bluuebunny/crossref_metadata_2025 huggingface dataset:
Planning a cluster randomized trial with unequal cluster sizes: practical issues involving continuous outcomes
Authors: Guittet Lydia , Ravaud Philippe , Giraudeau Bruno
Published: April 2006

Background

Cluster randomization design is increasingly used for the evaluation of health-care, screeening or educational interventions. At the planning stage, sample size calculations usually consider an average cluster size without taking into account any potential imbalance in cluster size. However, there may exist high discrepancies in cluster sizes.

Methods

We performed simulations to study the impact of an imbalance in cluster size on power. We determined by simulations to which extent four methods proposed to adapt the sample size calculations to a pre-specified imbalance in cluster size could lead to adequately powered trials.

Results

We showed that an imbalance in cluster size can be of high influence on the power in the case of severe imbalance, particularly if the number of clusters is low and/or the intraclass correlation coefficient is high. In the case of a severe imbalance, our simulations confirmed that the minimum variance weights correction of the variation inflaction factor (VIF) used in the sample size calculations has the best properties.

Conclusion

Publication of cluster sizes is important to assess the real power of the trial which was conducted and to help designing future trials. We derived an adaptation of the VIF from the minimum variance weights correction to be used in case the imbalance can be a priori formulated such as "a proportion (γ) of clusters actually recruit a proportion (τ) of subjects to be included (γ ≤ τ)".
Haematogenous Staphylococcus aureus meningitis. A 10-year nationwide study of 96 consecutive cases
Authors: Pedersen Michael , Benfield Thomas L , Skinhoej Peter , Jensen Allan G
Published: April 2006

Background

Haematogenous Staphylococcus aureus meningitis is rare but associated with high mortality. Knowledge about the disease is still limited. The objective of this study was to evaluate demographic and clinical prognostic features of bacteraemic S. aureus meningitis.

Methods

Nationwide surveillance in Denmark from 1991 to 2000 with clinical and bacteriological data. Risks of death were estimated by Cox proportional hazards regression analysis.

Results

Among 12480 cases of S. aureus bacteraemia/sepsis, we identified 96 cases of non-surgical bacteraemic S. aureus meningitis (0.8%). Incidence rates were 0.24 (95% confidence interval [CI], 0.18 to 0.30)/100 000 population between 1991–1995 and 0.13 (CI, 0.08 to 0.17)/100 000 population between 1996–2000. Mortality was 56%. After adjustment, only co morbidity (hazard ratio [HR], 3.45; CI, 1.15 to 10.30) and critical illness (Pitt score ≥ 4) (HR, 2.14; CI, 1.09 to 4.19) remained independent predictors of mortality.

Conclusion

The incidence, but not mortality of bacteraemic S. aureus meningitis decreased during the study period. Co morbidity and critical illness were independent predictors of a poor outcome.
Characterization of gastric adenocarcinoma cell lines established from CEA424/SV40 T antigen-transgenic mice with or without a human CEAtransgene
Authors: Nöckel Jessica , van den Engel Natasja K , Winter Hauke , Hatz Rudolf A , Zimmermann Wolfgang , Kammerer Robert
Published: April 2006

Background

Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murinein vivomodels which allow the stepwise improvement of immunotherapies for gastric cancer.

Methods

Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2CEA, mGC4CEA, mGC11CEA). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements.

Results

The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTLin vitro. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts. Although no spontaneous tumor rejection was observed, vaccination of C57BL/6 mice with lysates from gastric carcinoma cell lines protected C57BL/6 mice from tumor challenge, demonstrating the tumorigenicity of the tumor cell lines in nontransgenic mice of the H-2bhaplotype.

Conclusion

These tumor cell lines grafted in different syngeneic hosts should prove to be very useful to optimize immunotherapy regimens to be finally tested in transgenic animals developing primary gastric carcinomas.
Evaluation of MetriGenix custom 4D™ arrays applied for detection of breast cancer subtypes
Authors: Muggerud Aslaug Aamodt , Johnsen Hilde , Barnes Debra A , Steel Adam , Lønning Per Eystein , Naume Bjørn , Sørlie Therese , Børresen-Dale Anne-Lise
Published: April 2006

Background

Previously, a total of five breast cancer subtypes have been identified based on variation in gene expression patterns. These expression profiles were also shown to be associated with different prognostic value. In this study tumour samples from 27 breast cancer patients, previously subtyped by expression analysis using DNA microarrays, and four controls from normal breast tissue were included. A new MetriGenix 4D™ array proposed for diagnostic use was evaluated.

Methods

We applied MetriGenix custom 4D™ arrays for the detection of previously defined molecular subtypes of breast cancer. MetriGenix 4D™ arrays have special features including probe immobilization in microchannels with chemiluminescence detection that enable shorter hybridization time.

Results

The MetriGenix 4D™ array platform was evaluated with respect to both the accuracy in classifying the samples as well as the performance of the system itself. In a cross validation analysis using "Nearest Shrunken Centroid classifier" and the PAM software, 77% of the samples were classified correctly according to earlier classification results.

Conclusion

The system shows potential for fast screening; however, improvements are needed.
Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: An observational study
Authors: Bartsch Rupert , Wenzel Catharina , Hussian Dagmar , Pluschnig Ursula , Sevelda Ursula , Koestler Wolfgang , Altorjai Gabriela , Locker Gottfried J , Mader Robert , Zielinski Christoph C , Steger Guenther G
Published: April 2006

Background

Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression.

Methods

Fifty-four patients, median age 46 years, range 25–73 years, were included. We analysed for time to tumour progression (TTP) for first, second and beyond second line treatment, response rates and overall survival.

Results

Median time of observation was 24 months, range 7–51. Response rates for first line treatment were 7.4% complete remission (CR), 35.2% partial remissions (PR), 42.6% stable disease > 6 months (SD) and 14.8% of patients experienced disease progression despite treatment (PD). Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3rd line, 18 pts 4th line, 6 pts 5th line, 2 pts 6th line and 1 patient 7th line) were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m) in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed.

Conclusion

The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted.
An unusual cause of alveolar hemorrhage post hematopoietic stem cell transplantation: A case report
Authors: Gupta Sachin , Jain Amit , Fanning Tina V , Couriel Daniel R , Jimenez Carlos A , Eapen Georgie A
Published: April 2006

Background

Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported.

Case presentation

We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock.

Conclusion

Strongyloides stercoralis hyperinfection is an unusual cause of alveolar hemorrhage early after hematopoietic stem cell transplant with very high mortality.
Early lens aging is accelerated in subjects with a high risk of ischemic heart disease: an epidemiologic study
Authors: Kessel Line , Jørgensen Torben , Glümer Charlotte , Larsen Michael
Published: April 2006

Background

Ischemic heart disease (IHD) is one of the most important causes of mortality and morbidity in the Western world. There is a relationship between aging of the lens of the human eye and cardiovascular disease. The present study was conducted to examine if the risk of ischemic heart disease could be estimated by fluorophotometric assessment of lens aging.

Methods

A total of 421 subjects were included. Risk of IHD was estimated from non-ocular data using the Precard ® software. Lens aging was quantified by lens fluorometry.

Results

The risk of IHD was strongly related to lens fluorophore accumulation (p = 0.001). The relationship between IHD and lens aging was attributable to tobacco smoking and dysglycemia.

Conclusion

The risk of ischemic heart disease related to smoking and diabetes mellitus can be estimated using the aging of the lens of the eye as a biomarker for generalized tissue-damage.
Organizational aspects and implementation of data systems in large-scale epidemiological studies in less developed countries
Authors: Ali Mohammad , Park Jin-Kyung , von Seidlein Lorenz , Acosta Camilo J , Deen Jacqueline L , Clemens John D
Published: April 2006

Background

In the conduct of epidemiological studies in less developed countries, while great emphasis is placed on study design, data collection, and analysis, often little attention is paid to data management. As a consequence, investigators working in these countries frequently face challenges in cleaning, analyzing and interpreting data. In most research settings, the data management team is formed with temporary and unskilled persons. A proper working environment and training or guidance in constructing a reliable database is rarely available. There is little information available that describes data management problems and solutions to those problems. Usually a line or two can be obtained in the methods section of research papers stating that the data are doubly-entered and that outliers and inconsistencies were removed from the data. Such information provides little assurance that the data are reliable. There are several issues in data management that if not properly practiced may create an unreliable database, and outcomes of this database will be spurious.

Results

We have outlined the data management practices for epidemiological studies that we have modeled for our research sites in seven Asian countries and one African country.

Conclusion

Information from this model data management structure may help others construct reliable databases for large-scale epidemiological studies in less developed countries.
Surveillance of HIV and syphilis infections among antenatal clinic attendees in Tanzania-2003/2004
Authors: Swai Roland O , Somi G Geofrey R , Matee Mecky IN , Killewo Japhet , Lyamuya Eligius F , Kwesigabo Gideon , Tulli Tuhuma , Kabalimu Titus K , Ng'ang'a Lucy , Isingo Raphael , Ndayongeje Joel
Published: April 2006

Background

This paper presents the prevalence of human immunodeficiency virus (HIV) and syphilis infections among women attending antenatal clinics (ANC) in Tanzania obtained during the 2003/2004 ANC surveillance.

Methods

Ten geographical regions; six of them were involved in a previous survey, while the remaining four were freshly selected on the basis of having the largest population among the remaining 20 regions. For each region, six ANC were selected, two from each of three strata (urban, peri-urban and rural). Three of the sites did not participate, resulting into 57 surveyed clinics. 17,813 women who were attending the chosen clinics for the first time for any pregnancy between October 2003 and January 2004. Patient particulars were obtained by interview and blood specimens were drawn for HIV and syphilis testing. HIV testing was done anonymously and the results were unlinked.

Results

Of the 17,813 women screened for HIV, 1,545 (8.7% (95% CI = 8.3–9.1)) tested positive with the highest prevalence in women aged 25–34 years (11%), being higher among single women (9.7%) than married women (8.6%) (p < 0.07), and increased with level of education from 5.2% among women with no education to 9.3% among those at least primary education (p < 0.001). Prevalence ranged from 4.8% (95% CI = 3.8% – 9.8%) in Kagera to 15.3% (95% CI = 13.9% – 16.8%) in Mbeya and was; 3.7%, 4.7%, 9.1%, 11.2% and 15.3% for rural, semi-urban, road side, urban and 15.3% border clinics, respectively (p < 0.001).

Of the 17,323 women screened for syphilis, 1265 (7.3% (95%CI = 6.9–7.7)) were positive, with highest prevalence in the age group 35–49 yrs (10.4%) (p < 0.001), and being higher among women with no education than those with some education (9.8% versus 6.8%) (p < 0.0001), but marital status had no influence. Prevalence ranged from 2.1% (95% CI = 1.4% – 3.0%) in Kigoma to 14.9% (95% CI = 13.3%-16.6%) in Kagera and was 16.0% (95% CI = 13.3–18.9), 10.5% (95% CI = 9.5–11.5) and 5.8% (95% CI = 5.4–6.3) for roadside, rural and urban clinics, respectively. Syphilis and HIV co-infection was seen in 130/17813 (0.7%).

Conclusion

The high HIV prevalence observed among the ANC clinic attendees in Tanzania call for expansion of current voluntary counselling and testing (VCT) services and access to antiretroviral drugs (ARV) in the clinics. There is also a need for modification of obstetric practices and infant feeding options in HIV infection in order to prevent mother to child transmission of HIV. To increase uptake to HIV testing the opt-out strategy in which all clients are offered HIV testing is recommended in order to meet the needs of as many pregnant women as possible.
Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs
Authors: Chuang Yao-Chi , Tu Chieh-Hsien , Huang Chao-Cheng , Lin Hsin-Ju , Chiang Po-Hui , Yoshimura Naoki , Chancellor Michael B
Published: April 2006

Background

With the increasing interest with botulinum toxin – A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and also in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH).

Methods

Transperineal injection into the prostate using transrectal ultrasound (TRUS) was performed throughout the study. Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate. One or 3 months later, the prostate was harvested for morphologic and apoptotic study. In addition, eight BPH patients refractory to α-blockers were treated with ultrasound guided intraprostatic injection of 200 U of BTX-A.

Results

In the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom score, and quality of life index were significantly reduced by 18.8%, 73.1%, and 61.5% respectively. Maximal flow rate significantly increased by 72.0%.

Conclusion

Intraprostatic BTX-A injection induces prostate apotosis in dogs and relieves BOO in humans. It is therefore a promising alternative treatment for refractory BOO due to BPH.
Case report and summary of literature: giant perineal keloids treated with post-excisional radiotherapy
Authors: Jones Kristin , Fuller Clifton D , Luh Join Y , Childs Craig C , Miller Alexander R , Tolcher Anthony W , Herman Terence S , Thomas Charles R
Published: April 2006

Background

Keloids are common benign tumors of the dermis, typically arising after insult to the skin. While typically only impinging on cosmesis, large or recurrent keloids may require therapeutic intervention. While no single standardized treatment course has been established, several series report excellent outcomes for keloids with post-surgery radiation therapy.

Case presentation

We present a patient with a history of recurrent keloids arising in the absence of an ascribed trauma and a maternal familial history of keloid formation, whose physical examination several large perineal keloids of 6-20 cm in the largest dimension. The patient was treated with surgical extirpation and adjuvant radiation therapy. Radiotherapy was delivered to the scar bed to a total dose of 22 Gy over 11 daily fractions. Acute radiotherapy toxicity necessitated a treatment break due to RTOG Grade III acute toxicity (moderate ulceration and skin breakdown) which resolved rapidly during a 3-day treatment break. The patient demonstrated local control and has remained free of local recurrence for more than 2 years.

Conclusion

Radiotherapy for keloids represents a safe and effective option for post-surgical keloid therapy, especially for patients with bulky or recurrent disease.
The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β
Authors: Miller Mark JS , Ahmed Salahuddin , Bobrowski Paul , Haqqi Tariq M
Published: April 2006

Background

Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria®), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality.

Methods

Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β.

Results

RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β.

Conclusion

The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases.
A biobank management model applicable to biomedical research
Authors: Auray-Blais Christiane , Patenaude Johane
Published: April 2006

Background

The work of Research Ethics Boards (REBs), especially when involving genetics research and biobanks, has become more challenging with the growth of biotechnology and biomedical research. Some REBs have even rejected research projects where the use of a biobank with coded samples was an integral part of the study, the greatest fear being the lack of participant protection and uncontrolled use of biological samples or related genetic data. The risks of discrimination and stigmatization are a recurrent issue. In light of the increasing interest in biomedical research and the resulting benefits to the health of participants, it is imperative that practical solutions be found to the problems associated with the management of biobanks: namely, protecting the integrity of the research participants, as well as guaranteeing the security and confidentiality of the participant's information.

Methods

We aimed to devise a practical and efficient model for the management of biobanks in biomedical research where a medical archivist plays the pivotal role as a data-protection officer. The model had to reduce the burden placed on REBs responsible for the evaluation of genetics projects and, at the same time, maximize the protection of research participants.

Results

The proposed model includes the following: 1) a means of protecting the information in biobanks, 2) offers ways to provide follow-up information requested about the participants, 3) protects the participant's confidentiality and 4) adequately deals with the ethical issues at stake in biobanking.

Conclusion

Until a governmental governance body is established in Quebec to guarantee the protection of research participants and establish harmonized guidelines for the management of biobanks in medical research, it is definitely up to REBs to find solutions that the present lack of guidelines poses. The model presented in this article offers a practical solution on a day-to-day basis for REBs, as well as researchers by promoting an archivist to a pivotal role in the process. It assures protection of all participants who altruistically donate their samples to generate and improve knowledge for better diagnosis and medical treatment.
Methods underpinning national clinical guidelines for hypertension: describing the evidence shortfall
Authors: Campbell Fiona , Dickinson Heather O , Cook Julia VF , Beyer Fiona R , Eccles Martin , Mason James M
Published: April 2006

Background

To be useful, clinical practice guidelines need to be evidence based; otherwise they will not achieve the validity, reliability and credibility required for implementation.

Methods

This paper compares the methods used in gathering, analysing and linking of evidence to guideline recommendations in ten current hypertension guidelines.

Results

It found several guidelines had failed to implement methods of searching for the relevant literature, critical analysis and linking to recommendations that minimise the risk of bias in the interpretation of research evidence. The more rigorous guidelines showed discrepancies in recommendations and grading that reflected different approaches to the use of evidence in guideline development.

Conclusion

Clinical practice guidelines as a methodology are clearly still an evolving health care technology.
Rapid Urban Malaria Appraisal (RUMA) II: Epidemiology of urban malaria in Dar es Salaam (Tanzania)
Authors: Wang Shr-Jie , Lengeler Christian , Mtasiwa Deodatus , Mshana Thomas , Manane Lusinge , Maro Godson , Tanner Marcel
Published: April 2006

Background

The thinking behind malaria research and control strategies stems largely from experience gained in rural areas and needs to be adapted to the urban environment.

Methods

A rapid assessment of urban malaria was conducted in Dar es Salaam in June-August, 2003 using a standard Rapid Urban Malaria Appraisal (RUMA) methodology. This study was part of a multi-site study in sub-Saharan Africa supported by the Roll Back Malaria Partnership.

Results

Overall, around one million cases of malaria are reported every year by health facilities. However, school surveys in Dar es Salaam during a dry spell in 2003 showed that the prevalence of malaria parasites was low: 0.8%, 1.4%, 2.7% and 3.7% in the centre, intermediate, periphery and surrounding rural areas, respectively. Health facilities surveys showed that only 37/717 (5.2%) of presenting fever cases and 22/781 (2.8%) of non-fever cases were positive by blood slide. As a result, malaria-attributable fractions for fever episodes were low in all age groups and there was an important over-reporting of malaria cases. Increased malarial infection rates were seen in persons who travelled to rural areas within the past three months. A remarkably high coverage of insecticide-treated nets and a corresponding reduction in malarial infection risk were found.

Conclusion

The number of clinical malaria cases was much lower than routine reporting suggested. Improved malaria diagnosis and re-defined clinical guidelines are urgently required to avoid over-treatment with antimalarials.
Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions
Authors: Yin Weihong , Cheepala Satish , Roberts Jennifer N , Syson-Chan Keith , DiGiovanni John , Clifford John L
Published: April 2006

Background

Squamous cell carcinoma (SCC) of the skin is the most aggressive form of non-melanoma skin cancer (NMSC), and is the single most commonly diagnosed cancer in the U.S., with over one million new cases reported each year. Recent studies have revealed an oncogenic role of activated signal transducer and activator of transcription 3 (Stat3) in many human tumors, especially in those of epithelial origin, including skin SCC. Stat3 is a mediator of numerous growth factor and cytokine signaling pathways, all of which activate it through phosphorylation of tyrosine 705.

Results

To further address the role of Stat3 in skin SCC tumorigenesis, we have analyzed a panel of human skin-derived cell lines ranging from normal human epidermal keratinocytes (NHEK), to non-tumorigenic transformed skin cells (HaCaT), to highly tumorigenic cells (SRB1-m7 and SRB12-p9) and observed a positive correlation between Stat3 phosphorylation and SCC malignancy. We next determined the role of Stat3 activity in cell proliferation and viability under serum-free culture conditions. This was accomplished by suppressing Stat3 activity in the SRB12-p9 cells through stable expression of a dominant negative acting form of Stat3β, which contains a tyrosine 705 to phenylalanine mutation (S3DN). The S3DN cells behaved similar to parental SRB12-p9 cells when cultured in optimal growth conditions, in the presence of 10% fetal calf serum. However, unlike the SRB12-p9 cells, S3DN cells underwent apoptotic cell death when cultured in serum-free medium (SFM). This was evidenced by multiple criteria, including accumulation of sub-G1 particles, induced PARP cleavage, and acquisition of the characteristic morphological changes associated with apoptosis.

Conclusion

This study provides direct evidence for a role for Stat3 in maintaining cell survival in the conditions of exogenous growth factor deprivation produced by culture in SFM. We also propose that delivery of the S3DN gene or protein to tumor cells could induce apoptosis and/or sensitize those cells to the apoptotic effects of cancer therapeutic agents, raising the possibility of using S3DN as an adjunct for treatment of skin SCC.
Misinterpretation with norm-based scoring of health status in adults with type 1 diabetes
Authors: Supina Alison L , Feeny David H , Carroll Linda J , Johnson Jeffrey A
Published: April 2006

Background

Interpretations of profile and preference based measure scores can differ. Profile measures often use a norm-based scoring algorithm where each scale is scored to have a standardized mean and standard deviation, relative to the general population scores/norms (i.e., norm-based). Preference-based index measures generate an overall scores on the conventional scale in which 0.00 is assigned to dead and 1.00 is assigned to perfect health. Our objective was to investigate the interpretation of norm-based scoring of generic health status measures in a population of adults with type 1 diabetes by comparing norm-based health status scores and preference-based health-related quality of life (HRQL) scores.

Methods

Data were collected through self-complete questionnaires sent to patients with type 1 diabetes. The RAND-36 and the Health Utilities Index Mark 3 (HUI3) were included.

Results

A total of 216 (61%) questionnaires were returned. The respondent sample was predominantly female (58.8%); had a mean (SD) age of 37.1 (14.3) years and a mean duration of diabetes of 20.9 (12.4) years. Mean (SD) health status scores were: RAND-36 PHC 47.9 (9.4), RAND-36 MHC 47.2 (11.8), and HUI3 0.78 (0.23). Histograms of these scores show substantial left skew. HUI3 scores were similar to those previously reported for diabetes in the general Canadian population. Physical and mental health summary scores of the RAND-36 suggest that this population is as healthy as the general adult population.

Conclusion

In this sample, a preference-based measure indicated poorer health, consistent with clinical evidence, whereas a norm-based measure indicated health similar to the average for the general population. Norm-based scoring measure may provide misleading interpretations in populations when health status is not normally distributed.
Contributions of androgen and estrogen to fetal programming of ovarian dysfunction
Authors: Abbott David H , Padmanabhan Vasantha , Dumesic Daniel A
Published: April 2006

In female mammals, including humans, deviations from normal androgenic or estrogenic exposure during fetal development are detrimental to subsequent adult ovarian function. Androgen deficiency, without accompanying estrogen deficit, has little apparent impact on ovarian development. Fetal estrogen deficiency, on the other hand, results in impaired oocyte and follicle development, immature and abnormal adult ovaries, and excessive ovarian stimulation from endogenous gonadotropins ultimately generating hemorrhagic follicles. Complete estrogen deficiency lasting into adulthood results in partial ovarian masculinization. Fetal androgen excess, on the other hand, mediated either by direct androgen action or following androgen aromatization to estrogen, reprograms ovarian development and reproductive neuroendocrinology to mimic that found in women with polycystic ovary syndrome: enlarged, polyfollicular, hyperandrogenic, anovulatory ovaries with accompanying LH hypersecretion. Oocyte developmental competence is also compromised. Insulin is implicated in the mechanism of both anovulation and deficient oocyte development. Fetal estrogen excess induces somewhat similar disruption of adult ovarian function to fetal androgen excess. Understanding the quality of the fetal female sex steroid hormone environment is thus becoming increasingly important in improving our knowledge of mechanisms underlying a variety of female reproductive pathologies.
Disability weights for comorbidity and their influence on Health-adjusted Life Expectancy
Authors: van Baal Pieter HM , Hoeymans Nancy , Hoogenveen Rudolf T , de Wit Ardine G , Westert Gert P
Published: April 2006

Background

Comorbidity complicates estimations of health-adjusted life expectancy (HALE) using disease prevalences and disability weights from Burden of Disease studies. Usually, the exact amount of comorbidity is unknown and no disability weights are defined for comorbidity.

Methods

Using data of the Dutch national burden of disease study, the effects of different methods to adjust for comorbidity on HALE calculations are estimated. The default multiplicative adjustment method to define disability weights for comorbidity is compared to HALE estimates without adjustment for comorbidity and to HALE estimates in which the amount of disability in patients with multiple diseases is solely determined by the disease that leads to most disability (the maximum adjustment method). To estimate the amount of comorbidity, independence between diseases is assumed.

Results

Compared to the multiplicative adjustment method, the maximum adjustment method lowers HALE estimates by 1.2 years for males and 1.9 years for females. Compared to no adjustment, a multiplicative adjustment lowers HALE estimates by 1.0 years for males and 1.4 years for females.

Conclusion

The differences in HALE caused by the different adjustment methods demonstrate that adjusting for comorbidity in HALE calculations is an important topic that needs more attention. More empirical research is needed to develop a more general theory as to how comorbidity influences disability.
Interleukin-1β and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes
Authors: Jauneau Anne-christine , Ischenko Alexander , Chatagner Alexandra , Benard Magalie , Chan Philippe , Schouft Marie-therese , Patte Christine , Vaudry Hubert , Fontaine Marc
Published: April 2006

C3a and C5a anaphylatoxins are proinflammatory polypeptides released during complement activation. They exert their biological activities through interaction with two G protein-coupled receptors named C3aR and C5aR, respectively. In the brain, these receptors are expressed on glial cells, and some recent data have suggested that anaphylatoxins could mediate neuroprotection. In this study, we used RT-PCR and ribonuclease protection assays (RPA) to investigate the role of anaphylatoxins on neurotrophin expression by the human glioblastoma cell line T98G and by rat astrocytes. Our data show that for both cell types, anaphylatoxins upregulate expression of NGF mRNA. This response depended on a G protein-coupled pathway since pre-treatment of cells with pertussis toxin (PTX) completely blocked NGF mRNA increases. This effect was anaphylatoxin-specific since pre-incubation with anti-C3a or anti-C5aR antibodies abolished the effects of C3a and C5a, respectively. The regulation of NGF mRNA by anaphylatoxins was not accompanied by translation into protein expression, but there was a significant synergic effect of anaphylatoxins/IL-1b costimulation. Our demonstration of involvement of anaphylatoxins in the NGF release process by astrocytes suggests that C3a and C5a could modulate neuronal survival in the CNS.
Fast drying of Fine Needle Aspiration slides using a hand held fan : Impact on turn around time and staining quality
Authors: Baig Mirza A , Fathallah Lamia , Feng Jining , Husain Mujtaba , Grignon David G , Al-Abbadi Mousa A
Published: April 2006

To analyze the impact of using a hand held fan to speed the air-drying process during immediate adequacy evaluation of Fine Needle Aspirations. The effect on turn around time and staining quality is evaluated.

Two mirror image air-dried smears for each pass were prepared. One was subjected to a small hand-held fan with a fan diameter of 7 cm held an average distance of 3 to 5 cm from the slide. The other smear was left to dry without a fan. A total of 93 consecutive pairs were evaluated over a 2-month duration.

The average time needed for air-drying using the fan was 73 seconds (range 10-300 seconds, standard error 6.986), while it was 200 seconds (range 15-645 seconds, standard error 17.799) for those without fan. This difference was statistically significant (p < 0.001). Smears were then evaluated for single cells, cell clusters and background material and no appreciable difference in stain quality was noted between the 2 groups.

The use of a small hand-held fan for air-drying shortened the drying time for FNA adequacy by an average of 127 seconds (63% time reduction) for each pass. The quality of staining was comparable. Using a fan is highly recommended.
Comparison of knee motion on Earth and in space: an observational study
Authors: Pierre Mark C , Genc Kerim O , Litow Micah , Humphreys Brad , Rice Andrea J , Maender Christian C , Cavanagh Peter R
Published: April 2006

Background

Spaceflight has been shown to cause atrophy, reduced functional capacity, and increased fatigue in lower-limb skeletal muscles. The mechanisms of these losses are not fully understood but are thought to result, in part, from alteration in muscle usage.

Methods

Knee-joint angles and lower-extremity muscle activity were measured continually, via elecrogoniometry and surface electromyography respectively, from two subjects during entire working days of activity on Earth and onboard the International Space Station (ISS).

Results

On Earth the distribution of angular positions of the knee was typically bimodal, with peaks of >75 degrees of flexion and in almost full extension (<15 degrees of flexion). However, on the ISS, a single peak in the mid-range of the available range of motion was seen. The knee joint was also moved through fewer excursions and the excursions were smaller in amplitude, resulting in a reduced span of angles traversed. The velocities of the excursions in space were lower than those used on Earth.

Conclusion

These results demonstrate that, in space, overall knee-joint motion is reduced, and there is a transformation in the type of muscle action compared to that seen on Earth, with more isometric action at the expense of concentric and particularly eccentric action.
Predicting the subcellular localization of viral proteins within a mammalian host cell
Authors: Scott MS , Oomen R , Thomas DY , Hallett MT
Published: April 2006

Background

The bioinformatic prediction of protein subcellular localization has been extensively studied for prokaryotic and eukaryotic organisms. However, this is not the case for viruses whose proteins are often involved in extensive interactions at various subcellular localizations with host proteins.

Results

Here, we investigate the extent of utilization of human cellular localization mechanisms by viral proteins and we demonstrate that appropriate eukaryotic subcellular localization predictors can be used to predict viral protein localization within the host cell.

Conclusion

Such predictions provide a method to rapidly annotate viral proteomes with subcellular localization information. They are likely to have widespread applications both in the study of the functions of viral proteins in the host cell and in the design of antiviral drugs.
Leptin and adiponectin in relation to body fat percentage, waist to hip ratio and the apoB/apoA1 ratio in Asian Indian and Caucasian men and women
Authors: Smith Jessica , Al-Amri Maha , Sniderman Allan , Cianflone Katherine
Published: April 2006

Background

Asian Indian immigrants have an increased risk for developing cardiovascular disease (CVD); however, there is very little data examining how the adipokines leptin and adiponectin relate to CVD risk factors such as body fat percentage (BF%), waist to hip ratio (WHR) and the apoB/apoA1 ratio in Asian Indian men and women living in Canada.

Subjects and methods

A cross-sectional study comparing leptin, adiponectin, lipoproteins and anthropometric parameters in Asian Indian men and women to Caucasian men and women (4 groups). Anthropometric data (BMI, BF%, WHR), circulating lipids (apoA1, apoB, total cholesterol, and HDL-cholesterol), leptin and adiponectin were measured.

Results

Asian Indian men and women had higher leptin and lower adiponectin concentrations then Caucasian men and women, respectively. Leptin (positively) and adiponectin (negatively) correlated with anthropometric parameters and lipoproteins in all four groups. Using stepwise forward multiple regression, a model including TC/HDL-C ratio, WHR, BF%, hip circumference and waist circumference predicted 74.2% of leptin concentration in men. In women, apoB, BF%, waist circumference and age predicted 77.5% of leptin concentration. Adiponectin concentrations in men were predicted (30.2%) by HDL-C, total cholesterol, hip circumference and BF% while in women 41.2% of adiponectin concentration was predicted by the apoB/apoA1 ratio, WHR and age.

Conclusion

As is evident from our data, there is a strong relationship between leptin, adiponectin, and abdominal obesity with increased CVD risk, as assessed by the apoB/apoA1 ratio. Dysregulation of these parameters may account for the increased risk of CVD in Asian Indians.
Increased multiaxial lumbar motion responses during multiple-impulse mechanical force manually assisted spinal manipulation
Authors: Keller Tony S , Colloca Christopher J , Moore Robert J , Gunzburg Robert , Harrison Deed E
Published: April 2006

Background

Spinal manipulation has been found to create demonstrable segmental and intersegmental spinal motions thought to be biomechanically related to its mechanisms. In the case of impulsive-type instrument device comparisons, significant differences in the force-time characteristics and concomitant motion responses of spinal manipulative instruments have been reported, but studies investigating the response to multiple thrusts (multiple impulse trains) have not been conducted. The purpose of this study was to determine multi-axial segmental and intersegmental motion responses of ovine lumbar vertebrae to single impulse and multiple impulse spinal manipulative thrusts (SMTs).

Methods

Fifteen adolescent Merino sheep were examined. Tri-axial accelerometers were attached to intraosseous pins rigidly fixed to the L1 and L2 lumbar spinous processes under fluoroscopic guidance while the animals were anesthetized. A hand-held electromechanical chiropractic adjusting instrument (Impulse) was used to apply single and repeated force impulses (13 total over a 2.5 second time interval) at three different force settings (low, medium, and high) along the posteroanterior axis of the T12 spinous process. Axial (AX), posteroanterior (PA), and medial-lateral (ML) acceleration responses in adjacent segments (L1, L2) were recorded at a rate of 5000 samples per second. Peak-peak segmental accelerations (L1, L2) and intersegmental acceleration transfer (L1–L2) for each axis and each force setting were computed from the acceleration-time recordings. The initial acceleration response for a single thrust and the maximum acceleration response observed during the 12 multiple impulse trains were compared using a paired observations t-test (POTT, alpha = .05).

Results

Segmental and intersegmental acceleration responses mirrored the peak force magnitude produced by the Impulse Adjusting Instrument. Accelerations were greatest for AX and PA measurement axes. Compared to the initial impulse acceleration response, subsequent multiple SMT impulses were found to produce significantly greater (3% to 25%, P < 0.005) AX, PA and ML segmental and intersegmental acceleration responses. Increases in segmental motion responses were greatest for the low force setting (18%–26%), followed by the medium (5%–26%) and high (3%–26%) settings. Adjacent segment (L1) motion responses were maximized following the application of several multiple SMT impulses.

Conclusion

Knowledge of the vertebral motion responses produced by impulse-type, instrument-based adjusting instruments provide biomechanical benchmarks that support the clinical rationale for patient treatment. Our results indicate that impulse-type adjusting instruments that deliver multiple impulse SMTs significantly increase multi-axial spinal motion.
Estimating the Contribution of Mutation, Recombination and Gene Conversion in the Generation of Haplotypic Diversity
Authors: Morrell Peter L , Toleno Donna M , Lundy Karen E , Clegg Michael T
Published: April 2006

Recombination occurs through both homologous crossing over and homologous gene conversion during meiosis. The contribution of recombination relative to mutation is expected to be dramatically reduced in inbreeding organisms. We report coalescent-based estimates of the recombination parameter (ρ) relative to estimates of the mutation parameter (θ) for 18 genes from the highly self-fertilizing grass, wild barley, Hordeum vulgare ssp. spontaneum. Estimates of ρ/θ are much greater than expected, with a mean $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\hat{{\rho}}}}\) \end{document}$/$\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\hat{{\theta}}}}\) \end{document}$ ≈ 1.5, similar to estimates from outcrossing species. We also estimate $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\hat{{\rho}}}}\) \end{document}$ with and without the contribution of gene conversion. Genotyping errors can mimic the effect of gene conversion, upwardly biasing estimates of the role of conversion. Thus we report a novel method for identifying genotyping errors in nucleotide sequence data sets. We show that there is evidence for gene conversion in many large nucleotide sequence data sets including our data that have been purged of all detectable sequencing errors and in data sets from Drosophila melanogaster, D. simulans, and Zea mays. In total, 13 of 27 loci show evidence of gene conversion. For these loci, gene conversion is estimated to contribute an average of twice as much as crossing over to total recombination.