The effect of FloSeal on post-tonsillectomy pain: a randomised controlled pilot study.

OBJECTIVES: To determine whether FloSeal as a haemostatic agent in tonsillectomy is associated with less postoperative pain than conventional haemostasis with ligatures. DESIGN: Randomised, controlled, single-blinded pilot study. SETTING: James Cook University Hospital, Middlesbrough, Cleveland, UK. PARTICIPANTS: Thirty patients over 16 years of age undergoing tonsillectomy for recurrent tonsillitis were recruited for the study. At surgery both tonsils were removed by cold steel dissection. Following randomisation one tonsil fossa had FloSeal applied and the other ligatures for haemostasis. MAIN OUTCOME MEASURES: The primary outcome measure was postoperative pain following tonsillectomy measured on a visual analogue scale. Pain was recorded three times a day for the first 10 days following surgery. Haemorrhage rates were also recorded as a secondary outcome. RESULTS: Complete data was analysed for 26 patients (87%). The data was grouped into distinct time periods: 0-2, 3-6 and 7-10 days. The sum of the visual linear analogue scale over the time periods for each patient was calculated. Using Wilcoxon Signed Ranks Test, the data was analysed and it was found that there was no statistically significant difference in postoperative pain scores between the control and treatment side at any time. There was a postoperative reactionary haemorrhage rate of 6.7% on the FloSeal side. CONCLUSION: In our pilot study there was no reduction in pain on the FloSeal side in the first 10 days following tonsillectomy which contrasts with previous findings in the literature.

Paediatric obstructive sleep apnoea: is our operative management evidence-based?

BACKGROUND: Despite the plethora of publications on the subject of paediatric obstructive sleep apnoea, there seems to be wide variability in the literature and in practice, regarding recourse to surgery, the operation chosen, the benefits gained and post-operative management. This may reflect a lack of high-level evidence. METHODS: A systematic review of four significant controversies in paediatric ENT was conducted from the available literature: tonsillectomy versus tonsillotomy, focusing on the evidence base for each; anaesthetic considerations in paediatric obstructive sleep apnoea surgery; the objective evidence for the benefits of surgical treatment for obstructive sleep apnoea; and the medical treatment options for residual obstructive sleep apnoea after surgical treatment. RESULTS AND CONCLUSION: There are many gaps in the evidence base for the surgical correction of obstructive sleep apnoea. There is emerging evidence favouring subtotal tonsillectomy. There is continuing uncertainty around the prediction of the level of post-operative care that any individual child might require. The long-term benefit of surgical correction is a particularly fertile ground for further research.

Paediatric obstructive sleep apnoea: can our identification of surgical candidates be evidence-based?

BACKGROUND: Paediatric obstructive sleep apnoea is a common clinical condition managed by most ENT clinicians. However, despite the plethora of publications on the subject, there is wide variability, in the literature and in practice, on key aspects such as diagnostic criteria, the impact of co-morbidities and the indications for surgical correction. METHODS: A systematic review is presented, addressing four key questions from the available literature: (1) what is the evidence base for any definition of paediatric obstructive sleep apnoea?; (2) does it cause serious systemic illness?; (3) what co-morbidities influence the severity of paediatric obstructive sleep apnoea?; and (4) is there a medical answer? RESULTS AND CONCLUSION: There is a considerable lack of evidence regarding most of these fundamental questions. Notably, screening measures show low specificity and can be insensitive to mild obstructive sleep apnoea. There is a surprising lack of clarity in the definition (let alone estimate of severity) of sleep-disordered breathing, relying on what may be arbitrary test thresholds. Areas of potential research might include investigation of the mechanisms through which obstructive sleep apnoea causes co-morbidities, whether neurocognitive, behavioural, metabolic or cardiovascular, and the role of non-surgical management.

Laryngomalacia: is there an evidence base for management?

BACKGROUND: The advent of supraglottoplasty clearly has transformed the surgical management of severe laryngomalacia. The condition, however, generally runs a milder course, with spontaneous resolution the norm. OBJECTIVES: To identify gaps in the knowledge and identify topics for future study. METHOD: Systematic review of the literature. RESULTS: The literature suggests that there is a range of abnormalities leading to the typical collapsing upper airway, and that neurological disease, other airway abnormalities, syndromes and gastroesophageal reflux all contribute to disease severity and influence outcomes. The procedures involved in supraglottoplasty are rarely specified, the indications for surgery are vaguely defined and the role of medical therapy is unclear. CONCLUSION: Every review article or survey of opinion suggests that there is still a marked variation in individual practice and a lack of consensus.

Endoscopic sphenopalatine artery ligation for acute idiopathic epistaxis. Do anatomical variation and a limited evidence base raise questions regarding its place in management?

BACKGROUND: Endoscopic sphenopalatine artery ligation is widely accepted as effective and safe for acute spontaneous epistaxis that is unresponsive to conservative management. As with many new procedures, it has been progressively adopted as common practice, despite a limited evidence base for its efficacy. Early reviews called for comparative trials to support its adoption, but subsequent literature largely consists of case series and narrative reviews. These have attempted to derive an algorithm to establish its place in management, but consensus is still lacking. Intuitively, although there are theoretical objections, an operation regarded as relatively simple, fast and safe hardly seems to demand high-level evidence of efficacy. Rhinologists may be influenced by years of personal experience and success with the technique. However, estimates of the effect size and the added contribution to traditional surgical management are lacking. If the procedure could be shown to dramatically influence outcome, it should be standard practice and indispensable for all patients requiring operative intervention. OBJECTIVES: This paper systematically examined the literature, appraising the anatomical basis for such an approach and evidence for its efficacy. It questions whether any units unable to consistently offer endoscopic sphenopalatine artery ligation should be undertaking surgical management of acute epistaxis.

Eosinophilic oesophagitis: a systematic review for otolaryngologists.

BACKGROUND: Eosinophilic oesophagitis is a chronic, immune/antigen-mediated oesophageal disease, only recently, but increasingly, recognised in the world literature. It is diagnosed and managed primarily by medical gastroenterologists and allergy specialists, and is a distinct disease entity, affecting both children and adults. Few studies have been published in otolaryngology journals, although otolaryngologists will encounter patients with undiagnosed eosinophilic oesophagitis. Patients may present with dysphagia, bolus obstruction or with other ENT disorders, such as atopic rhinitis, reflecting the underlying systemic allergic disorder. OBJECTIVE: This paper systematically reviews the evidence base published on the epidemiology, clinical presentation, diagnosis, treatment and prognosis of eosinophilic oesophagitis, particularly as it relates to otolaryngology practice.

Cytokine expression in hepatocytes: role of oxidant stress.

Inflammatory mediators, including cytokines and chemokines, are associated with the pathology of chronic liver disease. Interleukin-8 (IL-8) in humans and macrophage inflammatory protein-2 (MIP-2) in rodents, both members of the C-X-C family of chemokines, are particularly potent neutrophil attractants and have been implicated in chronic liver diseases. In the liver, cytokine secretion is usually associated with non-parenchymal cells, particularly Kupffer cells. In the present studies, chemokine gene expression and secretion were investigated in hepatocytes treated with various stimulators. Using human Hep G2 cells, it was demonstrated that, in contrast to lipopolysaccharides (LPS), both tumor necrosis factor-alpha (TNF-beta) and H2O2 are potent inducers of IL-8, presumably acting via protein kinase C (PKC)-dependent pathways. MIP-2 expression occurred in freshly isolated rat hepatocytes following treatment with TNF-alpha, LPS, and to a lesser degree, H2O2. Both IL-8 and MIP-2 secretion were inhibited, although to varying degrees, by such antioxidants as TMTU, DMSO, catalase, and N-acetylcysteine. Furthermore, in vitro TNF-alpha neutralization experiments and transfection of Hep G2 cells with an IL-8 construct confirmed that TNF-alpha and H2O2 directly stimulate IL-8 secretion. RT-PCR analyses indicated that chemokine secretion induced by these agents operates via increased gene expression. Furthermore, a variety of cytokine genes were found to be expressed by hepatocytes, including MCP-1, cytokine-induced neutrophil chemoattractant (CINC), and IL-6. Taken together, these studies indicate that hepatocytes respond to biologically relevant levels of common activators, including H2O2, to produce cytokines and chemokines that contribute to pathophysiologic and repair processes in the liver.

Language development in a group of very low-birth-weight children whose postauricular myogenic response was tested in infancy.

A new instrument for the detection of the postauricular myogenic (PAM) response was used to test the hearing of 106 infants weighing less than or equal to 1,500 g when they were aged 1 to 21 months. Eighty-eight infants showed a positive response at 60 dB hearing level (HL) (normal). The other 18 did not respond; four were found to have sensory neural hearing loss and another six had conductive loss due to secretory otitis media. Of the 106 children, 90 aged 2 years or more (mean 27 months) were living in the United Kingdom, and their language development was assessed. It was normal in 67/75 children whose PAM response had been normal in infancy. The remaining eight children with normal PAM responses in infancy, had language delay. All eight children had problems that were thought to account for the delay, including three with mental retardation, three with cerebral palsy, and two whose families did not speak English. Language development was normal in 11/15 children tested whose PAM responses had been found to be abnormal, including all six whose secretory otitis media had been diagnosed and treated at the time of the PAM test. Delay in language development was found in 3/4 children with sensory neural hearing loss who were available for testing and in one child with overall developmental delay. It is concluded that a positive PAM response at 60 dB HL in infancy indicated hearing adequate for the development of normal speech in otherwise normal children among a group of infants at high risk of hearing loss.

Glucocorticoid receptor mRNA in patients with ulcerative colitis: a study of responders and nonresponders to glucocorticosteroid therapy.

BACKGROUND AND AIMS: Up to 30% of patients with severe-to-moderate attacks of ulcerative colitis (UC) respond poorly to glucocorticosteroid (GCS) treatment. The reason for this unresponsiveness is unknown. AIM: Our aim was to evaluate possible differences in glucocorticoid receptor (GR) density in peripheral leukocytes and effects of low-dose GCS treatment on GR density and on the hypothalamic-pituitary-adrenal axis in UC patients who had received high-dose GCS treatment due to a moderate or severe attack. Eleven UC patients in remission who were responders (Rs) to previous GCS treatment were compared with 10 patients who failed GCS therapy and had a colectomy (nonresponders. NRs). Ten healthy individuals served as controls. METHODS: Quantitation of GR mRNA by a solution hybridization assay in peripheral leukocytes and a low-dose adrenocorticotropin hormone stimulation test was performed before and after low-dose dexamethasone (DEX) treatment for 14 days. The glucocorticoid-responsive gene for metallothionein IIa (MTIIa) was also analyzed by a solution hybridization assay in peripheral leukocytes. RESULTS: Overall, basal GR mRNA levels were higher in patients than in controls (p < 0.0001). There were no significant differences between NRs and Rs. None of the groups down-regulated their GR mRNA levels in response to DEX treatment. Basal and stimulated cortisol levels decreased significantly only among NRs after DEX (p = 0.012 and 0.0093). MTIIa levels were lower in NRs as compared with Rs, both in mononuclear (p = 0.0059) and in polynuclear leukocytes (p = 0.030). CONCLUSION: Patients with UC in remission exhibit higher levels of GR mRNA in peripheral leukocytes. We speculate that this may be secondary to an underlying up-regulation of proinflammatory factors also present in patients in clinical remission. Differences in GR mRNA levels per se thus may not be important for the ability of patients with UC to respond to GCS treatment. The hypothalamic pituitary adrenal axis was suppressed by low-dose DEX treatment only in NRs, possibly indicating that steroid-resistance is not a generalized phenomenon. Lower levels of MTIIa in NRs may indicate a diminished efficiency of GR regulation in steroid-refractory patients.

Low molecular weight heparin as adjuvant therapy in active ulcerative colitis.

BACKGROUND: Heparin given intravenously has shown beneficial effects in the treatment of refractory ulcerative colitis in open trials. Low molecular weight heparin (LMWH) offers advantages in the method of administration but have not been evaluated in inflammatory bowel disease conditions. AIM: To assess the tolerability and safety of subcutaneous self-administered LMWH in outpatients with refractory ulcerative colitis and to evaluate any potential adjuvant therapeutic effect. PATIENTS AND METHODS: Twelve patients with mild to moderately active ulcerative colitis were included in the trial. The patients had either responded poorly to treatment with conventional therapy, including oral and/or rectal glucocorticosteroids, or had experienced a rapid relapse during or shortly after GCS therapy. Dalteparin sodium 5000 units s.c. injection was administered twice daily for 12 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms, and endoscopic and histological scores were analysed. Leucocyte scanning was performed at inclusion and at the end of the study. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. Eleven patients improved symptomatically and six (50%) attained complete remission after 12 weeks of treatment. Endoscopic, scintigraphic and histological scores were found to be significantly improved. CONCLUSION: Self-administered LMWH given s.c. may be a safe adjuvant therapy for patients with active, glucocorticosteroids-refractory ulcerative colitis. A controlled trial should be undertaken to confirm the positive effects found in this study.

Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis.

OBJECTIVE: To analyse the ability of simple clinical and biochemical parameters to predict glucocorticosteroid (GCS) treatment failure in patients with acute attacks of ulcerative colitis. DESIGN/METHODS: Retrospective analysis of clinical and biochemical data. SETTING: Four Swedish university hospitals. PATIENTS: Ninety seven patients with acute attacks of ulcerative colitis severe enough to warrant treatment with intravenous GCS, hospitalized during the years 1988-93. MAIN OUTCOME MEASURE: Colectomy within the first 30 days after hospitalization, defined as 'clinical steroid resistance'. RESULTS: Thirty days after admission, 39 patients (40%) were in complete clinical and endoscopic remission while 33 (34%) had undergone colectomy. During follow-up for 24 months, four patients among the 39 initially in remission underwent colectomy. Among the 25 patients (26%) not attaining remission after 30 days, an additional nine patients subsequently required colectomy. Steroid resistance was associated with duration of disease (2.7 vs 8.1 years, P=0.0037) and steroid treatment before hospitalization (70 vs 42%, P=0.010). In particular, elevation of body temperature (37.4 vs 36.9 degrees C, P=0.012), persistence of diarrhoea (6.8 vs 3.6 bowel movements/day, P<0.0001) and passage of blood (83 vs 42%, P=0.0003) as well as CRP elevation (36.3 vs 18.0 mg/l, P=0.007) on day 3 after treatment initiation were identified as predictors of a poor response. CRP > or = 25 mg/l and > 4 bowel movements/day on day 3 of hospitalization independently predicted a high risk for colectomy within 30 days. CONCLUSIONS: Sustained elevation of body temperature, persistent bloody diarrhoea and continued CRP elevation on day 3 of intravenous GCS treatment strongly predict clinical steroid resistance in acute attacks of ulcerative colitis. In the group of poor or non-responders, colectomy or more aggressive medical treatment should be considered at an early stage.

CT scanning of middle ear cholesteatoma: what does the surgeon want to know?

The history of surgery for middle ear cholesteatoma is of an evolution of techniques to meet the challenges of inaccessible disease and of post-operative cavity management. The concept has traditionally been of exploration guided by awareness and anticipation of all, possibly asymptomatic, complications. Modern imaging reliably demonstrates surgical anatomy, dictating the ideal approach, forewarns of complications and may reveal the extent of disease. An apparent resistance amongst otologists to universal CT scanning prior to mastoidectomy contrasts with the enthusiasm of skull base surgeons or rhinologists for appropriate imaging.

Fetal skin organ culture.

The fetal response to cutaneous injury has been investigated in a variety of models; most have studied the differences between fetal and adult healing mechanisms in vivo and in cell culture. Further disclosure of the cellular and biochemical events requires a model that can be manipulated to study single factors influencing fetal tissue repair without the complex interactions that occur in vivo, but in a system that more closely approximates normal skin than cell culture models. This paper presents a method for the organ culture of fetal skin and its advantages as a model to help elucidate fetal healing mechanisms. Skin sections (1 x 1 cm) excised from the backs of fetuses of New Zealand white rabbits on day 27 gestation (term = 31 days) were placed eccentrically in 65-mm culture dishes and fed daily with 2.5 mL of DMEM containing 10% fetal calf serum, antibiotics, and 10 mM ascorbic acid. A separate group, treated similarly, received 4-mm punch wounds to assess the in vitro response to wounding. The specimens were incubated at 37 degrees C in humidified room air on a rocker platform to provide alternate exposure of the skin to air and medium. Gross observation at 3 weeks showed cells extending into the central wound, indicating that viable cells were proliferating and/or migrating from the tissue. Skin was examined histologically and was viable over the 3-week period studied. Organ culture, by maintaining tissue in the natural extracellular matrix, allows cell-to-cell contact and communication to be maintained while allowing controlled environmental manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Operative techniques in the fetal rabbit.

The development of fetal surgical techniques has made the antenatal correction of congenital defects possible. These techniques have evolved from trials with animal models, permitting increasingly sophisticated operations with low morbidity and mortality. Experimental models range from large animals offering longer gestations but with single pregnancies and high cost, to smaller animals offering multiple pregnancies at reduced cost but with shorter gestations. This paper describes operative techniques in the fetal rabbit and its advantages as a fetal surgical model. Experience with the pregnant rabbit has shown it to be a suitable surgical model for several reasons. Pregnancies are multiple, increasing cost effectiveness and permitting operation on up to eight fetuses per litter without fetal loss. Techniques that promote fetal survival include local housing of does several days prior to operation and preoperative sedation. Spontaneous mask ventilation provides ease of anesthetic administration and titration. Overall surgery is well tolerated with a low incidence of intraoperative complications. Rabbit models have been used in the study of transamniotic fetal feeding, abdominal wall defects, and wound healing. These techniques have resulted in postoperative fetal viability approaching 90%, with negligible maternal mortality in over 4000 fetal operations, thereby making the rabbit a manageable cost-effective model of fetal surgery.

Analysis of skin grafting techniques in the fetal rabbit.

The experimental model reported here was developed initially to examine the possibility of in utero coverage of congenital soft tissue defects using several types of reconstructive techniques. To pursue this, full-thickness skin grafts, pedicle flaps, and skin "islands" were fashioned on the backs of fetal rabbits; equivalent adult control wounds were also created. While all pedicle flaps and skin islands remained viable, none of the full-thickness grafts survived in the fetus. All adult control flaps, skin islands, and skin grafts were viable. Angiogenesis is crucial to full-thickness skin graft survival. These observations suggest that the death of full-thickness fetal skin grafts may be related to a failure of neovascularization in the graft bed. Further analysis using this model may help elucidate the factors involved in fetal angiogenesis. Additionally, this model may permit testing of putative angiogenic factors applied under a full-thickness skin graft; graft survival offers an easy, objective, and quantifiable means of data analysis.

Effects of benzo(a)pyrene and tetrachlorodibenzo(p)dioxin on fetal dolphin kidney cells: inhibition of proliferation and initiation of DNA damage.

Dolphin kidney cells (CDK) were exposed in vitro to benzo(a)pyrene (BaP) in the presence or absence of 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), a cytochrome P450-inducing agent, and/or alpha-naphthoflavone (alpha NF), an inhibitor of cytochrome P450 induction. BaP inhibited mitosis in CDK cells in a dose-dependent manner. TCDD, while inhibiting cell proliferation, did not show a strict dose-dependent mode of action. BaP inhibition of mitosis was decreased by alpha NF, which also decreased the inhibitory effects of TCDD on CDK proliferation. BaP treatment initiated both 3H-thymidine incorporation and the increased alkali lability of DNA functions of the initiation of excision repair. Cells pre-treated with TCDD and then exposed to BaP exhibited increased BaP-DNA adduct levels and increased DNA excision repair. These data indicate that dolphin cells metabolized BaP in vitro as a function of cytochrome P450-associated activities, that BaP metabolites covalently bound to cellular DNA and initiated excision repair. Inhibition of the cytochrome P450-mediated metabolism of BaP decreased the BaP-associated inhibition of mitosis in dolphin cells.

Surgery in lesions of the petrous apex.

It is fortunate that lesions of the petrous apex are rarely encountered. The occult nature of the local disease and the poorly localizing clinical features favor a delayed diagnosis. Its site deep to the labyrinth and facial nerve and its proximity to the internal carotid artery and brain stem potentially make surgery a risky prospect. The reconciling of preservation of neurologic function and adequate surgical exposure requires an extensive knowledge of temporal bone anatomy and surgical approaches.

A matched observational study of survival in cats with enucleation due to diffuse iris melanoma.

Although a small number of cases of feline diffuse iris melanoma have been documented to metastasize, the prognosis is not known. In this matched observational study, the survival time of 34 cats with enucleation due to histologically confirmed diffuse iris melanoma was recorded. These results are compared to the survival times of 83 age-matched control cats. Affected cats had enucleation between 2 and 10 years prior to the study. One group of control cats with eye disease had enucleation for either lymphoplasmacytic uveitis (27 cases), ocular trauma (seven cases), or endophthalmitis (four cases). In these control cats, enucleations were performed between 2 and 10 years prior to this study. Forty-five additional control cats presented for vaccination between 2 and 10 years prior to the study. The extent of diffuse iris melanoma at the time of enucleation in affected cats was graded according to the extent of involvement of ocular tissues and the invasiveness of the tumor. Affected cats have a significantly decreased survival compared with control cats and cats with extensive tumors at the time of enucleation have the lowest survival rates. Cats with tumors confined to the iris survive at the same rate as controls. These results suggests that early enucleation is important to avoid premature death, presumed to be due to cancer metastasis in cats with diffuse iris melanoma.