Phylogeny and nucleotide sequence of a 23S rRNA gene from Neisseria gonorrhoeae and Neisseria meningitidis.
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Biomedical subjects
Publications and source records attributed to K Wolff.
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BACKGROUND: Pigmented Spitz nevi have distinct clinical features but often may be difficult to differentiate from malignant melanoma by clinical criteria. OBJECTIVE: The purpose of this study was to use a new noninvasive diagnostic approach to improve the clinical diagnosis of Spitz nevi. METHODS: Epiluminescence microscopy (ELM) is a new, noninvasive technique for which criteria for the diagnosis of melanocytic tumors, benign and malignant, recently have been established. These criteria were tested in an investigation of 54 pigmented Spitz nevi. RESULTS: With ELM the accuracy of clinical diagnosis of pigmented Spitz nevi improved from 56% (clinical) to 93% (ELM). CONCLUSION: Our findings suggest that ELM criteria are useful to improve the accuracy of clinical diagnosis of Spitz nevi.
19 patients with advanced malignant melanoma were treated with fotemustine and dacarbazine. Data recorded and available for evaluation in all patients included clinical and histopathological parameters of the primary melanoma, blood chemistry, blood cell count, chest X-ray, ultrasound and bone scan for initial staging of the site of metastases and follow-up during treatment. Dosage was fotemustine 100 mg/m2 and dacarbazine 200 mg/m2 intravenously twice monthly on days 1 and 8, repeated for a maximum of six courses. There were two complete and three partial responses in 5/19 patients (26%), and 8 patients (42%) had stable disease. 6 (32%) patients had no response. Median length of complete and partial responses was 3.9 months, and that of stable disease 4.2 months. The main side-effects were thrombocytopenia in 10 patients (53%) and nausea in 6 (32%); the nausea was easily suppressed by ondasetron. Thus, fotemustine-dacarbazine may be new treatment in advanced melanoma.
For a better understanding of the pathogenetic events operative in the cutaneous manifestations of human immunodeficiency virus type 1 (HIV-1) disease, we investigated whether epidermal cells (EC) from HIV-1-seronegative persons can be infected with HIV-1 and, vice versa, whether HIV-1 can be rescued from the epidermis of HIV-1-infected individuals. In a series of three experiments, we consistently found that exposure of EC from HIV-1-seronegative donors to HIV-1 led to viral replication in these cells as evidenced by the detection of HIV-1 p24 in culture fluids. Because EC had been substantially enriched for Langerhans cells (LC) before being exposed to HIV-1, it is reasonable to assume that these CD1a+/CD4+/MHC class II+ antigen-presenting cells of the epidermis represented the actual targets of infection. This assumption is further strengthened by the observation that T cell-depleted cell suspensions from Langerhans cell histiocytosis (LCH) lesions could be productively infected with HIV-1. Conversely, co-culture of epidermal sheets from HIV-1-seropositive individuals with mononuclear phagocytes (MNP) from HIV-1-seronegative donors resulted, after 3 to 5 weeks, in the detection of HIV-1 p24 in 12 of 23 cases. Immunocytochemical analysis, using a monoclonal antibody specific for p24, revealed the presence of HIV-1 in adherent MNP in three cocultures tested. In addition, cellular DNA from these cultures showed strong signals when hybridized to a HIV-1-specific DNA probe. The further finding that two isolates examined exhibited different restriction enzyme patterns indicates that they are separate entities rather than contaminants. Transmission of these isolates to MNP, B- or T-cell lines resulted in cultures strongly positive for p24 and, in the case of H9 cells, for viral particles as detected by electron microscopy. Our results therefore strongly suggest that EC not only can serve as targets for HIV-1, but also can allow efficient virus replication and transmit HIV-1 to various cell types of the hematopoietic lineage.
At present, tumor invasion represents the most reliable prognostic factor for primary malignant melanoma. The 10-year survival rate of "thin" melanomas (Breslow less than 0.76 mm) is more than 95%, but approximately 5% of these low-risk tumors do metastasize. In an attempt to determine prognostic markers for "thin" melanomas we investigated the volume-weighted mean nuclear volume (Vv) of primary melanomas with tumor invasions below 0.76 mm in 32 patients. Ten of these patients had developed melanoma metastases within a mean follow-up period of 49 months; 22 patients who had not developed metastases and who were comparable with regard to clinical and histologic criteria as well as to follow-up period were selected as a comparison group. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on hematoxylin-eosin-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. In addition, two-dimensional morphometric parameters (nuclear area and shape factors) as well as clinical (sex, age, location) and histologic characteristics (Breslow's thickness, Clark's level, and growth patterns) were recorded. The mean Vv (+/- SD) of primary melanomas with subsequent metastatic course was 273 microns 3 (+/- 81.3), whereas primary melanoma lesions without subsequent metastases exhibited a significantly lower Vv of 154 microns 3 (+/- 25.3) (p = 0.0008). On the other hand, two-dimensional morphometric and clinical and histologic parameters did not correlate with prognosis. Vv thus seems to represent a powerful and independent prognostic marker for "thin" primary melanomas. Assessment of Vv may provide a valuable tool in selecting patients with high-risk stage I, Breslow less than 0.76 mm, melanoma for adjuvant therapy.
In an attempt to find an effective therapy for necrobiosis lipoidica, we have treated six patients with this disease with a 5-week course of systemic corticosteroids. This treatment resulted in complete cessation of disease activity in all patients and no recurrence in a mean follow-up period of 7 months; however, restitution of atrophic skin lesions could not be achieved. The therapy was well tolerated and did not pose problems, even in diabetic patients. These results strongly suggest that short-course therapy of necrobiosis lipoidica with corticosteroids is of lasting benefit to these patients and should probably be considered early in the course of their skin disease.
Human studies using oral cyclosporin A (CyA; Sandimmun) therapy for psoriasis have been in progress for nearly 9 years. Cumulative data of the clinical effects of this therapy in 1000 patients have been collected, and are derived from multiple open and controlled studies. The efficacy of this treatment in psoriasis is well recognized, and the relative safety of up to 2 years of therapy is also established, provided that the guidelines are observed. However, there is concern regarding the long-term safety of CyA treatment of psoriasis as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory, and CyA should only be used by dermatologists who have expertise in its use. During treatment, co-operation with an experienced nephrologist is strongly recommended.
Cyclosporin A (CyA) has proved effective in various dermatological diseases, but its mechanisms of action within the skin are still ill-defined. In order to characterize more clearly the cellular targets of CyA we examined its effects on skin immune cells in normal and UVB- and PUVA-irradiated skin by means of a three-step immunoperoxidase reaction and immunofluorescence double-labelling technique. The CyA-induced depletion of epidermal Langerhans cells equals that seen with UVB or PUVA alone. CyA alone has no effect on the number and distribution of dermal cells. CyA modulates the UV irradiation-induced changes by: (i) inhibiting the UVB- and PUVA-induced ICAM-1 expression by keratinocytes and (ii) suppressing the PUVA-induced upregulation of CD11a expression by macrophages (72 +/- 12% of Ki-M8+ macrophages express CD11a with PUVA, compared with 20 +/- 5% with CyA + PUVA, P < 0.001). Neither treatment affected ICAM-1 expression by endothelial cells. In addition, CyA increases PUVA minimal phototoxicity dose from 10 +/- 2.6 J/cm2 (PUVA alone) to 15.3 +/- 3.1 J/cm2 (CyA + PUVA), (P < 0.001). In conclusion, the effects of CyA on the skin include a down-modulation of the PUVA-erythema reaction, associated with a direct or indirect modulation of adhesion molecule expression.
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We monitored eight patients who were receiving a decreasing dose of methadone for treatment for opioid addiction (detoxification). Patients with plasma concentrations of methadone less than 0.05 mg/L experienced withdrawal symptoms, relapsed, and re-abused illicit drugs. Four patients took extra methadone (illicitly obtained) during detoxification. None of the eight patients in our study were successfully weaned off methadone: all left the methadone detoxification program before the completion of treatment. Two patients subsequently returned to a fixed methadone program elsewhere, and four relapsed and returned to illicit drug misuse. Plasma measurements may help clinicians assess patients during methadone detoxification.
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Studies on minimum erythema doses, histological investigations and quantitative determination of DNA repair synthesis of epidermal cells revealed that a tan induced by the oral administration of 8-methoxy-psoralen (8-MOP) and subsequent UVA irradiation gives protection from the erythemogenic effects of sunlight, diminishes UVA-induced cellular injury in the epidermis and, possibly, also shields DNA from incident UV radiation. In a study of 14 patients with severe polymorphous light dermatosis the 8-MOP-UVA induced tan proved to be a clinically effective sunscreen. The uncontrolled use of this method for UV protection of normal individual is, however, not recommended.
Lupus erythematosus panniculitis is a rare clinical variant of lupus erythematosus. In this report we described a 38 year-old female patient who had suffered from chronic discoid lupus erythematosus for several years before developing widespread inflammatory, sclerotic and ulcerative lesions, which were first diagnosed as Weber-Christian panniculitis. It was only when the patient developed other signs and symptoms of systemic lupus erythematosus that the subcutaneous lesions were recognized as lupus panniculitis. A combined regimen of tetracyclines and chloroquine resulted in a remission, both with regard to regression of the lesions and suppression of the serological parameters of disease activity. The findings in this particular patient and similar reports in the literature form the basis for a discussion of the entity of lupus panniculitis.
Acute, febrile, neutrophilic dermatosis (Sweeet's syndrome) is an uncommon, distinct disease of unknown origin. It is characterized by typical skin lesions and systemic symptoms such as fever and leucocytosis. Ultrastructural data suggest a primary vascular process as the initial pathogenic mechanism. In this paper two patients are described and the clinical variability, incidence and pathogenesis of this syndrome are discussed.
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Danazol, an attenuated androgen, was administered to four patients with hereditary angioneurotic oedema, with rapid and complete response without side-effects. The follow-up period has now been up to 17 months. In all patients there was an indirect indication that their hormonal state influenced the course of the disease.