The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data.

BACKGROUND: Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans. OBJECTIVES: To determine the skin cancer incidence in a population treated with TL-01 phototherapy. PATIENTS AND METHODS: All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex. RESULTS: Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0.04-13). The median cumulative number of TL-01 treatments and dose were 23 (1-199) and 13 337 (30-284 415) mJ cm(-2), respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4.7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102-391); P < 0.05]. CONCLUSIONS: A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential.

The optimal time to determine the minimal phototoxic dose in skin photosensitized by topical 8 methoxypsoralen.

BACKGROUND: We recently investigated the characteristics of psoralen plus ultraviolet (UV) A erythema in skin photosensitized by topical 8-methoxypsoralen (8-MOP) in three independent studies. OBJECTIVES: In order to determine the optimal time to read the minimal phototoxic dose (MPD) after treatment with topical 8-MOP and irradiation with UVA, we assessed the overall data. METHODS: One forearm of each subject was immersed in 8-MOP solution for 15 min and test sites on the flexor surface of the forearm were immediately exposed to a UVA dose series. Erythema was assessed visually and objectively using a reflectance instrument at 24-h intervals for 7 days. RESULTS: Results were obtained from 44 subjects (predominantly Fitzpatrick skin phototype II). A broad erythemal plateau was evident beyond 72 h and the visual MPD was significantly lower at 96, 120 and 144 h than at 72 h (P < 0.01). Only 30% of subjects were at peak erythema at the conventional MPD assessment time of 72 h. The median time to reach maximal erythema was 96 h (range 48-144). Objectively, 85% of subjects were at peak erythema at or beyond 96 h. CONCLUSIONS: We recommend that (i) the optimal time to read the topical 8-MOP MPD is 4 days after UVA exposure as readings beyond this time may be difficult to interpret because of the development of pigmentation, and (ii) 40% of the topical 8-MOP MPD should be considered for the first treatment.

Whole-body UVB (TL-01) or UVA-1 irradiation does not alter the levels of immunomodulatory cytokines in the serum of human volunteers.

BACKGROUND/PURPOSE: Ultraviolet (UV) exposure of mammalian skin induces local and systemic immunosuppression. In mice it has been proposed that systemic immunosuppression is mediated by an UV-induced cytokine cascade involving systemic interleukin (IL)-4 and IL-10 and a reduction in IL-12 activity. To investigate whether there was a parallel mechanism in humans we examined the effect of whole-body narrowband ultraviolet B (UVB) (311-313 nm; TL-01) and ultraviolet A (UVA)-1 (340-400 nm) on serum cytokine levels. METHODS/RESULTS: In a first study, five male psoriatic subjects were whole-body irradiated with three sessions of a standard UVB (TL-01) phototherapy regimen previously shown to cause downregulation of natural killer cell activity and T helper 1 (Th1) and Th2 cytokine production by peripheral blood mononuclear cells. Enzyme-linked immunoabsorbent assay (ELISA) of sera taken before and after the third session showed no effect of phototherapy on IL-10 and tumour necrosis factor-alpha (TNF-alpha). In a second study, five healthy subjects received three whole-body exposures of UVB (TL-01) and five other healthy subjects received three exposures of UVA-1 on alternate days (total 22 J/cm(2)). Blood samples were taken before the first irradiation and at 0, 4, 8, 12, 14, 24 and 48 h after the third irradiation. The sera were subsequently analysed for IL-10, IL-12, IL-8, IL-1beta and TNF-alpha, by ELISA. The levels of IL-1beta and TNF-alpha were below detection limits (<5 pg/ml), while no significant change in the levels of IL-10, IL-12 or IL-8 was detected as a result of either TL-01 or UVA-1. CONCLUSIONS: It seems unlikely that a modulation in these circulating cytokines assessed in this study accounts for systemic UV-induced immunosuppression in human subjects.

A randomized controlled trial of narrowband ultraviolet B vs bath-psoralen plus ultraviolet A photochemotherapy for psoriasis.

BACKGROUND: In 1991, consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy (PUVA) for those requiring second-line therapy for psoriasis. Narrowband (TL-01) UVB has since become more widely available, replacing the less effective broadband sources. Objectives To compare the efficacy of TL-01 UVB phototherapy and trimethoxypsoralen (TMP) bath-PUVA for chronic plaque psoriasis. PARTICIPANTS AND METHODS: A randomized, observer-masked, intraindividually controlled, paired (half-body) study was done in the Photo(chemo)therapy Unit in Ninewells Hospital and Medical School, Dundee. The study comprised 28 patients (skin phototypes I-III) with chronic plaque psoriasis. Each patient's body halves (sagittal plane) were treated independently, one-half with TL-01 UVB, the other with bath-PUVA. Both treatments were administered according to standard, optimized regimens. Treatment was continued until clearance or minimal residual activity (MRA), or a maximum of 30 treatments. The main outcome measures were treatments and time to clearance/MRA, the proportion reaching clearance/MRA, change in psoriasis severity score (scaling, erythema and induration) and remission durations. RESULTS: Of 18 who completed the study, all reached clearance/MRA with TL-01, but three were still not clear after 30 PUVA exposures. TL-01 achieved clearance/MRA a median of 11 (6.5-25; P = 0.001) days more quickly than PUVA, but required a median of 24.5 compared with 19 exposures [95% confidence interval (CI) for difference 1.5-5.5; P = 0.01]. Ten patients were withdrawn (four because of inadequate response of PUVA-treated halves). Analysed on an intention-to-treat basis, 21 of 28 (75%) of all participants reached clearance/MRA with TL-01 compared with 15 of 28 (54%) with PUVA (95% CI for difference 4-37%; P = 0.03). Remission durations did not differ. CONCLUSIONS: When administered according to these regimens in a skin phototype I-III population, TL-01 UVB is more efficacious than TMP bath-PUVA in the treatment of chronic plaque psoriasis.

Time course of PUVA erythema.

Optimization of the PUVA regime requires knowledge of the time-course and dose-response characteristics of PUVA erythema. Although existing guidelines recommend determination of the minimal phototoxic dose (MPD) 72 hours after UVA exposure and treatment administered 72 hours apart, recent evidence suggests that maximal PUVA erythema occurs beyond this time point, and hence the current assessment time underestimates the phototoxic effect of PUVA. This report reviews the current literature, including the authors' own experience of the characteristics of PUVA erythema, and recommends that the optimal time to read the PUVA MPD is 96 h.

Time course of skin photosensitivity following trimethylpsoralen bath PUVA.

One aspect of bath photochemotherapy (PUVA) that requires clarification is the duration of psoralen-induced cutaneous photosensitisation under conditions simulating clinical use. Using a half back comparison study technique, we investigated the persistence of trimethylpsoralen (TMP)-induced photosensitivity in skin irradiated to simulate a first PUVA exposure compared with un-irradiated skin. Baseline UVA minimal erythema dose and minimal phototoxic dose (MPD) were determined in 13 healthy volunteers. After readings at 72 h, subjects were bathed in TMP bath water for 15 min and one half of the back was immediately exposed to 40% of the MPD. Test sites (1.5 cm2) on both halves of the back were then irradiated with a UVA dose series at 15 min, 5, 10, 24, 34, 48 and 72 h after the bath. MPD readings were recorded visually at 72 h after each UVA exposure. The UVA MED was >25 J/cm2 in all the subjects. At each time point, a phototoxic index (PI) was calculated as UVA MED/MPD. In un-irradiated skin, photosensitivity returned to normal (PI=1) within 24 h after the TMP bath. In contrast, skin pre-irradiated to simulate the first PUVA treatment was still significantly photosensitive (PI=2.3; P=0.002) at 48 h. Contrary to previous recommendations, these data suggest that patients should be advised to avoid ambient or artificial sources of UVA throughout their course of TMP bath PUVA to reduce the risk of phototoxic erythema.

[Vanadium compounds--a new class of therapeutic agents for the treatment of diabetes mellitus]. / Vanadiisoderzhashchie soedineniia--novyi klass terapevticheskikh sredstv dlia lecheniia sakharnogo diabeta.

Vanadium compounds as insulin mimics with promising therapeutic properties are reviewed. The biological effects of both inorganic forms of vanadium and vanadyl organic complexes are decried for various animal models. These effects include hypoglycemic and insulin reserve actions, insulin sensitivity enhance, cholesterol lowering and other manifestations. The effectiveness of vanadium compounds in diabetes treatment is confirmed with clinical trials. The possible mechanisms of insulin-like effects of vanadium are discussed. The various nutritional supplements for patients with diabetes mellitus including vanadium-contained used in Russia and abroad are also considered.

Hydroa vacciniforme: A clinical and follow-up study of 17 cases.

BACKGROUND: Hydroa vacciniforme (HV) is a rare, sporadic, idiopathic photodermatosis characterized by vesicles and crust formation after sunlight exposure. The lesions typically heal with vacciniform scarring. OBJECTIVE: We identify and review the clinical features and follow-up data of Scottish patients with HV and report on the prevalence of this condition. This is the largest recent study of HV patients from a single center. METHODS: In this retrospective study, patients with HV were identified by means of the diagnostic database from the Photobiology Unit, Dundee. Patients were contacted and details of clinical features, duration of disease, results of investigations, and treatment were recorded. At review, disease progress was assessed. RESULTS: Between 1973 and 1997, 17 patients (9 males and 8 females) with a diagnosis of HV were investigated. Data from 15 patients showed a mean age at onset of 7.9 years (range, 1 to 16 years), with females (mean, 6.7 years; range, 2 to 12 years) having an earlier onset than males (mean, 8.7 years; range, 1 to 16 years). A bimodal age distribution was also identified with onsets between the ages of 1 and 7 years and 12 and 16 years. At review, spontaneous clearing had occurred in 9 patients (60%) with mean duration of disease being 9 years (range, 4 to 17 years). Males had longer disease duration (mean, 11 years; range, 5 to 17 years) than females (mean, 5 years; range, 4 to 7 years). Eight patients (53%) were sensitive in the UVA wave-band on monochromator phototesting, and 6 (40%) experienced papulovesicular lesions on repetitive broad-spectrum UVA irradiation. All patients received broad-spectrum sunscreens with variable results. Of the 5 patients treated with narrow-band UVB (TL-01) phototherapy, 3 reported beneficial results with an increase in tolerance to sunlight exposure and associated reduction in disease severity. CONCLUSION: The estimated prevalence of HV was at least 0.34 cases per 100,000 with an approximately equal sex ratio. Males had a later onset and longer duration of disease than females. Phototesting showed abnormal responses in the UVA wavebands in 53% of cases, whereas 60% of patients treated with prophylactic TL-01 phototherapy found it beneficial.

Artificial hardening for polymorphic light eruption: practical points from ten years' experience.

The conservative approach of sunlight avoidance and broad-spectrum sunscreen is often disappointing in patients with moderate to severe polymorphic light eruption. A springtime course of prophylactic artificial hardening with ultraviolet B (UVB) phototherapy or psoralen plus ultraviolet A (PUVA) photochemotherapy will often allow patients to tolerate more sunlight and give them greater freedom during the summer. In this retrospective study we describe ten years' experience of such "desensitization" treatment. Individualized therapy with attention to detail will maximize the effectiveness of this treatment.

The photosensitivity dermatitis and actinic reticuloid syndrome (chronic actinic dermatitis) occurring in seven young atopic dermatitis patients.

Seven young patients with atopic dermatitis (AD) who presented with a marked photoexposed site dermatitis have been investigated in detail. The results of phototesting, patch testing and other investigations were compatible with the diagnosis of photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) (chronic actinic dermatitis). It is known that AD patients may have photoaggravation of their dermatitis or exacerbation secondary to a photodermatosis, such as polymorphic light eruption, actinic prurigo or drug-induced phototoxicity. The patients we describe, however, appear to be an uncommon AD subgroup affected by PD/AR. We recommend that all AD patients who have a history of sunlight-induced exacerbation or marked intolerance of PUVA or ultraviolet B phototherapy should have phototesting and patch testing conducted.

[Compensatory capabilities of the symmetrical regions of the dominant and subdominant hemispheres of the human brain]. / O kompensatornykh vozmozhnostiakh simmetrichnykh oblastei dominantnogo i subdominantnogo polusharii golovnogo mozga cheloveka

A comparison was made between the EEG characteristics and spectral power of EEG frequencies in symmetrical parts of both cerebral hemispheres in order to elucidate the involvement of these areas in compensatory processes in patients with tumours localized in one of the cerebral hemispheres, before and after the removal of the tumour. Before the operation, the presence of a focus of pathological activity causing inactivation of adjacent cortical cells, is attended with activation of cells in the symmetrical areas of the intact hemisphere. Elimination of the pathological focus results in the fluctuation of interhemispheric asymmetry; for certain time periods inactivation in the sick hemisphere is replaced by activation, while in the intact hemisphere activation changes over to inactivation. The revealed properties are termed by the authors as interhemispheric compensatory conjugation of reactions. They probably reflect the potential possibilities of different areas in the process of compensation.

[Correlation between electrical activity in symmetrical regions of the cerebral cortex and unilateral lesions]. / O sootnoshenii elektricheskoi aktivnosti v simmetrichnykh oblastiakh kory mozga pri ego odnostoronnikh proazheniiakh

Functional interrelations between cerebral hemispheres, and particularly, between their symmetrical areas, were studied during compensatory processes in patients with tumours localized in one of the hemispheres. Analysis of spontaneous electrical activity before the operation on the tumour revealed several types of interhemispheric relations. The existence of a sharply pronounced pathological activity in one hemisphere, testifying to inactivation of cortical cells, is, as a rule, accompanied by activation in the intact hemisphere, especially in the areas symmetrical with those injured. In cases of less pronounced pathology, with partial retention of activity of the cortical cells in the injured areas of the affected hemisphere, a lesser degree of activation is observed in the intact hemisphere. The data point to a development of substituting-compensatory processes in the areas of the intact hemisphere symmetrical with the injured ones and to the possibility of testing the processes electrophysiologically.