bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Management of Skull Base Chondroblastoma
Authors: Kutz J Walter , Verma Sunil , Tan Hongying Tina , Lo William W. M. , Slattery William H. , Friedman Rick A.
Published: April 2007

Objectives: Chondroblastoma is a rare tumor accounting for 1% of primary bone tumors. Chondroblastoma involving the skull base is exceedingly rare with approximately 60 cases reported. We reviewed our experience with chondroblastoma of the skull base with an emphasis on current lateral skull base approaches and long‐term tumor control.

Study Design and Setting: A retrospective case review at a tertiary neurotology private practice group was performed over a 20‐year period. Five patients were identified with skull base chondroblastoma. All patients underwent surgical intervention, and success of surgery was determined by disease‐free status at last follow‐up. Mean follow‐up time was 5.8 years.

Results: Two patients underwent gross tumor removal as primary therapy. One patient underwent partial tumor removal at an outside institution, and follow‐up magnetic resonance imaging demonstrated rapid growth of residual tumor. This patient was successfully treated with gross total removal of residual tumor with an infratemporal craniotomy approach. Near total tumor removal was performed in two patients because of intimate involvement of vital structures. At last follow‐up, no patient had radiographic evidence of tumor recurrence. There were no significant postoperative complications.

Conclusions: Gross total or near total resection of skull base chondroblastomas through lateral skull base approaches results in long‐term tumor control and low complication rates.
Cholesteatoma in the Normal Hearing Ear
Authors: Smouha Eric E. , Javidfar Javanshir
Published: April 2007

Objectives/Hypothesis: Surgical treatment of cholesteatoma in ears with normal or near‐normal hearing represents a challenge, in that complete removal of disease may require sacrifice of the ossicular chain. Our aim was to identify the predictive factors and surgical strategies that favor hearing preservation in these patients.

Study Design: Retrospective case review.

Methods: Fifty‐four procedures were performed in 50 patients with cholesteatoma and a preoperative speech reception threshold or pure‐tone average (PTA) of less than 25 dB. Complete audiometric data were available in 51 cases. All patients had complete surgical removal of cholesteatoma. Whenever feasible, ossicular reconstruction was performed at the time of the initial surgical procedure.

Results: The median PTA changed by −3 dB, and hearing was preserved to within 10 dB of preoperative level in 72% of patients. An intact ossicular chain was found in 72% of the cases and could often be preserved at surgery. However, similar hearing outcomes resulted after intact versus reconstructed ossicular chains and in open versus closed mastoidectomies. The recidivism rate was 26%, and recidivistic cases had worse hearing outcomes. Congenital cholesteatomas and Prussak space cholesteatomas had better outcomes with respect to hearing preservation and recidivism.

Conclusions: Cholesteatoma in the normal hearing ear should be treated with the same surgical priorities as all other cholesteatomas. Preventing recidivism has a significant effect on hearing preservation, whereas preserving an intact ossicular chain and maintaining an intact canal wall do not.
Clinical Aspects of Type 1 Posterior Laryngeal Clefts: Literature Review and a Report of 31 Patients
Authors: van der Doef Hubert P. , Yntema Jan Bart , van den Hoogen Frank J. , Marres Henri A.
Published: April 2007

Objectives: The clinical relevance of posterior laryngeal clefts (PLCs) of type 1 has only recently been highlighted in the medical literature. We present a review of the literature and a report of a contributive series of 31 type 1 PLC patients.

Study Design and Methods: We performed a MEDLINE search of studies published between 1966 and September 2005 and a retrospective cohort study in children aged 0 to 16 years.

Results: In the reviewed articles as well as in the presented study, a high degree of comorbidity in patients with PLC type 1 is reported. The majority of patients (90%) with severe problems with oral feedings were treated conservatively by means of nasogastric tube feeding.

Conclusions: Increased awareness improves the chances of an accurate diagnosis of type 1 PLC in patients with congenital stridor. Type 1 PLC may be present in all patients with congenital stridor and laryngomalacia, particularly when stridor is accompanied by symptoms such as feeding difficulties and choking.
Quantitative Analysis of Syndecan‐1 Expression in Dysplasia and Squamous Cell Carcinoma of the Oral Cavity
Authors: Jackson Lana L. , Wade Zane , Hessler Richard B. , Abdelsayed Rafik , Rogers Jeremy B. , Gourin Christine G.
Published: April 2007

Introduction: Decreased expression of syndecan‐1 has been reported in dysplasia and squamous cell carcinoma (SCCA) of the oral cavity and appears to correlate with decreasing histological differentiation and poor clinical outcome. Assays of syndecan‐1 expression to date have utilized manual microscopic analysis with qualitative grading of immunohistochemical staining intensity, which may introduce observer bias. We evaluated syndecan‐1 expression in dysplasia and squamous cell carcinoma (SCCA) of the oral cavity, using a novel automated cellular imaging system that incorporates both staining intensity as well as the percentage of positively stained cells to yield a quantitative value for syndecan‐1 expression.

Materials and Methods: We performed a quantitative immunohistochemical analysis of syndecan‐1 expression using an automated cellular image analysis system. We analyzed specimens from cases of mild dysplasia (N = 55), moderate dysplasia (N = 38), severe dysplasia (N = 25), carcinoma in situ (CIS) (N = 43), and SCCA of the oral cavity (N = 45), using normal mucosal epithelium (N = 21) as a positive control. The SCCA specimens were further subdivided by degree of differentiation. We retrospectively reviewed patient charts to identify tumor stage at diagnosis, recurrence, and disease‐specific survival.

Results: Syndecan‐1 expression was significantly greater in normal controls than in specimens of mild, moderate, or severe dysplasia, CIS, or invasive SCCA (P < .05). Syndecan‐1 expression did not differ significantly among specimens of mild, moderate, or severe dysplasia, CIS or SCCA. There was no significant difference in syndecan‐1 expression between specimens from patients with no evidence of disease at 3 years follow‐up and patients with local, regional, or distant recurrence.

Conclusions: Syndecan‐1 expression does not appear to be useful as a marker of differentiation or as a prognostic indicator in dysplasia and SCCA of the oral cavity. The search for a suitable and reliable marker of biological aggressiveness is ongoing.
Prolonged Allergen Challenge in Murine Nasal Allergic Rhinitis: Nasal Airway Remodeling and Adaptation of Nasal Airway Responsiveness
Authors: Nakaya Muneo , Dohi Makoto , Okunishi Katsuhide , Nakagome Kazuyuki , Tanaka Ryoichi , Imamura Mitsuru , Yamamoto Kazuhiko , Kaga Kimitaka
Published: April 2007

Background: Nasal airway remodeling exists in allergic rhinitis, but it appears to be far less extensive than in asthma. However, there has been little study about nasal airway remodeling and no study using mice models. It has been reported that airway hyperresponsiveness decreased after prolonged allergen challenge in a chronic murine asthma model together with the progression of remodeling. However, there has been no study of the relation of remodeling and airway responsiveness in nasal allergy. Therefore, we have undertaken this investigation to characterize nasal airway structural changes after prolonged allergen challenge and to examine the relationship between nasal airway hyperresponsivity and remodeling.

Methods: We prepared murine allergic rhinitis for ovalbumin. Mice were subsequently challenged three times a week with ovalbumin from day 19 to days 53, 88, and 130. We examined allergen‐induced nasal symptoms and objective nasal hyperresponsiveness using the enhanced pause system. Moreover, the pathologic changes were investigated after allergen challenge.

Results: The extended allergen challenge protocol caused significant nasal airway remodeling. Specifically, remodeling was characterized by goblet cell hyperplasia and deposition of collagen in the submucosal area. Allergen‐induced nasal hyperresponsiveness was first increased but gradually decreased in nasal symptoms and Penh after prolonged allergen challenge.

Conclusions: We have demonstrated that a remodeling of nasal mucosa in a murine allergic rhinitis model prolonged allergen exposure. Moreover, prolonged allergen exposure induced a reduction of nasal hyperresponsiveness together with a progression of nasal remodeling.
Bilateral Myringoplasty in Chronic Otitis Media
Authors: Caye‐Thomasen Per , Nielsen Torfinnur Rubek , Tos Mirko
Published: April 2007

Objective: A theoretical risk of iatrogenic sensorineural hearing loss (HL) during surgery has induced a reluctance to perform bilateral myringoplasty/tympanoplasty type I among some otosurgeons. This paper presents results of bilateral surgery in 26 patients.

Material and Methods: Twenty‐six patients with bilateral, dry tympanic membrane perforations caused by chronic otitis media were selected prospectively for bilateral myringoplasty/tympanoplasty type I (52 ears) at a tertiary referral center. All patients had a HL corresponding to the size and localization of the perforation (no suspicion of ossicular chain defect or other pathology). Mean age was 13.3 years, and the male to female ratio was 1.36. All but one ear were operated through a transcanal approach, and the onlay technique was used most frequently (83%), with use of fascia (56%), tragal perichondrium (38%), or cartilage palisades (6%) as graft material. Follow‐up examination and hearing tests (pure tone and speech audiometry) were performed at a mean of 13.8 months after surgery.

Results: Perforation closure was obtained in 49 (94%) of the 52 ears. Hearing improved significantly, and the air‐bone gap was significantly reduced. The air‐bone gap was closed to within 10 dB in 92% and within 20 dB in 100% of the ears. Surprisingly good hearing was found during postoperative, bilateral ear canal gauze packing. Iatrogenic sensorineural HL did not occur.

Conclusions: We conclude that bilateral myringoplasty is safe, with good results, reduces costs, and leaves the patient satisfied. The hearing impairment during postoperative ear canal packing is surprisingly modest and readily acceptable by the patients.
Upper Airway Mucin Gene Expression: A Review
Authors: Ali Mahmoud S. , Pearson Jeffrey P.
Published: April 2007

Introduction: The gel‐like properties of mucus depend primarily on its content of mucins. The protein backbones of mucins are encoded by mucin genes. Of the currently known 20 mucin genes that encode protein backbone of mucins, 16 have been identified in the airways.

Method: We explored the current knowledge about upper airway mucin expression in health and disease conditions using a Medline search. We have also studied upper airway mucin gene expression and compared our results with the results from other studies.

Results: MUC5AC, MUC5B, and MUC2 are the principal gel‐forming mucins secreted in the airway. However, the spectrum of mucin expression in chronic upper airway diseases such as nasal polyps, chronic sinusitis, middle ear effusion, and cystic fibrosis is generally wide and variable.

Discussion: The wide spectrum of upper airway mucin expression is possibly caused by various anatomic and histologic features as well as physiologic and pathologic variables. These variables have not been fully explored yet, and the majority of airway mucin expression studies used small numbers of samples.

Conclusion: Studies including adequate numbers of samples (patients) are more likely to reveal a clearer profile and more precise expression patterns. Generating a clear profile of mucin expression patterns in health and disease requires the analysis of different variables, which can alter that expression. It is also essential to understand the various molecular mechanisms controlling mucin gene and protein expression. This could lead to the invention of novel therapeutic modalities to treat upper airway diseases.
Cost‐Effective Diagnosis of Ingested Foreign Bodies
Authors: Shrime Mark G. , Johnson Paul E. , Stewart Michael G.
Published: April 2007

Objectives: To compare the cost effectiveness of plain film radiography, computed tomography (CT), and endoscopy as initial diagnostic modalities in adult patients complaining of retained ingested foreign bodies.

Design: A systematic literature review was conducted to determine key statistics for the analysis, such as prevalence of disease, prevalence of complications, and the sensitivity and specificity of each diagnostic modality. Costs were estimated using 2006 Medicare reimbursement for hospital and professional fees. A deterministic cost‐effectiveness analysis was then conducted using decision analysis software and a decision tree model to evaluate the various diagnostic strategies. After identifying initial results, we also performed sensitivity and threshold analysis to assess the strength of the recommendations.

Results: We reviewed 316 abstracts, identified 16 pertinent studies that included a total of 7,088 patients with possible foreign bodies, and extracted key statistics from those papers. Decision analysis showed that CT scanning as an initial diagnostic strategy proved more cost effective than plain film or operative endoscopy. The incremental cost of immediate endoscopy for every additional correctly diagnosed patient was $5,238. Plain radiography was more costly and less effective, even with the addition of confirmatory CT scanning after a negative plain film. Sensitivity and threshold analyses demonstrated that these results are robust.

Conclusions: Patients presenting with a complaint of a retained ingested foreign body are most cost‐effectively managed with CT scan, after history and physical. Immediate endoscopy may be considered if CT is not available, although it adds significant cost. Plain films are dominated by these two diagnostic strategies.
Extreme sex ratio variation in relation to change in condition around conception
Authors: Cameron Elissa Z , Linklater Wayne L
Published: April 2007

Adaptive theory predicts that mothers would be advantaged by adjusting the sex ratio of their offspring in relation to their offspring's future reproductive success. Studies investigating sex ratio variation in mammals have produced notoriously inconsistent results, although recent studies suggest more consistency if sex ratio variation is related to maternal condition at conception, potentially mediated by changes in circulating glucose level. Consequently, we hypothesized that change in condition might better predict sex ratio variation than condition
per se
. Here, we investigate sex ratio variation in feral horses (
Equus caballus
), where sex ratio variation was previously shown to be related to maternal condition at conception. We used condition measures before and after conception to measure the change in condition around conception in individual mothers. The relationship with sex ratio was substantially more extreme than previously reported: 3% of females losing condition gave birth to a son, whereas 80% of those females that were gaining condition gave birth to a son. Change in condition is more predictive of sex ratio than actual condition, supporting previous studies, and shows the most extreme variation in mammals ever reported.
A system's view of the evolution of life
Authors: Williams Robert J.P
Published: April 2007

Previous treatments of biological evolution have concentrated upon either the general appearance or habits of organisms or the sequences of molecules, such as their proteins and DNA (RNA), within species. There is no consideration of the changing relationship of the chemistry of organisms to the elements and energy available from the environment. In essence, organisms at all times had to accumulate certain elements while rejecting others. Central to accumulation were C, N, H, P, S, K, Mg and Fe while, as ions, Na, Cl, Ca and other heavy metals were largely rejected. In order to form the vital biopolymers, C and H, from CO2and H2O, had to be combined generating oxygen. The oxygen then slowly oxidized the environment over long periods of time. These environmental changes were relatively rapid, unconstrained and continuous, and they imposed a necessary sequential adaptation by organisms while increasing the use of energy. Then, evolution has a chemical direction in a combined organism/environment ecosystem. Joint organization of the initial reductive chemistry of cells and the later need to handle oxidative chemistry has also forced the complexity of chemistry of organism in compartments. The complexity increased to take full advantage of the environment from bacteria to humans in a logical, physical, compartmental and chemical sequence of the whole system. In one sense, rejected material can be looked upon as waste and, in the context of this article, leads to the consideration of the importance of waste from the activities of humankind.
Bile acids as constituents for dental composites:
in vitro
cytotoxicity of (meth)acrylate and other ester derivatives of bile acids
Authors: Gauthier Marc A , Simard Pierre , Zhang Zhao , Zhu X.X
Published: April 2007

Methacrylic derivatives of bile acids have been synthesized for use as monomers in dental composites. Polymeric dental materials are known to leach cytotoxic unreacted monomers and degradation products. In this study, the
in vitro
cytotoxicity of bile acids and their derivatives towards 3T3 fibroblasts has been evaluated by colorimetric MTT assay and compared with that of the common dental monomers BisGMA, UDMA and TEGDMA. In general, the bile acids and their derivatives induced mitochondrial dysfunction at similar or higher concentrations than the commercial dental monomers. Certain monomers did not influence MTT response over their entire range of solubility.
Tensile and dynamic mechanical analysis of the distal portion of mussel (Mytilus edulis) byssal threads
Authors: Aldred N , Wills T , Williams D.N , Clare A.S
Published: April 2007

Dynamic mechanical analysis was used to record the behaviour of hydrated and dehydrated byssal threads under tensile stress and during dynamic thermal cycling. Fresh byssi, and byssi aged two weeks prior to testing, were used to further study the effects of age on the mechanical properties of this material. It was found that while older threads demonstrated increased stiffness, age did not necessarily affect their ultimate tensile strength. Dehydration had a more pronounced effect on thread stiffness and also increased the ultimate strength of the material. In their dry state, byssal threads displayed multiple yield points under tension and these, it is suggested, could equate to different phases within the bulk of the material. Dynamic analysis revealed glass transition (Tg) and ecologically relevant operational temperatures for byssi, where their modulus (E′) remained constant. These discoveries are related to the ecological function of byssal threads and to the emerging field of biomimetics.
Virus infection causes specific learning deficits in honeybee foragers
Authors: Iqbal Javaid , Mueller Uli
Published: April 2007

In both mammals and invertebrates, virus infections can impair a broad spectrum of physiological functions including learning and memory formation. In contrast to the knowledge on the conserved mechanisms underlying learning, the effects of virus infection on different aspects of learning are barely known. We use the honeybee (Apis mellifera), a well-established model system for studying learning, to investigate the impact of deformed wing virus (DWV) on learning. Injection of DWV into the haemolymph of forager leads to a RT-PCR detectable DWV signal after 3 days. The detailed behavioural analysis of DWV-infected honeybees shows an increased responsiveness to water and low sucrose concentrations, an impaired associative learning and memory formation, but intact non-associative learning like sensitization and habituation. This contradicts all present studies in non-infected bees, where increased sucrose responsiveness is linked to improved associative learning and to changes in non-associative learning. Thus, DWV seems to interfere with molecular mechanism of learning by yet unknown processes that may include viral effects on the immune system and on gene expression.
The evolution of sexual dimorphism in parasitic cuckoos: sexual selection or coevolution?
Authors: Krüger O , Davies N.B , Sorenson M.D
Published: April 2007

Sexual dimorphism is ubiquitous in animals and can result from selection pressure on one or both sexes. Sexual selection has become the predominant explanation for the evolution of sexual dimorphism, with strong selection on size-related mating success in males being the most common situation. The cuckoos (family Cuculidae) provide an exceptional case in which both sexes of many species are freed from the burden of parental care but where coevolution between parasitic cuckoos and their hosts also results in intense selection. Here, we show that size and plumage differences between the sexes in parasitic cuckoos are more likely the result of coevolution than sexual selection. While both sexes changed in size as brood parasitism evolved, we find no evidence for selection on males to become larger. Rather, our analysis indicates stronger selection on parasitic females to become smaller, resulting in a shift from dimorphism with larger females in cuckoos with parental care to dimorphism with larger males in parasitic species. In addition, the evolution of brood parasitism was associated with more cryptic plumage in both sexes, but especially in females, a result that contrasts with the strong plumage dimorphism seen in some other parasitic birds. Examination of the three independent origins of brood parasitism suggests that different parasitic cuckoo lineages followed divergent evolutionary pathways to successful brood parasitism. These results argue for the powerful role of parasite–host coevolution in shaping cuckoo life histories in general and sexual dimorphism in particular.
Multiple breeders, breeder shifts and inclusive fitness returns in an ant
Authors: Bargum Katja , Sundström Liselotte
Published: April 2007

In social insects, colonies may contain multiple reproductively active queens. This leads to potential conflicts over the apportionment of brood maternity, especially with respect to the production of reproductive offspring. We investigated reproductive partitioning in offspring females (gynes) and workers in the antFormica fusca, and combined this information with data on the genetic returns gained by workers. Our results provide the first evidence that differential reproductive partitioning among breeders can enhance the inclusive fitness returns for sterile individuals that tend non-descendant offspring. Two aspects of reproductive partitioning contribute to this outcome. First, significantly fewer mother queens contribute to gyne (new reproductive females) than to worker brood, such that relatedness increases from worker to gyne brood. Second, and more importantly, adult workers were significantly more related to the reproductive brood raised by the colony, than to the contemporary worker brood. Thus, the observed breeder shift leads to genetic benefits for the adult workers that tend the brood. Our results also have repercussions for genetic population analyses. Given the observed pattern of reproductive partitioning, estimates of effective population size based on worker and gyne samples are not interchangeable.
Species-specific acquisition and consolidation of long-term memory in parasitic wasps
Authors: Smid Hans M , Wang Guohong , Bukovinszky Tibor , Steidle Johannes L.M , Bleeker Maartje A.K , van Loon Joop J.A , Vet Louise E.M
Published: April 2007

Long-term memory (LTM) formation usually requires repeated, spaced learning events and is achieved by the synthesis of specific proteins. Other memory forms require a single learning experience and are independent of protein synthesis. We investigated in two closely related parasitic wasp species,Cotesia glomerataandCotesia rubecula, whether natural differences in foraging behaviour are correlated with differences in LTM acquisition and formation. These parasitic wasp species lay their eggs in young caterpillars of pierid butterflies and can learn to associate plant odours with a successful egg laying experience on caterpillars on the odour-producing plant. We used a classical conditioning set-up, while interfering with LTM formation through translation or transcription inhibitors. We show here thatC. rubeculaformed LTM after three spaced learning trials, whereasC. glomeratarequired only a single trial for LTM formation. After three spaced learning trials, LTM formation was complete within 4 h inC. glomerata, whereas inC. rubecula, LTM formation took 3 days. Linking neurobiology with ecology, we argue that this species-specific difference in LTM acquisition and formation is adaptive given the extreme differences in both the number of foraging decisions of the two wasp species and in the spatial distributions of their respective hosts in nature.
Origins of radial symmetry identified in an echinoderm during adult development and the inferred axes of ancestral bilateral symmetry
Authors: Morris Valerie B
Published: April 2007

How the radial body plan of echinoderms is related to the bilateral body plan of their deuterostome relatives, the hemichordates and the chordates, has been a long-standing problem. Now, using direct development in a sea urchin, I show that the first radially arranged structures, the five primary podia, form from a dorsal and a ventral hydrocoele at the oral end of the archenteron. There is a bilateral plane of symmetry through the podia, the mouth, the archenteron and the blastopore. This adult bilateral plane is thus homologous with the bilateral plane of bilateral metazoans and a relationship between the radial and bilateral body plans is identified. I conclude that echinoderms retain and use the bilateral patterning genes of the common deuterostome ancestor. Homologies with the early echinoderms of the Cambrian era and between the dorsal hydrocoele, the chordate notochord and the proboscis coelom of hemichordates become evident.
Systemic complications after head injury: a clinical review
Authors: Lim H. B. , Smith M.
Published: April 2007

Non‐neurological organ dysfunction is common after traumatic brain injury and is an independent contributor to morbidity and mortality. It represents a risk factor that is potentially amenable to treatment, and early recognition and prompt intervention may improve outcome. This article reviews the current evidence for the mechanisms and treatment of non‐neurological organ dysfunction after head injury.
Manual displacement of the uterus during Caesarean section
Authors: Kundra P. , Khanna S. , Habeebullah S. , Ravishankar M.
Published: April 2007

Ninety ASA 1 and 2 pregnant women with term singleton pregnancies and no maternal and fetal complications, scheduled for elective or emergency Caesarean section, were randomly allocated to group LT (15° left lateral table tilt, n = 45) and group MD (leftward manual displacement, n = 45). Subarachnoid block was established with a 25‐gauge spinal needle at the L3‐L4 interspace using 1.5 ml of 0.5% hyperbaric bupivacaine. A median sensory level of T6 was observed in both groups but the incidence of hypotension was markedly lower in group MD when compared to group LT (4.4% vs 40%; p < 0.001) with a significant reduction in mean (SD) ephedrine requirement (6 (0) vs 11.3 (4.9) mg; p < 0.001). The mean (SD) fall in systolic blood pressure was 28.8 (7.3) mmHg in group LT and 20 (12.7) mmHg in group MD. The time to maximum fall in systolic blood pressure was similar in both groups (4.5 min). We conclude that manual displacement of the uterus effectively reduces the incidence of hypotension and ephedrine requirements when compared to 15° left lateral table tilt in parturients undergoing Caesarean section.
An evaluation of the filtration performance of paediatric breathing system filters at low flows
Authors: Malan C. A. , Wilkes A. R. , Hall J. E. , Gildersleve C.
Published: April 2007

The filtration performance of five different types of filter intended for use in paediatric anaesthesia was measured. A total of 120 unused filters (24 samples of each filter type) were evaluated. The pressure drop and filtration performance, using challenges of sodium chloride particles, were measured for each filter at 3 l min−1 and 15 l min−1. The pressure drop was less at the lower flow; there was a wide variation in the pressure drop across some filters. The filtration performance of all filter types showed an improvement at 3 l min−1 compared to 15 l min−1. Four filter types had filtration efficiencies greater than 95% at 15 l min−1 and greater than 99% at 3 l min−1. The remaining filter type had a filtration efficiency less than 90% at 15 l min−1 and greater than 95% at 3 l min−1. These levels of performance are comparable to that of breathing system filters intended for use in adult anaesthesia using flows representing mean inspiratory flow.
SLCO1B1 521T→C functional genetic polymorphism and lipid‐lowering efficacy of multiple‐dose pravastatin in Chinese coronary heart disease patients
Authors: Zhang Wei , Chen Bi‐Lian , Ozdemir Vural , He Yi‐Jing , Zhou Gan , Peng Dao‐Di , Deng Sheng , Xie Qi‐Ying , Xie Wei , Xu Lin‐Yong , Wang Lian‐Ci , Fan Lan , Wang An , Zhou Hong‐Hao
Published: April 2007

What is already known about this subject

• Both oral clearance as well as delivery of pravastatin to its molecular targets in hepatoctyes are greatly influenced by the organic anion transporting polypeptide 1B1 (OATP1B1), encoded by SLCO1B1.

• The role of genetic factors that determine the marked interindividual variability in lipid‐lowering efficacy of pravastatin in Chinese patients is not known.

• The present study was designed to evaluate the impact of a common functional genetic polymorphism in SLCO1B1 (521T→C: Val174Ala) on pravastatin efficacy in Chinese patients with coronary heart disease.

What this study adds

521T→C functional genetic polymorphism of SLCO1B1 is significantly associated with an attenuated total cholesterol‐lowering efficacy of pravastatin in Chinese patients with coronary heart disease.

Aims

Pravastatin is a 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor, which is widely used both in primary and secondary prevention of coronary heart disease (CHD). Pravastatin is not subject to metabolism by cytochrome P450s, but it is actively transported from blood into target tissues (e.g. hepatocytes in the liver) by the organic anion transporting polypeptide 1B1 (OATP1B1), encoded by SLCO1B1. The aim of the present study was to evaluate the impact of SLCO1B1 521T→C (Val174Ala) functional genetic polymorphism on the lipid‐lowering efficacy of multiple‐dose pravastatin in Chinese patients with CHD.

Methods

Forty‐five hospitalized patients with CHD prospectively received pravastatin as a single‐agent therapy (20 mg day−1 p.o.) for 30 days. Serum triglycerides, total cholesterol, low‐density lipoprotein‐cholesterol and high‐density lipoprotein‐cholesterol concentrations were determined before and after pravastatin treatment.

Results

Pravastatin treatment significantly decreased plasma lipids in all patients (P < 0.001). Importantly, we showed an attenuated pravastatin pharmacodynamic effect on total cholesterol in patients with 521TC heterozygote genotype (from 5.52 ± 0.51 mmol l−1 to 4.70 ± 0.35 mmol l−1, % change  −14.5 ± 6.6%, N = 9) compared with 521TT homozygote genotype (from 5.47 ± 1.15 mmol l−1 to 4.21 ± 0.89 mmol l−1, % change −22.4 ± 10.3%, N = 36) (mean ± SD, P = 0.03, two‐tailed test with α set at 5%). SLCO1B1 521T→C functional polymorphism did not significantly influence pravastatin pharmacodynamics on other plasma lipids (P > 0.05).

Conclusions

The 521T→C polymorphism of SLCO1B1 appears to modulate significantly the total cholesterol‐lowering efficacy of pravastatin in Chinese patients with CHD. Further studies are warranted to determine the extent to which SLCO1B1 genetic variation may contribute to resistance to pravastatin in Asian patients treated with standard doses of pravastatin.
Pharmacokinetics of inhaled monodisperse beclomethasone as a function of particle size
Authors: Esposito‐Festen J. E. , Zanen P. , Tiddens H. A. W. M. , Lammers J.‐W. J.
Published: April 2007

What is already known about this subject

• For asthmatic adults, bronchodilators with a MMAD between 3 and 6 µm were shown to give the best improvement in lung function and the least systemic side‐effects.

• It is not known, however, what is the most efficacious particle size for inhaled steroids in asthmatic adults. Clinical efficacy and systemic side‐effects of inhaled steroids should be measured to define the optimal particle size.

What this study adds

• Our study investigated the systemic absorption of inhaled steroids. We found that a particle size of 2.5 µm and 4.5 µm gave a higher pulmonary bioavailability compared with the 1.5 µm monodisperse aerosols in adults with mild asthma and therefore were more likely to elicit systemic adverse effects.

Aims

For optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP) aerosols of different particle sizes.

Methods

In a randomized single‐blind crossover trial, 10 mild asthmatic patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters (MMADs) of 1.5, 2.5 and 4.5 µm. Gastrointestinal absorption was blocked by activated charcoal. Plasma concentrations of 17‐beclomethasone monopropionate (17‐BMP) were measured by liquid chromatography plus mass spectrometry.

Results

Aerosols with MMADs of 1.5 µm, 2.5 µm, and 4.5 µm gave mean maximum concentrations (Cmax) of 17‐BMP of 475 pg ml−1, 1300 pg ml−1, and 1161 pg ml−1, respectively. The area under the curve (AUC) values of 17‐BMP for MMADs of 1.5 µm, 2.5 µm, and 4.5 µm were 825 pg ml−1 h, 2629 pg ml−1 h, and 2276 pg ml−1 h, respectively. The mean terminal half‐time of 17‐BMP for all three aerosol sizes was around 1.5 h.

Conclusions

Monodisperse BDP aerosols with a MMAD of 1.5 µm gave two‐three fold lower values for Cmax and AUC than those with MMADs of 2.5 and 4.5 µm.
Switching statins in Norway after new reimbursement policy – a nationwide prescription study
Authors: Sakshaug Solveig , Furu Kari , Karlstad Øystein , Rønning Marit , Skurtveit Svetlana
Published: April 2007

What is already known about this subject

• Use of statins is growing worldwide and costs represent a burden to public budgets.

• The introduction of simvastatin generics, generic substitution and price regulations have contributed to price reductions and resulted in overall cost reductions of statin use in Norway.

What this study adds

• New reimbursement regulations for statins in Norway in June 2005, making simvastatin the drug of choice, had a great impact on physicians' prescribing of statins.

• Nearly 40% of the atorvastatin users switched to simvastatin during the 13‐month period after implementation of the new regulations.

• Among the new users of statins the proportion receiving simvastatin increased from 48% in May 2005 to 92% in June 2006.

• The new regulations have reduced costs of statins, even though the prevalence of statin use has increased.

Aims

To assess the changes in prescribing of statins in Norway after implementation of the new reimbursement regulations for statins in June 2005.

Methods

Data were retrieved from the Norwegian Prescription Database covering the total population in Norway (4.6 million). Outcome measures were the proportion of atorvastatin users switching to simvastatin and changes in the proportion of new statin users receiving simvastatin. Based on retail costs for all statin prescriptions dispensed in Norway, expenditure was measured in Norwegian currency.

Results

One‐year prevalences of statin use increased from 6.3 to 6.8% for women and from 7.5 to 8.1% for men from the year before to the year after the new statin regulations. Of atorvastatin users (N = 131 222), 39% switched to simvastatin during the 13‐month period after the implementation. The proportion of switching was higher in women (41%) than in men (36%). In May 2005, 48% of the new statin users received simvastatin. The proportion of new users receiving simvastatin increased rapidly after implementation of the new regulations to 68% in June 2005 and reached 92% in June 2006. Expenditure was reduced from €120 million to €95 million when comparing the year before with the year after the new statin regulations.

Conclusions

The new reimbursement policy for statins has had a great impact on physicians' prescribing of statins in Norway. Physicians in Norway acknowledge the importance of contributing to cost containment.
Caractérisation par PCR de deux souches d’Erwinia carotovora isolées de la rhizosphère de la pomme de terre dans la région du grand Casablanca au Maroc
Authors: Anajjar B. , Aitmhand R. , Timinouni M. , Ennaji M. M.
Published: April 2007

Les infections latentes de la pomme de terre causées par les bactéries du genre Erwinia sont responsables de pertes importantes de cette culture, surtout au cours du transport et du stockage au Maroc. Le sol constitue l’un des substrats potentiels dans ces infections. Deux souches bactériennes ont été isolées de la rhizosphère des plantations de pomme de terre dans la province de Mediouna (wilaya du Grand Casablanca). La méthode de PCR (Polymerase Chain Reaction) utilisant les amorces Y1 et Y2 a permis l’identification de ces souches comme étant Erwinia carotovora. Leur pouvoir pathogène a étéévalué sur des tubercules de pomme de terre de la variété Désirée en comparaison avec une souche d’Erwinia carotovora subsp. carotovora isolée de la pomme de terre dans la même rhizosphère.
Etude de la compétition entre la morelle jaune (Solanum elaeagnifolium Cav.) et le maïs de printemps (Zea mays L.)*
Authors: Baye Y. , Bouhache M.
Published: April 2007

La compétition entre la morelle jaune (Solanum elaeagnifolium Cav.) et le maïs (Zea mays L.) a étéétudiée au champ au cours de la saison 2001. Des durées de compétition avec la morelle jaune plus ou moins longues, tardives et précoces ont été imposées à la culture au cours du cycle. Les résultats montrent que les paramètres de croissance (hauteur, surface foliaire, matière sèche) du maïs ont été affectés par la présence de la mauvaise herbe. Plus la durée de compétition est longue, plus ces paramètres sont réduits. Les principales composantes du rendement, à savoir le nombre de grains/épi et le poids de 1000 grains ont été fortement influencées par la morelle jaune. Il en est de même pour le rendement global qui diminue d’autant plus que la compétition avec l’adventice dure longtemps. Ce dernier a été réduit de 64% en cas de non désherbage. Pour des pertes de rendements tolérées de 15%, la période critique de sensibilitéà la mauvaise herbe serait située entre le stade floraison de la culture et le stade grain laiteux avancé. La mauvaise herbe arrive à accomplir parfaitement son cycle biologique lorsque aucun désherbage n’est effectué. Des désherbages se poursuivant jusqu’au stade grain pâteux de la culture ont permis de réduire la production de fruits de la mauvaise herbe.
Strategie de lutte chimique contre la morelle jaune (Solanum elaeagnifolium Cav.) au Maroc*
Authors: Baye Y. , Ameur A. , Bouhache M. , Taleb A.
Published: April 2007

La lutte chimique contre Solanum elaeagnifolium Cav. a fait l’objet de nombreux travaux de recherche, et ce grâce aux nombreuses expérimentations menées sur un grand nombre d’herbicides (doses, stades d’application, conditions climatiques, biotopes traités, etc.). Les résultats montrent que les herbicides appliqués en cours de végétation n’aboutissent générallement pas à un bon contrôle de l’adventice. En effet, les doses d’herbicides sélectifs de ces cultures sont peu efficaces contre S. elaeagnifolium. Le glyphosate, le sulfosate et l’aminotriazole – herbicides systémiques – se sont montrés très performants et sont préconisés principalement pour le traitement non sélectif des vergers d’oliviers, d’agrumes et d’arbres fruitiers ainsi que des parcelles en postrécolte des cultures (céréales, betterave à sucre, maraîchage). Ils nécessitent des conditions d’application particulières et sont conseillés surtout en cas de fortes infestations. Les phytohormones, l’imazapyr et le bromacile sont utilisés pour le désherbage des bordures de routes publiques boisées et/ou non boisées et éventuellement les parcelles non exploitées. Le bromacile peut être utilisé dans les vergers d’agrumes agés de plus de 4 ans, mais uniquement sur des zones fortement infestées compte tenu de son coût élevé. Par le biais du transfert de technologie chez les agriculteurs, ces derniers ont été convaincus de la possibilité de contrôler cette adventice par le glyphosate et d’autres herbicides lorsqu’un certain nombre de conditions sont respectées. En se basant sur ces résultats, des opérations de lutte chimique ont été menées à grande échelle par les organismes de développement.
Biology, distribution and impacts of silverleaf nightshade (Solanum elaeagnifolium Cav.)*
Authors: Mekki M.
Published: April 2007

Silverleaf nightshade, Solanum elaeagnifolium, is listed as a noxious weed in its native range (Americas) and as an invasive alien plant in many countries across the world. Its local pattern of distribution in the EPPO region indicates that it is still in an establishment phase. S. elaeagnifolium invasiveness could be related to several biological traits: copious production of sexual and asexual propagules, its facility for long‐distance dispersion, its ability to endure considerable drought and to dominate shallow‐rooted vegetation, especially during summer dry periods, and its capacity to suppress more valuable species because it is unpalatable and toxic to cattle. Invasion of the Mediterranean semi‐arid region by S. elaeagnifolium was mainly facilitated by irrigation and animal production. Low moisture stress may favour this invasive species and sheep are an important pathway for its long‐distance dispersal. Once established, it is one of the most difficult weeds to eradicate because of its network of creeping horizontal and deep vertical roots. Its phenotypic plasticity enables it to adopt a rosette‐like growth pattern to escape control by repeated slashing. Thus, S. elaeagnifolium monitoring in the EPPO region is vital in order to contain established populations and prevent invasion.
Solanum elaeagnifolium, a potential source of Potato virus Y (PVY) propagation*
Authors: Boukhris‐Bouhachem S. , Hullé M. , Rouzé‐Jouan J. , Glais L. , Kerlan C.
Published: April 2007

In the context of an epidemiological study on Potato virus Y (PVY) in potato crops, Solanum elaeagnifolium Cav. was included in the weeds prospected. Surveys were carried out in four seed potato areas: Cap Bon, Manouba, Jendouba and Kairouan. S. elaeagnifolium was found in all areas, except Cap Bon. Virus‐like symptoms were observed on some S. elaeagnifolium plants in the field, i.e. leaf mottling and curling. Aphids were collected on these plants and were identified as Myzus persicae and Aphis fabae, both known to colonize potatoes and to transmit the standard PVYN isolate with transmission efficiencies of 95% and 43%, respectively. Forty‐seven plant samples were tested with ELISA for the presence of PVY. Positive reactions were obtained from 2/6, 5/18, 8/23 samples collected in Manouba, Jendouba and Kairouan, respectively. Virus transmission was carried out using M. persicae as vector from two samples of each region onto plantlets of Nicotiana tabacum cv Xanthi. All inoculated plantlets displayed typical symptoms of the PVYN strain group, confirmed by serological testing using specific antibodies. This is the first report of a PVY natural infection on S. elaeagnifolium in Tunisia. The abundance of this weed, its over‐wintering status and the high rate of PVY‐infected plants (31.9%) allow us to deduce that S. elaeagnifolium must be considered a reservoir species of PVY under natural conditions in Tunisia and probably in other Mediterranean countries. The presence of efficient aphid vectors of PVY on this weed in crops is additional evidence that S. elaeagnifolium may become a problem by acting as a source plant for PVY spread in potato crops.
Revue des moyens de lutte contre la morelle jaune (Solanum elaeagnifolium Cav.) au Maroc
Authors: Ameur A. , Baye Y. , Bouhache M. , Taleb A.
Published: April 2007

Cette revue présente les méthodes de lutte contre la morelle jaune explorées au Maroc. Concernant la lutte culturale, l’emploi d’une culture étouffante comme la luzerne (Medicago sativa L.) en début de rotation réduit sensiblement l’infestation de cette adventice grâce aux fréquentes coupes, à la grande compétition et à l’effet allélopathique qu’exerce cette culture sur la morelle jaune. En lutte mécanique, trois méthodes ont démontré leur efficacité : le labour profond à la charrue à trois disques, le sweep (outil de 2,5 m de largeur composé de trois lames en V) et la sape (outil manuel qui coupe la plante au niveau du sol). Le labour profond (> 30 cm) et le sweep sont préconisés en début d’été et en post‐récolte des cultures. L’intervention à la sape, utilisée 2 à 3 fois par an au stade initiation florale dans différents biotopes, permet l’affaiblissement progressif de l’adventice à moyen terme. La luzerne, le labour profond et le sweep sont conseillés pour les infestations moyennes àélevées. En outre, les interventions mécaniques combinées aux herbicides (le glyphosate, le sulfosate, l’aminotriazole et les phytohormones) donnent souvent de bonnes efficacités. La combinaison de ces méthodes est vivement souhaitable pour les grandes superficies où l’infestation est moyenne à forte.
Influence de certains facteurs sur l’efficacité du glyphosate et de l’aminotriazole contre Solanum elaeagnifolium Cav.*
Authors: Baye Y.
Published: April 2007

L’effet du stress hydrique, du stade d’application et des adjuvants sur l’efficacité du glyphosate contre Solanum elaeagnifolium Cav. ont étéétudiés en 1995 et 1996. Il en est de même pour l’effet de la qualité de l’eau de bouillie pour l’aminotriazole en 1996 et 1997. Les résultats montrent que le sulfate d’ammonium améliore nettement l’efficacité du glyphosate utiliséà des doses de 2160 g s.a./ha. Les efficacités obtenues à 360 jours après traitement sont très significativement meilleures dans les parcelles irriguées légèrement (82%) que dans celles maintenues sous stress hydrique (45%). Le contrôle de la mauvaise herbe par le glyphosate s’est avéré bon aussi bien pour les traitements au stade floraison que pour ceux au stade fructification (baies vertes). Les semences issues de plantes traitées au stade floraison ne sont généralement pas viables, contrairement à celles issues de traitements au stade fructification, qui sont viables dans la majorité des cas. Pour ce qui est de l’aminotriazole, les résultats montrent que de bonnes efficacités ne sont obtenues qu’à partir des doses de 7200 g s.a./ha et que cet herbicide est efficace même lorsque l’eau de bouillie est dure, contenant des ions antagonistes tels que Na+, Fe++, etc.