Characterization of isolated liver sinusoidal endothelial cells for liver bioengineering.

BACKGROUND: The liver sinusoidal capillaries play a pivotal role in liver regeneration, suggesting they may be beneficial in liver bioengineering. This study isolated mouse liver sinusoidal endothelial cells (LSECs) and determined their ability to form capillary networks in vitro and in vivo for liver tissue engineering purposes. METHODS AND RESULTS: In vitro LSECs were isolated from adult C57BL/6 mouse livers. Immunofluorescence labelling indicated they were LYVE-1+/CD32b+/FactorVIII+/CD31-. Scanning electron microscopy of LSECs revealed the presence of characteristic sieve plates at 2 days. LSECs formed tubes and sprouts in the tubulogenesis assay, similar to human microvascular endothelial cells (HMEC); and formed capillaries with lumens when implanted in a porous collagen scaffold in vitro. LSECs were able to form spheroids, and in the spheroid gel sandwich assay produced significantly increased numbers (p = 0.0011) of capillary-like sprouts at 24 h compared to HMEC spheroids. Supernatant from LSEC spheroids demonstrated significantly greater levels of vascular endothelial growth factor-A and C (VEGF-A, VEGF-C) and hepatocyte growth factor (HGF) compared to LSEC monolayers (p = 0.0167; p = 0.0017; and p < 0.0001, respectively), at 2 days, which was maintained to 4 days for HGF (p = 0.0017) and VEGF-A (p = 0.0051). In vivo isolated mouse LSECs were prepared as single cell suspensions of 500,000 cells, or as spheroids of 5000 cells (100 spheroids) and implanted in SCID mouse bilateral vascularized tissue engineering chambers for 2 weeks. Immunohistochemistry identified implanted LSECs forming LYVE-1+/CD31- vessels. In LSEC implanted constructs, overall lymphatic vessel growth was increased (not significantly), whilst host-derived CD31+ blood vessel growth increased significantly (p = 0.0127) compared to non-implanted controls. LSEC labelled with the fluorescent tag DiI prior to implantation formed capillaries in vivo and maintained LYVE-1 and CD32b markers to 2 weeks. CONCLUSION: Isolated mouse LSECs express a panel of vascular-related cell markers and demonstrate substantial vascular capillary-forming ability in vitro and in vivo. Their production of liver growth factors VEGF-A, VEGF-C and HGF enable these cells to exert a growth stimulus post-transplantation on the in vivo host-derived capillary bed, reinforcing their pro-regenerative capabilities for liver tissue engineering studies.

Socioeconomic deprivation and the burden of head and neck cancer-Regional variations of incidence and mortality in Merseyside and Cheshire, North West, England.

OBJECTIVES: The aim of this longitudinal study was to examine the distribution of head and neck cancer (HANC) disease burden across the region comparing it to national trends. DESIGN: We undertook a retrospective study of routine data combining it with indicators of deprivation and lifestyle at small geographical areas within the 9 Local Authorities (LAs) of Merseyside and Cheshire Network (MCCN) for head and neck cancers. Data from the North West of England and England were used as comparator regions. SETTING: This research was undertaken by the Cheshire and Merseyside Public Health Collaborative, UK. PARTICIPANTS: The Merseyside and Cheshire region serves a population of 2.2 million. Routine data allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and C30-C32 within 3 cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis. MAIN OUTCOME MEASURES: Directly age-standardised incidence rates and directly age-standardised mortality rates in the LAs and comparator regions were measured. Lifestyle and deprivation indicators were plotted against them and measured by Pearson's correlation coefficients. RESULTS: The incidence of head and neck cancer has increased across the region from 1998-2000 to 2008-2010 with a peak incidence for Liverpool males at 35/100 000 population. Certain Middle Super Output Areas contribute disproportionately to the significant effect of incidence and mortality within LAs. Income deprivation had the strongest correlation with incidence (r = .59) and mortality (r = .53) of head and neck cancer. CONCLUSION: Our study emphasises notable geographical variations within the region which need to be addressed through public health measures.

Diphtheria: a case report.

OBJECTIVE: We report a case of diphtheria in an elderly patient, with a fatal outcome. METHOD: Case report and a review of the literature concerning the current recommended guidelines on detection of, and response to, diphtheria. RESULTS: Although still rare, cases of diphtheria are being reported with increasing frequency in the UK, possibly as a result of immigration and travel. A high index of suspicion, rapid detection of carriers, and instigation of treatment and vaccination are the mainstays of management. CONCLUSION: Diphtheria can mimic other forms of acute upper airway obstruction and can lead to a fatal outcome. Otorhinolaryngological surgeons need to consider this re-emergent disease as a potential diagnosis in patients with an unusual presentation of airway obstruction.

Inflammatory pseudotumour in the submandibular region.

We present a rare case of inflammatory pseudotumour in the submandibular region. A review of the literature revealed that this is only the second case of inflammatory pseudotumour in the submandibular region to be reported. Clinical presentation and management of this condition are discussed.

Real-time detection of epileptiform activity in the EEG: a blinded clinical trial.

The aim of this study was to determine the performance of a PC-based system for real-time detection and topographical mapping of epileptiform activity (EA) in the EEG during routine clinical recordings. The system incorporates a mimetic stage to locate candidate spikes (including sharp-waves) followed by two expert-system-based stages, which utilize spatial and wide-temporal contextual information in deciding whether candidate events are epileptiform or not. The data comprised 521 consecutive routine clinical EEG recordings (173 hours). Performance was evaluated by comparison with three independent electroencephalographers (EEGers-I). A second group of two EEGers (EEGers-II) separately interpreted the spike topographical maps and, for EEGs categorized as containing only questionable EA by the detection system, reviewed 6 sec segments of raw EEG centered on each questionable event. Thirty-eight of the EEGs were considered to contain definite EA by at least two of EEGers-I. The false detection rate of the system was 0.41 per hour. The system was found to have a sensitivity of 76% and a selectivity of 41% for EEGs containing definite EA. However, it only missed detection of EA in 5% of the recordings. EEGers-II agreed with EEGers-I on the distribution (generalized, lateralized, focal, multifocal) of EA in 79% of cases. This is by far the largest clinical evaluation of computerized spike detection reported in the literature and the only one to apply this in routine clinical recordings. The false detection rate is the lowest ever reported, suggesting that this multi-stage rule-based system is a powerful and practical tool in clinical electroencephalography and long-term EEG monitoring.

Self-reported depression and suicide attempts among U.S. women physicians.

OBJECTIVE: Studies examining suicide rates for U.S. women physicians and other U.S. women have found odds ratios as high as 4 to 1. Although such reports are controversial and are based on small groups (N = 17 to 49 suicides), they are often cited as evidence of a high prevalence of psychopathology among women physicians. METHOD: The authors used the results of the Women Physicians' Health Study (N = 4,501), a large, nationally distributed questionnaire, to assess the lifetime prevalence of self-identified depression and suicide attempts among U.S. women physicians. RESULTS: An estimated 1.5% (N = 61) of U.S. women physicians have attempted suicide, and 19.5% (N = 808) have a history of depression. Those who were born in the United States, were not Asian, had histories of cigarette smoking, alcohol abuse or dependence, sexual abuse, domestic violence, poor current mental health, more severe harassment, or a family history of psychiatric disorders were significantly more likely to report suicide attempts or depression. Depression was more common among those who were not partnered, were childless, had a household gun, had more stress at home, drank alcohol, had worse health, or had a history of obesity, chronic fatigue syndrome, substance abuse, an eating disorder, or another psychiatric disorder and among those who reported working too much, career dissatisfaction, less control at work, and high job stress. Strata reporting higher rates of depression tended to show higher (although usually nonsignificant) rates of suicide attempts. CONCLUSIONS: Depression is approximately as common among U.S. women physicians as among other U.S. women, but suicide attempts may be fewer. A number of conditions may help identify women physicians at high risk for suicide attempts and depression.

Evaluation of the Amicus Separator in the collection of apheresis platelets.

BACKGROUND: A new apheresis instrument, the Amicus Separator with software versions 2.13 and 2.34, was evaluated for component yields, collection efficiency, and incidence of donor and transfusion recipient reactions. The Amicus was also compared to the Spectra Leukocyte Reduction System (LRS) with version 5 software. STUDY DESIGN AND METHODS: Single and double apheresis platelets (APs) were collected at two locations. The targeted platelet yields were 4.0 x 10(11) for single APs and 6.8 x 10(11) for double APs. One location used a double-needle procedure, and the other used a single-needle procedure. Along with 28 of the Amicus procedures (14 at each of two locations), the same donors underwent single or double AP collections on the Spectra LRS. APs were tested for platelet yields and residual white cells. APs were transfused in three hospitals. Donor and transfusion recipient reactions and technical problems were documented. RESULTS: The Amicus Separator efficiently collected single APs (n = 59) and double APs (n = 62) with mean platelet yields of 4.2 x 10(11) and 6.5 x 10(11), respectively. When inlet line alarms occurred in single-needle procedures, platelet yields were lower and collection times were longer. All APs were white cell-reduced below 5.0 x 10(6), and all but one AP were white cell-reduced below 1.0 x 10(6) without filtration. Component yields from the paired Amicus and Spectra LRS procedures were comparable. Collection times (excluding reinfusion/rinseback) were 20 to 23 minutes faster on the Amicus Separator. No serious donor or transfusion recipient reactions occurred. CONCLUSION: The Amicus Separator provided satisfactory platelet yields and collection efficiency, with shorter collection times than did the Spectra LRS, and it white cell-reduced components without filtration.

Otitis media with effusion: a disability or not?

Otitis media with effusion (OME) is a disease most commonly affecting the paediatric population. However, it is a condition that is also seen in adults and does lead to significant morbidity. We studied the effect of surgical treatment of OME in an adult population and found that the subjective relief of symptoms exceeded the objective audiometric gain. In children where subjective symptoms are perhaps more difficult to assess the clinician needs to beware of underestimating the effect of a hearing loss.

Pharyngocutaneous fistula following total laryngectomy and post-operative vomiting.

The significance of post-operative vomiting as a risk factor in the development of a pharyngocutaneous fistula was examined. The case records of 50 consecutive patients undergoing laryngectomies (39 men, 11 women, average age 64 years) were examined, 17 also underwent a simultaneous radical neck dissection. A fistula developed in eight patients (16%) and the median time to its diagnosis was 11 days (range 3-15 days). Several potential risk factors were examined including age, gender, previous radiotherapy, TNM stage, differentiation of tumour, simultaneous radical neck dissection and also the occurrence of vomiting post-operatively. In this series of patients only vomiting in the early post-operative period appeared to be related to the development of a fistula (regression summary: R2 = 0.6, t-value 5.6, P < 0.0001). An episode of vomiting was recorded in eight patients and of these six (75%) subsequently developed a fistula. The median time of post-operative vomiting was 7.5 days (range 1-10 days) and the diagnosis of a fistula occurred at a mean of 1.2 +/- 0.4 days after the episode of vomiting. In a study of this nature it is not possible to conclude that a causal relationship exists between vomiting and fistula development. However, if this is the case a potential means of decreasing the incidence of fistulae following laryngectomy may be available.

Tympanosclerosis and mini grommets: the relevance of grommet design.

Fifty children with otitis media with effusion undergoing grommet insertion had into one ear a Mini-titanium grommet inserted and into the other ear a Mini-teflon grommet. Post-operative follow-up until after extrusion of the grommets demonstrated only a small difference between the extrusion times of the two grommets (a significant difference of 41 days) and no difference in the degree of tympanosclerosis seen with each grommet. We propose that the mass of a grommet appears to play less of a role than has previously been suggested in the pathogenesis of tympanosclerosis following grommet insertion and that duration of intubation may be the most significant factor.

Airway obstruction with stridor due to nasal secretions.

Two cases of non-fatal airway obstruction by nasal secretions are described. The diagnosis was made after laryngoscopy and the features which suggested this previously undescribed aetiology were: depression of conscious level; poor oral hygiene; and irregular friable mass with mucoid areas obstructing the airway. The diagnosis was confirmed by histological examination of the obstructing material which was composed of laminated fragments of squamous epithelium, keratin debris and mucus. It is suggested that these masses form in the post-nasal space and then become dislodged descending into the larynx, where they cause partial laryngeal obstruction and stridor. In patients whose conscious level is depressed and who have poor oral hygiene, nasal secretions should be considered as a cause of sudden unexplained airway obstruction and stridor.

A multistage system to detect epileptiform activity in the EEG.

A PC-based system has been developed to automatically detect epileptiform activity in sixteen-channel bipolar EEG's. The system consists of three stages: data collection, feature extraction, and event detection. The feature extractor employs a mimetic approach to detect candidate epileptiform transients on individual channels, while an expert system is used to detect focal and nonfocal multichannel epileptiform events. Considerable use of spatial and temporal contextual information present in the EEG aids both in the detection of epileptiform events and in the rejection of artifacts and background activity as events. Classification of events as definite or probable overcomes, to some extent, the problem of maintaining high detection rates while eliminating false detections. So far, the system has only been evaluated on development data but, although this does not provide a true measure of performance, the results are nevertheless impressive. Data from 11 patients, totaling 180 minutes of sixteen-channel bipolar EEG's, have been analyzed. A total of 45-71% (average 58%) of epileptiform events reported by the human expert in any EEG were detected as definite with no false detections (i.e., 100% selectivity) and 60-100% (average 80%) as either definite or probable but at the expense of up to nine false detections per hour. Importantly, the highest detection rates were achieved on EEG's containing little epileptiform activity and no false detections were made on normal EEG's.

Pre-admission assessment clinics: an answer to non-attendance for ENT operations.

Non-attendance by patients for elective surgery with insufficient time to find replacement leads to wasted theatre time and wasted resources. The introduction of pre-admission clinics at the North Riding Infirmary, Middlesbrough has alleviated this problem and has led to considerable financial savings. A 12 month prospective study has shown an increase in operations performed from 3738 to 3944. Financial savings have not been taken into consideration in this publication.

Retropharyngeal haematoma: a diagnosis for concern?

Three cases of retropharyngeal haematoma are described. In one case there was underlying aneurysm of the carotid artery which could have led to significant morbidity if undetected.

The mini-grommet and tympanosclerosis: results at two years.

One hundred and sixteen children with otitis media with effusion (OME) underwent surgery with grommet insertion. A conventional Shah grommet was used in one ear, and a Mini-Shah grommet in the other. Final review of the subjects two years after surgery revealed a significantly lesser degree of tympanosclerosis in the ear into which the Mini-Shah grommet had been inserted. This benefit might have resulted from the lesser mass of the mini-tube or its shorter duration in situ.

Fistula between the external auditory canal and the temporomandibular joint: a rare complication of otitis externa.

Otitis externa is a relatively common complication of ear syringing. Temporomandibular joint complications of otitis externa are rare. A case of otitis externa with communication between the external auditory canal and the temporomandibular joint is described.

Fenestration and occlusion of the posterior semicircular canal for benign positional vertigo.

Benign positional vertigo is a potentially disabling condition characterized by episodic vertigo following certain provocative head movements. In most patients it is self limiting; however, in a few it may prove intractable, causing considerable social morbidity. In these patients surgery may be considered. Surgery previously involved section of the vestibular or singular nerves, involving a significant risk to hearing and to the facial nerve. Ablation of the labyrinth may even be considered. The new surgical technique of occlusion of the posterior semicircular canal has proved to be curative in most patients with benign positional vertigo with little risk of hearing. This paper describes our experience of fenestration and occlusion of the posterior semicircular canal in four patients.

The implementation of audit in an ENT unit.

ENT Departments in the United Kingdom are faced with increasing pressure from government, management and the Colleges responsible for surgical training to introduce formal medical self audit. The plethora of guidelines and publications on the subject rarely address the differences in clinical practice between general medicine or surgery and that of otolaryngology. Clearly the lead in the introduction of medical audit will come from the appropriate specialist associations; however, this paper aims to share the experience of the implementation of audit in one otolaryngology, head and neck surgery unit and offer suggestions for a programme elsewhere.