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Biomedical subjects

T B Fitzpatrick

Publications and source records attributed to T B Fitzpatrick.

At least 73 records · Page 4Linked to original sources
PubMed1984

The nature and origin of the melanin macroglobule.

The melanin macroglobule (MMG), formerly called "macromelanosome," is a cytoplasmic spherical granule formed in the melanocyte, varying in size from one to several microns, much larger than normal ellipsoidal melanosomes. Although ultrastructural features of MMG have been adequately described in the past, there has been a disagreement about the formation process of MMG. In order to further elucidate the nature and origin of MMG, electron microscopic studies were conducted in several pigmentary disorders. Our findings included: (1) The most remarkable characteristics of MMG are (a) the pleomorphism of their internal structure and (b) the variation of their size. (2) MMG do not represent true melanosomes but unique forms of autolysosomes resulting from the fusion of autophagosomes (containing various numbers of melanosomes) with primary and/or secondary lysosomes. (3) MMG are retained within melanocytes or transferred to keratinocytes and to Langerhans cells in the epidermis, and to macrophages in the dermis in any of their developmental stages. After transfer, MMG can fuse with other heterolysosomes and probably increase in size in these cells. We regard melanosome complexes as but one step in an autophagic process within melanocytes which can, on occasion, produce MMG as residual bodies.

Acid Phosphatase↗
PubMed1984

Acid phosphatase in melanosome formation: a cytochemical study in normal human melanocytes.

A cytochemical study of acid phosphatase (AcPase) activity was conducted in normal epidermal melanocytes from both sun-exposed and sun-protected human skin to define the relationship between enzyme activity and melanosome formation. In the perikarya of melanocytes of both sun-exposed and sun-protected skin, it was determined that only a small proportion of stage 1 and 2 melanosomes had AcPase activity (20-33% and 9-26%, respectively). The proportion of AcPase-positive melanosomes in perikarya increased in stage 3 (39-56%), reaching a maximum in stage 4 (67-84%). In the dendrite of melanocytes, where melanosomes were mostly in stages 3 and 4, the vast majority of melanosomes demonstrated AcPase activity (79-87% and 88-93%, respectively). The preferential incorporation of AcPase in the later stages of melanogenesis is more consistent with a possible role for this enzyme in the degradation or transfer of melanosomes, rather than as an essential component in the early process of melanization.

Acid Phosphatase↗
PubMed1984

Lentigo maligna melanoma has no better prognosis than other types of melanoma.

We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.

Actuarial Analysis↗
PubMed1984

Prognosis in Stage 1 malignant melanoma: seven-year follow-up study of splenic radiocolloid uptake as predictor of death.

In an earlier study we found that patients with clinical Stage 1 and 2 cutaneous malignant melanoma and increased splenic radiocolloid uptake had more frequent recurrence at 24 mo, compared with melanoma patients having normal liver-spleen scintigrams. This report, an 80-mo follow-up study, gives further information on 119 clinical Stage 1 patients. Fifteen of 35 patients with increased splenic uptake (42.9%) died from melanoma as opposed to only 16 of 84 (19.1%) with normal liver-spleen images (p less than 0.01). Multivariate analysis showed that augmented splenic uptake of technetium-99m sulfur colloid is a marker for adverse prognosis in patients with malignant melanoma but does not appear to be an independent variable in predicting death. In clinical Stage 1 patients, increased splenic uptake correlated significantly with pathologic stage (positive elective node biopsy) as well as thickness and mitotic rate in patients with thicker lesions. It may be that patients with thicker, pathologically aggressive tumors have an increased splenic blood flow and/or enhanced immune and reticuloendothelial response (as manifested by abnormal liver-spleen scintigram). If so, the enhanced immune response does not appear to contribute to overall survival.

Adult↗
PubMed1984

Skin markings in the diagnosis and prognosis of cutaneous melanoma.

Skin markings and pathologic findings in 105 patients with cutaneous melanoma were reviewed to determine relationship between clinical findings, pathologic findings, and prognosis. Lesions with decreased or absent markings are significantly thicker than those with increased or normal markings and therefore carry a worse prognosis. Loss of skin markings is a late sign of melanoma and should not be relied on as an aid in early diagnosis.

Humans↗
PubMed1984

Safety and therapeutic effectiveness of 8-methoxypsoralen, 4,5',8-trimethylpsoralen, and psoralen in vitiligo.

In this paper, we report on 366 East Indian patients with vitiligo who were treated for 2 to 3 years with either 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP), or psoralen and sunlight. These patients with amelanotic macules had 10 to 70% skin involvement of 1 to 50 years duration. Male and female patients from ages 12 to 70 years were randomly assigned to 8 treatment groups; the study was conducted on a double-blind protocol. Patients in prone and supine positions were exposed to the sun for 45-60 minutes in gradually increasing doses between 11 a.m. and 2 p.m. thrice weekly and 2 hours after oral ingestion of the drug. The various drug dosage schedules investigated included 9 groups: 0.3 and 0.6 mg 8-MOP/kg; 0.8, 1.8, and 3.6 mg TMP/kg; a combination of 0.3 mg 8-MOP and 0.6 mg TMP/kg; 0.6 and 1.2 mg psoralen/kg, and a placebo. For ethical reasons, the placebo group was terminated after 9 to 12 months of therapy. All patients were photographed before enrollment and at intervals of 6, 12, 18, and 26 months during therapy. Of these patients treated for nearly 2 years, the faces of those 45% receiving the combination dose of 8-MOP plus TMP or low-dose 8-MOP (0.3 mg/kg) were fully repigmented, and nearly 60% achieved 75 to 100% repigmentation of the head and neck. The chest, abdomen, and back were repigmented nearly as well and better than the arms and legs. The patients receiving high-dose schedules of TMP and psoralen achieved better repigmentation response than those on lower dosage but still not as good as patients on 8-MOP or the combination group of 8-MOP plus TMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Ficusin↗
PubMed1984

Chronic cutaneous effects of long-term psoralen and ultraviolet radiation therapy in patients with vitiligo.

Vitiligo is refractory to most therapeutic modalities. To assess the efficacy of a variety of PUVA therapies, we enrolled 596 subjects in a prospective study, and 230 were followed for up to 55 months. Various psoralen derivatives and dosage schedules were used. Each subject was examined at yearly intervals for therapeutic response and evidence of chronic PUVA toxicity. At 4 years after therapeutic inception, 29 (13%) developed lesions in remaining vitiliginous macules. Clinically, hyperkeratotic macules and hyperkeratotic, lichenoid, and telangiectatic papules were discerned. Histologic examination of these lesions revealed them to be actinic and lichenoid keratoses, verruca vulgaris, and hyperkeratosis with either hyperplasia or atrophy. No tumors were present. In perilesional skin, dermal collagen and elastic tissue degeneration, much greater in degree than reported in psoriatic skin, was observed. In this group of PUVA-treated patients, no increased risk of carcinoma was apparent during the follow-up period.

Adult↗
PubMed1983

Dysplastic melanocytic nevi in histologic association with 234 primary cutaneous melanomas.

Dysplastic melanocytic nevi (DMN) are irregularly pigmented lesions characterized by (1) atypical melanocytic hyperplasia in a lentiginous epidermal pattern (AMHL), (2) one or more dermal mesenchymal changes, and (3) frequently a dermal nevocellular nevus. In order to determine an association between DMN and cutaneous melanoma, the dominant histologic feature of DMN (namely, AMHL) was sought in histologic contiguity with 234 primary melanomas. Of these 234 cases, 9 were lentigo maligna melanomas. Of the remaining 225 cases, 49 (21.8%) were associated with AMHL in the same histologic section as (but beyond the most lateral margin of) intraepidermal and invasive melanoma. AMHL was directly associated with the presence of dermal nevocellular nevi in histologic contiguity with melanoma, and a greater number of histologic slides with melanoma available for review. AMHL was inversely associated with nodular melanoma. Most of the AMHL cases were not associated with familial melanoma, but the total number of familial cases was low. The histologic association between AMHL and melanoma in one fifth of cases in this series supports the hypothesis that at least some cutaneous melanomas may have an origin in DMN.

Adult↗
PubMed1983

Malignant melanoma and vitiligo-like leukoderma: an electron microscopic study.

We report clinical and ultrastructural results in eight patients with melanoma and widespread leukoderma. Leukoderma appears to be a good prognostic sign. Although some features of this entity are suggestive of vitiligo, the patients' age, the distribution and appearance of body lesions, and ultrastructural results show a more varied clinical and ultrastructural spectrum. The high frequency of ocular pigmentary disturbances and uveitis in this patient population is noteworthy and deserves further study. We would recommend routine use of Wood's light examination in following patients with thick stage I, stage II, or stage III melanoma to facilitate detection of this phenomenon.

Adult↗
PubMed1983

Increased intraepidermal melanocyte frequency and size in dysplastic melanocytic nevi and cutaneous melanoma. A comparative quantitative study of dysplastic melanocytic nevi, superficial spreading melanoma, nevocellular nevi, and solar lentigines.

Dysplastic melanocytic nevi (DMN) are distinguished histologically by a hyperplasia of variably atypical intraepidermal melanocytes in a lentiginous epidermal pattern. In order to further characterize the intraepidermal melanocytes of DMN, 4 representative specimens each of DMN, acquired nevocellular nevi (NCN), solar lentigines (SL), and superficial spreading melanoma (SSM) were selected on the basis of predetermined criteria, confirmed in a blind histologic assessment, and compared in a quantitative morphologic study using 6 micron-thick hematoxylin and eosin stained sections of L-dihydroxyphenylalanine (dopa) preincubated vertical tissue slices of lesion and adjacent normal skin. The average melanocyte frequency, expressed as the percent of dopa-reactive perikarya among 600 consecutive basal unit cells, was significantly greater in DMN (60 +/- 23%) than in NCN (18 +/- 3%), SL (25 +/- 7%), and adjacent skin (14 +/- 3%), but similar to that in SSM (71 +/- 11%). The average mean diameter of 200 consecutive epidermal basal unit melanocytes was significantly larger in DMN (11 +/- 2 microns) than in NCN (7 +/- 0.4 microns), SL (6 +/- 0.1 microns), and adjacent skin (6 +/- 0.4 microns), but significantly smaller than in SSM (16 +/- 3 microns). The observed similarities of intraepidermal melanocytes in selected DMN and SSM, as well as distinct differences from melanocytes in selected NCN and SL, support the hypothesis that some varieties of DMN may represent potential precursors of cutaneous melanoma.

Adult↗
PubMed1983

Sun exposure habits in patients with cutaneous melanoma: a case control study.

Telephone interviews were conducted with 111 patients with cutaneous melanoma and 107 controls to determine sun-exposure habits during various life periods. Painful or blistering sunburns during either childhood or adolescence were associated with subsequent increased risk of developing cutaneous melanoma. While solar exposure does not appear to be a factor in some patients, when patients were divided into subgroups by age, sex, or sun type, each subset showed some increased risk associated with a factor related to short-term excessive sun exposure. Ill effects due to such exposures appeared to increase the risk of melanoma.

Adult↗
PubMed1983

Rapid progression of lentigo maligna to deeply invasive lentigo maligna melanoma. Report of two cases.

Two patients had lesions of lentigo maligna that evolved into deeply invasive (level 4-5) lentigo maligna melanoma during a relatively short period (two years and four years, respectively). In both patients, the clinical impression of lentigo maligna had been difficult to confirm by histopathologic analysis until the invasive tumor had developed. Both patients were actively followed up during this period of evolution, with our intention of detecting any early changes suggestive of invasive melanoma. Since deep invasion developed despite close clinical supervision, a more aggressive approach to the treatment of lentigo maligna may be warranted.

Facial Neoplasms↗
PubMed1983

Early death from clinical stage I melanoma.

We studied 13 prognostic factors in 582 patients with clinical stage I melanoma to determine which factor or combination of factors was associated with death from melanoma within the first 24 months following diagnosis. Thirty-six patients died during this period. Only 2 deaths occurred in patients with primary tumors thinner than 1.70 mm, and only 2 patients of 189 died with tumors located on the non-BANS extremities, excluding the hands and feet. Individual factors associated with high risk for death within 2 years included level V tumors, acral location, thickness greater than or equal to 3.65 mm, histologic ulceration greater than 3 mm, nodular type, presence of microscopic satellites, greater than 6 mitoses/mm2, positive elective node dissection, absence of lymphocyte response at the tumor base, and absence of an associated nevus histologically. Many of the preceding individual factors are highly correlated. By the use of logistic regression analysis, only one very high risk group was found: 71 percent of patients with level V tumors greater than 1.70 mm thick with histologic ulceration width greater than 3 mm located in an area other than the extremities (excluding hands and feet) had died within 2 years of diagnosis. The ability to select high-risk groups should be useful to investigators involved with the design and evaluation of adjuvant therapy studies.

Adult↗