Interaction between synaptic inhibition and glial-potassium dynamics leads to diverse seizure transition modes in biophysical models of human focal seizures.

How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K (+)] o ) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30-60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2-3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10-20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K (+)] o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K (+)] o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K (+)] o glial buffering under abnormal conditions may explain different types of ictal transitions and dynamics during propagated seizures in human focal epilepsy.

Reversible hearing loss following cryptococcal meningitis: case study.

BACKGROUND: Sensorineural hearing loss is a recognised complication of cryptococcal meningitis. The mechanism of hearing loss in patients with cryptococcal meningitis is different from that in bacterial meningitis. CASE REPORT: An immune-competent man with cryptococcal meningitis presented with sudden onset, bilateral, severe to profound sensorineural hearing loss and vestibular dysfunction. He was initially evaluated for cochlear implantation. However, he had a significant recovery; he no longer required surgery and was able to cope without a hearing aid. CONCLUSION: Typically, cochlear implantation is performed with some urgency in patients with hearing loss post-bacterial meningitis, because of the risk of labyrinthitis ossificans. However, this process has not been described in patients with cryptococcal meningitis. Furthermore, patients with hearing loss associated with cryptococcal meningitis have shown varying degrees of reversibility. In this case report, hearing loss from cryptococcal meningitis is compared with that from bacterial meningitis, and the need for cochlear implantation in patients with cryptococcal meningitis is discussed.

Pulmonary balloon dilation for valvular and arterial stenosis.

The use of balloon catheters to dilate obstructed vascular lesions represents one of the major advances in cardiology and dates back to 1964 when Dotter and Judkins reported their experience in dilating arteriosclerotic obstructive lesions. Since that time, the technique of balloon dilation has been used extensively for coronary and peripheral vascular lesions but also has been applied to such diverse cardiac lesions as pulmonic stenosis, mitral stenosis, aortic stenosis, aortic coarctation, superior vena caval and pulmonary venous obstructions. Balloon dilation has been used for both valvular and arterial pulmonary stenosis. The purpose of this study is to report on our initial experience in Hawaii with balloon dilation of valvular pulmonic stenosis and also with dilation of peripheral pulmonary artery stenosis due to congenital causes and as a residual postoperative lesion.

Facial nerve outcomes in functional vestibular schwannoma surgery: less than total tumour excision significantly improves results.

OBJECTIVES: To determine the implications of a functional approach to vestibular schwannoma surgery, with facial nerve function prioritised higher than total tumour excision. STUDY DESIGN: A case-control study in a tertiary referral neurotology clinic. PATIENTS: A 'functional' surgical group treated after April 2007 (n = 44, mean cerebellopontine angle dimension 27 mm), and an 'excisional' surgical group matched for tumour size, treated from 1997 to April 2007 (n = 115). INTERVENTION: Change to more functional surgical approach. PRIMARY OUTCOME: facial nerve status. Secondary outcome: tumour recurrence in less-than-total tumour excision. RESULTS: Facial nerve preservation: 77 per cent House-Brackmann grade I-II in functional group at 12 months, versus 57 per cent grade I-II in excisional group (p = 0.027). Tumour recurrence: 1 per cent in total excision group, 2 per cent in near-total group and 40 per cent in sub-total group. CONCLUSION: A functional approach to vestibular schwannoma surgery improves facial nerve preservation outcomes and reduces the requirement for facial nerve rehabilitative interventions. Tumour recurrence rates are low in near-totally excised lesions but significant if only sub-total excision is achieved.

Front-line epistaxis management: let's not forget the basics.

OBJECTIVE: We postulated that epistaxis patients frequently have their nose packed in the accident and emergency department without any reasonable prior attempt at nasal assessment and nasal cautery. DESIGN: Telephone survey of 104 accident and emergency departments. RESULTS: A 100 per cent response rate was achieved. In all but one of the departments surveyed, first line management was carried out by accident and emergency doctors. Seventy-four per cent of accident and emergency doctors perform nasal cautery as first line management. Within accident and emergency departments, the availability and usage of head illumination, nasal speculums, topical anaesthesia and suction was grossly suboptimal. Only one-sixth of the accident and emergency doctors surveyed had received training in the management of epistaxis, whilst 81 per cent of accident and emergency departments would admit nasally packed patients under the ENT team. CONCLUSION: Despite the majority of accident and emergency doctors claiming to attempt nasal cautery before packing, this is unlikely to be effective if performed without the correct equipment. Better training and equipment need to be provided to accident and emergency doctors in order to optimise the management of epistaxis patients. This could potentially reduce inappropriate admissions.

Lateral soft tissue neck X-rays: are they useful in management of upper aero-digestive tract foreign bodies?

OBJECTIVES: To assess the value of lateral soft tissue neck X-rays in patients presenting with upper aero-digestive tract foreign bodies. DESIGN: Retrospective study. INCLUSION CRITERIA: (1) Patients referred to the ENT team, via either the accident and emergency department or their general practitioner; (2) a history of a non-aspirated, upper airway, aero-digestive tract foreign body; and (3) a lateral soft tissue neck X-ray taken on admission. RESULTS: A total of 62 patients met the inclusion criteria. Twenty-four patients (38.7 per cent) had positive findings on lateral soft tissue neck X-ray. 'Soft' signs, such as widened pre-vertebral shadow and loss of lordosis, were seen in all 24 patients, and foreign bodies were visualised in six patients. Overall, lateral soft tissue neck X-rays were helpful in the management of 32 patients (51.6 per cent). Rather worryingly, doctors in the accident and emergency and ENT departments missed 79.2 and 66.6 per cent of the positive findings, respectively. CONCLUSIONS: A lateral soft tissue neck X-ray is a helpful tool in the management of patients presenting with upper aero-digestive tract foreign bodies. Junior doctors need better radiology training.

Topical antibiotic ototoxicity: does it influence our practice?

INTRODUCTION: We hypothesised that general practitioners and ENT specialists manage discharging ears differently. This study was designed to investigate this further. METHODS AND MATERIALS: Postal questionnaires were sent to all general practitioners in the Birmingham area and all UK consultants on the British Association of Otolaryngology-Head and Neck Surgery address list. RESULTS AND DISCUSSION: In the presence of an intact tympanic membrane, 99 per cent of consultants and 90 per cent of general practitioners would use topical antibiotics. In the presence of a perforated tympanic membrane, 97 per cent of consultants would continue to use topical antibiotics, compared with only 43 per cent of general practitioners. This was attributed to a fear of ototoxicity. If a topical non-ototoxic antibiotic of proven efficacy could be made available, 93 per cent of consultants and 88 per cent of general practitioners in this study would seriously consider using it as first line treatment. CONCLUSION: The majority of general practitioners would not use topical antibiotics in the presence of a perforated tympanic membrane. Most doctors would consider using a non-ototoxic topical antibiotic as first line treatment should one be made available.

Treatment of pinna haematoma with compression using Leonard buttons.

The standard treatment of a pinna haematoma involves drainage and compression to prevent recurrence and subsequent disfigurement. Compressive methods can be non-invasive or invasive, utilising a head bandage or through and through sutures, respectively, to keep compression in place. Leonard buttons are effective alternative compressive devices. They are simple to use and easily available.

How we do it: blood contamination during management of epistaxis--awareness, utilization and availability of barrier protection.

There is a significant risk of blood contamination during the non-surgical management of epistaxis. Contamination beyond gloves happens in 55% of cases and the contamination risk to eyes as high as 18%. There is a lack of awareness and a majority of ENT doctors underestimate this risk. Protective barrier equipment and eye protection in particular are suboptimally available in all clinical areas where epistaxis is dealt with. Consequently, there is poor utilization of protective barrier equipment.

How we do it: a practical approach to Foley catheter posterior nasal packing.

KEY POINTS: There are various effective treatment options for refractory posterior epistaxis including endoscopic diathermy or endoscopic artery ligation. If these treatment options are not immediately available, posterior nasal packing with Foley catheter is an effective and rapid non-surgical treatment alternative. A systematic approach is presented. The principles and mechanisms of action of the posterior nasal packing are explained. Nevertheless, there are morbidities involved and posterior packing can be painful and uncomfortable for the patient. Marking and modifying the catheter will help one inflate the balloon in the correct place and avoid the problem of nasal alar pressure necrosis.

Isolation and chromosomal assignment of 100 highly informative human simple sequence repeat polymorphisms.

One hundred highly informative simple sequence repeat (SSR) polymorphisms have been isolated and mapped to specific human chromosomes by somatic cell hybrid analysis. These markers include 97 (CA)n, 2 (AGAT)n, and a single (AACT)n repeat. All the SSRs have heterozygosities greater than 0.50 and can be amplified using identical PCR conditions. At least one SSR was detected on every chromosome, except for chromosomes 22 and Y. The frequency of (CA)n repeats on each chromosome was proportional to the relative chromosomal length, except for chromosome 15, on which a substantial excess of markers was identified.

Further evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) on chromosome 1p, and evidence for genetic heterogeneity.

Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. We examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three linkage analyses were performed: (1) CMM alone--all individuals without confirmed melanoma or borderline lesions were considered unaffected (model I); (2) CMM/DN with variable age at onset and sporadics (model II); and (3) CMM/DN using the model of Bale et al. (model III). For CMM alone and D1S47, Zmax = 3.12 at theta = .10. For D1S160 and CMM alone, Zmax = 1.76 at theta = .10. PND showed no evidence for linkage to CMM alone. Models II and III showed strong evidence for linkage to D1S47, D1S160, and PND in the set A pedigrees but not in the set B families. We tested for homogeneity of CMM/DN (model II) by splitting families into two groups on the basis of (1) the proportion of CMM/DN cases and (2) the occurrence of immune-related tumors. In group 1 there was significant evidence of heterogeneity with both D1S47 and D1S160, and in group 2 there was significant evidence of heterogeneity with D1S160. Thus, diagnostic, clinical, and genetic heterogeneity are the likely reasons that previous studies have failed to confirm linkage of CMM/DN to chromosome 1p. The results showed significant evidence for a CMM locus linked to D1S47, as well as significant evidence for heterogeneity with only a subset of the families appearing linked to chromosome 1p.