bluuebunny/crossref_metadata_2025 huggingface dataset:
"Bacterial Meningitis in children and adolescents: an observational study based on the national surveillance system"
Authors: Dickinson Félix O , Pérez Antonio E
Published: November 2005

Background

Bacterial meningitis is a group of life threatening infections that mostly affect children and adolescents, and may be the cause of severe neurological sequelae. Cuba has implemented massive vaccination programmes against both Neisseria meningitidis (serogroup C in 1979 and B in 1987), and Haemophilus influenzae type b (1999), two of the main causal pathogens. We described and discussed some epidemiological aspects of the current status of bacterial meningitis to learn from the Cuban experience.

Methods

A nationwide observational study on children and adolescents from 1 to 18 years old was carried out from 1998 to 2003, estimating the incidence and case-fatality rate by age group and causal pathogens, as well as the seasonality and frequency of overcrowded dormitories. The association between disease and attendance to day care centres or boarding schools was estimated by using relative risk (Chi-squared test and Fisher Exact Test).

Results

The overall number of cases was 1023; the incidence ranged from 3.4 to 8.5 per 100 000 population, with the higher figures in children 1–5 years old (16.8 per 100 000 population). Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis serogroup B were the main identified agents. The average case-fatality rate was 10.5% and the most lethal agents were Streptococcus pneumoniae (27%) and Haemophilus influenzae type b (10.7%). Overall percentage of cases who slept in overcrowded dormitories was 15%, reaching 30.6% in adolescents. Seasonality was only evident among meningococcal meningitis cases between September–October. The attendance to boarding high school showed an association with disease only in 1998 and 1999 (RR = 2.1; p > 0.05).

Conclusion

The highest incidence of bacterial meningitis was observed among children from 1–5 years old. Pneumococcus was both the leading causal and the most lethal agent. Sleeping in overcrowded dormitories was more frequent among adolescents. No strong association was observed between the bacterial meningitis and attendance to day care centres or boarding schools. The incidence of bacterial meningitis in Cuba is declining after massive vaccination programmes against Neisseria meningitidis serogroup B and C and Haemophilus influenzae type b through a national immunisation program.
The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency
Authors: Bayley Jean-Pierre , Devilee Peter , Taschner Peter EM
Published: November 2005

Background

The SDHA, SDHB, SDHC and SDHD genes encode the subunits of succinate dehydrogenase (succinate: ubiquinone oxidoreductase), a component of both the Krebs cycle and the mitochondrial respiratory chain. SDHA, a flavoprotein and SDHB, an iron-sulfur protein together constitute the catalytic domain, while SDHC and SDHD encode membrane anchors that allow the complex to participate in the respiratory chain as complex II. Germline mutations of SDHD and SDHB are a major cause of the hereditary forms of the tumors paraganglioma and pheochromocytoma. The largest subunit, SDHA, is mutated in patients with Leigh syndrome and late-onset optic atrophy, but has not as yet been identified as a factor in hereditary cancer.

Description

The SDH mutation database is based on the recently described Leiden Open (source) Variation Database (LOVD) system. The variants currently described in the database were extracted from the published literature and in some cases annotated to conform to current mutation nomenclature. Researchers can also directly submit new sequence variants online. Since the identification of SDHD, SDHC, and SDHB as classic tumor suppressor genes in 2000 and 2001, studies from research groups around the world have identified a total of 120 variants. Here we introduce all reported paraganglioma and pheochromocytoma related sequence variations in these genes, in addition to all reported mutations of SDHA. The database is now accessible online.

Conclusion

The SDH mutation database offers a valuable tool and resource for clinicians involved in the treatment of patients with paraganglioma-pheochromocytoma, clinical geneticists needing an overview of current knowledge, and geneticists and other researchers needing a solid foundation for further exploration of both these tumor syndromes and SDHA-related phenotypes.
Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives
Authors: Durando Xavier , Thivat Emilie , D'Incan Michel , Sinsard Anne , Madelmont Jean-Claude , Chollet Philippe
Published: November 2005

Background

Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2).

Case presentation

We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone.

Conclusion

Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.
Are associations between socio-economic characteristics and exposure to air pollution a question of study area size? An example from Scania, Sweden
Authors: Stroh Emilie , Oudin Anna , Gustafsson Susanna , Pilesjö Petter , Harrie Lars , Strömberg Ulf , Jakobsson Kristina
Published: November 2005

Background

Numerous studies have shown that exposure to air pollutants in the area of residence and the socio-economic status of an individual may be related. Therefore, when conducting an epidemiological study on the health effect of air pollution, socio-economy may act as a confounding factor. In this paper we examine to what extent socio-economic status and concentrations of NO2 in the county/region of Scania, southern Sweden, are associated and if such associations between these factors differ when studying them at county or city level. To perform this study we used high-resolution census data and modelled the annual exposure to NO2 using an emission database, a dispersion modelling program and a geographical information system (GIS).

Results

The results from this study confirm that socio-economic status and the levels of NO2 in the area of residence are associated in some cities. The associations vary considerably between cities within the same county (Scania). Even for cities of similar sizes and population bases the associations observed are different. Studying the cities together or separately yields contradictory results, especially when education is used as a socio-economic indicator.

Conclusion

Four conclusions have been drawn from the results of this study. 1) Adjusting for socio-economy is important when investigating the health effects of air pollution. 2) The county of Scania seems to be heterogeneous regarding the association between air pollution and socio-economy. 3) The relationship between air pollution and socio-economy differs in the five cities included in our study, depending on whether they are analysed separately or together. It is therefore inadvisable to determine and analyse associations between socio-economy and exposure to air pollutants on county level. This study indicates that the size and choice of study area is of great importance. 4) The selection of socio-economic indices (in this study: country of birth and education level) is important.
A refined in vitro model to study inflammatory responses in organotypic membrane culture of postnatal rat hippocampal slices
Authors: Huuskonen Jari , Suuronen Tiina , Miettinen Riitta , van Groen Thomas , Salminen Antero
Published: November 2005

Background

Propagated tissue degeneration, especially during aging, has been shown to be enhanced through potentiation of innate immune responses. Neurodegenerative diseases and a wide variety of inflammatory conditions are linked together and several anti-inflammatory compounds considered as having therapeutic potential for example in Alzheimer's disease (AD). In vitro brain slice techniques have been widely used to unravel the complexity of neuroinflammation, but rarely, has the power of the model itself been reported. Our aim was to gain a more detailed insight and understanding of the behaviour of hippocampus tissue slices in serum-free, interface culture per se and after exposure to different pro- and anti-inflammatory compounds.

Methods

The responses of the slices to pro- and anti-inflammatory stimuli were monitored at various time points by measuring the leakage of lactate dehydrogenase (LDH) and the release of cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) from the culture media. Histological methods were applied to reveal the morphological status after exposure to stimuli and during the time course of the culture period. Statistical power analysis were made with nQuery Advisor®, version 5.0, (Statistical Solutions, Saugus, MA) computer program for Wilcoxon (Mann-Whitney) rank-sum test.

Results

By using the interface membrane culture technique, the hippocampal slices largely recover from the trauma caused by cutting after 4–5 days in vitro. Furthermore, the cultures remain stable and retain their responsiveness to inflammatory stimuli for at least 3 weeks. During this time period, cultures are susceptible to modification by inflammatory stimuli as assessed by quantitative biochemical assays and morphological characterizations.

Conclusion

The present report outlines the techniques for studying immune responses using a serum-free slice culture model. Statistically powerful data under controlled culture conditions and with ethically justified use of animals can be obtained as soon as after 4–5 DIV. The model is most probably suitable also for studies of chronic inflammation.
Brazilian obstetrician-gynecologists and abortion: a survey of knowledge, opinions and practices
Authors: Goldman Lisa A , García Sandra G , Díaz Juan , Yam Eileen A
Published: November 2005

Background

Abortion laws are extremely restrictive in Brazil. The knowledge, opinions of abortion laws, and abortion practices of obstetrician-gynecologists can have a significant impact on women's access to safe abortion.

Methods

We conducted a mail-in survey with a 10% random sample of obstetrician-gynecologists affiliated with the Brazilian Federation of Obstetricians and Gynecologists. We documented participants' experiences performing abortion under a range of legal and illegal circumstances, and asked about which abortion techniques they had experience with. We used chi-square tests and crude logistic regression models to determine which sociodemographic, knowledge-related, or practice-related variables were associated with physician opinion.

Results

Of the 1,500 questionnaires that we mailed out, we received responses from 572 (38%). Less than half (48%) of the respondents reported accurate knowledge about abortion law and 77% thought that the law should be more liberal. One-third of respondents reported having previous experience performing an abortion, and very few of these physicians reported having experience with manual vacuum aspiration (MVA) or with misoprostol with either mifepristone or methotrexate. Physicians that favored liberalization of the law were more likely to have correct knowledge about abortion law, and to be in favor of public funding for abortion services.

Conclusion

Brazilian obstetrician-gynecologists need more information on abortion laws and on safe, effective abortion procedures.
Ethnomedicinal botany of the Apatani in the Eastern Himalayan region of India
Authors: Kala Chandra Prakash
Published: November 2005

This paper investigates the wealth of medicinal plants used by the Apatani tribe of Arunachal Pradesh. Apatani have traditionally settled in seven villages in the Ziro valley of Lower Subansiri district of Arunachal Pradesh in the Eastern Himalayan region of India. The present study has resulted in the documentation of 158 medicinal plant species used by the Apatani group of villages. These medicinal plant species were distributed across 73 families and 124 genera. Asteraceae was the most dominant family (19 species, 11 genera) of medicinal plants, followed by Zingiberaceae, Solanaceae, Lamiaceae and Araceae. For curing ailments, the use of aboveground plant parts was higher (80%) than the belowground plant parts in the Apatani group of villages. Of the aboveground plant parts, leaf was used in the majority of cases (56 species), followed by fruit. Different belowground plant forms such as root, tuber, rhizome, bulb and pseudo-bulb were used by Apatani as a medicine. About 52 types of ailments were cured by using these 158 medicinal plant species. The results of this study are further discussed in the changing socio-economic contexts.
Meta-analysis of hemodynamic optimization: relationship to methodological quality
Authors: Poeze Martijn , Greve JanWillem M , Ramsay Graham
Published: November 2005

Introduction

To review systematically the effect of interventions aimed at hemodynamic optimization and to relate this to the quality of individual published trials.

Methods

A systematic, computerized bibliographic search of published studies and citation reviews of relevant studies was performed. All randomized clinical trials in which adult patients were included in a trial deliberately aiming at an optimized or maximized hemodynamic condition of the patients (with oxygen delivery, cardiac index, oxygen consumption, mixed venous oxygen saturation and/or stroke volume as end-points) were selected. A total of 30 studies were selected for independent review. Two reviewers extracted data on population, intervention, outcome and methodological quality. Agreement between reviewers was high: differences were eventually resolved by third-party decision. The methodological quality of the studies was moderate (mean 9.0, SD 1.7), and the outcomes of the randomized clinical trials were not related to their quality.

Results

Efforts to achieve an optimized hemodynamic condition resulted in a decreased mortality rate (relative risk ratio (RR) 0.75 (95% confidence interval (CI) 0.62 to 0.90) in all studies combined. This was due to a significantly decreased mortality in peri-operative intervention studies (RR 0.66 (95% CI 0.54 to 0.81). Overall, patients with sepsis and overt organ failure do not benefit from this method (RR 0.92 (95% CI 0.75 to 1.11)).

Conclusion

This systematic review showed that interventions aimed at hemodynamic optimization reduced mortality. In particular, trials including peri-operative interventions aimed at the hemodynamic optimization of high-risk surgical patients reduce mortality. Overall, this effect was not related to the trial quality.
Long term effect of a medical emergency team on cardiac arrests in a teaching hospital
Authors: Jones Daryl , Bellomo Rinaldo , Bates Samantha , Warrillow Stephen , Goldsmith Donna , Hart Graeme , Opdam Helen , Gutteridge Geoffrey
Published: November 2005

Introduction

It is unknown whether the reported short-term reduction in cardiac arrests associated with the introduction of the medical emergency team (MET) system can be sustained.

Method

We conducted a prospective, controlled before-and-after examination of the effect of a MET system on the long-term incidence of cardiac arrests. We included consecutive patients admitted during three study periods: before the introduction of the MET; during the education phase preceding the implementation of the MET; and a period of four years from the implementation of the MET system. Cardiac arrests were identified from a log book of cardiac arrest calls and cross-referenced with case report forms and the intensive care unit admissions database. We measured the number of hospital admissions and MET reviews during each period, performed multivariate logistic regression analysis to identify predictors of mortality following cardiac arrest and studied the correlation between the rate of MET calls with the rate of cardiac arrests.

Results

Before the introduction of the MET system there were 66 cardiac arrests and 16,246 admissions (4.06 cardiac arrests per 1,000 admissions). During the education period, the incidence of cardiac arrests decreased to 2.45 per 1,000 admissions (odds ratio (OR) for cardiac arrest 0.60; 95% confidence interval (CI) 0.43–0.86; p = 0.004). After the implementation of the MET system, the incidence of cardiac arrests further decreased to 1.90 per 1,000 admissions (OR for cardiac arrest 0.47; 95% CI 0.35–0.62; p < 0.0001). There was an inverse correlation between the number of MET calls in each calendar year and the number of cardiac arrests for the same year (r2 = 0.84; p = 0.01), with 17 MET calls being associated with one less cardiac arrest. Male gender (OR 2.88; 95% CI 1.34–6.19) and an initial rhythm of either asystole (OR 7.58; 95% CI 3.15–18.25; p < 0.0001) or pulseless electrical activity (OR 4.09; 95% CI 1.59–10.51; p = 0.003) predicted an increased risk of death.

Conclusion

Introduction of a MET system into a teaching hospital was associated with a sustained and progressive reduction in cardiac arrests over a four year period. Our findings show sustainability and suggest that, for every 17 MET calls, one cardiac arrest might be prevented.
Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial
Authors: Wrigge Hermann , Zinserling Jörg , Neumann Peter , Muders Thomas , Magnusson Anders , Putensen Christian , Hedenstierna Göran
Published: November 2005

Introduction

Experimental and clinical studies have shown a reduction in intrapulmonary shunt with spontaneous breathing during airway pressure release ventilation (APRV) in acute lung injury. This reduction was related to reduced atelectasis and increased aeration. We hypothesized that spontaneous breathing will result in better ventilation and aeration of dependent lung areas and in less cyclic collapse during the tidal breath.

Methods

In this randomized controlled experimental trial, 22 pigs with oleic-acid-induced lung injury were randomly assigned to receive APRV with or without spontaneous breathing at comparable airway pressures. Four hours after randomization, dynamic computed tomography scans of the lung were obtained in an apical slice and in a juxtadiaphragmatic transverse slice. Analyses of regional attenuation were performed separately in nondependent and dependent halves of the lungs on end-expiratory scans and end-inspiratory scans. Tidal changes were assessed as differences between inspiration and expiration of the mechanical breaths.

Results

Whereas no differences were observed in the apical slices, spontaneous breathing resulted in improved tidal ventilation of dependent lung regions (P < 0.05) and less cyclic collapse (P < 0.05) in the juxtadiaphragmatic slices. In addition, with spontaneous breathing, the end-expiratory aeration increased and nonaerated tissue decreased in dependent lung regions close to the diaphragm (P < 0.05 for the interaction ventilator mode and lung region).

Conclusion

Spontaneous breathing during APRV redistributes ventilation and aeration to dependent, usually well-perfused, lung regions close to the diaphragm, and may thereby contribute to improved arterial oxygenation. Spontaneous breathing also counters cyclic collapse, which is a risk factor for ventilation-associated lung injury.
btn1, theSchizosaccharomyces pombehomologue of the human Batten disease geneCLN3, regulates vacuole homeostasis
Authors: Gachet Yannick , Codlin Sandra , Hyams Jeremy S. , Mole Sara E.
Published: November 2005

We have cloned the Schizosaccharomyces pombe homologue of the human Batten disease gene, CLN3. This gene, btn1, encodes a predicted transmembrane protein that is 30% identical and 48% similar to its human counterpart. Cells deleted for btn1 were viable but had enlarged and more alkaline vacuoles. Conversely overexpression of Btn1p reduced both vacuole diameter and pH. Thus Btn1p regulates vacuole homeostasis. The vacuolar defects of btn1Δ cells were rescued by heterologous expression of CLN3, proving that Btn1p and CLN3 are functional homologues. The disease severity of Batten disease-causing mutations (G187A, E295K and V330F), when expressed in btn1 appeared to correlate with their effect on vacuolar pH, suggesting that elevated lysosomal pH contributes to the disease process. In fission yeast, both Btn1p and CLN3 trafficked to the vacuole membrane via early endocytic and pre-vacuolar compartments, and localisation of Btn1p to the vacuole membrane was dependent on the Ras GTPase Ypt7p. Importantly, vacuoles in cells deleted for both ypt7 and btn1 were larger and more alkaline than those of cells deleted for ypt7 alone, indicating that Btn1p has a functional role prior to reaching the vacuole. Consistently, btn1 and vma1, the gene encoding subunit A of the V1 portion of vATPase, showed conditional synthetic lethality, and in cells deleted for vma1 (a subunit of the vacuolar ATPase) Btn1p was essential for septum deposition during cytokinesis.
TheC. eleganshomologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception
Authors: Winkelbauer Marlene E. , Schafer Jenny C. , Haycraft Courtney J. , Swoboda Peter , Yoder Bradley K.
Published: November 2005

Nephronophthisis (NPH) is a cystic kidney disorder that causes end-stage renal failure in children. Five nephrocystin (nephrocystin-1 to nephrocystin-5) genes, whose function is disrupted in NPH patients, have been identified and data indicate they form a complex at cell junctions and focal adhesions. More recently, the nephrocystin proteins have also been identified in cilia, as have multiple other cystic kidney disease related proteins. Significant insights into this cilia and cystic kidney disease connection have come from analyses in simpler eukaryotic organisms such as Caenorhabditis elegans. In this regard, we became interested in the C. elegans homologs of nephrocystin-1 (nph-1) and nephrocystin-4 (nph-4) from a database screen to identify genes coordinately regulated by the ciliogenic transcription factor DAF-19. Here we show that expression of nph-1 and nph-4 is DAF-19 dependent, that their expression is restricted to ciliated sensory neurons, and that both NPH-1 and NPH-4 concentrate at the transition zones at the base of the cilia, but are not found in the cilium axoneme. In addition, NPH-4 is required for the localization of NPH-1 to this domain. Interestingly, nph-1 or nph-4 mutants have no obvious cilia assembly defects; however, they do have abnormalities in cilia-mediated sensory functions as evidenced by abnormal chemotaxis and lifespan regulation. Our data suggest that rather than having a ciliogenic role, the NPH proteins play an important function as part of the sensory or signaling machinery of this organelle. These findings suggest that the defects in human NPH patients may not be the result of aberrant ciliogenesis but abnormal cilia-sensory functions.
Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced endothelial cell migration and angiogenesis
Authors: Michaelis U. Ruth , Fisslthaler Beate , Barbosa-Sicard Eduardo , Falck John R. , Fleming Ingrid , Busse Rudi
Published: November 2005

Recent studies suggest that cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) elicit cell proliferation and promote angiogenesis. The aim of this study was to determine the role of CYP 2C8/9-derived EETs in the process of angiogenesis under hypoxic conditions. In human endothelial cells, hypoxia enhanced the activity of the CYP 2C9 promoter, increased the expression of CYP 2C mRNA and protein and augmented 11,12-EET production. In Transwell assays, the migration of endothelial cells pre-exposed to hypoxia to increase CYP expression was abolished by CYP 2C antisense oligonucleotides as well as by the CYP inhibitor MS-PPOH and the EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE). Similar findings were obtained in porcine coronary artery endothelial cells. CYP 2C9 overexpression in endothelial cells increased the association of PAK-1 with Rac, a response also elicited by the CYP 2C9 product 11,12-EET. Matrix metalloprotease (MMP) activity was increased in CYP-2C9-overexpressing cells and correlated with increased invasion through Matrigel-coated Transwell chambers: an effect sensitive to the CYP 2C9 inhibitor sulfaphenazole as well as to EEZE and the MMP inhibitor GM6001. In in vitro angiogenesis models, the EET antagonist inhibited tube formation induced by CYP 2C9 overexpression as well as that in endothelial cells exposed to hypoxia to increase CYP 2C expression. Furthermore, in the chick chorioallantoic membrane assay, EEZE abolished hypoxia-induced angiogenesis. Taken together, these data indicate that CYP 2C-derived EETs significantly affect the sequence of angiogenic events under hypoxic conditions.
Search for Predictors of Nontherapeutic INR Results with Warfarin Therapy
Authors: McGriff-Lee Nayahmka J , Csako Gyorgy , Chen Judy T , Dang Devra K , Rosenfeld Kathryn G , Cannon Richard O , Macklin L Rose , Wesley Robert A
Published: November 2005

BACKGROUND

The effectiveness and safety of warfarin require maintaining an international normalized ratio (INR) within the therapeutic range.

OBJECTIVE

To identify predictors of nontherapeutic INR results in patients receiving warfarin.

METHODS

A retrospective study was conducted using 350 ambulatory care patients from a broad geographic region, all receiving long-term warfarin therapy and followed in a tertiary-care cardiology clinic. Possible predictors of nontherapeutic INR results (gender, age, body weight, body mass index, height, race, tobacco use, alcohol use, warfarin dose, therapeutic indication, regimen intensity, INR monitoring frequency/category, interacting medications, adverse events) were assessed with logistic regression models. Subset analysis involved 146 patients concurrently monitored with capillary whole blood INR (CoaguChek).

RESULTS

As measured on venous specimens, 52% (182/350) of the patients had subtherapeutic INR results and 13% (44/350) had supratherapeutic INR results despite frequent (≤4 wk) monitoring in 75% of the patients. Due to the small sample size, supratherapeutic INR results could not be further analyzed. Of 19 predictors tested, only daily warfarin dose (p < 0.02) and regimen intensity (p < 0.03) were significant independent and additive predictors of subtherapeutic results. Patients on the high-intensity regimen (INR 2.5–3.5) and receiving warfarin ≤6 mg/day had >50% risk of having subtherapeutic INR results. Subtherapeutic CoaguChek results were independent predictors of subtherapeutic venipuncture INR results in the subset (p = 0.001).

CONCLUSIONS

In the absence of readily identifiable predictors, only higher warfarin dosing and/or more frequent monitoring (possibly with point-of-care/home monitoring devices) may minimize the time that INRs are subtherapeutic, especially in patients receiving low-dose and/or high-intensity anticoagulation therapy.
Pregabalin: A New Neuromodulator with Broad Therapeutic Indications
Authors: Shneker Bassel F , McAuley James W
Published: November 2005

OBJECTIVE

To review pregabalin's pharmacology, pharmacokinetics, efficacy, and adverse effects in the treatment of neuropathic pain, epilepsy, and anxiety.

DATA SOURCES

A MEDLINE search (1993–October 2005) for peer-reviewed English-language publications was performed. Abstracts from professional meetings were also included. Key terms were anxiety, diabetic neuropathy, epilepsy, neuropathic pain, postherpetic neuralgia, pregabalin, and seizures.

STUDY SELECTION AND DATA EXTRACTION

Basic pharmacology data were extracted from animal studies; pharmacokinetic data were extracted from human studies. Multicenter, double-blind, placebo-controlled, parallel-group studies were included to describe the efficacy and adverse effects of pregabalin.

DATA SYNTHESIS

Pregabalin is a new agent that exerts its pharmacodynamic effect by modulating voltage-gated calcium channels. Pregabalin has a linear pharmacokinetic profile. It is completely absorbed, not bound to plasma proteins, not metabolized, and eliminated unchanged through the kidneys. Doses must be adjusted in patients with renal insufficiency. Clinical trials showed that pregabalin is effective in neuropathic pain associated with postherpetic neuralgia, diabetic peripheral neuropathy, in partial epilepsy as adjunctive therapy, and in generalized and social anxiety disorders. The most common adverse effects were dizziness and somnolence. Few serious adverse effects were reported. Pregabalin should not be discontinued rapidly.

CONCLUSIONS

Pregabalin is an effective and safe analgesic, antiepileptic, and anxiolytic medicine. It will provide a new treatment option for patients with neuropathic pain and partial epilepsy.
Acute Renal Failure Secondary to Imatinib Mesylate Treatment in Prostate Cancer
Authors: Foringer John R , Verani Regina R , Tjia Vincent M , Finkel Kevin W , Samuels Joshua A , Guntupalli Jayarama S
Published: November 2005

OBJECTIVE

To report a case of acute renal failure associated with the administration of imatinib mesylate.

CASE SUMMARY

A 64-year-old man diagnosed with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus taxotere on a protocol that required a run-in period of imatinib mesylate alone. During therapy with imatinib mesylate, the patient developed acute renal failure, requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal failure resolved with cessation of imatinib mesylate.

DISCUSSION

Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Prostate cancer has been identified as a target for therapy with imatinib mesylate. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment determined that imatinib mesylate was the probable cause of the acute renal failure. The presence of a primary glomerular disease was excluded by biopsy.

CONCLUSIONS

Imatinib mesylate–induced acute renal failure has now been linked to toxic effects on renal tubular cells in 3 cases. Renal function should be closely monitored during imatinib mesylate therapy.
Acute Hyperammonemic Coma with Chronic Valproic Acid Therapy
Authors: Cuturic Miroslav , Abramson Ruth K
Published: November 2005

OBJECTIVE

To report a case of dose-related hyperammonemic coma without liver failure in a patient receiving chronic valproate therapy.

CASE SUMMARY

A 56-year-old woman with poorly controlled epilepsy, receiving valproate at subtherapeutic levels for 6 years, developed a life-threatening hyperammonemic coma following a moderate dosage increase.

DISCUSSION

Hyperammonemic coma without associated liver failure is an extremely rare complication of valproate therapy, described primarily in patients with inborn errors of metabolism and occurring idiosyncratically during initial stages of therapy. In our case, family history was suggestive of an X-linked disorder, raising the possibility that our patient may have been an asymptomatic carrier of a urea cycle enzyme deficiency unmasked by valproate therapy. To our knowledge, as of October 24, 2005, only one prior case of hyperammonemic coma in the context of chronic valproate monotherapy has been described. Application of the Naranjo probability scale score suggests that a causal relationship between valproic acid and hyperammonemic coma was probable.

CONCLUSIONS

The widespread use of valproic acid emphasizes the need to maintain a high degree of suspicion with respect to this rare but potentially fatal adverse effect at all times, regardless of therapy duration.
Vitamin E Supplementation in Alzheimer's Disease, Parkinson's Disease, Tardive Dyskinesia, and Cataract: Part 2
Authors: Pham David Q , Plakogiannis Roda
Published: November 2005

OBJECTIVE

To review clinical trials evaluating the safety and efficacy of vitamin E supplementation in Alzheimer's disease, Parkinson's disease, tardive dyskinesia, and cataract.

DATA SOURCES

Using the MeSH terms alpha-tocopherol, tocopherols, vitamin E, Parkinson disease, tardive dyskinesia, Alzheimer disease, cataract, and clinical trials, a literature review was conducted to identify peer-reviewed articles in MEDLINE (1966–July 2005).

STUDY SELECTION AND DATA EXTRACTION

Published materials including original research, review articles, and meta-analyses were reviewed. Only English-language articles and trials that included vitamin E alone or in combination with other vitamins or minerals were reviewed. Emphasis was placed on prospective, randomized, double-blind, placebo-controlled clinical trials.

DATA SYNTHESIS

The clinical studies demonstrated contradicting results regarding the benefits of vitamin E in Parkinson's disease, tardive dyskinesia, and cataract. The study reviewed for Alzheimer's disease seemed to show benefit when vitamin E was used; however, the statistical methods employed are questionable. There is enough evidence from large, well-designed studies to discourage the use of vitamin E in Parkinson's disease, cataract, and Alzheimer's disease. We recommend that vitamin E be considered a treatment option in patients with tardive dyskinesia only if they are newly diagnosed.

CONCLUSIONS

We encourage patients to supplement with vitamin E–rich foods. The use of a daily multivitamin, which usually contains 30 IU of alpha-tocopherol, may be beneficial; however, we discourage individual vitamin E supplements that usually contain 400 IU of alpha-tocopherol.
The Lifestyle Challenge Program: A Multidisciplinary Approach to Weight Management
Authors: Malone Margaret , Alger-Mayer Sharon A , Anderson Drew A
Published: November 2005

BACKGROUND

The increasing prevalence of overweight and obesity in the US has received widespread attention and is highlighted in recent government-issued health priorities. While there are many weight loss programs in different settings, few include pharmacist involvement in spite of pharmacists’ recognized easy accessibility to the public.

OBJECTIVE

To provide insight into a successful, collaborative, multidisciplinary approach to weight management and to encourage pharmacists and other healthcare professionals to adopt a similar approach to patient management.

METHODS

Adult patients >18 years of age were recruited from an outpatient university-based setting to participate in a weight management program. The principles of the program included diet, exercise, and behavior modification. The program was conducted through weekly one-hour group sessions held over a 20-week period. Faculty involved in the program included an attending physician specializing in nutrition, a pharmacist, and a behavioral psychologist. All data are expressed as mean ± SD unless otherwise specified.

RESULTS

Ninety participants (74 female, mean age 48 ± 10 y) entered the program between April 2001 and April 2004. Participants had multiple obesity-related comorbid diseases. The weight of completers (n = 59) decreased from 100.9 ± 20 kg at baseline to 97.3 ± 19.5 kg at 10 weeks and 95.9 ± 20 kg at 20 weeks. Thirty-nine patients completed both baseline and final assessments, which showed improvement in health-related quality of life, binge-eating behavior, and depressive symptoms (p < 0.05).

CONCLUSIONS

This program is a successful multidisciplinary model for the management of overweight and obese patients in an outpatient-based hospital setting.
Penicillin-Induced Jarisch–Herxheimer Reaction
Authors: See Sharon , Scott Emilie K , Levin Marc W
Published: November 2005

OBJECTIVE

To report a case of Jarisch–Herxheimer reaction (JHR) in a patient with presumed neurosyphilis and HIV.

CASE SUMMARY

A 45-year-old HIV-positive man (CD4+ count 450 cells/mm3 and history of AIDS-defining illness) presented with JHR after an initial intravenous dose of penicillin G for presumed neurosyphilis. The patient described feeling cold with worsening headache and chills approximately one hour after infusion of the first dose of penicillin. On examination, rigors, shallow inspirations, and chills were noted. He was afebrile, tachycardic, and tachypneic and had an oxygen saturation of 94% while breathing room air. His symptoms resolved within 10 minutes. Initially, this reaction was thought to be a result of a drug allergy, but upon further review, we determined that it was JHR.

DISCUSSION

It is not uncommon to confuse drug allergy with JHR. An objective causality assessment suggests that the JHR in our patient was probably related to penicillin. JHR is a self-limiting condition that warrants the continuation of antibiotic treatment in syphilis patients.

CONCLUSIONS

JHR should be an anticipated reaction to early doses of antibiotic treatment for treponemal diseases, such as syphilis. Treatment of JHR is largely supportive, such as administering antipyretic and antiinflammatory agents. Antibiotic treatment should be continued.
Children's friendships and learning in school: Cognitive enhancement through social interaction?
Authors: Kutnick Peter , Kington Alison
Published: November 2005

Background. Recent literature has identified that children's performance on cognitive (or problem‐solving) tasks can be enhanced when undertaken as a joint activity among pairs of pupils. Performance on this ‘social’ activity will require quality relationships between pupils, leading some researchers to argue that friendships are characterized by these quality relationships and, therefore, that friendship grouping should be used more frequently within classrooms.

Aims. Children's friendship grouping may appear to be a reasonable basis for cognitive development in classrooms, although there is only inconsistent evidence to support this argument. The inconsistency may be explained by the various bases for friendship, and how friendship is affected by cultural contexts of gender and schooling. This study questions whether classroom‐based friendship pairings will perform consistently better on a cognitive task than acquaintance pairings, taking into account gender, age, and ability level of children. The study also explores the nature of school‐based friendship described by young children.

Sample. 72 children were paired to undertake science reasoning tasks (SRTs). Pairings represented friendship (versus acquaintance), sex (male and female pairings), ability (teacher‐assessed high, medium, and low), and age (children in Years 1, 3, and 5 in a primary school).

Method. A small‐scale quasi‐experimental design was used to assess (friendship‐ or acquaintance‐based) paired performance on SRTs. Friendship pairs were later interviewed about qualities and activities that characterized their friendships.

Results. Girls' friendship pairings were found to perform at the highest SRT levels and boys' friendship pairing performed at the lowest levels. Both boy and girl acquaintance pairings performed at mid‐SRT levels. These findings were consistent across Year (in school) levels and ability levels. Interviews revealed that male and female friendship pairs were likely to participate in different types of activity, with girls being school‐inclusive and boys being school‐exclusive.

Conclusion. Recommendations to use friendship as a basis for classroom grouping for cognitive tasks may facilitate performance of some pairings, but may also inhibit the performance of others. This is shown very clearly with regard to gender. Some of the difference in cognitive task performance may be explained by distinct, cultural (and social capital) orientations to friendship activities, with girls integrating school and educational considerations into friendship, and boys excluding school and educational considerations.
Perceiving classroom aggression: The influence of setting, intervention style and group perceptions
Authors: Lawrence Claire , Green Karen
Published: November 2005

Background. Violence and aggression in the classroom are often cited as a major concern within the teaching community. Teachers' perceptions of the appropriateness of intervention behaviours during aggressive incidents, however, are less often examined (Meyer, Astor, & Behre, 2002), nor how they compare to the perceptions of training teachers (John, 2002).

Aims. This paper examines differences in the perceptions of practising and training teachers after exposure to an account of a violent incident where a school teacher is assaulted. The paper also investigates the relative and combined influence of classroom condition and teacher intervention on perceptions of classroom violence.

Sample(s). Participants included 48 practising teachers, and 48 students undertaking a Postgraduate Certificate in Education (PGCE) also took part in the study.

Methods. The study utilized a 2 × 2×2 between‐subjects factorial design, manipulating the impact of classroom condition, teacher intervention, and observer status on evaluations of the teacher, assailant and school following an incident of violence against the teacher.

Results. Classroom environment, teacher intervention, and observer status influenced evaluations of the teacher and school, but not the assailant.

Conclusions. Implications of these findings and the applied importance of these results are discussed in relation to school policy, teacher training, and classroom maintenance.
The relationship between epistemological beliefs, implicit theories of intelligence, and self‐regulated learning among Norwegian postsecondary students
Authors: Bråten Ivar , Strømsø Helge I.
Published: November 2005

Background. More empirical work is needed to examine the dimensionality of personal epistemology and relations between those dimensions and motivational and strategic components of self‐regulated learning. In particular, there is great need to investigate personal epistemology and its relation to self‐regulated learning across cultures and academic contexts. Because the demarcation between personal epistemology and implicit theories of intelligence has been questioned, dimensions of personal epistemology should also be studied in relation to implicit theories of intelligence.

Aims. The primary aim was to examine the dimensionality of personal epistemology and the relation between those dimensions and implicit theories of intelligence in the cultural context of Norwegian postsecondary education. A secondary aim was to examine the relative contribution of epistemological beliefs and theories of intelligence to motivational and strategic components of self‐regulated learning in different academic contexts within that culture.

Samples. The first sample included 178 business administration students in a traditional transmission‐oriented instructional context; the second, 108 student teachers in an innovative pedagogical context.

Methods. The dimensionality of the Schommer Epistemological Questionnaire was examined through factor analyses, and the resulting dimensions were examined in relation to implicit theories of intelligence. We performed multiple regression analyses, separately for the two academic contexts, to try to predict motivational (i.e. self‐efficacy beliefs, mastery goal orientation, and interest) and strategic (i.e. self‐regulatory strategy use) components of self‐regulated learning with epistemological beliefs and implicit theories of intelligence.

Results. Considerable cross‐cultural generalizability was found for the dimensionality of personal epistemology. Moreover, the dimensions of personal epistemology seemed to represent constructs separate from the construct of implicit theories of intelligence. Differences in the predictability of the epistemological dimensions were found for the two samples. For the student teachers, belief about knowledge construction and modification was a better predictor of self‐regulated learning. For the business administration students, belief about the certainty of knowledge played a more important role in self‐regulated learning.

Conclusions. Epistemological beliefs predict self‐regulated learning among Norwegian postsecondary students and play more important roles than implicit theories of intelligence. Relations between epistemological beliefs and self‐regulated learning may vary with academic context.
Parent versus professional views of the developmental impact of a multi‐faceted condition at school age: Otitis media with effusion (glue ear)
Authors: Higson Josephine , Haggard Mark
Published: November 2005

Background.Several aspects of children's health and development are known from empirical studies to be associated with otitis media with effusion (OME; ‘glue ear’). The ‘diffuse image’ has been an obstacle to defining a core set of impacts about which inter‐profession and parent‐professional communication can be effective.

Aims.The study quantifies similarities and differences in how the signs, symptoms, and developmental impact of OME are attributed and construed, between teachers, parents, and ear, nose, and throat (ENT)surgeons.

Sample.Convenience samples were achieved of 118 teachers and 154 parents of affected children; 178 ENT surgeons from a professional sampling frame (association membership) responded.

Method.Questionnaires elicited the perceived frequency and concern‐value of over 30 manifestations of OME ‐ the various signs, symptoms, and behaviours suggested by the literature. Factor scores derived on the combined sample were compared between respondent groups.

Results.Teachers assign high importance to education and language problems but, relative to parents, they accord lower importance to continuing hearing problems. Teachers and parents weighted behaviour and balance problems similarly, placing behaviour higher, but balance lower, than the ENT specialists did.

Conclusions.

A four‐factor reduction of simple questionnaire items well defines the domains of impact of OME, and can express the ways in which views of impact differ between teachers, ENT specialists and parents.

Considerable differences of perspective exist between the groups examined.

In valuing a set of measured outcomes on actual children, or for other policy research, sets of weights are now available to represent the differing perspectives of parents and professionals (e.g. in testing robustness of a conclusion across differing stakeholder perspectives).

The research and development need in respect of teachers' involvement with OME could profitably play to existing strengths. This implies the systematic and structured acquisition and evaluation of teacher‐provided impact information.