bluuebunny/crossref_metadata_2025 huggingface dataset:
How we do it: Evaluation of nurse‐led ENT services in the UK: a preliminary descriptive postal questionnaire survey
Authors: Duvvi S , Gollapalli R , Sankar V , Walker T , Kumar B.N , Reddy K.T.V.
Published: December 2006

Keypoints

• There has been a steady growth in the volume and range of nurse led services in ENT practise in the UK.

• There was very little consistency in the titles of the nurses providing nurse led services but those nurses working in advanced practice roles now require courses, diplomas, degrees and study days related to ENT.

• Locally or nationally agreed practice guidelines can define nursing practice boundaries and ensure accountability.

• Monitoring and evaluation of nurse led services also requires attention.
How we do it: Switching from mechanical perforation to the CO2 laser; audit results of primary small‐fenestra stapedotomy in a district general hospital
Authors: Badran K. , Gosh S. , Farag A. , Timms M.S.
Published: December 2006

Keypoints

• The use of laser for stapedotomy was introduced in our department in the year 2002, and since then has taken over the mechanical technique.

• A total of 85 patients who had undergone primary stapedotomy with either technique are reported with regards to effectiveness and rate of side effects.

• Although footplate complications were reduced with the laser, short‐term hearing outcomes were similar between the two techniques.

• In four occasions, the surgeon had to switch back to the mechanical technique unexpectedly.

• Stapedotomy will continue to be performed with the laser in our department, bearing in mind the occasional need for the older technique.
Prospective randomised single‐blind controlled trial of glacial acetic acid versus glacial acetic acid, neomycin sulphate and dexamethasone spray in otitis externa and infected mastoid cavities
Authors: Johnston M.N. , Flook E.P. , Mehta D. , Mortimore S.
Published: December 2006

Objectives:  The literature reports the merits of antibacterial, antibiotic and steroid agents in treating otological infections but no controlled clinical trial has directly compared 2% glacial acetic acid (EarCalm; Stafford‐Miller Ltd, Brentford, UK) against 2% glacial acetic acid, 0.1% dexamethasone and 3250 U/ml of neomycin sulphate (Otomize; Stafford‐Miller Ltd) in the treatment of otitis externa and infected mastoid cavities.

Design:  Prospective, single‐blind randomised controlled trial.

Setting:  Outpatients, Derby Royal Infirmary, Derby, UK.

Patients:   Emergency and GP referrals with acute otitis externa (n = 53) and infected mastoid cavities (n = 56).

Main outcome measures:  Otoscopy was performed at initial randomisation and then at 2 and 4 weeks, the ear assessed for active and inactive disease.

Results:  Patients with active otitis externa, 71% (15/21) resolved with glacial acetic acid, dexamethasone and of neomycin sulphate after 2 weeks, increasing to 86% (18/21) after 4 weeks treatment. Patients on glacial acetic acid had only 38% (12/32) resolution after 4 weeks (P < 0.0005). Two per cent glacial acetic acid, dexamethasone and neomycin sulphate resolved only 30% (8/27) of infected mastoid cavities compared to only 10% (3/29) on glacial acetic acid (P < 0.07). A further 2 weeks treatment this increased to 67%, (18/27) with glacial acetic acid, dexamethasone and neomycin sulphate and 48% (14/29) with glacial acetic acid. These results are not statistically significant.

Conclusion:  Glacial acetic acid, dexamethasone and neomycin sulphate is significantly more effective in treating otitis externa when compared with glacial acetic acid. This effect failed to be significant in the infected mastoid cavities group. We therefore recommend that in conjunction with aural toilet, antibiotic/steroid combination is more effective than an antibacterial agent for otitis externa. Larger numbers of infected mastoid cavities are required to be studied.
Can objective parameters derived from videofluoroscopic assessment of post‐laryngectomy valved speech replace current subjective measures? An e‐tool‐based analysis
Authors: Kazi R. , Singh A. , Mullan G.P.J. , Venkitaraman R. , Nutting C.M. , Clarke P. , Rhys‐Evans P. , Harrington K.J.
Published: December 2006

Objectives:  The primary purpose of this study was to assess the pharyngoesophageal segment in total laryngectomy patients using a videofluoroscopy e‐tool.

Study design:  Cross‐sectional study.

Setting:   Head and Neck Oncology Unit, Tertiary Referral Centre.

Patients:  Forty‐two patients following total laryngectomy.

Intervention:  Videofluoroscopy using an e‐tool (JRuler).

Main outcome measures:  Subjective and objective videofluoroscopy parameters correlated with the GRBAS scale and treatment variables.

Results:  Of 32 men and 10 women, mean age 63.5 years (10.8) the majority (64.3%) had a reasonable voice (good = 11 and poor = 4 patients). Comparing subjective and objective parameters, significant correlations were only seen with a smaller minimal neoglottic distance at phonation with no regurgitation of barium at phonation (P = 0.05) and a type 1 shape of neoglottis at phonation (P = 0.02). There were also significant correlations between smaller maximum sub‐neoglottic distance at phonation and type 1 shape of neoglottis (P = 0.02), smaller maximum sub‐neoglottic distance at rest and absence of stasis of barium at phonation (P = 0.05) and the length of neoglottis at phonation and type 1 shape of neoglottis (P = 0.01). For perceptual evaluation, significant correlation was seen only between G1 voice and a smaller minimal neoglottic distance at phonation (P = 0.03) amongst the subjective and objective parameters. There were no correlations between visual parameters and the clinical parameters.

Conclusions:  Our observations suggest that this interesting concept has limitations. While objective and quantifiable data can be obtained using videofluoroscopy in laryngectomees, only a few correlate with each other and with voice quality.
Safe magnetic resonance scanning of patients with metallic middle ear implants
Authors: Wild D.C. , Head K. , Hall D.A.
Published: December 2006

Objective:  To determine the MR scanning risk to patients with otologic implants.

Design:  We used a repeated‐measures study with an additional control measure to assess two aspects of risk; (i) movement of the device in the magnetic field, and (ii) absorption of energy leading to local heating. We used an ex vivo test method that met with international standards. We measured the effects in a Philips Intera Achieva 3 Tesla (T) MR scanner using a Sense Head 8 channel RF coil.

Setting:  University‐based magnetic resonance research facility.

Main outcome measures:  Heating or displacement of the stapedectomy pistons.

Results:  No evidence of displacement or heating was found.

Conclusion:  Complying with the ex vivo standard testing protocols, the Schuknecht and McGee wire pistons (device product numbers 140106 and 140108, respectively) were found to be safe in a 3 T MR scanner. These conclusions can be extrapolated to the in vivo case.
Epidermal hyperplasia of the tympanic membrane and deep external ear canal: novel histo‐pathological features, embryological and clinical correlates
Authors: Upile T. , Michaels L. , Jerjes W. , Howard D. , Hopper C. , Wright A.
Published: December 2006

Objectives.  To study the histology and developmental biology of epidermis of tympanic membrane and deep ear canal and to correlate the histo‐pathological features with clinical conditions.

Method.  Histo‐pathological and electron microscopic examination was performed of deep meatal skin, keratosis, keratosis obturans, external canal cholesteatoma, retraction pockets, acquired cholesteatoma and tympanic membrane perforations.

Results.  In some mature ears, a marked change in the normal flat thin epidermis to one resembling that of the fetus is seen in the presence of local inflammation. This hyperplastic epidermis is present in varying lengths on the tympanic membrane and deep ear canal and displayed as hyperplastic bands growing down into sub‐epidermal tissue and sometimes penetrated the collagen layer of the tympanic membrane to enter the middle ear. Keratosis was frequent on the surfaces of the tympanic membrane and deep ear canal, which may also be found in the invading bands, where they produced small keratin cysts.

Conclusions.  Severe chronic otitis media, with inflammatory exudates, glandular metaplasia or tympanosclerosis, may be associated with hyperplasia. This type of epidermal hyperplasia appeared to be pathogenic and was observed in several structurally distinct entities such as keratosis, keratosis obturans, retraction pockets, and cholesteatoma of the deep external canal. Invading epidermis in the middle ear, in some cases, is indistinguishable from acquired cholesteatoma. This reverse differentiation highlights a primordial property of auditory epithelium, which was not previously recognised. Furthermore, hyperplastic epidermis appears to be pathogenic and may be the cause of some specific conditions or their complications.

References 1 Johnson A., Hawke M., Berger G. (1984) Hodge memorial Award‐surface wrinkles, cell ridges, and desquamation in the external auditory canal. J Otolaryngol.13, 345–354

2 Johnson A., Hawke M. (1985) Cell shape in the migratory epidermis of the external auditory canal. J Otolaryngol.14, 273–281
Is there an association between blood group O and epistaxis?
Authors: Reddy V.M. , Broad S. , Daniel M. , Moir A.A.
Published: December 2006

Objectives.  Blood group O is associated with lower expression of von Willebrand factor 2, although the clinical significance of this is unclear. Earlier work demonstrated lower admission rate for epistaxis among Asians compared with Caucasians in our unit (P < 0.01) 1, with one of the possible explanations being higher prevalence of blood group O among Caucasians. This study investigates whether blood group O is over‐represented in patients admitted with epistaxis.

Method.  Retrospective comparison of blood groups of Caucasian patients admitted at our institution (HISS data) with epistaxis during a six‐year period (2000–2005) with blood groups of the UK Caucasian population in general, determined from National Blood Service data.

Results.  A total of 1,261 Caucasians admitted with epistaxis were identified (readmissions excluded). Among epistaxis patients, 50% were blood group O (636/1261), but among the general population this was 46% (chi‐square test P < 0.05).

Conclusions.  Blood group O appears over‐represented in Caucasian patients admitted with epistaxis, compared with the Caucasian population in general. Although a causal relationship cannot be confirmed in this study, the possibility that blood group O is a risk factor for epistaxis warrants further investigation.

References 1 Daniel M., Jaberoo M.C., Stead R.E., Reddy V.M., Moir A.A. Is admission for epistaxis more common in Caucasian than in Asian people? A preliminary study. Clin Otolaryngol Allied Sci. (in press)

2 Miller C.H., Haff E., Platt S.J., Rawlins P., Drews C.D., Dilley A.B., et al. (2003) Measurement of von Willebrand factor activity: relative effects of ABO blood type and race. J Thromb Haemost. 1, 2191–2197
Oral Sub‐mucous fibrosis (OSMF): a study of associated habits and their impact
Authors: Supriya M. , Patel S. , Vishwakarma R.
Published: December 2006

Objective.  To determine the incidence of associated habits in patients with OSMF. The relationship between the different habits and the severity of the disease.

Design.  Cross‐sectional Survey.

Setting.  Tertiary Referral Centre.

Participants.  Adult patients with OSMF.

Outcomes Measured.  (1) Association of different habits with OSMF. (2) Duration of chewing before onset of symptoms related to OSMF. (3) Severity of OSMF with respect to different chewing habits.

Results. A total of 500 patients with OSMF were included in this study over 2‐year period. Except 3 patients (0.6%) rest all gave history of one of these chewing habits–(Pan‐Masala is a mixture of Arecnuts, Lime, Catechu and undisclosed sweetening and Flavouring agents). 432 (86.4%) of Pan‐Masala with Tobacco, 56 (11.2%) of only Tobacco, 8 (1.6%) of only Betel Nut, 1 (0.2%) of pan‐Masala without Tobacco. Smoking Tobacco had no statistically significant effect on the incidence of OSMF in any of these groups. In the above mentioned order the other associated factors were respectively. The mean duration of chewing before onset of symptoms in years 3.28, 3.95, 8.37 and 10. The proportion of patients with <2 finger mouth opening was 249/432 (57.63%), 28/56 (50%), 3/8 (37.5%), 0 (0%).

Conclusion.  The occurrence of OSMF is strongly associated with the habit of chewing Pan‐Masala with Tobacco and less so with only Tobacco or Betel Nut. Patients consuming Pan‐Masala with Tobacco develop this disease earlier then chewers of Tobacco and Betel Nut. Restriction of mouth opening is worst with Pan‐Masala with Tobacco.

References 1 Ariyawardana A., Athukorala A.D., Arulanandam A. (2006) Effect of betel chewing, tobacco smoking and alcohol consumption on oral sub‐mucous fibrosis: a case‐control study in Sri Lanka. J Oral Path & Med35, 197–201

2 Ranganathan K., Devi M.U., Joshua E., Kirankumar K., Saraswathi T.R. (2004) Oral sub‐mucous fibrosis: a case‐control study in Chennai, South India. J Oral Path & Med33, 274–277
Oncolytic virotherapy for nasopharyngeal cancer
Authors: Bapat U. , Wang Y. , Alusi G. , Chisholm E. , Francis J. , Hallden G. , Lemoine N.
Published: December 2006

Objectives.  To evaluate the oncolytic potential of a replication‐selective mutant adenovirus (VAI‐deleted adenovirus) in an established EBV‐positive cancer cell line and to develop a new regime to enhance the potency of the virus by combination with additional agents.

Methods.  In vitro (cytotoxicity) assays to determine cell survival were performed to assess the viral potency of replicating adenovirus (wild‐type and the VAI‐deleted mutant) in established EBV‐negative and EBV‐positive cancer cell lines. Various drugs including a histone deacetylase inhibitor (HDACi), phenylbutyrate and standard chemotherapeutic agents used in nasopharyngeal cancer (cisplatin, 5‐fluorouracil and paclitaxel) were evaluated for their cytotoxic effect on these tumour cells. Subsequent experiments were performed to determine whether addition of these increased the anti‐tumour efficacy of the VAI‐deleted adenovirus and/or lowered the required viral dose. Sequencing studies with the virus and drugs were carried out to determine the most synergistic combination causing cytotoxicity. Viral infectivity and replication studies with and without HDACi were also undertaken.

Results.  The mutant adenovirus was found to be more potent than the wild‐type virus against the EBV‐positive cells. Combination with various therapeutic agents (phenylbutyrate, cisplatin, 5‐fluorouracil and paclitaxel) results in lowering of the virus dose and a synergistic effect. Sequencing of drug followed by virus achieves the best results. There was no significant change in infectivity or replication with addition of the HDACi.

Conclusion.  Combination of the VAI‐deleted adenovirus with agents already in clinical use results in synergy. In vivo and thereafter translational studies would enable the clinical application of such treatment for EBV‐associated tumours.

Reference 1 Wang, Y., et al. (2005) Virus‐associated RNA I‐deleted adenovirus, a potential oncolytic agent targeting EBV‐associated tumors. Cancer Res. 65, 523–531
Elastic scattering spectroscopy in the head & neck
Authors: Upile T. , Jerjes W. , Howard D. , Michaels L. , Hopper C. , Wright A.
Published: December 2006

Objectives.  To develop the a technique of optical biopsy of oral dysplastic lesions that will provide real‐time diagnosis, allow in situ monitoring, and which will be feasible in the clinical environment especially for patient follow‐up.

Method.  Ethics approval was granted. Ex‐vivo specimens were evaluated to determine the optimal protocol before use in vivo. 75 spectra were obtained from 25 patients with oral leukoplakia. The spectral readings were mapped, and the area was then biopsied. Photographic images were co‐registered with the histological specimen. The sensitivity and specificity of the technique was determined compared to the gold standard of histo‐pathological examination of paraffin sections.

Results.  The sensitivity and specificity in determining dysplastic from benign conditions were 70% and 78.6% respectively at 580 nm.

Conclusions.  The use of Elastic Scattering Spectroscopy may aid the differentiation of normal and dysplastic mucosal lesions in the head & neck.

References 1 Chung, A., Karlan, S., Lindsley, E., et al. (2006) In vivo cytometry: a spectrum of possibilities. Cytometry A. 69, 142–146

2 Dhar, A., Johnson, KS., Novelli, MR., et al. (2006) Elastic scattering spectroscopy for the diagnosis of colonic lesions: initial results of a novel optical biopsy technique. Gastrointest Endosc.63, 257–261
The effect of co‐morbidity on quality of life in patients treated with radiotherapy for head and neck squamous cell cancer
Authors: Oozeer N.B. , Paleri V. , Benbow J. , Downs C. , Kelly C.
Published: December 2006

Objective:  To identify the impact of co‐morbidity on the quality of life (QoL) of patients suffering from head and neck squamous cell cancer (HNSCC) during radiation treatment.

Methods:  A total of 250 patients diagnosed with HNSCC between August 2001 and February 2003 underwent QoL and psychological profile assessment using the University of Washington QoL instrument (UWQoL) and the Hospital Anxiety and Depression Scale (HADS) respectively. The assessment was performed prospectively at the beginning and at two time points during radiation therapy. Co‐morbidity burden was assessed retrospectively by case note analysis of 112 patients using the Adult Co‐morbidity Evaluation 27 (ACE‐27) index, which is a previously described and validated instrument. Demographic and tumour data were obtained from prospective databases. Co‐morbidity burden and impact of co‐morbidity on QoL were the main outcome measures estimated.

Results:  All data was analysed using SPSS for Windows V 10. Mean co‐morbidity burden in this group was 1.10. Fifty eight percent of patients had some form of co‐morbid illness. Co‐morbidity grades did not influence the QoL and HADS scores before treatment (one way anova). QoL and HADS scores deteriorated during radiation treatment. The change in scores after treatment was not influenced by co‐morbidity in this population (one way anova).

Conclusions:  This study shows that the co‐morbidity burden seen in HNSCC bears no influence on the treatment related QoL and psychological profile during radiation therapy. Severe co‐morbidity may have a greater effect on patients QoL and HADS score, but small sample size does not make this statistically significant.
Dissection of level IIb in squamous cell cancer of the upper aerodigestive tract: prospective study and systematic review of the literature
Authors: Paleri V. , Subramaniam S. , Oozeer N. , Rees G. , Krishnan S.
Published: December 2006

Objectives.  Selective neck dissection is commonly used to clear occult metastases in the N0 neck. The aim of this study is to identify the incidence of micrometastases in level IIb nodes in patients with upper aerodigestive tract squamous cell carcinoma with clinically and radiologically staged N0 necks and to perform a systematic review of the literature on the incidence of metastases in this setting.

Methods.  Thirty‐eight patients were selected and 50 neck dissection (ND) specimens were examined prospectively. Tissue dissected from level IIb was sent separately for histo‐pathological analysis. All the relevant literature in the English language was systematically reviewed.

Results.  On average, 2.9 ± 0.4 nodes (range 0–10) were harvested. One patient had a metastatic node in level IIb with extracapsular spread in the ipsilateral neck. No other positive nodes were detected. There was an incidental finding of a deposit of papillary thyroid carcinoma. Sixteen of the 50 NDs showed micrometastases at other levels, predominantly in level IIa (75%). The systematic review identified 11 papers with 704 patients suitable for inclusion. The overall incidence of metastatic disease at level IIb in the context of an N0 neck from any site is 2.3% (16/704). 3.5% (11/312) of oral cavity cancer metastasise to level IIb and none of the 244 patients with laryngeal cancer had level IIb metastatic nodes.

Conclusions.  Nodal metastasis is rare in the level IIb even in the presence of positive nodes in adjacent level IIa. There appears to be no advantage in performing contralateral level IIb dissection in N0 necks.
The role of platelet‐derived lysophospholipids in the progression of head and neck cancer
Authors: Lucey D. , Walsh M.A. , Costello R.
Published: December 2006

Objectives.  Platelets are known to have an important role in cancer progression but their function remains to be fully elucidated. In this study, we tested the hypothesis that platelet derived lysophospholipids are important in the spread and survival of head and neck cancer cells. Lysophospholipids are known to promote many of the hallmarks of cancer, including adhesion, proliferation, invasion and angiogenesis.

Methods.  In our study we utilised ‘paired’ primary and metastatic cell lines isolated from a primary tongue cancer lesion and a metastatic lymph node, respectively, from the same patient. This facilitates the study of the nature of head and neck cancer metastasis by comparing the local and metastatic neoplastic population from the same cancer. To investigate the role of lysophospholipids in squamous cell carcinoma of the tongue we compared the receptor profile of these cell lines at the RNA and protein level using PCR and flow cytometry. In addition, we analysed the functional significance of these findings using cell migration and chemoresistance assays.

Results.  We demonstrated for the first time that lysophospholipid receptors known to be critical in white blood cell migration are present in metastasising but not localised cancer cells. In addition, we proved that lysophospholipids are important in HNSCC migration and delineated many of the molecular pathways involved. Finally, we demonstrated that the presence of lysophospholipids protects cancer cells from chemotherapy‐induced apoptosis.

Conclusions.  Platelet derived lysophospholipids appear to be important in HNSCC metastasis. They may also explain why HNSCC nearly always metastasise to lymph nodes.
The symmetry of paediatric tympanograms
Authors: Cruise A. , Georgalas C. , Wareing M.
Published: December 2006

Objectives.  The poorer outcome of myringoplasty in children in comparison with adults is commonly attributed to poor Eustachian tube function. The only routine test giving an indication of Eustachian tube function is tympanometry. It is common practice to look at the contralateral tympanogram as a predictor of the child's Eustachian tube function when deciding whether to proceed with myringoplasty. This relies on the assumption that Eustachian tube function is symmetrical. This study seeks to assess whether this assumption is correct.

Method.  We collected copies of 297 pairs of tympanograms carried out in a paediatric ENT clinic over a ten‐month period. We compared the symmetry of tympanograms of children aged from 5 to 16 years.

Results.  We looked at the association between normal Eustachian tube functions (type A) or abnormal Eustachian tube function (type B, C1 or C2) in one ear and Eustachian tube function in the other ear. A type‐A tympanogram in one ear predicted a type‐A tympanogram in the other ear with a sensitivity of 0.81 (95% CI 0.74–0.86) and specificity of 0.75 (0.66–0.82). The positive predictive value of a type‐A tympanogram was 0.82 (0.75–0.87) and the negative predictive value was 0.73 (0.65–0.81).

Conclusions.  There is a good correlation of Eustachian tube function, as demonstrated by tympanometry, between the ears of a child. If Eustachian tube function does have an impact on myringoplasty outcome then the contralateral tympanogram should provide some help in the decision on timing of myringoplasty.
The use of the weber tuning fork test and ‘scratch test’ in postoperative tympanomastoid surgery
Authors: Buckland J.R. , Geyer M. , Maleki N. , Mitchell T.E.
Published: December 2006

Objective.  To compare the use of the Weber tuning fork test and ‘Scratch test’ in postoperative patients following tympanomastoid surgery.

Method.  Prospective cohort study with control group. Southampton University Hospitals NHS Trust. Secondary care. 19 patients undergoing routine tympanomastoid surgery for middle ear disease and 18 patients undergoing translabyrinthine surgery for lateral skull base lesions.

Main Outcome Measures.  Localisation of Weber tuning fork. Positive or negative Scratch test: clinician applies a gentle scratch using index finger to the bandage over the operated ear. Postoperative pure tone audiometry.

Results.  In the context of diagnosing a hearing or non‐hearing ear, the Weber test had a specificity of 78% and sensitivity of 100%. The scratch test had a specificity of 100% and sensitivity of 100%. The Weber was 93% specific and 93% sensitive for diagnosing a unilateral conductive hearing loss.

Conclusions.  As a means of diagnosing an acute postoperative dead ear the Scratch test is an accurate alternative to the Weber test.

References 1 Miltenburg D.M. (1994) The validity of tuning fork tests in diagnosing hearing loss. J Otolaryngol. 23, 254–259

2 Behn A., Laszlo C.A., Black D., et al. (2005) Which is mightier, the tuning fork or the bone oscillator? J Otolarygol. 34, 135–139
Systematic reviews – triumph of form over substance?
Authors: Thomas L. , Wilson J.A.
Published: December 2006

Keypoints

• Cochrane systematic reviews are conducted to identify level 1a evidence. So far the ENT group have published 24 reviews, while around 70 titles are in various stages of the review process. Only one review has been able to produce Ia evidence and the rest recommended further trials.

• The majority of otorhinolaryngology reviews are unable to identify level 1a evidence due to the paucity of high quality randomised control trials.

• This presents a challenge, therefore – to identify and discuss alternate methods of evidence gathering for future research?
Heparanase expression: a potential ancillary diagnostic tool for distinguishing between malignant cells and reactive mesothelium in body cavity effusions
Authors: Doviner V. , Maly B. , Reinhartz T. , Vlodavsky I. , Sherman Y.
Published: December 2006

Objective: Heparanase, an endoglycosidase that cleaves heparan sulphate, is frequently expressed in carcinomas and was suggested to play a role in cell invasion and metastasis. We investigated whether heparanase expression may serve as a reliable marker to discriminate benign mesothelial cells from malignant cells shed into body cavities.

Methods and results: Cytological smears of effusions from 51 hospitalized patients were immunostained for heparanase. Strong immunoreactivity was noted in 35 of 40 (88%) carcinoma samples and in all three malignant mesothelioma cases. Only rare (<3%) reactive mesothelial cells were noted showing a faint negligible staining. Specificity was 100%, sensitivity 88%, and positive and negative predictive values were 100% and 89% respectively.

Conclusions: Our results suggest that heparanase may be of value as a complementary component in a diagnostic panel of markers, contributing to its reliability and accuracy.
Transbronchial fine needle aspiration cytology in the diagnosis of mediastinal/hilar sarcoidosis
Authors: Smojver‐Ježek S. , Peroš‐Golubičić T. , Tekavec‐Trkanjec J. , Mažuranić I. , Alilović M.
Published: December 2006

Objective:  The diagnostic value of transbronchial/transtracheal fine needle aspiration (TBFNA) cytology in the patients with mediastinal and/or hilar lymphadenopathy has been investigated.

Method:  Out of 116 patients with mediastinal/hilar lymphadenopathy, the diagnosis of sarcoidosis was established in 88 (75.9%). One hundred and seventy‐one TBFNAs from different lymph node stations were performed using a cytological 26‐gauge needle. Adequate lymph node samples were obtained in 157 of 171 (91.8%) TBFNA and 14 of 171 (8.2%) TBFNA samples were inadequate.

Results:  Cytological findings consistent with sarcoidosis were found in 79 of 88 (89.77%) patients and 133 of 157 (84.71%) samples. The sensitivity of TBFNA cytology in sarcoidosis presenting as mediastinal/hilar lymphadenopathy was 78.7%, specificity 92.3%.

Conclusions:  Overall diagnostic accuracy of TBFNA cytology in the diagnosis of sarcoidosis was 86.2%, and cytological findings consistent with sarcoidosis were the only morphological diagnosis of sarcoidosis in 63.6% of patients.
Fine‐needle aspiration of renal angiomyolipoma: a report of four cases
Authors: Handa U. , Nanda A. , Mohan H.
Published: December 2006

Objective:  Renal angiomyolipoma is an uncommon benign tumour composed of smooth muscle cells, blood vessels and adipose tissue. The cytological findings of this tumour are described.

Methods:  A retrospective analysis of four cases of angiomyolipoma diagnosed on fine‐needle aspiration cytology (FNAC) during the period 1998–2004 was carried out. All the aspirations were carried out under ultrasonographic image guidance.

Results:  Smears from three cases showed oval‐ to spindle‐shaped tumour cells, cohesive stromal fragments embedded in adipose tissue and branching blood vessels in a haemorrhagic background. No mitotic figures were seen. Smears from one case showed adipose tissue and blood. In this case, sections from the cell block showed mature adipose tissue and small blood vessels.

Conclusion:  The diagnosis of angiomyolipoma can be made by FNAC under image guidance and a cell block may be quite helpful in making a correct diagnosis. It is important to establish a correct preoperative diagnosis as treatment of these tumours is conservative and this obviates the need for total nephrectomy.
Pitfalls in the diagnosis of Wegener's granulomatosis on fine needle aspiration cytology
Authors: Awasthi A. , Malhotra P. , Gupta N. , Gupta D. , Rajwanshi A.
Published: December 2006

Objective:  To review the clinical and pathological findings in six suspected cases of Wegener's granulomatosis (WG) and highlight the diagnostic difficulties faced by the cytopathologist.

Methods:  Retrospective review of records of the Cytopathology Department to identify patients who underwent image‐guided transthoracic pulmonary fine needle aspiration cytology (FNAC) for pulmonary lesions of suspected WG and those who were subsequently confirmed to have WG. Detailed evaluation of cytomorphological features was carried out.

Results:  A total of six cases were identified in whom the initial procedure to obtain a pathological diagnosis was transthoracic FNAC. In one case, atypical squamous cells on cytology initially suggested a diagnosis of squamous cell carcinoma while in another a diagnosis of WG was made on cytology; however, a subsequent lung biopsy revealed silicosis.

Conclusion:  Acute inflammation and necrosis are the most consistent cytopathological findings in WG. In selected cases FNAC can provide supportive pathological evidence to establish a diagnosis of WG.
Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis
Authors: Hughes A. D. , Coady E. , Raynor S. , Mayet J. , Wright A. R. , Shore A. C. , Kooner J. S. , Thom S. A. McG. , Chaturvedi N.
Published: December 2006

Background  Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs.

Materials and methods  A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi‐slice computerized tomography (CT), carotid and femoral intima‐media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non‐senescent EPCs (ns‐EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6‐week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry.

Results  Individuals with femoral plaques had reduced total and ns‐EPCs. The number of ns‐EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects.

Conclusion  The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk.
Expression of the target receptor CD33 in CD34+/CD38−/CD123+ AML stem cells
Authors: Hauswirth A.W. , Florian S. , Printz D. , Sotlar K. , Krauth M.‐T. , Fritsch G. , Schernthaner G.‐H. , Wacheck V. , Selzer E. , Sperr W.R. , Valent P.
Published: December 2006

Background  CD33 (Siglec‐3) is becoming increasingly important as a target of antibody‐mediated therapy in acute myeloid leukaemia (AML). In normal myelopoiesis, expression of CD33 is restricted to advanced stages of differentiation, whereas primitive stem cells do not express CD33. In the present study, we asked whether leukaemic stem cells in patients with AML express CD33.

Materials and methods  A multicolour‐staining technique was applied in 11 patients with AML, and leukaemic progenitors defined as CD34+/CD38−/CD123+ cells. AML stem cells were purified by cell sorting and were examined for expression of CD33 mRNA by reverse transcriptase–polymerase chain reaction (RT–PCR).

Results  In all patients in whom the majority of myeloblasts expressed CD33 (n = 8), AML progenitors reacted with the CD33 antibody P67·6. Repopulation experiments utilizing irradiated NOD/SCID mice confirmed that AML stem cells in these patients reside within the CD33+ subpopulation of the leukaemic clone. Moreover, highly purified AML stem cells (> 98% purity) from patients with CD33+ AML were found to express CD33 mRNA in RT–PCR analyses. CD33 was neither detectable on CD34+/CD38− cells in normal bone marrow nor on leukaemic stem cells in patients with CD33‐negative AML.

Conclusions  Leukaemic stem cells in patients with CD33+ AML express CD33. This observation is in favour of novel treatment concepts employing CD33‐targeting antibodies in AML.
Relaxation of human placental arteries and veins by ATP‐sensitive potassium channel openers
Authors: Jewsbury S. , Baker P. N. , Wareing M.
Published: December 2006

Background  Adenosine triphosphate (ATP)‐sensitive potassium channels (KATP) are important modulators of vascular tone. Preliminary data from our laboratory suggests that KATP channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific KATP opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative KATP channel openers.

Materials and methods  Functional activity of KATP channels was assessed in chorionic plate arteries and veins using wire myography. Cromakalim‐, KRN2391‐ and KRN4884‐induced relaxations were assessed in the presence and absence of agonist‐induced pretone. Cromakalim, an established KATP channel opener, acted as control.

Results  KRN2391 evoked significantly greater relaxation of chorionic plate arteries and veins than either KRN4884 or cromakalim. KRN2391‐induced relaxation of precontracted arteries and veins was reduced in the presence of inhibitiors of the nitric oxide pathway (L‐NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation.

Conclusions  We conclude that KATP channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of KATP channels and via activation of nitric oxide‐dependent pathways.
Impaired cardiac autonomic function in women with prior gestational diabetes mellitus
Authors: Gasic S. , Winzer Ch. , Bayerle‐Eder M. , Roden A. , Pacini G. , Kautzky‐Willer A.
Published: December 2006

Background  Cardiac autonomic neuropathy is a common dysfunction in manifest diabetes mellitus and is associated with duration of diabetes and/or an inadequate glycaemic control. Heart rate variability (HRV) reflects autonomic heart function. The aim of the present study was to investigate whether in women with prior gestational diabetes (GD; pre‐type 2 diabetes) alterations of cardiac autonomic function can be observed after delivery in relation to insulin sensitivity and glycaemic control.

Materials and methods  Forty‐eight healthy women with prior GD were consecutively admitted to the study. HRV was analysed by both time, as well as frequency, domain methods using 24‐h Holter monitoring. In addition, 20 women with normal glucose tolerance during and after pregnancy were investigated as control subjects. All women underwent a frequently sampled intravenous glucose tolerance test (FSIGT) for measurement of insulin sensitivity.

Results  Time domain analysis (standard deviation of normal RR intervals; SDNN) showed a reduced HRV in 25 out of the 48 (52%) women with prior GD. Frequency domain analysis revealed that in these 25 subjects both low and high frequency components of power spectral density (reflecting mainly sympathetic respectively parasympathetic activity) were reduced, indicating that sympathetic as well as parasympathetic functional impairment may be assumed. However, a relative predominance of the sympathetic over parasympathetic cardiac function was observed. The impairment of cardiac autonomic function (reduced SDNN) was correlated with HbA1c values and the 2‐h blood glucose concentration (oral glucose tolerance test) but not with insulin sensitivity.

Conclusion  The present results demonstrate that in 52% of the women examined who had prior GD, an impairment of cardiac sympathetic as well as parasympathetic function was present, which related to glycaemic control, but not to insulin sensitivity. This infers that functional autonomic changes could be an early prognostic indicator in pre‐type 2 diabetes.
Induction of hepatitis C virus (HCV)‐specific T cells by needle stick injury in the absence of HCV‐viraemia
Authors: Kubitschke A. , Bahr M. J. , Aslan N. , Bader C. , Tillmann H. L. , Sarrazin C. , Greten T. , Wiegand J. , Manns M. P. , Wedemeyer H.
Published: December 2006

Background  The risk of hepatitis C virus (HCV) infection after occupational exposure is low with seroconversion rates between 0 and 5%. However, factors associated with natural resistance against HCV after needle stick injury are poorly defined. HCV‐specific T‐cell responses have been described in cross‐sectional studies of exposed HCV‐seronegative individuals.

Materials and methods  In this study, we prospectively followed 10 healthcare professionals who experienced an injury with an HCV‐contaminated needle. Blood samples were taken on the day or the day after the event and at different time points during follow‐up for up to 32 months. HCV‐specific T‐cell responses were investigated directly ex vivo and in T‐cell lines.

Results  None of the individuals became positive for HCV‐RNA in serum tested with the highly sensitive transcription‐mediated amplification (TMA)‐assay or in peripheral blood mononuclear cells (PBMC). All of them remained anti‐HCV negative throughout follow‐up. At the time of injury, HCV‐specific CD4+ T‐cell responses were already detectable in two individuals and became detectable thereafter in three additional persons. Transient HCV‐specific CD8+ T‐cell responses developed in two HLA‐A2 positive patients, which became negative until the most recent follow‐up after 5 and 17 months, respectively.

Conclusion  We demonstrate the development of HCV‐specific T cells in HCV‐exposed individuals after needle stick injury indicating subinfectious exposure to HCV. T‐cell immunity against HCV may contribute to the low prevalence of HCV in medical healthcare professionals in Western countries.
The metabolic syndrome: metabolic changes with vascular consequences
Authors: Wassink A. M. J. , Olijhoek J. K. , Visseren F. L. J.
Published: December 2006

Despite criticism regarding its clinical relevance, the concept of the metabolic syndrome improves our understanding of both the pathophysiology of insulin resistance and its associated metabolic changes and vascular consequences. Free fatty acids (FFA) and tumour necrosis factor‐alpha (TNF‐α) play prominent roles in the development of insulin resistance by impairing the intracellular insulin signalling transduction pathway. Obesity is an independent risk factor for cardiovascular disease and strongly related to insulin resistance. In case of obesity, FFAs and TNF‐α are produced in abundance by adipocytes, whereas the production of adiponectin, an anti‐inflammatory adipokine, is reduced. This imbalanced production of pro‐ and anti‐inflammatory adipokines, as observed in adipocyte dysfunction, is thought to be the driving force behind insulin resistance. The role of several recently discovered adipokines such as resistin, visfatin and retinol‐binding protein (RBP)‐4 in the pathogenesis of insulin resistance is increasingly understood. Insulin resistance induces several metabolic changes, including hyperglycaemia, dyslipidaemia and hypertension, all leading to increased cardiovascular risk. In addition, the dysfunctional adipocyte, reflected largely by low adiponectin levels and a high TNF‐α concentration, directly influences the vascular endothelium, causing endothelial dysfunction and atherosclerosis. Adipocyte dysfunction could therefore be regarded as the common antecedent of both insulin resistance and atherosclerosis and functions as the link between obesity and cardiovascular disease. Targeting the dysfunctional adipocyte may reduce the risk for both cardiovascular disease and the development of type 2 diabetes. Although lifestyle intervention remains the cornerstone of therapy in improving insulin sensitivity and its associated metabolic changes, medical treatment might prove to be important as well.
Contemporary carbon balance and late Holocene carbon accumulation in a northern peatland
Authors: ROULET NIGEL T. , LAFLEUR PETER M. , RICHARD PIERRE J. H. , MOORE TIM R. , HUMPHREYS ELYN R. , BUBIER JILL
Published: December 2006

Northern peatlands contain up to 25% of the world's soil carbon (C) and have an estimated annual exchange of CO2‐C with the atmosphere of 0.1–0.5 Pg yr−1 and of CH4‐C of 10–25 Tg yr−1. Despite this overall importance to the global C cycle, there have been few, if any, complete multiyear annual C balances for these ecosystems. We report a 6‐year balance computed from continuous net ecosystem CO2 exchange (NEE), regular instantaneous measurements of methane (CH4) emissions, and export of dissolved organic C (DOC) from a northern ombrotrophic bog. From these observations, we have constructed complete seasonal and annual C balances, examined their seasonal and interannual variability, and compared the mean 6‐year contemporary C exchange with the apparent C accumulation for the last 3000 years obtained from C density and age‐depth profiles from two peat cores. The 6‐year mean NEE‐C and CH4‐C exchange, and net DOC loss are −40.2±40.5 (±1 SD), 3.7±0.5, and 14.9±3.1 g m−2 yr−1, giving a 6‐year mean balance of −21.5±39.0 g m−2 yr−1 (where positive exchange is a loss of C from the ecosystem). NEE had the largest magnitude and variability of the components of the C balance, but DOC and CH4 had similar proportional variabilities and their inclusion is essential to resolve the C balance. There are large interseasonal and interannual ranges to the exchanges due to variations in climatic conditions. We estimate from the largest and smallest seasonal exchanges, quasi‐maximum limits of the annual C balance between 50 and −105 g m−2 yr−1. The net C accumulation rate obtained from the two peatland cores for the interval 400–3000 bp (samples from the anoxic layer only) were 21.9±2.8 and 14.0±37.6 g m−2 yr−1, which are not significantly different from the 6‐year mean contemporary exchange.
Seedling survival in a northern temperate forest understory is increased by elevated atmospheric carbon dioxide and atmospheric nitrogen deposition
Authors: SEFCIK LESLEY T. , ZAK DONALD R. , ELLSWORTH DAVID S.
Published: December 2006

We tested the main and interactive effects of elevated carbon dioxide concentration ([CO2]), nitrogen (N), and light availability on leaf photosynthesis, and plant growth and survival in understory seedlings grown in an N‐limited northern hardwood forest. For two growing seasons, we exposed six species of tree seedlings (Betula papyrifera, Populus tremuloides, Acer saccharum,Fagus grandifolia,Pinus strobus, andPrunus serotina) to a factorial combination of atmospheric CO2(ambient, and elevated CO2at 658 μmol CO2 mol−1) and N deposition (ambient and ambient +30 kg N ha−1 yr−1) in open‐top chambers placed in an understory light gradient. Elevated CO2exposure significantly increased apparent quantum efficiency of electron transport by 41% (P<0.0001), light‐limited photosynthesis by 47% (P<0.0001), and light‐saturated photosynthesis by 60% (P<0.003) compared with seedlings grown in ambient [CO2]. Experimental N deposition significantly increased light‐limited photosynthesis as light availability increased (P<0.037). Species differed in the magnitude of light‐saturated photosynthetic response to elevated N and light treatments (P<0.016). Elevated CO2exposure and high N availability did not affect seedling growth; however, growth increased slightly with light availability (R2=0.26,P<0.0001). Experimental N deposition significantly increased average survival of all species by 48% (P<0.012). However, seedling survival was greatest (85%) under conditions of both high [CO2] and N deposition (P<0.009). Path analysis determined that the greatest predictor for seedling survival in the understory was total biomass (R2=0.39,P<0.001), and that carboxylation capacity (Vcmax) was a better predictor for seedling growth and survival than maximum photosynthetic rate (Amax). Our results suggest that increasing [CO2] and N deposition from fossil fuel combustion could alter understory tree species recruitment dynamics through changes in seedling survival, and this has the potential to alter future forest species composition.