bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing perinatal mortality among Indigenous babies in Queensland: should the first priority be better primary health care or better access to hospital care during confinement?
Authors: Johnston Trisha , Coory Michael
Published: May 2005

Background

The perinatal mortality rate among Indigenous Australians is still double that of the rest of the community. The aim of our study was to estimate the extent to which increased risk of low birthweight and preterm birth among Indigenous babies in Queensland account for their continuing mortality excess. If a large proportion of excess deaths can be explained by the unfavourable birthweight and gestational age distribution of Indigenous babies, then that would suggest that priority should be given to implementing primary health care interventions to reduce the risk of low birthweight and preterm birth (eg, interventions to reduce maternal smoking or genitourinary infections). Conversely, if only a small proportion is explained by birthweight and gestational age, then other strategies might need to be considered such as improving access to high-quality hospital care around the time of confinement.

Methodology

Population-based, descriptive study of perinatal mortality rates among Indigenous and non-Indigenous babies, in Queensland, stratified by birthweight and gestational age.

Results

Indigenous babies are twice as likely to die as their non-Indigenous counterparts (rate ratio1998–2002: 2.01; 95%ci 1.77, 2.28). However, within separate strata of birth weight and gestational age, Indigenous and non-Indigenous rates are similar. The Mantel-Haenszel rate ratio adjusted for birth weight and gestational age was 1.13 (0.99, 1.28). This means that most of the excess mortality in Indigenous babies is largely due to their unfavourable birth weight and gestational-age distributions. If Indigenous babies had the same birth weight and gestational age distribution as their non-Indigenous counterparts, then the relative disparity would be reduced by 87% and 20 fewer Indigenous babies would die in Queensland each year.

Conclusion

Our results suggest that Indigenous mothers at high risk of poor outcome (for example those Indigenous mothers in preterm labour) have good access to high quality medical care around the time of confinement. The main reason Indigenous babies have a high risk of death is because they are born too early and too small. Thus, to reduce the relative excess of deaths among Indigenous babies, priority should be given to primary health care initiatives aimed at reducing the prevalence of low birth weight and preterm birth.
Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy
Authors: Stuckey D J , Anthony D C , Lowe J P , Miller J , Palm W M , Styles P , Perry V H , Blamire A M , Sibson N R
Published: May 2005

Macrophages are key components of the inflammatory response to tissue injury, but their activities can exacerbate neuropathology. High-resolution magnetic resonance spectroscopy was used to identify metabolite levels in perchloric acid extracts of cultured cells of the RAW 264.7 murine macrophage line under resting and lipopolysaccharide-activated conditions. Over 25 metabolites were identified including γ-aminobutyric acid (GABA), an inhibitory neurotransmitter not previously reported to be present in macrophages. The presence of GABA was also demonstrated in extracts of human peripheral blood monocyte-derived macrophages. This finding suggests that there may be communication between damaged central nervous system (CNS) tissue and recruited macrophages and resident microglia, which could help orchestrate the immune response. On activation, lactate, glutamine, glutamate, and taurine levels were elevated significantly, and GABA and alanine were reduced significantly. Strong resonances from glutathione, evident in the macrophage two-dimensional 1H spectrum, suggest that this may have potential as a noninvasive marker of macrophages recruited to the CNS, as it is only present at low levels in normal brain. Alternatively, a specific combination of spectroscopic changes, such as lactate, alanine, glutathione, and polyamines, may prove to be the most accurate means of detecting macrophage recruitment to the CNS.
Percutaneous absorption of arsenic from environmental media
Authors: Lowney Yvette W , Ruby Michael V , Wester Ronald C , Schoof Rosalind A , Holm Stewart E , Hui Xiao-Ying , Barbadillo Sherry , Maibach Howard I
Published: May 2005

Current knowledge of percutaneous absorption of arsenic is based on studies of rhesus monkeys using soluble arsenic in aqueous solution, and soluble arsenic mixed with soil (Wester et al., 1993). These studies produced mean dermal absorption rates in the range of 2.0-6.4% of the applied dose. Subsequently, questions arose as to whether these results represent arsenic absorption from environmental media. Factors such as chemical interactions, the presence of other metals, and the effects of weathering on environmental media all can affect the nature of arsenic and its potential for percutaneous absorption. Therefore, research specific to more relevant matrices is important. The focus of this effort is to outline study design considerations, including particle size, application rates, means of ensuring skin contact and appropriate statistical evaluation of the data. Appropriate reference groups are also important. The potential for background exposure to arsenic in the diet possibly obscuring a signal from a dermally applied dose of arsenic will also be addressed. We conclude that there are likely to be many site-or sample-specific factors that will control the absorption of arsenic, and matrix-specific analyses may be required to understand the degree of percutaneous absorption.
Ratios of N-(2,3,4-trihydroxybutyl) valine and N-(2-hydroxy-3-butenyl) valine formed hemoglobin adducts in female mice inhalation exposure with 1,3-butadiene
Authors: Lee Jin Heon , Kang Hee Sook , Han Don-Hee
Published: May 2005

1,3-Butadiene (BD) is a known rodent and probable human carcinogen (IARC, group 2A) or ‘known to be a human carcinogen’ (Department of Health and Human Services, 2000). Exposure to BD can occur either via petrochemical products or through the general environment. Adducts can be used as biomarkers for biological monitoring of carcinogen exposure. This study investigated the hemoglobin adducts in blood after inhalation exposure to BD in ICR female mice for three weeks (5 h/day-5 days/week). During the inhalation exposure, the body weights of mice were significantly lower from day 9 onward for the 500 ppm BD group and from day 4 onward for the 1000 ppm BD group. On the 1st, 2nd and 3rd weeks after inhalation exposure, the concentrations of HB Val adducts were 1.8, 3.7 and 6.2 pmol/mg globin for the 500 ppm BD group, and 5.7, 7.4 and 16.0 pmol/mg globin for the 1000 ppm BD group. The concentrations of THB Val adducts were 32.0, 42.0 and 55.0 pmol/mg globin for the 500 ppm BD group, and 67.8, 72.7 and 83.5 pmol/mg globin for the 1000 ppm BD group. Their defined ratios were higher at the earlier exposure period and at the lower concentration. They were 17.8, 11.4 and 8.87 for the 500 ppm BD group, and 11.9, 9.8 and 5.2 for the 1000 ppm BD group, on the 1st, 2nd and 3rd weeks after inhalation exposure. THB Val and HB Val adducts appear to be the important hemoglobin adducts for monitoring BD exposure, with the latter being a more predictable biomarker than the former.
Propylene glycol monomethyl ether. A three-generation study of isomer β effects on reproductive and developmental parameters in rats
Authors: Lemazurier Emmanuel , Lecomte Anthony , Robidel Franck , Bois Frédéric Y
Published: May 2005

Propylene glycol monomethyl ether (PGME) is widely used as a solvent in numerous commercial products. Its chemical synthesis leads to the formation of two isomers: a and b, the latter being usually present in the range of 0.5-1.5%. Isomer α has been shown to be of low toxicity. Isomer β raises concerns as to its reproductive and developmental effects. We evaluated the reproductive and developmental toxicity of two different commercial mixes of PGME (Mix A: 99% isomer α and 0.5% isomer β, Mix B: 98.5% isomer α and 1.5% isomer β) on Sprague-Dawley rats. The use of two mixes allowed us to differentiate between isomer α and isomer β effects. Male and female rats were exposed through drinking water to mixes A or B during a gametogenesis cycle (64 days for males and 15 days for females) to 0, 2, 5, 10 and 15% (v/v) of each mix. These animals (F0) and the three following generations (F1, F2 and F3) were followed. We observed a statistically significant decrease in the number of pups in isomer α-treated animals of generation F1 and a nondose-related variation of the sex ratio in F1 and F2 generations after PGME mix B treatment. The most important effect observed was a decrease in testicular and epididymal sperm counts in relation to PGME isomer β in acute daily exposure, on the first parental generation. The effect evidenced on sex ratio needs further work in order to assay the potential persistent effects of PGME exposure.
A rat model to evaluate the pesticide permeability and stress effects of protective clothing
Authors: You Kyung-Sook , Lee Myoung-Hee , Park Kwan Ha
Published: May 2005

No animal model exists for testing the suitability of a protective garment before actual application in humans. The animal testing model is valuable in particular as the assessment of permeability of hazardous chemicals in humans cannot be easily performed due to possible toxicity to test subjects. We explored a rat model by designing a protective garment to fit rats, and then examining pesticide permeability and physiological responses. When nongarmented rats were exercised in a treadmill, there were increases in heart rate, mean arterial pressure and body temperature. The increases in heart rate and body temperature were further augmented by wearing the protective garment. Fenitrothion, an organophosphate insecticide, was detected in plasma after application on the dorsal area in plasma of nongarmented and garmented (comparable to regular human work clothes) rats. Plasma acetylcholine esterase activity was decreased, suggesting intoxication in these animals. Fenitrothion intoxication was not observed in rats wearing a protective garment. In humans, heart rate and body temperature augmentation were also observed when wearing a protective garment. This result suggests that the present rat model provides a useful assessment of chemical permeability and stress effects of protective garments.
The activities of liver adenosine deaminase, xanthine oxidase, catalase, superoxide dismutase enzymes and the levels of malondialdehyde and nitric oxide after cisplatin toxicity in rats: protective effect of caffeic acid phenethyl ester
Authors: Yilmaz H Ramazan , Sogut Sadik , Ozyurt Birsen , Ozugurlu Fikret , Sahin Semsettin , Isik Bunyamin , Uz Ebru , Ozyurt Huseyin
Published: May 2005

The aim of this experimental study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on cisplatin-induced hepatotoxicity through adenosine deaminase (AD), xanthine oxidase (XO), catalase (CAT), superoxide dismutase (SOD) activities and malondialdehyde (MDA) and nitric oxide (NO) levels in liver tissue of rats. Wistar albino rats were divided into three groups: control group (n-6), cisplatin group (n-9) and CAPE+cisplatin group (n-8). All the chemicals used were applied intraperitoneally. Spectrophotometric methods were used to determine the activities of the above-mentioned enzymes in the liver tissue. NO level and XO activity were found to be increased in the cisplatin group compared to the control group. NO level was found to be decreased in the cisplatin+CAPE group in comparison with the cisplatin group. There was no significant change in the activity of XO between the cisplatin and cisplatin+CAPE groups. The activity of SOD was lower in the cisplatin group than both the control and cisplatin+CAPE groups. There was no significant change in the activity of CAT between the control and cisplatin groups. CAT activity was increased in the cisplatin+CAPE group compared to the cisplatin group. The AD activity and MDA level remained unchanged in all groups. The results obtained suggested that CAPE significantly attenuated the hepatotoxicity as an indirect target of cisplatin in an animal model of cisplatin-induced nephrotoxicity.
Airborne particulates and asthma: a Maine case study
Authors: Langley-Turnbaugh Samantha J , Gordon Nancy R , Lambert Thomas
Published: May 2005

Maine currently has the second fastest growing asthma rate in the nation- 9.4% of the adult population has asthma and one out of eight children is affected. The factors behind this increase are poorly understood, but previous reports suggest that biologically soluble metal ions from particulate matter (PM10) may play a role in asthma episodes. In an effort to study this issue, we first identified geographic and temporal trends in Maine asthma hospitalizations. Clinical data show a strong fall peak in asthma admissions with weaker peaks in January and May, and a summer low in asthma admissions. Asthma admissions are also higher in the cities than in the rural areas in Maine. We then analysed PM10 collected by the Maine Department of Environmental Protection in three different Maine locations in the years 2000 and 2001, at times when clinical asthma data showed peaks and during the summer low period. We also collected soil samples in the same locations. The PM10 and soils were analysed for 10 metals by acid extraction to determine total metal content and then with cell culture medium, DMEM/F12+CCS growth medium, to determine metal biosolubility. Our results showed that Mn, Cu, Pb, As, V, Ni and Al were present in the Maine PM samples. V, Ni and Pb showed seasonal variation, while the others were relatively constant throughout the year. Pb and Al did not appear to be soluble in the biological medium. There was also variation from location to location with the urban area showing the highest concentrations for most metals. Aluminium was present in the highest concentration in soil samples, followed by Mn and V. Only Cu was biologically available in soils. We determined from M/Al ratios that most of the PM10 did not originate from local crustal material.
Randomization-based nonparametric methods for the analysis of multicentre trials
Authors: LaVange Lisa M , Durham Todd A , Koch Gary G
Published: May 2005

Multicentre trials offer several advantages over single centre trials in clinical research, including the ability to recruit patients at a faster rate over the course of the study, increased generalizability through the use of a broader patient population, and the ability to shed light on the replication of findings at multiple centres in a single study. A nonparametric approach to the analysis of multicentre trial data provides a convenient way for addressing the role of centres as well as baseline covariables during data analysis. With the use of randomization-based nonparametric methods, the strategy for evaluating the null hypothesis of no treatment effect can be prespecified during study planning without requiring a specific structure for the relationship of response criteria (or endpoints) to centres, covariables, or potential interaction terms. Further, the basis of inference for the application of these methods is the randomization mechanism, and the population to which inference can be directly made is the study population itself. No assumptions about underlying distributions, data structures, likelihood functions, or samples from super populations of inference are required. A three-step approach is proposed for handling centres via randomization-based nonparametric methods. In Step 1, a test of overall treatment effect is carried out using data from all centres simultaneously, without any assumption about treatment by centre interaction. In Step 2, the question of treatment by centre interaction is addressed, usually through the use of parametric multiple regression methods. In cases with suggestion of such interaction, Step 3 is conducted to evaluate different weighting schemes in forming pairwise treatment comparisons averaged across centres to assess the robustness of treatment effects observed in Step 1. An attractive inferential feature of this three-step approach is that the Type I error for the test of treatment effect is controlled by requiring statistical significance at each step to proceed to the next step. Extended Mantel-Haenszel methods with stratification adjustment for centre can be used to provide a nonparametric assessment of treatment effect. When adjustment for other covariates, such as baseline values, is desired, the more recent nonparametric analysis of covariance methods are available. Both methods are easy to use, require no assumptions beyond that of a valid randomization mechanism, and can be applied in a similar manner to dichotomous, ordinal, failure time, or continuous response criteria (endpoints). The methods are illustrated using data from a confirmatory clinical trial of a therapeutic agent for the treatment of dry eye disease.
Multicentre trials: a US regulatory perspective
Authors: Anello Charles , O’Neill Robert T , Dubey Satya
Published: May 2005

Multicentre trials are very common in the field of drug development. In recent years, multicentre trials have taken on a multinational and multiregional aspect. We provide a conceptual framework for the use of multicentre trials in the context of drug development, from the perspective of drug regulation in the United States. In this paper, we review some regulatory history, milestones and standards as they relate to multicentre trials. Special attention is given to the similarities and differences in the approaches to multicentre trials in the following documents; Guideline for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, International Conference on Harmonization, Draft Guideline on Statistical Principles for clinical trials and the Guidance for Industry Providing Clinical Evidence of Effectiveness for Human Drug and Biologic Products. The paper includes a consideration of some of the issues in the analysis of data from multicentre trials.
The design of multicentre trials
Authors: Fedorov Valerii , Jones Byron
Published: May 2005

The analysis of data collected in multicentre trials offers challenges because the data from the individual centres must be combined in some way to give an overall evaluation of the differences between the treatments in the trial. We propose that the combined response to treatment (CRT) be used as this overall measure. The definition and estimation of the CRT can be derived from either a fixed-effects or a random-effects model. For the latter we introduce the ECRT - the expected combined response to treatment. We describe and compare both types of model and express our preference for the random-effects model. We stress that the number of patients enrolled at a centre is a random variable and show that this source of randomness inflates the variance of the estimated ECRT. Variability in enrolment rates over the centres further inflates this variance. A simple conclusion from our results is that if variability in the treatment and centre effects, in the enrolment time, in the number of patients enrolled at a centre and in the enrolment rates is not properly accounted for, then an underpowered trial may result. Using properties of estimators generated by the random-effects model we propose methods for determining the optimal number of centres and total number of patients to enrol in a trial to minimize a loss function that accounts for centre and patient costs and loss of revenue. We discuss variants of the loss function and corresponding optimization problems for different types of enrolment. We end the paper with brief generalizations of the developed techniques to the case where the response is binary.
The Chemical Dimension of the Gallipoli Campaign: Introducing Chemical Warfare to the Middle East
Authors: Sheffy Yigal
Published: May 2005

Studies of the history of chemical warfare ignore the chemical dimension of the campaigns in the Middle East during the First World War. They miss the fact that the British first considered using gas in the region during the Gallipoli campaign in 1915. At that time, the political and military leadership in London, as well as senior commanders of the Mediterranean Expeditionary Force (MEF), were alarmed by the possibility of Turkish chemical attacks and repeatedly debated whether they should pre-empt this move by initiating the use of gas. This raised ethical, moral and prestige considerations, related to the British reputation in the Middle East. Eventually, gas cylinders were shipped to the MEF but never used. The British waited another year and a half before attacking the Turks with chemical munitions in Palestine.
Some Observations on Administration and Logistics of the Siege of Nicaea
Authors: Bachrach Bernard S.
Published: May 2005

The writing of medieval military history, at present, is dominated by a romantic emphasis on ‘chivarly’ and ‘knightly’ individualism. This parti pris fundamentally distorts the history of medieval warfare and undermines a proper understanding of medieval society by making it seem intrinsically alien to both Roman and early modern military culture. In this study of a siege, which dominated warfare during the Middle Ages, the material realities have been emphasized, e.g., administration and logistics, as contrasted to literary propaganda and religious propaganda, in an effort to stimulate discussion regarding the ineluctable facts that undergird war throughout history.
Childhood Cancer Survival Trends in Europe: A EUROCARE Working Group Study
Authors: Gatta Gemma , Capocaccia Riccardo , Stiller Charles , Kaatsch Peter , Berrino Franco , Terenziani Monica ,   the EUROCARE Working Group
Published: May 2005

Purpose

EUROCARE collected data from population-based cancer registries in 20 European countries. We used this data to compare childhood cancer survival time trends in Europe.

Patients and Methods

Survival in 44,129 children diagnosed under the age of 15 years during 1983 to 1994 was analyzed. Sex- and age-adjusted 5-year survival trends for 10 common cancers and for all cancers combined were estimated for five regions (West Germany, the United Kingdom, Eastern Europe, Nordic countries, and West and South Europe) and Europe as a whole. Europe-wide trends for 14 rare cancers were estimated.

Results

For all cancers combined, 5-year survival increased from 65% for diagnoses in 1983 to 1985 to 75% in 1992 to 1994. Survival improved for all individual cancers except melanoma, osteosarcoma, and thyroid carcinoma; although for retinoblastoma, chondrosarcoma, and fibrosarcoma, improvements were not significant. The most marked improvements (50% to 66%) occurred in Eastern Europe. For common cancers, the greatest improvements were for leukemia and lymphomas, with risk of dying reducing significantly by 5% to 6% per year. Survival for CNS tumors improved significantly from 57% to 65%, with risk reducing by 3% per year. Risk reduced by 4% per year for neuroblastoma and 3% per year for Wilms’ tumor and rhabdomyosarcoma. The survival gap between regions reduced over the period, particularly for acute nonlymphocytic leukemia, CNS tumors, and rhabdomyosarcoma. For rare Burkitt’s lymphoma, hepatoblastoma, gonadal germ cell tumors, and nasopharyngeal carcinoma, risk reductions were at least 10% per year.

Conclusion

These gratifying improvements in survival can often be plausibly related to advances in treatment. The prevalence of European adults with a history of childhood cancer will inevitably increase.
Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Detected by Clonotypic Polymerase Chain Reaction Despite Continuous Pathologic Remission Induced by Involved-Field Radiotherapy
Authors: Noy Ariela , Yahalom Joachim , Zaretsky Leah , Brett Ian , Zelenetz Andrew D.
Published: May 2005

Purpose

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is indolent and often associated with Helicobacter pylori bacterial infection. H pylori–independent MALT develops either in the absence of the bacteria or persists after bacterial eradication. We have previously demonstrated long-term pathologic remission after involved-field radiotherapy therapy (IFRT). We determined molecular remission status by clonotypic polymerase chain reaction (PCR).

Patients and Methods

Twenty-four consecutive patients with stage I to IIE gastric MALT lymphoma who obtained a pathologic remission after IFRT alone were evaluated. All had at least two follow-up endoscopic gastroduodenal biopsies at Memorial Sloan-Kettering Cancer Center. IFRT median dose was 30 Gy (range, 28.5 to 43.5 Gy). Post-treatment biopsies were subjected to semi-nested clonotypic PCR.

Results

All patients obtained a complete response based on routine immunohistochemical pathologic analysis of random post-treatment gastric biopsies. Median follow-up from completion of IFRT was 63 months (range, 19 to 117 months). Event-free survival was 96%; 23 of 34 patients remained in clinical and pathologic complete remission. Baseline DNA extraction yielded 17 clone-specific primer pairs. At the first follow-up test, 14 of 17 pairs were PCR positive. Eight remained persistently positive; and one was persistently negative. Others were intermittently positive.

Conclusion

Despite sustained biopsy-proven remissions for as long as 117 months after radiation, the vast majority of patients remain positive by clonotypic PCR. This suggests that the malignant clone is present but missing either an internal or external signal essential to the cancer phenotype. One possibility is that radiation eradicates the polyclonal H pylori–specific T cells eliminating critical local factors necessary for proliferation of the monoclonal B cells.
Synovial Sarcoma Translocation (SYT) Encodes a Nuclear Receptor Coactivator
Authors: Iwasaki Toshiharu , Koibuchi Noriyuki , Chin William W.
Published: May 2005

We previously cloned and characterized a novel RNA-binding motif-containing coactivator, named coactivator activator (CoAA), as a thyroid hormone receptor-binding protein-interacting protein using a Sos-Ras yeast two-hybrid screening system. A database search revealed that CoAA is identical with synovial sarcoma translocation (SYT)-interacting protein. Thus, we hypothesized that SYT could also function as a coactivator. Subsequently, we isolated a cDNA encoding a larger isoform of SYT, SYT-long (SYT-L), from the brain and liver total RNA using RT-PCR. SYT-L possesses an additional 31 amino acids in its C terminus compared with SYT, suggesting that these two SYT isoforms may be expressed from two mRNAs produced by alternative splicing of a transcript from a single gene. By Northern blot analysis, we found that SYT-L mRNA is expressed in several human embryonic tissues, such as the brain, liver, and kidney. However, we could not detect SYT-L in adult tissues. Glutathione-S-transferase pull-down studies showed that SYT binds to the C-terminus of CoAA, but not to the coactivator modulator. Both isoforms of SYT function as transcriptional coactivators of nuclear hormone receptors in a ligand- and dose-dependent manner in CV-1, COS-1, and JEG-3 cells. However, the pattern of transactivation was different between SYT and SYT-L among these cells. SYT synergistically activates transcription with CoAA. In addition, SYT activates transcription through activator protein-1, suggesting that SYT may function as a general coactivator. These results indicate that SYT activates transcription, possibly through CoAA, to interact with the histone acetyltransferase complex.
Development and Function of the Adult Generation of Leydig Cells in Mice with Sertoli Cell-Selective or Total Ablation of the Androgen Receptor
Authors: De Gendt Karel , Atanassova Nina , Tan Karen A. L. , de França Luiz Renato , Parreira Gleydes Gambogi , McKinnell Chris , Sharpe Richard M. , Saunders Philippa T. K. , Mason J. Ian , Hartung Stefan , Ivell Richard , Denolet Evi , Verhoeven Guido
Published: May 2005

It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age. LC number in SCARKOs was normal on d 12, but was reduced by more than 40% at later ages, although LC were larger and contained more lipid droplets and mitochondria than control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls, and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, although testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, insulin-like factor-3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas the expression of both was reduced more than 90% in ARKOs. Changes in EST expression, coupled with reduced platelet-derived growth factor-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development, and this could be mediated indirectly via platelet-derived growth factor-A and/or estrogens/EST.
Decreased Gonadotropin-Releasing Hormone Neuronal Activity Is Associated with Decreased Fertility and Dysregulation of Food Intake in the Female GPR-4 Transgenic Rat
Authors: Gomez Francisca , la Fleur Susanne E. , Weiner Richard I. , Dallman Mary F. , El Majdoubi Mohammed
Published: May 2005

Expression of a cAMP-specific phosphodiesterase in GnRH neurons in the GPR-4 transgenic rat resulted in decreased LH levels and pulse frequency and diminished fertility. We have characterized changes in fertility, adiposity, and reproductive and metabolic hormones with age. Although LH levels were decreased in 3-, 6-, and 9-month-old GPR-4 females relative to wild-type (WT) controls, GPR-4 females did not become anovulatory until 6 months of age. No differences were observed in FSH, estradiol, or androstenedione levels in 3-, 6-, or 9-month-old GPR-4 and WT females. At 9 months of age, GPR-4 females had significantly increased abdominal and sc fat depot weights that were associated with increased leptin and insulin levels not observed in WT females. We tested the hypothesis that metabolic changes observed at 9 months of age were the result of dysregulation of the mechanisms controlling energy balance. Two-month-old female GPR-4 rats placed on a high-energy diet gained weight at a rate significantly greater than WT females and, after 24 d, developed the same metabolic phenotype observed in 9-month-old GRP-4 females (increased abdominal and sc fat associated with elevated leptin and insulin concentrations). Overeating did not correlate with changes in estradiol or androstenedione levels. We conclude that decreased GnRH neuronal activity is closely associated with decreased reproductive function and dysregulation of food intake.
The Differential Effects of the Gonadotropin Receptors on Aromatase Expression in Primary Cultures of Immature Rat Granulosa Cells Are Highly Dependent on the Density of Receptors Expressed and the Activation of the Inositol Phosphate Cascade
Authors: Donadeu Francesc Xavier , Ascoli Mario
Published: May 2005

Signaling pathways mediating the divergent effects of FSH and LH on aromatase in immature rat granulosa cells were studied by infecting cells with increasing amounts of adenoviral vectors for the human LH receptor (hLHR) or FSH receptor (hFSHR). Increasing amounts of Ad-hLHR, used at a multiplicity of infection (MOI) of 20 or 200 viable viral particles/cell, increased human chorionic gonadotropin (hCG) binding and hCG-induced cAMP and Akt phosphorylation, but inositol phosphates only increased in response to hCG in cells infected with 200 MOI Ad-hLHR. In contrast, hCG increased aromatase expression in cells infected with 20, but not in cells infected with 200, MOI Ad-hLHR. Cells infected with 20 or 200 MOI Ad-hFSHR showed increased hFSH binding and hFSH-induced Akt phosphorylation, but the hFSH-induced cAMP response was unchanged relative to control cells. However, hFSH was able to stimulate the inositol phosphate cascade in the Ad-hFSHR-infected cells, and the hFSH induction of aromatase was abolished. We also found that activation of C kinase or expression of a constitutively active form of Gαq inhibited the induction of aromatase by hFSH or 8Br-cAMP. We conclude that the differential effects of FSH and LH on aromatase in immature granulosa cells are highly dependent on gonadotropin receptor density and on the signaling pathways activated. We propose that aromatase is induced by common signals generated by activation of the FSHR and LHR (possibly cAMP and Akt) and that the activation of the inositol phosphate cascade in cells expressing a high density of LHR or FSHR antagonizes this induction.
Androgen Receptor Mutations Identified in Prostate Cancer and Androgen Insensitivity Syndrome Display Aberrant ART-27 Coactivator Function
Authors: Li Wenhui , Cavasotto Claudio N. , Cardozo Timothy , Ha Susan , Dang Thoa , Taneja Samir S. , Logan Susan K. , Garabedian Michael J.
Published: May 2005

The transcriptional activity of the androgen receptor (AR) is modulated by interactions with coregulatory molecules. It has been proposed that aberrant interactions between AR and its coregulators may contribute to diseases related to AR activity, such as prostate cancer and androgen insensitivity syndrome (AIS); however, evidence linking abnormal receptor-cofactor interactions to disease is scant. ART-27 is a recently identified AR N-terminal coactivator that is associated with AR-mediated growth inhibition. Here we analyze a number of naturally occurring AR mutations identified in prostate cancer and AIS for their ability to affect AR response to ART-27. Although the vast majority of AR mutations appeared capable of increased activation in response to ART-27, an AR mutation identified in prostate cancer (AR P340L) and AIS (AR E2K) show reduced transcriptional responses to ART-27, whereas their response to the p160 class of coactivators was not diminished. Relative to the wild-type receptor, less ART-27 protein associated with the AR E2K substitution, consistent with reduced transcriptional response. Surprisingly, more ART-27 associated with AR P340L, despite the fact that the mutation decreased transcriptional activation in response to ART-27. Our findings suggest that aberrant AR-coactivator association interferes with normal ART-27 coactivator function, resulting in suppression of AR activity, and may contribute to the pathogenesis of diseases related to alterations in AR activity, such as prostate cancer and AIS.
A group III steroid solution without antibiotic components: an effective cure for external otitis
Authors: Emgård Per , Hellström Sten
Published: May 2005

The present study was undertaken to compare the clinical benefits of prescribing ear drops containing 0.05% solution of betamethasone dipropionate (BD), and ear drops containing hydrocortisone with oxytetracycline hydrochloride and polymyxin B (HCPB), for topical treatment of external otitis.

Fifty-one patients were enrolled in this open randomized, parallel-group, multicentre study,performed in eight different ENT departments. The patients were randomly assigned to one of thetwo treatment groups: BD (n= 26) and HCPB (n= 25). Only ENT specialists investigated the patients. Bacterial and fungal cultures were raised on days 1 and 11, using swabbedmaterial from ear canals. Twice daily the patients recorded their symptoms during the acute phase, using special diary cards.

BD proved a significantly more effective cure than HCPB during the acute
phase of external otitis and afforded a lower relapse frequency during a six-month follow-up period. The patients of the BD group were significantly less troubled by itching (p <0.01) than those in the HCPB group. On day 11, at the end of the acute phase, growth of bacteria (p= 0.03) and fungi (p < 0.01) was less frequent in the BD group than inthe HCPB group. No serious adverse events occurred, and those minor events observed were comparable between the two groups.

Our conclusion is that the group III steroid solution, BD, cured the external otitismore effectively than did the HCPB solution, whether infected by bacteria or by fungi. No difference was evident regarding adverse effects. Furthermore, price favours a solution without any antibiotic component. In view of these observations, a group III steroid solution ought to be the preferred remedy for external otitis, whether infected or not.
Otic barotrauma from air travel
Authors: Mirza S , Richardson H
Published: May 2005

Otic barotrauma occuring during air travel involves traumatic inflammation of the middle ear, caused by a pressure difference between the air in the middle ear and the external atmosphere, developing after ascent or more usually descent. The pressure difference occurs because of failure of the eustachian tube to equilibrate middle ear and atmospheric pressures. It is a common problem, presenting with ear fullness, otalgia and deafness. Severe cases may result in tympanic membrane perforation and even round window membrane rupture. Of three randomized controlled trials, one showed that oral pseudoephedrine decongestants reduced otalgia inadults with recurrent ear pain during air travel, whilst another found that oral pseudoephedrine did not decrease in-flight ear pain in children. The third trial showed that oxymetazoline decongestant nasal spray, taken 30 minutes before descent, did not produce a statistically significant reduction in symptoms of barotrauma in adults with recurrent ear pain during air travel. We review the causes, prevention and treatment of this condition.
Endoscopic sinus surgery for antrochoanal polyp using CO2 laser and/or microresector: a long–term result
Authors: Sato Kiminori , Nakashima Tadashi
Published: May 2005

Endoscopic sinus surgery procedure using CO2 laser and/or microresector for paediatric and adult chronic sinusitis with antrochoanal polyp (ACP), with long-term follow-up, was examined. Twelve children and 13 adults underwent the surgical procedure.

The following two techniques were used to remove the antral portion of an ACP with a 70°endoscope:

(1) CO2 laser – The base of the ACP was vaporized and removed via an enlarged natural ostium with a pipe-guide handpiece with a deflective tip.

(2) Microresector – The ACP was resected via
an enlarged natural ostium and/or nasoantral window opened under the inferior turbinate with the curved and straight blade of a microresector.

In the endoscopic follow up for 10 to 57 months, no patient who underwent the primary surgery required reoperation for ACP recurrence. One out of
the seven patients who underwent secondary surgery required a revised operation with microresector and CO2 laser.
Agenesis of the unilateral parotid gland associated with pleomorphic adenoma of the contralateral parotid gland
Authors: Karakoc Omer , Akcam Tímur , Kocaoglu Murat , Yetiser Sertac
Published: May 2005

Congenital absence of the parotid gland is extremely infrequent. We presenthere a case of unilateral parotid gland agenesis with pleomorphic adenoma of the contralateral parotid gland. Even though pleomorphic adenoma is the most common tumour of the parotid gland, to our knowledge this is the first case of these two conditions being seen together.
Recurrent squamous cell carcinoma in the neopharynx treated successfully with topical 5-fluorouracil
Authors: Banga Rupan , Ramsden James , Cox Graham
Published: May 2005

We present the first reported case of a squamous cell carcinoma recurrence on a reconstructed flap in the pharynx treated successfully with topical chemotherapy. The patient, treated for a pharyngeal cancer with resection and reconstruction with a free radial forearm flap, and post-operative radiotherapy, developed a tumour on the flap more than two years after surgery. The recurrence was also squamous carcinoma, but there was only superficial infiltration. This was treated with 5-fluorouracil paste placed in the pharynx, with resolution of thetumour. The patient was alive and well more than 28 months after this treatment, with no sign of disease recurrence. Topical chemotherapy for treatment of oral cancer is well described for early disease, but we show that it may be a useful treatment in recurrent disease in selected patients.
A new head and neck surgical drain fixation technique
Authors: Lim Mingyann , Pitkin Lisa , Spraggs Paul
Published: May 2005

We describe a simple technique of drain fixation in head and neck surgery using a beaded 2/0 nylon suture and a ’clove hitch’ to achieve a non-slip fixation to the drain.
Referral letters: are we prioritizing consistently?
Authors: Pothier David D , Repanos Costa
Published: May 2005

Objectives: To determine the levels of intra- and inter-grade variability of the vetting of general practice (GP) letters as well as the intra-rater reliability of letterprioritization.

Design: Prospective assessment of letter vetting and questionnaire survey.

Setting: Three otolaryngology secondary referral centres in Bristol and Bath, UK.

Participants: Twelve consultants, nine registrars, four staff and associate specialists (SAS) and 16 senior house officers (SHOs) in otolaryngology.

Methods: Fifty GP letters (not including ’fast-track’ referrals) addressed
to one of the ENT departments were chosen sequentially. These were anonymized, photocopied and included in the questionnaire to all participating staff. Participants were asked to vet the letters as ’urgent’, ’soon’ or ’routine’ according to supplied waiting time criteria. The same letters were sent out again six weeks later.

Results: There was no significant difference between grades for the mean number of letters vetted into each category. Intra-grade variability was high; the number of letters vetted urgentvaried from one out of 50 to 15 out of 50 for the consultants.The intra-rater reliability was high.

Conclusion: The grade of trainee seems to make little difference with regard to ability to prioritize referrals, but within grades there is little agreement on what constitutes an urgent referral. We suggest further research, looking at the final outcome of patients, needs to be done to try to establish evidence-based guidelines to assist with letter vetting.
Association between methylenetetrahydrofolate reductase polymorphisms, alcohol intake and oropharyngolaryngeal carcinoma in northern Italy
Authors: Capaccio Pasquale , Ottaviani Francesco , Cuccarini Valeria , Cenzuales Salvatore , Cesana Bruno Mario , Pignataro Lorenzo
Published: May 2005

Folate metabolism dysregulation may lead to abnormal cell proliferation andpredispose to carcinogenesis by inducing DNA hypomethylation. Folate pathways may be modified by polymorphisms in relevant genes, such as that for methylenetetrahydrofolate reductase (MTHFR), or by alcohol consumption. We investigated the relationship between MTHFR mutations at nucleotides C677T and A1298C, which cause reduced MTHFR enzyme activity, and susceptibility to oropharyngolaryngeal carcinoma in 65 patients and 100 controls. We isolated DNA from peripheral bloodleukocytes. In oropharyngolaryngeal carcinoma cases the C677T heterozygous genotype was more frequent (p = 0.018), the allele frequency of MTHFR 677T was greater (p = 0.019) and the genotype 677TT/1298AA was more frequent (p = 0.001). A higher risk of carcinoma was found in the case of moderate drinkers with mutant MTHFR homozygosis or double heterozygosis (OR = 21.2 and OR = 9.1, respectively; p trend = 0.002), and the association wasmaintained for the different cancer sites (glottic, supraglottic, oropharyngeal). Our findings support the hypothesis that the interaction of alcohol intake and MTHFR polymorphisms might contribute to susceptibility to carcinogenesis of the oropharyngolaryngeal tract.
Adenoidectomy with the coblator: a logical extension of radiofrequency tonsillectomy
Authors: Timms Michael S , Ghosh Sudip , Roper Alexandra
Published: May 2005

This paper describes a method of radiofrequency ablation of adenoid tissue using a coblator, comparing it with conventional and other newer methods of adenoidectomy. Its chief advantages are that it produces a bloodless field, precision of tissue removal and leads to less damage to surrounding tissues.
Lignocaine as a topical analgesia for post-operative nasal pack removal: a prospective, randomized, double-blind, controlled trial
Authors: Durvasula V S P , Brewis C , Syeda F , Leong P
Published: May 2005

The objective of this study was to assess the efficacy of topical lignocaine in reducing the pain of pack removal after nasal surgery. Fifty-eight patients with Merocel nasal packs in situ after nasal surgery were randomized to receive 10 ml of either 2 per cent lignocaine or 0.9 per cent saline on the packs 10 minutes prior to their removal and thepain experienced on their removal was recorded on a visual analogue scale. The median pain score was 3.4 in the lignocaine group and 2.9 in the saline group with no statistical evidence of adifference between the two groups. There was no statistical evidence of an association between the group and the operation performed, the use of intra-operative Moffat’s solution or the use of post-operative oral analgesia. We conclude that lignocaine used in this way does not reduce the pain of pack removal after nasal
surgery.
Experimental selective posterior semicircular canal laser deafferentation
Authors: Naguib Maged B
Published: May 2005

In this experimental study, we attempted to perform selective deafferentation of the posterior semicircular canal ampulla of guinea pigs using carbon dioxide laser beam. The results of this study document the efficacy of this procedure in achieving deafferentation of the posterior semicircular canal safely with regards to the other semicircular canals, the otolithic organ and the organ of hearing. Moreover, the procedure is performed with relative ease compared with other procedures previously described for selective deafferentation of the posterior semicircular canal. The clinical application of such a procedure for the treatment of intractable benign paroxysmal positional vertigo in humans is suggested.
Cerebellopontine angle arachnoid cysts in adult patients: what is the appropriate management?
Authors: Alaani A , Hogg R , Siddiq M A , Chavda S V , Irving R M
Published: May 2005

Arachnoid cysts can occur at different intracranial sites, including the cerebellopontine angle (CPA). The incidence of arachnoid cysts is 1 per cent of all intracranial lesions. Recent advances in MRI (magnetic resonance imaging) scan techniques have led to CPA arachnoid cysts being more frequently diagnosed and with a higher degree of certainty. The need for further understanding of their natural history as well as for the development of a management rationale has been highlighted with this increased rate of diagnosis.

We present a series of five adult patients with
different clinical presentations attributed to CPA arachnoid cysts. These lesions have a characteristic location in the posterior-inferior aspect of the CPA below the facial and vestibulocochlear nerves. These cysts did not show change in size on repeated MRI scan and the patients’ symptoms did not progress over the period of follow up. Our findings would support a conservative management approach to the majority of these cysts.