bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a systematic approach for identifying injury scenarios. Kids'n' Cars Teams.
Authors: Christoffel K. K. , Schofer J. L.
Published: October 2008

OBJECTIVE: To assess the effectiveness of a new multidisciplinary method for reconstructing the causal sequences that lead to child pedestrian injuries. SETTING: Subjects were 5-12 year old residents of Chicago, Illinois, USA, presenting for care due to pedestrian injury at one pediatric trauma center. METHODS: The interactions of medical, child, psychosocial, and traffic factors contributing to the injury were analysed. For 142 cases, information about the victim, his/her family, the injury site, and the activities just before the injury, was used in a structured manner by a multidisciplinary team to produce injury scenarios. Each scenario comprised a list of contributing factors, an estimate of the importance of each, and a narrative description of the causal sequence leading to the injury event. Face validity was assessed by two outside teams that performed a structured review of a subsample of cases (n = 11). Reliability was evaluated by comparison of the results of parallel teams assessing the same cases (n = 14). Process consistency and bias were assessed by analysis of the correlations of factor-importance rating patterns between members and over time. RESULTS: The outside team's agreement scores were based on a 1-5 Likert scale; these showed a mean of 3.6 and median of 4.0. Parallel teams consistently showed agreement greater than 85% on global attributes of cases. Intraclass correlation coefficient scores showed fair or better agreement for all classes of contributors, and excellent agreement for more than one third. Rating pattern analyses showed strong agreement by team members. Agreement did not increase over the period of the study. CONCLUSIONS: This causal sequence reconstruction method has acceptable face validity, reliability, and internal consistency. Although labor intensive and thus costly, it can produce unique, rich information for understanding injury causation and for guiding the search for promising interventions.
Work patterns and occupational hazard exposures of North Carolina adolescents in 4-H clubs.
Authors: Cohen L. R. , Runyan C. W. , Dunn K. A. , Schulman M. D.
Published: October 2008

OBJECTIVES: This study documents sex differences in work patterns, injuries, and hazard exposures among adolescents in homes, farms, and other work sites. METHODS: 14 to 17 year old 4-H club members were asked to complete self administered questionnaires regarding their lifetime experience of work, hazard exposure, and injuries. RESULTS: Of 323 respondents, more than two thirds had ever worked paid jobs. Fifty seven per cent were injured during non-farm work and hazards were part of the non-farm work environment for 54% of the respondents. Males were more likely to work in hazardous conditions, including operating heavy equipment on farms or construction sites. Almost three quarters of the teens who worked on farms reported being injured there and 100% were exposed to at least one farm hazard. CONCLUSIONS: Adolescents perform jobs at homes, farms, or other work sites where they are exposed to numerous safety hazards. Prevention efforts should target specific hazards youths are exposed to rather than the general work site.
A community based approach to bicycle helmet use counts.
Authors: Becker L. R. , Mandell M. B. , Wood K. , Schmidt E. R. , O'Hara F.
Published: October 2008

OBJECTIVE: Bicycle helmet use has become an important measure of the effectiveness of bicycle safety programs and the effectiveness of helmet legislation. Accounts of analytical comparisons of observation site selection methods are scarce. This report addresses this gap by reporting the relative effectiveness and costs of two alternative approaches to the selection of observation sites for helmet use counts. METHODS: The community based (COBA) method of site selection entailed asking community informants to identify locations frequented by young bicycle riders. In the bicycle club/map (CLMA) method, site selections were based on recommendations from club members of sites at which cyclists were likely to be found and through examination of maps, keying on local features. These alternative site selection methods were compared in terms of their overall and cost effectiveness in locating youth riders. RESULTS: Despite fewer observer hours and fewer sites in a sparsely populated rural county, the COBA method yielded greater numbers of riding youth and from 1.9 to 4.6 times more youth riders per observer hour than did the CLMA method in two densely populated suburban counties. In addition, costs per youth rider observed associated with the COBA method were 2.9 to 7.0 times lower than those associated with the CLMA method. CONCLUSIONS: Community based site identification is both more efficient in locating youth riders and more cost effective.
Demographics of alpine skiing and snowboarding injury: lessons for prevention programs.
Authors: Macnab A. J. , Cadman R.
Published: October 2008

OBJECTIVE: To establish the demographics of ski injury in relation to age, gender, and perceived cause during a representative season to identify potential injury prevention strategies. SETTING: Blackcomb Mountain, a world class ski resort in British Columbia, Canada. METHODS: Data were collected from the lift ticket records and from ski patrol injury reports for one season, November to May 1991-2. RESULTS: There were 720,066 skier and snowboarder day visits counted by the mountain's lift ticket records, with a total of 2,092 injury reports (incidence 2.91 per 1,000 day visits). Of those with significant injuries (those requiring physician care), 1,210 (58%) were male. The highest injury rate was among children (age 7-12) and teens (age 13-17) with incidences of 3.18 and 3.34 significant injuries per 1,000 skier days, respectively. Head and face injuries constituted 17% and 22% of injuries, respectively in these groups. Overall 22% of head and face injuries were severe enough to cause loss of consciousness or clinical signs of concussion. This was the body region injured most frequently in males. For females over 7 years of age, the knee was the most common site of injury. For youths, the incidence of injuries during school organized activities was 25% higher than during other outings. CONCLUSIONS: The vulnerability of school group participants suggests special education is warranted. The high incidence of head injuries, particularly among young males, needs to be addressed. In light of the high proportion of this group who already wear helmets, the role of helmets in both protection and possible causation of head injury needs objective research.
Childhood injury deaths: rural and urban differences, Colorado 1980-8.
Authors: Hwang H. C. , Stallones L. , Keefe T. J.
Published: October 2008

OBJECTIVES: The purpose of this study is to describe and compare the distribution of injury deaths among rural and urban Colorado children that occurred between 1980-8. METHOD: Death certificates coded E800-E969 were obtained for children who were 0-14 years of age at death between 1980-8 and who were Colorado residents. Average annual rates were computed for rural and urban children, separately by gender. The 1980 census was used to compute rates. Rate ratios were calculated to summarize information related to specific external causes of deaths, contrasting rural and urban children. These differences were evaluated using Z tests. RESULTS: Statistically significant elevated risks were found along rural children for motor vehicle injury deaths. Firearms were involved more often in rural deaths among unintentional injury deaths of children older than 4 years of age, and among homicide related deaths of children 5 years and younger. All rural children who committed suicide used a firearm. CONCLUSIONS: Comparisons between rural and urban injury deaths provide important information that can be used to guide prevention strategies. For example, in Colorado, a child restraint law, passed in 1984, covered children under 4 years of age or under 40 pounds. It was not until 1995, however, that legislation was passed requiring restraint of children 5-16 years of age. Traditionally, rural residents are slower to accept new ideas and to alter current practices than urban residents.
Bike speed measurements in a recreational population: validity of self reported speed.
Authors: Thompson D. C. , Rebolledo V. , Thompson R. S. , Kaufman A. , Rivara F. P.
Published: October 2008

OBJECTIVE: Speed at the time of a bicycle crash is an important determinant of the amount of energy transmitted. Controlling for speed is thus important in the evaluation of outcomes and effectiveness of intervention strategies. This study was conducted to evaluate the accuracy of self reported speed in a population of recreational cyclists. METHODS: Children's and adults' bicycle speeds were measured with a radar gun as they rode along a closed road at weekend recreational events. Cyclists were then stopped and asked to estimate their speed. Measured speed, cyclist's estimate of their speed, age, and sex were documented. Parents were also asked to estimate their child's speed. RESULTS: One hundred and fifty two cyclists from 4 to 80 years of age participated. Seventy per cent were children 13 years of age or younger. The mean (SD) speed of this group was 8.9 (2.5) mph. Cyclists age 14 and older were traveling at a mean speed of 9.7 (2.87) mph. Estimated speeds were significantly higher than measured speeds for this older group, but there was no significant difference between mean measured and estimated speeds for the younger riders. There was also no significant difference between measured and estimated speed for males and females. Parents estimated their child's speed quite accurately. CONCLUSIONS: Self reported speeds for children were in close agreement with measured speeds and, thus, are sufficiently accurate to be a useful measure of crash severity in evaluating helmet effectiveness.
Understanding suicide among indigenous adolescents: a review using the PRECEDE model.
Authors: Clarke V. A. , Frankish C. J. , Green L. W.
Published: October 2008

AIM: To use the available literature to identify the causes of suicide among indigenous adolescents. METHOD: The PRECEDE model provided a framework to organize the material and identify the areas where relatively little research had been reported. RESULTS: The epidemiological diagnosis showed that suicide was greater in indigenous than non-indigenous populations and particularly high among adolescent males. Environments of native persons are characterized by remoteness, poverty, cultural displacement, and family disintegration. The educational and organizational diagnosis identified predisposing factors reflecting the social environments previously identified, the enabling factors of televised suicides, and firearm and alcohol availability, in conjunction with an absence of positive expectations. Finally the administrative and policy diagnosis identified a piecemeal, short term perspective, often lacking cultural sensitivity. Although there was more literature from the United States than from Canada, Australia or New Zealand, the pictures emerging were consistent, with problems being identified across continents. Literature was more abundant in relation to the epidemiological, environmental, and educational/ organizational diagnoses than in relation to policy and administration. CONCLUSION: The increased suicide rates among indigenous adolescents were not a product of their native origins, but of the social milieu in which these people generally found themselves.
Non-fatal asphyxiation and foreign body ingestion in children 0-14 years.
Authors: Altmann A. E. , Ozanne-Smith J.
Published: October 2008

OBJECTIVES: To examine the frequency and nature of non-fatal asphyxiation and foreign body ingestion injuries among children in the state of Victoria, Australia, and to identify possible areas for prevention. METHODS: For children under 15 years, all Victorian public hospital admissions, July 1987 to June 1995, due to asphyxiation or 'foreign body entering through other orifice' (which includes ingestions), were reviewed. Emergency department presentations due to asphyxiation and foreign body ingestion provided information on circumstances of, and the type of foreign bodies involved in the injuries. RESULTS: The childhood average annual admission rate for asphyxiation was 15.1 per 100,000. Food related asphyxiation peaked in infants under 1 year, and declined to low levels by 3 years. The main foods involved were nuts, carrot, apple, and candy. The rate of non-food related asphyxiation was relatively constant to 3 years of age and then declined by 6 years. Mechanical suffocation was less common. The annual admission rate for 'foreign body entering through other orifice' was 31.7 per 100,000. These injuries peaked in 2-3 year olds then gradually declined. About 80% of these foreign body admissions were ingestions, with coins being the major object ingested. Admission rates for these causes remained constant over the eight years. Asphyxiation resulted in a higher proportion admitted and longer hospital stays. CONCLUSIONS: Prevention of suffocation and strangulation needs to focus on a safe sleeping environment and avoidance of ropes and cords, while foreign body asphyxiation and ingestion needs a focus on education of parents and child carers regarding age, appropriate food, risk of play with coins, and other small items. Legislation for toy small parts could be extended to those used by children up to the age of 5 years, and to other products marketed for children. Design changes and warning labels also have a place in prevention.
Injury mortality among children and teenagers in New Zealand compared with the United States of America.
Authors: Langley J. D. , Smeijers J.
Published: October 2008

OBJECTIVES: New Zealand (NZ) has an unenviable track record in childhood injury mortality. We sought to describe this burden and to compare it with the United States of America (USA), with a view to taking the first step in identifying potential areas in which NZ might benefit from injury control as practiced in the USA. METHODS: We identified all children and teenagers who had died of injury for the period 1984-93 from the NZ Health Information Service mortality data files. We compared their rates of injury with previously published rates for USA. RESULTS: The age specific rates follow a J shaped distribution, with high rates in the first year of life followed by a decline to the lowest rate, among 5-9 year olds, a marginally higher rate among 10-14 year olds, and a dramatic rise among those in the 15-19 age group. The specific causes of death vary considerably by age group. NZ's overall rate of child and adolescent injury is not substantially different from that of the USA, but marked differences are apparent when examining cause specific rates. CONCLUSIONS: In terms of the theoretical potential to reduce the total injury mortality rate, priority must be given to 15-19 year olds who account for 61% of all NZ injury deaths. Priorities for this age group are: motor vehicle traffic crashes (especially those involving occupants and motorcyclists), and suicide. Among the children, priorities are: pedestrian and occupant deaths, and drownings. Among infants, the priority is suffocation.
Medically attended injuries among young children: observations in a suburban area. 1964.
Authors: Dickson D. G. , Schlesinger E. R. , Westaby J. R. , Lowen L.
Published: October 2008

A control study of the effect of public health education on the rate of accidental injuries among children under 7 years of age in a newly developing suburban area provided an opportunity to gain an insight into the nature and extent of the accident problem itself during a one year baseline period preceding the educational phase of the study. An accident was arbitrarily defined as any actual or presumed trauma following an incident for which direct medical or dental attention was obtained. Data were gathered through regular visits of data collectors to physicians, dentists, and hospitals in the area. An annual accident rate of 124 per 1000 children under 7 years of age was found. Two or more accident occurred to 10% of the children. The highest injury rate by age (179 per 1000 children) was found among 2 year old children, with the rate amount 2 year old boys 75% higher than any other age-sex group. The possible relationships of suburban living to the type and location of accidents by age and sex and to the variation in accidents by day of week are also presented.
Home drowning among preschool age Mexican children.
Authors: Celis A.
Published: October 2008

OBJECTIVES: To estimate the risk of drowning by different bodies of water in and near the home for children aged 1 to 4 years. SETTING: The Metropolitan Area of Guadalajara, Mexico. METHODS: A population case-control study. Cases (n=33) were children 1 to 4 years old who drowned at their home; controls (n=200) were a random sample of the general population. RESULTS: The risk of drowning for children whose parents reported having a water well at home was almost seven times that of children in homes without a water well (adjusted odds ratio (OR)=6.8, 95% confidence interval (CI)=2.2 to 20.5). Risk ratio estimates for other bodies of water were: swimming pools (OR=5.8, 95% CI=0.9 to 37.5), water barrel (OR=2.4, 95% CI=1.0 to 5.6), underground cistern (OR=2.1, 95% CI=0.8 to 5.2), and a basin front (courtyard pool to store water) of 35 or more litres (OR=1.8, 95% CI=0.8 to 4.4). CONCLUSION: Drowning at home is frequent in the Metropolitan Area of Guadalajara, but the causes are different from those reported in developed countries. Accordingly, the preventive strategies must also be different.
Relative harm of snus and cigarettes: what do Norwegian adolescents say?
Authors: Øverland S , Hetland J , Aarø L E
Published: October 2008

Background:

The public receives mixed messages about the harmfulness of alternative tobacco products to cigarettes, and little is known about what present and potential users of these products actually think about their relative harmfulness.

Methods:

In a nationally representative survey of 2415 Norwegian adolescents aged 16–20 years, participants were asked to rate the harmfulness of various available tobacco products and their own use of snus and cigarettes. A study was undertaken to examine how adolescents rate the relative harm of tobacco products in general, and snus and cigarettes in particular, and how this varies with age, gender and their own use of snus and smoking.

Results:

Cigarettes were generally rated as more harmful than snus, but 41% still rated snus as equally or more harmful than cigarettes. Male participants reported lower harm from all products than females. Being a snus user was associated with lower ratings of harm for snus, but being a smoker was not associated with reporting of harm for cigarettes.

Conclusions:

Compared with the current scientific consensus, the participants overrated the harmfulness of snus and, as such, our results suggest a potential for changing peoples’ perceptions of the relative health risks of various tobacco products. To the extent that health information affects consumption, accurate information on relative risks may lead more people to choose snus over cigarettes.
Age impairs Flk-1 signaling and NO-mediated vasodilation in coronary arterioles
Authors: LeBlanc Amanda J. , Shipley Robert D. , Kang Lori S. , Muller-Delp Judy M.
Published: October 2008

Impairment of flow-induced vasodilation in coronary resistance arterioles may contribute to the decline in coronary vasodilatory reserve that occurs with advancing age. This study investigated the effects of age on flow-induced signaling and activation of nitric oxide (NO)-mediated vasodilation in coronary resistance arterioles. Coronary arterioles were isolated from young (∼6 mo) and old (∼24 mo) male Fischer-344 rats to assess vasodilation to flow, vascular endothelial growth factor (VEGF), and ACh. Flow- and VEGF-induced vasodilation of coronary arterioles was impaired with age ( P ≤ 0.05); however, ACh-induced vasodilation was preserved with age. NG-nitro-l-arginine methyl ester (l-NAME) (1 × 10−5 M) eliminated vasodilation to flow, VEGF, and ACh, indicating dependence of these responses on NO. SU-1498, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR, also known as Flk-1), abolished age-related differences in flow-induced vasodilation. Flow-stimulated phosphorylation of Flk-1 in coronary arterioles from young but not old rats and Flk-1 protein was reduced in coronary arterioles from old rats compared with those from young rats. Flow stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) in coronary arterioles from both young and old rats. VEGF induced phosphorylation of both protein kinase B (Akt) and eNOS in coronary arterioles. VEGF-induced phosphorylation of Akt, but not eNOS, was significantly reduced in arterioles from old rats compared with arterioles from young rats. Wortmannin, an inhibitor of phosphatidylinositol (PI) 3-kinase, eliminated age-related differences in both flow- and VEGF-induced vasodilation. These results indicate that impairment of Flk-1/PI3-kinase signaling contributes to the reduction of flow-induced vasodilation in coronary arterioles with advancing age.
VEGF is critical for stem cell-mediated cardioprotection and a crucial paracrine factor for defining the age threshold in adult and neonatal stem cell function
Authors: Markel Troy A. , Wang Yue , Herrmann Jeremy L. , Crisostomo Paul R. , Wang Meijing , Novotny Nathan M. , Herring Christine M. , Tan Jiangning , Lahm Tim , Meldrum Daniel R.
Published: October 2008

Bone marrow mesenchymal stem cells (MSCs) may be a novel treatment modality for organ ischemia, possibly through the release of beneficial paracrine factors. However, an age threshold likely exists as to when MSCs gain their beneficial protective properties. We hypothesized that 1) VEGF would be a crucial stem cell paracrine mediator in providing postischemic myocardial protection and 2) small-interfering (si)RNA ablation of VEGF in adult MSCs (aMSCs) would equalize the differences observed between aMSC- and neonatal stem cell (nMSC)-mediated cardioprotection. Female adult Sprague-Dawley rat hearts were subjected to ischemia-reperfusion injury via Langendorff-isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). MSCs were harvested from adult and 2.5-wk-old neonatal mice and cultured under normal conditions. VEGF was knocked down in both cell lines by VEGF siRNA. Immediately before ischemia, one million aMSCs or nMSCs with or without VEGF knockdown were infused into the coronary circulation. The cardiac functional parameters were recorded. VEGF in cell supernatants was measured via ELISA. aMSCs produced significantly more VEGF than nMSCs and were noted to increase postischemic myocardial recovery compared with nMSCs. The knockdown of VEGF significantly decreased VEGF production in both cell lines, and the pretreatment of these cells impaired stem cell-mediated myocardial function. The knockdown of VEGF in adult stem cells equalized the myocardial functional differences observed between adult and neonatal stem cells. Therefore, VEGF is a critical paracrine mediator in facilitating postischemic myocardial recovery and likely plays a role in mediating the observed age threshold during stem cell therapy.
TGF-β1is a negative regulator of lymphatic regeneration during wound repair
Authors: Clavin Nicholas W. , Avraham Tomer , Fernandez John , Daluvoy Sanjay V. , Soares Marc A. , Chaudhry Arif , Mehrara Babak J.
Published: October 2008

Although clinical studies have identified scarring/fibrosis as significant risk factors for lymphedema, the mechanisms by which lymphatic repair is impaired remain unknown. Transforming growth factor -β1(TGF-β1) is a critical regulator of tissue fibrosis/scarring and may therefore also play a role in the regulation of lymphatic regeneration. The purpose of this study was therefore to assess the role of TGF-β1on scarring/fibrosis and lymphatic regeneration in a mouse tail model. Acute lymphedema was induced in mouse tails by full-thickness skin excision and lymphatic ligation. TGF-β1expression and scarring were modulated by repairing the wounds with or without a topical collagen gel. Lymphatic function and histological analyses were performed at various time points. Finally, the effects of TGF-β1on lymphatic endothelial cells (LECs) in vitro were evaluated. As a result, the wound repair with collagen gel significantly reduced the expression of TGF-β1, decreased scarring/fibrosis, and significantly accelerated lymphatic regeneration. The addition of recombinant TGF-β1to the collagen gel negated these effects. The improved lymphatic regeneration secondary to TGF-β1inhibition was associated with increased infiltration and proliferation of LECs and macrophages. TGF-β1caused a dose-dependent significant decrease in cellular proliferation and tubule formation of isolated LECs without changes in the expression of VEGF-C/D. Finally, the increased expression of TGF-β1during wound repair resulted in lymphatic fibrosis and the coexpression of α-smooth muscle actin and lymphatic vessel endothelial receptor-1 in regenerated lymphatics. In conclusion, the inhibition of TGF-β1expression significantly accelerates lymphatic regeneration during wound healing. An increased TGF-β1expression inhibits LEC proliferation and function and promotes lymphatic fibrosis. These findings imply that the clinical interventions that diminish TGF-β1expression may be useful in promoting more rapid lymphatic regeneration.
Soluble guanylyl cyclase contributes to ventilator-induced lung injury in mice
Authors: Schmidt Eric P. , Damarla Mahendra , Rentsendorj Otgonchimeg , Servinsky Laura E. , Zhu Bing , Moldobaeva Aigul , Gonzalez Alfredo , Hassoun Paul M. , Pearse David B.
Published: October 2008

High tidal volume (HVT) ventilation causes pulmonary endothelial barrier dysfunction. HVTventilation also increases lung nitric oxide (NO) and cGMP. NO contributes to HVTlung injury, but the role of cGMP is unknown. In the current study, ventilation of isolated C57BL/6 mouse lungs increased perfusate cGMP as a function of VT. Ventilation with 20 ml/kg VTfor 80 min increased the filtration coefficient ( Kf), an index of vascular permeability. The increased cGMP and Kfcaused by HVTwere attenuated by nitric oxide synthase (NOS) inhibition and in lungs from endothelial NOS knockout mice. Inhibition of soluble guanylyl cyclase (sGC) in wild-type lungs (10 μM ODQ) also blocked cGMP generation and inhibited the increase in Kf, suggesting an injurious role for sGC-derived cGMP. sGC inhibition also attenuated lung Evans blue dye albumin extravasation and wet-to-dry weight ratio in an anesthetized mouse model of HVTinjury. Additional activation of sGC (1.5 μM BAY 41-2272) in isolated lungs at 40 min increased cGMP production and Kfin lungs ventilated with 15 ml/kg VT. HVTendothelial barrier dysfunction was attenuated with a nonspecific phosphodiesterase (PDE) inhibitor (100 μM IBMX) as well as an inhibitor (10 μM BAY 60-7550) specific for the cGMP-stimulated PDE2A. Concordantly, we found a VT-dependent increase in lung cAMP hydrolytic activity and PDE2A protein expression with a decrease in lung cAMP concentration that was blocked by BAY 60-7550. We conclude that HVT-induced endothelial barrier dysfunction resulted from a simultaneous increase in NO/sGC-derived cGMP and PDE2A expression causing decreased cAMP.
Population Stratification in a Case-Control Study of Brain Arteriovenous Malformation in Latinos
Authors: Kim Helen , Hysi Pirro G. , Pawlikowska Ludmila , Choudhry Shweta , González Burchard Esteban , Kwok Pui-Yan , Sidney Stephen , McCulloch Charles E. , Young William L.
Published: October 2008

Background: Genetic association studies conducted in admixed populations may be confounded by population stratification resulting in spurious associations. The purpose of this pilot study was to determine the presence and effect of population stratification in a case-control study of brain arteriovenous malformation (BAVM). Methods: We tested 83 ancestry informative markers in BAVM cases and healthy controls of self-reported Latino race/ethnicity (n = 294). Individual ancestry estimates (IAE) were obtained using the Structure program, assuming 3 underlying subpopulations. Summary χ2 tests comparing genotype frequency of ancestry informative markers were used to detect stratification and IAE were included as covariates in logistic regression analysis to account for differences in genetic background. Results: Admixture estimates for Latinos (overall 47% native American, 45% European and 8% African ancestry) revealed heterogeneity between individuals within ancestral groups. The summary χ2 test was significant (p = 0.005), suggesting ancestral differences between cases and controls. Furthermore, genetic ancestry was associated with frequency differences in a promoter variant in the IL-6 gene (IL-6 –174G>C). On average, subjects with the IL6 –174 GG genotype had 6% greater Native American ancestry (p = 0.023). Age- and sex-adjusted risk of BAVM associated with the IL-6 –174 GG genotype was 1.85 (95% CI 0.99–3.48, p = 0.055), and further adjustments for IAE yielded an OR of 1.96 (95% CI 1.03–3.72, p = 0.039). Conclusion: The IL-6 –174G>C polymorphism was associated with increased risk of BAVM among Latinos after accounting for differences in ancestral background. These results suggest subtle, negative confounding and illustrate the importance of addressing population stratification in case-control studies conducted in admixed populations.
Novel Mutation in the ABCA1 Gene Identified in a Chinese Patient with Dementia and Atherothrombotic Cerebral Infarction
Authors: Xue Xie-Hua , Wang Ning , Lin Yi , Zhao Gui-Xian , Fang Ling , Murong Shenxing , Wu Zhi-Ying
Published: October 2008

Background: To date, 81 mutations of ATP-binding cassette transporter 1 (ABCA1) have been reported. However, no ABCA1 mutation has been reported in the Chinese population. Methods: We used direct sequencing to screen for ABCA1 mutations in 72 patients with both atherosclerotic cerebral infarction (ACI) and plasma high-density lipoprotein cholesterol (HDL-C) < 0.8 mmol/l. The functionality of the mutation was verified using 200 unrelated controls and 76 patients with ACI and normal HDL-C by PCR-RFLP analysis. Results: One patient with dementia prior to ACI was found to carry the heterozygous Y2206D mutation, which has not been reported previously. The patient had a medical history of atherosclerosis in the coronary and carotid arteries going back 40 years and splenohepatomegalia for 13 years, with a low plasma HDL-C level (0.66 mmol/l) and apolipoprotein A1 level (0.61 mmol/l). During the past decade, he had developed symptoms of dementia. Sixteen months prior to the study, he was admitted to hospital for an ACI. Conclusion: The results suggest that this patient is most likely a patient with familial hypoalphalipoproteinemia and that the Y2206D mutation may be associated with not only a lower level of HDL-C, but also with dementia.
Orthostatic Hypotension, Hypotension and Cognitive Status: Early Comorbid Markers of Primary Dementia?
Authors: Yap Philip Lin Kiat , Niti Mathew , Yap Keng Bee , Ng Tze Pin
Published: October 2008

Objective: Few studies have explored the relationship between orthostatic hypotension (OH) and cognition. The aim of this study was to examine the association of OH with cognitive impairment and decline in a cohort of Chinese elderly, and its effect modification by blood pressure (BP) status at baseline. Method: Among 2,321 community-living older adults, free of cardiovascular disease and stroke, baseline BP measurements were used to determine the presence of OH and categorize participants as hypotensives, normotensives or hypertensives. The Mini-Mental State Examination (MMSE) was used to assess cognitive impairment (MMSE score <24). Cognitive decline (decrease in MMSE score by ≧1) was assessed from 1 to 2 years of follow-up for 1,347 participants without baseline cognitive impairment. Results: Mean age of the subjects was 65.5 years and 381 (16.6%) showed OH. OH was not associated with cognitive impairment overall. However, among hypotensives, OH increased the odds of cognitive impairment (OR = 4.1, 95% CI = 1.11–15.1), while hypertensives with OH showed reduced odds of cognitive impairment (OR = 0.48, 95% CI = 0.26–0.90). Among cognitively intact participants, OH was not associated with cognitive decline overall or in BP subgroups. Conclusion: The increased risk of cognitive impairment in hypotensives with OH suggests that hypotension with OH may be an early comorbid marker of a primary incipient dementia.
Deficiency of CARD8 Is Associated with Increased Alzheimer’s Disease Risk in Women
Authors: Fontalba Ana , Gutiérrez Olga , Llorca Javier , Mateo Ignacio , Berciano José , Fernández-Luna José Luis , Combarros Onofre
Published: October 2008

NF-ĸB, a major transcription factor controlling inflammation, is activated in Alzheimer’s disease (AD) brains. CARD8 protein has been implicated in the suppression of NF-ĸB activity, but a truncating polymorphism (p.C10X, rs2043211) renders a non-functional CARD8 protein that gives rise to a more active NF-ĸB and an amplification of the inflammatory process. Apolipoprotein E (ApoE) Ε4 allele, the major genetic risk factor of AD, is associated with hyperactivation of NF-ĸB and enhanced brain inflammation. In a case-control study in 300 AD patients and 300 healthy controls, we examined whether the CARD8 (p.C10X) polymorphism, independently or in concert with the ApoE Ε4 allele, might predispose to AD. Women, but not men, carrying the CARD8 AA genotype (truncated protein) had a 2.39-fold higher risk of developing AD than subjects with the CARD8 TT genotype (full-length protein). This association with susceptibility to AD was independent of the ApoE Ε4 allele.
Investigation of the Role of the Dopamine Transporter in Susceptibility to Behavioural and Psychological Symptoms of Patients with Probable Alzheimer’s Disease
Authors: Pritchard Antonia L. , Pritchard Colin W. , Bentham Peter , Lendon Corinne L.
Published: October 2008

Background/Aims: Alzheimer’s disease patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD); a genetic component to the development of BPSD has been demonstrated. Genetic risk factors for other psychiatric disorders have been implicated in BPSD; however, this is the first known investigation of the dopamine transporter (DAT1) gene in BPSD. Methods: Our large cohort of 395 patients with probable Alzheimer’s disease was dichotomised into whether they had ever suffered from a given symptom over the study period or not, based on longitudinal data using the BPSD (Neuropsychiatric Inventory). These measures were related to the DAT1 3′-untranslated region (UTR) variable number tandem repeat (VNTR) polymorphism. Results: Potential associations were revealed between the 9-repeat allele and presence of irritability and between the 10-repeat allele and aberrant motor behaviour (AMB); however, these do not remain significant after correction for multiple testing. No associations were observed with delusions, hallucinations, depression, agitation/aggression or elation. Conclusion: Our data suggest that the DAT1 3′-UTR VNTR could play a role in susceptibility to irritability and AMB. The findings presented here require replication in large well-characterised cohorts.
Effect of Intra-Amygdala Injection of Nicotine and GABA Receptor Agents on Anxiety-Like Behaviour in Rats
Authors: Zarrindast Mohammad-Reza , Solati Jalal , Oryan Shahrbanoo , Parivar Kazem
Published: October 2008

There is evidence that both cholinergic and GABAergic systems are involved in the neurobiology of anxiety. In the present study, we investigated the effects and interaction of nicotinic and GABAergic systems in the central amygdala of rats, using the elevated plus maze test of anxiety. Bilateral administration of nicotine (1 and 2 µg/rat; 1 µl/rat; 0.5 µl/rat in each side) into the central amygdala (intra-CeA) induced an anxiogenic-like effect, shown by specific decreases in the percentage of open-arm time (%OAT) and percentage of open arm entries (%OAE). Intra-CeA injection of mecamylamine, a selective nicotine acetylcholine receptor antagonist (20, 30 and 50 ng/rat; 1 µl/rat; 0.5 µl/rat in each side) produced significant anxiolytic-like behaviour. The intra-CeA injection of the GABAA receptor agonist muscimol (0.25, 0.5 and 0.75 µg/rat; 1 µl/rat; 0.5 µl/rat in each side) decreased %OAT and %OAE, indicating anxiogenic-like behaviour. However, intra-CeA administration of the GABAA receptor antagonist bicuculline (0.25, 0.5 and 1 µg/rat; 1 µl/rat; 0.5 µl/rat in each side) produced significant anxiolytic-like behaviour. Nicotine in a subeffective dose (0.25 µg/rat) when co-administered with muscimol did not significantly increase the anxiety behaviour. An effective dose of nicotine (2 µg/rat) in combination with bicuculline (0.25, 0.5 and 1 µg/rat) had no interaction on %OAT, %OAE and locomotor activity. It can be concluded that in the central amygdala, the GABAergic system is not involved in the anxiogenic response to nicotine.
Limited Clinical Benefit from Trastuzumab in Recurrent Endometrial Cancer
Authors: Vandenput I. , Vanden Bempt I. , Leunen K. , Neven P. , Berteloot P. , Moerman P. , Vergote I. , Amant F.
Published: October 2008

Background: It is hypothesized that the HER-2/neu receptor could be used for targeted therapy in recurrent endometrial cancer. Cases: A patient with type II endometrial cancer (serous), showing strong HER-2/neu overexpression and gene amplification in both primary and recurrent tumor, received single-agent trastuzumab (3× weekly, 8 mg/kg loading, 6 mg/kg maintenance dose). Because of progression after 4 cycles, weekly paclitaxel-trastuzumab (80 mg/m2 paclitaxel; trastuzumab 4 mg/kg loading, 2 mg/kg maintenance dose) was initiated. However, progressive disease was also noted after 11 weeks of combined treatment. A second patient, with recurrent type II endometrial cancer (grade III endometrioid), had HER-2/neu gene amplification in the primary tumor. However, biopsy from a lung metastasis 3 years later appeared to be HER-2/neu-negative. Conclusion: Based on lack of response and changes in tumor biology, trastuzumab was of little clinical value in 2 cases of recurrent type II endometrial cancer. This report underscores the importance of reassessment of a recurrent tumor before initiating targeted treatment.
Therapeutic Effect of Kakkonto in a Mouse Model of Food Allergy with Gastrointestinal Symptoms
Authors: Yamamoto Takeshi , Fujiwara Kanae , Yoshida Minako , Kageyama-Yahara Natsuko , Kuramoto Hirofumi , Shibahara Naotoshi , Kadowaki Makoto
Published: October 2008

Background: The number of patients with food allergy has increased dramatically over the last several decades. However, there is no effective drug for food allergies. In the present study, we evaluated the effects of kakkonto, a traditional Japanese herbal medicine, in a mouse model of food allergy with gastrointestinal symptoms. Methods: BALB/c mice were systemically sensitized twice with ovalbumin (OVA) and then were repeatedly given OVA by oral intubation (OVA mice). Kakkonto was administered orally before the OVA challenges. Results: The OVA mice developed allergic diarrhea (91.8 ± 3.8% after 6 OVA challenges), and myeloperoxidase (MPO) activity was dramatically elevated in the colons of the OVA mice. Kakkonto significantly suppressed the occurrence of allergic diarrhea and MPO activity in the OVA mice. Furthermore, the number of mucosal mast cells was greatly increased in the proximal colons of the OVA mice, and this was also suppressed by kakkonto. Interestingly, mRNA expression of helper T cell type 1 (Th1) cytokines (IFN-γ) and Th2 cytokines (IL-4, IL-5 and IL-10) were significantly upregulated in the proximal colons of the OVA mice, an effect which was also reduced by kakkonto. Transcriptome analysis detected increased mRNA expression of suppressor of cytokine signaling-3 in the proximal colons of OVA mice, which was decreased by kakkonto administration. Conclusion: Kakkonto has immunosuppressive effects and interferes with the infiltration of mucosal mast cells in the colons of mice with induced food allergy, leading to improvement of allergic symptoms. Kakkonto has potential as a therapeutic drug for treatment of allergic symptoms induced by the disruption of intestinal mucosal immunity.
Insufficient Increment of CD4+CD25+ Regulatory T Cells after Stimulation in vitro with Allergen in Allergic Asthma
Authors: Wang Li-Hui , Lin Yu-Hui , Yang Jiong , Guo Wei
Published: October 2008

Background: Allergen exposure can lead to the development of allergic asthma, sensitized asymptomatic or nonallergic responses in different conditions. Regulatory T (Treg) cells are involved in controlling the immune response direction. The aim of this study was to determine whether allergic asthmatics had defects in CD4+CD25+ Treg cells and CD4+IL (interleukin)-10+ Treg cells after specific allergen exposure. Methods: Peripheral-blood mononuclear cells (PBMCs) were isolated from 20 patients with asthma sensitized to house dust mite, 24 asymptomatic subjects sensitized to house dust mite and 22 nonallergic subjects. Cells were cultured without stimulation and with rDer p 1. Frequencies and proliferations of CD4+CD25+ T cells and CD4+IL-10+ T cells were measured by flow cytometry. Concentrations of IL-10, IL-4, interferon (IFN)-γ and tumor growth factor β1 in culture supernatants and sera were determined by ELISA. Results: PBMCs derived from sensitized asthmatic patients had the lowest percentage of CD4+CD25+ Treg cells and the highest IL-4 level in response to allergen among the 3 groups. PBMCs derived from sensitized asymptomatic subjects had higher percentages of both CD4+CD25+ Treg cells and CD4+IL-10+ T cells than those from sensitized asthmatic patients in rDer-p-1-stimulated cultures, and they had the highest levels of IL-10 and IFN-γ responses to allergen among the 3 groups. Conclusions: Patients with allergic asthma had an insufficient CD4+CD25+ Treg cell response and an excessive Th2 response to specific allergen. The high levels of Treg cell response and IL-10 and IFN- γ responses to specific allergen can partly explain the immunological characteristics associated with sensitized asymptomatic subjects.
Isolierung von vier neuen Salmonella- bzw. Arizona-Serotypen bei Reptilien einer «Schlangenausstellung»
Authors: Pagon S. , Rohde R. , Schweizer R.
Published: October 2008

Bacteriological investigations were performed with 31 samples of feces from reptiles, mainly from snakes of a snake exhibition in St. Gall. 27 Salmonella and Arizona serotypes were recovered from 20 specimens (64.5%). Seven of the Salmonella isolates belonged to the sub-genus I, two to the sub-genus II, while 14 could be classified as belonging to the sub-genus III (Arizona). Single infections have occurred in 13, and double infections in 7 of the cases under study. One Salmonella serotype of the sub-genus II – Salmonella II 13,23,36:1, Z281,5 – and three Arizona serotypes – Arizona 7a,7b:23:31, Arizona 23:29:21 and Arizona 24:26:30 – could be declared as new types.
Nonlinear Response of the Reticuloendothelial System upon Stimulation
Authors: Bliznakov E.G. , Adler A.D.
Published: October 2008

Various single reaction variables of the reticuloendothelial system (RES) may often be measured independently of others, but the total defense response of the host arises from a complex, interconnected set of these reactions. It is important, therefore, to study and attempt to understand the overall effects of substances having RES-modifying properties, as well as their specific effects on subsystems. The results reported here demonstrate that the overall response of a modified RES is strongly dose-dependent and that a specific typical response can be identified as characteristic of the entire system. This implies a biologically integrated system. If a wide enough range of doses can be used, an irregular, nonlinear, nonmonotonic curve is always observed. The plotted data generally show two peaks of maximal action which form a W- or M-shaped curve, with the response occurring at lower doses usually being weaker than that occurring at higher doses. The results described here were obtained by using the following experimental models: Ps. aeruginosa, S. typhimurium, Friend virus and PI. berghei infection in mice, Rous sarcoma virus infection in chicks, endotoxin shock in mice and dibenz-pyrene-induced tumors in mice. Modification of the RES was accomplished by using: bacterial lipopolysaccharide, cholesteryl oleate, coenzyme Q10 and Restim (shark-liver lipid). Additional data published from other laboratories supporting our results are also presented. The characteristics of the described type of dose-response relationship require that multiple dose ranges must be employed in evaluation experiments both to establish efficacy and to design optimum dose schedules for experimental or clinical use of agents modifying the RES.
Adherence of Candida albicans to Human Vaginal Epithelial Cells: Inhibition by Amino Sugars
Authors: Segal Esther , Lehrer Nurith , Ofek Itzhak
Published: October 2008

In vitro adherence of Candida albicans to human vaginal epithelial cells was studied, aimed at identifying the surface components involved in this binding. The inhibitory effect of yeast cell wall components and their constituents on the adherence of yeasts to epithelial cells was tested. Only chitin, its hydrolysate derivative and N-acetylglucosamine, the constituent of chitin, acted as inhibitors. Binding was also inhibited by the amino sugars glucosamine and mannosamine, while none of the other sugars tested (methylated or nonmethylated) exhibited such an effect. These data suggest that the amino groups of sugars are responsible for the inhibition of adherence of this eucaryotic microorganism to epithelial cells.
Inhibiting Effect of Dehydroascorbic Acid on Cell Division in Ascites Tumors in Mice
Authors: Poydock Eymard , Reikert D. , Rice J. , Aleandri L.
Published: October 2008

The transplantable murine ascites tumors, P388 leukemia and Ehrlich carcinoma, demonstrated complete inhibition of mitotic activity after treatment with dehydroascorbic acid in mice. Citric acid at the same pH value (2.4), however, showed no diminution of mitoses. Microscopic examination of the stained ascites exudate taken from the mice treated with 10 mg dehydroascorbic acid revealed few tumor cells and a pronounced increase in white blood cells, whereas the ascites tumor exposed to citric acid appeared normal.
Ultrastructural Localization of Acid Phosphatase in Germ Cells of Chick Embryo Left Ovary
Authors: Civinini Annalena , Mastrolia Lucia
Published: October 2008

The ultracytochemical localization of acid phosphatase was studied in oogonia and oocytes of the chick embryo left ovary. The reaction products are evident in lysosomes of various types and, in some cells, in the GERL as well. Furthermore, from the onset of the meiotic prophase, the enzymatic reaction also appears in the rough endoplasmic reticulum. Non-incubated sections of the same stages were observed, with the aim of identifying and describing the structure of the organelles, in particular lysosomes which appeared positive in incubated sections. The significance of the presence of the enzyme is discussed.
Lysosomal Enzyme Secretion from Human Placental Villi Is Increased by Serum Albumin and IgG
Authors: Douglas Gordon C.
Published: October 2008

Human serum albumin and IgG increased the secretion of the lysosomal enzyme, β-hexosaminidase, from human placental villi in a dose- and time-dependent manner. Release was also enhanced by bovine serum albumin and ovalbumin. β-Hexosaminidase secretion was not increased by the non-endocytosable substrate, IgG-Sepharose, indicating that the signal for release is not given by the interaction of protein with the cell surface. Experiments with 125I-labelled albumin and IgG showed that both proteins were actively internalised by placental villi giving credence to the idea that secretion is triggered after uptake.