On the redshift distribution and physical properties of ACT-selected DSFGs.

We present multi-wavelength detections of nine candidate gravitationally-lensed dusty star-forming galaxies (DSFGs) selected at 218GHz (1.4mm) from the ACT equatorial survey. Among the brightest ACT sources, these represent the subset of the total ACT sample lying in Herschel SPIRE fields, and all nine of the 218GHz detections were found to have bright Herschel counterparts. By fitting their spectral energy distributions (SEDs) with a modified blackbody model with power-law temperature distribution, we find the sample has a median redshift of z = 4.1 - 1.0 + 1.1 (68 per cent confidence interval), as expected for 218GHz selection, and an apparent total infrared luminosity of log 10 ( µ L IR / L ⊙ ) = 13.86 - 0.30 + 0.33 , which suggests that they are either strongly lensed sources or unresolved collections of unlensed DSFGs. The effective apparent diameter of the sample is µ d = 4.2 - 1.0 + 1.7 kpc , further evidence of strong lensing or multiplicity, since the typical diameter of dusty star-forming galaxies is 1.0-2.5 kpc. We emphasize that the effective apparent diameter derives from SED modelling without the assumption of optically thin dust (as opposed to image morphology). We find that the sources have substantial optical depth. ( τ = 4.2 - 1.9 + 3.7 ) to dust around the peak in the modified blackbody spectrum (λ obs ⩽ 500µm), a result that is robust to model choice.

Auditory canal exostoses in Irish surfers.

AIM: Surfing is increasing in popularity in Ireland. Exostoses of the external auditory canal are a common finding in those who surf in cold water. The aim of this study was to examine the prevalence of external canal exostoses in a population of Irish surfers. METHODS: A cross-sectional study of Irish surfers was carried out. Patients were examined and questioned on their knowledge of exostoses, surfing routine, use of barrier protection and symptoms experienced. RESULTS: 119 surfers were analysed. 66 % of the surfers examined exhibited exostoses and 88 % were unaware of their diagnosis. Those that developed exostoses had surfed for a mean of 5,028 h, those that did not had surfed for a significantly shorter mean of 1,909 h (p = 0.0002). CONCLUSIONS: This is first study of this nature in the UK or Ireland. With a 5- to 6-year lag phase for exostoses to develop, these patients are likely to become an increasing part of Otolaryngologist's workload.

Viral gene therapy for head and neck cancer.

BACKGROUND: Viral gene therapy is a promising new treatment modality for head and neck cancer. This paper provides the reader with a review of the relevant literature in this field. RESULTS: There are government licensed viral gene therapy products currently in use for head and neck cancer, utilised in conjunction with established treatment modalities. The viruses target tumour-associated genes, with the first licensed virus replacing p53 gene function, which is frequently lost in tumourigenesis. Oncolytic viruses selectively destroy cancer cells through viral replication and can be armed with therapeutic transgenes. CONCLUSION: Despite considerable advances in this field over the last 40 years, further research is needed to improve the overall efficacy of the viruses and allow their widespread utilisation in the management of head and neck cancer.

Influence of HIV-1 and/or HIV-2 infection and CD4 count on cervical HPV DNA detection in women from Senegal, West Africa.

BACKGROUND: HIV infection is associated with greater risk of precancerous lesions and cervical cancer in women. However, several factors remain unclarified regarding the association between HIV infection and HPV detection, especially among those with HIV type 2 versus type 1 infection and severely immunocompromised persons. OBJECTIVES: To evaluate HPV overall and type-specific detection among HIV-infected and uninfected women in Senegal. STUDY DESIGN: Detection of HPV DNA for 38 genotypes in cervical swabs using PCR-based methods was evaluated in HIV-positive (n=467) and HIV-negative (n=2139) women participating in studies in Senegal. Among HIV-1 and/or HIV-2 positive women, CD4 counts were assessed. Adjusted multivariable prevalence ratios (PR) were calculated. RESULTS: The prevalence of any HPV DNA and multiple HPV types was greater among HIV-infected individuals (78.2% and 62.3%, respectively) compared with HIV-negative women (27.1% and 11.6%). This trend was also seen for HPV types 16 and 18 (13.1% and 10.9%) compared to HIV-negative women (2.2% and 1.7%). HIV-infected women with CD4 cell counts less than 200 cells/µl had a higher likelihood of any HPV detection (PRa 1.30; 95% CI 1.07-1.59), multiple HPV types (PRa 1.52; 95% CI 1.14-2.01), and HPV-16 (PRa 9.00; 95% CI 1.66-48.67), but not HPV-18 (PRa 1.20, 95% CI 0.45-3.24) compared to those with CD4 counts 500 cells/µl or above. CONCLUSION: HIV-infected women, especially those most severely immunocompromised, are more likely to harbor HPV. Measures to prevent initial HPV infection and subsequent development of cervical cancer through focused screening efforts should be implemented in these high risk populations.

YouTube resources for the otolaryngology trainee.

Contemporary surgical training faces many challenges. However, modern technology, including internet-based resources, provides the trainee with a wealth of materials to complement their traditional teaching. YouTube is an online repository of video clips, and contains many instructional resources of value to the otolaryngology trainee.

Principles of early drug discovery.

Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12-15 years and cost in excess of $1 billion. The idea for a target can come from a variety of sources including academic and clinical research and from the commercial sector. It may take many years to build up a body of supporting evidence before selecting a target for a costly drug discovery programme. Once a target has been chosen, the pharmaceutical industry and more recently some academic centres have streamlined a number of early processes to identify molecules which possess suitable characteristics to make acceptable drugs. This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development.

Safety implications of the Boyle-Davis mouth gag and tracheal tube position in tonsillectomy.

BACKGROUND: The risk of death after tonsillectomy is extremely small, and is mostly caused by the direct or indirect effects of haemorrhage or anaesthetic complications. These complications include aspiration, accidental dislodgement of the tracheal tube (TT), and pneumothorax or pneumomediastinum. The Boyle-Davis mouth gag (BDG) is a device used to visualize the oropharynx and stabilize the TT during tonsillectomy. We postulate that a deployed BDG may influence the position of the TT, and potentially result in silent aspiration, accidental extubation, and unilateral pulmonary ventilation. This has not, to our knowledge, been evaluated before. The aim of this prospective, pilot study was to evaluate the displacement of the TT upon opening and closing the BDG, in an objective manner. METHODS: Patients undergoing tonsillectomy with/without adenoidectomy at a regional department underwent flexible bronchoscopy to evaluate the changes in position of the TT tip with the BDG in an open and closed position, relative to the position of the carina. RESULTS: Twenty-three patients were enrolled into the study. Deploying the BDG resulted in TT displacement in 96% of patients. The mean displacement was 9.5 mm (range -10 to +27 mm). CONCLUSIONS: We believe that this study raises concerns not previously highlighted, on how manipulating a BDG may influence the TT position. It may serve to explain additional mechanisms of potentially fatal anaesthetic complications such as TT dislodgement, unilateral ventilation, and pneumothorax, particularly in paediatric patients, after tonsillectomy.

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury.

Spinal release of cytokines may play a critical role in the maladapted nociceptive signaling underlying chronic pain states. In order to investigate this biology, we have developed a novel 'high flux' intrathecal microdialysis approach in combination with multiplex bead-based immunoassay technology to concurrently monitor the spinal release of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)alpha in rats with unilateral sciatic nerve chronic constriction injury (CCI). Intrathecal microdialysis was performed under isoflurane/N(2)O anaesthesia in rats with confirmed mechanical hypersensitivity. In a first study, C-fiber strength electrical stimulation of the operated nerve in neuropathic rats was found to evoke a dramatic increase in IL-1beta efflux ( approximately 15-fold) that was significantly greater than that observed in the sham-operated group. Spinal IL-6 efflux was also responsive to primary afferent stimulation, whereas TNFalpha was not. In a second study, treatment with the glial inhibitor propentofylline for 7days normalized CCI-induced mechanical hypersensitivity. In the same animals, this treatment also significantly reduced intrathecal IL-1beta, IL-6 and TNFalpha and prevented afferent stimulation-evoked cytokine release of both IL-1beta and IL-6. These results provide support for glia as the source of the majority of intrathecal IL-1beta, IL-6 and TNFalpha that accompanies mechanical hypersensitivity in the CCI rat. Moreover, our studies demonstrate the ability of a neurone-glia signaling mechanism to dynamically modulate this release and support a role of spinal IL-1beta in the phasic transmission of abnormal pain signals.

Morell Mackenzie and Crown Prince Frederick: an unpublished manuscript from the Royal Society of Medicine Library.

The story of Morell Mackenzie and his involvement in the case of Crown Prince Frederick III (the future Emperor of Germany) is as well known as it is controversial. The consequences of the case were profound, both medically and politically. Most documents concerning the case are affected by varying degrees of bias, and as a result our understanding of the true events is incomplete. We present a brief summary of the case, and review an unpublished manuscript which adds to our understanding of the events. This manuscript is supportive of Mackenzie's early management of the Crown Prince's illness and acknowledges the importance of the case in medical history.

Controversies in the management of tongue base cancer.

BACKGROUND: Tongue base cancer is one of the most lethal head and neck cancers. There is considerable controversy in the management of this disease with wide variation of opinion within the literature. METHODS: We discuss the presentation, diagnostic and therapeutic strategies which exist in the literature. Articles were reviewed from 1970 to 2007 within the Medline, Pubmed and Cochrane libraries. CONCLUSIONS: Smokers with a history of persistent unilateral neck pain, even in the absence of clinical signs warrant MRI neck imaging. Tongue base cancer organ preservation therapeutic strategies, radiation and concomitant platinum based chemotherapy, currently optimise oncologic and quality of life outcomes.

The effect of head protection on the hearing of rugby players.

OBJECTIVE: Professional rugby players utilise various methods of head protection to prevent against the development of a pinna haematoma. This study tests the hypothesis that these measures, whilst preventing injury, decrease the wearers' hearing threshold and therefore their performance. DESIGN AND PARTICIPANTS: Eight patients had free field audiometry performed in a soundproof room, with warble tones. All patients were young men (mean 24.75 years (range 22-34)). No participant had ear symptomatology or a past history of ear surgery. Three separate audiological assessments were performed on each patient: normal free field audiometry in a sound field room, following application of adhesive tape and whilst wearing a scrum cap. All measurements were performed by a single audiological scientist. A significant clinical drop in hearing threshold was defined as an increase of 10 dB. RESULTS: No patient demonstrated a significant drop in hearing threshold following the application of either tape or a scrum cap, nor was there a significant difference in the mean (SD) warble tone average: air 7.03 (5.47); tape 7.19 (6.40); scrum cap 6.56 (5.58). CONCLUSION: Theoretical concerns that "ear taping" and scrum caps affect hearing of rugby players are unfounded and should not discourage their use.

KTP laser and nitinol alloy stents: are they compatible?

BACKGROUND/OBJECTIVE: Nitinol alloy stents are in frequent use in recanalizing malignant airway stenoses. Potassium titanyl phosphate (KTP) is one of the lasers of choice in removal of obstructing airway lesions. There is a paucity of research regarding the safety of these advances working together. STUDY DESIGN/MATERIALS AND METHODS: In vitro study involving direct contact application of KTP laser with nitinol alloy stents under microscope guidance in varying gaseous environments. RESULTS: Stent damage can occur once power settings exceed one watt. Complete stent destruction occurs regardless of gaseous environment at a mere three watts of power. CONCLUSIONS: Our results suggest that KTP laser is unsafe to use in the presence of a nitinol alloy stent, regardless of the gaseous environment.

How we do it: Changes in thyroid and salivary gland surgery since 1989: who's doing it and what are they doing?

Keypoints * The aim of this study was to identify changes in the provision of parotid, submandibular and thyroid gland surgery between surgical specialties since 1989, as well as changes in surgical practice. * Data from the Department of Health's Hospital Episode Statistics (HES) was extracted from 1989/1990 and 2003/2004 records by operation and surgical specialty in England. * The data reveals a considerable decline in the amount of parotid and submandibular surgery performed by General surgeons; with the majority of this surgery currently being performed by ENT surgeons, and to a lesser extent, Oral and Maxillo-Facial surgeons. * Thyroid surgery has undergone less radical change, with General surgeons continuing to perform the majority of cases; however, an increasing proportion is now provided by ENT surgeons. * There also seems to be changes in the types of thyroid operation being performed; with large increases in total thyroidectomy and reductions in subtotal thyroidectomies.

High risk of human immunodeficiency virus in men who have sex with men with herpes simplex virus type 2 in the EXPLORE study.

The relation between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) acquisition was evaluated among 4,295 high-risk, HIV-negative men who have sex with men in an intensive behavioral intervention (colloquially referred to as "EXPLORE") study in the United States from 1999 to 2003. Sexual behavior data were obtained by computer-assisted self-interview, and sera were collected semiannually for HIV and HSV-2 serology. HSV-2 infection was classified as "recent incident" (at the first HSV-2 seropositive visit), "remote incident" (within 24 months of the first positive visit), and "prevalent" (for visits >24 months after the first HSV-2 positive visit). Baseline HSV-2 prevalence was 20.3%. HSV-2 incidence was 1.9 (95% confidence interval (CI): 1.6, 2.2) per 100 person-years; significant risk factors were African-American race, unprotected receptive anal intercourse, an HIV-positive male sex partner, and six or more male partners in the prior 6 months. The behavioral intervention did not reduce HSV-2 acquisition (adjusted hazard ratio (HR) = 1.2, 95% CI: 0.9, 1.6). Overall HIV incidence was 1.9 (95% CI: 1.7, 2.2) per 100 person-years. HIV risk was elevated among men who have sex with men with recent incident HSV-2 (adjusted HR = 3.6, 95% CI: 1.7, 7.8), remote incident HSV-2 (adjusted HR = 1.7, 95% CI: 0.8, 3.3), and prevalent HSV-2 (adjusted HR = 1.5, 95% CI: 1.1, 2.1) infection compared with HSV-2 seronegative participants. HIV intervention strategies targeting HSV-2 prevention and suppression among men who have sex with men should be evaluated.

Amyloid beta-peptide(1-42) and hydrogen peroxide-induced toxicity are mediated by TRPM2 in rat primary striatal cultures.

Amyloid beta-peptide (Abeta) is the main component of senile plaques which characterize Alzheimer's disease and may induce neuronal death through mechanisms which include oxidative stress. To date, the signalling pathways linking oxidant stress, a component of several neurodegenerative diseases, to cell death in the CNS are poorly understood. Melastatin-like transient receptor potential 2 (TRPM2) is a Ca(2+)-permeant non-selective cation channel, which responds to increases in oxidative stress levels in the cell and is activated by oxidants such as hydrogen peroxide. We demonstrate here that Abeta and hydrogen peroxide both induce death in cultured rat striatal cells which express TRPM2 endogenously. Transfection with a splice variant that acts as a dominant negative blocker of TRPM2 function (TRPM2-S) inhibited both hydrogen peroxide- and Abeta-induced increases in intracellular-free Ca(2+) and cell death. Functional inhibition of TRPM2 activation by the poly(ADP-ribose)polymerase inhibitor SB-750139, a modulator of intracellular pathways activating TRPM2, attenuated hydrogen peroxide- and Abeta-induced cell death. Furthermore, a small interfering RNA which targets TRPM2, reduced TRPM2 mRNA levels and the toxicity induced by hydrogen peroxide and Abeta. These data demonstrate that activation of TRPM2, functionally expressed in primary cultures of rat striatum, contributes to Abeta- and oxidative stress-induced striatal cell death.

Tophaceous gout presenting as a dorsal nasal lump.

A literature review reveals that gout has been described as affecting many sites in the head and neck region, both in the arthritic and tophaceous form. Gout can often mimic malignancy or infection, and has been described as causing acute airway problems requiring emergency tracheotomy. Here we describe the first published case of tophaceous gout affecting the soft tissues overlying the nasal bones. The patient presented with a bony, hard, dorsal hump and requested aesthetic rhinoplasty. We also describe an endoscopic technique for removal of tophi using a powered microdebrider system with a protected burr head. Endoscopic powered microdebrider blade excision of tophi affecting the limbs has already been described, with reduced complications when compared with conventional curettage and debridement techniques. This is the first such application to the nose.

Use of a ureteric pigtail stent as a self-retaining frontal sinus stent.

There have been many frontal sinus stents described in the medical literature. Here we describe the first application of a ureteric pigtail stent to an extensively operated frontal sinus and lateral mucocele cavity. There are two properties of the design of this stent that make it ideal for this case. Firstly, it is self-retaining, eliminating the need for fixation sutures. Secondly, the stent has a considerable available length (220-300 mm between pigtails), allowing ventilation of a distant mucocele cavity.

Avoiding risky sex partners: perception of partners' risks v partners' self reported risks.

BACKGROUND: Key strategies advocated for lowering personal risk of sexual exposure to STD/HIV include having fewer partners and avoiding risky partners. However, few studies have systematically examined how well people can actually discern their sex partners' risk behaviours. METHODS: We conducted face to face interviews with 151 heterosexual patients with gonorrhoea or chlamydial infection and 189 of their sex partners. Interviews examined the patients' perceptions of their sex partners' sociodemographic characteristics and risk behaviours. Patients' perceptions of partners were then sociometrically compared for agreement with partner self reports, using the kappa statistic for discrete variables and concordance correlation for continuous variables. RESULTS: Agreement was highest for perceived partner age, race/ethnicity, and duration of sexual partnership; and lowest for knowledge of partner's work in commercial sex, number of other sex partners, and for perceived quality of communication within the partnership. Index patients commonly underestimated or overestimated partners' risk characteristics. Reported condom use was infrequent and inconsistent within partnerships. CONCLUSION: Among people with gonorrhoea or chlamydial infection, patients' perceptions of partners' risk behaviours often disagreed with the partners' self reports. Formative research should guide development and evaluation of interventions to enhance sexual health communication within partnerships and within social networks, as a potential harm reduction strategy to foster healthier partnerships.