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Biomedical subjects

J L Hawk

Publications and source records attributed to J L Hawk.

At least 109 records · Page 6Linked to original sources

Evidence for eosinophil degranulation with deposition of granule major basic protein in solar urticaria.

Multiple sequential biopsy specimens of wheals elicited by a solar simulator in four patients with severe solar urticaria were studied with the use of indirect immunofluorescence for eosinophil granule major basic protein. Examination of control biopsy specimens from normal, unstimulated skin did not show eosinophils or major basic protein deposition. Five minutes after solar simulation, eosinophils were observed in vessels in the dermis, and 2 hours later there was marked tissue eosinophilia. Extracellular major basic protein was extensively deposited in the dermis at 2 and 24 hours, suggesting eosinophil degranulation. Thus evolution of the solar urticaria wheal is accompanied by infiltration of eosinophils and neutrophils and by tissue deposition of the eosinophil major basic protein, suggesting eosinophil degranulation.

Blood Proteins↗

Chronic actinic dermatitis: an immunohistologic and photobiologic study.

Photobiologic, histologic, and immunohistochemical findings in 14 patients with chronic actinic dermatitis were compared. Grading of routine histologic features of involved skin demonstrated a spectrum of abnormalities ranging from changes resembling chronic dermatitis to those of cutaneous T cell lymphoma. Immunohistochemical staining showed dermal infiltrates to consist predominantly of T lymphocytes, with a significant trend toward lower CD4+/CD8+ ratios in cases with more florid histologic findings. Circulating CD4+/CD8+ cell ratios were normal in five patients and reduced in one patient. Photosensitivity extending to wavelengths longer than 340 nm was detected in eight patients, but the spectrum of photobiologic abnormality did not appear to correlate with either grading of histologic severity or variation in T cell subsets in lesional skin.

Aged↗

Sunbed-induced pseudoporphyria.

The clinical details of four fair-skinned women with recurrent blistering and skin fragility are presented. All had considerable sun-exposure and had used sunbeds for years. Specific causes of bullous dermatoses including drug ingestion, porphyria, cutaneous amyloidosis and epidermolysis bullosa acquisita were excluded. Long-term recurrent exposure to high doses of sunbed radiation in chronically sun-damaged skin appears to be a further cause of pseudoporphyria.

Adult↗

UVA sunbeds: tanning, photoprotection, acute adverse effects and immunological changes.

The effects on 31 normal subjects following exposure to sunbeds containing UVA lamps with minimal UVB emission have been compared in a double-blind study with the effects on nine control subjects of a similar exposure course three times weekly for 4 weeks to sunbeds emitting visible light. On previously untanned areas, all those subjects on active treatment developed a mild tan; in tanned areas they all developed a moderate tan, while all control subjects developed a minimal to mild tan. The mean protection factor against later UVB-induced erythema was 3.2 +/- 0.3 after the active course and 1.6 +/- 0.2 among the controls. Significantly more frequent adverse cutaneous effects for active subjects were pruritus, erythema, freckling, burning sensation, dryness and polymorphic light eruption. Cutaneous Langerhans cell numbers, and blood CD3+ (pan T-cell) and CD4+ (helper T-cell) lymphocyte subsets were reduced in both active and control groups. CD8+ (cytotoxic/suppressor T-cell) counts were similarly but not significantly reduced in both groups. Pityrosporum yeast counts were significantly reduced in both groups. The changes found in both groups seem attributable to small amounts of UVB emission from both active and control lamps.

Adolescent↗

Polymorphic light eruption: an immunopathological study of evolving lesions.

Polymorphic light eruption (PLE) papules were successfully induced on previously affected sites in 11 out of 14 patients with PLE 4-20 h after single exposures to suberythemogenic doses of solar simulated radiation. Histological examination of biopsies performed 1 h, 5 h, 24 h, 72 h and 144 h post-irradiation revealed onset within 5 h of perivascular cellular infiltration. The infiltrate was dominated by lymphocytes in both early and established lesions, without evident epidermal pathology. Immunohistochemistry demonstrated a predominance of CD4+ cells in lesions up to 72 h post-induction, but later biopsies were dominated by a CD8+ infiltrate. Significantly increased numbers of dermal macrophages and CD1b+ cells were detected 1 h and 5 h post-irradiation, respectively. These findings are consistent with a delayed type hypersensitivity response underlying the pathogenesis of polymorphic light eruption.

Adult↗

Azathioprine treatment in chronic actinic dermatitis: a double-blind controlled trial with monitoring of exposure to ultraviolet radiation.

Oral azathioprine was compared with placebo in a double-blind controlled trial of therapy in chronic actinic dermatitis (CAD), a rare eczematous photodermatosis. Eighteen severely affected patients were randomly allocated to azathioprine 50 mg t.d.s. or placebo over a 2-year period. Severity of itch and rash were assessed weekly by each patient on a visual analogue scale and overall clinical status monthly by a medical observer. Monitoring of patient ultraviolet radiation (UVR) exposure was undertaken throughout treatment by polysulphone film lapel-badge dosimetry. Five of 8 patients treated with azathioprine but none of 10 placebo patients achieved remission within 6 months. One patient could not tolerate treatment because of gastrointestinal effects. No haematological or hepatic abnormality was noted. The marked improvement in clinical status of actively treated patients (P less than 0.02, Fisher's exact test), led to early termination of the trial. Oral azathioprine therapy is an effective and usually well tolerated treatment in chronic actinic dermatitis.

Aged↗

Actinic folliculitis--response to isotretinoin.

Two female patients with an identical facial eruption, consisting of severe outbreaks of folliculitic pustules occurring 6 to 24 h following periods of intense sun exposure and persisting for several days, are reported. Both failed to improve with standard acne treatments, but responded well to oral isotretinoin therapy.

Adult↗

A flow cytometric study of actinic reticuloid.

Potential progression of actinic reticuloid to malignant lymphoma was studied by DNA flow cytometry of affected formalin-fixed skin from six patients with histological and photobiological evidence of actinic reticuloid. DNA aneuploidy was absent in all patients providing no evidence that actinic reticuloid is a premalignant condition.

Aged↗

A modified dosage schedule for increased efficiency in PUVA treatment of psoriasis.

Ten patients with chronic widespread plaque psoriasis, all of whom had previously completely cleared and suffered a subsequent widespread relapse after conventional PUVA therapy, were treated with a modified UVA dosage schedule, with psoralen formulation and dosage unchanged. Initial and incremental UVA doses were maximized to near-erythemogenic levels as determined by weekly testing for minimal phototoxic dose (MPD), treatment being given three times a week. A comparison of complete psoriasis clearing between the modified treatment and the last PUVA course showed a geometric mean reduction in treatment duration of 55% (P less than 0.001) for a similar number of treatments each week, and a cumulative UVA dose of 31% (P less than 0.05), representing a reduction in treatment duration from 9.1 to 4.1 weeks and cumulative UVA dose reduction of 100.8 to 69.9 J/cm2. Such an improvement in efficiency permits a marked increase in treated patient numbers for the same cost, and is more convenient. The reduction in the total cumulative UVA dose given as larger individual doses also seems likely to lead to a lower incidence of cutaneous long-term, especially carcinogenic, adverse effects.

Humans↗

Monitoring of patients taking canthaxanthin and carotene: an electroretinographic and ophthalmological survey.

1. Patients who have taken canthaxanthin and beta-carotene to avert phototoxicity have been monitored by electroretinographic testing. 2. Patients took the compounds only during the summer months, but were monitored for more than 1 year to determine if seasonal changes in the ERG were visible. 3. The characteristic refractile retinal crystals reduced during the winter. 4. The scotopic b-wave amplitude increased during the winter, whether evoked by red or blue flashes. 5. No other ERG parameter altered. 6. Changes noted in 3 and 4 above are reversible. 7. A dose/ERG-amplitude response relationship was established, but no correlation between blood level or total cumulative dose and b-wave amplitude could be found. 8. It is suggested that the Müller cells concentrate canthaxanthin and this is the mechanism which affects the ERG.

Aged↗

Effect of simulated sunlight on Langerhans' cells in malignant melanoma patients.

The effect of artificial sunlight on the number and HLA class II expression of Langerhans' cells was studied in 10 patients with malignant melanoma and 10 control volunteers. The total number of Langerhans' cell decreased in both groups but at 96 h there was a greater and significant decrease (p less than 0.01) in the number of Langerhans' cells in the melanoma group, compared with controls. This decrease persisted and was still greater in the melanoma group (p less than 0.02) at one week post-irradiation. There was a rise in Langerhans' cell count over the following 3 weeks in both groups. Unexpectedly, during this period in the melanoma group-but not controls-there was a significant median peak rise above pre-irradiation levels (p less than 0.001). Alteration in the response of Langerhans' cells to sunlight may play a part in the aetiology of malignant melanoma.

Adult↗

Successful treatment of severe polymorphous light eruption with azathioprine.

Two patients with severe, disabling polymorphous light eruption, who were unable to tolerate photochemotherapy and who were unresponsive to alternative recognized therapies, are described. In both cases short-term treatment with azathioprine achieved a marked clinical improvement, confirmed by testing with an irradiation monochromator. This response suggests an immunological basis for polymorphous light eruption. Patients with polymorphous light eruption vary considerably with regard to degree of photosensitivity, and while azathioprine therapy should not be considered in the majority of sufferers, we have shown that it can be very helpful in rare patients with exceptionally severe disease.

Azathioprine↗

Zinc chelatase in human lymphocytes: detection of the enzymatic defect in erythropoietic protoporphyria.

We describe a fluorometric assay for heme synthetase, the enzyme that is genetically deficient in erythropoietic protoporphyria. The method, which can readily detect activity in 1 microliter of packed human lymphocytes, is based on the formation of zinc protoheme from protoporphyrin IX. That zinc chelatase and ferrochelatase activities reside in the same enzyme was shown by the competitive action of ferrous ions and the inhibitory effects of N-methyl protoporphyrin (a specific inhibitor of heme synthetase) on zinc chelatase. The Km for zinc was 11 micrograms and that for protoporphyrin IX was 6 microM. The Ki fro ferrous ions was 14 microM. Zinc chelatase was reduced to 15.3% of the mean control activity in lymphocytes obtained from patients with protoporphyria, thus confirming the defect of heme biosynthesis in this disorder. The assay should prove to be useful for determining heme synthetase in tissues with low specific activity and to investigate further the enzymatic defect in protoporphyria.

Erythropoiesis↗

Xeroderma pigmentosum complementation group F in a non-Japanese patient.

Genetic complementation studies allowed assignment of a 22-year-old-white woman to the rare complementation group of classic, excision-defective xeroderma pigmentosum (group F cell strain), previously reported only in patients from Japan. She manifested mild cutaneous changes, with no tumors and normal sensitivity to monochromatic ultraviolet irradiation. Unscheduled deoxyribonucleic acid synthesis in cultured fibroblasts (XP126LO) after irradiation with germicidal ultraviolet light was reduced to 13% of control values during the first 2 hours and rose to 45% of normal by 7 to 8 hours.

Adult↗

Dermatopharmacology: drugs around the corner.

This article describes impending advances in drug treatment of skin diseases. We have included the following categories: (1) interesting new drugs for which there are reasonable prospects of eventual licensing for skin indications, (2) important novel compounds whose progress through licensing procedures, although incomplete at the time of writing, is advanced, and (3) new indications or improved regimens that have recently emerged for established drugs.

Azathioprine↗

The presence of neutrophils in human cutaneous ultraviolet-B inflammation.

We report the first observation of neutrophils in the dermal inflammatory infiltrate in human skin soon after moderate ultraviolet-B (UVB) irradiation. Thus human UVB-induced cutaneous inflammation, in this as in other respects, appears to resemble other human acute inflammatory responses to injury.

Adult↗