bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial Nonsyndromic Pheochromocytoma
Authors: OPOCHER GIUSEPPE , SCHIAVI FRANCESCA , IACOBONE MAURIZIO , TONIATO ANTONIO , SATTAROVA SABINA , ERLIC ZORAN , MARTELLA MADDALENA , MIAN CATERINA , MERANTE BOSCHIN ISABELLA , ZAMBONIN LAURA , DE LAZZARI PAOLA , MURGIA ALESSANDRA , PELIZZO MARIA ROSA , FAVIA GENNARO , MANTERO FRANCO
Published: November 2006

Abstract:  Judging from recent data, heritable forms account for 30–40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon‐intron boundaries included).
The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5‐cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family.
The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2 + 43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.
The Occurrence of SDHB Gene Mutations in Pheochromocytoma
Authors: VAN NEDERVEEN FRANCIEN H. , DINJENS WINAND N. M. , KORPERSHOEK ESTHER , DE KRIJGER RONALD R.
Published: November 2006

Abstract:  Pheochromocytomas (PCCs) are rare tumors arising from neural crest–derived chromaffin cells. The majority of these tumors are located in the adrenals and gives rise to catecholamine overproduction. In at least 10% of the cases the tumors are located outside the adrenal gland, in extra‐adrenal sites like the bladder and the organ of Zuckerkandl. Recent investigations have found mutations in succinate dehydrogenase subunit B (SDHB), the gene coding for subunit B of the respiratory chain complex II. Mutations in the SDHB gene, with additional loss of the wild‐type allele, result in loss of function of respiratory complex II and appear to correlate with extra‐adrenal location of PCCs. Also, a link has been established between malignant behavior and inactivating mutations of SDHB. In this article we review the published SDHB gene mutations, as well as the location and behavior of the resulting PCCs.
Transcription Association of VHL and SDH Mutations Link Hypoxia and Oxidoreductase Signals in Pheochromocytomas
Authors: DAHIA PATRICIA L.M. ,   for the FAMILIAL PHEOCHROMOCYTOMA CONSORTIUM
Published: November 2006

Abstract:  Pheochromocytomas and paragangliomas are neural‐crest–derived tumors that arise from mutations in RET, VHL, NF1, and in the genes‐encoding succinate dehydrogenase (SDH) subunits B (SDHB), C (SDHC), and D (SDHD). Despite their genetic diversity, these tumors cannot be clearly distinguished on the basis of their primary mutation. We recently identified two major transcriptional programs embedded within familial and sporadic pheochromocytomas and paragangliomas using global expression profiling. This review will summarize the major results of these studies and discuss their implications. The transcription data revealed that: (a) tumors with mutations in VHL, SDHB, and SDHD genes share a transcription signature of hypoxia, angiogenesis, and oxidoreductase imbalance; (b) SDHB protein is suppressed in tumors with mutations in SDHB and SDHD, and also in a subset of tumors with VHL mutations; and (c) HIF1α is involved in the SDHB downregulation observed in these tumors. These results are consistent with the existence of a close interconnection between the VHL and SDH pathways mediated predominantly by hypoxia and oxidoreductase signals. It further suggests that low SDHB levels indicative of impaired mitochondrial complex II function may be a shared element of these pheochromocytomas. SDHB may thus constitute a marker for tumors with abnormal hypoxic profile.
DHEA Reduces NGF‐Mediated Cell Survival in Serum‐Deprived PC12 Cells
Authors: ZIEGLER CHRISTIAN G. , SICARD FLAVIE , SPERBER SIMONE , EHRHART‐BORNSTEIN MONIKA , BORNSTEIN STEFAN R. , KRUG ALEXANDER W.
Published: November 2006

Abstract:  Adrenocortical androgens, including dehydroepiandrosterone (DHEA), are produced in the inner zone of the adrenal cortex that is in direct contact with the neural crest–derived catecholamine‐producing chromaffin cells. DHEA has recently been identified as a crucial regulator of neuronal stem cell proliferation. Thus, DHEA might play a hitherto unknown role in intra‐adrenal tissue formation. In the present study, we examined the influence of DHEA on nerve growth factor (NGF)–mediated survival in serum‐deprived PC12 cells and analyzed the influence of DHEA on NGF‐induced ERK1/2 mitogen‐activated protein (MAP) kinase activation by enzyme‐linked immunosorbent assay (ELISA). Cell survival promoted by NGF in serum‐deprived PC12 cells and neurite outgrowth was reduced by DHEA, pointing toward a role of DHEA in the differentiation process of chromaffin cells. Furthermore, NGF‐induced ERK 1/2 activation was significantly inhibited by DHEA. Hence, we speculate that DHEA might influence NGF‐mediated chromaffin differentiation processes using the ERK1/2 MAP kinase pathway during adrenal tissue development.
Treatment of Bilateral Pheochromocytoma and Adrenal Medullary Hyperplasia
Authors: JANSSON SVANTE , KHORRAM‐MANESH AMIR , NILSSON OLA , KÖLBY LARS , TISELL LARS‐ERIK , WÄNGBERG BO , AHLMAN HÅKAN
Published: November 2006

Abstract:  The risk for bilateral tumors and long‐term outcome after conservative cortical‐sparing adrenal surgery was studied in a consecutive single‐center series. One hundred fifty‐four patients were operated on (1950–2004) for pheochromocytoma (PC = 137), or abdominal paraganglioma (PG = 17). Twenty had MEN 2 (16 MEN 2A; 4 MEN 2B), 15 von Recklinghausen's disease (VRD), and 1 von Hippel–Lindau (VHL) disease. Twelve patients had, or developed, bilateral adrenal medullary tumors; four with MEN 2A, four with MEN 2B, three with VRD, and one with probably hereditary PC associated with brain tumors/meningioma. Two patients with MEN 2B and one with MEN 2A with had bilateral adrenalectomy (adx). Three VRD patients, two MEN 2B and one MEN 2A patients had cortical‐sparing surgery. Two patients were operated on unilaterally, but developed small contralateral tumors; one of these (MEN 2A) had a second asymptomatic PC diagnosed at an older age, so surgery was withheld; the other patient (hereditary PC syndrome) had a small contralateral PC diagnosed at autopsy 9 years later. Only three of nine patients with bilateral operations needed corticosteroid replacement after surgery. Four of six patients died of associated tumors (MTC and meningioma). The mean follow‐up was 13 (1–25) years. Twelve MEN 2A patients with unilateral adx have been followed up for 20 (4–36) years without developing a second PC. Cortical‐sparing adrenal surgery can safely be performed in the majority of patients with bilateral PC. On the basis of our long‐term experience of MEN 2A we perform contralateral adrenal resection only if a second PC is confirmed. Five patients underwent adrenal exploration because of clinical and biochemical findings compatible with PC. Four had asymmetrical positive MIBG scans. They all underwent unilateral adx and diffuse medullary hyperplasia was confirmed (medullary weight estimated morphometrically to 1.0–3.4 g vs. normal weight 0.3–0.5 g in matched controls). These patients have been followed for 19 (5–27) years with normal clinical and biochemical findings. In this rare condition removal of the largest adrenal seems adequate.
Pathology of Pheochromocytoma and Extra‐adrenal Paraganglioma
Authors: TISCHLER ARTHUR S. , KIMURA NORIKO , MCNICOL ANNE MARIE
Published: November 2006

Abstract:  The 2004 WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra‐adrenal sympathetic and parasympathetic paraganglia are classified as extra‐adrenal paragangliomas. A pheochromocytoma is an intra‐adrenal sympathetic paraganglioma. While arbitrary, this nomenclature serves to emphasize important distinctive properties of intra‐adrenal tumors that must be taken into account in clinical practice and research. Those include an often adrenergic phenotype, a relatively low rate of malignancy, and a predilection to occur in particular hereditary syndromes. Current roles of pathology are limited to distinguishing primary or metastatic pheochromocytomas/paragangliomas from other endocrine or nonendocrine tumors, and flagging tumors that show features suggestive of malignant potential or syndromic disease. Future roles may involve more definitive assessment of malignancy, genotype–phenotype correlation, and identification of targets for therapy. Pathology practice currently rests mostly on interpretation of conventional histological sections stained with hematoxylin and eosin, with variable ancillary application of immunohistochemical staining. Malignancy is currently defined by the presence of metastases, not local invasion. Local invasion alone is a poor predictor of metastases, and the absence of apparent invasion does not preclude development of metastases. The two types of aggressive behavior might therefore have different biological underpinnings, and those will be resolved most effectively if consistent terminology is employed. In order to be optimally informative, pathology reports must employ consistent nomenclature and incorporate standard elements. Templates or checklists for minimal standard reporting are recommended by several pathology associations, but identification of some recommended and optional elements is currently subjective or inconsistent.
Pain Assessments and the Provision of Analgesia: The Effects of a Templated Chart
Authors: Baumann Brigitte M. , Holmes John H. , Chansky Michael E. , Levey Helen , Kulkarni Miriam , Boudreaux Edwin D.
Published: November 2006

Objectives

Many emergency departments (EDs) have incorporated pain assessment scales in the medical record to improve compliance with the requirements of the Joint Commission on Accreditation of Healthcare Organizations. The authors conducted a pre‐post trial investigating the effects of introducing a templated chart on the documentation of pain assessments and the provision of analgesia to ED patients.

Methods

A total of 2,379 charts were reviewed for inclusion based on the presence of a chief complaint related to trauma or nontraumatic pain, with 1,242 charts included in the analysis.

Results

Baseline demographic characteristics, mechanism of injury, location of injury, and initial pain severity were similar in the two groups. The proportion of patients with documentation of pain assessment increased from 41% to 57% (p < 0.001). In particular, traumatic mechanisms and chest, abdominal, and extremity pain yielded the largest improvements in documentation after introduction of the templated charts. Documentation of pain descriptors also improved for time of onset, duration, timing, and context (p < 0.01). Pain control in the templated chart group, however, remained unchanged and the provision of analgesia in the ED was not altered, with the exception of nonsteroidal medications, which decreased from 46% to 36% (p < 0.01).

Conclusions

Although documentation is improved with a templated chart, this improvement did not translate into improved patient care.
On the Path to Knowledge Development
Authors: Maheswaran Durairaj
Published: November 2006

I consider the facilitation of knowledge development to be my central focus as editor. The editor makes the final decision on whether a specific research effort significantly advances our understanding of a substantive phenomenon. To that extent, the editor assumes a leadership role and responsibility in deciding the future direction of the field. Such important decisions should reflect the prevailing norms of the field and transcend the editor's individual research agenda or his/her selective worldview. I strive to make decisions that are shared by reviewers and associate editors with the common goal of moving the field forward in productive ways. As a result, articles published in JCP represent a collective view of what is considered significant theoretical contribution and rigorous methodology. In this note, I highlight some central elements of my philosophy related to knowledge development and share a few observations about policies that I have employed in managing the consensual review process.
Individualism and Collectivism
Authors: Schwarz Norbert
Published: November 2006

Psychologists have long portrayed the mind “as a machine or computer that is the same in all times and places, while only the raw materials processed by the machinery or the data in the computer vary” (Fiske, Kitayama, Markus, & Nisbett, 1998, p. 918). This state of affairs changed dramatically over the last decade and a rapidly growing body of experimental research documents profound cultural differences in basic psychological processes. To date, much of this work has addressed the influence of individualism or collectivism, often framed in terms of independent vs. interdependent self‐construals (Markus & Kitayama, 1991; for a comprehensive review, see Oyserman, Coon, & Kemmelmeier, 2002). Other dimensions of culture, which figured prominently in Hofstede's (1980) groundbreaking analysis, received less attention. In this issue's Research Dialogue, Shavitt, Lalwani, Zhang, and Torelli (2006) draw attention to one of these dimensions, namely the distinction between horizontal and vertical cultural orientations, which value equality or emphasize hierarchy, respectively. They review the importance of this distinction for understanding personal values, advertising and consumer persuasion, self‐presentational patterns, and gender differences, noting that the influence of horizontal/vertical orientations is often obscured by their conflation with differences in individualism and collectivism. Commentaries by Aaker (2006), Meyers‐Levy (2006), and Oyserman (2006) elaborate on their analysis and suggest additional avenues for future research. In combination, this set of papers makes a compelling case for extending the analysis of cultural differences in cognition, emotion, motivation, and behavior beyond the individualism/collectivism distinction that has captured the lion's share of recent attention.
High Power, Low Power, and Equality: Culture Beyond Individualism and Collectivism
Authors: Oyserman Daphna
Published: November 2006

Models of culture are operationalized as individualism and collectivism and have not given sufficient attention to other organizing axes—especially how a society handles power, dependence, and equality. Shavitt, Lalwani, Zhang, and Torelli (2006) make a significant contribution by first reminding the field of power distance (Hofstede, 1980) and then moving beyond a single factor to highlight benefits of Triandis’ (1995) horizontal (valuing equality) individualism–collectivism and vertical (emphasizing hierarchy) individualism–collectivism model. But this approach makes it difficult to disentangle the effects of power and individualism or collectivism; priming procedures and experimental variations of power can counter this limitation. Moreover, current horizontal/vertical approaches do not distinguish between having and not having power, although social cognition research documented differential effects of high and low power on content of self‐concept, relationality, and cognition, which suggest previously neglected cultural differences.
Formulation and evaluation of nimodipine-loaded lipid microspheres
Authors: Yu Jia , He Hai Bing , Tang Xing
Published: November 2006

The purpose of this study was to develop an alternative, improved and better tolerated formulation and investigate the pharmacokinetic profile of the new formulation of nimodipine (NM) compared with nimodipine ethanol solutions. Lipid microspheres (LMs) prepared using lecithin and vegetable oils have attracted a lot of interest owing to their versatile properties, such as non-immunogenicity, being easily biodegradable and exhibiting high entrapment efficiency. NM incorporated in LMs could reduce irritation by avoiding the use of ethanol as a solubilizer. The solubility of NM was also increased by dissolving it in the oil phase. The particle size distribution, zeta potential, entrapment efficacy and assay of the NM-loaded LMs were found to be 188.2 ± 5.4 nm, −31.6 mV, 94.2% and 1.04 mg mL−1, respectively. The preparation was stable for 1 year at 4–10°C. The formulation and some physicochemical properties of NM-loaded LMs were investigated. The pharmacokinetic and biodistribution studies were performed in rats at a dose of 1.2 mg kg−1. From the observed data, there is no obvious retention of NM-loaded LMs in plasma. Moreover, incorporation of NM in LMs did not alter the tissue distribution significantly except for the relatively greater drug accumulation in the liver and spleen. The stimulation studies demonstrate that LMs of NM reduce irritation markedly compared with NM solutions. These results suggest that the LM system is a promising option to replace NM ethanol solutions as an intravenous treatment.
Pharmacokinetics of selected stilbenes: rhapontigenin, piceatannol and pinosylvin in rats
Authors: Roupe Kathryn A , Yáñez Jaime A , Teng Xiao Wei , Davies Neal M
Published: November 2006

The pharmacokinetics of piceatannol, pinosylvin and rhapontigenin were characterized in male Sprague-Dawley rats after single intravenous doses of 10 mg kg−1 of each stilbene. Serial blood samples were collected via a catheter inserted into the right jugular vein and plasma samples were analysed for the selected stilbenes concentrations using reverse phase HPLC methods. After an acute intravenous dose of piceatannol, plasma AUC, urine t½, CL and Vd were 8.48 ± 2.48 μgh mL−1, 19.88 ± 5.66 h, 2.13 ± 0.92 Lh−1 kg−1 and 10.76 ± 2.88 Lkg−1 (mean ± s.e.m.), respectively. The acute intravenous dose of pinosylvin yielded the plasma AUC, urine t ½, CL and Vd values of 5.23 ± 1.20 μgh mL−1, 13.13 ± 2.05 h, 1.84 ± 0.44 Lh−1 kg−1 and 2.29 ± 0.56 Lkg−1 (mean ± s.e.m.), respectively. Rhapontigenin intravenous dosing yielded the plasma AUC, urine t½, CL and Vd values of 8.39 ±0.10 μgh mL−1, 25.31 ± 1.46 h, 1.18 ± 0.035 Lh−1 kg−1 and 11.05 ± 0.17 Lkg−1 (mean ± s.e.m.), respectively. Each stilbene was extensively glucuronidated. These stilbenes were predominantly eliminated via non-urinary routes. All three stilbenes were highly distributed into tissues and were highly extracted by the liver. The detectable plasma half-lives of these xenobiotics appear to be relatively short. However, utilizing urinary concentration-time data, much longer elimination half-lives were evident. The estimates of oral bioavailability characterize these stilbenes as poorly bioavailable compounds.
Permeation of WIN 55,212-2, a potent cannabinoid receptor agonist, across human tracheo-bronchial tissue in vitro and rat nasal epithelium in vivo
Authors: Agu Remigius U , Valiveti Satyanarayana , Paudel Kalpana S , Klausner Mitch , Hayden Patrick J , Stinchcomb Audra L
Published: November 2006

The aim of this study was to investigate the intranasal absorption of R-(+)-WIN 55,212-2 mesylate in vivo and in vitro. Permeation experiments of R-(+)-WIN 55,212-2 formulations with 2% dimethyl-β-cyclodextrin (DMβCD), 2% trimethyl-β-cyclodextrin (TMβCD) or 2% randomly methylated-β-cyclodextrin (RAMβCD) in 1:1 propylene glycol/saline and 1.5% propylene glycol + 3% Tween 80 in saline were conducted using EpiAirway™ tissue and an anesthetized rat nasal absorption model, respectively. Samples were analysed by liquid chromatography-mass spectrometry. Mucosal tolerance was screened using paracellular marker permeation and tissue viability as indices. Nasal absorption of WIN 55,212-2 was rapid, with a tmax (time of peak concentration) of 0.17 to 0.35 h in vivo. Relative to 1.5% propylene glycol + 3% Tween 80 (control), 1:1 propylene glycol/saline, RAMβCD, DMβCD and TMβCD resulted in 24-, 20-, 17- and 10-fold WIN 55,212-2 permeation increases in vitro, respectively. The in vivo absolute bioavailabilities were also increased with 1:1 propylene glycol/saline, RAMβCD, DMβCD and TMβCD compared to 1.5% propylene glycol + 3% Tween 80 (0.15 vs. 0.66-0.77). The viability of the EpiAirway™ tissues was significantly reduced by DMβCD and TMβCD formulations. This study showed that WIN 55,212-2 mesylate can be delivered via the nasal route. Absorption of R-(+)-WIN 55,212-2 was rapid and bioavailability was significantly improved using methylated cyclodextrins and propylene glycol-based cosolvent.
Classification of torasemide based on the Biopharmaceutics Classification System and evaluation of the FDA biowaiver provision for generic products of Class I drugs
Authors: Khan M Zahirul I , Raušl Dragica , Radošević Senka , Filić Darko , Danilovski Aleksandar , Dumić Miljenko , Knežević Zdravka
Published: November 2006

The biopharmaceutical properties of an in-house developed new crystal modification of torasemide (Torasemide N) were investigated in comparison with the most well known crystal modification form of torasemide (Torasemide I) in order to classify the drug according to the Biopharmaceutics Classification System (BCS), and to evaluate the data in line with current US Food and Drug Administration (FDA) guidance (with biowaiver provision for Class I drugs) to determine if the biowaiver provision could be improved. The solubility profiles of Torasemide I and Torasemide N were determined, and tablets prepared from both forms of the drug were studied for in-vitro release characteristics in media recommended by the current FDA guidance for biowaiver of generic products, and in other media considered more appropriate for the purpose than the ones recommended by the FDA. Two separate bioequivalence studies in healthy humans (following oral administration) were performed with two test products (both prepared from Torasemide I) against a single reference product (prepared from Torasemide N). The absorption profiles of the drug from the tablets were determined by deconvolution for comparison with the in-vitro release profiles to determine the appropriateness of some dissolution media for predicting in-vivo performance and to determine the comparative rate and extent of absorption. The drug was absorbed from the tested products quickly and almost completely (about 95% within 3.5 h of administration). However, one test product failed to meet the bioequivalence criteria and had a significant initial lower absorption rate profile compared with the reference product (P ≤ 0.05), whereas the other product was bioequivalent and had a similar absorption profile to the reference product. A dissolution medium at pH 5.0, in which torasemide has minimum solubility, was found to be more discriminatory than the media recommended by the FDA. Torasemide has been classified as a Class I drug according to the BCS up to a maximum dose of 40 mg and the data suggest that the current FDA guidance could be improved by giving more emphasis to selection of appropriate dissolution media than is given in its current form for approving biowaiver to generic products of Class I drugs.
Bacterial meningitis and sensorineural hearing loss: A prospective investigation
Authors: Berlow Susan J. , Caldarelli David D. , Matz Gregory J. , Meyer Dianne H. , Harsch Gail G.
Published: November 2006

The objectives of the present investigation are as follows: to prospectively assess the incidence of sensorineural hearing loss (SHL) associated with bacterial meningitis; to evaluate the onset and degree of SHL; and to describe the audiometric pattern.

Forty‐seven patients were studied otologically and audiologically. The incidence of SHL was 11%. Late onset of SHL was not observed, however, one patient demonstrated a probable progressive hearing loss. Both bilateral and unilateral hearing loss were noted. The degree of hearing loss varied from mild to profound, with no consistent audiometric pattern. Intensive follow‐up on one hearing‐impaired patient included temporal bone polytomograms. Obliterative labyrinthitis is detailed.

Antibiotic treatment and laboratory data are evaluated. Suggestions are provided for the post‐meningitic course.
Correction of the drooping brow: Analysis of approach
Authors: O'Neill John V.
Published: November 2006

The attainment of a more youthful appearance is one of the goals of cosmetic facial surgery. In the orbital area this is usually accomplished by performing a blepharoplasty. There are, however, a number of cases in which performance of a blepharoplasty of the upper or lower lids or both does not produce as much of an improvement as the patient or the surgeon would desire. Proper preoperative analysis enables one to determine that the blepharoplasty alone will not produce the desired result. In those instances in which the ptosis of the blow is a contributing factor to the aged appearance, an operative procedure to correct the brow would be undertaken prior to or in conjunction with the blepharoplasty procedure. The various operative procedures will be discussed and analyzed from their positive and negative aspects.
Clinical hearing aid dispensing: A five year review
Authors: Pappas James J. , Bailey H. A. Ted , Graham Sharon S.
Published: November 2006

Constant reassessment of professional services is necessary in order to maintain responsiveness to patient needs. As a result of current trends in patient population, amplification technology and legislative intervention, many otolaryngologists and audiologists have included the dispensing of hearing aids as a part of their provision of clinical services. The primary philosophical objective in dispensing hearing aids is to provide a more allencompassing total hearing health care within the clinic setting for patients with all types of hearing loss, whether their needs are medical, surgical or prosthetic. Procedures for each patient receiving a hearing aid fitting include the following: audiological evaluation, otolaryngological examination, physician counseling, audiological counseling, ear mold fabrication, hearing aid evaluation and fitting, 30 day trial period, and follow‐up hearing aid counseling.

A total of 1319 aids have been dispensed over a five year period. The large majority of the aids are postauricular instruments, fitted on adults over 60 years of age with sensorineural hearing loss. Dispensing aids within the clinic has established a constant quality service, improved patient follow‐up, improved the convenience for patients, offered research opportunities, and reduced the cost to our patients. Having a within‐clinic dispensary provides a coordinated program of professional management for the aural rehabilitative process; when a hearing aid is dispensed through such a program, the quality of patient care for the hearing impaired population can be improved.
Cervical approaches to the surgery of cervicothoracic neoplasia
Authors: Travis Lawrence W. , Tabb Harold G. , Hebert A. Foster , Spector Richard A.
Published: November 2006

Seven cases are presented to illustrate four cervical surgical approaches to the upper mediastinum and thorax. These surgical approaches are described and illustrated, and we have termed these the retrosternal, retroclavicular, posterior, and lateral approaches. Two cases of thymic cyst, one of recurrent metastatic pretracheal adenopathy, a case of tracheal stenosis, a foreign body of the left subclavian artery, a large Zenker's diverticulum, and a neoglottic reconstruction are presented to illustrate the surgical anatomy, dissection technique, and postoperative complications.
Suture technique for caudal septal deviations
Authors: Ellis Michael S.
Published: November 2006

The “buckled” or severely deviated nasal septum has resisted a variety of techniques devised for its correction. This paper will present a new technique which the author has found useful in many of these cases. This method utilizes in reverse the procedure popularized by Mustardé for managing the protruding ear. Instead of bending the cartilage into a harmonious shape, the bent cartilage is straightened with submucosal permanent sutures. The paper will illustrate this technique.
Radiofrequency Ablation (RFA) as A Cytoreductive Strategy for Hepatic Metastasis from Breast Cancer
Authors: Lawes D , Chopada A , Gillams A , Lees W , Taylor I
Published: November 2006

INTRODUCTION

Patients with liver metastasis from breast cancer have a poor prognosis, although this may be improved by hepatectomy in a selected group with disease confined to the liver. We evaluate the effectiveness of radiofrequency ablation (RFA) as a cytoreductive strategy in the management of liver metastasis from primary breast cancer.

PATIENTS AND METHODS

Nineteen patients with hepatic metastasis from primary breast cancer underwent RFA of their liver lesions between April 1998 and August 2004.

RESULTS

The median age of the patients was 52 years (range, 32–69 years), 8 had disease confined to the liver, with 11 having stable extrahepatic disease in addition. Seven patients with disease confined to the liver at presentation are alive, as are 6 with extrahepatic disease, median follow-up after RFA was 15 months (range, 0–77 months). Survival at 30 months was 41.6%. In addition, 7 patients followed up for a median of 14 months (range, 2–29 months) remain alive and disease-free. RFA failed to control hepatic disease in 3 patients. RFA was not associated with any mortality or major morbidity.

CONCLUSIONS

Control of hepatic metastasis from breast cancer is possible using RFA and may lead to a survival benefit, particularly in those patients with disease confined to the liver.
Should We Apply Suction During Fine Needle Cytology of Thyroid Lesions? A Systematic Review and Meta-Analysis
Authors: Pothier David D , Narula AA
Published: November 2006

INTRODUCTION

Fine needle aspiration cytology (FNAC) is a well-established investigation in thyroid disease. Fine needle sampling without aspiration (FNS) is less commonly used but often easier to perform. Both methods have advantages and disadvantages but, as yet, there is no agreement on which method produces better specimens for cytological diagnosis.

MATERIALS AND METHODS

We undertook a review of the literature and performed a meta-analysis of the results of four crossover trials.

RESULTS

The resulting odds ratio favoured FNS (OR = 0.99; 95% CI 0.88–1.11) but was not statistically significant. A fifth paper not included in the meta-analysis reported results in favour of FNS (P = 0.003).

CONCLUSIONS

There is no evidence from the meta-analysis that one method is superior to the other; however, taking into consideration all available evidence, it seems that FNS may be easier to perform and may produce better samples.
Broken Bones and Fractures – An Audit of Patients' Perceptions
Authors: Kampa RJ , Pang J , Gleeson R
Published: November 2006

INTRODUCTION

‘Have I got a fracture or a break doctor?’ remains a commonly posed question in fracture clinics, suggesting that patients frequently feel a ‘fracture’ and a ‘break’ are two separate entities. This apparent misconception amongst fracture clinic patients may result in confusion and occasionally anger that doctors appear to have inconsistent views on the severity of their injury. Compliance and outcome of patient care can also be affected by poor communication.

PATIENTS AND METHODS

Our questionnaire-based study was conducted in two stages. The initial objective was to establish whether this misconception surrounding the words ‘fracture’ and ‘break’ is commonly held amongst our out-patient trauma patients. The second stage of the audit was to determine whether a patient information leaflet on fractures/broken bones could help reduce this misconception.

RESULTS

The preliminary audit involving 50 new patients attending our fracture clinic showed that 84% thought there was a difference between a ‘fracture’ and a ‘break’, with 68% believing a ‘break’ to be worse than a ‘fracture’. Following the introduction of an information leaflet, a re-audit of 61 new patients took place. This time 67% felt there was a difference between a ‘fracture’ and a ‘break’, with 65% believing a ‘break’ to be worse than a ‘fracture’. Only 21% had read the supplied information leaflet, and 69% of those still believed there was a difference between a ‘fracture’ and a ‘break’.

CONCLUSIONS

The majority of patients believed that there was a difference between a ‘fracture’ and a ‘break’. Access to information leaflets did not appear to alter this misconception. Verbal communication and explanation may be more beneficial and practical than visual aids and leaflets in overcoming this problem.
Day-Care Surgery for Pilonidal Sinus
Authors: Abdul-Ghani AKM , Abdul-Ghani AN , Clark CL Ingham
Published: November 2006

INTRODUCTION

The surgical approach to symptomatic pilonidal sinus is open to debate. Many techniques have been described and no single technique fulfils all the requirements of an ideal treatment. Ambulatory treatment with minimal morbidity and rapid return to activity is desirable. The aim of this work was to study the feasibility of day-care surgery for excision and primary asymmetric closure of symptomatic pilonidal sinus.

PATIENTS AND METHODS

All patients referred electively over 2 years were assessed in a single-consultant, colorectal clinic and booked for day-care surgery. All patients had excision and primary asymmetric closure under general anaesthesia in the left lateral position. Whenever possible, they were discharged on the same day according to the day-surgery protocol. Patients were subsequently seen in the out-patient clinic for removal of stitches and were followed up further if there was any wound breakdown.

RESULTS

Fifty-one patients were operated on electively for pilonidal sinus over the 2 years. Two patients were excluded as the final diagnosis was not pilonidal sinus. At 4 weeks following operation, 43 (88%) had complete healing and 6 (12%) had dehiscence of the wound. Recurrence rate was 8% (4 patients) for follow-up of 12–38 months. There was no admission from the day-surgery unit and no unplanned re-admissions. The cost for day-care pilonidal sinus surgery was estimated to be £672.00 per patient compared with in-patient cost of £2405.00.

CONCLUSIONS

Excision and primary asymmetric closure for pilonidal sinus is safe and feasible as day-care surgery and is associated with potential cost saving.
Inflamed Solitary Caecal Diverticulum – It is Not Appendicitis, What Should I Do?
Authors: Connolly D , McGookin RR , Gidwani A , Brown MG
Published: November 2006

We describe three cases that presented with symptoms suggestive of appendicitis but were found at operation to have an inflamed solitary caecal diverticulum. All were treated successfully with diverticulectomy or inversion of the diverticulum. We wish to highlight this diagnosis and its surgical management so that informed decisions can be made if this is first encountered in the operating theatre.
BAUS meets challenges of broadening specialty
Authors: Towell Elaine
Published: November 2006

Worldwide changes in urological practice have increasingly made urology as much a medical specialty as a surgical one. The introduction of Modernising Medical Careers (MMC) has significantly modified urological training. The European Working Time Directive has threatened the provision of urological services in smaller hospital units and the National Institute of Clinical Excellence's guidance on cancer services has concentrated major cancer surgery in a few larger units.
A restructured College
Authors: Ribeiro Bernard
Published: November 2006

The old FRCS examination, which I passed in 1971 and proudly cherish, ensured that I would be recognised as a surgeon not only because of my title, but because I held a Diploma that the public recognised as a mark of distinction and which would determine my future practice as a surgeon.
Social care research: a suitable case for systematic review?
Authors: Sharland Elaine , Taylor Imogen
Published: November 2006

English

This article examines how systematic reviews might best address social care research. In the context of broader methodological debate, it draws on recent first-hand experience of undertaking systematic reviews in this field, to propose that research inclusion, quality assessment and synthesis should be guided by certain key characteristics of social care knowledge, research and practice. It explores the potential of the TAPUPAS framework, developed by Pawson and colleagues (2003) to address qualities of social care knowledges in general, for informing and moving forward our thinking about systematic reviews of social care research in particular.
Book Reviews
Authors: Birtchnell John
Published: November 2006

The wayward mind: An intimate history of the unconscious

By Guy Claxton London, Little, Brown, 2005. Pp. 402, ISBN 0 316 72451 3
Mindfulness and the psychology of presence
Authors: Childs David
Published: November 2006

Mindfulness, as ‘being in the present on purpose’ has become of practical and theoretical interest to clinical psychologists. It is an element in several influential and effective treatment methods. Research concentrates on the effects of practice but neglects the experience of presence. A common requirement that the clinician also practice mindfulness leads to an interest in describing clinical presence. This stance has been of interest in psychoanalysis but not studied in mainstream clinical psychology. The description of that as a state of being and the similarity between mindfulness practice and the phenomenological method provide a link with a 6‐year series of seminars given to psychotherapists by the philosopher Martin Heidegger. His demonstrations of the relation between experiential and scientific knowledge offer a way to make links between a reflective clinical psychology, mindfulness, and current developments in the understanding of consciousness.
A Distinctive Set of Genes Is Upregulated During the Inflammation-Carcinoma Sequence in Mouse Stomach Infected by Helicobacter felis
Authors: Kobayashi Motohiro , Lee Heeseob , Schaffer Lana , Gilmartin Tim J. , Head Steven R. , Takaishi Shigeo , Wang Timothy C. , Nakayama Jun , Fukuda Minoru
Published: November 2006

Helicobacter pylori infects over half the population worldwide and is a leading cause of chronic gastritis and gastric cancer. However, the mechanism by which this organism induces inflammation and carcinogenesis is not fully understood. In the present study we used insulin-gastrin (INS-GAS) transgenic mice that fully develop gastric adenocarcinoma after infection of H. pylori-related Helicobacter felis. Histological examination revealed that more than half of those mice developed invasive adenocarcinoma after 8 months of infection. These carcinomas were stained by NCC-ST-439 and HECA-452 that recognize 6-sulfated and non-sulfated sialyl Lewis X. Lymphocytic infiltration predominantly to submucosa was observed in most H. felis-infected mice, and this was associated with the formation of peripheral lymph node addressin (PNAd) on high endothelial venule (HEV)-like vessels detected by MECA-79. Time-course analysis of gene expression by using gene microarray revealed upregulation of several inflammation-associated genes including chemokines, adhesion molecules, surfactant protein D (SP-D), and CD74 in the infected stomach. Immunohistochemical analysis demonstrated that SP-D is expressed in hyperplasia and adenocarcinoma whereas CD74 is expressed in adenocarcinoma in situ and invasive carcinoma. These results as a whole indicate that H. felis induces HEV-like vessels and inflammation-associated chemokines and chemokine receptors, followed by adenocarcinoma formation.
Residual Stress Distributions for Plate T-Butt Welds in Defect Assessment Applications
Authors: Lee H-Y , Lee S-H , Lee J-H , Wimpory R , Nikbin KM
Published: November 2006

The residual stress distributions for plate T-butt welds were determined from a detailed finite element analysis of the welding process and they were compared with those of the measured data for validation. The residual stress distributions from the analyses and measurements were shown to be in similar shape. The distributions were found to be below the master curve for the residual stresses that were previously determined from a statistical analysis for a range of weld geometries and materials. A failure assessment for the T-butt weld with cracks under residual stress distributions has been carried out. The conservatism in the current life assessment procedures regarding the residual stresses were quantified based on the stress intensity factor (SIF) calculations for the T-butt weld. It was shown that the master curve profile provides more realistic values for the SIFs with reasonable conservatism than the profiles recommended in the existing assessment procedures.
Vitamin K Prophylaxis for Preterm Infants: A Randomized, Controlled Trial of 3 Regimens
Authors: Clarke Paul , Mitchell Simon J. , Wynn Robert , Sundaram Shanmuga , Speed Valerie , Gardener Elizabeth , Roeves Donna , Shearer Martin J.
Published: November 2006

OBJECTIVE. Preterm infants may be at particular risk from either inadequate or excessive vitamin K prophylaxis. Our goal was to assess vitamin K status and metabolism in preterm infants after 3 regimens of prophylaxis.

METHODS. Infants <32 weeks’ gestation were randomized to receive 0.5 mg (control) or 0.2 mg of vitamin K1 intramuscularly or 0.2 mg intravenously after delivery. Primary outcome measures were serum vitamin K1, its epoxide metabolite (vitamin K1 2,3-epoxide), and undercarboxylated prothrombin assessed at birth, 5 days, and after 2 weeks of full enteral feeds. Secondary outcome measures included prothrombin time and factor II concentrations.

RESULTS. On day 5, serum vitamin K1 concentrations in the 3 groups ranged widely (2.9–388.0 ng/mL) but were consistently higher than the adult range (0.15–1.55 ng/mL). Presence of vitamin K1 2,3-epoxide on day 5 was strongly associated with higher vitamin K1 bolus doses. Vitamin K1 2,3-epoxide was detected in 7 of 29 and 4 of 29 infants from the groups that received 0.5 mg intramuscularly and 0.2 mg intravenously, respectively, but in none of 32 infants from group that received 0.2 mg intramuscularly. After 2 weeks of full enteral feeding, serum vitamin K1 was lower in the infants who received 0.2 mg intravenously compared with the infants in the control group. Three infants from the 0.2-mg groups had undetectable serum vitamin K1 as early as the third postnatal week but without any evidence of even mild functional deficiency, as shown by their normal undercarboxylated prothrombin concentrations.

CONCLUSIONS. Vitamin K1 prophylaxis with 0.2 mg administered intramuscularly maintained adequate vitamin K status of preterm infants until a median age of 25 postnatal days and did not cause early vitamin K1 2,3-epoxide accumulation. In contrast, 0.2 mg administered intravenously and 0.5 mg administered intramuscularly led to vitamin K1 2,3-epoxide accumulation, possibly indicating overload of the immature liver. To protect against late vitamin K1 deficiency bleeding, breastfed preterm infants given a 0.2-mg dose of prophylaxis should receive additional supplementation when feeding has been established.
Fundamental tone estimates for elliptic operators in divergence form and geometric applications
Authors: Bessa Gregório P. , Jorge Luquésio P. , Lima Barnabé P. , Montenegro José F.
Published: November 2006

We establish a method for giving lower bounds for the fundamental tone of elliptic operators in divergence form in terms of the divergence of vector fields. We then apply this method to the Lr operator associated to immersed hypersurfaces with locally bounded (r + 1)-th mean curvature Hr + 1 of the space forms Nn+ 1(c) of constant sectional curvature c. As a corollary we give lower bounds for the extrinsic radius of closed hypersurfaces of Nn+ 1(c) with Hr + 1 > 0 in terms of the r-th and (r + 1)-th mean curvatures. Finally we observe that bounds for the Laplace eigenvalues essentially bound the eigenvalues of a self-adjoint elliptic differential operator in divergence form. This allows us to show that Cheeger's constant gives a lower bounds for the first nonzero Lr-eigenvalue of a closed hypersurface of Nn+ 1(c).
Lines of principal curvature on canal surfaces in R³
Authors: Garcia Ronaldo , Llibre Jaume , Sotomayor Jorge
Published: November 2006

In this paper are determined the principal curvatures and principal curvature lines on canal surfaces which are the envelopes of families of spheres with variable radius and centers moving along a closed regular curve in R³. By means of a connection of the differential equations for these curvature lines and real Riccati equations, it is established that canal surfaces have at most two isolated periodic principal lines. Examples of canal surfaces with two simple and one double periodic principal lines are given.
Neurohumoral activation in heart failure: the role of adrenergic receptors
Authors: Brum Patricia C. , Rolim Natale P.L. , Bacurau Aline V.N. , Medeiros Alessandra
Published: November 2006

Heart failure (HF) is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality. The development of end-stage HF often involves an initial insult to the myocardium that reduces cardiac output and leads to a compensatory increase in sympathetic nervous system activity. Acutely, the sympathetic hyperactivity through the activation of beta-adrenergic receptors increases heart rate and cardiac contractility, which compensate for decreased cardiac output. However, chronic exposure of the heart to elevated levels of catecholamines released from sympathetic nerve terminals and the adrenal gland may lead to further pathologic changes in the heart, resulting in continued elevation of sympathetic tone and a progressive deterioration in cardiac function. On a molecular level, altered beta-adrenergic receptor signaling plays a pivotal role in the genesis and progression of HF. beta-adrenergic receptor number and function are decreased, and downstream mechanisms are altered. In this review we will present an overview of the normal beta-adrenergic receptor pathway in the heart and the consequences of sustained adrenergic activation in HF. The myopathic potential of individual components of the adrenergic signaling will be discussed through the results of research performed in genetic modified animals. Finally, we will discuss the potential clinical impact of beta-adrenergic receptor gene polymorphisms for better understanding the progression of HF.