Broadband ultraviolet A vs. psoralen ultraviolet A in the treatment of vitiligo: a randomized controlled trial.

BACKGROUND: Psoralen ultraviolet A (PUVA) and narrowband (NB)-UVB have been shown to be efficacious in the treatment of vitiligo. With large and repeated doses, UVA may lead to immediate skin darkening and to delayed tanning. Our previous experience with broadband (BB)-UVA in vitiligo showed encouraging results. AIM: To test the efficacy of BB-UVA in vitiligo and to evaluate if it could provide an alternative treatment for this condition. METHODS: This prospective, randomized, controlled, comparative clinical trial enrolled 45 patients with vitiligo, who were randomly divided into three groups, with group A receiving UVA 15 J/cm(2) /session, group B receiving UVA 10 J/cm(2) /session, and group C receiving PUVA. The patients received three sessions/week for 5 months, with 60 sessions in total. RESULTS: At the mid-point of treatment, clinical response was significantly higher in patients receiving PUVA than in the other two groups At the end of the study, clinical response was comparable for groups A and C (UVA 15 J/cm(2) and PUVA, respectively), and both were significantly higher than the group receiving UVA 10 J/cm(2) . Patients in the PUVA group responded mainly with perifollicular pigmentation, whereas those receiving UVA responded mainly with lesional tanning. CONCLUSIONS: BB-UVA at a dose of 15 J/cm(2) /session gives results for vitiligo that are comparable to PUVA, suggesting it might be useful when oral psoralens are contraindicated.

A large scale analytical study on efficacy of different photo(chemo)therapeutic modalities in the treatment of psoriasis, vitiligo and mycosis fungoides.

Psoriasis, vitiligo, and mycosis fungoides (MF) are among the most frequently treated dermatological diseases by photo(chemo)therapy. The objectives are to determine which photo (chemo) therapeutic modality could achieve the best response in the treatment of psoriasis, vitiligo, and MF. The design used in this study is retrospective analytical study. The study included 745 patients' records; 293 with psoriasis, 309 with vitiligo, and 143 with early MF, treated in the Phototherapy Unit, Dermatology Department, Kasr El-Aini Hospital, Cairo University by either psoralen and ultraviolet A (PUVA), narrow band ultraviolet B (NB-UVB), psoralen and narrow band UVB (P-NBUVB), broad band UVB (BB-UVB), or broad band UVA (BetaBeta-UVA). Data were retrieved from the computer database of the unit and statistically analyzed. In psoriasis, oral and topical PUVA and NB-UVB were found to be equally effective, whereas oral PUVA had significantly better results than both UVA and BB-UVB at the end of therapy. In generalized vitiligo, PUVA and P-NBUVB had significantly better results than NB-UVB alone. In early MF, there was no statistically significant difference between the response to oral PUVA and NB-UVB. PUVA and NB-UVB are good choices in patients with psoriasis and early stage MF, whereas PUVA appears the best choice in the treatment of vitiligo.

Role of Synchrotron infra red microspectroscopy in studying epidermotropism of cutaneous T-cell lymphoma.

BACKGROUND: The molecular mechanisms of epidermotropism in mycosis fungoides (MF) are not well understood to date. OBJECTIVES: The aim of this study was to differentiate between epidermal and dermal lymphocytes within the skin of MF patients. METHODS: This study was done on 10 MF patients with a mean age of 50 years diagnosed clinically in the Department of Dermatology, Cairo University, Egypt. A 6 mm biopsy was taken from each patient in order to confirm the diagnosis. Skin biopsies were cut, put on low e-slides and then stained with H&E. Further examination with Synchrotron infrared (IR) microspectroscopy was done in National Synchrotron Light Source--Brookhaven National Laboratory, New York, USA. Immunophenotyping using antibodies CD3, CD4, CD8, CD20 and CD30 was also done. Statistical analysis was done by Student's t-test and cluster analysis. RESULTS: Both epidermal and dermal lymphocytes were clustered separately. Also, Amide I and RNA and DNA within the lymphocytes were significantly different between the epidermis and the dermis. CONCLUSIONS: The biochemical analysis of protein, RNA and DNA with Synchrotron IR microspectroscopy is a promising tool for studying epidermotropism in cutaneous T-cell lymphoma.

Narrow band Ultraviolet B 311 nm in the treatment of vitiligo: two right-left comparison studies.

AIM: Evaluation of narrow band ultraviolet B (NB UVB 311 nm) in the treatment of vitiligo by two independent studies. The first study compared NB UVB with a well-established therapeutic modality, psoralen ultraviolet A (PUVA), and the second study was conducted to find out whether psoralen might add to its efficacy. METHODS: In the first study, 15 patients were exposed on the left half of their body to UVB 311 nm and then exposed on their right half to UVA after ingestion of psoralen. In the second study, 20 patients were exposed to UVB 311 nm on the left side of the body, followed by ingestion of psoralen and exposure to NB UVB 311 nm 90 min later to the right side of the body. In both studies, while exposing one side, the other was protected by an UV-proof gown. Thus two right-left comparative studies were carried out simultaneously, namely: UVB 311 nm vs. PUVA and UVB 311 nm vs. PUVB 311 nm. RESULTS: In the first study, comparison of PUVA and NB UVB 311 nm showed no difference either in the degree of response or in the incidence of complications. In the second study, comparison of PUVB and UVB showed equal clinical improvement on both sides. The cumulative dose needed to achieve the same response on the PUVB side was lower than that on the UVB side, but the difference was not statistically significant. The incidence of phototoxic reactions was significantly higher on the PUVB treated body half. CONCLUSION: NB UVB 311 nm has similar repigmentary effects as PUVA. The addition of psoralen does not increase its efficacy.

Narrow band UVB (311 nm), psoralen UVB (311 nm) and PUVA therapy in the treatment of early-stage mycosis fungoides: a right-left comparative study.

BACKGROUND: Psoralen ultraviolet A (PUVA) is a widely used first-line therapy for treatment of early cutaneous T-cell lymphoma. Narrow band UVB (UVB-NB) (311 nm) has been recently introduced as another effective line of treatment. It is postulated that the efficacy of UVB-NB could be enhanced by addition of psoralen. AIM: The aim of the present work was to compare the clinical and histopathologic efficacy of PUVA and UVB-NB in the treatment of early-stage MF (stages IA, IB and IIA), and to evaluate whether psoralen adds to the efficacy of UVB-NB or not. PATIENTS AND METHODS: Twenty patients (stage IA, IB or IIA) were divided into two equal groups: group I received UVB-NB on the right body half vs. PUVA on the left side of the body for 48 sessions, and group II received PUVB-NB on the right side of the body vs. PUVA on the left side for 36 sessions. The sessions were administered three times weekly. RESULTS: In group I, almost equal results were obtained on both sides, i.e., UVB-NB and PUVA were equally effective in the treatment of early stages of MF, both clinically and histopathologically. In group II, PUVB-NB was found to be as effective as conventional PUVA in the treatment of early-stage mycosis fungoides, also on both clinical and histopathological grounds. CONCLUSION: UVB-NB phototherapy should be included among the initial therapeutic options of mycosis fungoides in view of its efficacy, convenience, and likelihood of fewer long-term adverse effects. Addition of psoralen does not seem to enhance its therapeutic efficacy.

Different low doses of broad-band UVA in the treatment of morphea and systemic sclerosis.

BACKGROUND: Numerous treatment modalities, some with potentially hazardous side effects, are currently used for morphea (M) and systemic sclerosis (SS) with limited success. Low-dose ultraviolet A (UVA) phototherapy (20 J/cm(2)) was found to be highly effective for sclerotic patches, even in patients with advanced and rapidly evolving lesions. OBJECTIVE: To determine the effectiveness of different low doses of UVA in treating patients with M and SS. METHODS: Sixty-three patients complaining of M and 15 patients complaining of SS received 20 sessions of UVA (320-400 nm) each. Patients were divided randomly into three groups that received 5, 10 and 20 J/cm(2), with cumulative UVA doses of 100, 200, and 400 J/cm(2), respectively. The efficacy of therapy was judged clinically (by sequential inspection and palpation) and histopathologically by morphometry in M cases. RESULTS: Obvious clinical improvement, with no comparable differences between various low UVA doses, was noted in patients with M and SS, accompanied by histopathological changes towards normalization of collagen. CONCLUSIONS: After 20 sessions, it appears that lower doses of UVA (5, 10 J/cm(2)) are as beneficial as the relatively higher dose (20 J/cm(2)) in the treatment of M and SS.

Suggested mechanisms of action of UVA phototherapy in morphea: a molecular study.

BACKGROUND: Ultraviolet A (UVA) phototherapy proved to be an efficient line of treatment of scleroderma. The mechanism through which it acts is still not clear. OBJECTIVES: To detect the mechanism of action of UVA phototherapy in morphea through measuring its effect on the levels of different parameters related to collagen metabolism. METHODS: Twenty-one cases of morphea were treated with low-dose broad-band UVA for 20 sessions. Twelve cases received 20 J/cm(2)/session with a cumulative dose of 400 J/cm(2) and nine cases received 10 J/cm(2)/session with a cumulative dose of 200 J/cm(2). The response was assessed clinically every week. Two skin biopsies were taken from the lesional skin of each patient before starting and after the end of therapy. Paraffin sections were examined for quantitative polymerase chain reaction measurement of collagen I, collagen III, collagenase, transforming growth factor-beta (TGF-beta) and interferon gamma (IFNgamma). RESULTS: Eighteen patients reported remarkable softening of the skin lesions, with variable degrees ranging from moderate in 57.1% of them good in 19% to very good response in 9.5%. After treatment, all the studied parameters revealed statistically significant changes. There was a significant decrease in collagen I, collagen III and TGF-beta and a significant increase in collagenase (MMP-1) and IFNgamma. The relative change was found to be greatest in collagenase, followed by IFNgamma then TGF-beta and finally collagen I. The changes in collagen I, collagenase, IFNgamma and TGF-beta were found to increase gradually with the degree of clinical response. In all the parameters studied the relative change was significantly higher in cases treated with 20 J/cm(2)/session in contrast to those treated with 10 J/cm(2)/session although no statistically significant difference could be detected in the clinical response to those doses. CONCLUSIONS: The efficacy of low-dose UVA phototherapy in the treatment of localized scleroderma is mainly obtained by the increased production of MMP-1 and IFNgamma, and to a lesser extent by decreasing TGF-beta and collagen production. Concerning the use of 10 or 20 J/cm(2)/session those effects are dose dependent, but the clinical response does not significantly differ.

Low-dose broad-band UVA in morphea using a new method for evaluation.

Until recently, various therapies for localized scleroderma have been used with limited success. Recently, phototherapy, with or without psoralen, was proposed as a successful treatment modality. The aim of this study was to evaluate the effect of broad-band low-dose ultraviolet A (UVA) phototherapy in patients with localized scleroderma, using a new method for evaluation. Twelve patients complaining of morphea were exposed to UVA irradiation at a dose of 20 J/cm2 3 times per week for 20 sessions. Selected covered plaques served as internal controls. The efficacy of therapy was judged clinically by sequential inspection and palpation. In biopsy specimens from exposed and covered plaques stained with hematoxylin and eosin (H & E) and Masson trichrome stains, the concentration of collagen per dermal surface area was measured with the use of a computerized image analyzer. All patients reported remarkable softening of skin lesions, confirmed by sequential palpatory assessment. A significant reduction in the mean concentration of collagen per surface area was detected in the plaques exposed to UVA (the P value being 0.007, P<0.01), whereas in the covered plaques the difference was not statistically significant (the P value being 0.10, P>0.05). The conclusion is that low-dose broad-band UVA phototherapy is a very effective and safe treatment modality for localized scleroderma.

Induction of leukaemia in chloramphenicol-treated toads.

Chloramphenicol has been associated with the development of aplastic anaemia. As it is still widely used in Egypt, we studied its effect on 100 Egyptian toads (Bufo regularis) given a dose of chloramphenicol of 5 mg/40 g body weight for 12 weeks. We found it induced numerous, severe ultrastructural changes in almost all types of leukocytes. These changes were similar to those induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene in 100 toads used as the carcinogen control group, and similar to those in leukocytes reported in humans with leukaemia. We recommend regulations be applied on the use of this antibiotic in countries where it is still widely used.

Experimental intravenous inoculation of Klebsiella rhinoscleromatis bacilli in albino rats: a histopathological and bacteriological study.

Scleroma, chronic specific granuloma of the nose and upper respiratory tract, is endemic in Egypt and many other countries. The exact pathogenesis of the disease as regards the aetiological role of Klebsiella rhinoscleromatis is contradictory. This work investigated the effect of experimental intravenous injection of K. rhinoscleromatis in albino rats to demonstrate that the micro-organism can fulfil Koch's postulates. Micro-organisms were isolated from biopsy specimens taken from nasal lesions of 10 patients in the granulomatous stage of scleroma. Specimens were subjected to bacteriological and histopathological examinations to confirm the diagnosis. A 100 microl volume of freshly prepared bacterial inoculum containing 10(8) cfu/ml was injected weekly in the tail vein of each of 30 albino rats for 5 consecutive weeks. Biopsy specimens were taken from sacrificed animals and subjected to bacteriological and histopathological examinations. Positive histopathological diagnosis of scleroma was reported in the nose of 66.7% of rats, the larynx of 46.7%, the lungs of 26.7% and liver of 20% of rats. Bacteriological techniques were successful in revealing K. rhinoscleromatis from the nose of 36.7% of rats, the larynx of 30% and the lungs of 20% of rats. Various techniques were carried out to demonstrate the micro-organisms in tissue sections. Two histochemical stains for bacteria were employed: silver and Periodic Acid Schiff (PAS) stains. Immunoperoxidase technique using Klebsiella capsular type 3 antiserum was applied. It gave positive results in 66.7% of the 6 stained liver sections in spite of negative bacteriological cultures. The histiocytic nature of the Mikulicz cells was confirmed using alpha-1 antitrypsin, an immunohistochemical marker of histiocytes, and by studying the ultrastructural features of Mikulicz cells using the transmission electron microscope.

Induction of leukaemia in chloramphenicol-treated toads

Chloramphenicol has been associated with the development of aplastic anaemia. As it is still widely used in Egypt, we studied its effect on 100 Egyptian toads [Bufo regularis] given a dose of chloramphenicol of 5 mg/40 g body weight for 12 weeks. We found it induced numerous, severe ultrastructural changes in almost all types of leukocytes. These changes were similar to those induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene in 100 toads used as the carcinogen control group, and similar to those in leukocytes reported in humans with leukaemia. We recommend regulations be applied on the use of this antibiotic in countries where it is still widely used

Double-blind comparison of alizapride, droperidol and ondansetron in the treatment of post-operative nausea.

To compare the efficacy in the treatment of post-operative nausea and/or vomiting (PONV), 75 patients undergoing gynaecological procedures under general anaesthesia using N2O/enflurane who suffered from PONV in the first hour after surgery were randomly allocated to three groups containing 25 patients each to receive either alizapride 100 mg, droperidol 1 mg or ondansetron 8 mg (i.v.). Patients expressed the severity of their nausea on a Visual Analogue Scale (VAS) ranging from 0 (none) to 10 (as bad as possible). Vomiting was recorded as present or absent, and the number of emetic events was noted. Data were recorded until rescue medication was given or until 4 h after the administration of the study drug. There were no significant differences between the three groups in the average VAS scores and the presence of vomiting at the time of entry into the study. Fifteen and 30 min after the administration of the study drug, VAS decreased notably in all groups. This decreases was similar and statistically significant within each group. However, comparison between the three groups showed no statistically significant differences. There was no statistically significant difference between the three groups in the number of patients receiving rescue medication, the number of emetic events and the time from administration of the study drug until rescue medication was given. It is concluded that alizapride 100 mg, droperidol 1 mg and ondansetron 8 mg intravenously are equally effective in the treatment of PONV after gynaecological procedures and that the newer drugs alizapride and ondansetron offer no advantage over droperidol.

Ultrastructural criteria that prove the similarities between amphibian and human tumors.

Toads fed with 0.5 mg 7,12-dimethylbenz(a)anthracene twice a week for 12 weeks displayed liver tumors in 27 out of 100 cases. Electron micrographs of liver tumors showed some criteria of malignancy, such as the presence of nuclear pockets, pseudoinclusions, dilatation of the cisternae of rough endoplasmic reticulum and loss of cell junctions. These features are closely similar to those of true malignancy described in humans and other mammals.

Clinical study of a new preparation of 8-methoxypsoralen in photochemotherapy.

BACKGROUND: Oral 8-methoxypsoralen is the drug of choice in photochemotherapy of several dermatoses, e.g., vitiligo and psoriasis. The aim of this trial is to produce a new preparation of the drug, which is able to overcome the difficulties met with the oral use of the older preparations. METHODS: A new preparation containing ultramicronized methoxypsoralen (8-MOP) in 10 mg capsules was tried in an open trial. The trial included 53 patients (15 psoriasis, 26 vitiligo, and 12 tinea versicolor). Light testing showed that the strongest erythema appeared 30 minutes after ingesting the capsules. Patients were exposed to UVA after that period. Laboratory studies were also performed using high performance liquid chromatography to assay the serum concentrations of the drug on normal individuals. RESULTS: Thirteen of the 15 psoriasis patients (87%) showed an excellent response (a remission) after 30 sittings. Twenty-two of the 26 vitiligo patients (85%) showed an excellent response (acceptable repigmentation) after 70 sittings. The 12 patients with tinea versicolor (100%) showed complete repigmentation after 12 sittings. The laboratory studies showed the optimum time to be between 35 to 55 minutes, verifying the clinical observation. CONCLUSIONS: The therapeutic effective dose was found to be 0.25 mg/kg. This new preparation of 8-MOP proved to be well tolerated by the patients, causing no epigastric discomfort, nausea, or vomiting, overcoming the biggest obstacle of oral 8-MOP therapy. It was also well tolerated by patients known to be sensitive to oral and/or topical 8-MOP therapy.

Carcinogenic effect of gibberellin A3 in Swiss albino mice.

Gibberellin A3 is a plant growth regulator used in many countries, including Egypt, to increase the growth of fruits and vegetables. The carcinogenic effect of gibberellin A3 was investigated in this study with Swiss albino mice. Administration of gibberellin A3 by gavage for 22 months induced a significant increase in their body weights. Tumors were induced in 18% of the males and 36% of the females and were located in the skin of the axillary region (sebaceous adenomas), breast (adenocarcinomas), and lung (adenocarcinomas and secondary metastatic deposits from breast tumors). Bronchocentric granulomas were induced in animals exposed to gibberellin A3 for 14 months. These results indicate that gibberellin A3 was carcinogenic in mice.

Preventive action of garlic on aflatoxin B1-induced carcinogenesis in the toad Bufo regularis.

The action of fresh minced garlic and garlic oil on aflatoxin B1- (AFB1) induced carcinogenesis in the toad Bufo regularis was studied. Feeding toads with AFB1 induced tumors in 19% of the animals. Animals given AFB1 together with fresh garlic or garlic oil showed a significant reduction in tumor incidence. The tumor incidences were 3% and 9% in animals given AFB1 plus garlic and AFB1 plus garlic oil, respectively. In all three groups, the tumors were located in the liver (hepatocellular carcinomas), in addition to the kidney in animals treated with AFB1 alone and together with garlic. The kidney tumors were diagnosed as metastatic deposits from the primary liver tumors. It is speculated that one or more constituents of garlic may be responsible for inhibition of AFB1-induced carcinogenesis in B. regularis.

Induction of hepatocellular carcinomas in the Egyptian toad Bufo regularis by an antifungal drug (griseofulvin).

Neoplastic lesions (hepatocellular carcinomas) were induced in the liver in 18 of 100 experimental toads (Bufo regularis) force fed with the antifungal drug griseofulvin, at a dose level of 0.4 mg/50 g every day. Maximal time of exposure and observation was 12 weeks. The first tumors appeared in 2 male toads 4 weeks after the initiation of feeding.

Carcinogenicity testing of some constituents of black pepper (Piper nigrum).

In mice, injection of safrole, tannic acid or methylcholanthrene (MCA) during the preweaning period induced tumors in different organs. Safrole and tannic acid (constituents of black pepper) were weak carcinogens when compared with MCA which was used as a carcinogenic control substance. Force feeding of d-limonene (one of the pepper terpenoids) for a long time to the mice which were injected with any of the above 3 substances reduced their carcinogenic activity, while force feeding of piperine (one of black pepper alkaloids) was ineffective.

The carcinogenicity of some antimalarial drugs using the Egyptian toad Bufo regularis as a biological test animal.

Feeding Egyptian toads (Bufo regularis) with chloroquine and primaquine separately induced tumor formation in 14% and 19% of the animals, respectively. When chloroquine and primaquine were given in combination, the tumor incidence increased to 23.5%. Chloroquine feeding resulted in tumors located in the liver (lymphosarcomas) and primaquine in tumors in the kidney (histiocytic sarcomas). Toads fed chloroquine plus primaquine developed tumors in the liver, kidney, lung, and urinary bladder, and all the tumors were diagnosed as histiocytic sarcomas. It is speculated that one or more metabolites of chloroquine and primaquine (e.g., quinone) may be responsible for tumor induction in the toads.

Effect of adriamycin on the morphology of the erythrocytes and blood parameters of the toad Bufo regularis.

The effect of the anticancer drug adriamycin on the morphology of the erythrocytes as well as some blood parameters were studied in the Egyptian toad Bufo regularis. Injecting the toads subcutaneously in the dorsal lymph sac with adriamycin at a dose level of 2 mg/kg body weight once every three weeks for 12 weeks induced the formation of abnormalities in the cytoplasm and nuclei of the erythrocytes. Its administration also caused severe anaemia, since the number of red blood corpuscles, haemoglobin content and haematocrit values were obviously decreased throughout the whole experimental period. The total leucocytic count was also diminished. On the other hand, the erythrocyte sedimentation rate was increased all over the experiment.