Aerosolisation during tracheal intubation and extubation in an operating theatre setting.

Aerosol-generating procedures such as tracheal intubation and extubation pose a potential risk to healthcare workers because of the possibility of airborne transmission of infection. Detailed characterisation of aerosol quantities, particle size and generating activities has been undertaken in a number of simulations but not in actual clinical practice. The aim of this study was to determine whether the processes of facemask ventilation, tracheal intubation and extubation generate aerosols in clinical practice, and to characterise any aerosols produced. In this observational study, patients scheduled to undergo elective endonasal pituitary surgery without symptoms of COVID-19 were recruited. Airway management including tracheal intubation and extubation was performed in a standard positive pressure operating room with aerosols detected using laser-based particle image velocimetry to detect larger particles, and spectrometry with continuous air sampling to detect smaller particles. A total of 482,960 data points were assessed for complete procedures in three patients. Facemask ventilation, tracheal tube insertion and cuff inflation generated small particles 30-300 times above background noise that remained suspended in airflows and spread from the patient's facial region throughout the confines of the operating theatre. Safe clinical practice of these procedures should reflect these particle profiles. This adds to data that inform decisions regarding the appropriate precautions to take in a real-world setting.

Cross-sectional follow-up of voice outcomes in children who have a history of airway reconstruction surgery.

OBJECTIVES: This study reports vocal function in a cross-section of children with subglottic stenosis. Each child had a history of laryngotracheal reconstruction and/or cricotracheal resection surgery. Vocal function was measured using laryngoscopy, acoustic analysis, perceptual evaluation and impact of voice on quality of life. DESIGN: All patients aged >5 years with history of laryngotracheal reconstruction and/or cricotracheal resection surgery at the Scottish National Complex Airways service were invited to participate. SETTING: Data were gathered in the Royal Hospital for Children in Glasgow in a single outpatient appointment. PARTICIPANTS: Twelve of 56 former patients (aged 5-27) provided a voice sample and eleven consented to awake laryngoscopy. All consented for detailed evaluation of their medical records. MAIN OUTCOME MEASURES: Acoustic analysis of fundamental frequency and pitch perturbation was conducted on sustained vowel [a]. Perceptual evaluation was conducted by 4 trained listeners on a series of spoken sentences. Impact on quality of life was measured using the paediatric voice-related quality of life questionnaire. Laryngeal function was descriptively evaluated. RESULTS: Four children had normal voice acoustically, perceptually and in relation to voice-related quality of life. One of these had vocal fold nodules unrelated to surgical history. Two other children had "near normal" vocal function, defined where most voice measurements fell within the normal range. CONCLUSIONS: Normal or "near normal" voice is a possible outcome for children who have had this surgery. Where there is an ongoing complex medical condition, voice outcome may be poorer.

Validation of a family-centred outcome questionnaire for pinnaplasty: a cross-sectional pilot study.

OBJECTIVES: Comparison of pinnaplasty techniques is difficult due to variation in the reporting of outcomes. We aimed to develop a family-centred outcome questionnaire for use after pinnaplasty and assess it for reliability and validity. DESIGN: Cross-sectional study. SETTING: Tertiary referral paediatric otolaryngology centre. PARTICIPANTS: 20 prospective and 71 retrospective pinnaplasty patients and their parent(s). METHODS: The Post-Operative Pinnaplasty Questionnaire (POPQ) was developed after semi-structured interview with families of children undergoing pinnaplasty. Children aged 4-16 were recruited. Three different ear measurements (auriculocephalic angle, helix-mastoid distance and Walker's ratio) were performed pre-operatively. Children were reviewed 3 months post-operatively and asked to complete a POPQ and Glasgow Children's Benefit Inventory with their parent(s). Ear measurements were repeated and data collected on surgical technique and complications. 200 retrospective pinnaplasty patients were posted a POPQ and Glasgow Children's Benefit Inventory and data collected on surgical technique, complication rate and Walker's angle. MAIN OUTCOMES MEASURES: Validity and reliability of the POPQ. RESULTS: Age range was 4-16 (median 12). POPQ correlated well with Glasgow Children's Benefit Inventory (Spearman's rho = 0.776, P < 0.001). There was no correlation of POPQ scores with age, sex, complication or surgical technique. POPQ score was not associated with severe prominence pre-op nor change or degree of prominence post-op. POPQ displayed good internal consistency (Cronbach's alpha 0.850) and ease-of-use scores. CONCLUSIONS: We have developed a family-focused outcome tool for pinnaplasty that displays good face validity, internal consistency and correlation with health-related quality of life and that is simple and easy to use. No correlation was seen with more traditional measures of outcome such as complications or ear measurements. Further refinement and testing of validity and reliability on a larger sample is planned.

Socioeconomic influence on orofacial cleft patient care.

BACKGROUND: Cleft lip and palate is the most common craniofacial birth defect in the UK. Orofacial clefts have functional and aesthetic implications requiring intensive multi-disciplinary follow-up to optimise development. Failure to attend follow-up is likely to have a negative impact on patient outcomes. The aim of this retrospective audit is to establish if socioeconomic status influences attendance, DNA and cancellation rates in cleft patients. METHODS AND RESULTS: A retrospective audit of 74 orofacial cleft patients born and operated on at the Royal Hospital for Sick Children Glasgow between 2006 and 2007. There was higher rate of DNA in more deprived social groups-21% (SIMD 1) against 10% (SIMD 5). A higher rate of DNA in cleft lip and palate patients was noted. This group of patients showed a marked difference in attendance between SIMD 1 (38%) and SIMD 5 (78%). CONCLUSION: More deprived areas have a higher outpatient DNA rate for cleft patients resulting in suboptimal follow-up. Ultimately, causation of poorer outcomes in this group is likely to be multi-factorial but the financial implication of travelling to multiple clinics should be considered and it may be that resource reallocation is the answer to address the current inequality of health care provision.

Cholesteatoma has a high prevalence in Turner syndrome, highlighting the need for earlier diagnosis and the potential benefits of otoscopy training for paediatricians.

AIM: Girls with Turner syndrome are prone to cholesteatoma, a serious suppurative middle ear disease. We aimed to confirm its high prevalence in Turner syndrome, identify risk factors and suggest possible strategies for earlier detection. METHODS: We reviewed 179 girls with Turner syndrome between 1989 and 2012 to identify cases of cholesteatoma. RESULTS: Seven girls (3.9%) had cholesteatoma (index girls) and each was compared with three age-matched girls without cholesteatoma (comparison girls). All the index girls had either the 45,X or 45,X/46X,i(Xq) karyotypes. Nine ears were initially affected, with three recurrences in two girls. Median age at first cholesteatoma presentation was 11.9 years (range: 7.5-15.2), with otorrhoea for three (range: one to seven) months in all 12 affected ears. Index girls had a significantly higher proportion of previous recurrent acute (p = 0.007) and chronic otitis media (p = 0.008), chronic perforation (p = 0.038) aural polyps (p < 0.0001) and tympanic membrane retraction (p = 0.0001) than comparison girls. CONCLUSION: Cholesteatoma has a high prevalence in Turner syndrome. Risk factors include 45,X and 46,XiXq karyotypes; a history of chronic otitis media, tympanic membrane retraction and persistent otorrhoea; and older age. Earlier recognition of ear disease is needed and otoscopy training for paediatricians caring for Turner syndrome patients may be beneficial.

Evaluating the outcomes of children undergoing lacrimal surgery for congenital nasolacrimal duct obstruction with the aim of developing a patient pathway for children presenting to a tertiary paedatric service with epiphora.

OBJECTIVE: Nasolacrimal duct obstruction is the most common cause of epiphora in children. Management has classically focused on probing and syringing followed by stent insertion and dacryocystorhinostomy either externally or endonasally. This study aimed to assess the effectiveness and safety of these procedures. METHODS: This was a retrospective analysis of the outcomes of all patients under the age of 16 who have undergone a surgical lacrimal intervention for nasolacrimal duct obstruction under general anaesthetic over a 10-year period. Outcomes included success rates and complications. RESULTS: A total of 432 patients were identified. Primary probe and syringing had a success rate of 83 per cent. Primary endonasal dacryocystorhinostomy had a success rate of 71 per cent, and revision surgery had a success rate of 82 per cent. CONCLUSION: Endonasal dacryocystorhinostomy is an effective and safe technique for the treatment of epiphora, and this study has provided a suggested protocol for management of patients presenting with epiphora.

Retrograde viral vector-mediated inhibition of pontospinal noradrenergic neurons causes hyperalgesia in rats.

Pontospinal noradrenergic neurons form a component of an endogenous analgesic system and represent a potential therapeutic target. We tested the principle that genetic manipulation of their excitability can alter nociception using an adenoviral vector (AVV-PRS-hKir(2.1)) containing a catecholaminergic-selective promoter (PRS) to retrogradely transduce and inhibit the noradrenergic neurons projecting to the lumbar dorsal horn through the expression of a potassium channel (hKir(2.1)). Expression of hKir(2.1) in catecholaminergic PC12 cells hyperpolarized the membrane potential and produced a barium-sensitive inward rectification. LC neurons transduced by AVV-PRS-hKir(2.1) in slice cultures also showed barium-sensitive inward rectification and reduced spontaneous firing rate (median 0.2 Hz; n = 19 vs control 1.0 Hz; n = 18, p < 0.05). Pontospinal noradrenergic neurons were retrogradely transduced in vivo by injection of AVV into the lumbar dorsal horn (L4-5). Rats transduced with AVV-PRS-hKir(2.1) showed thermal but not mechanical hyperalgesia. Similar selective augmentation of thermal hyperalgesia was seen in the CFA-inflammatory pain model after AVV-PRS-hKir(2.1). In the formalin test, rats transduced with hKir(2.1) showed enhanced nocifensive behaviors (both Phase I and II, p < 0.05, n = 11/group) and increased c-Fos-positive cells in the lumbar dorsal horn. Transduction with AVV-PRS-hKir(2.1) before spared nerve injury produced no change in tactile or cold allodynia. Thus, the selective genetic inhibition of approximately 150 pontospinal noradrenergic neurons produces a modality-specific thermal hyperalgesia, increased nocifensive behaviors, and spinal c-Fos expression in the formalin test, but not in the spared nerve injury model of neuropathic pain, indicating that these neurons exert a selective tonic restraining influence on in vivo nociception.

Acute paediatric neck abscesses.

Acute neck swellings in a paediatric setting are often treated with antibiotics, proceeding to incision and drainage if an abscess is suspected. A variety of investigations are available and the causative organism can vary. A five-year retrospective study analysing trends in microbiology, antibiotic sensitivity, clinical evaluation and management of children presenting with an acute cervical abscess of four weeks duration or less was performed. The case notes of 175 children admitted between January 1996 and December 2000 to the acute surgical admission unit at the Royal Hospital of Sick Children, Glasgow were studied. During this period there were 90 males and 85 females with a mean age of three years (range: one month to 13 years). One hundred and twenty three (70%) children underwent surgery with pus being confirmed in 114 (93%) of cases. Ultrasound was performed in 70 (40%) patients with 48 proceeding to surgery. Positive culture of pus from abscess cavities revealed Staphylococcus aureus in 46% (85% sensitive to both flucloxacillin and erythromycin) and Streptococcus pyogenes in 15% (80% sensitive to penicillin and 75% to erythromycin). The role of investigations and the available treatment options are discussed.

Current and future therapies for Pseudomonas aeruginosa infection in patients with cystic fibrosis.

Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients. Better detection of P. aeruginosa infection using biomarkers may enable more successful eradication before chronic infection is established. In chronic infection P. aeruginosa adapts to avoid immune clearance and resist antibiotics via efflux pumps, ß-lactamase expression, reduced porins and switching to a biofilm lifestyle. The optimal treatment strategies for P. aeruginosa infection are still being established, and new antibiotic formulations such as liposomal amikacin, fosfomycin in combination with tobramycin and inhaled levofloxacin are being explored. Novel agents such as the alginate oligosaccharide OligoG, cysteamine, bacteriophage, nitric oxide, garlic oil and gallium may be useful as anti-pseudomonal strategies, and immunotherapy to prevent infection may have a role in the future. New treatments that target the primary defect in cystic fibrosis, recently licensed for use, have been associated with a fall in P. aeruginosa infection prevalence. Understanding the mechanisms for this could add further strategies for treating P. aeruginosa in future.

Labial pit and ectopic salivary gland tissue.

We report the unusual case of a girl who presented with a lesion on her soft palate and subsequently was found to have a sinus in her labial sulcus. This case report discusses investigation and management of the patient. Further to this we discuss the postulated embryological development of both the parotid gland and labial pit.

Paediatric tracheostomy-An 11 year experience at a Scottish paediatric tertiary referral centre.

AIMS: The aim of this paper was to review the indications, complications and outcomes for tracheostomy at a Scottish paediatric tertiary referral hospital. METHODS: All patients undergoing tracheostomy between January 2001 and September 2012 were identified. A retrospective case note analysis was performed. RESULTS: 111 tracheostomies were done in the study period. The mean number per year was 11 (3-12). Full data was available for 95 patients. There were 56 (59%) males and 39 (41%) females. Age at time of tracheostomy ranged from one day to 15 years, the mean age of tracheostomy insertion was 69 weeks. The majority of patients, 75 (79%), were under one year old when they had their tracheostomy. The most common indication was long-term ventilation (20%), followed by craniofacial abnormality causing airway obstruction (18%), followed by subglottic stenosis (14%). 37% of patients were decannulated. CONCLUSIONS: This series reflects current trends in the indications for paediatric tracheostomy, with chronic lung disease of prematurity being the most common indication.

An interventional airway delivery service for congenital high airway obstruction.

BACKGROUND: Congenital airway obstruction is rare but potentially fatal. We developed a complex airways interventional delivery team to manage such cases. Antenatal imaging detects airway compromise at an early stage and facilitates the planning of delivery procedures ('ex utero intrapartum treatment' and 'operation on placental support') which maintain feto-placental circulation whilst an airway is secured. METHOD: A retrospective review was performed of cases in which ENT input was required at birth for airway obstruction. RESULTS: Four neonates were delivered before implementation of the service: two were intubated and another two underwent tracheostomy but died in the peri-natal period. Seven neonates were delivered after implementation of the service: six were intubated and one underwent immediate tracheostomy. Five subsequently underwent tracheostomy (three have since been decannulated). One child with multiple congenital anomalies died due to respiratory failure. Airway obstruction was caused by lymphatic malformation, teratoma, costo-craniomandibular syndrome and choristoma. CONCLUSION: In the absence of other anomalies, interventional airway delivery led to reduced mortality and improved outcomes.

Phase I trial of interferon gamma retroviral vector administered intratumorally with multiple courses in patients with metastatic melanoma.

The purpose of this study was to determine the safety and antitumor activity of IFN-gamma retroviral vector in patients with advanced melanoma. Seventeen patients (9 single courses, 8 multiple courses) received a total of 363 intratumor injections of IFN-gamma retroviral vector (1 x 10(7) PFU/ml administered at 0.3, 0.5, and 1.0 ml per cohort). No grade III/IV adverse events were attributed to study medication. Replication-competent retrovirus was not detected in any of the 17 patients by polymerase chain reaction studies. Eight patients showed elevated anti-tumor antibody responses in comparison with baseline by ELISA. One of nine patients treated with a single course had an optimal response of stable disease, compared with eight of eight multiple-injected patients. Median survival of single-injected patients was 150 days, and patients who received multiple injections have still not achieved median survival duration, with four of eight still living (p = 0.0462, Wilcoxon; p = 0.0273, log rank). We conclude that intratumor injection of IFN-gamma is safe and well tolerated. Evidence of antitumor activity is suggested in patients with advanced malignancy that received multiple injections.

Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects.

OBJECTIVE: The purpose of this study was to explore central serotonergic functions in subgroups of alcoholics and in healthy comparison subjects. METHOD: The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP) was administered to male alcoholic patients who were classified according to the criteria of von Knorring et al. as type I alcoholics (late onset) (N = 16) or type II alcoholics (early onset with antisocial traits) (N = 24) and to 22 healthy comparison subjects. Psychological, physiological, and neuroendocrine measures were obtained before and after the m-CPP infusion. RESULTS: m-CPP elicited subtype-related differential effects among the alcoholics; the type I alcoholics reported more anger and anxiety, and the type II alcoholics reported increased euphoria and a greater likelihood of drinking. The healthy comparison subjects exhibited a greater increase in plasma ACTH response to the m-CPP infusion than the alcoholics regardless of subtype. CONCLUSIONS: Differences in certain 5-HT receptor functions may explain some of the clinical characteristics that differentiate the type II and type I subgroups of alcoholic patients. Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in comparison with healthy subjects.

Cyclopropanation enantioselectivity is pressure dependent in supercritical fluoroform.

The tunable dielectric constant ε of supercritical fluoroform is the explanation for pressure-dependent enantioselectivity in a reaction conducted at low pressure. For the cyclopropanation of styrene and methyl phenyldiazoacetate with a dirhodium catalyst, the enantioselectivity was significantly higher at 52 bar than above 80 bar (see plot).

Phase I trial of interferon-gamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma.

BACKGROUND: Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral injection of IFN-gamma retroviral vector in advanced melanoma patients. METHODS: This was a phase I study, in which 13 patients received a single daily injection of a retroviral vector with the IFN-gamma gene for 5 consecutive days (1.5 x 10(8) colony-forming units total dose); patients subsequently underwent resection of the injected lesion to confirm DNA transduction in situ. RESULTS: No toxicity related to the injected vector was observed. Replication competent retrovirus was not observed in any prepared samples (n = 65). IFN-gamma expression was confirmed in 3 of 10 harvested tumor samples; one was equivocal, and DNA transduction was unable to be confirmed by enzyme-linked immunospot assay in six samples. CONCLUSIONS: An injection of IFN-gamma gene/retroviral vector is well tolerated. DNA transduction was demonstrated in human subjects, confirming the feasibility of the direct injection approach for the gene therapy of solid tumors. Further trials to determine optimal schedule and potential efficacy are indicated.

Phase I trial of retroviral vector-mediated interferon (IFN)-gamma gene transfer into autologous tumor cells in patients with metastatic melanoma.

The purpose of this study was to determine the safety of treating melanoma patients with retroviral vector-mediated interferon (IFN)-gamma gene-transduced autologous tumor cells. We designed a phase I study, in which irradiated, autologous, transduced melanoma cells expressing the IFN-gamma gene were injected subcutaneously every 2 weeks with escalating cell doses for six injections. Tumor tissue was harvested from 58 patients with metastatic melanoma. Twelve patients had sufficient expansion of autologous tumor (0.56-160 x 10(7) cells) and adequate IFN-gamma expression after gene transduction (2-79,000 U/10(6) cells/24 hours) for injections. Five patients received injections. No toxicity was attributed to the IFN-gamma retroviral vector in the patients injected. One of the injected patients remains disease-free after 13 injections, following the surgical removal of brain, adrenal, and lung metastases. We found that injections of autologous tumor cells transduced by IFN-gamma gene were well tolerated. However, the ability to develop primary autologous melanoma cell lines was limited, and only a minority of patients were injected.

Preparation of ferritin-avidin conjugates by reductive alkylation for use in electron microscopic cytochemistry.

An improved technique was developed for the unidirectional covalent binding of avidin to ferritin by reductive alkylation. The method is based on the oxidation of sugar moieties on avidin and subsequent coupling to amino groups of ferritin via Schiff's bases followed by reduction with sodium borohydride. The resultant conjugate was used as an ultrastructural marker for the localization of surface receptor sites on biotin-derivatized whole cells. Erythrocytes were treated chemically with sodium meta-periodate and biotin hydrazide in succession. The ferritin-avidin conjugates were used to label the biotin sites either before or after fixation of the cells. The density and distribution of ferritin avidin conjugates on cell surfaces were anlyzed on thin sections and compared with those of cationized ferritin, which were shown to bind anionic sites of the erythrocyte membrane. The extensions of this method for the visualization of other systems is discussed.