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At least 127 records · Page 7Linked to original sources
PubMed1988

5-Methoxypsoralen (Bergapten) for photochemotherapy. Bioavailability, phototoxicity, and clinical efficacy in psoriasis of a new drug preparation.

In a previous study we evaluated a microcrystalline preparation of 5-methoxypsoralen (5-MOP; Bergapten) for its photochemotherapeutic properties. Preliminary data indicated that the clinical efficacy of 5-MOP is comparable to that of 8-methoxypsoralen. 5-MOP appeared as a promising alternative photosensitizer for the management of psoriasis because of the almost complete lack of phototoxic and drug intolerance reactions that are frequently encountered in patients undergoing 8-MOP photochemotherapy. With a new liquid preparation of 5-MOP we have now extended our earlier investigation on a larger clinical scale and have correlated the clinical response with the bioavailability of the drug. Serum level determinations showed an absorption rate of only approximately 25% that of 8-MOP. When administered in the same dosage as 8-MOP, 5-MOP turned out to be significantly less effective; however, by doubling the oral dosage, comparable results in terms of clearing of psoriasis were obtained. Also with this high-dose 5-MOP regimen, no drug intolerance was noted and other side effects, such as severe erythema, pruritus, and nausea, occurred only rarely. We propose 5-MOP as a valuable alternative for photochemotherapy (PUVA) of PUVA-responsive diseases.

5-Methoxypsoralen↗
PubMed1995

Human papillomavirus and widespread cutaneous carcinoma after PUVA photochemotherapy.

BACKGROUND: Oral psoralen with UV-A (PUVA) photochemotherapy is known to cause cutaneous malignancies and has been associated with cutaneous immunosuppression. Human papillomavirus infection has also been associated with cutaneous malignancies and with immunosuppressed individuals. We therefore sought evidence of human papillomavirus infection in a patient with a long history of PUVA therapy and multiple cutaneous malignancies. OBSERVATIONS: During a 15-year period, an otherwise healthy patient with psoriasis who had undergone a 10-year course of PUVA photochemotherapy developed 13 squamous cell carcinomas, eight lesions diagnosed as "squamous cell carcinoma vs keratoacanthoma," 14 other keratoacanthomas, six basal cell carcinomas, one melanoma in situ, and 18 other keratinocytic dysplasias. Twenty-two of the 30 lesions tested for human papillomavirus DNA by polymerase chain reaction were positive for type 16/18, including six of the seven basal or squamous cell carcinomas tested. CONCLUSION: We hypothesize that PUVA therapy-induced immunosuppression may play an important role in PUVA-related carcinogenesis by affecting the extent and pathogenicity of human papillomavirus infection.

Carcinoma↗
PubMed1994

Use of extracorporeal photochemotherapy in heart transplant recipients during acute rejection: a case study.

Despite the growing availability of improved immunosuppressive agents, acute and chronic rejection episodes remain a major complication in heart transplant recipients. The rejection of allografts is a normal part of the body's response to foreign antigens. The key to controlling this response is to administer a regimen of multiple immunosuppressive drugs. Evidence indicates that by adding extracorporeal photochemotherapy to a standard immunomodulatory regimen, the rejection process can be reversed without significantly increasing patient risk. In this case study we examine extracorporeal photochemotherapy and the care of patients receiving this therapy.

Graft Rejection↗
PubMed1994

[Treatment of organ graft rejection by extracorporeal photochemotherapy].

Extracorporeal photochemotherapy is a recently developed immunomodulator treatment against heart and lung graft rejection. The recipient's mononuclear cells are screened and irradiated with UV-A in the presence of 8-methoxy-psoralene (8-MOP), then reinjected. We treated 4 patients who had begun to reject their heart and/or lung grafts, with this technique, using one session per week for 4 weeks, followed by one session every 2 weeks for 2 months, then one session per month. In all cases, extracorporeal photochemotherapy appeared to improve the clinical and biological status of these patients. Episodes of rejection which could not be reversed with immunosuppressor treatment alone were controlled.

Adolescent↗
PubMed1999

Narrowband UV-B phototherapy vs photochemotherapy in the treatment of chronic plaque-type psoriasis: a paired comparison study.

OBJECTIVE: To compare the therapeutic efficacy of narrowband (TL-01) UV-B phototherapy vs photochemotherapy (psoralen-UV-A [PUVA]) in patients with chronic plaque-type psoriasis. DESIGN: Open, nonrandomized, intraindividually controlled paired comparison study. SETTING: Phototherapeutic unit in a university hospital. PATIENTS: Twenty-five patients with chronic plaque-type psoriasis. INTERVENTIONS: Paired irradiations with threshold erythemogenic doses of narrowband UV-B and PUVA were given to the patients' dorsal aspect including the arms and legs. Treatment was performed 3 times weekly until complete or almost complete clearing with one or both regimens or over a maximum period of 18 exposures. MAIN OUTCOME MEASURES: Assessment of the Psoriasis Area and Severity Index (PASI) in each half of the patient's dorsal aspect before and after treatment with the 2 regimens. RESULTS: The median pretreatment PASI score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5 (range, 0-12.6) by the narrowband UV-B treatment and by 89% to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical analysis of these data showed a tendency for PUVA being superior to narrowband UV-B although the difference remained below the level of significance (P = .17). However, a clear effect of the pretreatment PASI score on the therapeutic outcome was found. Patients with higher baseline PASI scores responded significantly better to PUVA than to narrowband UV-B (P = .03). CONCLUSIONS: Our data demonstrate that in many patients with plaque-type psoriasis, narrowband UV-B is comparably as effective as PUVA and, given the lack of photosensitizer-related adverse reactions and the possibly lower long-term cancer risk, can be considered as first-line treatment. Treatment with PUVA, on the other hand, remains the mainstay for patients with high PASI scores who do not respond or whose psoriasis cannot be controlled adequately by narrowband UV-B.

Chronic Disease↗
PubMed1998

Improved photochemotherapy of malignant cells with daunomycin and the KTP laser.

Laser photochemotherapy of malignancies may become an effective palliative treatment for advanced had and neck cancer using light-sensitive, chemotherapeutic drugs activated in tumors via interstitial laser fiberoptics. Previously, it was reported that cultured human P3 squamous cells incubated 2 hours with daunomycin (Dn) exhibited tenfold enhanced cytotoxicity after exposure to argon laser light at 514 nm. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and daunomycin topoisomerase inhibition. In the current study phototoxicity of Dn-sensitized human cancer cells was tested using broad-spectrum white light compared to monochromatic green-wavelength light. Drug uptake and laser energy levels were optimized for maximum synergy. To test light-enhanced chemotherapy in vitro, the kinetics of cell uptake and toxicity of daunomycin was measured at 1, 2, and 5 microg/ml in three human tumor cell lines: P3 squamous-cell carcinoma, M26 melanoma, and TE671 fibrosarcoma. After 2 hr Dn uptake, all cell lines were tested for phototherapy response by exposure to 300- to 900-nm visible light from a xenon lamp or monochromatic 532-nm green light from a KTP laser. When the KTP laser output was varied from 0 to 120 Joules in Dn-sensitized tumor cells, a linear phototherapy response was seen with energy as low as 12 J inducing drug phototoxicity. These results provide evidence that daunomycin cytotoxicity is enhanced when exposed to 532-nm laser illumination in the three tumor types tested and confirm that the response is related to both energy level and drug dose.

Carcinoma, Squamous Cell↗
PubMed1996

Effects of the inhibitors of energy metabolism, lonidamine and levamisole, on 5-aminolevulinic-acid-induced photochemotherapy.

The ability of endogenously synthesized protoporphyrin IX (PpIX) to damage Chinese hamster lung fibroblasts of the line V79 by exposure to light was examined. This treatment induced reduction of cellular ATP, GTP, of the NADH/NAD+ ratio and of oxygen consumption. The present results indicate a close relationship between inhibition of respiration of irradiated cells and their ability to survive, e.g. 1 min of light exposure induced 90% inhibition of oxygen consumption and inactivation of approximately 95% of the cells, while the cellular content of ATP was reduced by only 15%. This indicates that the mitochondria are one of the primary targets of 5-aminolevulinic acid (ALA)-mediated photochemotherapy (PCT). In the present study, ALA-PCT was combined with the modulators of the glycolysis and the respiration chain, levamisole (LEV) and lonidamine (LND). A synergistic effect of combining ALA-PCT with non-toxic concentrations of LND was observed when LND was given prior to light exposure. This synergism was observed despite a substantial LND-induced inhibition of PpIX formation. At increasing doses of LND (>0.15 mM) the combination treatment becomes less efficient. This is due to the inhibition of PpIX synthesis induced by LND. A synergistic effect of ALA-PDT and LEV was found when LEV was given prior to light exposure. This was at least partly due to an LEV-stimulated effect on ALA-induced PpIX formation. However, it is not clear from the present results whether LEV may perturb energy metabolism in V79 cells since LEV alone did not reduce the energy charge or the NADH/NAD+ ratio. When LEV or LND were given after ALA-PCT, these 2 treatment modalities acted in an additive or slightly synergistic manner.

Aminolevulinic Acid↗
PubMed1992

Extracorporeal photochemotherapy for the treatment of systemic lupus erythematosus. A pilot study.

OBJECTIVE: To investigate the effectiveness and feasibility of extracorporeal photochemotherapy (ECP) in the treatment of an autoimmune disease with known cutaneous photosensitivity. METHODS: Ten patients with systemic lupus erythematosus (SLE) were treated with ECP in an open clinical trial. The efficacy of treatment was analyzed by means of established disease activity scores. RESULTS: Eight patients completed the trial. In 7 of the 8, there was a significant response to the treatment, with no or minor side effects. The clinical activity score in the group of 8 patients decreased from a median of 7 (range 4-9) to a median of 1 (range 0-5) (P less than 0.05). Laboratory abnormalities did not change significantly, but were mild at the outset. CONCLUSION: ECP led to clinical improvement of SLE without side effects. The effectiveness of this method should be investigated further in controlled clinical trials.

Adult↗
PubMed1990

Photochemotherapy of hypervascular dermal lesions: a possible alternative to photothermal therapy?

Continued improvement in the results of laser treatment of port wine stain, with reduction in scarring, will depend on the ability to use lasers to induce selective injury of only the abnormal blood vessels in the dermis while sparing the normal overlying epidermis. Photodynamic therapy, using an exogenous photosensitizing drug specifically activated by certain wavelengths of light, may be used to destroy selectively certain targets in biological systems. The current study demonstrates, in the chicken comb model, that photochemotherapy can be used to treat hypervascular dermal lesions while leaving the normal overlying epidermis completely intact.

Animals↗
PubMed2007

Intensive extracorporeal photochemotherapy in pediatric patients with chronic graft-versus-host disease (cGVHD).

Extracorporeal photochemotherapy (ECP) is an alternative treatment approach in the management of chronic graft-versus-host disease (cGVHD). However, few reports have investigated the optimal treatment schedule of ECP. We treated seven pediatric patients with steroid-resistant or -dependent cGVHD with ECP. Using the Therakos UVAR XTS system, ECP was begun three (three patients) or five (four patients) times a week initially. Complete and partial responses were obtained in three patients. Three of seven patients died of GVHD-related complications. In this group initial intensive ECP did not improve the rate of response. However, this schedule appeared well tolerated.

Adolescent↗
PubMed1979

An estimate of genetic risk from 8-methoxypsoralen photochemotherapy.

A method based on a combination of cell culture and pharmacokinetic data is explored as a way of estimating the possible genetic risk to man from a mutagenic chemical. 8-methoxypsoralen, which is given to psoriasis patients as part of a photochemotherapy regime, is used, since it represents a 'real-life' situation and possesses properties that make it particularly amenable to this approach. It is concluded that treatment of males for a mean period of 10 years before their spermatozoa were involved in conception would increase the gene mutation rate in the male germ line by a factor of 0.00125. The implications of this for the incidence of sex-linked and dominant disease in man are elaborated and the assumptions and limitations are set out. The fragility of the estimates is emphasized.

DNA↗
PubMed1982

Microenema of 8-methoxypsoralen in photochemotherapy of psoriasis.

Reasonably high plasma levels were obtained 1/2 h after 8-methoxypsoralen (8-MOP) administration by microenema. This method was used in photochemotherapy of psoriasis and reasonably good clinical results with no serious side effects were obtained. The advantages of this modality include noninvolvement of the upper gastrointestinal tract, high bioavailability of psoralen, peak levels at a predictable time, and rapid elimination of the drug.

Adult↗
PubMed1984

A semiquantitative light and electron microscopic analysis of histopathologic changes in photochemotherapy-induced freckles.

Photochemotherapy(PUVA)-induced freckles were found in 25 patients (41%) who had received more than 1,000 J/cm2 of PUVA. The patients had been treated with PUVA for more than 2 years, with more than 150 exposures before PUVA lentigines appeared on the thighs, the upper arm, the mid-lower arm, the waist, and the buttocks. The histopathology of these freckles was analyzed by light and electron microscopy. Light microscopy showed an increased amount of pigment and melanophages and increased numbers and size of melanocytes. The keratinocytes often displayed atypical features such as enlarged nuclei, giant size, or fibrillar degeneration. Homogenization of the papillary dermis was observed in 11 patients. The activation of melanocytes was confirmed electron microscopically, and pathological features such as large amounts of lipid droplets and lysosome-melanosome complexes within the melanocytes were seen. The Langerhans cells were mostly normal, whereas the keratinocytes showed cytolytic changes, fibrillar degeneration, and vacuolization. A close follow-up of patients with prolonged PUVA treatment is recommended.

Epidermis↗
PubMed1979

Quantification of HTLA-positive lymphocytes during oral photochemotherapy of psoriasis.

T-lymphocyte count in the peripheral blood, based on the identification of anti-human lymphocyte antigen (HTLA) by an immunocytochemical method, was determined in 25 PUVA-treated psoriatics and in 25 controls matched by sex and age. The results demonstrate that the HTLA-positive lymphocyte counts of these two groups do not differ significantly. It is concluded that oral photochemotherapy does not induce quantitative modifications in the population of T-lymphocytes of the blood.

Administration, Oral↗
PubMed1979

[Semen analysis under photochemotherapy (PUVA-therapy) (author's transl)].

In 9 male patients with psoriasis vulgaris a semen analysis before and during photochemotherapy with 8-methoxypsoralen and UVA (PUVA) was performed to rule out drug-induced toxic damage of spermatogenesis or impairment of fertility due to scrotal hyperthermia. Two hours after oral application of 40--60 mg 8-methoxypsoralen the patients had been irradiated in UVA high intensity treatment units. PUVA-treatments were performed four times weekly until total body clearing was achieved. For complete remission 13--26 (mean 20.5) PUVA-treatments were necessary. Corresponding total UVA-doses were 35.3--191.0 (mean 83.2) Joule/cm2. The investigated parameters total motility, progressive motility, spermatozoa density, total spermatozoa count, spermatozoa morphology, and seminal plasma fructose remained unchanged. Only the volume of the ejaculate showed a small decrease during 3 months of therapy. From this pilot study there is no evidence that PUVA-therapy leads to an impairment of fertility in male patients within their reproductive age.

Humans↗
PubMed1978

Stimulation of lymphocytes in patients with psoriasis under photochemotherapy. A study of lymphocyte transformation.

Lymphocyte-transformation by phytohaemagglutinine (PHA) was examined in 21 patients with generalized psoriasis during photochemotherapy (PUVA). Lymphocyte-transformation-tests (LTT) were performed before and after 8-methoxypsoralen (8-MOP) medication, before and after the initial irradiation and before and after the first maintenance irradiation four to six weeks later. Spontaneous and PHA-induced lymphocyte-transformation was not altered by 8-MOP alone or in combination with UVA irradiation.

Adult↗
PubMed1990

Experimental treatment of chronic lymphocytic leukemia with extracorporeal photochemotherapy. Initial observations.

Based on the encouraging results obtained with extracorporeal photochemotherapy (EP) in the treatment of the exfoliative erythrodermic form of cutaneous T-cell lymphoma (CTCL), leukemic form, as well as other T-cell-mediated diseases we evaluated the therapeutic potential of EP in patients with chronic lymphocytic leukemia (B-CLL). Three patients with B-CLL were treated for a period of 1 year. Two patients showed stabilization of disease, as demonstrated by reduction in their peripheral white blood cell count, with one patient showing lymph-node resolution. A third patient with significant intolerance to previous chemotherapy did not respond within the observed period. No significant side effects of EP were observed. Our observations suggest that EP may have a positive effect on the course of B-CLL in selected patients. Additional clinical trials are warranted to further define the role of EP alone or in combination therapy in the management of B-CLL.

Adult↗
PubMed1996

[Therapy of Sézary syndrome by extracorporeal photochemotherapy].

Sézary syndrome is the leukemic and erythrodemic form of cutaneous T-cell lymphoma (CTCL). Since 1987 extracorporeal photochemotherapy (ECP) has been available for treatment of erythrodermic CTCL in the USA. Through a group of case reports, we want to emphasize ECP as the treatment of choice for erythrodermic CTCL.

Biopsy↗