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L Michaels

Publications and source records attributed to L Michaels.

At least 19 recordsLinked to original sources
PubMed2006

The uncertainty of the surgical margin in the treatment of head and neck cancer.

We discuss our surgical philosophy concerning the subtle interplay between the size of the surgical margin taken and the resultant morbidity from ablative oncological procedures, which is ever more evident in the treatment of head and neck malignancy. The extent of tissue resection is determined by the "trade off" between cancer control and the perioperative, functional and aesthetic morbidity and mortality of the surgery. We also discuss our dilemmas concerning recent minimally invasive endoscopic microsurgical techniques for the trans-oral laser removal or co-ablation of aero-digestive tract tumours, which result in a minimal surgical margin of oncological clearance. By a process of inductive argument as to the nature of the surgical margin, we consider whether the risks of taking a lesser margin with adjuvant therapy is justified by the attendant gain in reduced surgical morbidity and the possible costs in tumour control.

Head and Neck Neoplasms↗
PubMed2006

Metastasizing pleomorphic salivary adenoma.

OBJECTIVE: To address questions about the etiology, behavior, optimal treatment, and prognosis of metastasizing pleomorphic adenoma (MPA), we undertook a review of the literature (1953-2005) and constructed a virtual series of all identified cases of MPA, metastatic lesions that are very occasionally identified in patients with a history of pleomorphic salivary adenoma and, on detailed pathological evaluation, found to exhibit all the histological hallmarks of the preceding benign lesions. DATA SOURCES: A review of the English-language literature between 1953 and 2005 using MEDLINE, secondary references identified from bibliographies of pertinent articles, and a further case from one of our institutions. DATA SYNTHESIS: A virtual case series was constructed and quantitatively analyzed. Forty-two patients with an average age of 33 years were identified. There were 20 male and 22 female patients. There was an overwhelming history of incomplete surgery for pleomorphic salivary adenoma. Most patients had locoregional recurrences before metastasis, and the mean presentation-to-metastasis latency was 16 years. Bone was the most common site for metastases (45%), followed by the head and neck (43%) and lung (36%). There was significant morbidity and mortality from distant disease, with 5-year disease-specific and disease-free survival of 58% and 50%, respectively. Developing distant lesions within 10 years of the primary tumor and presence of metastases in multiple sites were independent predictors of survival on Cox regression analysis. Metastasectomy conferred significant survival advantage over nonoperative treatment (log-rank analysis, P<.02). Chemotherapy and radiotherapy were of limited value. CONCLUSIONS: Meticulous surgery is crucial in preventing MPA. Metastatic disease carries significant morbidity and mortality and should be treated surgically when feasible.

Adenoma, Pleomorphic↗
PubMed2006

Study of a combined percutaneous local anaesthetic and the TDS system for venepuncture.

Transdermal Delivery System (TDS) is a liquid formulation which can be applied to the skin via a metered pump spray to deliver drug across skin. This placebo controlled, double blind trial compared anaesthetic properties of two TDS systems (TDS alpha and TDS beta) with placebo. The active and placebo treatments were applied to the dorsum of the hands, bilaterally and simultaneously for 5 min on 100 healthy volunteers. Following cannulation, pain perception was measured using the verbal rating score (VRS) and visual analogue score (VAS). Lidocaine plasma levels were assessed at 0 and 2 h. The VRS and VAS results show that TDS beta significantly decreased pain score compared to placebo (p < 0.02). Blood lidocaine at 2 h post application was also higher for TDS beta than for TDS alpha, suggesting that a 5 min application of TDS beta was effective in delivering local anaesthetic and accelerating the onset of skin anaesthesia prior to venous cannulation in adults.

Administration, Cutaneous↗
PubMed2006

Pharmacokinetics of a new testosterone transdermal delivery system, TDS-testosterone in healthy males.

AIMS: The Transdermal Delivery System (TDS) is a liquid formulation that can be applied to the skin via a metered pump spray to deliver drug to the systemic circulation. The aims of this study were to assess the ability of the TDS preparation to deliver testosterone systemically, and to characterize the pharmacokinetic profiles of the hormone in healthy males. METHODS: An open label, comparative, randomized placebo controlled study involving three treatments and three periods with a minimum of a 1 week washout period was conducted. Twelve healthy males received 50 mg TDS-testosterone, TDS-placebo, and 50 mg of a commercially available topical testosterone preparation (Androgel, 1% topical testosterone gel). RESULTS: The mean AUC(0,12 h) was higher following application of TDS-testosterone (61.8 ng ml-1 h), compared with Androgel (57.7 ng ml-1 h) and TDS-placebo (50.7 ng ml-1 h. The mean Cmax (0,12 h) was similar for TDS-testosterone (6.6 ng ml-1) and Androgel (6.5 ng ml-1) and these values were higher than those for TDS-placebo (5.7 ng ml-1). Analysis of variance showed that the 90% confidence intervals on the relative difference of the ratio for the AUC(0,12 h) and the Cmax (0,12 h) between TDS-testosterone and Androgel, were contained within the bioequivalence limit (80, 125%) (Cmax 89.2, 112.3% and AUC 93.5, 120.5%). Serum testosterone concentrations were lower following TDS-Placebo and were not bioequivalent either to the gel or spray. CONCLUSIONS: The TDS preparation was shown to deliver testosterone systemically to humans and the concentrations of the hormone in the 12 h following TDS administration were bioequivalent to an existing topical delivery gel.

Administration, Cutaneous↗
PubMed2006

The development of the spiral ganglion in the human foetus.

The development of the spiral ganglion was studied in steps sections of 81 human temporal bones. By the 8th week, the spiral ganglion has already separated from the vestibular ganglion. At 13 weeks two distinct populations are observed that correspond to neuron and Schwann cells. At 15 weeks the spiral ganglion has increased its distance from the cochlear duct and is surrounded by mesenchyme near the scala tympani. At 14 weeks a gradual decrease in the nucleus-to-cell area ratio was observed in spiral ganglion neurons that may reflect a morphological adaptation to function. By the 23rd week the modiolus begins to ossify and the spiral ganglion is surrounded by bony trabeculae. The time course of spiral ganglion development follows that of the stria vascularis and organ of Corti, although maturation changes are still observed in the neuronal population even beyond 20 weeks.

Cell Nucleus↗
PubMed2002

APOE genotype influences acquisition and recall following traumatic brain injury.

APOE has been demonstrated to influence traumatic brain injury (TBI) outcome. The relationship between APOE genotype and memory following TBI was examined in 110 participants in the Defense and Veterans' Head Injury Program. Memory performance was worse in those who had an APOE epsilon 4 allele (n = 30) than those who did not (n = 80), whereas genotype groups did not differ on demographic or injury variables or on measures of executive functioning. These data support a specific role for the APOE protein in memory outcome following TBI, and suggest an APOE isoform-specific effect on neuronal repair processes.

Adult↗
PubMed2002

Ossicular fixation caused by bone dust after saccus decompression surgery.

HYPOTHESIS: To highlight the clinical and histologic features of ossicular fixation produced by bone dust during mastoid surgery. BACKGROUND: Bone dust deposition in the middle ear may occur during temporal bone surgery, but the ossicular fixation that may result from it remains underreported. METHODS: A case is reported of delayed conductive hearing loss after saccus decompression surgery resulting from ossicular fixation by bone dust deposition. RESULTS: Six months after the initial surgery, the patient experienced a 45 dB conductive hearing loss. The findings on second-look tympanotomy were stapes fixation and round window niche occlusion by newly formed tissue. Histologic examination of the latter showed fibrosis and new bone formation in reaction to particles of bone dust. New bone formation is a frequent concomitant of fibrosis in the middle ear and is probably not a growth from the bone dust. CONCLUSION: The use of high-speed drilling of bone in temporal bone surgery carries the risk of bone dust particle deposition in the middle ear. Measures are discussed that can be used to prevent this complication.

Audiometry, Pure-Tone↗
PubMed2001

Prevalence of otosclerosis in an unselected series of temporal bones.

BACKGROUND: Histologic otosclerosis is a disease process without clinical symptoms or manifestations that can be discovered only by sectioning of the temporal bone at autopsy. Clinical otosclerosis is otosclerosis at a site where it causes conductive hearing loss by interfering with the motion of the stapes or of the round window membrane. Various authors have studied the prevalence of histologic otosclerosis on laboratory collections of temporal bones. Some 12% to 15% of temporal bones with histologic otosclerosis have demonstrated stapedial fixation. Using these figures for calculating the prevalence of clinical otosclerosis gives an extrapolated clinical prevalence of 0.99% to 1.2%. This does not correlate well with the clinical data on otosclerotic families, from which a clinical prevalence of 0.3% has been estimated. OBJECTIVE: To study the prevalence of histologic otosclerosis in an unselected series of temporal bones. STUDY DESIGN: During a 1-year period, 118 consecutive pairs of temporal bones of deceased patients at a tertiary care center were collected to determine the prevalence of otosclerosis. Although histology remains the gold standard for evaluation of otosclerosis, the gross observation of temporal bone slices combined with microradiography was used to screen for otosclerotic lesions more rapidly and with a lower cost/benefit ratio. The temporal bones, which were suspected of having otosclerosis with these techniques, were further analyzed by conventional histology. RESULTS: 2.5% of the 236 temporal bones (or 3.4% of patients) studied demonstrated histologic otosclerosis. CONCLUSIONS: Although the prevalence of 2.5% is much lower than previously published figures on histologic otosclerosis, the extrapolated data (extrapolated clinical prevalence = 0.30% to 0.38%) correlate well with clinical studies of otosclerotic families. The previous studies based on laboratory collections were likely biased by hearing loss or other otologic diseases.

Adolescent↗
PubMed2001

Development of the fallopian canal in humans: a morphologic and radiologic study.

AIMS: This study investigated the development of the fallopian canal with particular reference to the mode of ossification and dehiscences, sites of incomplete closure around the facial nerve. BACKGROUND: The precise sequence of events surrounding ossification of the tissues around the facial nerve is uncertain. Incomplete ossification results in dehiscence of the adult structure, which places the nerve at increased risk of damage from disease processes in the middle ear and iatrogenic trauma during otologic surgery. METHODS: Twenty-four temporal bones from 12-to 36-week human fetuses were resected. Eight temporal bones from 22-to 36-week fetuses were microsliced to produce 1.5-mm horizontal sections and radiographed. Sixteen temporal bones from 12-to 35-week fetuses were serially microtomed to produce 7-microm slices, which were stained with hematoxylin and eosin. Quantitative and qualitative analyses of these sections were performed to document patterns of closure of the primitive canal and dehiscence formation. RESULTS: The tympanic part of the primitive fallopian canal, the facial sulcus, developed anteroposteriorly from the geniculate fossa to enclose the facial nerve. The mesenchyme that formed the facial sulcus underwent endochondral ossification, while the bone which capped or closed the sulcus developed in membrane. In the tympanic segment, permanent congenital dehiscences were elliptical and about 1 mm in length. CONCLUSIONS: This study clarifies the mode of development of the fallopian canal, with particular reference to dehiscences, and provides a scientific basis for otologic practice.

Facial Nerve↗
PubMed2000

The development of the stria vascularis in the human foetus.

The development of the stria vascularis in the human cochlea was studied in step sections of 81 human foetal temporal bones. The stria vascularis primordium can be identified as a ridge of epithelial cells on the lateral wall of the cochlear duct. The first signs of differentiation appear at the 11th week, but it is not until the 17th-18th week that the typical trilaminar structure is observed. The appearance of similar cells with notched nuclei in both marginal and mesenchymal layers at this stage suggests the possibility that some of the intermediate cells may be of epithelial origin. By the 21st week, the overall appearance resembles that of the adult structure. This occurs 1 week after the opening of the tunnel of Corti, and possibly marks the onset of cochlear function.

Cochlear Duct↗
PubMed2000

Origin and spread of allergic fungal disease of the nose and paranasal sinuses.

Although expansion of bony walls occurs in allergic fungal disease of the nose and paranasal sinuses by increased mucus secretion and fungal growth, the latter is apparently confined to the lumen and does not invade the tissues. Nevertheless, spread of the disease process from paranasal sinuses to orbit, cheek and intracranial cavity is well described. An imaging and histopathological study was carried out in 16 cases to determine how the disease originates and spreads. The infection starts in the nasal cavity, the lumen of a sinus or in a seromucinous gland or duct. A thin vascular zone of intense allergic inflammation surrounds the infected mucin. Erosion of bone takes place focally, probably by substances produced by the inflammatory tissue, allowing intromission by the thin vascular layer together with its underlying fungus-containing mucus and so extension of the disease process through the eroded bone.

Adult↗
PubMed2000

The Ljubljana classification: a practical strategy for the diagnosis of laryngeal precancerous lesions.

There is no internationally accepted classification of epithelial hyperplastic laryngeal lesions (EHLL). The majority of current classifications follow criteria similar to those commonly used for cervical epithelial lesions. However, the different etiology of laryngeal cancer and its particular clinical and histologic features necessitate a grading system more appropriate to this region. The Ljubljana classification of EHLL was devised in 1971 to cater to this requirement. Detailed criteria for histologic grading in this classification were formulated by a working group on EHLL of the European Society of Pathology in 1999. The system recognizes four grades: simple and abnormal hyperplasia are benign categories; atypical hyperplasia ("risky" epithelium) is potentially malignant, and carcinoma in situ actually malignant. The main features by which the proposed grading system differs from other classifications are: 1. the distinction between benign and potentially malignant lesions; 2. the positive separation of carcinoma in situ from atypical hyperplasia; 3. the lack of prognostic significance for any surface keratin layer. The eventual outcome of EHLL patients so graded justifies the proposal for separating the lesions into a benign group, showing malignant transformation in only 0.9% of cases, from a potentially malignant group showing malignant transformation in 11% of cases. For diagnostically difficult cases, supplementary techniques such as those using morphometry, immunohistochemical and molecular biology are advised to improve the accuracy of diagnosis and predictions of their biological behavior.

Carcinoma in Situ↗
PubMed2000

Congenital malformations of the ear and cochlear implantation in children: review and temporal bone report of common cavity.

The objective of this review is to analyze aspects of congenital malformation of the ear in relation to cochlear implantation in children. Having briefly described the in utero development of the ear and the classification of types of external, middle and inner ear malformation, five practical aspects of these malformations are discussed. It seems likely that the combination of bilateral profound sensorineural deafness with bilateral microtia severe enough to make a surgical approach to the cochlea difficult will be extremely uncommon. No such cases have been reported, although Klippel-Feil deformity seems the syndrome most likely to produce this set of circumstances. Abnormalities in the intratympanic course of the facial nerve have been associated with cochlear malformation, emphasizing the benefit of intra-operative facial nerve monitoring, and a technique suggested for safely avoiding an abnormally placed nerve. Fistulae of cerebrospinal fluid (CSF) and perilymph can complicate surgery and are relatively common in common cavity and Mondini malformations. Strategies for facilitating surgery in the presence of 'gushers', for measuring the pressure of a gusher and for placement of the cochlear implant electrode array are reviewed, with reports of fluctuating levels of electric current when implants lie in dysplastic cochleas. The relationship of implant performance to VIIIth nerve tissue in malformed cochleas is discussed, with a description of the histological findings in a common cavity cochlea. Techniques for identifying the absence of the cochlear nerve are reviewed. Stimulation of the facial nerve by cochlear implants has been described in cases of congenital malformation of the labyrinth but is relatively uncommon. Case reports of the benefit received by implanted children with congenital cochlear malformation have appeared since 1988. Most cases reported have not yet been followed for long enough to establish a clear picture of the outcome following cochlear implantation in such children; no centre has yet built up a large series of cases, but there have been two multicentre postal surveys. It seems likely that in cochlear malformation the range of potential outcomes in terms of hearing threshold and the development of speech perception and production will be similar to the range found in implanted children without cochlear dysplasia. However there is, as yet, no clear picture of the mean level of performance within this range.

Adolescent↗
PubMed1999

Family with low-grade neuroendocrine carcinoma of salivary glands, severe sensorineural hearing loss, and enamel hypoplasia.

Four sibs in a family on the Isle of Man, two brothers and two sisters ranging in age from 33 to 45 years, presented with low-grade malignant tumors of the submandibular gland in three cases and of the nasal cavities and maxillary sinuses in one. The neoplasms were all of the same histological type, apparently hitherto undescribed, showing well-differentiated neoplastic ducts, surrounded by neoplastic myoepithelial cells, together with sheets of epithelial cells expressing neuroendocrine markers by immunohistochemistry. Cervical neck node metastases have developed in all four cases. In the sib with a primary sinonasal neoplasm, widespread bloodstream metastases also became manifest and a single such metastasis in his brother. All four sibs have severe enamel hypoplasia and the same lesion is present in 5 of their 11 children. In the two male patients, severe sensorineural hearing loss has developed in adult life, unilateral in the left ear in one brother, bilateral in the other. In the brother with bilateral sensorineural hearing loss, magnetic resonance imaging revealed a vestibular schwannoma on the left side, which is currently under treatment. The inherited hearing loss is thought to be unilateral in this case also.

Adolescent↗
PubMed1999

Histopathological findings suggest the diagnosis in an atypical case of Pendred syndrome.

Radiological malformation of the labyrinth, specifically dilatation of the vestibular aqueduct, has been clearly established as a feature in the majority of patients with Pendred syndrome. Mutations of the Pendred syndrome (PDN) gene have been identified in this autosomal recessive form of deafness. There is no direct correlation between the nature of the underlying mutation and the clinical features of deafness, thyroid dysfunction and cochlear malformation. We report a family, the proband of which was thought to deafness secondary to congenital hypothyroidism. At autopsy, histopathological examination of this patient revealed a dilated vestibular aqueduct. Subsequent work on the family has confirmed the diagnosis of Pendred syndrome in the proband and her affected sister.

Adolescent↗
PubMed1999

Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology.

AIMS: To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix. METHODS AND RESULTS: Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion). CONCLUSIONS: Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semiobjective methods of quantitative morphometry and immunohistochemistry.

Epithelium↗