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We describe an unusual case of recurrent, refractory anterior epistaxis in an 86-year-old man with two mechanical heart valves who was on permanent warfarin therapy. His numerous episodes of epistaxis were incited by chronic nose-picking and strong nose-blowing, practices that he continued to engage in despite repeated medical advice to stop. Stopping his anticoagulation therapy was not considered as a management option because of an unacceptably high risk that this would lead to a thromboembolic event. Eventually, we temporarily sutured his nares closed, and his nosebleeds ceased. The suturing was performed in the ward with local anesthesia. This procedure was simple to perform, fairly well tolerated, easily reversible, and highly effective.

When the embryonic forebrain (the prosencephalon) fails to sufficiently divide into the two cerebral hemispheres, holoprosencephaly (HPE) results. This disorder can result in various skull and facial defects with brain abnormalities of varying severity. These brain defects ultimately dictate the prognosis. This varies from death in utero, to normal or near normal brain development. In these less severe cases, otherwise normally developing babies are born with rarely seen midfacial cleft deformities, giving away a structural brain deformity. We report a case of an otherwise developmentally normal seven-year-old boy who was being assessed for nasal obstruction and rhinorrhea. Investigation directed by a high index of suspicion uncovered an occult case of holoprosencephaly.

A gene library was constructed coding for all possible variants of two amino acids (101, 102) in a solvent-exposed surface return loop (alpha E-beta D) of Bacillus stearothermophilus L-lactate dehydrogenase (bsLDH). All but one of 38 enzyme variants examined were thermally stable and had native-like hydrodynamic properties. In this sample, there was no bias detected in either the DNA or amino acid sequences encoded. We argue that the alpha E-beta D surface loop sequence is unimportant for protein folding or stability and can be fully varied to select enzymes with new substrate specificities. The selection of NAD-dependent dehydrogenases with specificity for: malate, phenyllactate, hydroxyisocaproate and 4-phenyl-2-hydroxy-butanoate from two bsLDH libraries is described. This required a highly discriminatory screen for 2-hydroxy acid dehydrogenase activity to select enzymes which, in the absence of the natural allosteric activator fructose-1,6-bisphosphate (FBP), maintained high temperature stability and catalytic activity without substrate inhibition. In general the amino acid residues at positions 101 and 102 which determined substrate specificity were as expected from hydrophobic and ionic complementarity to the substrate. For example, a bsLDH variant with Asn101Va1102 is as efficient with phenylpyruvate as is the wild-type enzyme (Asn101Gln102) with pyruvate. Using molecular modelling, the valine at position 102 can be fitted into the active site without significant structural distortion caused by the aromatic side-chain of the substrate. Similarly, nine out of ten malate dehydrogenases (MDHs) selected had an arginine residue at position 102 to complement the negatively charged carboxyl group in oxaloacetate. One, Arg101Arg102 (Kcat/Kmoxaloacetate = 1.6 x 10(6) M-1 S-1) is 25% more active than the previous best synthetic MDH. There were surprises: present understanding would not have predicted the oxaloacetate transforming activity of Ser101Leu102 or the phenylpyruvate activity of Pro101Lys102. The former is about one-third as efficient as the best malate dehydrogenase selected, whilst the latter had about one-seventh of the best phenylpyruvate dehydrogenase activity.

The flexible nasendoscope is now an integral tool in most otorhinolaryngology departments for visualizing the hypopharyngolarynx. A technique has been described using themodified Valsalva manoeuvre to improve visualization of the hypopharynx during flexible nasopharyngoscopy. The authors report an alternative technique for visualizing the upper oesophagus using the flexible nasendoscope, and highlight three cases where there was accurate visualization of an impacted oesophageal food bolus. Subsequently, these patients underwent flexible oesophagoscopy to dislodge the foreign body. The authors also describe three cases where the flexiblenasendoscope was successfully used to visualize and negotiate the impacted food bolus beyond the cricopharyngeus. This is a safe and simple procedure performed without any sedation and reduces the need for prolonged hospitalization.

Healthy ear canal skin has an acidic pH. Evidence suggests that reacidification of the ear canal may lead to resolution of otitis externa. The pH of 15 commonly prescribed topical ear drop preparations used in the treatment of otitis externa was measured using a Jenway 3020 pH meter with temperature compensation at 37.5°C. The pH values ranged from 2.89 to 7.83. Two-thirds of preparations tested were of acidic pH. The remaining one-third were alkaline. Reacidification of the ear canal may help in the treatment of otitis externa.

Introduction: The relative incidence of paediatric Bell’s palsy is two to four times less than the condition in adults. The number encountered in our otolaryngology department falls short of the above prediction. This could either reflect the general practitioners' (GPs) patterns of referral or a lower incidence in our locality.Methods: Postal questionnaires were sent to our local GPs to determine their referral practice when managing children presenting with acute facial paralysis.Results: Of 233 questionnaires, 172 (74 per cent) were returned and analysed. Fifty-four per cent of GPs referred their patients to the local paediatric services, 22 per cent to an otolaryngologist, and the remaining 24 per cent of GPs were confident in diagnosing and managing Bell's palsy in children themselves.Discussion and Conclusion: Of the GPs surveyed 78 per cent did not refer children presenting with acute facial paralysis to an otolaryngologist. We suggest minimum investigations for acute facial paralysis in children before diagnosing Bell's palsy and stipulate otolaryngology referral for all.

When the embryonic forebrain (the prosencephalon) fails to sufficiently divide into the two cerebral hemispheres, holoprosencephaly (HPE) results. This disorder can result in various skull and facial defects with brain abnormalities of varying severity. These brain defects ultimately dictate the prognosis. This varies from death in utero, to normal or near normal brain development. In these less severe cases, otherwise normally developing babies are born with rarely seen midfacial cleft deformities, giving away a structural brain deformity. We report a case of an otherwise developmentally normal seven-year-old boy who was being assessed for nasal obstruction and rhinorrhea. Investigation directed by a high index of suspicion uncovered an occult case of holoprosencephaly.

Current methods for reengineering enzyme substrate specificities rely heavily on the use of static x-ray crystallographic models. In this article we detail the use of a molecular mechanics approach for suggesting regions of Bacillus stearothermophilus L-lactate dehydrogenase (EC 1.1.1.27) involved in substrate specificity, and hence areas of interest for protein engineers. The approach combines molecular dynamics with energy minimization (MD/EM) to search the conformational space available to a 15-A sphere of the ternary complex centered on the catalytic histidine. The search is carried out by calculating a 30-ps dynamics trajectory at 300 K and minimizing structures at 1-ps intervals. The protocol has been performed on 14 systems containing different combinations of substrate and mutant/wt LDH. In order to discover which interactions are important in defining substrate specificity, eight conformational parameters representing substrate-active site interactions were measured in each of the 420 minimized structures. These parameters were then compared to the measured catalytic activity of the protein-substrate combinations. These comparisons show that arginine 109 orientation is a major determining factor in LDH specificity. Using this methodology it is possible to estimate the catalytic activity of proteins of varied sequence by computer simulation before synthesis.

Case Presentation A previously healthy eight-month-old girl was admitted to the pediatric intensive care unit at Stollery Children's Hospital (Edmonton, Alberta) following a waxing and waning course of respiratory distress. She had initially presented 11 days earlier to the emergency room with stridor and a brassy cough, and laryngotracheobronchitis was diagnosed. Treatment with racemic adrenaline and one dose of oral dexamethasone was effective and she was discharged after overnight observation. Nasopharyngeal aspirate was negative by direct fluorescent antibody and by viral culture for influenza A and B, parainfluenza and respiratory syncytial virus. Over the next three days, the child had increasing stridor and was admitted and again treated with racemic adrenaline and a four-day course of oral dexamethasone. She was subsequently discharged. White lesions were noted on the tongue and were treated with topical nystatin. Four days later, the child presented to the emergency room with recurrence of stridor and fever and new onset of drooling. She had a respiratory rate of 44 breaths/min, heart rate of 170 beats/min, blood pressure of 90/58 mmHg, oxygen saturation of 98% and temperature of 39.6°C. She was in moderate respiratory distress, with marked stridor. Examination of the oropharynx revealed ulcerative lesions on the anterior tongue, hard and soft palate, and posterior pharynx. Laboratory studies revealed a white blood cell count of 18.1x109/L (74% neutrophils, 23% lymphocytes and 3% monocytes). Other hematological values were normal. A laryngobronchoscopy was performed and revealed that the mucosa of the laryngopharynx was studded with discrete white lesions on a background of mucosal inflammation with severe reduction of airway calibre requiring intubation (Figure 1). The subglottis and the tracheobronchial tree were severely inflamed but had no discrete lesions.

Patients commonly complain of discomfort at the angle of the mouth following tonsillectomy. This can be attributed to trauma sustained during the procedure. A prospective, patient-blinded, controlled trial of 34 tonsillectomies was performed using a protective, plastic oral guard. A blinded observer recorded postoperative pain and clinically evident trauma to the angle of the mouth. The patient group in whom the guard was used had a significantly lower incidence of labial trauma (pp