (IG), n=459; control group (CG), n=483).

Intervention: Education session for nurses, who subsequently educated residents, and provision of three hip protectors per resident. CG care was optimized by providing brief information to nurses about hip protectors and providing two protectors per nursing home for demonstration purposes.

Measurements: Main outcomes were hip fractures, costs, and incremental cost‐effectiveness ratio (ICER).

Results: The intervention was effective in reducing hip fractures (21 in the IG vs 42 in the CG) and resulted in a cost difference of $51 per participant in favor of the CG (95% confidence interval covering cost saving of $242 to cost expense of $325). Costs per additional hip fracture avoided were $1,234. Sensitivity analyses aimed at investigating robustness of the results to a real practice implementation scenario resulted in ICERs varying from $439 to $1,693. Taking into account lower hip protector reimbursement levels, the intervention program would be cost saving (break‐even point within the base case analysis=$22 per hip protector).

Conclusion: A program consisting of education and provision of hip protectors might produce a slight increase in costs or might even be cost saving if the price of the hip protector could be decreased.
Resistance Exercise Dosage in Older Adults: Single‐ Versus Multiset Effects on Physical Performance and Body Composition
Authors: Galvão Daniel A. , Taaffe Dennis R.
Published: October 2005

Objectives:To determine whether variation in resistance exercise volume affects muscle function and physical performance response in older adults.

Design:A randomized trial with subjects assigned to a single‐set (1‐SET) or three‐set (3‐SET) exercise group.

Setting:An exercise facility at the University of Queensland.

Participants:Twenty‐eight community‐dwelling men and women aged 65 to 78.

Intervention:Progressive resistance training consisting of seven exercises targeting the major muscle groups of the upper and lower body performed on exercise machines twice weekly for 20 weeks at eight‐repetition maximum (RM) intensity.

Measurements:Muscle function included isotonic muscle strength (1‐RM) of the seven exercises, isokinetic and isometric knee extensor strength, and muscle endurance for the chest press and leg press exercises. Physical performance included timed chair rise, usual and fast 6‐m walk, 6‐m backwards walk, 400‐m walk, floor rise to standing, and stair climbing ability. In addition, body composition was determined using dual energy x‐ray absorptiometry.

Results:Isotonic muscle strength increased in both exercise groups for all seven exercises (P<.01), with the gain in the 3‐SET group greater (P<.05) for the seated row, triceps extension, and knee extension (analysis of covariance). Similarly, muscle endurance gains were greater for the 3‐SET than the 1‐SET group (P<.01), with no significant difference between groups for isokinetic and isometric knee extensor strength. Both groups improved (P<.05) in the chair rise (1‐SET, 10.1%; 3‐SET, 13.6%), 6‐m backwards walk (1‐SET, 14.3%; 3‐SET, 14.8%), 400‐m walk (1‐SET, 3.8%; 3‐SET, 7.4%), and stair climbing test (1‐SET, 7.7%; 3‐SET, 6.4%), with the only difference between groups for the 400‐m walk (P<.05). There was no difference between groups for change in body composition.

Conclusion:Resistance training consisting of only single‐set exercises is sufficient to significantly enhance muscle function and physical performance, although muscle strength and endurance gains are greater with higher‐volume work. These findings have application in designing time‐efficient exercise regimens to enhance neuromuscular function in older adults.
Association analyses of the neuregulin 1 gene with schizophrenia and manic psychosis in a Hispanic population
Authors: Walss‐Bass C. , Raventos H. , Montero A. P. , Armas R. , Dassori A. , Contreras S. , Liu W. , Medina R. , Levinson D. F. , Pereira M. , Leach R. J. , Almasy L. , Escamilla M. A.
Published: October 2005

Objective:  This study used the population of the Central Valley of Costa Rica (CVCR) and phenotyping strategies alternative to DSMIV classifications to investigate the association of neuregulin 1 with schizophrenia.

Method:  Using 134 family trios with a history of psychosis, we genotyped six of the seven markers originally identified to be associated with schizophrenia in Iceland.

Results:  The neuregulin Icelandic haplotype was not associated with schizophrenia in the CVCR population. However, a novel haplotype was found to be overrepresented in subjects with functional psychosis (global P‐value > 0.05). Stratification of the sample by history of mania suggests that this haplotype may be preferentially over‐transmitted to persons with a history of manic psychosis.

Conclusion:  These results suggest that the neuregulin 1 gene is unlikely to play a major role in predisposing to schizophrenia in the CVCR. Further studies in the CVCR and other Latin American populations should be performed in order to corroborate these findings.
CSF 5‐HIAA, suicide intent and hopelessness in the prediction of early suicide in male high‐risk suicide attempters
Authors: Samuelsson M. , Jokinen J. , Nordström A.‐L. , Nordström P.
Published: October 2005

Objective:  To study the predictive value of the Beck Suicide Intent Scale (SIS), the Beck Hopelessness Scale (BHS) and of 5‐hydroxyindoleacetic acid (5‐HIAA) in the cerebrospinal fluid for future early suicide in a group of high‐risk male suicide attempters.

Method:  Fifteen consecutive male suicide attempters admitted to a psychiatric ward at the Karolinska Hospital, who were not receiving any treatment with antidepressants were diagnosed according to DSM‐III, assessed with SIS and BHS and submitted to lumbar puncture. All patients were followed up for cause of death.

Results:  Five early suicides (within 2 years) were identified. Mean cerebrospinal fluid (CSF) 5‐HIAA differed between suicides and survivors. Low CSF 5‐HIAA was identified in those who committed early suicide. Neither the Suicide Intent Score nor the Hopelessness Score distinguished suicides from survivors.

Conclusion:  In high suicide risk hospitalized male psychiatric patients CSF 5‐HIAA may be a better predictor of early suicide after attempted suicide than SIS or BHS.
Coronally advanced flap with or without enamel matrix derivative for root coverage: a 2‐year study
Authors: Del Pizzo M. , Zucchelli G. , Modica F. , Villa R. , Debernardi C.
Published: October 2005

Aim: The purpose of this study was to assess the ability of enamel matrix derivative (EMD) to improve root coverage with a coronally advanced flap (CAF) during a 2‐year follow‐up.

Methods: Fifteen patients each with two single and similar bilateral Miller Class I or II gingival recessions (30 recessions) were selected. Each recession was randomly assigned to the test group (CAF+EMD) or the control group (CAF only). Clinical parameters recorded at baseline and at 6, 12 and 24 months were recession depth (R), recession width (WR), probing depth (PD), clinical attachment level (CAL) and keratinized tissue (KT).

Results: Reduction of R resulted in a significant CAL gain in both groups, whereas PD was not altered. In the test group, R decreased from 4.07 mm (SD±0.59) at baseline to 0.47 mm (SD±0.74) at 24 months, corresponding to a mean root coverage (MRC) of 90.67%, whereas in the control group R shrank from 4.13 mm (SD±0.74) at baseline to 0.60 mm (SD±0.83) at 24 months (MRC=86.67%). Complete root coverage was achieved at 24 months in 73.33% and 60% of the two groups. A significant KT increase was observed in both groups.

Conclusions: Root coverage outcomes were similar in both groups and no statistically significant differences were found at all between them. Hence, the additional use of EMD to CAF is not justified for clinical benefits of root coverage, but as an attempt of achieving periodontal regeneration rather than repair.
Modulation of clinical expression of plaque‐induced gingivitis: effects of personality traits, social support and stress
Authors: Trombelli Leonardo , Scapoli Chiara , Tatakis Dimitris N. , Grassi Luigi
Published: October 2005

Background: Studies have shown an association between an acute stressful event and gingivitis. However, the possible effects of personality traits associated with stress resistance/susceptibility and current level of stress on the clinical expression of plaque‐induced inflammation remain to be examined. The aim of this study was to characterize the subject‐based clinical behaviour of the gingiva during experimental gingivitis in relation to personality profile, psychological stress and coping behaviour.

Methods: Ninety‐six systemically and periodontally healthy subjects (mean age: 23.6±1.7 years), 46 males and 50 females, non‐smokers, participated in a randomized, split‐mouth, localized experimental gingivitis trial. Prior to the trial, subjects were asked to complete self‐administered questionnaires evaluating personality traits (Hardiness scale and Courtauld Emotional Control Scale), subjective stress (Visual Analogue Scale – Total Distress), social support (Multidimensional Scale of Perceived Social Support, MSPSS) and life events (Life Experiences Survey (LES)). The influence of psychosocial factors was investigated in the overall population as well as in two sub‐populations with different inflammatory response to plaque accumulation.

Results: No significant relationships were found between gingival inflammation variables and psychological measures. No significant differences were detected between subjects with different susceptibilties to plaque‐associated gingivitis for any considered psychological variable. A significant association between plaque variables and LES (negative) or MSPSS (positive) was found; however, the variance explained by the model was low.

Conclusions: Differences in the current level of stress and psychosocial variables indicative of stress susceptibility do not account for variability in plaque accumulation and gingival inflammation during experimental gingivitis in young adults.
Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment
Authors: Ficarra G. , Beninati F. , Rubino I. , Vannucchi A. , Longo G. , Tonelli P. , Pini Prato G.
Published: October 2005

Background/Aim: Osteonecrosis of the jaws is being increasingly reported in patients with bone metastasis from a variety of solid tumours and disseminated multiple myeloma receiving intra‐venous bisphosphonates. The signs and symptoms that may occur before the appearance of clinical evident osteonecrosis include changes in the health of periodontal tissues, non‐healing mucosal ulcers, loose teeth and unexplained soft‐tissue infection. A series of nine periodontally involving patients showing osteonecrosis of the jaws that appeared following the intra‐venous use of bisphosphonates is reported.

Material and Methods: Nine consecutive patients with osteonecrosis of the jaws were prospectically studied. Patients' past medical histories and the drugs that they had received for their malignant disease were systematically documented. Clinical, histopathological and radiographic features and proposal for treatment modalities of osteonecrosis are also reported.

Results: Of the nine patients (six women and three men) observed, all had osteonecrosis in the mandible; two had maxillary involvement as well. All nine patients had a history of extraction of periodontally hopeless teeth preceding the onset of osteonecrosis. In two patients, the lesions also appeared in edentulous areas spontaneously. All the patients had received intra‐venous bisphosphonates as treatment for their disseminated haematological neoplasms or metastatic bone disease. The duration of bisphosphonate therapy at presentation ranged from 10 to 70 months (median: 33 months).

Conclusions: Jaw osteonecrosis appears to be associated with the intra‐venous use of bisphosphonates. Dental professionals should be aware of this potentially serious complication in periodontal patients receiving long‐term treatment with bisphosphonates.
Effect of Clathrin Assembly Lymphoid Myeloid Leukemia Protein Depletion on Clathrin Coat Formation
Authors: Meyerholz Anika , Hinrichsen Lars , Groos Stephanie , Esk Peter‐Christopher , Brandes Gudrun , Ungewickell Ernst J.
Published: October 2005

The endocytic accessory clathrin assembly lymphoid myeloid leukemia protein (CALM) is the ubiquitously expressed homolog of the neuron‐specific protein AP180 that has been implicated in the retrieval of synaptic vesicle. Here, we show that CALM associates with the α‐appendage domain of the AP2 adaptor via the three peptide motifs 420DPF, 375DIF and 489FESVF and to a lesser extent with the amino‐terminal domain of the clathrin heavy chain. Reducing clathrin levels by RNA interference did not significantly affect CALM localization, but depletion of AP2 weakens its association with the plasma membrane. In cells, where CALM levels were reduced by RNA interference, AP2 and clathrin remained organized in somewhat enlarged bright fluorescent puncta. Electron microscopy showed that the depletion of CALM drastically affected the clathrin lattice structure. Round‐coated buds, which are the predominant features in control cells, were replaced by irregularly shaped buds and long clathrin‐coated tubules. Moreover, we noted an increase in the number of very small cages that formed on flat lattices. Furthermore, we noticed a redistribution of endosomal markers and AP1 in cells that were CALM depleted. Taken together, our findings indicate a critical role for CALM in the regulation and orderly progression of coated bud formation at the plasma membrane.
Testosterone and Sleep-Related Erections: An Overview*
Authors: Montorsi Francesco , Oettel Michael
Published: October 2005

Montorsi F, Oettel M. Testosterone and sleep-related erections: an overview.J Sex Med 2005;2:771–784

Sleep-related erections have been reported to occur from the intrauterine life to senescence. It has been speculated that the main function of nocturnal erections is to provide adequate engorgement of the corpora cavernosa, which then leads to increased tissue oxygenation. This is in turn to prevent cavernous fibrosis, the histopathological basis for corporeal venoocclusive dysfunction, which probably is the most common cause of organic erectile dysfunction. It has been suggested that sleep-related erections are triggered by the release of nitric oxide by the nitrergic nerve fibers within the cavernous nerves. Androgens regulate this mechanism as well as some other non-nitrergic processes within the corpora cavernosa and within the central nervous system. By contrast, the erectile response to tactile or visual erotic stimuli in wakefulness predominantly involves an androgen-independent system, although it may, at least to a certain degree, also be influenced by androgen-sensitive mechanisms. No doubt, androgens are key players in the physiology of nocturnal erections, and the availability of new, user-friendly testosterone preparations such as transdermal gel and intramuscularly administered testosterone undecanoate stimulates further investigations on this field. The prospect that the quality of sleep may also be improved by an androgen therapy administered to improve sleep-related erections in hypogonadal men needs further basic research and appropriate clinical studies.
Testosterone Therapy in Erectile Dysfunction and Hypogonadism
Authors: Shabsigh Ridwan
Published: October 2005

Introduction

Laboratory experiments indicate that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction (ED) and reduction in nitric oxide synthase and in phosphodiesterase type 5 (PDE5) in the erectile tissue. Furthermore, castration causes apoptosis adversely affecting smooth muscle content and penile hemodynamics leading to veno-occlusive dysfunction. Testosterone therapy reverses these structural, biochemical, and physiological changes. In humans, testosterone therapy improves erectile function in men with hypogonadism. However, the efficacy of testosterone monotherapy may not be adequate because of the multifactorial nature of the pathophysiology of ED.

Methods

Preliminary data from a number of studies have been reviewed.

Results

There are emerging evidence-based benefits to using the combination of testoterone and PDE5 inhibitors. A recently published multicenter, randomized, placebo-controlled study evaluated the safety and efficacy of testosterone gel 1% plus sildenafil vs. placebo gel plus sildenafil, in producing an erectile response in hypogonadal men who had failed prior sildenafil alone for ED. Screening yielded a prevalence of hypogonadism in ED patients who failed prior sildenafil. Following randomization, the double-blinded treatment phase was 12 weeks. Testosterone therapy with testosterone gel significantly improved erectile function in response to sildenafil. In addition, it significantly improved orgasmic function and patient satisfaction.

Conclusion

It is important to screen all men with ED for hypogonadism, especially those with a history of inadequate response to prior PDE5 inhibitors. The combination of testosterone plus PDE5 inhibitors may be considered for the treatment of ED in men with low to low–normal testosterone levels, who had inadequate response to prior treatment with PDE5 inhibitors alone.
Women's Sexual Function Improves When Partners are Administered Vardenafil for Erectile Dysfunction: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Goldstein Irwin , Fisher William A. , Sand Michael , Rosen Raymond C. , Mollen Martin , Brock Gerald , Karlin Gary , Pommerville Peter , Bangerter Keith , Bandel Tiemo-Joerg , Derogatis Leonard R.
Published: October 2005

Introduction

There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED).

Aim

One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners’ sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment.

Methods

A randomized, double-blind, placebo-controlled, multi-institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED >6 months and untreated woman partner). Co-primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman partner).

Main Outcome Measures

Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ-QOL and Female Sexual Function Index (FSFI).

Results

Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS was correlated reliably with improvement in women partners’ FSFI total and individual domain scores.

Conclusions

Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners’ sexual function improvements relate significantly and consistently to treatment-related improvements in men's erectile function. ED management should emphasize both members of the couple.