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Biomedical subjects

Richard Williamson

Publications and source records attributed to Richard Williamson.

12 recordsLinked to original sources

Sun exposure and host phenotype as predictors of cutaneous melanoma associated with neval remnants or dermal elastosis.

Recent research suggests that cutaneous melanomas may arise through 2 distinct pathways, characterized by chronic sun exposure on one hand and nevus-prone phenotype of the host on the other. Two histological characteristics of melanoma consistent with these divergent origins are dermal elastosis in adjacent skin and neval remnants contiguous with the tumor, respectively. To further explore causal heterogeneity in melanoma, we compared sun exposure histories and phenotypic characteristics among a population-based sample of patients newly diagnosed with cutaneous melanoma with and without contiguous neval remnants or dermal elastosis. Tissue blocks were obtained for 141 patients: 53 with superficial spreading melanoma (SSM) of the back, 42 with SSM of head and neck (H & N), and 39 and 7 with lentigo maligna/lentigo maligna melanoma (LM/LMM) of the H & N and back, respectively. Melanomas of the H & N were less likely than those on back to have neval remnants (adjusted OR 0.6, 95% CI 0.3-1.4), but were significantly more likely to have dermal elastosis (adjusted OR 9.3, 95% CI 3.5-25). In site-specific analyses, we found that H & N melanomas with neval remnants were more likely than those without neval remnants to arise in people with more than 60 nevi (adjusted OR 2.1, 95% CI 0.3-14.3), but were less likely to arise in those with more than 20 actinic keratoses. Less marked associations were observed for melanomas of the back. High levels of sun exposure strongly predicted dermal elastosis for H & N melanomas (OR 22.5, 95% CI 2.1-245), but not for melanomas of the back (OR 2.1, 95% CI 0.4-11). We conclude that melanomas with different histologic characteristics have different risk factor profiles, particularly on the head and neck. These data accord with the hypothesis that melanomas arise through different causal pathways.

Age Factors↗

Pulmonary extranodal marginal zone lymphoma with massive crystal storing histiocytosis.

We present an incidentally discovered, unusual case of pulmonary bronchial mucosa-associated lymphoid tissue lymphoma associated with massive crystal storing histiocytosis in a 69-year-old woman. The neoplastic process was masked by large numbers of epithelioid and spindled histiocytes containing crystalline material. Histochemical stains showed intracytoplasmic crystals and immunoperoxidase staining confirmed the histiocytic nature of the swollen cells. Electron microscopy demonstrated the characteristic appearance of immunoglobulin crystals. Lymphoepithelial lesions were identified on immunohistochemical staining, compounding suspicions of an underlying lymphoid neoplasm. Molecular studies later revealed a monoclonal B-cell population. The patient had no systemic evidence of a paraproteinemia. Crystal storing histiocytosis is a rare phenomenon in which macrophages accumulate light chain or immunoglobulin crystalline inclusions. The disease may be systemic, or localized as in this case. It is usually associated with the excess production of a monoclonal immunoglobulin, although there have been many case reports without this feature. An overview of crystal storing histiocytosis is given.

Aged↗

Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study with statistical analysis of 69 patients.

PURPOSE: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. METHODS: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific survival, relapse-free survival, local control, and distant control. RESULTS: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific survival. CONCLUSIONS: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Adolescent↗

Gianotti-Crosti syndrome in an adult following recent Mycoplasma pneumoniae infection.

A 44-year-old insulin-dependant diabetic woman presented with a pruritic papular eruption involving her hands, forearms and elbows. One week prior to the eruption, the patient had an upper respiratory tract infection and had taken oral ibuprofen 400 mg q.i.d. p.r.n. Skin biopsy revealed histological features consistent with Gianotti-Crosti syndrome. Serology was consistent with recent Mycoplasma pneumoniae infection and past Epstein-Barr viral infection. Her liver function tests were deranged and serum protein electrophoresis showed two sharp discrete monoclonal immunoglobulin bands. The eruption resolved completely 15 days after onset. Her serum protein studies and liver function tests subsequently normalized and she had no recurrences of her cutaneous eruption. It was concluded that the patient had Gianotti-Crosti syndrome associated with Mycoplasma pneumoniae infection.

Acrodermatitis↗

Parental familial vulnerability, family environment, and their interactions as predictors of depressive symptoms in adolescents.

OBJECTIVE: Familial risk for depression results from both biological and social influences. These may also be associated with other characteristics, including alcohol use, smoking, and body mass index (BMI), and with environmental risks such as social problems, life events, and educational level, all of which may be associated with depression in offspring. The authors examined the links between (1) parental familial vulnerability to depression and (2) the role of associated parental characteristics on severe adolescent depressive symptoms. Third, the authors explored the influence of family environment variables. Fourth, the authors sought interactions between parental familial vulnerability and family environment. METHOD: Questionnaires were obtained from 1,294 parents of 1,818 adolescent offspring. RESULTS: The odds of severe adolescent depressive symptoms increased by a factor of 1.5 per standard deviation increase in parental familial vulnerability to depression (odds ratio [OR] = 1.50). Parental BMI (OR = 1.05) and educational level (OR = 2.60) had significant influences independent of parental vulnerability. Analyses indicated a significant interaction such that those with high parental familial vulnerability, whose parents also had no qualifications, had a threefold risk of severe depressive symptoms. CONCLUSIONS: Adolescents with a family history of depression whose parents also lack qualifications may be a target for intervention.

Adolescent↗

Visual perception in a blind subject with a chronic microelectronic retinal prosthesis.

A retinal prosthesis was permanently implanted in the eye of a completely blind test subject. This report details the results from the first 10 weeks of testing with the implant subject. The implanted device included an extraocular case to hold electronics, an intraocular electrode array (platinum disks, 4 x 4 arrangement) designed to interface with the retina, and a cable to connect the electronics case to the electrode array. The subject was able to see perceptions of light (spots) on all 16 electrodes of the array. In addition, the subject was able to use a camera to detect the presence or absence of ambient light, to detect motion, and to recognize simple shapes.

Aged↗

Role of TIMPs (tissue inhibitors of metalloproteinases) in pericellular proteolysis: the specificity is in the detail.

Pericellular proteolysis represents one of the key modes by which the cell can modulate its environment, involving not only turnover of the extracellular matrix but also the regulation of cell membrane proteins, such as growth factors and their receptors. The metzincins are active players in such proteolytic events, and their mode of regulation is therefore of particular interest and importance. The TIMPs (tissue inhibitors of metalloproteinases) are established endogenous inhibitors of the matrix metalloproteinases (MMPs), and some have intriguing abilities to associate with the pericellular environment. It has been shown that TIMP-2 can bind to cell surface MT1-MMP (membrane-type 1 MMP) to act as a 'receptor' for proMMP-2 (progelatinase A), such that the latter can be activated efficiently in a localized fashion. We have examined the key structural features of TIMP-2 that determine this unique function, showing that Tyr36 and Glu192-Asp193 are vital for specific interactions with MT1-MMP and proMMP-2 respectively, and hence activation of proMMP-2. TIMP-3 is sequestered at the cell surface by association with the glycosaminoglycan chains of proteoglycans, especially heparan sulphate, and we have shown that it may play a role in the regulation of some ADAMs (a disintegrin and metalloproteinases), including tumour necrosis factor alpha-converting enzyme (TACE; ADAM17). We have established that key residues in TIMP-3 determine its interaction with TACE. Further studies of the features of TIMP-3 that determine specific binding to both ADAM and glycosaminoglycan are required in order to understand these unique properties.

Amino Acid Sequence↗

Progression of a myxoid pleomorphic fibroma to myxofibrosarcoma.

A 75-year-old man presented with a protuberant stable lesion of many years on his left second toe. Histology on an incisional biopsy showed myxoid pleomorphic fibroma. Over the subsequent 21 months, the lesion enlarged and became exophytic and irregular. Repeat biopsy showed features consistent with a grade III myxofibrosarcoma. Treatment involved amputation of his toe. Six months later he remains well, with no evidence of local recurrence or systemic spread.

Aged↗