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Antineoplastic Agents↗
Biomedical subjects
G Burg
Publications and source records attributed to G Burg.
CD4 + /CD7- T cell frequency and polymerase chain reaction-based clonality assay correlate with stage in cutaneous T cell lymphomas.
In cutaneous T cell lymphomas, tumor cells can be found in skin and in other compartments. A precise definition of extracutaneous spread including blood involvement is necessary for staging and treatment design. We investigated peripheral blood in 51 patients with various types of cutaneous T cell lymphomas by the analysis of blood smears for Sézary cells, the CD4 + /CD7- T helper cell frequency in the peripheral blood by fluorescence activated cell sorter analysis and by polymerase chain reaction for the T cell receptor gamma-chain followed by denaturing gradient gel electrophoresis. Eleven polymerase chain reaction products were sequenced. Thirty-five per cent of patients with stage Ia-IIb cutaneous T cell lymphomas presented a peripheral blood T cell clone. In patients with stage III-IVb cutaneous T cell lymphomas 75% were positive for clonality in the peripheral blood by polymerase chain reaction. Interestingly, three of 13 Sézary patients showed a TCR-gamma joining region pseudogene (JgammaP1/JgammaP2) usage. CD4 + /CD7- cell counts were significantly higher in patients with advanced cutaneous T cell lymphomas than in patients with early cutaneous T cell lymphomas. There was a correlation between increased percentage of circulating CD4 + /CD7- cells and detection of clonality by polymerase chain reaction (p = 0.001). There was no significant correlation between the polymerase chain reaction data and the percentage of Sézary cells on blood smears. A significant correlation between CD4 + /CD7- cells and Sézary cells was found, however. Stepwise logistic regression analysis showed that the CD4 + /CD7- cell count and clonal T cell detection in peripheral blood are independently correlated with stage. The combination of both parameters gives more information than each one separately. In conclusion, our data indicate that fluorescence activated cell sorter analysis of peripheral blood and polymerase chain reaction-based clonality assays can improve the accuracy of staging investigations in cutaneous T cell lymphomas patients.
Antigens, CD7↗
Instruction of compression therapy by means of interface pressure measurement.
BACKGROUND: Compression therapy of the leg is the cornerstone in the conservative treatment of venous ulcers. The application of compression bandages, however, is largely a matter of personal experience. OBJECTIVE: To evaluate the interface pressure under compression bandages and to improve the technique. METHODS: Six courses on wound healing with 24-28 participants as well as individual training at our hospital were provided. Interface pressure at the distal medial calf was measured using a simple, but accurate pressure sensor that was built for this purpose (accuracy: +/-3 mm Hg). RESULTS: During the wound healing courses, the absolute difference from the target pressure of 35-45 mmHg improved from 8.4 mm Hg (95% CI 0.0-34.1) to 3.5 mm Hg (95% CI 0.0-14.0) (P = .0001). After four sessions, interface pressures greater than 60 mmHg were avoided. During individual training, even nurses with everyday experience in compression therapy improved their accuracy. CONCLUSION: There is a need for objective measurement of interface pressure in the teaching of compression therapy with bandages. The principles can be taught during a few exercises. However, repeated practice over a longer period of time is necessary to reach a certain accuracy.
Bandages↗
Teledermatology as a new tool in sub-saharan Africa: an experience from Tanzania.
Large areas of sub-Saharan Africa suffer a substantial lack of skin care. Hence teledermatology, meaning the online visual exchange of clinical and histologic data, could develop into a powerful medical resource. We report the first established teledermatologic connection in this area: between the Regional Dermatology Training Centre (RDTC) in Moshi, Northern Tanzania, and the Department of Dermatology, University Hospital of Zürich, Switzerland. This report illustrates local difficulties as well as the considerable potential of teledermatology in such a setting.
Dermatology↗
Leg ulcers in peripheral arterial disease (arterial leg ulcers): impaired wound healing above the threshold of chronic critical limb ischemia.
BACKGROUND: Peripheral arterial disease is the only identifiable etiology in approximately 10% of leg ulcers. Clinical data on the management of these chronic wounds are scarce. OBJECTIVE: We attempted to outline the threshold of systolic ankle pressure and ankle-brachial-index (ABI) below which arterial leg ulcers can occur and to outline the indication for revascularization in arterial leg ulcers. METHODS: Diagnostic and outcome analysis was performed for 26 consecutive patients with arterial leg ulcers. We calculated sensitivities, specificities, and receiver operating characteristic (ROC) curves for the identification of arterial leg ulcers among all 223 consecutive leg ulcer patients within a 3-year period, as well as the ROC curve for patients who required revascularization. RESULTS: The systolic ankle pressure was 88 (18-130) mm Hg (median; 95% confidence interval) and the ABI was 0.60 (0.15-0.86), respectively. Eighteen patients (69%) were subjected to revascularization. By the end of the study, 24 patients (92%) healed completely, 1 improved (90% wound closure), and 1 patient had to undergo below-knee amputation for chronic osteomyelitis. During this study, the ankle pressure and ABI were poor in distinguishing those patients who required revascularization from those who healed without revascularization. CONCLUSION: Most arterial leg ulcers do not meet the criteria of chronic critical limb ischemia, but they do not heal under conservative measures, either. A majority of these patients benefit from revascularization and should, therefore, be referred for arterial duplex ultrasound investigation or angiography. In our study, an ankle pressure below 110 mm Hg identified all patients (100%) who were subjected to revascularization procedures. However, controlled clinical studies are required to find the systolic ankle pressure and ABI below which revascularization can be recommended to speed up the healing time.
Aged↗
Management of leg ulcers in patients with rheumatoid arthritis or systemic sclerosis: the importance of concomitant arterial and venous disease.
PURPOSE: We assessed the etiology and the prevalence of peripheral arterial and venous disease in leg ulcers in patients with rheumatoid arthritis and systemic sclerosis and analyzed the outcome after treatment of macrovascular disease. METHODS: A clinical study on 15 consecutive patients with chronic leg ulcers in collagen vascular disease (nine patients with rheumatoid arthritis, six patients with systemic sclerosis) was carried out in a referral center. Angiography was used when the ankle-arm index was less than 0.8; venography was used when venous reflux was detectable by means of a hand-held Doppler examination. Therapies included percutaneous transluminal angioplasty (seven patients), femoropopliteal bypass grafting surgery (one patient), saphenectomy of the greater saphenous vein (six patients), and split skin graft (11 patients). RESULTS: All patients with rheumatoid arthritis exhibited a multifactorial etiology of their ulcers: four of nine patients had peripheral arterial disease, and five of nine patients had venous insufficiency. In one of these patients, arterial and venous disease was combined. Five of six patients with systemic sclerosis exhibited a multifactorial etiology of their ulcers: three of six patients had peripheral arterial disease, and three of six patients had venous insufficiency. One of these patients had both arterial and venous disease. In patients with rheumatoid arthritis, healing was achieved in six of nine patients, and marked improvement occurred in two of nine patients. A below-knee amputation was necessary in one patient with rheumatoid vasculitis. In patients with systemic sclerosis, healing was achieved in three of six patients, and marked improvement occurred in the other three patients. CONCLUSION: Most leg ulcers in patients with rheumatoid arthritis and systemic sclerosis disclose a multifactorial etiology. Relevant arterial and venous disease can be found in approximately half the patients. Our study suggests that revascularization and vein surgery improve the healing of leg ulcers in patients with collagen vascular disease. A prospective trial is now required to confirm these results.
Aged↗
Angiogenesis in cutaneous lymphoproliferative disorders: microvessel density discriminates between cutaneous B-cell lymphomas and B-cell pseudolymphomas.
The role of angiogenesis in neoplastic disorders is supported by the evidence that tumor growth beyond a certain size requires induction of new blood vessels. The extent of tumor-associated angiogenesis, measured as microvessel density (MVD), has shown to correlate with aggressiveness and the prognostic outcome in several malignant neoplasms. Few data have been reported on the angiogenic response in lymphoproliferative diseases. In this study, the MVD has been assessed in benign and malignant primary cutaneous B-cell lymphoproliferative disorders. MVD was determined in formaldehyde-fixed, paraffin-embedded specimens of primary cutaneous B-cell lymphomas (CBCL; n = 18) and cutaneous B-cell pseudolymphomas (B-PSL; n = 22) according to previously described protocols but was performed using computer-aided microscopic morphometry. The endothelial cells of microvessels were identified by immunohistochemical staining for factor VIII-related antigen and CD31. The MVD was 99 dots/mm2 for CBCL and 68 dots/mm2 for PSL, and a MVD of 115 dots/mm2 for CBCL and 73 dots/mm2 for PSL by using an antibody against factor VIII-related antigen and CD31 antigen, respectively. Univariate analysis revealed statistically highly significant differences in MVD between CBCL and B-PSL (P = 0.0036 with staining for factor VIII-related antigen and P = 0.0002 with staining for CD31 antigen). This study analyzes for the first time the angiogenic response in CBCL compared with that of B-PSL and demonstrates that MVD discriminates between CBCL and B-PSL. However, because of an overlap in the ranges of MVD in CBCL and PSL, the MVD is not useful as a diagnostic tool in individual cases.
Blood Vessels↗
Efficacy of histologic criteria for diagnosing early mycosis fungoides: an EORTC cutaneous lymphoma study group investigation. European Organization for Research and Treatment of Cancer.
The correct classification of lymphoproliferative disorders provides valuable information regarding subsequent clinical evolution of the disease. The ability of pathologists to distinguish such lesions is generally low, especially when dealing with minimal lymphoid infiltrates. To improve the efficacy of histopathology in the diagnosis of early lesions of mycosis fungoides (MF), we reviewed 24 skin biopsies from 18 patients with patch stage lesions of MF early in the course of their disease and 13 slides of lichenoid, spongiotic, or psoriasiform simulators of MF as a control series. A series of cytoarchitectural features was assessed, and differences in the distribution of histopathologic parameters between the two groups (early MF lesions and MF simulators) were evaluated by the chi-square test and Fisher's exact test. For these parameters, sensitivity and specificity also were calculated. A multivariate log-linear analysis was performed to estimate which of the morphologic parameters yielded independent diagnostic information. We found that the most important feature for the diagnosis of lymphoma was the presence of lymphocytes with extremely convoluted, medium-large (7-9 microm in diameter) nuclei (medium-large cerebriform cells), singly or clustered in the epidermis and in small sheets in the dermis. Additional significant histologic features were epidermotropism as single cells lined up along the basal keratinocytes of the dermal-epidermal junction, absence of significant papillary dermis fibrosis, and absence of significant numbers of dermal blastlike cells. We conclude that the efficacy of single histopathologic features in the diagnosis of early MF is generally poor. Only the presence of medium-large cerebriform cells in the epidermis or in clusters in the dermis proved to be a highly reliable feature. However, the histopathologic diagnosis of early MF lesions and their discrimination from inflammatory simulators can be achieved using the constellation of cytoarchitectural parameters proposed.
Biopsy↗
Upregulation of interleukin-12 receptor on peripheral blood mononuclear cells and HLA class I, HLA class II or ICAM-1 on melanoma cells by B7.1 and interleukin-12: a mechanism for immunostimulatory impact of melanoma cells adenovirally transfected with B7.1 and IL12?
Melanoma is an immunogenic tumour and may express both HLA class I and class II molecules. These can be recognized by cytotoxic T-cells. Melanoma cells can evade immunosurveillance due to the lack of co-stimulatory molecules such as B7.1 or B7.2. Interleukin-12 (IL12) exerts antitumour effects, and B7.1 and IL12 synergistically induce effective antitumour immunity. We investigated the immunostimulatory potential of melanoma cells adenovirally transduced with B7.1, IL12 or B7.1 plus IL12. We observed that: (i) melanoma cells transduced with B7.1 plus IL12 can elicit a strong proliferative response from peripheral blood mononuclear cells (PBMCs); (ii) a high level of TH1 cytokine production from PBMCs was induced by melanoma cells transduced with Adv-B7.1 plus Adv-IL12; (iii) the expression of HLA class I antigens, HLA class II antigens or ICAM-1 antigens was higher on melanoma cells transduced with Adv-lL12 or Adv-B7.1 plus IL12 than those transduced with Adv-LacZ or wild-type melanoma cells; and (iv) the expression of IL12 receptors on PBMCs was upregulated by melanoma cells transfected with Adv-IL12 or Adv-B7.1 plus IL12. Thus, melanoma cells transduced with both Adv-lL12 and B7.1 may represent another clinical approach for antimelanoma gene therapy.
Adenoviridae↗
Clinical efficacy of narrow-band UVB (311 nm) combined with dithranol in psoriasis. An open pilot study.
BACKGROUND: For UVB, the most effective wavelength in clearing psoriatic lesions was found to be of 313 nm. The efficacy of whole body exposure to narrow-band UVB (311 nm) combined with dithranol in psoriasis has not been evaluated to date. OBJECTIVE: Evaluation of the clinical efficacy of phototherapy with narrow-band UVB (311 nm) and dithranol for psoriasis by means of whole body exposures and analysis of the mean cumulative irradiation dose. METHODS: In this open pilot study, 13 patients were treated for 4-5 weeks. Evaluation of the therapeutic efficacy was performed by comparing the Psoriasis Area and Severity Index (PASI) scores at baseline and after 4 weeks of treatment. The cumulative irradiation dose was also calculated. RESULTS: Evaluation of the PASI scores showed a significant overall reduction of psoriatic lesions after 4 weeks of treatment. The cumulative irradiation dose was similar or lower to those found for phototherapy with narrow-band UVB alone. DISCUSSION: In patients with widespread psoriasis, treatment with narrow-band UVB (311 nm) combined with dithranol is safe and effective, allowing reduction of the cumulative irradiation dose.
Administration, Topical↗
Leg ulcers in patients with myeloproliferative disorders: disease- or treatment-related?
Leg ulcers are a relatively frequent problem in patients with myeloproliferative disorders under treatment with hydroxyurea (HU). The pathogenesis is currently unknown and may be multifactorial. Concomitant arterial or venous disease may play a contributing role in the development of these wounds. Vasculitis, cryoglobulinemia and pyoderma gangrenosum should be considered if typical clinical signs are present. We report on 3 patients with myeloproliferative disorders who developed HU-induced leg ulcers and review the literature. HU-induced leg ulcers share clinical features which can help to differentiate them from leg ulcers of other etiologies: occurrence under long-term treatment with HU at a dose of at least 1 g/day, localization in the malleolar region and spontaneous healing when HU is discontinued. We conclude that differentiation between disease-related and treatment-induced leg ulcers can be difficult and may not always be possible. In HU-induced leg ulcers, cessation of the drug typically leads to wound healing.
Aged↗
Revival of the use of botulinum toxin: application in dermatology.
Botulinum toxins (BTXs) comprise a family of neurotoxins designated as types A-G, which are produced by the anerobic bacterium Clostridium botulinum. BTX-A blocks the cholinergic transmission resulting in flaccid paralysis and autonomous nerve dysfunction. It has become a powerful therapeutic tool in a variety of conditions over the last decades. Primarily used in the treatment of strabismus, blepharospasm and hemifacial spasms, BTX has only recently been recognized in dermatology. The use of BTX in dermatology includes the treatment of focal hyperhidrosis, hyperfunctional facial lines as well as paralysis of the anal sphincter in the therapy of anal fissures. The mechanism of action is described and the current literature is reviewed.
Botulinum Toxins↗
Multifocal fixed drug eruption to paracetamol, tropisetron and ondansetron induced by interleukin 2.
Fixed drug eruptions (FDEs) represent an uncommon subset of drug reactions where typically dusky red skin eruptions recur at the same site each time a drug is administered. Multifocal FDEs are defined by skin eruptions at more than one site. We describe a patient with metastatic melanoma who developed a multifocal FDE to paracetamol, tropisetron and ondansetron during chemoimmunotherapy with interleukin 2 (IL-2) and dacarbazine. This case is unique since to our knowledge there has been no previous report of such a drug reaction to tropisetron. Moreover, recurrences were induced by drugs which were chemically unrelated (i.e. tropisetron and paracetamol). We propose that this unusual skin reaction to multiple drugs was induced by IL-2 administered during immunochemotherapy for the metastatic melanoma.
Acetaminophen↗
Cutaneous ulceration after injection of polyethylene-glycol-modified interferon alpha associated with visual disturbances in a melanoma patient.
Interferons are used in the therapy of multiple sclerosis, Kaposi's sarcoma, hepatitis and melanoma. Their short half-life that requires frequent injections can be increased by polyethylene glycol (PEG) modification. A 50-year-old patient was diagnosed as having an acrolentiginous melanoma (Breslow >5 mm, Clark level IV) and inguinal lymph node metastases. After surgical excision and lymphadenectomy, immune therapy with 6.0 microg pegylated interferon alpha(2b)/kg body weight, s.c., was started. Cutaneous ulcerations at the injection sites developed 9 months after treatment initiation. The patient also developed blurred vision and presented with binasal scotomas and pathological visually evoked potentials and electroretinogram. The cutaneous ulcerations slowly healed under local therapy and reduction of the concentration of the PEG-modified interferon from 0.86 to 0.43 mg/ml. The dosage was maintained. Two months later, the therapy was stopped due to disease progression. Vision subsequently recovered. Cutaneous reactions evolved at the sites of subcutaneous injections of PEG-modified interferon alpha(2b). Changes in vision can probably be attributed to immunotherapy.
Humans↗
Carpal tunnel syndrome with ulcerous skin lesions.
We report on a patient suffering from an advanced stage of carpal tunnel syndrome (CTS) with entire loss of cutaneous sensibility and impaired motor function who developed ulcerous skin lesions. In the present case, we would like to focus the attention of the dermatologist on CTS, when skin changes, i.e. atrophy, anhidrosis and ulcerations are found in the sensory zones of the median nerve. The necessity to explore a potential trauma is stressed.
Aged↗
Cocaine-related Stevens-Johnson syndrome.
We report the case of a 26-year-old student with erosive skin changes on his oral and genital mucosa and skin as well as on his thighs twice after cocaine snorting. The second of these two episodes was documented histologically, and other underlying causes of disease were excluded. A diagnosis of recurring Stevens-Johnson syndrome was made. Treatment was initiated with bed rest, systemic prednisone at 1 mg/kg body weight and liquid nutrition. Mucosal changes resolved within 4 days. On follow-up the patient remained free of symptoms while abstaining from the particular cocaine street mix in question. Cocaine has been involved in seizures, headaches, ischemic strokes, intracerebral hemorrhage, cerebral vasculitis, Churg-Strauss vasculitis, palpable purpura and Henoch-Schönlein vasculitis. Bullous skin disease in association with cocaine has been reported in 1 patient. To our knowledge, we report the first case of Stevens-Johnson syndrome associated with cocaine snorting.
Adult↗
Primary cutaneous T-cell-rich B-cell lymphoma and Hodgkin's disease in a patient with Gardner's syndrome.
A 50-year-old patient, suffering from familial polyposis (Gardner's syndrome), initially presented with several nodules on his left arm. Histological examination revealed primary cutaneous T-cell-rich B-cell lymphoma (TCRBCL). Staging procedures failed to detect any systemic involvement. Three years after total excision of the tumours, the patient presented with a non-specific dermatitis, enlarged axillary lymph nodes and splenomegaly. Histological and immunohistochemical examination of lymph node and spleen biopsy specimens resulted in the diagnosis of Hodgkin's disease (HD) of the nodular sclerosis type. Sequence analysis of single cells micromanipulated from skin and from lymph node lesions indicated that both lymphoma infiltrates were derived from the same precursor germinal centre B-cell clone. This is a case showing a clonal relationship between TCRBCL and HD, providing support to the B-cell origin of Hodgkin and Reed-Sternberg cells.
Gardner Syndrome↗
Cutaneous T-cell lymphomas: prognosis and quality-of-life issues.
Cutaneous lymphomas (CL) include lymphocytic malignancies derived from B cells, T cells, or other cell types such as natural killer cells. Cutaneous T-cell lymphomas are the most common CL, especially mycosis fungoides, Sézary syndrome, and the spectrum of large-cell CD30(+) lymphoproliferative disorders. It is important to understand that these diseases have a much better prognosis than their nodal counterparts; therefore, treatment has to be stage adapted and palliative. Due to the anatomical localization, these lymphomas have significant impact on the quality of life of the patient.
Humans↗