bluuebunny/crossref_metadata_2025 huggingface dataset:
The molecular basis of defective lens development in the Iberian mole
Authors: Carmona F David , Jiménez Rafael , Collinson J Martin
Published: October 2008

Background

Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development. We have studied eye development in a species of true mole, the Iberian moleTalpa occidentalis, and present the molecular basis of abnormal lens development. This is the first embryological developmental study of the eyes of any fossorial mammal at the molecular level.

Results

Lens fibre differentiation is not completed in the Iberian mole. Although eye development starts normally (similar to other model species), defects are seen after closure of the lens vesicle.PAX6is not down-regulated in developing lens fibre nuclei, as it is in other species, and there is ectopic expression ofFOXE3, a putative downstream effector ofPAX6, in some, but not all lens fibres. FOXE3-positive lens fibres continue to proliferate within the posterior compartment of the embryonic lens, but unlike in the mouse, no proliferation was detected anywhere in the postnatal mole lens. The undifferentiated status of the anterior epithelial cells was compromised, and most of them undergo apoptosis. Furthermore, β-crystallin andPROX1expression patterns are abnormal and our data suggest that genes encoding β-crystallins are not directly regulated by PAX6, c-MAF and PROX1 in the Iberian mole, as they are in other model vertebrates.

Conclusion

In other model vertebrates, genetic pathways controlling lens development robustly compartmentalise the lens into a simple, undifferentiated, proliferative anterior epithelium, and quiescent, anuclear, terminally differentiated posterior lens fibres. These pathways are not as robust in the mole, and lead to loss of the anterior epithelial phenotype and only partial differentiation of the lens fibres, which continue to express 'epithelial' genes. Paradigms of genetic regulatory networks developed in other vertebrates appear not to hold true for the Iberian mole.
Tropical parabiotic ants: Highly unusual cuticular substances and low interspecific discrimination
Authors: Menzel Florian , Blüthgen Nico , Schmitt Thomas
Published: October 2008

Background

Associations between animal species require that at least one of the species recognizes its partner. Parabioses are associations of two ant species which co-inhabit the same nest. Ants usually possess an elaborate nestmate recognition system, which is based on cuticular hydrocarbons and allows them to distinguish nestmates from non-nestmates through quantitative or qualitative differences in the hydrocarbon composition. Hence, living in a parabiotic association probably necessitates changes of the nestmate recognition system in both species, since heterospecific ants have to be accepted as nestmates.

Results

In the present study we report highly unusual cuticular profiles in the parabiotic species Crematogaster modiglianii and Camponotus rufifemur from the tropical rainforest of Borneo. The cuticle of both species is covered by a set of steroids, which are highly unusual surface compounds. They also occur in the Dufour gland of Crematogaster modiglianii in high quantities. The composition of these steroids differed between colonies but was highly similar among the two species of a parabiotic nest. In contrast, hydrocarbon composition of Cr. modiglianii and Ca. rufifemur differed strongly and only overlapped in three regularly occurring and three trace compounds. The hydrocarbon profile of Camponotus rufifemur consisted almost exclusively of methyl-branched alkenes of unusually high chain lengths (up to C49). This species occurred in two sympatric, chemically distinct varieties with almost no hydrocarbons in common. Cr. modiglianii discriminated between these two varieties. It only tolerated workers of the Ca. rufifemur variety it was associated with, but attacked the respective others. However, Cr. modiglianii did not distinguish its own Ca. rufifemur partner from allocolonial Ca. rufifemur workers of the same variety.

Conclusion

We conclude that there is a mutual substance transfer between Cr. modiglianii and Ca. rufifemur. Ca. rufifemur actively or passively acquires cuticular steroids from its Cr. modiglianii partner, while the latter acquires at least two cuticular hydrocarbons from Ca. rufifemur. The cuticular substances of both species are highly unusual regarding both substance classes and chain lengths, which may cause the apparent inability of Cr. modiglianii to discriminate Ca. rufifemur nestmates from allocolonial Ca. rufifemur workers of the same chemical variety.
Genetic characterization of Measles Viruses in China, 2004
Authors: Zhang Yan , Ji Yixin , Jiang Xiaohong , Xu Songtao , Zhu Zhen , Zheng Lei , He Jilan , Ling Hua , Wang Yan , Liu Yang , Du Wen , Yang Xuelei , Mao Naiying , Xu Wenbo
Published: October 2008

Genetic characterization of wild-type measles virus was studied using nucleotide sequencing of the C-terminal region of the N protein gene and phylogenetic analysis on 59 isolates from 16 provinces of China in 2004. The results showed that all of the isolates belonged to genotype H1. 51 isolates were belonged to cluster 1 and 8 isolates were cluster 2 and Viruses from both clusters were distributed throughout China without distinct geographic pattern. The nucleotide sequence and predicted amino acid homologies of the 59 H1 strains were 96.5%–100% and 95.7%–100%, respectively. The report showed that the transmission pattern of genotype H1 viruses in China in 2004 was consistent with ongoing endemic transmission of multiple lineages of a single, endemic genotype. Multiple transmission pathways leaded to multiple lineages within endemic genotype.
The genome and proteome of the Kluyvera bacteriophage Kvp1 – another member of the T7-like Autographivirinae
Authors: Lingohr Erika J , Villegas Andre , She Yi-Min , Ceyssens Pieter-Jan , Kropinski Andrew M
Published: October 2008

Background

Kluyvera, a genus within the family Enterobacteriaceae, is an infrequent cause of human infections. Bacteriophage Kvp1, the only bacteriophage isolated for one of its species, Kluyvera cryocrescens, is a member of the viral family Podoviridae.

Results

The genome of Kvp1, the first Kluyvera cryocrescens-specific bacteriophage, was sequenced using pyrosequencing (454 technology) at the McGill University and Genome Québec Innovation Centre. The two contigs were closed using PCR and the sequence of the terminal repeats completed by primer walking off the phage DNA. The phage structural proteome was investigated by SDS-PAGE and mass spectrometry.

Conclusion

At 39,472 bp, the annotated genome revealed a closer relationship to coliphage T3 than T7 with Kvp1 containing homologs to T3 early proteins S-adenosyl-L-methionine hydrolase (0.3) and protein kinase (0.7). The quantitative nature of the relationships between Kvp1 and the other members of the T7-like virus genus (T7, T3, φA1122, φYeO3-12, Berlin, K1F, VP4 and gh-1) was confirmed using CoreGenes.
Widespread distribution and a new recombinant species of Brazilian virus associated with cotton blue disease
Authors: Silva TF , Corrêa RL , Castilho Y , Silvie P , Bélot J-L , Vaslin MFS
Published: October 2008

Background

Cotton blue disease (CBD), an important global cotton crop pathology responsible for major economic losses, is prevalent in the major cotton-producing states of Brazil. Typical CBD symptoms include stunting due to internodal shortening, leaf rolling, intense green foliage, and yellowing veins. Atypical CBD symptoms, including reddish and withered leaves, were also observed in Brazilian cotton fields in 2007. Recently, a Polerovirus named Cotton leafroll dwarf virus (CLRDV) was shown to be associated with CBD.

Results

To understand the distribution and genetic diversity of CLRDV in Brazil, we analyzed 23 CBD-symptomatic plants from susceptible cotton varieties originating from five of the six most important cotton-growing states, from 2004–2007. Here, we report on CLRDV diversity in plants with typical or atypical CBD symptoms by comparing viral coat protein, RNA polymerase (RdRp), and intergenic region genomic sequences.

Conclusion

The virus had a widespread distribution with a low genetic diversity; however, three divergent isolates were associated with atypical CBD symptoms. These divergent isolates had a CLRDV-related coat protein but a distinct RdRp sequence, and probably arose from recombination events. Based on the taxonomic rules for the family Luteoviridae, we propose that these three isolates represent isolates of a new species in the genus Polerovirus.
Randomized controlled trial to treat migraine with acupuncture: design and protocol
Authors: Li Ying , Liang Fanrong , Yu Shuguang , Liu Xuguang , Tang Yong , Yang Xuguang , Tian Xiaoping , Yan Jie , Sun Guojie , Chang Xiaorong , Zheng Hui , Zhang Hongxing , Ma Tingting
Published: October 2008

Background and motivation

The effectiveness of using acupuncture to treat migraine is rarely and even suspectedly reported in the literature. In this article, we report the design and the protocol of a randomized controlled large-scale trial to treat migraine using acupuncture, aiming at testifying it is effective to use acupuncture to treat migraine. We demonstrate also that the effectiveness of the treatment may vary due to using acupoints of different meridians or different acupoints of one meridian.

Methods and design

A multi-center randomized controlled trial is currently undergoing, with three acupoints treatment groups and one non-acupoints control group. The acupuncture treatment consists of 20 sessions per patient with a observation period of 20 weeks. In total, 480 patients with Migraine are registered in this study within 8 hospitals in China from March 2008 to June 2009. These patients are randomly assigned to receive one of the following four acupoints treatment groups, i.e. 1) specific acupoints of Shaoyang meridians (120 patients), 2) non-specific acupoints of Shaoyang meridians (120 patients), 3) acupoints of other meridians (120 patients); or 4) non-acupoints control group (120 patients). The main outcome measurement in this trial is the effect comparison achieved among these four groups in terms of number of days with migraine and intensity of migraine during and after the baseline phase, i.e. the first 4 weeks before randomization and 4, 8 and 16 weeks after randomization. The intensity of headache including Headache intensity grade (0–3) and visual analogue scale (VAS) score will also be used in this study. In addition, the differences of Migraine-Specific Quality-of-Life Questionnaire (MSQ) and Transcranial Doppler Sonography (TCD) before and after randomization are also used as the secondary outcome measurement.

Discussion

The result of this trial (which will be available in 2009) will demonstrate the efficacy of using acupuncture to treat migraine, and verify whether the specific effect of acupoints exists and whether this specific effect of acupoints is related to meridian and a collection of meridian Qi.

Trials registration

Clinical Trials.gov NCT00599586
Breastfeeding in the workplace: Other employees' attitudes towards services for lactating mothers
Authors: Suyes Kathryn , Abrahams Sheryl W , Labbok Miriam H
Published: October 2008

Background

Workplace accommodations for breastfeeding mothers are an important step towards achieving United States Healthy People 2010 goals for continued breastfeeding. However, evidence suggests that some employers wishing to accommodate lactating mothers fear negative reactions from other workers.

Methods

This study conducted in February 2007, used descriptive statistics and linear regression to assess attitudes towards workplace breastfeeding/milk expression among employees (n = 407) of a large U.S. corporation providing a wide variety of workplace accommodations for lactating mothers.

Results

Overall, attitudes about the impact of breastfeeding on the work environment were favorable. Previous exposure to a co-worker who breastfed or expressed milk during the work day was associated with a positive attitude towards workplace breastfeeding, even after controlling for respondents' gender, length of employment and personal breastfeeding history.

Conclusion

These preliminary findings suggest that lactation accommodations did not have negative repercussions for other employees, and that a corporate environment designed to enable and encourage continued breastfeeding does not endanger positive attitudes towards breastfeeding in other employees.
Fourier-transform infrared anisotropy in cross and parallel sections of tendon and articular cartilage
Authors: Ramakrishnan Nagarajan , Xia Yang , Bidthanapally Aruna
Published: October 2008

Background

Fourier Transform Infrared Imaging (FTIRI) is used to investigate the amide anisotropies at different surfaces of a three-dimensional cartilage or tendon block. With the change in the polarization state of the incident infrared light, the resulting anisotropic behavior of the tissue structure is described here.

Methods

Thin sections (6 μm thick) were obtained from three different surfaces of the canine tissue blocks and imaged at 6.25 μm pixel resolution. For each section, infrared imaging experiments were repeated thirteen times with the identical parameters except a 15° increment of the analyzer's angle in the 0° – 180° angular space. The anisotropies of amide I and amide II components were studied in order to probe the orientation of the collagen fibrils at different tissue surfaces.

Results

For tendon, the anisotropy of amide I and amide II components in parallel sections is comparable to that of regular sections; and tendon's cross sections show distinct, but weak anisotropic behavior for both the amide components. For articular cartilage, parallel sections in the superficial zone have the expected infrared anisotropy that is consistent with that of regular sections. The parallel sections in the radial zone, however, have a nearly isotropic amide II absorption and a distinct amide I anisotropy.

Conclusion

From the inconsistency in amide anisotropy between superficial to radial zone in parallel section results, a schematic model is used to explain the origins of these amide anisotropies in cartilage and tendon.
Evaluation of Dimebon in cellular model of Huntington's disease
Authors: Wu Jun , Li Qin , Bezprozvanny Ilya
Published: October 2008

Background

Dimebon is an antihistamine compound with a long history of clinical use in Russia. Recently, Dimebon has been proposed to be useful for treating neurodegenerative disorders. It has demonstrated efficacy in phase II Alzheimer's disease (AD) and Huntington's disease (HD) clinical trials. The mechanisms responsible for the beneficial actions of Dimebon in AD and HD remain unclear. It has been suggested that Dimebon may act by blocking NMDA receptors or voltage-gated Ca2+ channels and by preventing mitochondrial permeability pore transition.

Results

We evaluated the effects of Dimebon in experiments with primary striatal neuronal cultures (MSN) from wild type (WT) mice and YAC128 HD transgenic mice. We found that Dimebon acts as an inhibitor of NMDA receptors (IC50 = 10 μM) and voltage-gated calcium channels (IC50 = 50 μM) in WT and YAC128 MSN. We further found that application of 50 μM Dimebon stabilized glutamate-induced Ca2+ signals in YAC128 MSN and protected cultured YAC128 MSN from glutamate-induced apoptosis. Lower concentrations of Dimebon (5 μM and 10 μM) did not stabilize glutamate-induced Ca2+ signals and did not exert neuroprotective effects in experiments with YAC128 MSN. Evaluation of Dimebon against a set of biochemical targets indicated that Dimebon inhibits α-Adrenergic receptors (α1A, α1B, α1D, and α2A), Histamine H1 and H2 receptors and Serotonin 5-HT2c, 5-HT5A, 5-HT6 receptors with high affinity. Dimebon also had significant effect on a number of additional receptors.

Conclusion

Our results suggest that Ca2+ and mitochondria stabilizing effects may, in part, be responsible for beneficial clinical effects of Dimebon. However, the high concentrations of Dimebon required to achieve Ca2+ stabilizing and neuroprotective effects in our in vitro studies (50 μM) indicate that properties of Dimebon as cognitive enhancer are most likely due to potent inhibition of H1 histamine receptors. It is also possible that Dimebon acts on novel high affinity targets not present in cultured MSN preparation. Unbiased evaluation of Dimebon against a set of biochemical targets indicated that Dimebon efficiently inhibited a number of additional receptors. Potential interactions with these receptors need to be considered in interpretation of results obtained with Dimebon in clinical trials.
Permutation – based statistical tests for multiple hypotheses
Authors: Camargo Anyela , Azuaje Francisco , Wang Haiying , Zheng Huiru
Published: October 2008

Background

Genomics and proteomics analyses regularly involve the simultaneous test of hundreds of hypotheses, either on numerical or categorical data. To correct for the occurrence of false positives, validation tests based on multiple testing correction, such as Bonferroni and Benjamini and Hochberg, and re-sampling, such as permutation tests, are frequently used. Despite the known power of permutation-based tests, most available tools offer such tests for either t-test or ANOVA only. Less attention has been given to tests for categorical data, such as the Chi-square. This project takes a first step by developing an open-source software tool, Ptest, that addresses the need to offer public software tools incorporating these and other statistical tests with options for correcting for multiple hypotheses.

Results

This study developed a public-domain, user-friendly software whose purpose was twofold: first, to estimate test statistics for categorical and numerical data; and second, to validate the significance of the test statistics via Bonferroni, Benjamini and Hochberg, and a permutation test of numerical and categorical data. The tool allows the calculation of Chi-square test for categorical data, and ANOVA test, Bartlett's test and t-test for paired and unpaired data. Once a test statistic is calculated, Bonferroni, Benjamini and Hochberg, and a permutation tests are implemented, independently, to control for Type I errors. An evaluation of the software using different public data sets is reported, which illustrates the power of permutation tests for multiple hypotheses assessment and for controlling the rate of Type I errors.

Conclusion

The analytical options offered by the software can be applied to support a significant spectrum of hypothesis testing tasks in functional genomics, using both numerical and categorical data.
Bladder incarceration following anterior external fixation of a traumatic pubic symphysis diastasis treated with immediate open reduction and internal fixation
Authors: Finnan Ryan P , Herbenick Michael A , Prayson Michael J , McCarthy Mary C
Published: October 2008

Anterior pelvic ring disruptions are often associated with injuries to the genitourinary structures with the potential for considerable resultant morbidity. Herniation of the bladder into the symphyseal region after injury with subsequent entrapment upon reduction of the symphyseal diastasis has seldom been reported in the literature. We report such a case involving bladder herniation and subsequent entrapment after attempted closed reduction with anterior pelvic external fixation immediately treated with open reduction and internal fixation along with a review of the literature.
Seroprevalence and epidemiological correlates of Toxoplasma gondii infections among patients referred for hospital-based serological testing in Doha, Qatar
Authors: Abu-Madi Marawan A , Al-Molawi Naema , Behnke Jerzy M
Published: October 2008

Background

The city of Doha in Qatar has a high density of feral cats and there is a high risk of toxoplasmosis for the resident human population. No data currently exist for the prevalence of infection with Toxoplasma gondii in the city.

Methods

We analysed the serological response to Toxoplasma gondii of 1625 subjects referred for routine hospital based serological tests in Doha, Qatar. Prevalence of current/recent infection was assessed through an enzyme-linked immunosorbent assay (ELISA) for the presence of specific anti-T. gondii IgM antibodies, and previous history of infection through IgG.

Results

Overall prevalence of IgG responses was 29.8% and this did not differ between the sexes nor between the three years of the study although there was a marked age effect. Among children less than 1 year old prevalence was 22.9%, but then dropped to <4% in the 1 year old group, indicating that these antibodies were most likely acquired in utero from immune mothers. Prevalence then increased steadily to peak at 41.2% among the oldest age class (>45 years). The prevalence of IgG antibody also varied significantly with region of origin, with higher rates for subjects from Africa, followed by those from the Eastern Mediterranean or Asia and lowest rates for subjects from the Arabian Peninsula. No IgM antibodies were detected in any subjects younger than 19 years, but prevalence increased to plateau at 7 – 9% in subjects aged over 20 years, and also varied with region of origin. In this case prevalence was highest among subjects from the Arabian Peninsula and least among those from Asia. Prevalence of IgM was higher among male subjects but did not vary between the three years of the study.

Conclusion

Although these data are based on a selected subset of the population, they nevertheless provide the first evidence that toxoplasmosis is endemic in Qatar in the human population, and that both age and region of origin play a role in the epidemiology of the infection. Concerns relating to the role of high density of feral cats in sustaining the infection were highlighted.
Hypermethylation of the DPYD promoter region is not a major predictor of severe toxicity in 5-fluorouracil based chemotherapy
Authors: Amstutz Ursula , Farese Simone , Aebi Stefan , Largiadèr Carlo R
Published: October 2008

Background

The activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme of pyrimidine catabolism, is thought to be an important determinant for the occurrence of severe toxic reactions to 5-fluorouracil (5-FU), which is one of the most commonly prescribed chemotherapeutic agents for the treatment of solid cancers. Genetic variation in the DPD gene (DPYD) has been proposed as a main factor for variation in DPD activity in the population. However, only a small proportion of severe toxicities in 5-FU based chemotherapy can be explained with such rare deleterious DPYD mutations resulting in severe enzyme deficiencies. Recently, hypermethylation of the DPYD promoter region has been proposed as an alternative mechanism for DPD deficiency and thus as a major cause of severe 5-FU toxicity.

Methods

Here, the prognostic significance of this epigenetic marker with respect to severe 5-FU toxicity was assessed in 27 cancer patients receiving 5-FU based chemotherapy, including 17 patients experiencing severe toxic side effects following drug administration, none of which were carriers of a known deleterious DPYD mutation, and ten control patients. The methylation status of the DPYD promoter region in peripheral blood mononuclear cells was evaluated by analysing for each patient between 19 and 30 different clones of a PCR-amplified 209 base pair fragment of the bisulfite-modified DPYD promoter region. The fragments were sequenced to detect bisulfite-induced, methylation-dependent sequence differences.

Results

No evidence of DPYD promoter methylation was observed in any of the investigated patient samples, whereas in a control experiment, as little as 10% methylated genomic DNA could be detected.

Conclusion

Our results indicate that DYPD promoter hypermethylation is not of major importance as a prognostic factor for severe toxicity in 5-FU based chemotherapy.
PTTG: an important target gene for ovarian cancer therapy
Authors: Panguluri Siva Kumar , Yeakel Casey , Kakar Sham S
Published: October 2008

Pituitary tumor transforming gene (PTTG), also known as securin is an important gene involved in many biological functions including inhibition of sister chromatid separation, DNA repair, organ development, and expression and secretion of angiogenic and metastatic factors. Proliferating cancer cells and most tumors express high levels of PTTG. Overexpression of PTTG in vitro induces cellular transformation and development of tumors in nude mice. The PTTG expression levels have been correlated with tumor progression, invasion, and metastasis. Recent studies show that down regulation of PTTG in tumor cell lines and tumors in vivo results in suppression of tumor growth, suggesting its important role in tumorigenesis. In this review, we focus on PTTG structure, sub-cellular distribution, cellular functions, and role in tumor progression with suggestions on possible exploration of this gene for cancer therapy.
Prevention of the sexual transmission of HIV‐1: preparing for success
Authors: Cohen Myron S , Kaleebu Pontiano , Coates Thomas
Published: October 2008

There are four opportunities for HIV prevention: before exposure, at the moment of exposure, immediately after exposure, and as secondary prevention focused on infected subjects. Until recently, most resources have been directed toward behavioral strategies aimed at preventing exposure entirely. Recognizing that these strategies are not enough to contain the epidemic, investigators are turning their attention to post‐exposure prevention opportunities. There is increasing focus on the use of ART–either systemic or topical (microbicides)–to prevent infection at the moment of exposure. Likewise, there is growing evidence that ART treatment of infected people could serve as prevention as well. A number of ongoing clinical trials will shed some light on the potential of these approaches. Above all, prevention of HIV requires decision‐makers to focus resources on strategies that are most effective. Finally, treatment of HIV and prevention of HIV must be considered and deployed together.
The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability
Authors: Waeschle Reiner M , Moerer Onnen , Hilgers Reinhard , Herrmann Peter , Neumann Peter , Quintel Michael
Published: October 2008

Introduction

The purpose of this study was to assess the relation between glycaemic control and the severity of sepsis in a cohort of patients treated with intensive insulin therapy (IIT).

Methods

In a prospective, observational study, all patients in the intensive care unit (ICU) (n = 191) with sepsis, severe sepsis or septic shock were treated with IIT (target blood glucose (BG) level 80 to 140 mg/dl instead of strict normoglycaemia). BG values were analysed by calculating mean values, rate of BG values within different ranges, rate of patients experiencing BG values within different levels and standard deviation (SD) of BG values as an index of glycaemic variability.

Results

The number of patients with hypoglycaemia and hyperglycaemia was highly dependent on the severity of sepsis (critical hypoglycaemia ≤ 40 mg/dl: sepsis: 2.1%, severe sepsis: 6.0%, septic shock: 11.5%, p = 0.1497; hyperglycaemia: >140 mg/dl: sepsis: 76.6%, severe sepsis: 88.0%, septic shock: 100%, p = 0.0006; >179 mg/dl: sepsis: 55.3%, severe sepsis: 73.5%, septic shock: 88.5%, p = 0.0005; >240 mg/dl: sepsis: 17.0%, severe sepsis: 48.2%, septic shock: 45.9%, p = 0.0011). Multivariate analyses showed a significant association of SD levels with critical hypoglycaemia especially for patients in septic shock (p = 0.0197). In addition, SD levels above 20 mg/dl were associated with a significantly higher mortality rate relative to those with SD levels below 20 mg/dl (24% versus 2.5%, p = 0.0195).

Conclusions

Patients with severe sepsis and septic shock who were given IIT had a high risk of hypoglycaemia and hyperglycaemia. Among these patients even with a higher target BG level, IIT mandates an increased awareness of the occurrence of critical hypoglycaemia, which is related to the severity of the septic episode.
Does Age Really Matter? Recall of Information Presented to Newly Referred Patients With Cancer
Authors: Jansen Jesse , Butow Phyllis N. , van Weert Julia C.M. , van Dulmen Sandra , Devine Rhonda J. , Heeren Thea J. , Bensing Jozien M. , Tattersall Martin H.N.
Published: October 2008

Purpose

To examine age- and age-related differences in recall of information provided during oncology consultations.

Patients and Methods

Two hundred sixty patients with cancer diagnosed with heterogeneous cancers, seeing a medical or radiation oncologist for the first time, participated in the study. Patients completed questionnaires assessing information needs and anxiety. Recall of information provided was measured using a structured telephone interview in which patients were prompted to remember details physicians gave about diagnosis, prognosis, and treatment. Recall was checked against the actual communication in audio-recordings of the consultations.

Results

Recall decreased significantly with age, but only when total amount of information presented was taken into account. This indicates that if more information is discussed, older patients have more trouble remembering the information than younger ones. In addition, recall was selectively influenced by prognosis. First, patients with a poorer prognosis recalled less. Next, the more information was provided about prognosis, the less information patients recalled, regardless of their actual prognosis.

Conclusion

Recall is not simply a function of patient age. Age only predicts recall when controlling for amount of information presented. Both prognosis and information about prognosis are better predictors of recall than age. These results provide important insights into intervention strategies to improve information recall in patients with cancer.
Clinical Outcome and Predictors of Survival in Late Relapse of Germ Cell Tumor
Authors: Sharp David S. , Carver Brett S. , Eggener Scott E. , Kondagunta G. Varuni , Motzer Robert J. , Bosl George J. , Sheinfeld Joel
Published: October 2008

Purpose

Late relapse (LR) of germ cell tumor (GCT) is a well recognized entity associated with poor survival. We report on our experience with LR and determine predictors of survival.

Patients and Methods

From 1990 to 2004, 75 patients were managed for LR of GCT at our institution. Clinical and pathologic parameters were reviewed. Estimates of cancer-specific survival were generated using the Kaplan-Meier method, and a Cox proportional hazards model was used to assess potential predictors of outcome.

Results

The median time to LR was 6.9 years (range, 2.1 to 37.7 years). Overall, 56 patients (75%) had LR in the retroperitoneum, including 25 (93%) of 27 patients initially managed without retroperitoneal lymph node dissection. The 5-year cancer-specific survival (CSS) was 60% (95% CI, 46% to 71%). Patients who underwent complete surgical resection at time of LR (n = 45) had a 5-year CSS of 79% versus 36% for patients without complete resection (n = 30; P < .0001). The 5-year CSS for chemotherapy-naive patients was significantly greater than patients with a prior history of chemotherapy as part of their initial management (5-year CSS, 93% v 49%, respectively). In multivariable analysis of pretreatment parameters available at the time of LR, the presence of symptoms (hazard ratio [HR] = 4.9) and multifocal disease (HR = 3.0) were associated with an inferior CSS.

Conclusion

The data suggest that meticulous control of the retroperitoneum is critical to prevent LR in the retroperitoneum. In multivariable analysis, patients with a symptomatic presentation and those with multifocal disease have a significantly decreased survival. Survival is greatly improved if complete surgical excision of disease is attained.
Chemotherapy As an Alternative to Radiotherapy in the Treatment of Stage IIA and IIB Testicular Seminoma: A Spanish Germ Cell Cancer Group Study
Authors: Garcia-del-Muro Xavier , Maroto Pablo , Gumà Josep , Sastre Javier , López Brea Marta , Arranz José A. , Lainez Nuria , de Prado Diego Soto , Aparicio Jorge , Piulats José M. , Pérez Xavier , Germá-Lluch Josep R.
Published: October 2008

Purpose

To assess the long-term efficacy and toxicity of front-line cisplatin-based chemotherapy in patients with stage IIA or IIB testicular seminoma.

Patients and Methods

Untreated patients with pure seminoma of the testis after orchiectomy, with clinical stage IIA or IIB, were considered eligible for this prospective observational study. Chemotherapy consisted of either four cycles of cisplatin and etoposide or three cycles of cisplatin, etoposide, and bleomycin.

Results

Between April 1994 and March 2003, 72 patients were entered onto the study at 26 participating centers. Eighteen patients had stage IIA disease, and 54 patients had stage IIB disease. Eighty-three percent of patients achieved complete response, and 17% achieved partial response with residual mass. After a median follow-up time of 71.5 months, six patients with stage IIB disease experienced relapse, and one of these patients died as a result of seminoma. Three patients experienced non–seminoma-related deaths (two died from a further esophageal carcinoma, and one died from an upper digestive hemorrhage). The estimated 5-year progression-free survival rates for patients with stage IIA or IIB disease were 100% and 87% (95% CI, 77.5% to 97%), respectively. Five-year progression-free and overall survival rates for the whole group were 90% (95% CI, 82% to 98%) and 95% (95% CI, 89% to 100%), respectively. Severe granulocytopenia and thrombocytopenia were observed in eight and two patients, respectively. Mild to moderate emesis, stomatitis, and diarrhea were the most common nonhematologic effects.

Conclusion

Chemotherapy is a highly effective and well-tolerated treatment for patients with stage IIA or IIB seminoma and represents an available alternative that could avoid some of the serious late effects associated with radiotherapy. Further studies focusing on long-term toxicities of different treatment modalities are needed.
Pathologic Response to Preoperative Chemotherapy: A New Outcome End Point After Resection of Hepatic Colorectal Metastases
Authors: Blazer Dan G. , Kishi Yoji , Maru Dipen M. , Kopetz Scott , Chun Yun Shin , Overman Michael J. , Fogelman David , Eng Cathy , Chang David Z. , Wang Huamin , Zorzi Daria , Ribero Dario , Ellis Lee M. , Glover Katrina Y. , Wolff Robert A. , Curley Steven A. , Abdalla Eddie K. , Vauthey Jean-Nicolas
Published: October 2008

Purpose

The primary goal of this study was to evaluate whether pathologic response to chemotherapy predicts patient survival after preoperative chemotherapy and resection of colorectal liver metastases (CLM). The secondary goal of the study was to identify the clinical predictors of pathologic response.

Patients and Methods

A retrospective review was performed of 305 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by resection of CLM. Pathologic response was systematically evaluated and reported as the mean of the percentage of cancer cells remaining within each tumor. Univariate and multivariate analyses were performed to identify the predictors of pathologic response and survival.

Results

Cumulative 5-year overall survival rates by pathologic response status were as follows: 75% complete response (no residual cancer cells), 56% major response (1% to 49% residual cancer cells), and 33% minor response (≥ 50% residual cancer cells; complete v major response, P = .037; major v minor response, P = .028). Multivariate analysis revealed that only surgical margin status (P = .050; hazard ratio [HR], 1.77) and pathologic response (major response: P = .034; HR, 4.80; minor response: P = .007; HR, 6.93) were independent predictors of survival. Multivariate analysis of the predictors of pathologic response revealed that carcinoembryonic antigen level ≤ 5 ng/mL, tumor size ≤ 3 cm, and chemotherapy with fluoropyrimidine plus oxaliplatin and bevacizumab were independent predictors of pathologic response.

Conclusion

Pathologic response predicts survival after preoperative chemotherapy and resection of CLM. Degree of pathologic response represents a new outcome end point for prognosis after resection of CLM.
Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by un-derivatized liquid chromatography-tandem mass spectrometry
Authors: Carling R S , Hogg S L , Wood T C , Calvin J
Published: October 2008

Background

Creatine plays an important role in the storage and transmission of phosphate-bound energy. The cerebral creatine deficiency syndromes (CCDS) comprise three inherited defects in creatine biosynthesis and transport. They are characterized by mental retardation, speech and language delay and epilepsy. All three disorders cause low-creatine signal on brain magnetic resonance spectroscopy (MRS); however, MRS may not be readily available and even when it is, biochemical tests are required to determine the underlying disorder.

Methods

Analysis was performed by liquid chromatography-tandem mass spectrometry in positive ionization mode. Samples were analysed underivatized using a rapid ‘dilute and shoot’ approach. Chromatographic separation of the three compounds was achieved. Stable isotope internal standards were used for quantification.

Results

Creatine, creatinine and guanidinoacetate were measured with a 2.5 minute run time. For guanidinoacetate, the standard curve was linear to at least 5000 μmol/L and for creatine and creatinine it was linear to at least 25 mmol/L. The lower limit of quantitation was 0.4 μmol/L for creatine and guanidinoacetate and 0.8 μmol/L for creatinine. Recoveries ranged from 86% to 106% for the three analytes. Intra- and inter-assay variation for each analyte was <10% in both urine and plasma.

Conclusion

A tandem mass spectrometric method has been developed and validated for the underivatized determination of guanidinoacetate, creatine and creatinine in human urine and plasma. Minimal sample preparation coupled with a rapid run time make the method applicable to the routine screening of patients with suspected CCDS.
Three cases of congenital adrenal hypoplasia with novel mutations in the (NROB1) DAX-1 gene
Authors: Wheeler B , George P M , MacKenzie K , Hunt P , Potter H C , Florkowski C M
Published: October 2008

Abnormalities in the DAX-1 gene (dosage-sensitive sex reversal–adrenal hypoplasia gene on the X chromosome) are a well-recognized cause of congenital adrenal hypoplasia. DAX-1 is expressed in the adrenal cortex, gonads, hypothalamus and anterior pituitary, which gives rise to the clinical features of this deletion. Presentations are varied but salt-wasting and/or hypoglycaemia are the most common in an infant, with late onset of hypogonadotrophic hypogonadism. Over 80 different mutations in this gene have been identified. We present three unrelated cases with variable clinical presentations, all with novel mutations in the DAX-1 gene.
Median parameters for Down's syndrome screening should be calculated using a moving time-window method
Authors: Reynolds T M , Aldis J
Published: October 2008

Background

In Down's syndrome screening, the change in analyte concentrations in maternal serum with advancing gestational age is compensated for by converting concentration to multiples of the median (MoM) by using a mathematical equation describing the expected relationship. However, owing to assay drifts and shift, the equation may be incorrect, leading to deviation of the observed MoM distribution from the ideal MoM distribution. The NHS Fetal Anomaly Screening Programme has produced standards limiting acceptable deviation, and has provided the Down's Syndrome Screening Quality Assurance Service (DQASS) to monitor it. DQASS recommends monitoring by cumulative sum plot.

Methods

Down's screening data for 61,368 consecutive samples (12 October 2004 to 31 December 2007) was evaluated using different median assignment techniques.

Results

A change in the paradigm for median equation derivation is described, which significantly improves the probability that medians will be correct at any point in time.

Conclusion

Software developers need to change the way medians are derived in their programmes.
The effect of paraproteins on the erythrocyte sedimentation rate: a comparison between the StarrSed and TEST 1
Authors: Raijmakers Maarten T M , Kuijper Philip H M , Bakkeren Dirk L , Vader Huib L
Published: October 2008

Background

The principle of the erythrocyte sedimentation rate (ESR) as assessed by TEST 1 is different from that of Westergren-based methods. This could result in different influences on the tests by paraproteins.

Methods

We investigated the effect of paraproteins on ESR readings by TEST 1 ( y) and the StarrSed ( x), a Westergren-based method, in 142 patients with paraproteinaemia. Agreement (Passing-Bablok) and bias (Bland–Altman) between methods was investigated and compared with that of a control population.

Results

A poor agreement between the two methods was found in patients with a paraprotein ( y = 0.67 x + 3.3) in comparison with that of the control population ( y = 0.96 x + 0.2). Large differences between methods were present when ESR readings were >40 mm/hour, but clinical interpretation was similar in 90% of cases. Linear regression showed a concentration dependent influence of paraproteins on ESR readings by the StarrSed, especially for immunoglobulin class IgM.

Conclusion

ESR readings by TEST 1 result in similar clinical interpretation for most subjects, but readings are less influenced by the presence of a paraprotein than those of a Westergren-based method.
High iodine (substrate) turnover Graves' disease: the intriguing ‘rapid responder’ variant of thyrotoxicosis
Authors: Dalan Rinkoo , Leow Melvin Khee-Shing , Ng David Chee-Eng
Published: October 2008

Factors determining the responsiveness to antithyroid drugs (ATDs) in Graves' disease are not fully known. Notwithstanding the typical pattern and tempo of thyroid hormone responses to thionamides, the existence of an unusual subset of Graves' disease with extraordinarily rapid thyroid hormone responses to ATDs will prove challenging even to the expert clinician. Termed ‘rapid responder Graves' disease’ or ‘high turnover Graves' disease’, the serum thyroxine (FT4) and triiodothyronine (FT3) of patients with this variant of thyrotoxicosis can decline precipitously during the initiation of ATDs and yet escalate acutely upon discontinuation of pharmacological intervention. We describe a case that presented with low serum FT4 and FT3 in association with suppressed serum thyrotropin (TSH) concentrations soon after starting carbimazole even at a low dose. The erratic clinical course comprising largely of serum FT4 nadirs and peaks is elaborated to facilitate appreciation of the difficulty in the stabilization of the thyroid with ATDs. The possible pathogenetic mechanisms for the chaotic fluctuations in thyroid hormones to minor changes in thionamide dose adjustments are discussed as well.
Uncertainty of sweat chloride testing: does the right hand know what the left hand is doing?
Authors: Mackay R J , Florkowski C M , George P M , Sies C W , Woods S
Published: October 2008

Although analytical variation in sweat electrolyte testing can be easily estimated, there is limited data on total variation. This study aims to evaluate the total variation of the sweat test by measuring the difference between sweat electrolyte values in specimens obtained simultaneously from two sites. Chloride is recommended in published guidelines as the only discriminant for the diagnosis of cystic fibrosis, and sodium may be measured as a guide to the adequacy of collection and analysis. Both are reported here. Sweat was collected in patients by the Gibson Cooke method from two sites simultaneously. Coefficient of variation in this laboratory is 4.1 and 5% for chloride and sodium, respectively. 295 patients had sufficient sweat collected from both sites for analysis. The values for chloride and sodium were compared between the two sites. The total coefficient of variation (CVt) calculated for the whole group between the two sites was 20.2% for chloride and 16.9% for sodium, and the standard deviations 4.3 mmol/L and 4.8 mmol/L, respectively. In patients with intermediate chloride concentrations; in different age groups; and when those tests with a difference between sodium and chloride concentration of more than 15 were excluded, minimal differences in these figures were observed. Use of strictly defined cut-off points to discriminate between normal and intermediate electrolyte values, and between intermediate and raised electrolyte values, does not reflect the variation in sweat electrolyte content found within an individual patient. This has important implications for reporting.
Berkeley, Human Agency and Divine Concurrentism
Authors: McDonough Jeffrey K.
Published: October 2008

This paper aims to offer a sympathetic reading of Berkeley’s often maligned account of human agency. The first section briefly revisits three options concerning the relationship between human and divine agency available to theistically minded philosophers in the medieval and early modern eras. The second argues that, of those three views, only the position of concurrentism is consistent with Berkeley’s texts. The third section explores Berkeley’s reasons for adopting concurrentism by highlighting three motivating considerations drawn from his larger philosophical system. Finally, the fourth section attempts to flesh out Berkeley’s understanding of human activity by looking at how we might understand his claim that “we move our legs ourselves” in light of his commitments to idealism and concurrentism.
Necessary Connections and Continuous Creation: Malebranche’s Two Arguments for Occasionalism
Authors: Lee Sukjae
Published: October 2008

Malebranche presents two major arguments for occasionalism: the “no necessary connection” argument (NNC) and the “conservation is but continuous creation” argument (CCC). NNC appears prominently in his Search After Truth but virtually disappears and surrenders the spotlight to CCC in his later major work, Dialogues on Metaphysics and on Religion . This paper investigates the possible reasons and motivations behind this significant shift. I argue that the shift is no surprise if we consider the two ways in which the CCC is preferable to NNC: it is not only more effective against opponents but also more consistent with his own views on freedom.
Desgabets as a Cartesian Empiricist
Authors: Cook Monte
Published: October 2008

A long tradition regards Robert Desgabets as a Cartesian empiricist. He says things that sound strikingly like Locke, and he argues against anti-empiricist reasoning in Descartes, Malebranche, and Arnauld. Moreover, throughout his writings he endorses the empiricist principle that nothing is in the intellect except what was previously in the senses. Since the Cartesians are generally supposed to be prototypical non -empiricists, Desgabets’s being a Cartesian empiricist would make him a particularly interesting specimen. In this paper, however, I challenge the case for taking Desgabets to be an empiricist.
François Lamy, Occasionalism, and the Mind-Body Problem
Authors: Ablondi Fred
Published: October 2008

There is a long-standing view that Malebranche and his fellow occasionalists accepted occasionalism to solve the problem of interaction between immaterial souls and extended bodies. Recently, however, scholars have shown this story to be a myth. Malebranche, Geulincx, La Forge, and Cordemoy adopted occasionalism for a variety of reasons, but none did so because of a need to provide a solution to a perceived mind-body problem. Yet there is one Cartesian for whom the “traditional” reading is largely on the mark. François Lamy argues in the second volume of his De la Connoissance de Soi-Meme much as the standard story has it. In this article I discuss and analyze Lamy’s argument, showing how he deals with some of the many concerns that made occasionalism attractive, and how he brings out some of the thorny questions that an occasionalist must face.