Medial upper eyelid shortening to correct medial eyelid laxity in floppy eyelid syndrome: A new surgical approach

Purpose: To describe and present the results of a new surgical technique for patients with floppy eyelid syndrome, based on the medial upper eyelid stretching encountered in this condition. Methods: A case series of 24 patients with floppy eyelid syndrome who where found to have symptomatic predominately medial upper eyelid laxity was analyzed. The history, clinical features, histopathology, and outcome were reviewed after patients underwent medial upper eyelid shortening with or without upper eyelid skin reduction as the first surgical procedure. Results: Of the 24 patients, 18 were men (75%) with a mean age at referral of 56 years, having ocular discomfort and conjunctival irritation/papillary conjunctivitis as the main complaints at presentation. Obesity was present in 96% of cases, with lower eyelid laxityl/ectropion (50%) and upper eyelid eyelash ptosis (29%) in conjunction with the upper eyelid laxity. The affected side was related to sleeping habits or recurrent mechanical eyelid trauma. Histologic studies showed a nonspecific inflammatory cell infiltrate and loss of elastin with loose dermal connective tissue. After surgery, complete relief of ocular symptoms and good functional and cosmetic results were present in all cases after 18 months of follow-up. Conclusions: This new surgical approach is based on the presence of predominately medial upper laxity in patients with floppy eyelid syndrome. The excision of this stretched area stabilized the upper eyelid in an anatomic fashion, providing a good and stable long-term result. The possible mechanisms involved in the medial upper eyelid stretching are discussed.

Live cell imaging of heavy-ion-induced radiation responses by beamline microscopy

To study the dynamics of protein recruitment to DNA lesions, ion beams can be used to generate extremely localized DNA damage within restricted regions of the nuclei. This inhomogeneous spatial distribution of lesions can be visualized indirectly and rapidly in the form of radiation-induced foci using immunocytochemical detection or GFP-tagged DNA repair proteins. To analyze faster protein translocations and a possible contribution of radiation-induced chromatin movement in DNA damage recognition in live cells, we developed a remote-controlled system to obtain high-resolution fluorescence images of living cells during ion irradiation with a frame rate of the order of seconds. Using scratch replication labeling, only minor chromatin movement at sites of ion traversal was observed within the first few minutes of impact. Furthermore, time-lapse images of the GFP-coupled DNA repair protein aprataxin revealed accumulations within seconds at sites of ion hits, indicating a very fast recruitment to damaged sites. Repositioning of the irradiated cells after fixation allowed the comparison of live cell observation with immunocytochemical staining and retrospective etching of ion tracks. These results demonstrate that heavy-ion radiation-induced changes in sub-nuclear structures can be used to determine the kinetics of early protein recruitment in living cells and that the changes are not dependent on large-scale chromatin movement at short times postirradiation. © 2005 by Radiation Research Society.

Clinical features and management of tumors affecting the lacrimal drainage apparatus

Purpose: To report the clinical features of a series of patients with lacrimal drainage apparatus tumors and present guidelines for management based on histopathology. Methods: A noncomparative retrospective chart review of the clinical, imaging, and pathologic findings of 37 patients presenting to four regional orbital Surgery departments with tumors affecting the lacrimal drainage apparatus between 1990 and 2004. Results: There were 37 patients, of whom 62% were male. The mean age at referral was 54 years. Epiphora, a palpable mass, and dacryocystitis were the most common presentations. Two thirds of the tumors were epithelial. with carcinomas being the most frequent (38%). followed by papillomas (27%). Lymphomas were the most common nonepithelial malignancy (30%). Epithelial tumors were more common in men (87%), whereas lymphomas were more common in women (57%). Treatment modalities included surgery, in addition to radiotherapy and/or chemotherapy and immunotherapy. Mean follow-up was 38 months. Thirty-three patients (89%) remain alive without evidence of disease and 4 patients died of recurrence and/or metastases. Conclusions: Lacrimal drainage apparatus tumors require careful initial management to ensure adequate local and systemic disease control. Atypical mucosa encountered during dacryocystorhinostomy should be biopsied and small papillomas or pedunculated tumors excised and analyzed with frozen sections. If a diffuse or infiltrative mass is encountered, it should be biopsied and managed on the basis of histopathology and extent of disease. Lymphomas should be treated according to protocols. whereas noninvasive carcinoma and extensive papillomas require complete excision of the system. Invasive disease requires en bloc excision. Long-term follow-up is essential for early detection of recurrence.

Skin cancer clinics in Australia: workload profile and performance indicators from an analysis of billing data

Objective: To describe the workload profile in a network of Australian skin cancer clinics. Design and setting: Analysis of billing data for the first 6 months of 2005 in a primary-care skin cancer clinic network, consisting of seven clinics and staffed by 20 doctors, located in the Northern Territory, Queensland and New South Wales. Main outcome measures: Consultation to biopsy ratio (CBR); biopsy to treatment ratio (BTR); number of benign naevi excised per melanoma (number needed to treat [NNT]). Results: Of 69780 billed activities, 34 622 (49.6%) were consultations, 19 358 (27.7%) biopsies, 8055 (11.5%) surgical excisions, 2804 (4.0%) additional surgical repairs, 1613 (2.3%) non-surgical treatments of cancers and 3328 (4.8%) treatments of premalignant or non-malignant lesions. A total of 6438 cancers were treated (116 melanomas by excision, 4709 non-melanoma skin cancers [NMSCs] by excision, and 1613 NMSCs non-surgically); 5251 (65.2%) surgical wounds were repaired by direct suture, 2651 (32.9%) by a flap (of which 44.8% were simple flaps), 42 (0.5%) by wedge excision and 111 (1.4%) by grafts. The CBR was 1.79, the BTR was 3.1 and the NNT was 28.6. Conclusions: In this network of Australian skin cancer clinics, one in three biopsies identified a skin cancer (BTR, 3.1), and about 29 benign lesions were excised per melanoma (NNT, 28.6). The estimated NNT was similar to that reported previously in general practice. More data are needed on health outcomes, including effectiveness of treatment and surgical repair.

The absolute structural requirement for a proline in the P3 '-position of Bowman-Birk protease inhibitors is surmounted in the minimized SFTI-1 scaffold

SFTI-1 is a small cyclic peptide from sunflower seeds that is one of the most potent trypsin inhibitors of any naturally occurring peptide and is related to the Bowman-Birk family of inhibitors (BBIs). BBIs are involved in the defense mechanisms of plants and also have potential as cancer chemopreventive agents. At only 14 amino acids in size, SFTI-1 is thought to be a highly optimized scaffold of the BBI active site region, and thus it is of interest to examine its important structural and functional features. In this study, a suite of 12 alanine mutants of SFTI-1 has been synthesized, and their structures and activities have been determined. SFTI-1 incorporates a binding loop that is clasped together with a disulfide bond and a secondary peptide loop making up the circular backbone. We show here that the secondary loop stabilizes the binding loop to the consequences of sequence variations. In particular, full-length BBIs have a conserved cis-proline that has been shown previously to be required for well defined structure and potent activity, but we show here that the SFTI-1 scaffold can accommodate mutation of this residue and still have a well defined native-like conformation and nanomolar activity in inhibiting trypsin. Among the Ala mutants, the most significant structural perturbation occurred when Asp(14) was mutated, and it appears that this residue is important in stabilizing the trans peptide bond preceding Pro(13) and is thus a key residue in maintaining the highly constrained structure of SFTI-1. This aspartic acid residue is thought to be involved in the cyclization mechanism associated with excision of SFTI-1 from its 58-amino acid precursor. Overall, this mutational analysis of SFTI-1 clearly defines the optimized nature of the SFTI-1 scaffold and demonstrates the importance of the secondary loop in maintaining the active conformation of the binding loop.

Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia

center dot PURPOSE: To evaluate topical interferon alfa-2b (IFN-alpha 2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). center dot DESIGN: Prospective, noncomparative, interventional consecutive case series. center dot METHODS: Ten patients with recalcitrant OSSN were treated with topical IFN-alpha 2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow,up of six months. center dot RESULTS: Eight of 10 patients achieved clinical resolution from topical IFN-alpha 2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha 2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). center dot CONCLUSIONS: Topical IFN-alpha 2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision. (Am J Ophthalmol 2006; 142:568-571. (c) 2006 by Elsevier Inc. All rights reserved.)

Oral granular cell tumour of the lip in an adult patient

Oral granular cell tumour is a rare soft tissue tumour of mesenchymal origin. The most frequently affected site in the oral cavity is the tongue, followed by the floor of mouth, and buccal mucosa. In paediatric patients, 25% of cases have been reported to occur in the lip, but this presentation in adults is extremely rare. We report a case of oral granular cell tumour in a 35 year-old female, located in the lower lip. Histopathological examination revealed eosinophilic granular cells which stained positively for S-100 protein; a finding supportive of a neural origin. A history of trauma was elicited in this case, and the lesion was treated with surgical excision.

Anterior lamella actinic changes as a factor in involutional eyelid malposition

Purpose: We conducted a noncomparative, retrospective chart review of 45 patients and 51 eyelids with the diagnosis of involutional entropion or ectropion that underwent full-thickness lower eyelid shortening between June 2001 and February 2004, in whom the severity of actinic damage was analyzed in relation to the eyelid position. Patients with any different surgical approach or other primary causes of abnormal eyelid position, such as paralytic, congenital, or mechanical factors, were excluded. Methods: After excision, all eyelid specimens were examined by a single anatomic pathologist, who was masked to the type of eyelid malposition. The extent of dermal actinic change was evaluated under light microscopy, according to a previously validated grading system. Results: Fifty-one eyelids from 26 male and 19 female patients were analyzed. The mean age at the surgery was 76 +/- 10 years (range, 52 to 92 years), affecting one side in 39 cases and both sides in 6 cases. The most frequent eyelid malposition was ectropion, which affected two thirds of the cases (35 eyelids). Half of the patients presented with mild actinic skin changes; however, the severity of the histologic skin actinic changes was significantly worse in patients with ectropion in comparison to those with entropion (p < 0.0001). Conclusions: Actinic damage affecting the anterior lamella of the lower eyelid contributes as an additional factor in final eyelid position in patients with involutional eyelid changes. More severe and extensive actinic changes were present in eyelids with ectropion.

Periocular and Orbital Amyloidosis. Clinical Characteristics, Management, and Outcome

Objective: To present the clinical features and management outcome in a large series of patients with periocular and orbital amyloidosis. Design: Retrospective, noncomparative, interventional case series. Patients: All patients diagnosed with periocular and orbital amyloidosis in 6 oculoplastic and orbital units. Methods: Clinical records of all patients were reviewed. Main Outcome Measures: Clinical presentation, radiological and histological findings, treatment modalities, and outcome. Results. The study included 24 patients (15 female, 9 male) with a mean age of 57 17 years. Nineteen cases were unilateral, and 5 were bilateral. Clinical signs and symptoms included a visible or palpable periocular mass or tissue infiltration (95.8%), ptosis (54.2%), periocular discomfort or pain (25%), proptosis or globe displacement (21%), limitations in ocular motility (16.7%), recurrent periocular subcutaneous hemorrhages (12.5%), and diplopia (8.3%). Seven cases had orbital involvement, and 17 were periocular. Immunohistochemistry in 7 patients showed B cells or plasma cells producing monoclonal immunoglobulin chains that were deposited as amyloid light chains. Only 1 patient was diagnosed with systemic amyloid light chain amyloidosis. Treatment modalities were mainly observation and surgical debulking. During a mean follow-up period of 39 months, 21% showed significant progression after treatment, whereas 79% were stable or showed no recurrence after treatment. Conclusion: Periocular and orbital amyloidosis may present with a wide spectrum of clinical findings and result in significant ocular morbidity. Complete surgical excision is not feasible in many cases, and the goal of treatment is to preserve function and to prevent sight-threatening complications.

Urinary 8-oxo-2′-deoxyguanosine:Redox regulation of DNA repair in vivo?

DNA is susceptible to damage by reactive oxygen species (ROS). ROS are produced during normal and pathophysiological processes in addition to ionizing radiation, environmental mutagens, and carcinogens. 8-oxo-2′-deoxyguanosine (8-oxodG) is probably one of the most abundant DNA lesion formed during oxidative stress. This potentially mutagenic lesion causes G → T transversions and is therefore an important candidate lesion for repair, particularly in mammalian cells. Several pathways exist for the removal, or repair, of this lesion from mammalian DNA. The most established is via the base excision repair enzyme, human 8-oxoguanine glycosylase (hOgg1), which acts in combination with the human apurinic endonuclease (hApe). The latter is known to respond to regulation by redox reactions and may act in combination with hOgg1. We discuss evidence in this review article concerning alternative pathways in humans, such as nucleotide excision repair (NER), which could possibly remove the 8-oxodG lesion. We also propose that redox-active components of the diet, such as vitamin C, may promote such repair, affecting NER specifically. © 2002 Elsevier Science Inc.

Deoxycytidine glyoxal:Lesion induction and evidence of repair following vitamin C supplementation in vivo

Oxidative DNA damage is postulated to be involved in carcinogenesis, and as a consequence, dietary antioxidants have received much interest. A recent report indicates that vitamin C facilitates the decomposition of hydroperoxides in vitro, generating reactive aldehydes. We present evidence for the in vivo generation of glyoxal, an established product of lipid peroxidation, glucose/ascorbate autoxidation, or free radical attack of deoxyribose, following supplementation of volunteers with 400 mg/d vitamin C. Utilizing a monoclonal antibody to a deoxycytidine-glyoxal adduct (gdC), we measured DNA lesion levels in peripheral blood mononuclear cells. Supplementation resulted in significant (p = .001) increases in gdC levels at weeks 11, 16, and 21, with corresponding increases in plasma malondialdehyde levels and, coupled with previous findings, is strongly suggestive of a pro-oxidative effect. However, continued supplementation revealed a highly significant (p = .0001) reduction in gdC levels. Simultaneous analysis of cyclobutane thymine dimers revealed no increase upon supplementation but, as with gdC, levels decreased. Although no single mechanism is identified, our data demonstrate a pro-oxidant event in the generation of reactive aldehydes following vitamin C supplementation in vivo. These results are also consistent with our hypothesis for a role of vitamin C in an adaptive/repair response and indicate that nucleotide excision repair specifically may be affected. © 2003 Elsevier Science Inc.

Genetic risk factors and age-related macular degeneration (AMD)

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available. © 2013 Spanish General Council of Optometry.

A pre-post test evaluation of the impact of the PELICAN MDT-TME development programme on the working lives of colorectal cancer team members

Background - The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT-TME) Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer team members. Methods - The impact of participating in the programme on team members' self-reported job stress, job satisfaction and team performance was assessed in a pre-post course study. 333/568 (59%) team members, from the 75 multidisciplinary teams who attended the final year of the Programme, completed questionnaires pre-course, and 6-8 weeks post-course. Results - Across all team members, the main sources of job satisfaction related to working in multidisciplinary teams; whilst feeling overloaded was the main source of job stress. Surgeons and clinical nurse specialists reported higher levels of job satisfaction than team members who do not provide direct patient care, whilst MDT coordinators reported the lowest levels of job satisfaction and job stress. Both job stress and satisfaction decreased after participating in the Programme for all team members. There was a small improvement in team performance. Conclusions - Participation in the Development Programme had a mixed impact on the working lives of team members in the immediate aftermath of attending. The decrease in team members' job stress may reflect the improved knowledge and skills conferred by the Programme. The decrease in job satisfaction may be the consequence of being unable to apply these skills immediately in clinical practice because of a lack of required infrastructure and/or equipment. In addition, whilst the Programme raised awareness of the challenges of teamworking, a greater focus on tackling these issues may have improved working lives further.

Over-Expression of Endothelin 3 Sensitizes Mice to Uv-Induced Melanoma Metastasis

Melanomagenesis is influenced by environmental and genetic factors. In normal cells, ultraviolet (UV) induced photoproducts are successfully repaired by the nucleotide excision repair (NER) pathway. Mice carrying mutations in the xeroderma pigmentosum (Xp) complementation group of genes (Xpa-Xpg) lack the NER pathway and are therefore highly sensitive to UV light; however, they do not develop melanoma after UV exposure. In humans, the Endothelin 3 signaling pathway has been linked to melanoma progression and its metastatic potential. Transgenic mice that over-express Edn3 under the control of the Keratin 5 promoter (K5-Edn3) and exhibit a hyperpigmentation phenotype, were crossed with Xp deficient mice. Because melanoma is highly metastatic and many primary malignancies spread via the lymphatic system, analyzing the lymph nodes may serve useful in assessing the possible spread of tumor cells to other tissues. This study aimed to determine whether the over-expression of Edn3 is sufficient to lead to melanoma metastasis to the lymph nodes. Mice were exposed to UV radiation and analyzed for the presence of skin lesions. Mice presenting skin lesions were sacrificed and the nearest lymph nodes were excised and examined for the presence of metastasis. Mice with melanoma skin lesions presented enlarged and hyperpigmented lymph nodes. Diagnosis of melanoma was established by immunostaining with melanocyte and melanoma cell markers, and while UV radiation caused the development of skin lesions in both K5-Edn3 transgenic and control mice, only those mice carrying the K5-Edn3 transgene were found to develop melanoma metastasis to the lymph nodes. These results indicate that over-expression of Edn3 is sufficient to lead to lymph node metastasis in mice exposed to at least one dose of UV radiation.