bluuebunny/crossref_metadata_2025 huggingface dataset:
Persons With Varicose Veins Have a High Subsequent Incidence of Arterial Disease: A Population-Based Study in Tampere, Finland
Authors: Mäkivaara Liisa A. , Ahti Tiina M. , Luukkaala Tiina , Hakama Matti , Laurikka Jari O.
Published: January 2008

The aim of this population research was to find out the risk of arterial disease (defined as angina pectoris, myocardial infarction, peripheral occlusive arterial disease, and cerebrovascular disease) and hypertension in persons with varicose veins. A 5-year follow-up study was conducted in Tampere, Finland. A validated questionnaire was used in 3 middle-aged cohorts (40, 50, and 60 year olds) in a general population of 6874. In the follow-up study, 71% (n = 4903) replied. The incidence of arterial disease and hypertension was studied in those with varicose veins and those without at the entry to the study. During the follow-up, new arterial disease occurred significantly more often in individuals with varicose veins. The incidence odds ratio was 2.0 (95% confidence interval, 1.5-2.7; n = 3032), but the incidence odds ratio of new hypertension was 1.0 (95% confidence interval, 0.8-1.3; n = 2915). Varicose veins are a risk indicator of arterial disease but not of hypertension. Varicose veins likely do not cause arterial disease, but they may have common causes that, however, are not related with hypertension.
Outcomes of Intra-arterial Thrombolysis for Acute Limb Ischemia
Authors: Amonkar S.J. , Cleanthis M. , Nice Colin , Timmons Grace , Mudawi A.M. , Ashour H.Y. , Bhattacharya V.
Published: January 2008

Intra-arterial thrombolysis is an alternative treatment to surgery for acute limb ischemia. We report our own experiences by retrospectively assessing initial and long-term outcomes using this strategy. Patients (n = 48; 50 events) underwent thrombolysis according to our protocol (64.6% male, median age 68.5 years). Using thrombolysis as an initial treatment strategy, overall limb survival on index admission was 84%. Of this group who had successful limb salvage, 76% was attributable to thrombolysis alone, and 24% had limb salvage attributable to subsequent surgery after failed thrombolysis or anticoagulation. Significant complications occurred in 8% of cases, and no deaths were attributed to thrombolysis. Patients alive at 6 and 24 months after index admission who had limb salvage attributable to thrombolysis alone had limb survival rates of 89% and 82%, respectively. The majority of these patients had not required subsequent secondary procedures to maintain limb survival. Thrombolysis is an acceptable and less invasive treatment of acute limb ischemia, with many patients not needing subsequent surgery.
Sympathetic Skin Response and RR Interval Variation in Patients With Cardiac Syndrome X
Authors: Altun Armagan , Turgut Nilda , Tatli Ersan , Ugur-Altun Betul , Balci Kemal
Published: January 2008

Sympathetic skin response (SSR) and R-R interval variation (RRIV) are noninvasive electrophysiological tests used in the assessment of sympathetic and parasympathetic nervous system function, respectively. Cardiac syndrome X (CSX) is usually diagnosed in the presence of typical angina pectoris, a positive response to exercise testing, and normal-appearing coronary angiograms without spasm induced by hyperventilation or ergonovine. Alterations of autonomic nervous system control of cardiac function have been described in CSX. The aim of the study was to investigate autonomic nervous system function in patients with CSX. Nine patients with CSX (2 men, 7 women) and healthy controls (11 men, 19 women) were included in the study. SSRs were recorded from palm of hands by stimulation of the median nerve. RRIV recordings were taken from precordium during both rest position (R%) and deep inspiration of 6 times per minute (D%). In addition D% — R% and D%/R% values were calculated. SSR amplitude of CSX was lower than in controls (3.64 ±4.78 vs 6.36 ±3.4 mV, p = 0.017). There was no difference between groups for SSR latency values (CSX: 1,366 ±99; controls: 1,383 ±85 msec). Also, R% (CSX: 13.04 ±6.3; controls: 12.92 ±3.91) and D% (CSX: 16.63 ±8.88; controls: 21.43 ±7.3) values were similar in the 2 groups. However, D% — R% (CSX: 3.59 ±10.11; controls: 8.51 ±7.01) and D%/R% (CSX: 1.45 ±0.93; controls: 1.78 ±0.69) values were slightly lower in patients with CSX but were not statistically significant. A linear correlation was found between SSR amplitude and D%/R% (r = 0.336, p = 0.036). The authors conclude that, among patients with CSX, there are alterations of autonomic nervous control of skin as well as of other organs (ie, heart). SSR and RRIV testing can be done easily in the neurophysiology laboratory to assess the sympathetic and parasympathetic system, respectively.
Identifying Cardiovascular Risk Factors in a Patient Population With Coronary Artery Ectasia
Authors: Saglam Mustafa , Karakaya Osman , Barutcu Irfan , Esen Ali Metin , Turkmen Muhsin , Kargin Ramazan , Esen Ozlem , Ozdemir Nihal , Kaymaz Cihangir
Published: January 2008

Coronary artery ectasia (CAE) is frequently considered as a form of coronary artery disease. Cardiovascular risk factors were determined in a patient population with CAE. The 51 patients with isolated CAE (group 1), 61 patients with CAE coexisting with significant coronary stenosis (group 2), and 62 subjects with significant coronary stenosis (group 3) were included in the study, and the distribution of cardiovascular risk factors was compared. Thirty of 51 patients with isolated CAE had presented with typical angina pectoris, 8 patients with unstable angina pectoris, and 13 patients had atypical chest pain or palpitation. The 21 of 51 patients with isolated CAE had definitive positive treadmill exercise test results. Positive family history was similar in each group. The history of smoking was similar in group 1 and group 2 but higher than group 3. Frequency of hypertension was similar in group 1 and group 2 but higher than that in group 3. Frequency of diabetes mellitus was similar in group 1 and group 2 but lower than group 3. Plasma lipid levels and the number of patients with lipid disturbances were also similar in each group. In addition, C-reactive protein (CRP) levels were above the normal limits and there was no difference among groups with respect to plasma CRP levels. CAE appears to be associated with traditional cardiovascular risk factors such as hypertension, smoking, and hyperlipidemia. In addition, elevated CRP level in patients with CAE may suggest the role of inflammatory process in development of CAE.
Teachers' Perceptions of Connections and Disconnects Between Their Alternative Preparation and Teaching in Urban Classrooms
Authors: Junor Clarke Pier A. , Thomas Christine D.
Published: January 2008

This study is part of a larger ongoing research study on the impact of alternatively prepared teachers in urban mathematics classrooms. This report focuses on examining alternatively prepared high school mathematics teachers' perceptions of the connections and disconnects of their program experiences and the realities of the urban classrooms. Using phenomenology as the framework, a storytelling approach is employed to capture the perceptions of the teachers' experiences. This approach allows the teachers to convey their understanding of the relationship between their alternative preparation and teaching in urban classrooms. Five common themes are evident in their stories.
Survey of specialist palliative care services for noncancer patients in Ireland and perceived barriers
Authors: O'Leary Norma , Tiernan Eoin
Published: January 2008

Background: Specialist palliative care (SPC) services in Ireland are well developed by international standards. However, standardized information on all patients of SPC services is not collected so the proportion of patients seen with a noncancer diagnosis is just an estimate at 5%. Aims: To describe Irish SPC services' provision for, and attitudes to noncancer patients. Method: Postal questionnaire of clinical managers of all SPC services listed in the directory of SPC services in Ireland, September 2005. Results: Sixty-five questionnaires were returned representing a 100% response rate. Twenty four percent (n = 15) of services limited availability for noncancer patients in some way. Of those services available for noncancer patients, the type of care provided to them was the same as for cancer patients in 81% of services (n = 50). The percentage of all patients seen in 2004 who had a noncancer diagnosis was 7.21%. Only 68% (n = 42) of services had a written referral policy. The top three perceived barriers by SPC service providers were the unpredictable noncancer disease trajectory (mean intensity = 6.77), the resultant difficulties with developing referral criteria (mean intensity = 6.38) and the lack of noncancer disease specific expertise (mean intensity = 5.96). Discussion: There is a mismatch between availability of palliative care services for noncancer patients and uptake. The noncancer disease trajectory continues to be considered a barrier to care. Imaginative models of care need to be developed that are not prognosis based. Palliative Medicine 2008; 22: 77—83
Cancer specialists' palliative care referral practices and perceptions: results of a national survey
Authors: Johnson C.E. , Girgis A. , Paul C.L. , Currow D.C.
Published: January 2008

Purpose : Cancer specialists can facilitate timely and appropriate access to specialized palliative care (SPC) services. To better match patients' needs with access to SPC services, we must understand factors associated with referral. This study aimed to investigate cancer specialists' referral practices, perceptions of, barriers to and triggers for referral of people with advanced cancer to SPC services.Method : A self-report questionnaire was mailed to all oncologists, clinical haematologists, respiratory physicians and colorectal surgeons in Australia (N = 1713).Results : Out of 699 specialists who participated, 48% reported referring > 60% of patients to SPC services. Most frequent reasons for referral were: the future need for symptom control, the presence of a terminal illness or uncontrolled physical symptoms. Psychosocial issues rarely triggered referral. Main reasons reported for not referring included: ability to manage patients' symptoms; the absence of symptoms or rapid deterioration. Significant predictors of referral (P < 0.05) included: being female; > 10 years of practice in the speciality; agreeing all people with advanced cancer need referral, referral for the purpose of multidisciplinary management and having SPC services available.Conclusions : Specialists mainly refer people with advanced cancer for symptom-related reasons. Measures are needed to encourage ongoing needs-based assessments, especially of emotional, cultural and spiritual issues. Palliative Medicine 2008;22: 51—57
Fatigue in palliative care patients — an EAPC approach
Authors: Radbruch Lukas , Strasser Florian , Elsner Frank , Gonçalves Jose Ferraz , Løge Jon , Kaasa Stein , Nauck Friedemann , Stone Patrick ,   the Research Steering Committee of the European Association for Palliative Care (EAPC)
Published: January 2008

Fatigue is one of the most frequent symptoms in palliative care patients, reported in .80% of cancer patients and in up to 99% of patients following radio- or chemotherapy. Fatigue also plays a major role in palliative care for noncancer patients, with large percentages of patients with HIV, multiple sclerosis, chronic obstructive pulmonary disease or heart failure reporting fatigue.This paper presents the position of an expert working group of the European Association for Palliative Care (EAPC), evaluating the available evidence on diagnosis and treatment of fatigue in palliative care patients and providing the basis for future discussions. As the expert group feels that culture and language influence the approach to fatigue in different European countries, a focus was on cultural issues in the assessment and treatment of fatigue in palliative care.

As a working definition, fatigue was defined as a subjective feeling of tiredness, weakness or lack of energy. Qualitative differences between fatigue in cancer patients and in healthy controls have been proposed, but these differences seem to be only an expression of the overwhelming intensity of cancer-related fatigue.

The pathophysiology of fatigue in palliative care patients is not fully understood. For a systematic approach, primary fatigue, most probably related to high load of proinflammatory cytokines and secondary fatigue from concurrent syndromes and comorbidities may be differentiated. Fatigue is generally recognized as a multidimensional construct, with a physical and cognitive dimension acknowledged by all authors. As fatigue is an inherent word only in the English and French language, but not in other European languages, screening for fatigue should include questions on weakness as a paraphrase for the physical dimension and on tiredness as a paraphrase for the cognitive dimension. Treatment of fatigue should include causal interventions for secondary fatigue and symptomatic treatment with pharmacological and nonpharmacological interventions. Strong evidence has been accumulated that aerobic exercise will reduce fatigue levels in cancer survivors and patients receiving cancer treatment.

In the final stage of life, fatigue may provide protection and shielding from suffering for the patient and thus treatment may be detrimental. Identification of the time point, where treatment of fatigue is no longer indicated is important to alleviate distress at the end of life. Palliative Medicine 2008;22: 13—22.
The Effect of Glenohumeral Position on the Shoulder after Traumatic Anterior Dislocation
Authors: Limpisvasti Orr , Yang Bruce Y. , Hosseinzadeh Pooya , Leba Thu-Ba , Tibone James E. , Lee Thay Q.
Published: January 2008

Background

Previous cadaveric studies suggest that positioning the shoulder in an externally rotated position reduces displaced Bankart lesions through a coaptation effect.

Hypothesis

We hypothesized that positioning the glenohumeral joint in an externally rotated position creates contact pressure between the subscapularis and the anterior labrum.

Study Design

Descriptive laboratory study

Methods

Eight cadaveric shoulders were used. Contact pressure between the subscapularis and labrum was measured in varying glenohumeral positions using a Tekscan pressure monitor. The position of the anterior band of the inferior glenohumeral ligament was also digitized in those positions. All shoulders were tested in the intact condition, following a surgically created Bankart lesion and following anterior shoulder dislocation. These conditions were also verified by measuring glenohumeral translation and joint forces.

Results

For all 8 specimens, the contact pressure between the subscapularis and the anterior labrum was negligible with the humerus externally rotated up to 90° at all abduction angles in intact, surgically created Bankart, and dislocated specimens. There were several glenohumeral positions where the anterior band of the inferior glenohumeral ligament strain in the intact specimens was similar to the postdislocation condition, that is, no statistically significant difference between intact and dislocated specimens. These positions included 30° of glenohumeral abduction with external rotation between 0° and 60°, as well as 45° of abduction with external rotation of 0° and 60°. The anterior band of the inferior glenohumeral ligament strain and glenohumeral anterior-posterior translation measurements revealed that the surgically created Bankart lesion does not simulate the conditions after anterior dislocation of the shoulder.

Conclusion

External rotation of the shoulder does not create contact pressure between the subscapularis and the anterior labrum before or after anterior dislocation.

Clinical Relevance

The efficacy of external rotation immobilization after anterior-inferior shoulder dislocation is not likely to be related to coaptation of the Bankart lesion by the subscapularis.
Balancing Between Normality and Social Death: Black, Rural, South African Women Coping With HIV/AIDS
Authors: Dageid Wenche , Duckert Fanny
Published: January 2008

The millions of people living with HIV/AIDS are in urgent need of effective care and support interventions. Such interventions should take people's reported needs, coping strategies, and context into account. Usually, active problem-focused coping strategies have been encouraged because they are considered to be more beneficial than passive emotion-focused strategies. However, this may not be the case in the South African context. This study was based on in-depth interviews with Black, rural, South African women about their coping strategies. The overriding aim of coping was to solve the tasks of physical, psychological, and social survival. Strategies involving avoidance of, escaping from, or minimizing HIV/AIDS and its accompanying emotional distress were predominant. We argue that such strategies could be adaptive in a society with scarce resources and marked by gender inequalities. Our findings suggest that care and support interventions should be sensitive to culture and context, should be holistic and participatory, and should include income generation and child care services.
Using Analgesics as Tools: Young Women's Treatment for Headache
Authors: Hansen Dana Lee , Hansen Ebba Holme , Holstein Bjørn E.
Published: January 2008

In this study, the authors explore the context surrounding young women's use of analgesics to deal with headache. In-depth interviews were conducted with 20 young women between the ages of 16 and 20 in Copenhagen, Denmark. Interviews focused on the young women's experiences with medications within the context of their everyday lives. The central elements in the participants' accounts emerged via a phenomenological approach. Analysis revealed that participants attributed headache to stressful conditions in their everyday lives. Analgesic use in treating headache was found to serve highly valued performance- and participation-related functions. Accordingly, analgesics were employed as tools to reach these aims. The threshold for turning to analgesics varied across situations and among participants. Some relied heavily on analgesics, whereas others had success with non-medical strategies. This study's findings demonstrate a need for health education programs aimed at empowering young women to better manage headaches as well as everyday stress.
Perception of Bleeding as a Danger Sign During Pregnancy, Delivery, and the Postpartum Period in Rural Nepal
Authors: Matsuyama Akiko , Moji Kazuhiko
Published: January 2008

Many developing countries implement safe motherhood programs to tackle high maternal mortality rates. The approach requires recognition of the signs of emergency obstetric cases in order to facilitate immediate care seeking, followed by immediate medical care. Whether such signs are recognized in a timely manner at the community level is determined by how the community perceives health problems. We explore the local understanding of one danger sign—bleeding during pregnancy and at delivery—and the meaning attached to it. The study was conducted in the Kavrepalanchowk district of Nepal. Different qualitative methods were applied. The findings indicate that the community's perception of bleeding might be quite different from that of health professionals and that perceptions and meanings attached to bleeding vary depending on the actors in the family. They all have significant implications for what should be the focus of health education and who should be involved in promoting maternal health.
Women Living With a Spinal Cord Injury: Perceptions About Their Changed Bodies
Authors: Chau Lisa , Hegedus Lenke , Praamsma Monate , Smith Katey , Tsukada Michiko , Yoshida Karen , Renwick Rebecca
Published: January 2008

In this article we illuminate the narratives of women living with a spinal cord injury (SCI) with regard to (a) learning how to live with a changed body and (b) exploring the factors that influence how they feel toward their new bodies. An SCI produces immediate physical impairments resulting in a changed body, which can then have physical, emotional, and social consequences to these women. Through its focus on enhancing the body, physical therapy can help to promote a positive view of the self within the changed body. Our analysis of these women's experiences resulted in a fluid, three-phase framework of learning to live with a changed body that generally moves from (a) discomfort, to (b) moving toward comfort, to (c) comfort. Physical therapy can potentially influence the process of women's gaining comfort with their changed bodies following an SCI. The framework provides a basis for future research on adaptation following SCI.
Spiraling Between Qualitative and Quantitative Data on Women's Health Behaviors: A Double Helix Model for Mixed Methods
Authors: Mendlinger Sheryl , Cwikel Julie
Published: January 2008

A double helix spiral model is presented which demonstrates how to combine qualitative and quantitative methods of inquiry in an interactive fashion over time. Using findings on women's health behaviors (e.g., menstruation, breast-feeding, coping strategies), we show how qualitative and quantitative methods highlight the theory of knowledge acquisition in women's health decisions. A rich data set of 48 semistructured, in-depth ethnographic interviews with mother—daughter dyads from six ethnic groups (Israeli, European, North African, Former Soviet Union [FSU], American/Canadian, and Ethiopian), plus seven focus groups, provided the qualitative sources for analysis. This data set formed the basis of research questions used in a quantitative telephone survey of 302 Israeli women from the ages of 25 to 42 from four ethnic groups. We employed multiple cycles of data analysis from both data sets to produce a more detailed and multidimensional picture of women's health behavior decisions through a spiraling process.
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines
Authors: Hallek Michael , Cheson Bruce D. , Catovsky Daniel , Caligaris-Cappio Federico , Dighiero Guillaume , Döhner Hartmut , Hillmen Peter , Keating Michael J. , Montserrat Emili , Rai Kanti R. , Kipps Thomas J.
Published: January 2008

Standardized criteria for diagnosis and response assessment are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. Therefore, a National Cancer Institute–sponsored Working Group (NCI-WG) on chronic lymphocytic leukemia (CLL) published guidelines for the design and conduct of clinical trials for patients with CLL in 1988, which were updated in 1996. During the past decade, considerable progress has been achieved in defining new prognostic markers, diagnostic parameters, and treatment options. This prompted the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) to provide updated recommendations for the management of CLL in clinical trials and general practice.
Mutation of C/EBPα predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen
Authors: Hasemann Marie S. , Damgaard Inge , Schuster Mikkel B. , Theilgaard-Mönch Kim , Sørensen Annette B. , Mršić Alan , Krugers Thijs , Ylstra Bauke , Pedersen Finn S. , Nerlov Claus , Porse Bo T.
Published: January 2008

The CCAAT enhancer binding protein α (C/EBPα) is an important myeloid tumor suppressor that is frequently mutated in human acute myeloid leukemia (AML). We have previously shown that mice homozygous for the E2F repression–deficient CebpaBRM2 allele develop nonfatal AML with long latency and incomplete penetrance, suggesting that accumulation of secondary mutations is necessary for disease progression. Here, we use SRS19-6–driven retroviral insertional mutagenesis to compare the phenotypes of leukemias arising in Cebpa+/+, Cebpa+/BRM2, and CebpaBRM2/BRM2 mice, with respect to disease type, latency of tumor development, and identity of the retroviral insertion sites (RISs). Both Cebpa+/BRM2 and CebpaBRM2/BRM2 mice preferentially develop myeloid leukemias, but with differing latencies, thereby demonstrating the importance of gene dosage. Determination of RISs led to the identification of several novel candidate oncogenes, some of which may collaborate specifically with the E2F repression–deficient allele of Cebpa. Finally, we used an in silico pathway analysis approach to extract additional information from single RISs, leading to the identification of signaling pathways which were preferentially deregulated in a disease- and/or genotype-specific manner.
Inflammation induces hemorrhage in thrombocytopenia
Authors: Goerge Tobias , Ho-Tin-Noe Benoit , Carbo Carla , Benarafa Charaf , Remold-O'Donnell Eileen , Zhao Bing-Qiao , Cifuni Stephen M. , Wagner Denisa D.
Published: February 2008

The role of platelets in hemostasis is to produce a plug to arrest bleeding. During thrombocytopenia, spontaneous bleeding is seen in some patients but not in others; the reason for this is unknown. Here, we subjected thrombocytopenic mice to models of dermatitis, stroke, and lung inflammation. The mice showed massive hemorrhage that was limited to the area of inflammation and was not observed in uninflamed thrombocytopenic mice. Endotoxin-induced lung inflammation during thrombocytopenia triggered substantial intra-alveolar hemorrhage leading to profound anemia and respiratory distress. By imaging the cutaneous Arthus reaction through a skin window, we observed in real time the loss of vascular integrity and the kinetics of skin hemorrhage in thrombocytopenic mice. Bleeding—observed mostly from venules—occurred as early as 20 minutes after challenge, pointing to a continuous need for platelets to maintain vascular integrity in inflamed microcirculation. Inflammatory hemorrhage was not seen in genetically engineered mice lacking major platelet adhesion receptors or their activators (αIIbβ3, glycoprotein Ibα [GPIbα], GPVI, and calcium and diacylglycerol-regulated guanine nucleotide exchange factor I [CalDAG-GEFI]), thus indicating that firm platelet adhesion was not necessary for their supporting role. While platelets were previously shown to promote endothelial activation and recruitment of inflammatory cells, they also appear indispensable to maintain vascular integrity in inflamed tissue. Based on our observations, we propose that inflammation may cause life-threatening hemorrhage during thrombocytopenia.
High-throughput mammalian two-hybrid screening for protein-protein interactions using transfected cell arrays
Authors: Fiebitz Andrea , Nyarsik Lajos , Haendler Bernard , Hu Yu-Hui , Wagner Florian , Thamm Sabine , Lehrach Hans , Janitz Michal , Vanhecke Dominique
Published: February 2008

Background

Most of the biological processes rely on the formation of protein complexes. Investigation of protein-protein interactions (PPI) is therefore essential for understanding of cellular functions. It is advantageous to perform mammalian PPI analysis in mammalian cells because the expressed proteins can then be subjected to essential post-translational modifications. Until now mammalian two-hybrid assays have been performed on individual gene scale. We here describe a new and cost-effective method for the high-throughput detection of protein-protein interactions in mammalian cells that combines the advantages of mammalian two-hybrid systems with those of DNA microarrays.

Results

In this cell array protein-protein interaction assay (CAPPIA), mixtures of bait and prey expression plasmids together with an auto-fluorescent reporter are immobilized on glass slides in defined array formats. Adherent cells that grow on top of the micro-array will become fluorescent only if the expressed proteins interact and subsequently trans-activate the reporter. Using known interaction partners and by screening 160 different combinations of prey and bait proteins associated with the human androgen receptor we demonstrate that this assay allows the quantitative detection of specific protein interactions in different types of mammalian cells and under the influence of different compounds. Moreover, different strategies in respect to bait-prey combinations are presented.

Conclusion

We demonstrate that the CAPPIA assay allows the quantitative detection of specific protein interactions in different types of mammalian cells and under the influence of different compounds. The high number of preys that can be tested per slide together with the flexibility to interrogate any bait of interest and the small amounts of reagents that are required makes this assay currently one of the most economical high-throughput detection assays for protein-protein interactions in mammalian cells.
Treatment of isoniazid-resistant pulmonary tuberculosis
Authors: Kim Yee Hyung , Suh Gee Young , Chung Man Pyo , Kim Hojoong , Kwon O Jung , Lim Seong Yong , Lim Si Young , Koh Won-Jung
Published: January 2008

Background

Although resistance to isoniazid (INH) is the most common form of drug resistance seen among Mycobacterium tuberculosis isolates, there have been few studies on the efficacy and optimal duration of treatment for patients with INH-resistant tuberculosis (TB).

Methods

We evaluated retrospectively the treatment outcomes of 39 patients who were treated for INH-resistant pulmonary TB. The treatment regimens consisted of a 12-month regimen of rifampin (RIF) and ethambutol (EMB), with pyrazinamide (PZA) given during the first 2 months (2HREZ/10RE) (n = 21), a 9-month regimen of RIF and EMB with PZA during the first 2 months (2HREZ/7RE) (n = 5), and a 6-month regimen of RIF, EMB, and PZA (2HREZ/4REZ) (n = 13). After drug susceptibility testing confirmed the INH-resistance of the isolated M. tuberculosis strains, INH was discontinued for all the patients.

Results

Among the 39 patients, treatment was successfully completed by 36 patients (92%). However, treatment failure occurred, and acquired resistance to other first-line drugs, such as RIF, developed in three patients (8%). Cavitary and bilateral extensive lesions were commonly found in the chest radiographs of the patients who exhibited treatment failure.

Conclusion

These findings underline the seriousness of concerns regarding treatment failure and the development of multidrug-resistant TB in patients with INH-resistant TB following treatment with recommended regimens.
DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity
Authors: Fan Bao Jian , Pasquale Louis , Grosskreutz Cynthia L , Rhee Douglas , Chen Teresa , DeAngelis Margaret M , Kim Ivana , del Bono Elizabeth , Miller Joan W , Li Tiansen , Haines Jonathan L , Wiggs Janey L
Published: February 2008

Background

Pseudoexfoliation syndrome is a major risk factor for glaucoma in many populations throughout the world. Using a U.S. clinic-based case control sample with broad ethnic diversity, we show that three common SNPs in LOXL1 previously associated with pseudoexfoliation in Nordic populations are significantly associated with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.

Methods

Three LOXL1 SNPs were genotyped in a patient sample (206 pseudoexfoliation, 331 primary open angle glaucoma, and 88 controls) from the Glaucoma Consultation Service at the Massachusetts Eye and Ear Infirmary. The SNPs were evaluation for association with pseudeoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open angle glaucoma.

Results

The strongest association was found for the G allele of marker rs3825942 (G153D) with a frequency of 99% in pseudoexfoliation patients (with and without glaucoma) compared with 79% in controls (p = 1.6 × 10-15; OR = 20.93, 95%CI: 8.06, 54.39). The homozygous GG genotype is also associated with pseudoexfoliation when compared to controls (p = 1.2 × 10-12; OR = 23.57, 95%CI: 7.95, 69.85). None of the SNPs were significantly associated with primary open angle glaucoma.

Conclusion

The pseudoexfoliation syndrome is a common cause of glaucoma. These results indicate that the G153D LOXL1 variant is significantly associated with an increased risk of pseudoexfoliation and pseudoexfoliation glaucoma in an ethnically diverse patient population from the Northeastern United States. Given the high prevalence of pseudooexfoliation in this geographic region, these results also indicate that the G153D LOXL1 variant is a significant risk factor for adult-onset glaucoma in this clinic based population.
A longitudinal study of environmental tobacco smoke exposure in children: Parental self reports versus age dependent biomarkers
Authors: Puig Carme , Garcia-Algar Oscar , Monleon Toni , Pacifici Roberta , Zuccaro Piergiorgio , Sunyer Jordi , Figueroa Cecilia , Pichini Simona , Vall Oriol
Published: February 2008

Background

Awareness of the negative effects of smoking on children's health prompted a decrease in the self-reporting of parental tobacco use in periodic surveys from most industrialized countries. Our aim is to assess changes between ETS exposure at the end of pregnancy and at 4 years of age determined by the parents' self-report and measurement of cotinine in age related biological matrices.

Methods

The prospective birth cohort included 487 infants from Barcelona city (Spain). Mothers were asked about maternal and household smoking habit. Cord serum and children's urinary cotinine were analyzed in duplicate using a double antibody radioimmunoassay.

Results

At 4 years of age, the median urinary cotinine level in children increased 1.4 or 3.5 times when father or mother smoked, respectively. Cotinine levels in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 19.7 ng/ml; 95% CI 16.83–23.01) and exposed homes (GM 7.1 ng/ml; 95% CI 5.61–8.99) compared with non-exposed homes (GM 4.5 ng/ml; 95% CI 3.71–5.48). Maternal self-reported ETS exposure in homes declined in the four year span between the two time periods from 42.2% to 31.0% (p < 0.01). Nevertheless, most of the children considered non-exposed by their mothers had detectable levels of cotinine above 1 ng/mL in their urine.

Conclusion

We concluded that cotinine levels determined in cord blood and urine, respectively, were useful for categorizing the children exposed to smoking and showed that a certain increase in ETS exposure during the 4-year follow-up period occurred.
Validation of a French language version of the Early Childhood Oral Health Impact Scale (ECOHIS)
Authors: Li Shanshan , Veronneau Jacques , Allison Paul J
Published: January 2008

Background

An English language oral health-related negative impact scale for 0–5 year old infants (the Early Childhood Oral Health Impact Scale [ECOHIS]) has recently been developed and validated. The overall aim of our study was to validate a French version of the ECOHIS. The objectives were to investigate the scale's: i) internal consistency; ii) test-retest reliability; iii) convergent validity; and iv) discriminant validity.

Methods

Data were collected from two separate samples. Firstly, from 398 parents of children aged 12 months, recruited to a community-based intervention study, and secondly from 94 parents of 0–5 year-old children attending a hospital dental clinic. In a sub-sample of 101 of the community-based group, the scale was distributed a second time two weeks after initial evaluation. Internal consistency was evaluated through generation of Cronbach's alpha, test-retest reliability through intra-class-correlation coefficients (ICC), convergent validity through comparing scale total scores with a global evaluation of oral health and discriminant validity through investigation of differences in total scale scores between the community- and clinic-based samples.

Results

Cronbach's alpha for both the child and family impact sections was 0.79, and for the whole scale was 0.82. The ICC was 0.95. Mean ECOHIS scores for parents rating their child's oral health as "relatively poor", "good" and "very good" were 10.8, 3.4 and 2.7 respectively. In the community- and clinic-based samples, the mean ECOHIS scores were 3.7 and 4.9 respectively.

Conclusion

These results suggest this French language version of the ECOHIS is valid.
Correlation of in Vitro and in Vivo Somatotropic Adenoma Responsiveness to Somatostatin Analogs and Dopamine Agonists with Immunohistochemical Evaluation of Somatostatin and Dopamine Receptors and Electron Microscopy
Authors: Ferone Diego , de Herder Wouter W. , Pivonello Rosario , Kros Johan M. , van Koetsveld Peter M. , de Jong Ton , Minuto Francesco , Colao Annamaria , Lamberts Steven W. J. , Hofland Leo J.
Published: January 2008

Objective and Patients: Twenty-four pituitary adenomas from acromegalic patients (13 females, 11 males; age range 19–65 yr) were characterized for somatostatin receptor subtype 2A (sst2A), dopamine D2 receptor (D2R), GH, and prolactin (PRL) expression by immunohistochemistry, and results correlated with the in vitro and in vivo hormone responses to octreotide and quinagolide. In nine cases, GH and PRL content was further studied by immunoelectron microscopy.

Results: Immunoreactivity was semiquantitatively scored as 2 (>50% stained cells), 1 (10–50% stained cells), and 0 (<10% stained cells). Sst2A was scored as 2 in 13 cases, 1 in 10, and 0 in one; D2R was scored as 2 in 13 cases, 1 in nine, and 0 in 2; GH was 2 in 15 cases and 1 in nine; PRL was 2 in six cases, 1 in 13, and 0 in 5. Sst2A was positively correlated with in vitro (P = 0.003) and in vivo (P = 0.006) percent GH suppression by octreotide and with the chronic suppression of IGF-I by somatostatin analogs (P =0.008). D2R was positively correlated with in vitro percent GH (P =0.000) and PRL (P =0.005) suppression by quinagolide. Electron microscopy revealed two pure somatotroph adenomas, five somatomammotrophs with a variable coexpression of GH and PRL in the same cells, and two tumors consisting of mixed cell types, which were less sensitive to quinagolide and octreotide.

Conclusion: Sst2A and D2R are frequently coexpressed in adenomas from acromegalic patients, and immunohistochemistry may be helpful in characterizing receptor expression in pituitary adenomas to select patients responsive to different treatments.
Evaluation of Gene Expression Profiles in Thyroid Nodule Biopsy Material to Diagnose Thyroid Cancer
Authors: Durand Stéphanie , Ferraro-Peyret Carole , Selmi-Ruby Samia , Paulin Christian , El Atifi Michelle , Berger François , Berger-Dutrieux Nicole , Decaussin Myriam , Peix Jean-Louis , Bournaud Claire , Orgiazzi Jacques , Borson-Chazot Françoise , Rousset Bernard
Published: January 2008

Context: Detection of thyroid cancer among benign nodules on fine-needle aspiration biopsies (FNAB), which presently relies on cytological examination, is expected to be improved by new diagnostic tests set up from genomic data.

Objective: The aim of the study was to use a set of genes discriminating benign from malignant tumors, on the basis of their expression levels, to build tumor classifiers and evaluate their capacity to predict malignancy on FNAB.

Design: We analyzed the level of expression of 200 potentially informative genes in 56 thyroid tissue samples (benign or malignant tumors and paired normal tissue) using nylon macroarrays. Gene expression data were subjected to a weighted voting algorithm to generate tumor classifiers. The performances of the classifiers were evaluated on a series of 26 sham FNAB, i.e. FNAB carried out on thyroid nodules after surgical resection.

Results: A series of 19 genes with a similar expression in follicular adenomas and normal tissue and discriminating follicular adenomas+normal tissue from the following: 1) follicular thyroid carcinomas (FTCs), 2) papillary thyroid carcinomas (PTCs), or 3) both FTCs and PTCs. These were used to generate four classifiers, the FTCs, PTCs, common (FTC+PTCs), and global classifiers. In 23 of the 26 sham FNAB, the four classifiers yielded a diagnosis in agreement with the diagnosis of the pathologist used as reference; in the three other cases, the correct diagnosis was given by three of four classifiers.

Conclusions: We developed a procedure of molecular diagnosis of benign vs. malignant tumors applicable to the material collected by FNAB. The molecular test complied with a preclinical validation stage; it must be now evaluated on ultrasound-guided FNAB in a large-scale prospective study.
Extracellular matrix dynamics in development and regenerative medicine
Authors: Daley William P. , Peters Sarah B. , Larsen Melinda
Published: January 2008

The extracellular matrix (ECM) regulates cell behavior by influencing cell proliferation, survival, shape, migration and differentiation. Far from being a static structure, the ECM is constantly undergoing remodeling – i.e. assembly and degradation – particularly during the normal processes of development, differentiation and wound repair. When misregulated, this can contribute to disease. ECM assembly is regulated by the 3D environment and the cellular tension that is transmitted through integrins. Degradation is controlled by complex proteolytic cascades, and misregulation of these results in ECM damage that is a common component of many diseases. Tissue engineering strives to replace damaged tissues with stem cells seeded on synthetic structures designed to mimic the ECM and thus restore the normal control of cell function. Stem cell self-renewal and differentiation is influenced by the 3D environment within the stem cell niche. For tissue-engineering strategies to be successful, the intimate dynamic relationship between cells and the ECM must be understood to ensure appropriate cell behavior.
A dual role for IQGAP1 in regulating exocytosis
Authors: Rittmeyer Eric N. , Daniel Samira , Hsu Shu-Chan , Osman Mahasin A.
Published: January 2008

Polarized secretion is a tightly regulated event generated by conserved, asymmetrically localized multiprotein complexes, and the mechanism(s) underlying its temporal and spatial regulation are only beginning to emerge. Although yeast Iqg1p has been identified as a positional marker linking polarity and exocytosis cues, studies on its mammalian counterpart, IQGAP1, have focused on its role in organizing cytoskeletal architecture, for which the underlying mechanism is unclear. Here, we report that IQGAP1 associates and co-localizes with the exocyst-septin complex, and influences the localization of the exocyst and the organization of septin. We further show that activation of CDC42 GTPase abolishes this association and inhibits secretion in pancreatic β-cells. Whereas the N-terminus of IQGAP1 binds the exocyst-septin complex, enhances secretion and abrogates the inhibition caused by CDC42 or the depletion of IQGAP1, the C-terminus, which binds CDC42, inhibits secretion. Pulse-chase experiments indicate that IQGAP1 influences protein-synthesis rates, thus regulating exocytosis. We propose and discuss a model in which IQGAP1 serves as a conformational switch to regulate exocytosis.
Loss of galectin-3 impairs membrane polarisation of mouse enterocytes in vivo
Authors: Delacour Delphine , Koch Annett , Ackermann Waltraud , Parco Isabelle Eude-Le , Elsässer Hans-Peter , Poirier Francoise , Jacob Ralf
Published: January 2008

Epithelial cells are characterised by distinct apical and basolateral membrane domains that are separated by tight junctions. Establishment and maintenance of this polarity depend on specific gene expression and protein targeting to their correct location. Our former studies, performed with renal epithelial MDCK cells, revealed a new function for galectin-3, a member of a conserved family of lectins. There, galectin-3 is required for intracellular sorting and correct targeting of non-raft-associated glycoproteins to the apical plasma membrane. In the present study, we found transport defects of the intestinal brush border hydrolases lactase-phlorizin hydrolase (LPH) and dipeptidylpeptidase IV (DPPIV) in galectin-3-null mutant mice. We could show that, in enterocytes of wild-type mice, both glycoproteins directly interact with galectin-3 and transit through non-raft-dependent apical transport platforms. Therefore, this genetic analysis provides definitive evidence for the involvement of galectin-3 in protein intracellular trafficking in vivo. Further investigations revealed that gal3-null enterocytes also exhibit striking cytoarchitecture defects, with the presence of numerous and regular protrusions located along basolateral membranes. Moreover, β-actin and villin, two characteristic markers of brush borders, become abnormally distributed along these atypical basolateral membranes in gal3–/– mice. Taken together, our results demonstrate that, in addition to a pivotal role in apical trafficking, galectin-3 also participates in epithelial morphogenesis in mouse enterocytes.
vFLIP from KSHV inhibits anoikis of primary endothelial cells
Authors: Efklidou Sofia , Bailey Ranbir , Field Nigel , Noursadeghi Mahdad , Collins Mary K.
Published: January 2008

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) infection of endothelial cells is an early event in the aetiology of the endothelial cell tumour Kaposi's sarcoma (KS). We have examined the effect of the KSHV latent protein viral FLICE-like inhibitory protein (vFLIP) on dermal microvascular endothelial cell (MVEC) survival as vFLIP is expressed in the KSHV-infected cells within KS lesions. To do this, we have used a lentiviral vector to express vFLIP in MVECs in the absence of other KSHV proteins. vFLIP activates the classical NF-κB pathway in MVECs and causes nuclear translocation of RelA/p65. This NF-κB activation prevents detachment-induced apoptosis (anoikis) of MVECs but does not inhibit apoptosis induced by removal of essential survival factors, including vascular endothelial growth factor (VEGF). vFLIP expression inhibits anoikis in part by inducing the secretion of an additional paracrine survival factor(s). The implications of these results for KS development are discussed.
The nuclear affairs of PTEN
Authors: Planchon Sarah M. , Waite Kristin A. , Eng Charis
Published: January 2008

PTEN encodes a major tumor-suppressor protein that is a dual-specificity phosphatase. Inactivation of PTEN has been shown to be involved in heritable and sporadic cancers. Mutation or deletion of PTEN, historically the most commonly identified mechanisms of inactivation of tumor suppressors, is found only in the minority of sporadic non-cultured primary cancers, which indicates that there might be other, novel mechanisms of inactivation. Despite the absence of a classic nuclear localization signal, PTEN enters the nucleus by several mechanisms, including simple diffusion, active shuttling, cytoplasmic-localization-signal-dependent export and monoubiquitylation-dependent import. Cytoplasmic PTEN has a well-known role as a negative regulator of the PI3K/AKT pathway; however, it is becoming clear that cytosolic PTEN is not the same as nuclear PTEN. Nuclear PTEN plays a role in chromosome stability, DNA repair, cell cycle arrest and cellular stability. The balance between these functions is an important factor in determining whether a cell remains benign or becomes neoplastic.