bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of an Opioid Attractiveness Scale: a novel measure of the attractiveness of opioid products to potential abusers
Authors: Butler Stephen F , Benoit Christine , Budman Simon H , Fernandez Kathrine C , McCormick Cynthia , Venuti Synne Wing , Katz Nathaniel
Published: February 2006

Background

The growing trends in opioid abuse, assessment of the abuse liability of prescription opioid products, and growing efforts by the pharmaceutical industry to develop 'abuse-resistant' formulations highlight a need to understand the features that make one product more 'attractive' than another to potential abusers. We developed a scale to measure the 'attractiveness' of prescription opioids to potential abusers, and used the scale to measure the relative attractiveness of 14 opioid analgesic products.

Methods

First, the concept of attractiveness was empirically defined with a group of prescription opioid abusers and experts in opioid abuse using a process called Concept Mapping. Abuse liability consisted of two components: factors intrinsic to the drug formulation (e.g., speed of onset, duration) and factors extrinsic to drug formulation (e.g., availability, availability of alternatives, cost). A 17-item Opioid Attractiveness Scale (OAS) was constructed, focusing on factors intrinsic to the drug product.

Results

A total of 144 individuals participated in tests of validity and reliability. Internal consistency was excellent (Cronbach's α = 0.85–0.94). Drug rankings based on OAS scores achieved good inter-rater agreement (Kendall's W 0.37, p < 0.001). Agreement on drug OAS scores between the developmental sample and a confirmation sample was good (IntraClass Correlations [ICC] of 0.65–0.69). Global ratings of overall attractiveness of the 14 selected opioid products by substance abuse counselors corresponded with the rankings based on OAS ratings of the abuser group. Finally, substance abuse counselors completed the OAS, yielding a high level of correspondence with ratings by the abuser group (ICC = 0.83, p = 0.002). The OAS differentiated attractiveness among 14 selected pharmaceutical opioid products. OxyContin, Dilaudid, and Percocet were ranked highest (most attractive); Talwin NX and Duragesic were ranked lowest (least attractive).

Conclusion

An initial examination of the psychometric properties of the OAS suggests that it is a valid and reliable scale. The OAS may be useful in providing important guidance on product features that are attractive to potential abusers.
Pain in cancer. An outcome research project to evaluate the epidemiology, the quality and the effects of pain treatment in cancer patients
Authors: Apolone Giovanni , Bertetto Oscar , Caraceni Augusto , Corli Oscar , De Conno Franco , Labianca Roberto , Maltoni Marco , Nicora Mariaflavia , Torri Valter , Zucco Furio ,   the Cancer Pain Outcome Research Study Group
Published: February 2006

Background

Management of pain related to advanced or metastatic cancer, although the availability of several pharmacological and non-pharmacological interventions and the existence of well-known guidelines and protocols, is often difficult and inadequate. Evidence of the relative effectiveness of current options for treating cancer pain from comparative randomized studies is scanty.

Methods

In the context of a wider project, a multicenter, open label, prospective Outcome Research study will be launched in Italy in 2006 to investigate the epidemiology of cancer pain and of its treatments, the quality of analgesic-drug therapy and the effectiveness of alternative analgesic strategies in a large, prospective, unselected cohort of cancer patients using the state-of-the art of patient-reported-outcomes. About 100 Italian centers will recruit 2500 patients with advanced/progressive/metastatic cancer with pain (related to the cancer disease) requiring analgesic treatments. Each center is expected to recruit 25 consecutive and eligible patients during the study inception period. Approximately two months will be allowed for subject recruitment and enrollment. Subject evaluation and follow-up will be for 3 months. The effect on outcomes of various therapeutic analgesic options administered by physicians, given the observational approach where patients are not assigned at random to different treatments, will be compared using the propensity score approach, allowing the adjustment for treatment selection bias. Later, after the launch of the observational study and on the basis of results, in specific subsamples of patients and in select centers of the network, a Randomized Controlled Trial will be carried out to formally compare the efficacy of alternative analgesic strategies, with particular emphasis on oral morphine (as comparator) and buprenorphine patch (as experimental arm). Results from the outcome (cohort) and experimental (Randomized Controlled Trial) studies will ensure both the external and internal validity.
Female urogenital dysfunction following total mesorectal excision for rectal cancer
Authors: Daniels Ian R , Woodward Sheena , Taylor Fiona GM , Raja Ashraf , Toomey Paul
Published: February 2006

Background

The effect of Total Mesorectal Excision (TME) on sexual function in the male is well documented. However, there is little literature in female patients. The aim of this study was to review the pelvic autonomic nervous anatomy in the female and to perform a retrospective audit of urinary and sexual function in women following surgery for rectal cancer where TME had been performed. Urogenital dysfunction was assessed through interview and questionnaire.

Method

Twenty-three questionnaires, eighteen returned, were sent to women with a mean age 65.5 yrs (range 34–86). All had undergone total mesorectal excision for rectal cancer between 1998–2001. Mean follow-up was 18.8 months (range 3–35).

Results

Preoperatively 5/18 (28%) were sexually active, 3/18 (17%) of patients described urinary frequency and nocturia and 7/18 (39%) described symptoms of stress incontinence prior to surgery. Postoperatively all sexually active patients remained active although all described some discomfort with penetration. Two of the patients sexually active described reduced libido secondary to the stoma. Postoperative urinary symptoms developed with 59% reporting the development of nocturia, 18% developed stress incontinence and one patient required a permanent catheter. Of those with symptoms, 80% persisted longer than three months from surgery. Symptoms were predominant in those patients with low rectal cancers, particularly those undergoing abdomino-perineal excision and in those who had previously undergone abdominal hysterectomy.

Conclusion

The treatment of rectal cancer involves surgery to the pelvic floor. Despite nerve preservation this is associated with the development of worsening nocturia and stress incontinence. This is most marked in those patients who had previously undergone a hysterectomy. Further studies are warranted to assess the interaction with previous gynaecological surgery.
Is there a relationship between sperm chromosome abnormalities and sperm morphology?
Authors: Sun Fei , Ko Evelyn , Martin Renée H
Published: February 2006

This review explores the relationship between sperm chromosomal constitution and morphology. With the advent of techniques for obtaining information on the chromosome complements of spermatozoa, this relationship has been studied in fertile men and in men with a high frequency of chromosomal abnormalities. Using human sperm karyotype analysis, no relationship between sperm chromosome abnormalities and morphology was found in fertile men, translocation carriers or post-radiotherapy cancer patients. Fluorescence in situ hybridization (FISH) analysis has not generally revealed a specific association between morphologically abnormal sperm and sperm chromosome abnormalities, but has indicated that teratozoospermia, like other forms of abnormal semen profiles (aesthenozoospermia, oligozoospermia) is associated with a modest increase in the frequency of sperm chromosome abnormalities. However, FISH studies on some infertile men and mouse strains have suggested that certain types of morphologically abnormal spermatozoa, such as macrocephalic multitailed spermatozoa, are associated with a very significantly increased frequency of aneuploidy. Thus, there may be an association between sperm morphology and aneuploidy in infertile men with specific abnormalities.
Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraception
Authors: Schatz Frederick , Krikun Graciela , Baergen Rebecca N , Critchley Hilary OD , Kuczynski Edward , Lockwood Charles J
Published: February 2006

Background

Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1). Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle.

Methods

Endometrial biopsies were obtained from women across the menstrual cycle and from those on LTPOC treatment (either Mirena or Norplant). The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM-1.

Results

The current study found prominent ICAM-1 staining in the endometrial endothelium that was of equivalent intensity in different blood vessel types irrespective of the steroidal or inflammatory endometrial milieu across the menstrual cycle and during LTPOC therapy. Unlike the endothelial cells, the glands were negative and the stromal cells were weakly positive for ICAM immunostaining.

Conclusion

The results of the current study suggest that altered expression of ICAM-1 by endothelial cells does not account for the influx of neutrophils into the premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may depend on altered expression of neutrophil chemoattractants.
Studies of the role of steroid hormone in the regulation of oocyte maturation in cattle
Authors: Wang Hai Feng , Isobe Naoki , Kumamoto Kanako , Yamashiro Hideaki , Yamashita Yasuhisa , Terada Takato
Published: February 2006

Background

The objective of this study was to investigate whether the steroid hormone(s) secreted from cumulus-oocyte complexes (COCs) is a prerequisite for bovine oocyte maturation and cumulus expansion using aminoglutethimide (AGT), a P450 cholesterol side-chain cleavage inhibitor.

Methods

In experiment 1, COCs were cultured in maturation medium with various concentrations of AGT for 22 h to determine the effective concentration of AGT to inhibit steroid hormone secretion, meiotic maturation and cumulus expansion. In experiment 2, COCs were cultured in conditioned medium (CM) and TCM-199 medium with or without 10 mM AGT to check whether steroid hormones secreted from COCs were responsible for oocyte maturation and cumulus expansion. Experiments 3 and 4 were carried out to determine whether exogenous progesterone or estradiol-17beta was able to overcome the inhibitory effects of AGT on oocytes maturation and cumulus expansion. COCs cultured in 10 mM AGT-containing medium supplemented with various concentrations of progesterone or estradiol-17beta for 22 h were examined for oocyte maturation and cumulus expansion.

Results

Experiment 1 showed that a concentration of 10 mM AGT in medium was sufficient to block steroid hormone secretion, oocyte maturation and cumulus expansion, and that these inhibitory effects were fully reversible. In experiment 2, the addition of 10 mM AGT to CM did not significantly prevent oocyte maturation and cumulus expansion, implying that CM contains the steroid hormone(s) secreted from COCs, which are closely associated with oocyte maturation and cumulus expansion. The results in experiments 3 and 4 demonstrated that the addition of any concentration of progesterone or estradiol-17beta in the medium did not reduce the inhibitory effects of AGT on oocyte maturation and cumulus expansion.

Conclusion

Our results indicate that bovine oocytes surrounded by cumulus cells are prevented from maturation and cumulus expansion through the inhibition of steroid secretion due to AGT, and that these inhibitory effects of AGT on oocyte maturation and cumulus expansions can not be overcome by the addition of either progesterone or estradiol-17beta in the medium. These observations suggest that some steroid hormone(s) other than P4 and E2 secreted from bovine COCs is essential for their meiotic maturation and cumulus expansion.
Detection and quantification of lupus anticoagulants in plasma from heparin treated patients, using addition of polybrene
Authors: Jacobsen Eva M , Trettenes Elin J , Wisløff Finn , Abildgaard Ulrich
Published: February 2006

Background

Lupus anticoagulants prolong clotting times in phospholipid-dependent coagulation tests. Lupus Ratio assays are integrated tests for lupus anticoagulants that may be based on APTT, RVVT or dPT clotting times. If a patient is being treated with unfractionated heparin, however, the heparin prolong clotting times and the diagnosis of lupus anticoagulant is invalidated. Commercial assays may have heparin neutralising agents added to their reagents. However, the type and efficacy of the heparin neutralisation is often not documented. We wanted to test the influence and efficacy of heparin neutralisers in the Lupus Ratio assay.

Methods

Several heparin neutralisers were tested, and polybrene was chosen for further testing. Unfractionated heparin and/or polybrene were added to normal plasma and to plasma from patients with or without lupus anticoagulant and clotting times compared before and after the additions. Lupus anticoagulant-positive patients were given 5000 IU i.v. of unfractionated heparin and plasma was collected just before and five minutes after the injection. Lupus Ratios were calculated after polybrene was added to the postinjection samples.

Results

The Lupus Ratio became slightly lower when polybrene was added to plasma without heparin. Plasma heparinised in vitro and plasma from patients that had received heparin, both had Lupus Ratios nearly identical to the Lupus Ratios calculated before any additions.

Conclusion

By addition of polybrene to a final concentration of 7.9 μg/ml in test plasma, Lupus Ratio may be determined in lupus anticoagulant-negative as well as positive plasmas irrespective of the presence of heparin 0.0 – 1.3 U/ml.
Estimating health workforce needs for antiretroviral therapy in resource-limited settings
Authors: Hirschhorn Lisa R , Oguda Lulu , Fullem Andrew , Dreesch Norbert , Wilson Paul
Published: February 2006

Background

Efforts to increase access to life-saving treatment, including antiretroviral therapy (ART), for people living with HIV/AIDS in resource-limited settings has been the growing focus of international efforts. One of the greatest challenges to scaling up will be the limited supply of adequately trained human resources for health, including doctors, nurses, pharmacists and other skilled providers. As national treatment programmes are planned, better estimates of human resource needs and improved approaches to assessing the impact of different staffing models are critically needed. However there have been few systematic assessments of staffing patterns in existing programmes or of the estimates being used in planning larger programmes.

Methods

We reviewed the published literature and selected plans and scaling-up proposals, interviewed experts and collected data on staffing patterns at existing treatment sites through a structured survey and site visits.

Results

We found a wide range of staffing patterns and patient-provider ratios in existing and planned treatment programmes. Many factors influenced health workforce needs, including task assignments, delivery models, other staff responsibilities and programme size. Overall, the number of health care workers required to provide ART to 1000 patients included 1–2 physicians, 2–7 nurses, <1 to 3 pharmacy staff, and a much wider range of counsellors and treatment supporters. We estimate from these data that the equivalent of 20 000 to 100 000 physicians, nurses, pharmacists and other core clinical staff will be needed to meet the WHO target of treating 3 million people by the end of 2005. The total number of staff, including counsellors, administrators and other cadres, could be substantially higher.

Discussion

These data are consistent with other estimates of human resource requirements for antiretroviral therapy, but highlight the considerable variability of current staffing models and the importance of a broad range of factors in determining personnel needs. Few outcome or cost data are currently available to assess the effectiveness and efficiency of different staffing models, and it will be important to develop improved methods for gathering this information as treatment programmes are scaled up.
Identification of mitogen-activated protein kinase docking sites in enzymes that metabolize phosphatidylinositols and inositol phosphates
Authors: Caldwell Kevin K , Sosa Marcos , Buckley Colin T
Published: February 2006

Background

Reversible interactions between the components of cellular signaling pathways allow for the formation and dissociation of multimolecular complexes with spatial and temporal resolution and, thus, are an important means of integrating multiple signals into a coordinated cellular response. Several mechanisms that underlie these interactions have been identified, including the recognition of specific docking sites, termed a D-domain and FXFP motif, on proteins that bind mitogen-activated protein kinases (MAPKs). We recently found that phosphatidylinositol-specific phospholipase C-γ1 (PLC-γ1) directly binds to extracellular signal-regulated kinase 2 (ERK2), a MAPK, via a D-domain-dependent mechanism. In addition, we identified D-domain sequences in several other PLC isozymes. In the present studies we sought to determine whether MAPK docking sequences could be recognized in other enzymes that metabolize phosphatidylinositols (PIs), as well as in enzymes that metabolize inositol phosphates (IPs).

Results

We found that several, but not all, of these enzymes contain identifiable D-domain sequences. Further, we found a high degree of conservation of these sequences and their location in human and mouse proteins; notable exceptions were PI 3-kinase C2-γ, PI 4-kinase type IIβ, and inositol polyphosphate 1-phosphatase.

Conclusion

The results indicate that there may be extensive crosstalk between MAPK signaling and signaling pathways that are regulated by cellular levels of PIs or IPs.
Are fast food restaurants an environmental risk factor for obesity?
Authors: Jeffery Robert W , Baxter Judy , McGuire Maureen , Linde Jennifer
Published: February 2006

Objective

Eating at "fast food" restaurants has increased and is linked to obesity. This study examined whether living or working near "fast food" restaurants is associated with body weight.

Methods

A telephone survey of 1033 Minnesota residents assessed body height and weight, frequency of eating at restaurants, and work and home addresses. Proximity of home and work to restaurants was assessed by Global Index System (GIS) methodology.

Results

Eating at "fast food" restaurants was positively associated with having children, a high fat diet and Body Mass Index (BMI). It was negatively associated with vegetable consumption and physical activity. Proximity of "fast food" restaurants to home or work was not associated with eating at "fast food" restaurants or with BMI. Proximity of "non-fast food" restaurants was not associated with BMI, but was associated with frequency of eating at those restaurants.

Conclusion

Failure to find relationships between proximity to "fast food" restaurants and obesity may be due to methodological weaknesses, e.g. the operational definition of "fast food" or "proximity", or homogeneity of restaurant proximity. Alternatively, the proliferation of "fast food" restaurants may not be a strong unique cause of obesity.
Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FOXO to the cytoplasm
Authors: Weinkove David , Halstead Jonathan R , Gems David , Divecha Nullin
Published: February 2006

Background

The provision of stress resistance diverts resources from development and reproduction and must therefore be tightly regulated. In Caenorhabditis elegans, the switch to increased stress resistance to promote survival through periods of starvation is regulated by the DAF-16/FOXO transcription factor. Reduction-of-function mutations in AGE-1, the C. elegans Class IA phosphoinositide 3-kinase (PI3K), increase lifespan and stress resistance in a daf-16 dependent manner. Class IA PI3Ks downregulate FOXOs by inducing their translocation to the cytoplasm. However, the circumstances under which AGE-1 is normally activated are unclear. To address this question we used C. elegans first stage larvae (L1s), which when starved enter a developmentally-arrested diapause stage until food is encountered.

Results

We find that in L1s both starvation and daf-16 are necessary to confer resistance to oxidative stress in the form of hydrogen peroxide. Accordingly, DAF-16 is localised to cell nuclei after short-term starvation. However, after long-term starvation, DAF-16 unexpectedly translocates to the cytoplasm. This translocation requires functional age-1. H2O2 treatment can replicate the translocation and induce generation of the AGE-1 product PIP3. Because feeding reduces to zero in ageing adult C. elegans, these animals may also undergo long-term starvation. Consistent with our observation in L1s, DAF-16 also translocates to the cytoplasm in old adult worms in an age-1-dependent manner.

Conclusion

DAF-16 is activated in the starved L1 diapause. The translocation of DAF-16 to the cytoplasm after long-term starvation may be a feedback mechanism that prevents excessive expenditure on stress resistance. H2O2 is a candidate second messenger in this feedback mechanism. The lack of this response in age-1(hx546) mutants suggests a novel mechanism by which this mutation increases longevity.
Identification of metabolic system parameters using global optimization methods
Authors: Polisetty Pradeep K , Voit Eberhard O , Gatzke Edward P
Published: February 2006

Background

The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important.

Methods and results

Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA) models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined.

Conclusion

The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.
A stochastic model of oncogene expression and the relevance of this model to cancer therapy
Authors: Alfano Francis D
Published: February 2006

Background

Ablation of an oncogene or of the activity of the protein it encodes can result in apoptosis and/or inhibit tumor cell proliferation. Therefore, if the oncogene or set of oncogenes contributing maximally to a tumor cell's survival can be identified, such oncogene(s) are the most appropriate target(s) for maximizing tumor cell kill.

Methods and results

A mathematical model is presented that describes cellular phenotypic entropy as a function of cellular proliferation and/or survival, and states of transformation and differentiation. Oncogenes become part of the cellular machinery, block apoptosis and differentiation or promote proliferation and give rise to new states of cellular transformation. Our model gives a quantitative assessment of the amount of cellular death or growth inhibition that result from the ablation of an oncogene's protein product. We review data from studies of chronic myelogenous leukemia and K562 cells to illustrate these principles.

Conclusion

The model discussed in this paper has implications for oncogene-directed therapies and their use in combination with other therapeutic modalities.
An immune reaction may be necessary for cancer development
Authors: Prehn Richmond T
Published: February 2006

Background

The hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. Its correctness has been debated for many years.

In its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate.

Alternative model

There is an alternative to the surveillance hypothesis; numerous studies have shown that the effect of an immune reaction on a tumor is biphasic. For each tumor, there is some quantitatively low level of immune reaction that, relative to no reaction, is facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum level of this facilitating reaction may often be less than the level of immunity that the tumor might engender in a normal subject.

Conclusion

The failure of a tumor to grow as well in the normal as it does in the immunosuppressed host is probably not caused by a lack of tumor-cell killing in the suppressed host. Instead, the higher level of immune response in a normal animal, even if it does not rise to tumor-inhibitory levels, probably gives less positive support to tumor growth. This seems more than a semantic distinction.
A suboptimal 5' splice site downstream of HIV-1 splice site A1 is required for unspliced viral mRNA accumulation and efficient virus replication
Authors: Madsen Joshua M , Stoltzfus C Martin
Published: February 2006

Background

Inefficient alternative splicing of the human immunodeficiency virus type 1(HIV-1) primary RNA transcript results in greater than half of all viral mRNA remaining unspliced. Regulation of HIV-1 alternative splicing occurs through the presence of suboptimal viral 5' and 3' splice sites (5' and 3'ss), which are positively regulated by exonic splicing enhancers (ESE) and negatively regulated by exonic splicing silencers (ESS) and intronic splicing silencers (ISS). We previously showed that splicing at HIV-1 3'ss A2 is repressed by ESSV and enhanced by the downstream 5'ss D3 signal. Disruption of ESSV results in increased vpr mRNA accumulation and exon 3 inclusion, decreased accumulation of unspliced viral mRNA, and decreased virus production.

Results

Here we show that optimization of the 5'ss D2 signal results in increased splicing at the upstream 3'ss A1, increased inclusion of exon 2 into viral mRNA, decreased accumulation of unspliced viral mRNA, and decreased virus production. Virus production from the 5'ss D2 and ESSV mutants was rescued by transient expression of HIV-1 Gag and Pol. We further show that the increased inclusion of either exon 2 or 3 does not significantly affect the stability of viral mRNA but does result in an increase and decrease, respectively, in HIV-1 mRNA levels. The changes in viral mRNA levels directly correlate with changes in tat mRNA levels observed upon increased inclusion of exon 2 or 3.

Conclusion

These results demonstrate that splicing at HIV-1 3'ss A1 is regulated by the strength of the downstream 5'ss signal and that suboptimal splicing at 3'ss A1 is necessary for virus replication. Furthermore, the replication defective phenotype resulting from increased splicing at 3'ss A1 is similar to the phenotype observed upon increased splicing at 3'ss A2. Further examination of the role of 5'ss D2 and D3 in the alternative splicing of 3'ss A1 and A2, respectively, is necessary to delineate a role for non-coding exon inclusion in HIV-1 replication.
Causal analysis of case-control data
Authors: Newman Stephen C
Published: February 2006

In a series of papers, Robins and colleagues describe inverse probability of treatment weighted (IPTW) estimation in marginal structural models (MSMs), a method of causal analysis of longitudinal data based on counterfactual principles. This family of statistical techniques is similar in concept to weighting of survey data, except that the weights are estimated using study data rather than defined so as to reflect sampling design and post-stratification to an external population. Several decades ago Miettinen described an elementary method of causal analysis of case-control data based on indirect standardization. In this paper we extend the Miettinen approach using ideas closely related to IPTW estimation in MSMs. The technique is illustrated using data from a case-control study of oral contraceptives and myocardial infarction.
Y chromosome microdeletions in infertile men with idiopathic oligo- or azoospermia
Authors: Hellani Ali , Al-Hassan Saad , Iqbal Muhammed A , Coskun Serdar
Published: February 2006

About 30–40% of male infertility is due to unknown reasons. Genetic contributions to the disruption of spermatogenesis are suggested and amongst the genetic factors studied, Y chromosome microdeletions represent the most common one. Screening for microdeletions in AZFa, b and c region of Y chromosome showed a big variation among different studies. The purpose of this study was to investigate the prevalence of such deletions in Saudi men. A total of 257 patients with idiopathic oligo- or azoospermia were screened for Y chromosome microdeletions by 19 markers in AZF region. Ten (3.9%) patients had chromosomal rearrangements, six of them showed sex chromosome abnormalities and four patients had apparently balanced autosomal rearrengements. Eight of the remaining 247 patients (3.2%) with a normal karyotype and no known causes of impaired spermatogenesis had Y chromosome microdeletions. Among these, six patients had deletions in AZFc region, one case had a deletion in AZFb and another had both AZFa and AZFc deletions.

In conclusion, our study shows that Y chromosome microdeletions are low in our population. We also report for the first time a case with unique point deletions of AZFa and AZFc regions. The lower frequency of deletions in our study suggest that other genetic, epigenetic, nutritional and local factors may be responsible for idiopathic oligo- or azoospermia in the Saudi population.
Epstein-barr virus induced cellular changes in nasal mucosa
Authors: Gelardi Matteo , Tomaiuolo Marilena , Cassano Michele , Besozzi Gaspare , Fiorella Maria Luisa , Calvario Agata , Castellano Maria Antonia , Cassano Pasquale
Published: February 2006

A 21-year-old man presented with nasal obstruction of the right nasal fossa of 1 year duration. Nasal endoscopy revealed in the right inferior turbinate head a rounded neoplasm about 1 cm in diameter.

Cytologic study of a nasal scraping specimen disclosed numerous clusters containing columnar cells with cytomegaly, prominent multinucleation, markedly sparse shortened cilia; the cytoplasm contained an acidophil area and a small round area that stained poorly; cells with a large intracytoplasmic vacuole that was acidophil and PAS+. Serology tests using the nested polymer chain reaction (PCR) technique on serum, nasal and pharyngeal smears revealed an Epstein-Barr virus (EBV) infection that was confirmed at electron microscopy. The clinical and cytological features resolved 19 months after the initial evaluation.

Conclusion

The authors advise carrying out clinical (endoscopy, serology, etc.) evaluation of all endonasal neoplasms and to routinely perform cytological study on nasal scraping specimens. When samples test positive for EBV, nasal and nasopharyngeal endoscopy should be performed regularly to detect possible evidence for nasopharyngeal carcinoma (NPC).
Intrathecal Long-Term Gene Expression by Self-Complementary Adeno-Associated Virus type 1 Suitable for Chronic Pain Studies in Rats
Authors: Storek Benjamin , Harder Nina M , Banck Michaela S , Wang Cheng , McCarty Douglas M , Janssen William GM , Morrison John H , Walsh Christopher E , Beutler Andreas S
Published: February 2006

Background

Intrathecal (IT) gene transfer is an attractive approach for targeting spinal mechanisms of nociception but the duration of gene expression achieved by reported methods is short (up to two weeks) impairing their utility in the chronic pain setting. The overall goal of this study was to develop IT gene transfer yielding true long-term transgene expression defined as ≥ 3 mo following a single vector administration. We defined “IT” administration as atraumatic injection into the lumbar cerebrospinal fluid (CSF) modeling a lumbar puncture. Our studies focused on recombinant adeno-associated virus (rAAV), one of the most promising vector types for clinical use.

Results

Conventional single stranded rAAV2 vectors performed poorly after IT delivery in rats. Pseudotyping of rAAV with capsids of serotypes 1, 3, and 5 was tested alone or in combination with a modification of the inverted terminal repeat. The former alters vector tropism and the latter allows packaging of self-complementary rAAV (sc-rAAV) vectors. Combining both types of modification led to the identification of sc-rAAV2/l as a vector that performed superiorly in the IT space. IT delivery of 3 × 10e9 sc-rAAV2/l particles per animal led to stable expression of enhanced green fluorescent protein (EGFP) for ≥ 3 mo detectable by Western blotting, quantitative PCR, and in a blinded study by confocal microscopy. Expression was strongest in the cauda equina and the lower sections of the spinal cord and only minimal in the forebrain. Microscopic examination of the SC fixed in situ with intact nerve roots and meninges revealed strong EGFP fluorescence in the nerve roots.

Conclusion

sc-rAAVl mediates stable IT transgene expression for ≥ 3 mo. Our findings support the underlying hypothesis that IT target cells for gene transfer lack the machinery for efficient conversion of the single-stranded rAAV genome into double-stranded DNA and favor uptake of serotype 1 vectors over 2. Experiments presented here will provide a rational basis for utilizing IT rAAV gene transfer in basic and translational studies on chronic pain.
Color naming deficits and attention-deficit/hyperactivity disorder: A retinal dopaminergic hypothesis
Authors: Tannock Rosemary , Banaschewski Tobias , Gold David
Published: February 2006

Background

Individuals with Attention-Deficit/Hyperactive Disorder (ADHD) have unexplained difficulties on tasks requiring speeded processing of colored stimuli. Color vision mechanisms, particularly short-wavelength (blue-yellow) pathways, are highly sensitive to various diseases, toxins and drugs that alter dopaminergic neurotransmission. Thus, slow color processing might reflect subtle impairments in the perceptual encoding stage of stimulus color, which arise from hypodopaminergic functioning.

Presentation of hypotheses

1) Color perception of blue-yellow (but not red-green) stimuli is impaired in ADHD as a result of deficient retinal dopamine; 2) Impairments in the blue-yellow color mechanism in ADHD contribute to poor performance on speeded color naming tasks that include a substantial proportion of blue-yellow stimuli; and 3) Methylphenidate increases central dopamine and is also believed to increase retinal dopamine, thereby normalizing blue-yellow color perception, which in turn improves performance on the speeded color naming tasks.

Testing the hypothesis

Requires three approaches, including:1) direct assessment of color perception in individuals with ADHD to determine whether blue-yellow color perception is selectively impaired; 2) determination of relationship between performance on neuropsychological tasks requiring speeded color processing and color perception; and 3) randomized, controlled pharmacological intervention with stimulant medication to examine the effects of enhancing central dopamine on color perception and task performance

Implications of hypothesis

If substantiated, the findings of color perception problems would necessitate a re-consideration of current neuropsychological models of attention-deficit/hyperactivity disorder, guide psycho-education, academic instruction, and require consideration of stimulus color in many of the widely used neuropsychological tests.
Mutational hotspots in the TP53gene and, possibly, other tumor suppressors evolve by positive selection
Authors: Glazko Galina V , Babenko Vladimir N , Koonin Eugene V , Rogozin Igor B
Published: February 2006

Background

The mutation spectra of the TP53 gene and other tumor suppressors contain multiple hotspots, i.e., sites of non-random, frequent mutation in tumors and/or the germline. The origin of the hotspots remains unclear, the general view being that they represent highly mutable nucleotide contexts which likely reflect effects of different endogenous and exogenous factors shaping the mutation process in specific tissues. The origin of hotspots is of major importance because it has been suggested that mutable contexts could be used to infer mechanisms of mutagenesis contributing to tumorigenesis.

Results

Here we apply three independent tests, accounting for non-uniform base compositions in synonymous and non-synonymous sites, to test whether the hotspots emerge via selection or due to mutational bias. All three tests consistently indicate that the hotspots in the TP53 gene evolve, primarily, via positive selection. The results were robust to the elimination of the highly mutable CpG dinucleotides. By contrast, only one, the least conservative test reveals the signature of positive selection in BRCA1, BRCA2, and p16. Elucidation of the origin of the hotspots in these genes requires more data on somatic mutations in tumors.

Conclusion

The results of this analysis seem to indicate that positive selection for gain-of-function in tumor suppressor genes is an important aspect of tumorigenesis, blurring the distinction between tumor suppressors and oncogenes.

Reviewers

This article was reviewed by Sandor Pongor, Christopher Lee and Mikhail Blagosklonny.
Occupational medicine and toxicology
Authors: Groneberg David A , Fischer Axel
Published: February 2006

This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.
Chronic cough due to occupational factors
Authors: Groneberg David A , Nowak Dennis , Wussow Anke , Fischer Axel
Published: February 2006

Within the large variety of subtypes of chronic cough, either defined by their clinical or pathogenetic causes, occupational chronic cough may be regarded as one of the most preventable forms of the disease. Next to obstructive airway diseases such as asthma or chronic obstructive pulmonary disease, which are sometimes concomitant with chronic cough, this chronic airway disease gains importance in the field of occupational medicine since classic fiber-related occupational airway diseases will decrease in the future.

Apart from acute accidents and incidental exposures which may lead to an acute form of cough, there are numerous sources for the development of chronic cough within the workplace. Over the last years, a large number of studies has focused on occupational causes of respiratory diseases and it has emerged that chronic cough is one of the most prevalent work-related airway diseases. Best-known examples of occupations related to the development of cough are coal miners, hard-rock miners, tunnel workers, or concrete manufacturing workers.

As chronic cough is often based on a variety of non-occupational factors such as tobacco smoke, a distinct separation into either occupational or personally -evoked can be difficult. However, revealing the occupational contribution to chronic cough and to the symptom cough in general, which is the commonest cause for the consultation of a physician, can significantly lead to a reduction of the socioeconomic burden of the disease.
The description of cough sounds by healthcare professionals
Authors: Smith Jaclyn A , Ashurst H Louise , Jack Sandy , Woodcock Ashley A , Earis John E
Published: February 2006

Background

Little is known of the language healthcare professionals use to describe cough sounds. We aimed to examine how they describe cough sounds and to assess whether these descriptions suggested they appreciate the basic sound qualities (as assessed by acoustic analysis) and the underlying diagnosis of the patient coughing.

Methods

53 health professionals from two large respiratory tertiary referral centres were recruited; 22 doctors and 31 staff from professions allied to medicine. Participants listened to 9 sequences of spontaneous cough sounds from common respiratory diseases. For each cough they selected patient gender, the most appropriate descriptors and a diagnosis. Cluster analysis was performed to assess which cough sounds attracted similar descriptions.

Results

Gender was correctly identified in 93% of cases. The presence or absence of mucus was correct in 76.1% and wheeze in 39.3% of cases. However, identifying clinical diagnosis from cough was poor at 34.0%. Cluster analysis showed coughs with the same acoustics properties rather than the same diagnoses attracted the same descriptions.

Conclusion

These results suggest that healthcare professionals can recognise some of the qualities of cough sounds but are poor at making diagnoses from them. It remains to be seen whether in the future cough sound acoustics will provide useful clinical information and whether their study will lead to the development of useful new outcome measures in cough monitoring.
Diversity and utilization of antimalarial ethnophytotherapeutic remedies among the Kikuyus (Central Kenya)
Authors: Njoroge Grace N , Bussmann Rainer W
Published: February 2006

Plants in Kenya are becoming increasingly important as sources of traditional medicines. The World Health Organization (WHO) has estimated that malaria kills about 2.7 million people every year, 90% of who are from Africa. Malaria continues to be a national concern in Kenya as it plays a major role in the high mortality rates being experienced currently. The use and miss-use of chloroquine to prevent and treat falciparium malaria has led to widespread appearance of chloroquine resistant parasites in Kenya and other tropical countries. These factors and the rising costs of non-chloroquine drugs have made the local people to turn to traditional remedies for management of this menace.

This paper examines the current utilization of traditional plant medicines in managing malaria menace in Central Kenya. The results show both indigenous and introduced species are in use indicating traditional medicinal practices in this region are dynamic. In total 58 species in 54 genera and 33 families were identified. The family Rubiaceae was found to have the highest number of reported species. Use of the various taxa is compared between five districts within Central Province of Kenya. The commonest species in this pharmacopoeia are: Caesalpinia volkensii Harms, Strychnos henningsii Gilg, Ajuga remota Benth., Warbugia ugandensis Sprague and Olea europaea L. The first three species are used in all the five districts while the others are restricted in some of the districts. In 74% of the anti-malarial plant species reported in this study, the remedies are obtained in destructive manner and may need conservation measures to ensure sustainable utilization. The results of this study become a basis for selecting plants for further pharmacological and phytochemical studies in developing new and locally relevant anti-malarial agents.
Prevalence of virulence factors in Staphylococcus intermediusisolates from dogs and pigeons
Authors: Futagawa-Saito Keiko , Ba-Thein William , Sakurai Naomi , Fukuyasu Tsuguaki
Published: February 2006

Background

Staphylococcus intermedius has been isolated from healthy dogs and pigeons as well as diseased dogs. Similar to Staphylococcus aureus, S. intermedius is known to carry many virulence factors but most of these factors remain to be studied. In this study, we examined 106 S. intermedius isolates (44 dog isolates and 62 pigeon isolates) for their hemolytic activity, biofilm formation, protease activity, and clumping factor and protein A production.

Results

Forty-three dog isolates (97.7%) and all pigeon isolates were hemolytic on sheep RBCs with a mean hemolytic titer of 336.7 and 47.32, respectively, whereas 43 dog isolates (97.7%) and 11 pigeon isolates (17.7%) exhibited a significant difference in their hemolytic activity on rabbit RBCs with a mean hemolytic titer of 11.04 and 3.76, respectively (p < 0.0005). The mean biofilm formation activity for dog isolates was 0.49, which was significantly higher than that (0.33) for pigeon isolates (p < 0.0005). Twenty-four dog isolates (54.5%) and 11 pigeon isolates (17.7%) were protease positive. Twenty-four dog isolates (54.5%) were clumping factor- and protein A- positive.

Conclusion

S. intermedius strains carrying the virulence factors examined in this study were more prevalent in dogs than pigeons.