bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic regulation of natural variation in cortical and noncortical brain volume
Authors: Beatty Jackson , Laughlin Rick E
Published: February 2006

Background

The relative growth of the neocortex parallels the emergence of complex cognitive functions across species. To determine the regions of the mammalian genome responsible for natural variations in cortical volume, we conducted a complex trait analysis using 34 strains of recombinant inbred (Rl) strains of mice (BXD), as well as their two parental strains (C57BL/6J and DBA/2J). We measured both neocortical volume and total brain volume in 155 coronally sectioned mouse brains that were Nissl stained and embedded in celloidin. After correction for shrinkage, the measured cortical and noncortical brain volumes were entered into a multiple regression analysis, which removed the effects of body size and age from the measurements. Marker regression and interval mapping were computed using WebQTL.

Results

An ANOVA revealed that more than half of the variance of these regressed phenotypes is genetically determined. We then identified the regions of the genome regulating this heritability. We located genomic regions in which a linkage disequilibrium was present using WebQTL as both a mapping engine and genomic database. For neocortex, we found a genome-wide significant quantitative trait locus (QTL) on chromosome 11 (marker D11Mit19), as well as a suggestive QTL on chromosome 16 (marker D16Mit100). In contrast, for noncortex the effect of chromosome 11 was markedly reduced, and a significant QTL appeared on chromosome 19 (D19Mit22).

Conclusion

This classic pattern of double dissociation argues strongly for different genetic factors regulating relative cortical size, as opposed to brain volume more generally. It is likely, however, that the effects of proximal chromosome 11 extend beyond the neocortex strictly defined. An analysis of single nucleotide polymorphisms in these regions indicated that ciliary neurotrophic factor (Cntf) is quite possibly the gene underlying the noncortical QTL. Evidence for a candidate gene modulating neocortical volume was much weaker, but Otx1 deserves further consideration.
Human sensory-evoked responses differ coincident with either "fusion-memory" or "flash-memory", as shown by stimulus repetition-rate effects
Authors: Jewett Don L , Hart Toryalai , Larson-Prior Linda J , Baird Bill , Olson Marram , Trumpis Michael , Makayed Katherine , Bavafa Payam
Published: February 2006

Background:

A new method has been used to obtain human sensory evoked-responses whose time-domain waveforms have been undetectable by previous methods. These newly discovered evoked-responses have durations that exceed the time between the stimuli in a continuous stream, thus causing an overlap which, up to now, has prevented their detection. We have named them "A-waves", and added a prefix to show the sensory system from which the responses were obtained (visA-waves, audA-waves, somA-waves).

Results:

When A-waves were studied as a function of stimulus repetition-rate, it was found that there were systematic differences in waveshape at repetition-rates above and below the psychophysical region in which the sensation of individual stimuli fuse into a continuity. The fusion phenomena is sometimes measured by a "Critical Fusion Frequency", but for this research we can only identify a frequency-region [which we call the STZ (Sensation-Transition Zone)]. Thus, the A-waves above the STZ differed from those below the STZ, as did the sensations.

Study of the psychophysical differences in auditory and visual stimuli, as shown in this paper, suggest that different stimulus features are detected, and remembered, at stimulation rates above and below STZ.

Conclusion:

The results motivate us to speculate that:

1) Stimulus repetition-rates above the STZ generate waveforms which underlie "fusion-memory" whereas rates below the STZ show neuronal processing in which "flash-memory" occurs.

2) These two memories differ in both duration and mechanism, though they may occur in the same cell groups.

3) The differences in neuronal processing may be related to "figure" and "ground" differentiation.

We conclude that A-waves provide a novel measure of neural processes that can be detected on the human scalp, and speculate that they may extend clinical applications of evoked response recordings. If A-waves also occur in animals, it is likely that A-waves will provide new methods for comparison of activity of neuronal populations and single cells.
Inhibition of p38 mitogen-activated protein kinase enhances c-Jun N-terminal kinase activity: Implication in inducible nitric oxide synthase expression
Authors: Lahti Aleksi , Sareila Outi , Kankaanranta Hannu , Moilanen Eeva
Published: February 2006

Background

Nitric oxide (NO) is an inflammatory mediator, which acts as a cytotoxic agent and modulates immune responses and inflammation. p38 mitogen-activated protein kinase (MAPK) signal transduction pathway is activated by chemical and physical stress and regulates immune responses. Previous studies have shown that p38 MAPK pathway regulates NO production induced by inflammatory stimuli. The aim of the present study was to investigate the mechanisms involved in the regulation of inducible NO synthesis by p38 MAPK pathway.

Results

p38 MAPK inhibitors SB203580 and SB220025 stimulated lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression and NO production in J774.2 murine macrophages. Increased iNOS mRNA expression was associated with reduced degradation of iNOS mRNA. Treatment with SB220025 increased also LPS-induced c-Jun N-terminal kinase (JNK) activity. Interestingly, JNK inhibitor SP600125 reversed the effect of SB220025 on LPS-induced iNOS mRNA expression and NO production.

Conclusion

The results suggest that inhibition of p38 MAPK by SB220025 results in increased JNK activity, which leads to stabilisation of iNOS mRNA, to enhanced iNOS expression and to increased NO production.
Polarization of the endomembrane system is an early event in fucoid zygote development
Authors: Hadley Rhett , Hable Whitney E , Kropf Darryl L
Published: February 2006

Background

Fucoid zygotes are excellent experimental organisms for investigating mechanisms that establish cell polarity and determine the site of tip growth. A common feature of polarity establishment is targeting endocytosis and exocytosis (secretion) to localized cortical domains. We have investigated the spatiotemporal development of endomembrane asymmetry in photopolarizing zygotes, and examined the underlying cellular physiology.

Results

The vital dye FM4-64 was used to visualize endomembranes. The endomembrane system preferentially accumulated at the rhizoid (growth) pole within 4 h of fertilization. The polarized endomembrane array was initially labile and reoriented when the developmental axis changed direction in response to changing light cues. Pharmacological studies indicated that vesicle trafficking, actin and microtubules were needed to maintain endomembrane polarity. In addition, endocytosis required a functional cortical actin cytoskeleton.

Conclusion

Endomembrane polarization is an early event in polarity establishment, beginning very soon after photolocalization of cortical actin to the presumptive rhizoid site. Targeting of endocytosis and secretion to the rhizoid cortex contributes to membrane asymmetry. We suggest that microtubule-actin interactions, possibly involving microtubule capture and stabilization at actin-rich sites in the rhizoid, may organize the endomembrane array.
The reliability of the ankle-brachial index in the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS)
Authors: Weatherley Beth D , Chambless Lloyd E , Heiss Gerardo , Catellier Diane J , Ellison Curtis R
Published: February 2006

Background

A low ankle-brachial index (ABI) is associated with increased risk of coronary heart disease, stroke, and death. Regression model parameter estimates may be biased due to measurement error when the ABI is included as a predictor in regression models, but may be corrected if the reliability coefficient, R, is known. The R for the ABI computed from DINAMAP™ readings of the ankle and brachial SBP is not known.

Methods

A total of 119 participants in both the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS) had repeat ABIs taken within 1 year, using a common protocol, automated oscillometric blood pressure measurement devices, and technician pool.

Results

The estimated reliability coefficient for the ankle systolic blood pressure (SBP) was 0.68 (95% CI: 0.57, 0.77) and for the brachial SBP was 0.74 (95% CI: 0.62, 0.83). The reliability for the ABI based on single ankle and arm SBPs was 0.61 (95% CI: 0.50, 0.70) and the reliability of the ABI computed as the ratio of the average of two ankle SBPs to two arm SBPs was estimated from simulated data as 0.70.

Conclusion

These reliability estimates may be used to obtain unbiased parameter estimates if the ABI is included in regression models. Our results suggest the need for repeated measures of the ABI in clinical practice, preferably within visits and also over time, before diagnosing peripheral artery disease and before making therapeutic decisions.
Does sampling using random digit dialling really cost more than sampling from telephone directories: Debunking the myths
Authors: Yang Baohui , Eyeson-Annan Margo
Published: February 2006

Background

Computer assisted telephone interviewing (CATI) is widely used for health surveys. The advantages of CATI over face-to-face interviewing are timeliness and cost reduction to achieve the same sample size and geographical coverage. Two major CATI sampling procedures are used: sampling directly from the electronic white pages (EWP) telephone directory and list assisted random digit dialling (LA-RDD) sampling. EWP sampling covers telephone numbers of households listed in the printed white pages. LA-RDD sampling has a better coverage of households than EWP sampling but is considered to be more expensive due to interviewers dialling more out-of-scope numbers.

Methods

This study compared an EWP sample and a LA-RDD sample from the New South Wales Population Health Survey in 2003 on demographic profiles, health estimates, coefficients of variation in weights, design effects on estimates, and cost effectiveness, on the basis of achieving the same level of precision of estimates.

Results

The LA-RDD sample better represented the population than the EWP sample, with a coefficient of variation of weights of 1.03 for LA-RDD compared with 1.21 for EWP, and average design effects of 2.00 for LA-RDD compared with 2.38 for EWP. Also, a LA-RDD sample can save up to 14.2% in cost compared to an EWP sample to achieve the same precision for health estimates.

Conclusion

A LA-RDD sample better represents the population, which potentially leads to reduced bias in health estimates, and rather than costing more than EWP actually costs less.
Personal continuity and access in UK general practice: a qualitative study of general practitioners' and patients' perceptions of when and how they matter
Authors: Guthrie Bruce , Wyke Sally
Published: February 2006

Background

Personal continuity is a core value for family practice, but policy and performance targets emphasise other aspects of care, particularly waiting times for consultation. This study examined patient and general practitioner (GP) perceptions of the value of personal continuity and rapid access, and the relationship between them.

Methods

Qualitative analysis of semi-structured interviews with a purposive sample of 16 GPs and 32 patients in the Lothian region of Scotland, to identify whether, how, why and in which circumstances personal continuity and rapid access were valued.

Results

From the patients' perspective, what mattered was 'access to appropriate care' depending on the problem to be dealt with. For a few patients, rapid access was the only priority. For most, rapid access was balanced against greater involvement in the consultation when seeing 'their' trusted doctor, which was particularly valued for chronic, complex and emotional problems. GPs focused on the value of personal continuity in the consultation for improving the diagnosis and management of the same kinds of problem. GPs did not perceive enabling access to be a core part of their work. There was little evidence that GPs routinely discussed with patients when or how personal continuity and access should be balanced.

Conclusion

'Access to appropriate care' from the patients' perspective is not fully addressed by GPs' focus on personal continuity, nor by performance targets focused only on speed of access. GPs need to make enabling access as much a part of their core values as personal continuity, and access targets need to be based on less simplistic measures that account for the appropriateness of care as well as speed of access.
Human papillomavirus infections in women seeking cervical Papanicolaou cytology of Durango, Mexico: prevalence and genotypes
Authors: Sánchez-Anguiano Luis Francisco , Alvarado-Esquivel Cosme , Reyes-Romero Miguel Arturo , Carrera-Rodríguez Margarita
Published: February 2006

Background

HPV infection in women from developing countries is an important public health problem. Therefore, we sought to determine the prevalences of HPV infection and HPV genotypes in a female population of Durango City, Mexico. Also to determine whether any socio-demographic characteristic from the women associated with HPV infection exists.

Methods

Four hundred and ninety eight women seeking cervical Papanicolaou examination in three public Health Centers were examined for HPV infection. All women were tested for HPV DNA PCR by using HPV universal primers. In addition, all positive HPV DNA PCR samples were further analyzed for genotyping of HPV genotype 16, 18 and 33. Socio-demographic characteristics from each participant were also obtained.

Results

Twenty-four out of four hundred and ninety-eight (4.8%) women were found infected by HPV. HPV genotype 16 was found in 18 out of the 24 (75%) infected women. Two of them were also coinfected by HPV genotype 18 (8.3%). In the rest 6 PCR positive women, genotyping for HPV genotypes 16, 18 and 33 were negative.

Conclusion

The prevalence of HPV in women of Durango City is low; however, most infected women have high risk HPV genotype. The women who were studied showed low frequency of risk factors for HPV infection and this may explain the low prevalence of HPV infection. The high frequency of high risk HPV genotypes observed might explain the high rate of mortality for cervical cancer in our region.
A prospective study of hearing changes after beginning zidovudine or didanosine in HIV-1 treatment-naïve people
Authors: Schouten Jeffrey T , Lockhart David W , Rees Thomas S , Collier Ann C , Marra Christina M
Published: February 2006

Background

While hearing loss in HIV-infected people after beginning nucleoside reverse transcriptase inhibitors (NRTIs) has been reported, there have been no prospective studies that measured hearing changes longitudinally in treatment-naïve HIV-infected subjects following initiation of regimens containing NRTIs. The goal of this study was to conduct a prospective assessment of the contribution of zidovudine (ZDV) and didanosine (ddI) to hearing loss

Methods/design

A prospective observational pilot study to determine whether ZDV or ddI, alone or in combination, are associated with sensorineural hearing loss in HIV-infected persons. Changes in hearing levels at all frequencies and in low and high frequency pure tone averages were measured at baseline, 16, and 32 weeks after initiating antiretroviral therapy.

Discussion

Treatment with ZDV and ddI did not result in loss of hearing, even after taking into account noise exposure, immune status and age. The results of this prospective pilot study do not support the notion that treatment with nucleoside antiretrovirals damages hearing.
Assessment of routine surveillance data as a tool to investigate measles outbreaks in Mozambique
Authors: Jani Jagrati V , Jani Ilesh V , Araújo Carolina , Sahay Sundeep , Barreto Jorge , Bjune Gunnar
Published: February 2006

Background

Measles remains a major public health problem in Mozambique despite significant efforts to control the disease. Currently, health authorities base their outbreak control on data from the routine surveillance system while vaccine coverage and efficacy are calculated based on mathematical projections of the target population. The aim of this work was to assess the quality of the measles reporting system during two outbreaks that occurred in Maputo City (1998) and in Manica Province (2002).

Methods

Retrospectively, we collected data from the routine surveillance system, i.e. register books at health facilities and weekly provincial and national epidemiological reports. To test whether the provinces registered an outbreak, the distribution of measles cases was compared to an endemic level established based on cases reported in previous years.

Results

There was a significant under-notification of measles cases from the health facilities to the province and national level. Register books, the primary sources of information for the measles surveillance system, were found to be incomplete for two main variables: "age" and "vaccination status".

Conclusion

The Mozambican surveillance system is based on poor quality records, receives the notification of only a fraction of the total number of measles in the country and may result in failures do detect epidemics. The measles reporting system does not provide the data needed by Expanded Program on Immunisation managers to make evidence-based decisions, nor does it allow in-depth analysis to monitor measles epidemiology in the country. The progress of Mozambique to the next stage of measles elimination will require an improvement of the routine surveillance system and a stronger Health Information System.
Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in Sweden 2000–2003, increasing incidence and regional differences
Authors: Stenhem Mikael , Örtqvist Åke , Ringberg Håkan , Larsson Leif , Olsson-Liljequist Barbro , Hæggman Sara , Ekdahl Karl ,   The Swedish Study Group on MRSA Epidemiology
Published: February 2006

Background

The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) has gradually become more frequent in most countries of the world. Sweden has remained one of few exceptions to the high occurrence of MRSA in many other countries. During the late 1990s, Sweden experienced a large health-care associated outbreak which with resolute efforts was overcome. Subsequently, MRSA was made a notifiable diagnosis in Sweden in 2000.

Methods

From the start of being a notifiable disease in January 2000, the Swedish Institute for Infectious Disease Control (SMI) initiated an active surveillance of MRSA.

Results

The number of reported MRSA-cases in Sweden increased from 325 cases in 2000 to 544 in 2003, corresponding to an overall increase in incidence from 3.7 to 6.1 per 100000 inhabitants. Twenty five per cent of the cases were infected abroad. The domestic cases were predominantly found through cultures taken on clinical indication and the cases infected abroad through screening. There were considerable regional differences in MRSA-incidence and age-distribution of cases.

Conclusion

The MRSA incidence in Sweden increased over the years 2000–2003. Sweden now poises on the rim of the same development that was seen in the United Kingdom some ten years ago. A quarter of the cases were infected abroad, reflecting that international transmission is now increasingly important in a low-endemic setting. To remain in this favourable situation, stepped up measures will be needed, to identify imported cases, to control domestic outbreaks and to prevent transmission within the health-care sector.
Clarithromycin is an effective immunomodulator when administered late in experimental pyelonephritis by multidrug-resistant Pseudomonas aeruginosa
Authors: Giamarellos-Bourboulis Evangelos J , Antonopoulou Anastasia , Raftogiannis Maria , Koutoukas Pantelis , Tsaganos Thomas , Tziortzioti Vassiliki , Panagou Charalambos , Adamis Theodoros , Giamarellou Helen
Published: February 2006

Background

To apply clarithromycin as an immunomodulatory treatment in experimental urosepsis by multidrug-resistant Pseudomonas aeruginosa.

Methods

Acute pyelonephritis was induced in 40 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of sepsis in four groups: A, controls; B, intravenous clarithromycin; C, amikacin; and D, both agents. Survival and vital signs were recorded; blood was sampled for culture and estimation of pro-inflammatory mediators; monocytes were isolated for determination of apoptotic rate and ex vivo TNFα secretion. Quantitative cultures and biopsies of organs were performed after death.

Results

Increased rectal temperature and oxygen saturation were found in groups B and D compared to A and C. Mean survival of groups A, B, C and D was 2.65, 7.15, 4.25 and 8.70 days respectively. No differences were noted between groups concerning bacterial load in blood and tissues and serum endotoxins. Serum MDA and total caspase-3 activity of monocytes of group D decreased following treatment compared to other groups. Negative correlation was detected between cytoplasmic caspase-3 and ex vivo secretion of TNFα of blood monocytes of group A; similar correlation was not found for any other group. Pathology scores of liver and lung of group B were lower than group A.

Conclusion

Clarithromycin administered late in experimental urosepsis by multidrug-resistant P. aeruginosa prolonged survival and ameliorated clinical findings. Its effect is probably attributed to immunomodulatory intervention on blood monocytes.
The effects of nocturnal hemodialysis compared to conventional hemodialysis on change in left ventricular mass: Rationale and study design of a randomized controlled pilot study
Authors: Walsh Michael , Manns Braden J , Klarenbach Scott , Quinn Robert , Tonelli Marcello , Culleton Bruce F
Published: February 2006

Background

Nocturnal hemodialysis (NHD) is an alternative to conventional three times per week hemodialysis (CvHD) and has been reported to improve several health outcomes. To date, no randomized controlled trial (RCT) has compared NHD and CvHD. We have undertaken a multi-center RCT in hemodialysis patients comparing the effect of NHD to CvHD on left ventricular (LV) mass, as measured by cardiac magnetic resonance imaging (cMR).

Methodology/design

All patients in Alberta, Canada, expressing an interest in performing NHD are eligible for the study. Patients enrolled in the study will be randomized to either NHD or CvHD for a six month period. All patients will have a full clinical assessment, including collection of biochemical and cMR data at baseline and at 6 months. Both groups of patients will be monitored biweekly to optimize blood pressure (BP) to a goal of <130/80 mmHg post-dialysis using a predefined BP management protocol. The primary outcome is change in LV mass, a surrogate marker for cardiac mortality, measured at baseline and 6 months. The high sensitivity and reproducibility of cMR facilitates reduction of the required sample size and the time needed between measures compared with echocardiography. Secondary outcomes include BP control, anemia, mineral metabolism, health-related quality of life, and costs.

Discussion

To our knowledge, this study will be the first RCT evaluating health outcomes in NHD. The impact of NHD on LV mass represents a clinically important outcome which will further elucidate the potential benefits of NHD and guide future clinical endpoint studies.
Frequency and severity of myocardial perfusion abnormalities using Tc-99m MIBI SPECT in cardiac syndrome X
Authors: Saghari Mohsen , Assadi Majid , Eftekhari Mohammad , Yaghoubi Mohammad , Fard-Esfahani Armaghan , Malekzadeh Jan-Mohammad , Sichani Babak Fallhi , Beiki Davood , Takavar Abbas
Published: February 2006

Background

Cardiac syndrome X is defined by a typical angina pectoris with normal or near normal (stenosis <40%) coronary angiogram with or without electrocardiogram (ECG) change or atypical angina pectoris with normal or near normal coronary angiogram plus a positive none-invasive test (exercise tolerance test or myocardial perfusion scan) with or without ECG change. Studies with myocardial perfusion imaging on this syndrome have indicated some abnormal perfusion scan. We evaluated the role of myocardial perfusion imaging (MPI) and also the severity and extent of perfusion abnormality using Tc-99m MIBI Single Photon Emission Computed Tomography (SPECT) in these patients.

Methods

The study group consisted of 36 patients with cardiac syndrome X. The semiquantitative perfusion analysis was performed using exercise Tc-99m MIBI SPECT. The MPI results were analyzed by the number, location and severity of perfusion defects.

Results

Abnormal perfusion defects were detected in 13 (36.10%) cases, while the remaining 23 (63.90%) had normal cardiac imaging. Five of 13 (38.4%) abnormal studies showed multiple perfusion defects. The defects were localized in the apex in 3, apical segments in 4, midventricular segments in 12 and basal segments in 6 cases. Fourteen (56%) of all abnormal segments revealed mild, 7(28%) moderate and 4 (16%) severe reduction of tracer uptake. No fixed defects were identified. The vessel territories were approximately the same in all subjects. The Exercise treadmill test (ETT) was positive in 25(69%) and negative in 11(30%) patients. There was no consistent pattern as related to the extent of MPI defects or exercise test results.

Conclusion

Our study suggests that multiple perfusion abnormalities with different levels of severity are common in cardiac syndrome X, with more than 30 % of these patients having at least one abnormal perfusion segment. Our findings suggest that in these patients microvascular angina is probably more common than is generally believed.
HFE H63D mutation frequency shows an increase in Turkish women with breast cancer
Authors: Gunel-Ozcan Aysen , Alyılmaz-Bekmez Sibel , Guler Emine Nilufer , Guc Dicle
Published: February 2006

Background

The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls.

Methods

Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP.

Results

All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176) in the breast cancer patients, and 14% (28/200) in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers (P = 0.02).

Conclusion

Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios (odds ratio = 2.05) computed in this study suggest that H63D has a positive association with breast cancer.
Selection, affinity maturation, and characterization of a human scFv antibody against CEA protein
Authors: Pavoni Emiliano , Flego Michela , Dupuis Maria Luisa , Barca Stefano , Petronzelli Fiorella , Anastasi Anna Maria , D'Alessio Valeria , Pelliccia Angela , Vaccaro Paola , Monteriù Giorgia , Ascione Alessandro , De Santis Rita , Felici Franco , Cianfriglia Maurizio , Minenkova Olga
Published: February 2006

Background

CEA is a tumor-associated antigen abundantly expressed on several cancer types, including those naturally refractory to chemotherapy. The selection and characterization of human anti-CEA single-chain antibody fragments (scFv) is a first step toward the construction of new anticancer monoclonal antibodies designed for optimal blood clearance and tumor penetration.

Methods

The human MA39 scFv, selected for its ability to recognize a CEA epitope expressed on human colon carcinomas, was first isolated from a large semi-synthetic ETH-2 antibody phage library, panned on human purified CEA protein. Subsequently, byin vitromutagenesis of a gene encoding for the scFv MA39, a new library was established, and new scFv antibodies with improved affinity towards the CEA cognate epitope were selected and characterized.

Results

The scFv MA39 antibody was affinity-maturated byin vitromutagenesis and the new scFv clone, E8, was isolated, typed for CEA family member recognition and its CEACAM1, 3 and 5 shared epitope characterized for expression in a large panel of human normal and tumor tissues and cells.

Conclusion

The binding affinity of the scFv E8 is in a range for efficient,in vivo, antigen capture in tumor cells expressing a shared epitope of the CEACAM1, 3 and 5 proteins. This new immunoreagent meets all criteria for a potential anticancer compound: it is human, hence poorly or not at all immunogenic, and it binds selectively and with good affinity to the CEA epitope expressed by metastatic melanoma and colon and lung carcinomas. Furthermore, its small molecular size should provide for efficient tissue penetration, yet give rapid plasma clearance.
Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancer
Authors: Santini Daniele , Vincenzi Bruno , Schiavon Gaia , La Cesa Annalisa , Gasparro Simona , Vincenzi Angelo , Tonini Giuseppe
Published: February 2006

Background

The combination of capecitabine and gemcitabine at Fixed Dose Rate (FDR) has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. FDR gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. The goals of this phase I study were to determine the maximum-tolerated dose (MTD) of chronomodulated capecitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT), the safety profile of this way of administration.

Methods

Patients with advanced solid tumours who had failed to response to standard therapy or for whom no standard therapy was available were elegible for this study. Capecitabine was administered orally according to following schedule: 1/4 of dose at 8:00 a.m.; 1/4 of dose at 6:00 p.m. and 1/2 of dose at 11:00 p.m. each day for 14 consecutive days, followed by a 7-day rest period.

Results

All 27 patients enrolled onto the study were assessable for toxicity. The most common toxicities during the first two cycles of chemotherapy were fatigue, diarrhoea and hand foot syndrome (HFS). Only one out of the nine patients treated at capecitabine dose of 2,750 mg/m2 met protocol-specified DLT criteria (fatigue grade 4). However, at these doses the majority of cycles of therapy were delivered without dose reduction or delay. No other episodes of DLT were observed at the same dose steps and at the lower dose steps of capecitabine (1,500/1,750/2,000/2,250/2,500 mg/m2). The dose of 2,750 mg/m2 is recommended for further study. Tumor responses were observed in patients with metastatic breast and colorectal cancer.

Conclusion

High doses of chronomodulated capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies.
The knowledge and attitudes of breast self-examination and mammography in a group of women in a rural area in western Turkey
Authors: Dündar Pınar Erbay , Özmen Dilek , Öztürk Beyhan , Haspolat Gökçe , Akyıldız Filiz , Çoban Sümeyra , Çakıroğlu Gamze
Published: February 2006

Background

Breast cancer appears to be a disease of both the developing and developed worlds. Among Turkish women, breast cancer is the second leading cause of cancer-related deaths. The aims of this cross-sectional study were to determine levels of knowledge about breast cancer and to evaluate health beliefs concerning the model that promotes breast self- examination (BSE) and mammography in a group of women aged 20–64 in a rural area of western Turkey.

Methods

244 women were recruited by means of cluster sampling in this study. The questionnaire consisted of sociodemographic variables, a risk factors and signs of breast cancer form and the adapted version of Champion's Health Belief Model Scale (CHBMS). Bivariate correlation analysis, Chi square test, Mann-Whitney U test and logistic regression analysis were performed throughout the data analysis.

Results

The mean age of the women was 37.7 ± 13.7. 49.2% of women were primary school graduates, 67.6% were married. Although 76.6% of the women in this study reported that they had heard or read about breast cancer, our study revealed that only 56.1% of them had sufficient knowledge of breast cancer, half of whom had acquired the information from health professionals.

Level of breast cancer knowledge was the only variable significantly associated with the BSE and mammography practice (p = 0.011, p = 0.007). BSE performers among the study group were more likely to be women who exhibited higher confidence and perceived greater benefits from BSE practice, and those who perceived fewer barriers to BSE performance and possessed knowledge of breast cancer.

Conclusion

By using the CHBMS constructs for assessment, primary health care providers can more easily understand the beliefs that influence women's BSE and mammography practice.
Serum homocysteine, vitamin B 12 and folic acid levels in different types of glaucoma
Authors: Cumurcu Tongabay , Sahin Semsettin , Aydin Erdinc
Published: February 2006

Background

This study was performed to compare levels of serum homocysteine (Hcy), vitamin B12 and folic acid in patients with primary open-angle glaucoma (POAG), pseudoexfoliative glaucoma (PEXG), normotensive glaucoma (NTG) and healthy controls.

Methods

Twentyfive patients with POAG, 24 with PEXG, and 18 with NTG, along with 19 control healthy subjects were included this prospective study. Levels of serum Hcy were measured using immunoassay, and those of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay.

Results

The mean Hcy concentration in the PEXG group was significantly higher (P < 0.001) as compared to the other groups. There were no significant differences with respect to the mean Hcy concentrations among other groups (P > 0.05). There were no statistical differences in serum vitamin B12 levels among POAG, PEXG, NTG and control subjects (P > 0.05).

The mean serum folic acid level was significantly lower in the subjects with PEXG (P < 0.009). However, the mean folic acid concentrations among the other groups did not differ significantly (P > 0.05).

Conclusion

Elevated levels of Hcy in PEXG may explain the role of endothelial dysfunction among patients with PEXG.
Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia
Authors: Ascher-Svanum Haya , Zhu Baojin , Faries Douglas , Landbloom Ron , Swartz Marvin , Swanson Jeff
Published: February 2006

Background

There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia.

Methods

We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone) or oral typical antipsychotics (low, medium, or high potency) were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods). To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a) only 1 medication episode for each patient, the one with which the patient was treated first, and (b) all medication episodes, including those simultaneously initiated on more than 1 antipsychotic.

Results

Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days) compared to typical antipsychotics (N = 534, 197.2 days; p < .01), and longer on atypicals compared to typicals of high potency (N = 320, 187.5 days; p < .01), medium potency (N = 140, 213.5 days; p < .01), and low potency (N = 74, 208.7 days; p < .01). Among the atypicals, only clozapine, olanzapine, and risperidone had significantly longer time to all-cause medication discontinuation compared to typicals, regardless of potency level, and compared to haloperidol with prophylactic anticholinergic treatment. When compared to perphenazine, a medium-potency typical antipsychotic, only clozapine and olanzapine had a consistently and significantly longer time to all-cause medication discontinuation. Results were confirmed by sensitivity analyses.

Conclusion

In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium-potency typical antipsychotic.
Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls
Authors: Rapeli Pekka , Kivisaari Reetta , Autti Taina , Kähkönen Seppo , Puuskari Varpu , Jokela Olga , Kalska Hely
Published: February 2006

Background

Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover.

Methods

Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed.

Results

Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal.

Conclusion

The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient.
PRISM (Program of Resources, Information and Support for Mothers): a community-randomised trial to reduce depression and improve women's physical health six months after birth [ISRCTN03464021]
Authors: Lumley Judith , Watson Lyndsey , Small Rhonda , Brown Stephanie , Mitchell Creina , Gunn Jane
Published: February 2006

Background

In the year after birth one in six women has a depressive illness, 94% experience at least one major health problem (e.g. back pain, perineal pain, mastitis, urinary or faecal incontinence), 26% experience sexual problems and almost 20% have relationship problems with partners. Women with depression report less practical and emotional support from partners, less social support, more negative life events, and poorer physical health and see factors contributing to depression as lack of support, isolation, exhaustion and physical health problems. Fewer than one in three seek help in primary care despite frequent health care contacts.

Methods

Primary care and community-based strategies embedded in existing services were implemented in a cluster-randomised trial involving 16 rural and metropolitan communities, pair-matched, within the State of Victoria, Australia. Intervention areas were also provided with a community development officer for two years. The primary aim was to reduce the relative risk of depression by 20% in mothers six months after birth and to improve their physical health. Primary outcomes were obtained by postal questionnaires. The analysis was by intention-to-treat, unmatched, adjusting for the correlated nature of the data.

Results

6,248 of 10,144 women (61.6%) in the intervention arm and 5057/ 8,411 (60.1%) in the comparison arm responded at six months, and there was no imbalance in major covariates between the two arms. Women's mental health scores were not significantly different in the intervention arm and the comparison arm (MCS mean score 45.98 and 46.30, mean EPDS score 6.91 and 6.82, EPDS ≥ 13 ('probable depression') 15.7% vs. 14.9%, Odds ratioadj1.06 (95%CI 0.91–1.24). Women's physical health scores were not significantly different in intervention and comparison arms (PCS mean scores 52.86 and 52.88).

Conclusion

The combined community and primary care interventions were not effective in reducing depression, or in improving the physical health of mothers six months after birth.
Risk of ischaemic heart disease and acute myocardial infarction in a Spanish population: observational prospective study in a primary-care setting
Authors: Marín Alejandro , Medrano María José , González José , Pintado Héctor , Compaired Vicente , Bárcena Mario , Fustero María Victoria , Tisaire Javier , Cucalón José M , Martín Aurelio , Boix Raquel , Hernansanz Francisco , Bueno José
Published: February 2006

Background

Ischaemic heart disease is a global priority of health-care policy, because of its social repercussions and its impact on the health-care system. Yet there is little information on coronary morbidity in Spain and on the effect of the principal risk factors on risk of coronary heart disease. The objective of this study is to describe the epidemiology of coronary disease (incidence, mortality and its association with cardiovascular risk factors) using the information gathered by primary care practitioners on cardiovascular health of their population.

Methods

A prospective study was designed. Eight primary-care centres participated, each contributing to the constitution of the cohort with the entire population covered by the centre. A total of 6124 men and women aged over 25 years and free of cardiovascular disease agreed to participate and were thus enrolled and followed-up, with all fatal and non-fatal coronary disease episodes being registered during a 5-year period. Repeated measurements were collected on smoking, blood pressure, weight and height, serum total cholesterol, high-density and low-density lipoproteins and fasting glucose. Rates were calculated for acute myocardial infarction and ischaemic heart disease. Associations between cardiovascular risk factors and coronary disease-free survival were evaluated using Kaplan-Meier and Cox regression analyses.

Results

Mean age at recruitment was 51.6 ± 15, with 24% of patients being over 65. At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers. During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate analyses. After multivariate adjustments, age, male gender, smoking, high total cholesterol, high HDL/LDL ratio, diabetes and overweight remained strongly associated with risk. Relative risks for hypertension in women and for diabetes in men did not reach statistical significance.

Conclusion

Despite high prevalence of vascular risk factors, incidence rates were lower than those reported for other countries and other periods, but similar to those reported in the few population-based studies in Spain. Effect measures of vascular risk factors were mainly as reported worldwide and support the hypothesis that protective factors not considered in this study must exist as to explain low rates. This study shows the feasibility of conducting epidemiological cohort studies in primary-care settings.
Seasonal patterns of suicides over the period of socio-economic transition in Lithuania
Authors: Kalediene Ramune , Starkuviene Skirmante , Petrauskiene Jadvyga
Published: February 2006

Background

In Lithuania, suicides are a grave public health problem, requiring more extensive investigation. The aim of the study was to assess the seasonal variations of suicides in Lithuania throughout the years 1993–2002, describing patterns by gender, age and method of suicide.

Methods

The study material consisted of all registered suicides (n = 16,147) committed throughout 1993–2002 in Lithuania. Smoothed trends were inspected. The seasonal effect was explored using monthly ratio statistics and spectral analysis.

Results

Suicides in Lithuania have a distinct annual rhythm with peaks in summer and troughs in December. The December frequencies fell by more than 23% in men and 30% in women, while June peak reached nearly 23% in men and July peak exceeded 29% in women, compare with the average levels, (p < 0.05). Hanging was the most common method of suicide both in men and women comprising up to 90% among all suicides in 1998–2002. Among different methods, only hanging suicides showed significant seasonal variations, especially in men. The seasonal amplitude has decreased over time.

Conclusion

Substantial seasonal variations in suicides were associated with a high proportion of hanging. Extremely high suicide rates in Lithuania require further extensive studies and urgent preventive programs, taking into account the suggestions of this survey.