Samter's triad with aural involvement: a novel approach to management.

BACKGROUND: Samter's triad is a well described condition manifesting as chronic rhinosinusitis with nasal polyposis, asthma and aspirin intolerance in a non-atopic individual. The underlying mechanism is still to be fully elucidated. However, aural disease has not been widely reported in these patients. In the few reported cases, most patients underwent major surgery with varying degrees of success. CASE REPORT: We report two Samter's triad patients with aural involvement. Both were successfully managed by conservative treatment, thus avoiding the need for major surgery. It appears that more Samter's triad patients may have aural disease than previously thought. CONCLUSION: We report good outcomes with conservative treatment, which is relevant because aural disease tends to reoccur in these patients.

Infliximab for autoimmune inner ear disease: case report and literature review.

OBJECTIVES: This study aimed (1) to report the long-term effects of infliximab, a murine monoclonal antibody directed against tumour necrosis factor-α, on autoimmune inner ear disease, and (2) to discuss dilemmas surrounding the long-term management of autoimmune inner ear disease. CASE REPORT: A 49-year-old man presented with sudden-onset, left-sided, sensorineural hearing loss, tinnitus and vertigo. He was prescribed oral prednisolone, with benefit. Over several subsequent months, he experienced frequent relapses and progressive deterioration of high-frequency hearing bilaterally. Multiple agents failed to stabilise his condition. Following infliximab treatment, there was a documented and sustained improvement in his hearing and tinnitus. He stopped the treatment after 46 weeks, with rapid relapse of his condition. His hearing recovered quickly again after recommencing infliximab. CONCLUSION: The benefits of prolonged infliximab use and potential side effects must be balanced against allowing the disease to take its course, with progressive deafness. Randomised controlled trials are required to assess infliximab's optimal duration of use, long-term efficacy and safety in the treatment of autoimmune inner ear disease.

The fate of granulosa cells following premature oocyte loss and the development of ovarian cancers.

This review examines the importance of the epithelial origin of granulosa cells and their possible contribution to the development of ovarian cancers in three animal models. We hypothesise that undifferentiated granulosa cells, devoid of their germ cell regulator, retain their embryonic plasticity and may give rise to ovarian cancers of epithelial origin. Dazl-KO and FancD2-KO mice and BMP15-KO sheep are animal models in which germ cells or oocytes are lost at specific stages of follicular formation or growth, leaving behind clusters of residual, but healthy somatic cells. A common feature in Dazl- and Fancd2-KO animals following germ cell/oocyte loss is the presence of sex cords and intraovarian epithelial ducts or tubules. In Dazl-KO mice, cord/tubule-like structures, OSE invaginations and clusters of steroidogenic cells became increasingly prominent with age, but these abnormal structures remained benign. In Fancd2-KO mice, the formation of sex-cords and intraovarian tubules lead to the formation of tumours with multiple phenotypes including luteomas, papillary cysts and malignant carcinomas (e.g. adenocarcinomas). In BMP15-KO sheep, oocytes die as follicles start to grow, leaving 'nodules' containing granulosa cells with a capacity to respond to follicle stimulating hormone and synthesize inhibin. Thereafter, these nodules coalesced and a range of benign solid or semi-solid tumour phenotypes developed. We conclude that premature loss of oocytes, but not granulosa cells, leads to tumour formation with multiple phenotypes. Moreover, the severity of tumour development is linked to both the specificity of the mutation and the timing of oocyte loss relative to that of follicular formation.

Radiological airway changes following bipolar radiofrequency volumetric tissue reduction.

OBJECTIVE: To characterise the appearance of lesions of the tongue base and soft palate induced by bipolar radiofrequency volumetric tissue reduction, using magnetic resonance imaging up to six weeks post-procedure. METHODS: Five men with sleep-disordered breathing were treated with one session of bipolar radiofrequency volumetric tissue reduction to a number of sites, including the tongue base and soft palate. Magnetic resonance imaging was performed pre-operatively and one week and six weeks after surgery. RESULTS: Lesions were visible from day one. T1 (spine lattice relaxation Time)-weighted images demonstrated areas of central hyperintensity, reflecting haemorrhagic, coagulative necrosis, surrounded by hypointensity, representing oedema; corresponding short tau inversion recovery (STIR) sequences showed central hypointensity with surrounding high signal. The lesions expanded up to day three and then gradually diminished, but were still evident at week six on short tau inversion recovery images. CONCLUSION: The characterisation of lesions induced by bipolar radiofrequency volumetric tissue reduction enables us to elucidate the pathophysiology of this procedure, to optimise treatment benefits and clinical outcomes, and to explain patient symptoms.

Parotid duct ligation for treatment of drooling in children with neurological impairment.

OBJECTIVE: Multiple surgical procedures have been advocated for the management of problematic drooling in neurologically impaired children. Parotid duct ligation is a quick and simple operation conducted via an intra-oral approach and usually performed simultaneously with other procedures. In this study, we aimed to evaluate the effectiveness of parotid duct ligation as a discrete procedure. METHODS: All children who underwent bilateral parotid duct ligation as the solitary operative intervention at that time, between February 2003 and September 2006, were included in the study. RESULTS: Ten children were studied. Surgery was successful in 80 per cent of cases. One patient (10 per cent) had a post-operative wound infection. CONCLUSIONS: Bilateral parotid duct ligation is an effective yet conservative operation for drooling in neurologically impaired children. It requires minimal surgical dissection and has a low morbidity rate. It should be considered as a potential first-line procedure in children who aspirate, and as a further surgical option in anterior droolers or those who continue to drool unacceptably following prior surgical intervention.

Following anterior resection for rectal cancer, defunctioning ileostomy closure may be significantly delayed by adjuvant chemotherapy: a retrospective study.

OBJECTIVE: A temporary loop ileostomy is often created to minimize the impact of peritoneal sepsis from an anastomotic dehiscence following colo-anal or low colorectal anastomosis. These stomas are not without complications. Clinicians tend to advise patients that their loop ileostomy will be reversed within 6-12 weeks of formation. However, factors such as adjuvant chemotherapy may affect the timing of closure. The aim of this study was to review the time between formation and closure of loop ileostomies following total mesorectal excision in patients with rectal cancer. METHOD: A retrospective study of 50 patients with loop ileostomies to defunction total mesorectal excisions for rectal cancer, between April 2002 and July 2005. RESULTS: Of the 50 patients with defunctioning loop ileostomies, 24 received adjuvant chemo-radiotherapy, and 26 did not. There was a 28% morbidity. The overall median time from formation to closure was 142 days (35-575). Median time from formation to closure in those with adjuvant therapy was 197 days (35-575) and in those with no adjuvant therapy was 133 days (75-395). This was a significant delay (P = 0.049). Sixteen stomas were not closed to date. CONCLUSION: Time between formation and closure of loop ileostomy following anterior resection of rectum is significantly delayed by adjuvant chemotherapy. Because of their high morbidity, defunctioning ileostomies should be closed as early as medically possible, especially if adjuvant chemotherapy is planned.

An unusual case of segmental clavicle fracture.

Fracture of the clavicle is a common traumatic injury and comprises 4% of all fractures in adults. Amongst these, midshaft injuries account for the majority and medial fractures are uncommon. Whilst segmental fractures have been reported in the literature, concurrent lateral and medial injuries are very rare. These injuries are, therefore, susceptible to being missed, due to failure to look for a second injury after the initial diagnosis, and difficult X-ray interpretation around the area of the medial clavicle. The nature of segmental fractures can pose a difficult management problem for numerous reasons, and initial operative fixation is usually indicated. Early diagnosis is therefore imperative, and as such, clinical examination is essential even if an obvious mid or lateral shaft fracture is seen on X-ray. This unusual case of combined lateral and medial fractures was initially missed and the presentation and management is discussed.

Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

Formation of ovarian follicles during fetal development in sheep.

The origin of follicle (i.e., pregranulosa) cells that become the somatic component of primordial follicles is obscure. In addition, information regarding the structural changes that accompany the concomitant regression of ovigerous cords and the appearance of primordial follicles is lacking. In the present study, ovine ovaries collected at frequent time intervals between Day 38 and Day 100 of fetal life were examined by light and electron microscopy. To gain new information regarding the origin of follicular cells, incorporation of 5-bromo-2'-deoxyuridine was used to identify proliferating cells at selected stages of development. Based on the location and identity of proliferating cells, apoptotic cells, and sequential changes in histoarchitecture, we hypothesize 1) that most (i.e., >95%) of the granulosal cells in newly formed primordial follicles originate from the ovarian surface epithelium; 2) that the sequential events leading to follicle formation take place entirely within ovigerous cords, with the first follicles forming at the interface of the cortex and medulla; and 3) that the loss (i.e., >75%) of germ cells, but not of somatic cells, within the ovigerous cords is a means by which each surviving oocyte gains additional pregranulosal cells before follicle formation. Conceptual models detailing the chronology of developmental events involved in the formation of primordial follicles in sheep are discussed.

Quantification of polynuclear aromatic hydrocarbons in transformer oils by enzyme immunoassay.

Many polynuclear aromatic hydrocarbons (PAHs) are either known or suspected carcinogens and are a common constituent of mineral oils. Due to the large number of possible PAH structures, standard quantification methods fail since they either lack specificity or are too complex, requiring individual fractionation, identification, and quantification. A rapid, low-cost, novel analytical screening method, incorporating a silica-based solid-phase extraction (SPE) method linked to co-solvent dilution and quantification of total and carcinogenic PAH levels by immunoassay, is reported here. The method yielded high extraction efficiencies and minimal matrix effects. This novel approach yielded total and carcinogenic PAH levels x 5.7 and x 126, respectively, lower than that recorded by the industry-recognised BS2000 Pt. 346 (IP346) method which estimates the polyaromatic carbon (PAC) content of oils by gravimetry. The method is expected to be of benefit where an indication of PAH levels in oils is important for purchasing, management or disposal purposes and also for risk assessment and for appropriate labelling of oils in line with current legislation.

CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors.

The AC133 antigen is a novel antigen selectively expressed on a subset of CD34+ cells in human fetal liver, bone marrow, and blood as demonstrated by flow cytometric analyses. In this study, we have further assessed the expression of AC133 on CD34+ cells in hemopoietic samples and found that there was a highly significant difference between normal bone marrow and cord blood versus aphereses (p <0.0001) but not between bone marrow and cord blood. Most of the clonogenic cells (67%) were contained in the CD34+AC133+ fraction. Compared with cultures of the CD34+AC133- cells, generation of progenitor cells in long-term culture on bone marrow stroma was consistently 10- to 100-fold higher in cultures initiated with CD34+AC133+ cells and was maintained for the 8-10 weeks of culture. Only the CD34+AC133+ cells were capable of repopulating NOD/SCID mice. Human cells were detectable as early as day 20, with increased levels (67%) apparent 40 days post-transplantation. Five thousand CD34+AC133+ cells engrafted about 20% of the mice, while no engraftment was observed in animals transplanted with up to 1.2 x 10(5) CD34+AC133- cells. The CD34+AC133+ population was also enriched (seven-fold) in dendritic cell precursors, and the dendritic cells generated were functionally active in a mixed lymphocyte reaction assay. AC133+ cells should be useful in the study of cellular and molecular mechanisms regulating primitive hemopoietic cells.

Carcinogenicity assessment of lonidamine by dietary administration to Sprague-Dawley rats.

Following chronic dietary administration of 20, 60 and 180 mg/kg per day of lonidamine for 2 years to groups of Sprague-Dawley rats, treatment-related non-tumour findings seen microscopically included the following: atrophy of the testis with associated changes in epididymis and pituitary at all dosages; neuropathy in the sciatic nerve accompanied by skeletal muscle atrophy which was dose-related, particularly in male animals. Neither the incidence of tumour-bearing animals, nor the spectrum of tumours seen, was significantly changed. In the females given 180 mg/kg per day an overall reduction in tumour incidence was noted, which was reflected in a significant reduction (P < 0.001) in mammary tumours.

Age-related changes in thyroid structure and function in Sprague-Dawley rats.

Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.

Age-related variations in renal structure and function in Sprague-Dawley rats.

Data from 500 male and 500 female Sprague-Dawley rats used as controls in studies performed at Huntingdon Research Centre to assess the safety of drugs were sampled at 17, 30, 56, 82, or 108 weeks of age. Plasma urea nitrogen levels remained constant, except in aged males. Aging caused increased proteinuria and decreased urinary concentrating ability, in addition to increased size, weight, and degree of cortical scarring of kidneys. Chronic progressive nephropathy, first seen histopathologically at 30 weeks of age, accounted for these changes and ultimately affected 81% of male and 44% of female rats. One-fifth of two-year-old male rats had diffuse parenchymal damage and a small number also had secondary hyperparathyroidism. Other notable changes included basophilic (often colloid-filled) cortical tubules, mononuclear cell infiltrations, parenchymal and pelvic mineralization, urothelial hyperplasia, and pyelonephritis. Miscellaneous low incidence findings included one lipomatous tumour and generalized lymphosarcoma.

The toxicity of beta-carotene.

The safety of beta-carotene, a widely distributed food colorant was assessed in tests with cells and in sub-chronic and chronic experiments with animals. Mutagenicity evaluations which included the standard Ames test and the micro-nucleus test of bone marrow cells from mice showed that beta-carotene exerted no mutagenic properties. Embryotoxicity studies in rats and rabbits showed that there was no evidence of embryotoxicity and a multiple generation study in rats showed that there was no interference with the reproductive function in rats given oral doses of up to 1000 mg/kg/day. Chronic toxicity was studied in a 2-year study with dogs in a toxicity/tumorigenicity study in rats and in a mouse carcinogenicity study. Histological findings in the livers of treated dogs and mice, but not in rats, included vacuolated cells with eccentric nuclei which were distributed in periportal areas and which were frequently associated with minimal lipid deposition. There was no evidence that the vacuolisation was dose-related. It was considered that the vacuolated cells were fat storage cells. There was no effect on the tumor profiles in the rat and the mouse studies.

Tumorigenic and toxic effect of O,S-dibenzoyl thiamine hydrochloride in prolonged dietary administration to rats.

The chronic toxicity of O,S-dibenzoyl thiamine hydrochloride (DBT) was studied by prolonged dietary administration to rats at dosages of 1000 and 10 000 ppm. The study confirmed the low toxicity of this compound and absence of carcinogenicity.

Histopathological and laboratory assessment of visual dysfunction.

The currently available methods of assessing ocular toxicity are discussed. Manifestations of ocular toxicity are best described clinically; histopathological examination of the eye is beset with problems of preparing the eye for morphological examinations. Electron microscopy is essential to look for chemically induced side effects at the cellular level. Mechanisms of ocular toxicity are poorly understood, and the limitation of animal studies in predicting side effects in man must be appreciated.