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Biomedical subjects

T B Fitzpatrick

Publications and source records attributed to T B Fitzpatrick.

At least 55 records · Page 3Linked to original sources
PubMed1985

Actinic degeneration in association with long-term use of PUVA.

To determine the extent of clinical actinic damage that occurred in association with exposure to oral methoxsalen photochemotherapy (PUVA), dermatologists at 16 university centers assessed the wrinkling, telangiectasia, and altered skin markings on the buttocks and the dorsa of the hands among 1380 patients treated with PUVA. These changes are similar to those seen in skin that is chronically exposed to sunlight. After more than 5 years of prospective study, patients with psoriasis exposed to PUVA showed a significant dose-dependent increase in the prevalence of clinical actinic degeneration of the skin of the buttocks (p less than .05, F-test). The prevalence of moderate or severe change among those patients exposed to high doses of PUVA (more than 160 treatments) was low (11%). The degree of increased clinical actinic degeneration noted on the dorsa of the hands was also significantly related to total exposure to PUVA (p less than .05, F-test). Our findings indicate that long-term PUVA exposure is associated with an increase in clinical actinic degeneration of the skin. However, the magnitude of this increase is small and, after more than 5 years, is of limited clinical consequence to most patients.

Adult↗
PubMed1985

An evaluation of the effectiveness of azelaic acid as a depigmenting and chemotherapeutic agent.

In the past five years, it has been reported that certain dicarboxylic acids (C8-C13) and azelaic acid (C9) (AZA), in particular, have a remarkable effect in the management of lentigo maligna, human malignant melanoma, and certain disorders of hyperpigmentation. Preclinical trials, therefore, were undertaken in order to evaluate the effectiveness of AZA as a depigmenting agent and as a chemotherapeutic agent. Twenty-seven uniformly black pigmented guinea pigs were given topical applications of various concentrations (3, 5, 10, 15, and 20%) of AZA preparations for 8 weeks, and their effects on the melanocytes of epilated skin of the backs and the nonepilated ears of guinea pigs were compared to the effects of well-known depigmenting agents. Whereas 4-isopropylcatechol, monobenzylether of hydroquinone, monoethylether of hydroquinone, hydroquinone, and 4-hydroxyanisole were found to be selectively cytotoxic to melanocytes in black-skinned guinea pigs, AZA has little or no visually recognizable effect on melanocytes in these animals. The therapeutic effect of local s.c. injections of various concentrations of AZA preparations on the development of s.c. implanted B-16 melanoma tumor was evaluated in 96 C57BL/6J mice. In addition, 31 BDF1 mice, implanted i.p. with B-16 melanoma tumor, were used to assess the effect of 100-500 mg/kg concentrations of AZA administered i.p. In both studies, AZA revealed no significant tumoristatic or tumoricidal effect on the size, color, and growth of melanoma. The effect of AZA was also evaluated on S-91A (melanotic or pigmented) and S-91B (amelanotic) human melanoma cells in culture. Low concentrations (10(-5) and 10(-3) M) of AZA had no inhibitory effect on the growth of these cells. Only at higher concentrations (greater than 10(-3) M) was a cytotoxic effect on cell viability observed. These observations indicate AZA is not selectively cytotoxic to normal and proliferative melanocytes and has no apparent inhibitory effect on the formative process of melanin pigmentation.

Animals↗
PubMed1985

Ocular findings in patients treated with PUVA.

This 5-year prospective study of ophthalmologic findings in 1299 patients treated with oral 8-methoxypsoralen photochemotherapy (PUVA) for psoriasis failed to demonstrate a significant dose-dependent increase in the risk of developing symptomatic cataracts. These patients were instructed to wear UVA-blocking eyeglasses when exposed to sunlight and during treatment for a 12-h period beginning from the time of 8-methoxypsoralen ingestion. However, we did observe a small increase in the risk for development of nuclear sclerosis and posterior subcapsular opacities among patients who received at least 100 PUVA treatments, compared to patients with fewer than 100 treatments (relative risk = 2.3 and 3.0, respectively; p less than .05 both comparisons). We compared our results to those of a large, population-based study and found, after adjusting for differences in methods, that the prevalence of cataracts in our study patients, aged 52-75 years, was not significantly different. Since the latency period for development of symptomatic ocular abnormalities may be longer than 5 years, continued surveillance of our cohort and continued use of appropriate ocular protection by all patients treated with PUVA is indicated.

Aged↗
PubMed1985

Melanin macroglobules as a cellular marker of neurofibromatosis: a quantitative study.

To investigate the usefulness of melanin macroglobules (MMG) as a cellular marker for neurofibromatosis, their density was quantified in biopsies of café-au-lait spots (macules) (CALM) from 22 patients with von Recklinghausen's neurofibromatosis, 6 patients with bilateral acoustic neurofibromatosis, and 19 controls. The density of MMG was significantly higher in biopsies of the CALM of patients with von Recklinghausen's neurofibromatosis than in patients with bilateral acoustic neurofibromatosis (p less than .01) or controls (p less than .0008). The mode of acquisition of von Recklinghausen's neurofibromatosis (inherited vs new mutation) was not related to the density of MMG. On light microscopy, 14/22 (64%) patients with von Recklinghausen's neurofibromatosis had 11 or more MMG per 5 high-power fields. In contrast, none of the other two groups had more than 10 MMG per 5 high-power fields.

Adolescent↗
PubMed1984

Cigarette smoking and malignant melanoma. Prognostic implications.

Heavy cigarette smoking (current smoking with greater than 15-pack-year smoking history), along with 13 other variables, were tested for their ability to predict death in 196 patients with clinical Stage I melanoma. A stepwise proportional hazards general linear model (Cox multivariate analysis) showed that although heavy cigarette smoking as a single variable is an adverse prognostic marker (P = 0.0065), it has only suggestive prognostic significance once thickness factors are taken into account (P = 0.0747). People who stopped smoking had the same survival as nonsmokers. Clinical Stage I patients with melanoma who were heavy smokers presented with thicker lesions than their nonsmoking counterparts (P = 0.037). Although cigarette smoking may play a role in the biologic behavior of melanoma by mediating an effect on thickness, it need not be considered as an independent stratification criterion when analyzing results of melanoma prognosis or treatment.

Adult↗
PubMed1984

Cutaneous squamous-cell carcinoma in patients treated with PUVA.

A 5.7-year prospective study of 1380 patients treated for psoriasis with oral methoxsalen (8-methoxypsoralen) and ultraviolet A photochemotherapy (PUVA) revealed that after adjustment for exposures to ionizing radiation and topical tar preparations, the risk that cutaneous squamous-cell carcinoma would develop at least 22 months after the first exposure to PUVA was 12.8 times higher in patients exposed to a high dose than in those exposed to a low dose (95 per cent confidence interval, 5.8 to 28.5). No substantial dose-related increase was noted for basal-cell carcinoma. The dose-dependent risk of cutaneous squamous-cell carcinoma suggests that PUVA can act as an independent carcinogen. In our study, morbidity associated with these tumors has been limited, but further follow-up is needed. Meanwhile, patients treated with PUVA should be followed closely for the possible development of cutaneous squamous-cell carcinoma.

Adult↗
PubMed1984

Late recurrence (beyond ten years) of cutaneous malignant melanoma. Report of two cases and a review of the literature.

Two patients experienced a recurrence of cutaneous malignant melanoma more than ten years after initial diagnosis, treatment, and presumed cure. A review of the literature shows that delayed metastases (more than ten years) have been clearly documented in only seven previous patients with cutaneous malignant melanoma. With the rising incidence of cutaneous malignant melanoma, physicians may begin to see more cases of late recurrence in patients with a history of presumably cured disease. Although uncommon, late recurrence has important implications in the long-term management of all patients with malignant melanoma.

Adolescent↗
PubMed1984

Conservative surgical management of superficially invasive cutaneous melanoma.

Between 1976 and 1980, 136 patients were evaluated for primary treatment of cutaneous melanoma. Forty-nine lesions were invasive to Clark's Level II (38 patients) or III (11 patients) with a thickness of 0.3 to 1.2 mm. Conservative re-excision was advised as definitive therapy for these patients. The margin of resection was defined as the maximum excision that would allow primary closure of the wound. Pathology reports of the re-excised specimens revealed the narrowest margins to be 0.7 to 4 cm. Unexpected residual tumor was present in 2 specimens and melanocytic hyperplasia in 12 specimens. After a follow-up period of 2.5 to 7.0 years, there have been no local recurrences. One patient developed regional lymph node metastases 16 months and, then central nervous system (CNS) metastases 25 months after primary treatment. A second patient died with pulmonary metastases 4.5 years after initial therapy. Melanomas that are not deeply invasive do not require wide excision and skin grafting for local control. Occasionally these thin lesions do produce systemic metastases, emphasizing the need for long-term follow-up of even "low-risk" patients.

Adult↗
PubMed1984

Morphologic alterations of epidermal melanocytes and melanosomes in PUVA lentigines: a comparative ultrastructural investigation of lentigines induced by PUVA and sunlight.

Ultrastructural studies were conducted in order to determine morphologic and functional differences in melanocytes and melanosomes in PUVA lentigines and solar lentigines, and light-protected buttock skin. Compared to melanocytes in solar lentigines from 7 subjects and light-protected buttock skin from 5 subjects (none of these subjects had received UV radiation therapy), melanocytes in PUVA lentigines from 6 subjects generally had longer and more numerous dendrites, and showed more active melanogenesis. Basal keratinocytes in PUVA lentigines had a significantly increased frequency of large, single melanosomes, and revealed significantly larger individual melanosomes within compound melanosomes. Other findings in some PUVA lentigines included the close apposition of Langerhans cells to melanocytes, and atypical nuclear, cytoplasmic and melanosomal alterations, including melanosomal pleomorphism and melanin macroglobules. The presence of relatively large and predominantly single melanosomes in basal keratinocytes of PUVA lentigines suggests more active melanogenesis and/or an irreversible somatic alteration. It will be important to determine the clinical course and ultrastructural findings of PUVA lentigines that persist long after PUVA is discontinued.

Adult↗
PubMed1984

A new liquid formulation of 8-methoxypsoralen: bioactivity and effect of diet.

A new encapsulated liquid preparation of methoxsalen (8-MOP) and a commonly used crystalline preparation (Oxsoralen) were compared in 12 subjects. Each subject ingested 0.6 mg/kg body weight of each formulation on different days. Six subjects ingested a low-fat meal before ingestion of drug, and 6 subjects ingested a high-fat meal. Photosensitivity was tested from 1/2 to 6 h after ingestion of 8-MOP by exposure to 320-400 nm radiation (UVA) from a filtered xenon are lamp. A series of graduated doses of UVA were administered at each time point to determine the minimum phototoxic dose (MPD). Ingestion of 8-MOP and grading of erythema were conducted in a double-blind manner, and bilaterally symmetrical exposure sites were used to test each preparation. The phototoxic reaction was observed at 24, 48, and 72 h by two experienced observers who were unaware which formulation had been ingested. The two test days were separated by 48 h. The encapsulated liquid preparation induced greater photosensitivity than Oxsoralen (mean MPDs +/- SD: 7.1 +/- 4.7 vs 12.9 +/- 6.7 J/cm2, respectively; n = 12; p less than 0.05). The encapsulated liquid preparation also induced photosensitivity earlier than Oxsoralen (mean hours after ingestion to achieve peak photosensitivity +/- SD: 2.1 +/- 1.2 vs 3.9 +/- 1.6, respectively; n = 9; borderline significance). On a low-fat diet the encapsulated liquid peaked 2.5 h earlier than Oxsoralen, as well as showing the shortest and the most predictable period of photosensitivity. However, overall, the degree and time of peak photosensitivity induced by either preparation were unaffected by diet. Ingestion of the encapsulated liquid induced photosensitivity in all 12 subjects; Oxsoralen failed to sensitize 3 subjects. Side effects were similar after both preparations. A new encapsulated liquid preparation of 8-MOP may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy, and a shortened waiting period following ingestion of drug.

Adolescent↗
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↗