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Biomedical subjects

T B Fitzpatrick

Publications and source records attributed to T B Fitzpatrick.

At least 19 recordsLinked to original sources
PubMed1992

The evolution of photochemotherapy with psoralens and UVA (PUVA): 2000 BC to 1992 AD.

The therapeutic uses of naturally occurring psoralens in modern-day medicine (8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 4,5',8-trimethylpsoralen, and a few other synthetic psoralens) have evolved through five stages of development. (1) In the historical period (2000 BC to 1930 AD), the pigment-stimulating properties of naturally occurring plants containing psoralens were described anecdotally. (2) The second period (1930-1960) dealing with the chemistry of psoralens involved extraction, identification of their structure, synthesis, and the relationship between chemical structure and their photoreactivity and pigment-stimulating properties. The treatment of vitiligo with oral and topical 8-MOP became popular. (3) In the third period (1960-1974), we witnessed a new beginning and the growth of basic science studies and clinical investigations into various biological properties of psoralens including action spectrum studies, mutagenesis and carcinogenesis studies, in vitro and in vivo photoreactivity studies of various psoralens with DNA, RNA, proteins, and pharmacological and toxicological studies in vitiligo patients undergoing long-term therapy for repigmentation. (4) The fourth period (1974-1988) is recognized as the period of photochemotherapy and the development of the science of photomedicine which established the therapeutic effectiveness of psoralens in combination with newly developed UV irradiation systems that emitted high-intensity UVA radiation in the treatment of severe psoriasis, mycosis fungoides, and over 16 other skin diseases. The effectiveness of PUVA (psoralen + UVA) was confirmed by well controlled clinical trials in thousands of patients, both in the USA and in European countries. Combination therapy with oral retinoids and PUVA contributed to greater effectiveness and long-term safety of psoralen photochemotherapy. (5) In the fifth period (1989 and beyond), psoralens are now emerging as photochemoprotective agents against non-melanoma skin cancers and as immunologic modifiers in the management of certain patients with disorders of circulating T-cells using new techniques of photopheresis. In the final analysis, perhaps the application of pharmacological and therapeutic concepts and principles of using psoralens in combination with UVA has contributed to the development of a new science of photomedicine in which the interaction between basic scientists, photobiologists, and physicians has produced both basic and new clinical knowledge for the care and control of human suffering.

Furocoumarins↗
PubMed1991

Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme.

Dysplastic nevi are an important indicator of risk of cutaneous malignant melanoma. The study of and, particularly, international communication regarding this group of lesions have been hindered by a lack of precision in diagnosis. In an effort to broaden understanding, a panel of pathologists agreed upon a set of criteria for the diagnosis of dysplastic melanocytic nevi. Two major and four minor criteria were defined. The major criteria are (1) basilar proliferation of atypical nevomelanocytes (extending at least three rete ridges or "pegs" beyond any dermal nevo-cellular component), and (2) organization of this proliferation in a lentiginous or epithelioid-cell pattern. Minor criteria are (1) the presence of lamellar fibrosis or concentric eosinophilic fibrosis, (2) neovascularization, (3) inflammatory response, and (4) fusion of rete ridges. Diagnosis required presence of both major criteria and at least two minor criteria. One hundred fourteen histologic specimens of benign acquired nevi, dysplastic nevi, and radial-growth-phase melanomas were examined by the members of this panel; their diagnoses were compared to determine degree of concordance. The established criteria yielded 92% mean concordance overall.

Diagnosis, Differential↗
PubMed1989

Oral methoxsalen photochemotherapy for the treatment of psoriasis: a cooperative clinical trial. 1977.

Extensive psoriasis in 1,308 patients has been treated two or three times a week with oral 8-methoxypsoralen followed by high intensity, long-wave ultraviolet light (PUVA). Excluding 169 patients still under early treatment, psoriasis cleared in 88% and failed to clear in 3%. One percent dropped out due to complications of treatment, and 8% for other reasons. The twice-a-week schedule was superior for patients with lighter skin types. Once a remission was induced, there was no difference in its maintenance when patients were treated once a week, once every other week, or once every third week. Each of these schedules was superior to no maintenance treatment. Immediate side effects of the 45,000 treatments administered in the first 18 months of this study were uncommon, temporary, and generally mild. No clinically significant changes in laboratory screening or eye examinations attributable to PUVA have been uncovered.

Administration, Oral↗
PubMed1988

Melanosomal alterations in dysplastic melanocytic nevi. A quantitative, ultrastructural investigation.

Abnormal-looking melanosomes are observed commonly in both intraepidermal melanocytes of cutaneous melanoma and dysplastic melanocytic nevi (DMN). This was investigated by using transmission electron microscopic examination to determine the percentage of abnormal melanosomes among 8267 melanosomes assessed in at least five solitary intraepidermal basal unit melanocytes from each of five specimens of DMN, superficial spreading melanoma (SSM), common acquired nevomelanocytic nevi (NMN), and normal skin (NS) adjacent to DMN. The percentage of abnormal melanosomes in DMN (mean + SD, 44 + 23%) was seven times greater than that in NMN (6 + 7%) and 22 times greater than that in NS (2 + 5% [P less than 0.001, both comparisons]), but only 80% that in SSM (57 + 19% [P less than 0.02]). Melanocyte area, nuclear area, and the ratio of nuclear area to cytoplasmic area did not account for the observed differences. Melanosomal alterations may be a useful marker of atypicality in melanocytic tumors.

Adult↗
PubMed1988

Effect of BANS location on the prognosis of clinical stage I melanoma: new data and meta-analysis.

Intermediate thickness (0.76-1.69 mm) clinical stage I melanomas at BANS locations (upper Back, posterior Arm, posterior Neck, posterior Scalp) were initially reported to have worse prognosis than similar thickness lesions at other subsites. Subsequent investigation did not support this observation. We re-examined the hypothesis in 156 consecutive patients with clinical stage I melanomas in this thickness range, who were seen at the Massachusetts General Hospital from 1977 to 1985. Patients with BANS lesions suffered recurrences at twice the rate of those with non-BANS lesions (28% compared with 13% at 5 years after excision of the primary melanoma), but this difference was not statistically significant. A meta-analysis of the effect of BANS subsite on death risk was performed using data from our investigation and five comparable published studies. The original data set which led to the BANS hypothesis was excluded from the meta-analysis in order to avoid bias. BANS location was associated with a 60% increased risk of death (P = 0.002). The difference remained statistically significant after elimination of any two of the six studies from the analysis. This confirms the influence of anatomical subsite on the prognosis of intermediate thickness melanoma.

Adult↗
PubMed1988

Piebaldism.

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Female↗
PubMed1987

Risk factors for cutaneous melanoma. A practical method of recognizing predisposed individuals.

Cutaneous melanoma is rapidly becoming a potentially curable cancer if it is detected and properly treated in an early phase of development. Unlike other cancers, which are usually hidden from detection until they are relatively large or metastatic disease has occurred, cutaneous melanoma is readily detectable simply by examining the skin. Information is now available that will be useful in selecting individuals at greatest risk. The most important melanoma risk factors (in decreasing order of importance) for a given individual are as follows: a persistently changed or changing mole, adulthood, irregular varieties of pigmented lesions (including dysplastic moles and lentigo maligna), a congenital mole, Caucasian race, a previous cutaneous melanoma, a family history of cutaneous melanoma, immunosuppression, sun sensitivity, and excessive sun exposure. Selective screening and appropriate treatment of individuals who have these risk factors may reduce the morbidity and mortality of cutaneous melanoma.

Adult↗
PubMed1987

A comparison of the melanocyte response to narrow band UVA and UVB exposure in vivo.

The visible cutaneous pigmentary response to ultraviolet-A (UVA) is immediate and, following sufficient exposure, may persist, whereas ultraviolet-B (UVB)-induced pigmentation appears after a delay of several days. We compared the in vivo response of melanocytes to single and multiple exposures of narrow band UVA and UVB irradiation which produced visibly equal increases in pigmentation. Using a xenon-mercury source matched to a monochromator, human volunteers were exposed to 304 (+/- 5) and 365 (+/- 10) nm radiation. Biopsies were performed 1, 7, and 14 days after irradiation. For each biopsy, the number of melanocytes per square millimeter of epidermis was determined using L-3,4-dihydroxyphenylalanine (dopa)- and tyrosine-incubated split epidermal preparations. Vertical sections were also examined. At days 7 and 14, after both 304 and 365 nm radiation, melanocytes were more intensely dopa-positive than in unirradiated controls, and demonstrated enlarged perikarya and a greater number of enlarged dendrites. Following both 304 and 365 nm radiation the number of dopa-positive melanocytes was increased at days 7 and 14 by 44% and 58%, respectively. Tyrosine positivity, an indicator of enhanced tyrosinase activity and increased melanin formation, was absent in controls and at day 1, and became positive in all but one sample at day 7 and day 14. Therefore, one day after UVA exposure, visible pigmentation but not tyrosinase activity was increased. At day 7, the number of tyrosine-positive melanocytes approximately equaled the number of dopa-positive melanocytes. Although UVA and UVB induce different pigmentary responses, their effects on melanocyte number and function were indistinguishable.

Adult↗
PubMed1986

Ocular abnormalities associated with cutaneous melanoma and vitiligolike leukoderma.

Several varieties of ocular pathology are associated with acquired cutaneous hypomelanosis (leukoderma; vitiligo). Our current study was undertaken to investigate the relationship between ophthalmologic disorders and a specific depigmentary phenomenon, the vitiligolike leukoderma of cutaneous melanoma. Over the past 14 years, eight patients with cutaneous melanoma and widespread areas of hypopigmentation were identified at the Pigmented Lesion Clinic of the Massachusetts General Hospital. The seven patients who underwent ophthalmologic examination had pigment-related ocular abnormalities. Among these were inflammations of the uveal tract in three patients, heterochromia in two, halo nevi of the choroid in one, and hypopigmentation and/or atrophy of the retinal pigment epithelium or choroid in four. Our findings demonstrate that ocular disease may be a component in a syndrome consisting also of cutaneous melanoma and vitiligolike leukoderma and suggest the need for complete ophthalmologic examinations in patients with melanoma and leukoderma.

Adult↗
PubMed1986

Usefulness of retinoic acid in the treatment of melasma.

Melasma is a circumscribed brown macular hypermelanosis of the areas of the face and neck that are exposed to light. Clinical trials with various depigmenting formulations containing hydroquinone were conducted to determine the ideal concentration of hydroquinone, retinoic acid, and corticosteroids for the treatment of melasma. The compounds were tested with and without the concomitant use of topical sunscreen preparations. Based on the results of the trials and our earlier clinical experience, we conclude that treatment of melasma should involve the following: avoidance of sun exposure, constant use of broad-spectrum sunscreens, and topical application of a cream or lotion containing 2% hydroquinone and 0.05% to 0.1% retinoic acid (tretinoin). Patients should suspend use of oral contraceptives and other agents that promote skin pigmentation. The monobenzyl ether of hydroquinone should never be used in melasma therapy.

Administration, Topical↗