bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Nasopharyngeal Carcinoma: Stereotactic Radiosurgical Boost following Fractionated Radiotherapy
Authors: Chang Steven D. , Tate David J. , Goffinet Don R. , Martin David P. , Adler Jr. John R.
Published: April 2003

Treatment of patients with nasopharyngeal carcinoma (NPC) using external beam radiation therapy (XRT) alone results in significant local recurrence. To improve local control, stereotactic radiosurgery (SRS) was used to boost radiation to the primary tumor site following XRT in 23 patients with NPC. SRS was delivered utilizing a frame-based linear accelerator as a boost (range 7–15 Gy, median 12 Gy) following XRT (range 64.8– 70 Gy, median 66 Gy). In all 23 patients (100%) receiving SRS following XRT local control was achieved at a mean follow-up of 21 months (range 2–64 months). There have been no complications of treatment caused by SRS. However, 8 patients (35%) have subsequently developed regional or distant metastases. SRS boost following XRT provides excellent local control in NPC and should be considered for patients with skull base involvement.
Dose-Volume Effect in Gamma Knife Radiosurgery of Meningiomas
Authors: Kang C.S. , Zheng L.G. , Xu D.S.
Published: April 2003

Objective: To study the relationship between dose-volume effect and complication in gamma knife radiosurgery of intracranial meningiomas. Method: By using an integrated logistic formula to establish mathematical models, the authors analyzed the relationship between treatment volume and logistic probability for 15 Gy, and the relationship between prescribed dose and treatment volume in 3% logistic probability. Furthermore, 37 meningiomas treated by gamma knife radiosurgery were analyzed retrospectively to investigate how the 3% isoeffect curve impacted on complication. Result: There was a linear relation between treatment volume and logistic probability for 15 Gy. The regression formula was f(x) = 0.0042x + 0.0007. The 3% isoeffect curve indicated that the prescribed dose was inversely proportional to the treatment volume. During 16.3 months follow-up on average, 18 cases below the 3% isodose curve were without complication, but in 19 cases above the 3% isodose curve, 5 cases suffered complications, the difference being statistically significant. Conclusion: Dose selection in gamma knife radiosurgery is volume dependent. The 3% isodose curve may possibly be the guideline in gamma knife radiosurgery of meningiomas.
Surgical Management of Intractable Epilepsy in Children with Hemophilia
Authors: Yeh David John , Lee Mark , Park Yong D. , Smith Joseph R. , Lightsey Jr. Alton L.
Published: April 2003

Intracranial hemorrhage occurs in 2–8% of patients with hemophilia and can result in neurologic sequelae including seizure disorders. There is a paucity of data concerning the surgical treatment of epilepsy in children with hemophilia. We review our experience with 2 children who developed medically refractory seizure disorders. Both children underwent hemispherotomy, at 18 months (case 1) and 13 years of age (case 2), respectively. Perioperative management included continuous factor replacement. Both children tolerated surgical intervention without complications or increased neurologic deficit. Case 2 showed a 90% reduction in seizure frequency, and case 1 is seizure free. Surgical management of intractable epilepsy in children with hemophilia is safe and effective.
A 13-Year Experience with Epilepsy Surgery
Authors: Smith J.R. , Lee M.R. , Jenkins P.D. , King D.W. , Murro A.M. , Park Y.D. , Lee G.P. , Meador K.J. , Loring D.W.
Published: April 2003

Between 1985 and 1997, 563 therapeutic craniotomies were performed: 311 anterior temporal (ATL) and 158 extramesial temporal (XMT) resections, 67 callosotomies, 20 hemispherectomies and 7 multiple subpial transections. Sixty-seven percent of nonlesional ATL cases were seizure free (SF), and 76% of nonlesional ATL cases ≤18 years old were SF. Seventy-eight percent of lesional ATL cases with complete resection were SF. Seventy-three percent of lesional cases ≤18 were SF. Thirty-seven percent of nonlesional XMT cases were SF. Seventy percent of XMT lesional cases with complete resection were SF, and 82% of lesional XMT cases ≤18 were SF. Of the anterior callosotomy cases, there was a ≥90% decrease in generalized tonic-clonic seizures in 50% of patients, and in tonic seizures, drop attacks, absence and myoclonic seizures in approximately 60–70% of patients. Of 20 hemispherectomies, 65% were SF. Of 7 multiple subpial transections, 29% were SF.
Neurophysiological Navigation in the Trigeminal Nerve: Use of Masticatory Responses and Facial Motor Responses Evoked by Electrical Stimulationof the Trigeminal Rootlets for RF-Thermorhizotomy Guidance
Authors: Sindou M.P.
Published: April 2003

RF-thermorhizotomy of the trigeminal nerve is an effective and safe treatment of trigeminal neuralgia, provided lesioning of the sensory fibers is performed precisely. To control the accurate placement of the electrode tip, electrical stimulation testing, prior to thermal lesioning, is of prime importance. The clinical observation of direct masticatory responses (DMR) and facial evoked motor responses (EMR) produced by stimulation of the trigeminal rootlets (at 5 Hz) helps to place the electrode tip in the optimal location. The best location is the one where the threshold for eliciting DMR is high and the threshold for evoking facial EMR in the area corresponding to the trigger zone is low. EMR in orbicularis oculi indicates location in V1, levator labii EMR signifies V2 and orbicular oris EMR corresponds to V3.
An Update on Vitamin D3 Analogues in the Treatment of Psoriasis
Authors: van de Kerkhof P.C.M.
Published: April 2003

Vitamin D3 analogues have revolutionized the topical treatment of psoriasis during the last decade. The mode of action of this ligand for the vitamin D3 receptor is via modulation of the transcription of genes with vitamin D3 response elements in their promoter region. Vitamin D3 analogues cause inhibition of various aspects of cutaneous inflammation and epidermal proliferation with enhancement of normal keratinization. In vivo, active vitamin D3 analogues proved to have a substantial antipsoriatic effect. Calcipotriol (50 µg/g in ointment or cream), tacalcitol (4 µg/g in ointment) and calcitriol (3 µg/g in ointment) have been shown to have an antipsoriatic effect in placebo-controlled studies. The most extensive body of information on comparative studies and on combination therapies is available for the analogue calcipotriol. So far, calcipotriol is available as a routine treatment in most countries, whereas tacalcitol has been registered in Japan and some European countries. From the available data in the literature we may conclude that calcipotriol is a first-line treatment for psoriasis and is advantageous in the combination with several other antipsoriatic treatments suchs as topical corticosteroids, PUVA, cyclosporin and acitretin. Tacalcitol 4 µg/g as a once-daily principle is effective in psoriasis. Comparative studies will indicate the position of the existing and new vitamin D3 analogues.
Iron Overload Augments 7,12-Dimethyl- benz(a)anthracene-Initiated and 12-O-Tetradecanoylphorbol-13-Acetate- Promoted Skin Tumorigenesis
Authors: Rezazadeh Hassan , Julka P.K. , Athar Mohammad
Published: April 2003

Reactive oxygen species and free radicals have been implicated in the multistep cutaneous chemical carcinogenesis. Much of the experimental evidence in this regard is indirect and is based on observations that prooxidant status usually enhances and antioxidant treatments generally inhibit tumor yield. Iron overload is known to enhance peroxidative damage and cause oxidative stress. In this study, we report that iron overload augments 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated cutaneous tumor promotion. Female Swiss mice were subjected to iron overload by injecting 1 mg iron/mouse/day consecutively for 2 weeks. Tumors were initiated by applying a single dose of 7,12-dimethylbenz(a)anthracene and promoted with twice weekly applications of TPA for 20 weeks and the appearance of first tumor (latency period), percent incidence and number of tumors per mouse were recorded. It has been observed that the level of iron in involved (tumor-bearing) skin was about fourfold higher as compared to uninvolved (non-tumor) skin of iron overload animals and about tenfold higher as compared to the iron level in the skin of normal animals. When compared to the iron-unloaded control group, the iron overload mice showed an increased incidence of tumors. In iron overload animals, the tumors appeared 3 weeks earlier and also the number of tumors per mouse was significantly higher (2.5-fold). These data indicate that iron overload augments TPA-mediated tumor promotion. We propose that oxidative stress generated by iron overload may be responsible for the augmentation of cutaneous tumorigenesis.
Effects of Cetirizine Dihydrochloride on Human Lymphocytes in vitro: Evaluation of Chromosome Aberrations and Sister Chromatid Exchanges
Authors: Vlastos D. , Stephanou G. , Demopoulos N.A.
Published: April 2003

The ability of cetirizine dihydrochloride, an antihistaminic agent, to induce chromosome aberrations as well as sister chromatid exchanges (SCEs) was evaluated in human lymphocyte cultures treated in vitro. The following concentrations were tested: 25, 50, 75, 100 and 200 µg/ml. The results of our study revealed that cetirizine dihydrochloride is capable of inducing chromosome aberrations, at least at the higher concentrations studied, 100 and 200 µg/ml. The majority of aberrations was of chromatid type. Cetirizine is also a weak inducer of SCEs. Further studies are now warranted in order to define the in vivo cytogenetic activity of cetirizine in humans.
β-L-1,3-Dioxolane-Cytidine:A Novel Nucleoside ThatInhibits Proliferation andInduces Differentiation ofKeratinocytes in vitro
Authors: Schwartz P.M. , Haggerty J.G. , Cheng Y.-C.
Published: April 2003

β-L-1,3-Dioxolane-cytidine (L-(–)-OddC) is a novel L-nucleoside, and its antitumor activity is under investigation in clinical trials. To evaluate the potential of L-(–)-OddC for treating hyperproliferative diseases of the skin, we examined its activity in human keratinocytes in vitro. The dose of L-(–)-OddC that inhibited the rate of proliferation of keratinocytes by 50% was 50 nM. L-(–)-OddC was about as cytotoxic as 9-β-D-arabinofuranosylcytosine but was about 1,000 time more potent than 3′-azidothymidine. L-(–)-OddC caused irreversible growth arrest and induced differentiation of keratinocytes. L-(–)-OddC altered morphology, increased the cell size of keratinocytes and increased the expression of involucrin. These data suggest that L-(–)-OddC may have potential as a therapeutic agent against hyperproliferative skin diseases.
The Effects of the Glucocorticoids Prednisolone, Deflazacort and Beclomethasone-Dipropionate on the RM 3/1 Macrophage in Human Peripheral Blood
Authors: Zwadlo-Klarwasser Gabriele , Schmutzler Wolfgang
Published: April 2003

Different glucocorticoids (GC) applied intravenously, subcutaneously or in vitro exert only small differences in the ability to raise RM 3/1 macrophages from human blood monocytes. Dermal application however reveals a dose-dependent difference between GC. The present experiments were designed to study the efficacy of oral and topical application in this model. We also intended to obtain some information about the qualitative differences between the effects of prednisolone and deflazacort, which was reported to cause less adverse reactions than other GC. Both GC were orally administered to probands in doses regarded as equivalent with respect to general GC effects by the manufacturers of deflazacort (5–6 mg or multiples). A single dose of 5 mg prednisolone had no effect; 50 mg increased the number of RM 3/1 macrophages within 12 h from a basal level of 8.5% to about 80% similar to an intravenous or subcutaneous administration of GC. 10 mg prednisolone enhanced the number of RM 3/1 macrophages also within 12 h, reaching a mean maximum of about 60% at 24 h, declining thereafter. 12 mg deflazacort raised the number of RM 3/1 macrophages much slower, reaching a maximum of 30% (average) after 48 h. The interindividual variation was found to be mainly the time lag between dosage and maximum effect. Interindividual differences of prednisolone effects concerned mainly the maximal increase of RM 3/1 macrophages after 24 h. These results show that in this test system deflazacort was found to be less effective than expected. To elucidate the topical influence of GC, probands inhaled twice daily 0.5 mg beclomethasone-dipropionate over a period of 11 days. No effect on the number of RM 3/1 macrophages was observed, suggesting that beclomethasone applied in this dose did not cause systemic GC reactions.
Absorption and Metabolism of (all-trans-) Retinol Acetate, Retinol, and Retinoic Acid in the Single-Pass, Albumin-Perfused Rabbit Ear
Authors: Bast G.E. , Kampffmeyer H.G.
Published: April 2003

Background: Retinoic acid, a metabolite of retinol, is formed in the skin of various species. Purpose: Formation rates have not been determined in a dynamic skin perfusion model which may show the dehydrogenation of retinol to be rate limited. Methods: (all-trans-) Retinol acetate, retinol, or retinoic acid was applied dermally with isopropyl myristate. The ears were single-pass perfused with 6% hetastarch or 5% bovine serum albumin in the buffer solution. The effluent was analyzed by HPLC for these substances. Result: No ester hydrolysis of retinol acetate was observed, nor did this substrate appear in the effluent. Retinol or retinoic acid were detected in the effluent. The absorption rate was linearly related to the dermally applied concentration density. The absorption rate of retinoic acid was 70 times larger than that for retinol. The formation rate of retinoic acid from retinol was rate limited (apparent Vmax: 0.08 pmol/min/cm2 skin). Conclusion: Since retinoic acid is a recognized pharmacologically active ingredient in the skin, the dehydrogenation of retinol or retinal was also observed in the effluent of this skin perfusion model. The percutaneous retinol adds to the endogenous pool of retinoic acid by cytosolic dehydrogenation or microsomal oxidation elsewhere. The steady-state absorption rate of 0.1% retinoic acid in isopropyl myristate, referred to 500 cm2 of the human skin, would contribute about 20% of the daily requirement of vitamin A, without increase in endogenous retinoic acid plasma concentration.
Inhibition of Irritation and Contact Hypersensitivity by Ethacrynic Acid
Authors: Wille John J. , Kydonieus Agis F. , Kalish Richard S.
Published: April 2003

The immunosuppressive effect of topical ethacrynic acid (ECA) was tested on both the induction and elicitation phases of contact sensitization in a mouse model. ECA (0.5% in vehicle) reduced the sensitization response by >50% when the sensitizer was either dinitrochlorobenzene (DNCB), oxazalone (OX) or para-phenylenediamine (PPD), and was applied 1 day later to the ECA-pretreated skin site. The immunosuppressive effect of combining ECA with either hydrocortisone or with cis-urocanic acid was also tested. An additive suppressive effect was observed with ECA in both combinations. The effect of ECA (1% in vehicle) on blocking the elicitation phase was also examined in a mouse ear edema assay. ECA was highly effective in preventing the challenge response in mice previously sensitized to either DNCB, OX or PPD. ECA (1% in vehicle) was also tested for its ability to inhibit contact irritation. ECA (1% in vehicle) was highly effective in preventing ear edema due to topically applied skin irritants including arachidonic acid, capsaicin, lactic acid, phorbol myristate acetate, trans-retinoic acid, and sodium lauryl sulfate. ECA may be useful for both prophylaxis and therapeutic treatment of diverse skin conditions including contact dermatitis, eczema, and other related allergic skin disorders.
The Effect of Isotretinoin on Biotinidase Activity
Authors: Schulpis Kleopatra H. , Georgala Sophia , Papakonstantinou Evangelos D. , Michas Timos , Karikas George A.
Published: April 2003

Background: Among the reaction and effects of isotretinoin, mucocutaneous reactions, xerosis and erythema of the skin as well as elevation of liver enzymes and lipids except high density lipoprotein have been reported. Objective: Since biotinidase is mainly produced in the liver and partial biotinidase deficiency causes dermatological manifestations, seborrheic dermatitis, alopecia etc., isotretinoin side effects in relation to biotinidase activity were studied. Methods: Forty-two (n = 42) patients with severe cystic acne had liver function tests, lipid estimations, serum biotin as well as biotinidase activity evaluations before (value 1) and on the 30th day (value 2) of treatment with isotretinoin monotherapy (Roaccutane 0.5 mg/kg/24 h). The same laboratory tests were evaluated in 50 controls only once. Moreover, the effect of isotretinoin on a known plasma biotinidase activity was evaluated after incubation in vitro with various concentrations of the drug. Results: A statistically significant elevation of liver enzymes and lipids, except high density lipoprotein, was observed at the end of this study. On the contrary, biotinidase activity was found to be significantly decreased as compared to the initial values (value 1 = 4.70 ± 0.89 nmol/min/l, value 2 = 2.50 ± 0.8 nmol/min/l, p < 0.001) and to controls (5.2 ± 0.9 nmol/min/l vs. value 2 = 2.50 ± 0.8 nmol/min/l, p < 0.001). Additionally, biotin levels showed no significant alterations and the in vitro incubation of the enzyme with various concentrations of the drug exhibited no effect on its activity. Conclusion: It is suggested that isotretinoin isomers-metabolites act in the liver, resulting in low biotinidase activity.
Increased Activation of Ras in Psoriatic Lesions
Authors: Lin Pinpin , Baldassare Joseph J. , Voorhees John J. , Fisher Gary J.
Published: April 2003

Ras functions as an essential upstream regulator of growth-factor-receptor-coupled signal transduction pathways. Ras is converted from an inactive GDP-bound state to an active GTP-bound state in response to receptor activation. Thus, the ratio of GTP/GDP bound to Ras is a measure of its state of activation. Mutations that stabilize the GTP-bound form of Ras result in constitutive activation and cellular transformation. The most widely used method for measuring Ras activation utilizes [32P]PO4 to label cellular nucleotide pools and is therefore limited to use with cultured cells. We have modified and adapted an enzyme-based method for rapid, precise measurement of Ras-bound GTP and GDP in normal and psoriatic human skin. This method does not require radiolabeling of cellular nucleotides. In cultured fibroblasts, the enzymatic and [32P]PO4 incorporation methods yielded similar results. Application of the enzymatic method to human skin revealed that 6% of Ras was in the active GTP-bound state in normal skin, compared to 15.4% of Ras in psoriatic lesions. The total amount of Ras normalized to protein content was similar in normal and psoriatic skin. Enhanced activation of Ras is likely a critical mediator of the increased cell growth characteristic of psoriatic lesions.
Perspectives of Photodynamic Therapy for Skin Diseases
Authors: Colussi Valdir C. , Feyes Denise K. , Mukhtar Hasan
Published: April 2003

Photodynamic therapy (PDT) is largely an experimental modality for the treatment of neoplastic and selected nonneoplastic diseases. This therapeutic procedure, through a cascade of events, leads to cell killing. In the past few years, dermatology has taken advantage of PDT for the treatment of skin cancer and other skin diseases. The skin has considerable attributes over many other organs for the application of PDT. These include the accessibility to all three PDT essential requirements; the drug (photosensitizing agent), visible light and oxygen. The major benefit of experimental PDT in dermatology is the ability to assess the clinical response visually and the relative ease in obtaining biopsies for precise biochemical and histological analysis. Currently, PDT has received approval worldwide for the ablation of various tumor types. In the United States, the Food and Drug Administration has approved PDT for the treatment of advanced esophageal cancer and selected patients with lung cancer. Clinical trials, employing several types of photosensitizers for PDT, are ongoing for a variety of dermatological lesions. This review summarizes current knowledge of PDT in dermatology and highlights future perspectives of this modality for effective management of skin diseases.
Congenital Erythropoietic Porphyria
Authors: Fritsch C. , Lang K. , Bolsen K. , Lehmann P. , Ruzicka T.
Published: April 2003

Congenital erythropoietic porphyria (CEP) is one of the rarest autosomal-recessive disorders of the porphyrin metabolism caused by the homozygous defect of uroporphyrinogen III cosynthase. High amounts of uroporphyrin I accumulate in all cells and tissues, reflected by an increased erythrocyte porphyrin concentration and excretion of high porphyrin amounts in urine and feces. Dermal deposits of uroporphyrin frequently induce a dramatic phototoxic oxygen-dependent skin damage with extensive ulcerations and mutilations. Splenomegaly and hemolytic anemia are typical internal symptoms. Skeletal changes such as osteolysis and calcifications are frequent. Up to date 130 cases of CEP have been published. Splenectomy and erythrocyte transfusions showed some beneficial effect. Bone marrow transplantation was performed in 3 patients and stem cell transplantation in 1. The best therapy is the avoidance of sunlight. We give a report on our latest cases of CEP.
Successful Treatment of Oxidative Stress in Vitiligo
Authors: Schallreuter K.U.
Published: April 2003

Patients with vitiligo have low catalase levels in their involved and uninvolved epidermis in association with high levels of hydrogen peroxide (H2O2). H2O2 has been confirmed for the first time in vivo using Fourier Transform Raman spectroscopy. A topical substitution with a UVB-activated pseudocatalase can successfully remove epidermal H2O2 in vitiligo. This approach leads to recovery of the oxidative damage in the epidermis and remarkable repigmentation in this disorder.
Comparative Caustic and Biological Activity of Trichloroacetic and Glycolic Acids on Keratinocytes and Fibroblasts in vitro
Authors: Rakic L. , Lapière Ch.M. , Nusgens B.V.
Published: April 2003

Objectives: Beside their causticity, the biological mechanism by which trichloroacetic acid (TCA) and glycolic acid (GA), two agents extensively used for chemical peeling, might act remains unknown. The purpose of this study was to examine in vitro the effect of TCA and GA on human keratinocytes and the influence of the released epithelial mediators on collagen and matrix metalloproteinases (MMPs) production by human dermal fibroblasts. Method: Cultured keratinocytes were treated by TCA and GA at 10 mg/ml brought to pH 3, 5 and 7, and the conditioned media neutralized to pH 7 were added to human normal skin fibroblasts. Results: TCA was cytotoxic for keratinocytes at each tested pH. The conditioned medium depressed protein and collagen synthesis and the expression of MMPs when added to fibroblasts as did also TCA when added directly to fibroblasts. GA was not cytotoxic for keratinocytes at neutral pH and the conditioned medium obtained at each pH applied to fibroblasts did not alter protein, collagen nor MMPs production while causing an elevated secretion of IL-6. Conclusion: TCA exerts a toxic effect on keratinocytes and fibroblasts while GA does not alter the metabolism of fibroblasts but induces the secretion of IL-6.
Broad Spectrum Herbal Therapy against Superficial Fungal Infections
Authors: Shahi Sushil K. , Shukla A.C. , Bajaj A.K. , Banerjee U. , Rimek D. , Midgely G. , Dikshit Anupam
Published: April 2003

Skin disease associated with keratinized tissues in animal and human beings has been investigated. The essential oil of Eucalyptus pauciflora in vitro showed strong antifungal activity at 1.0 μl/ml against human pathogenic fungi, viz. Epidermophyton floccosum, Microsporum audouinii, M. canis, M. gypseum, M. nanum, Trichophyton mentagrophytes, T. rubrum, T. tonsurans and T. violaceum. The oil has heavy doses of inoculum potential at 1.0 μl/ml. Moreover, it did not exhibit any adverse effects on mammalian skin up to 5% concentrations. Further, we formulated the oil in the form of ointment ‘BSHT’ (broad spectrum herbal therapy) (1% v/v) and subjected it to topical testing on patients attending the outpatient department of M.L.N. Medical College, Allahabad. Fifty patients were selected on the basis of KOH-positive results and diagnosed as either tinea pedis, tinea corporis or tinea cruris. After the second week of treatment, all patients were KOH-negative. At the end of medication, 60% of patients recovered completely and 40% showed significant improvement from the disease. No KOH-negative cases of relapse were observed when patients were re-examined after 2 months following the end of treatment. Thus, the ointment can be exploited commercially after undergoing successful multicenter clinical trials, which are in progress.
Biomelanin Antioxidants in Cosmetics: Assessment Based on Inhibition of Lipid Peroxidation
Authors: Kalka K. , Mukhtar H. , Turowski-Wanke A. , Merk H.
Published: April 2003

Acute adverse effects of ultraviolet (UV) radiation in humans include sunburn, photosensitivity reactions and immunological suppression. Chronic exposure to UV light, particularly the UVB (290–320 nm) component of the UV radiation, and certain environmental chemicals increase the risk of nonmelanoma skin cancer and play a major role in cutaneous aging. The lipid peroxidation (LPO) of biomembranes, mediated by reactive oxygen species and free radicals, is one of the major causes of cellular damage induced by UV radiation and toxins. Antioxidants, such as vitamin E, vitamin C and melanins, are reactive oxygen and radical scavengers, thereby minimizing the light- and toxin-induced tissue destruction. We examined the influence of 8 biotechnically produced polyphenolic melanins on the LPO of microsomal membranes in comparison with α-tocopherol, ascorbate and synthetic melanin. All biomelanins showed better inhibition of peroxidative damage than synthetic melanin. Three of the 8 tested drugs inhibited the LPO at least as effectively as vitamin C and vitamin E. The combination of the most effective biomelanin with both vitamin C and vitamin E resulted in greater LPO inhibition than caused by each agent alone. Our data show that biomelanins are potent inhibitors of the peroxidative destruction of biomembranes, indicating that these compounds may be useful antioxidative agents in cosmetic preparations.
Preview of Potential Therapeutic Applications of Leukotriene B4 Inhibitors in Dermatology
Authors: Zhu Y. Isabel , Stiller Matthew J.
Published: April 2003

This article reviews the mechanisms and potential therapeutic uses of compounds with inhibitory effects on leukotriene B4 (LTB4) production or its activity, and focuses on compounds that have been shown in animal and/or human studies to have potential efficacy in treating dermatological disorders. These compounds, many of which are not familiar to many dermatologists, include inhibitors of 5-lipoxygenase such as ETH615, 15-hydroxyeicosatetraenoic acid, leflunomide, linetastine, lonapalene, MK886, R-68151 and zileuton, and antagonists of LTB4 such as SC53228, SC50605, SC51146 and VML295. The purpose of this paper is to introduce our colleagues to these potentially useful compounds currently in preclinical or early clinical testing.
Histamine Receptors on Lymphocytes: Distribution and Functional Significance
Authors: Sachs B. , Hertl M. , Merk H.F.
Published: April 2003

Several investigations reported modulation of lymphocyte functions following activation of the histamine H2 receptor. However, few data have accumulated with regard to the distribution of histamine H2 receptors on different lymphocyte subsets. Conversely, the distribution of histamine H1 receptors on different lymphocyte subsets has been thoroughly analyzed using specific radioligands, whereas the functional significance of histamine H1 receptor ligation on lymphocytes has not been fully elucidated yet. Recent investigations suggest that H1R signaling on lymphocytes may enhance whereas activation of the H2R may inhibit lymphocyte responses. In this review, the authors discuss the current knowledge on distribution and functional significance of histamine H1 and histamine H2 receptors on human lymphocytes.
Percutaneous Absorption of Sunscreens in vitro: Interspecies Comparison, Skin Models and Reproducibility Aspects
Authors: Benech-Kieffer F. , Wegrich P. , Schwarzenbach R. , Klecak G. , Weber T. , Leclaire J. , Schaefer H.
Published: April 2003

Appropriate evaluation of sunscreens is required to provide better knowledge of their safety and efficacy. One of the most important elements of this evaluation is the assessment of percutaneous absorption. In vitro methods are largely used for such assessments, and the accuracy of the measurements generated with these methods depends on the use of a proper methodology. This study was designed to evaluate an in vitro protocol for investigating the percutaneous absorption of two sunscreens under standardized experimental conditions. Octyl methoxycinnamate and benzophenone 4 were each incorporated in a typical oil-in-water emulsion and tested separately. Salicylic acid was tested as a reference compound. In vitro percutaneous absorption was evaluated using two species, the pig and human, and two models, full-thickness and split-thickness skin. The reproducibility of study results was evaluated by comparing the data generated by two industrial laboratories, L’Oréal and Hoffmann-La Roche. The correlation of quantitative data between pig skin and human skin was very good, and the split-thickness skin model seemed to be more appropriate for measuring the absorption of sunscreens. Results obtained for salicylic acid demonstrated the relevance of the protocol in terms of prediction of in vivo percutaneous absorption. Finally, the comparison of pig skin data between the two laboratories demonstrated a good correlation and underlined the need for a standardized in vitro procedure.
Normal Ranges of Renal Physiological Parameters for Technetium-99m Mercaptoacetyltriglycine and the Influence of Age and Sex Using a Camera-Based Method
Authors: Lin Wan-Yu , Changlai Sheng-Ping , Kao Chia-Hung
Published: April 2003

162 normal Chinese men and women underwent a 99mTc MAG3 renal study. Seventy-two males and 90 females were evaluated in 5 age groups: group 1, 61–80 years; group 2, 51–60 years; group 3, 41–50 years; group 4, 31–40 years, and group 5, 21–30 years. Each subject was required to fit the following criteria: (1) clinically no history of renal, urinary disorders and systemic diseases, normal blood pressure, kidney morphology, urinary examination and serum creatinine, and (2) for the gamma camera study normal hydration and renal images, and no pelvic, ureteric dilatation or retention of tracer should be found. The normal range of common physiological parameters for 99mTc MAG3 renal studies was measured in normal subjects. The effective renal plasma flow (ERPF, camera-based Schlegel method), percent function in each kidney (renal index, RI), time of peak renal parenchymal activity (Tmax) and half time of parenchymal activity following the peak (T1/2) were evaluated. The Tmax and T1/2 were determined with regions of interest over the entire kidney. The results showed that (1) between the sexes, there were no significant differences for any parameter; (2) between the age groups, the only significant difference was a decrease in ERPF, normalized for body surface area, with increasing age (group 1, 511.3 ± 91.2; group 2, 559.5 ± 102.1; group 3, 577.1 ± 79.2; group 4, 607.8 ± 101.1, and group 5, 610.2 ± 109.2), and (3) the RI, Tmax and T1/2 were symmetrical and did not vary between the sexes or age groups (left vs. right: RI = 49.6 ± 2.2 vs. 50.4 ± 2.2%, Tmax = 3.63 ± 1.13 vs. 3.75 ± 1.11 min, and T1/2 = 5.38 ± 1.65 vs. 5.83 ± 1.88 min). We find that (1) ERPF for 99mTc MAG3 decreases with age in normal Chinese, which is similar to the results of Western countries, and (2) the RI, Tmax and T1/2 were symmetrical and did not vary between the sexes or age groups in normal Chinese, and are also similar to the results of Western countries.
An Evaluation of Pharmacokinetics and Pharmacodynamics of Leuprorelin Acetate 3M-Depot in Patients with Advanced and Metastatic Carcinoma of the Prostate
Authors: Khan M.S. , O’Brien A.
Published: April 2003

Objectives: The investigational objectives of this open, noncomparative phase I study were to determine the pharmacokinetic profile of a single dose of 11.25 mg leuprorelin acetate, the effective duration of the chemical castration (serum testosterone ≤1.73 nmol/l) and safety in patients with locally advanced and/or metastatic carcinoma of the prostate foreseen for chemical castration, in the hope that such a dose of leuprorelin acetate may be suitable as a depot formulation to be administered 3-monthly to these patients. Methods: A total of 24 males up to 85 years old with histologically proven advanced carcinoma of the prostate were enrolled in the study to obtain 18 eligible patients. Each patient was given 11.25 mg of leuprorelin acetate in a depot formulation subcutaneously after reconstitution in 2 ml of a special suspension vehicle. The study period lasted 24 weeks. Patients whose serum testosterone levels reincreased prior to the end of the observation period of 24 weeks were withdrawn from the study and received the monthly depot formulation of 3.75 mg of leuprorelin acetate. Results: The 3M-depot formulation of leuprorelin acetate ensured continuous and constant drug release and effective suppression of testosterone serum levels to castration range for at least 13 weeks. After an initial rise, 5α-dihydrotestosterone as well as the gonadotropin serum levels of luteinizing hormone and follicular stimulating hormone reflected the testosterone serum pattern. Conclusion: The results of this study show that the 3M-depot preparation of leuprorelin acetate is effective in suppressing the serum testosterone levels to the castration range for a targeted period of at least 13 weeks.
Nephroblastoma in a 76-Year-Old Male
Authors: Shekhar Biyani Chandra , Lele Subhash K. , Steele P.R.M. , Powell Christopher S.
Published: April 2003

Nephroblastoma is an infantile neoplasia with a low incidence in adults. A case of Wilms’ tumour in a 76-year-old male is reported. In a literature review the current status of knowledge in the geriatric population is discussed.
Efficacy of Skeletal Alkaline Phosphatase and Prostate-Specific Antigen in the Diagnosis of Bone Metastasis in Cancer of the Prostate
Authors: Wolff J.M. , Ittel T. , Borchers H. , Brauers A. , Jakse G.
Published: April 2003

Purpose: To study the efficacy of prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers in discriminating patients with cancer of the prostate (CaP) with (M+) and without bone metastases (M0). Material and Methods: 73 patients with untreated CaP entered the study. After staging the patients were divided into 3 groups: group I, patients with CaP and bone metastases (n = 21); group II, patients with locally advanced CaP without bone metastases (n = 26), and group III, patients with clinically localized CaP without bone metastases (n = 26). Results: None of the M0 patients but 71% of the M+ patients exhibited an increased SAP. A corresponding cutoff point of 100 ng/ml for PSA showed that 19% of M0 patients and 71% of the M+ patients exhibited a value of >100 ng/ml. This resulted in a sensitivity and specificity of 71 and 100% of SAP and 71 and 81% for PSA, respectively. Conclusion: SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it provides additional information concerning the skeletal status of these patients.
Acute Onset of Coagulopathy in a Patient with Kasabach-Merritt Syndrome following Transurethral Resection of Bladder Tumor
Authors: Shoji Norifumi , Nakada Teruhiro , Sugano Osamu , Suzuki Hitoshi , Sasagawa Isoji
Published: April 2003

We report an unusual case of Kasabach-Merritt syndrome in a 62 year-old woman with bladder tumor who suffered from acute consumption coagulopathy that increased the fibrinolytic activity due to the presence of a huge hemangioma in the upper and lower extremities. Two days after the transurethral resection of the solitary bladder tumor, serious hematuria and life-threatening disseminated intravascular coagulation developed. Following treatments with heparin and subsequent steroid treatment, hemorrhage and abnormal hemostatic values improved. It is suggested that extensive investigation of the coagulation system should be done in patients with giant hemangioma, particularly before a surgical procedure.
Mineral Composition of Renal Stones from the Sudan
Authors: Balla A.A. , Salah A.M. , Khattab A.H.H. , Kambal A. , Bongartz D. , Hoppe B. , Hesse A.
Published: April 2003

Urolithiasis is a very frequent finding in the Sudan, but stone analysis is not routinely performed in this country. It would, however, give important evidence for the metabolic basis of stone formation. We therefore set out to analyze urinary stones in 80 Sudanese patients (45 male, 35 female), 12 of whom where children. Fourier-transformed infrared spectroscopy was used for stone analysis. As is known from other countries, calcium oxalate (CaOx) stones were the most frequent, with 68.7% of all stones in adults and 43.7% of childhood stones. Uric acid and uric acid dihydrate stones were more often seen in adults (13.2%) than in children (4.1%). Ammonium urate stones are common in the Sudan, especially in children (32.9%), which is typical for underdeveloped countries. Infectious stones (struvite and carbonate apatite) were more often found in women (7.0%) and in children (5.3%) than in men (1.4%). Brushite stones were seldom seen and cystine stones did not occur.
Management of Buried Penis in Adults
Authors: Alıcı B. , Çulha M. , Özkara H. , Akkuş E. , Hattat H.
Published: April 2003

Buried penis is rarely managed in adults. Two patients with buried penis were treated at 18 and 20 years of age. An autolog split-thickness graft was used for covering the dermal defect of the penis. Results were successful without any evidence of postoperative complications.
A Simple Technique for Vesicourethral Anastomosis in Retropubic Radical Prostatectomy
Authors: Mimata Hiromitsu , Kasagi Yasuhiro , Sakamoto Sadaaki , Nomura Yoshio
Published: April 2003

Vesicourethral anastomosis during radical retropubic prostatectomy is often difficult. We present a new simple technique using a Nélaton catheter to aid in accurate suture placement for vesicourethral anastomosis.
Retroperitoneoscopic Managementof Infected Cysts in Adult Polycystic Kidney Disease
Authors: Hemal A.K. , Gupta N.P. , Rajeev T.P. , Aron Monish , Bhowmik Dipankar , Jain Rajeev
Published: April 2003

Conservative measures are the mainstay of therapy in adult polycystic kidney disease (APKD). Pain, infection and obstructive uropathy are the major indications for intervention. Chronic pain has been treated with narcotic analgesics, needle aspiration of dominant cysts, and open renal cyst decortication. Laparoscopic cyst decortication, by either transperitoneal or retroperitoneal access, is a new emerging option with similar efficacy to open surgery and less morbidity. Cyst infection in these patients responds poorly to commonly used antibiotics. Patients with refractory cyst infection may even require nephrectomy. Herein, we present 2 cases with APKD that were treated by retroperitoneoscopic decortication for painful and infected cysts. Both patients showed prompt and sustained improvement in symptoms, with minimal morbidity and short convalescence. This approach has not hitherto been described for infected cysts in APKD. The retroperitoneoscopic route should be preferred in the presence of infected cysts so as to prevent intraperitoneal contamination.
Spontaneous Regression of Inflammatory Pseudotumor of the Urinary Bladder
Authors: Mochizuki Yasushi , Kanda Shigeru , Nomata Koichiro , Hayashi Tomayoshi , Yamasaki Yasuto , Kanetake Hiroshi , Saito Yutaka
Published: April 2003

Inflammatory pseudotumor of the urinary bladder is a benign proliferative lesion of the submucosa and its treatment has not yet been established. Here we present a case of spontaneously regressed inflammatory pseudotumor of the urinary bladder.
Pathophysiology of Lower Urinary Tract Symptoms in Aged Men without Bladder Outlet Obstruction
Authors: Kuo Hann-Chorng
Published: April 2003

Objective: To assess the pathophysiology of lower urinary tract symptoms (LUTS) in aged men without bladder outlet obstruction in a videourodynamic study. Methods: In a videourodynamic study of 324 consecutive men with moderate to severe LUTS suggestive for bladder outlet obstruction, 112 were found to be urodynamically nonobstructed. International prostatic symptom score (IPSS), uroflowmetry and transrectal sonography of the prostate were assessed before videourodynamic study. The pressure flow expression and the obstructive parameters were compared between the 212 obstructed and 112 nonobstructed men. Results: Of the 112 nonobstructed men investigated, 25 had a normal bladder and urethral trace (22.3%), 5 had detrusor instability (4.5%), 17 had a hypersensitive bladder and a normal urethra (15.2%), 3 had detrusor underactivity and a normal urethra (2.7%), while 61 were found to have a poorly relaxed external sphincter and low detrusor contractility (54.5%). Most of the patients in the normal and hypersensitive groups had normal voiding pressure and high flow (NPHF) tracings, whereas men with detrusor underactivity or a poorly relaxed external sphincter had normal voiding pressure and low flow (NPLF) tracings. Only the maximal flow rate and voided volume were significantly higher in patients with NPHF than in patients with NPLF tracings. However, both groups showed a significantly lower IPSS, less residual urine, and a smaller transition zone index than the obstructive group. After medical treatment, 78 patients (69.6%) had satisfactorily improved, 31 patients (27.6%) remained stationary, while 3 (2.7%) worsened. Conclusion: Nonobstructed men with LUTS have various pathophysiologies other than benign prostatic obstruction. In this study 54.5% of these patients had poorly relaxed external sphincter on videourodynamic study. Identification of the underlying pathology can not only prevent unnecessary prostate surgery but can also enable proper medical treatment to be selected.
‘Silent’ Surgical Disease Presenting with Severe Dysuria
Authors: Weirich Torsten , Schubert Jörg
Published: April 2003

We report a case of long-standing dysuria due to silent surgical abscess disease. The cause of our patient’s complaint was not expected because we focused on dysfunctional voiding and not dysfunction as result of pathology close to the bladder neck since the history given by the patient was unremarkable.
Urinary Fibronectin Levels in Patients Treated with Intravesical Bacillus Calmette-Guérin for Superficial Bladder Cancer
Authors: Danışman Ahmet , Bulut Kemal , Kukul Erdal , Özen İkbal , Sevük Metin
Published: April 2003

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0.05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy.
Incidence of Chromosome 8, 10, X and Y Aneuploidies in Sperm Nucleus of Infertile Men Detected by FISH
Authors: Acar Hasan , Kilinç Mehmet , Çora Tülin , Aktan Murat , Taşkapu Hakan
Published: April 2003

We studied the frequency of aneuploidy in sperm nuclei of six infertile men with abnormal semen profile and normal karyotype, using fluorescence in situ hybridization (FISH) with DNA probes for chromosomes 8, 10, X and Y. The control group consisted of four healthy fertile men with normal karyotype and semen profiles. The purpose of this study was to determine whether there are differences between infertile male donors and control donors for: (1) the incidence of sex chromosome aneuploidy, and (2) the number of disomies for chromosomes 8, and 10 cosegregating with chromosomes X and Y. FISH analysis showed no significant differences of sex ratios of the sperm nuclei in and between infertile and control groups. The most significant abnormalities in the infertile group were clusters of sperm nuclei bearing XY and XYY. In addition, the incidence of disomic sperm nuclei for chromosomes 8 and 10 consegregating with sex chromosomes was not significantly different beween the patient and control groups, nor within them. However, the total frequency of aneuploid sperm nuclei was significantly different beween the infertile group and the control group. We observed a significant excess of sperm nuclei bearing chromosome 10 along with disomy for chromosome Y (10YY). In conclusion, our results from FISH analysis demonstrate a significantly increased frequency of aneuploidy for the sex chromosomes in sperm nuclei from infertile men. Therefore it may be concluded that infertility is a risk factor for sex chromosome aneuploidy in sperm nuclei.