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Biomedical subjects

K Wolff

Publications and source records attributed to K Wolff.

At least 145 records · Page 8Linked to original sources

Epiluminescence microscopy: a new approach to the early detection of melanoma.

ELM is a new approach to the diagnosis of pigmented skin lesions that holds considerable promise. It reveals a new dimension of in vivo morphology that can be used when the diagnostic criteria employed in routine visual diagnosis fail. It does not add to the diagnostic armamentarium available for unequivocal lesions, but has significant value for those equivocal, small, pigmented skin lesions that pose major diagnostic problems even for experienced clinicians. Prerequisites for a sensible approach to ELM include recognition of new morphologic ELM criteria and employment of these criteria in an analytic process called pattern analysis. As in clinical dermatology, ELM depends heavily on a learning process and, of course, on experience. ELM increases diagnostic accuracy for pigmented skin lesions in that it helps to distinguish between melanocytic and non-melanocytic pigmented lesions, and between benign and malignant growth patterns. Thus, ELM has the potential to overcome the diagnostic limitations encountered in clinical dermatology when small, early pigmented lesions are encountered that do not yet express the full complement of diagnostic features needed to arrive at a correct diagnosis. The fact that it is a noninvasive, in vivo method makes it even more attractive as a diagnostic tool in clinical practice. ELM already has proven to be of great practical value in several centers by increasing the probability that early melanoma will not be overlooked and by helping to prevent unnecessary major surgery in patients in whom a non-melanocytic or benign pigmentary lesion is suspected clinically to be a melanoma. It eventually may prove valuable for patients with dysplastic nevi by helping determine which lesions need to be removed. Of course, ELM also has limitations. It does not provide 100% diagnostic accuracy and is of little help in small lesions that are pigmented maximally and uniformly because these do not reveal the criteria necessary for ELM pattern analysis. At this stage, therefore, ELM does not replace histopathologic examination. Undoubtedly, ELM can be improved, and continued studies will reveal just how reliable the individual criteria discussed here eventually will prove to be in clinical practice. This requires continuing to accumulate and analyze data, and instituting teaching programs to familiarize dermatologists with ELM criteria and their use in pattern analysis. It is certain, however, that, just as clinicians have learned to employ the "ABCD" rules in visually recognizing and diagnosing melanoma, they will learn this new and more subtle approach to the previously unknown morphologic features that characterize benign and malignant pigmentary lesions on ELM.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnosis, Differential↗

Estimation of the volume-weighted mean nuclear volume discriminates Spitz's nevi from nodular malignant melanomas.

BACKGROUND: Spitz's nevi are benign melanocytic skin tumors that are usually differentiated from nodular malignant melanomas by histopathologic criteria. Often, however, the architectural pattern and cytologic features of Spitz's nevi and nodular melanomas are similar. Hence, Spitz's nevi may be confused with nodular malignant melanomas at the histopathologic level. EXPERIMENTAL DESIGN: The determination of volume-weighted mean nuclear volume (Vv) uses a technique that permits an unbiased and efficient estimation of nuclear volumes in tissues. In this study, Vv was determined in 13 Spitz's nevi and 14 nodular malignant melanomas to investigate whether this stereologic approach may be of use in the differentiation of these two tumors. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on Feulgen-stained sections using stereologic estimation of the Vv. RESULTS: The Vv (+/- SD) of Spitz's nevi was 491.6 micron3 (SD +/- 175.1), whereas nodular malignant melanomas exhibit a significantly higher (p < 0.001) Vv of 775.2 micron3 (SD +/- 205.4). This difference was even more pronounced when the deeper portions of the lesions (Spitz's nevi: 443.1 micron3, SD +/- 142.4; nodular malignant melanomas: 864.1, SD +/- 169.6) were investigated. In addition, we found that in relation to the depth of the lesions the mean Vv decreased in Spitz's nevi, whereas it increased in nodular melanomas. CONCLUSIONS: We found that (i) nodular malignant melanomas reveal a larger Vv than Spitz's nevi in general, and (ii) in contrast to malignant melanomas, the Vv of nevomelanocytes in Spitz's nevi decreases in the deeper portions of the dermis. Thus, Vv may be regarded as a helpful tool for the differential diagnosis of Spitz's nevi and nodular malignant melanomas.

Cell Nucleus↗

Multipoint mapping of the central core disease locus.

A linkage analysis with 12 DNA markers from proximal 19q was performed in eight families with central core disease (CCO). Two-point analysis gave a peak lod score of Z = 4.95 at theta = 0.00 for the anonymous marker D19S190 and of Z = 2.53 at theta = 0.00 for the ryanodine receptor (RYR1) candidate gene. Multipoint linkage data place the CCO locus at 19q13.1, flanked proximally by D19S191/D19S28 and distally by D19S47. This map location includes the RYR1 gene. The results of the linkage study present no evidence for genetic heterogeneity of CCO.

Animals↗

Steady-state pharmacokinetics of methadone in opioid addicts.

Kinetic parameters were investigated in tolerant methadone maintenance patients. The disposition of methadone at steady-state was assessed on 8 occasions-in 5 opioid addicts prescribed wide ranging doses of methadone (10 mg to 60 mg per day)-providing unique pharmacokinetic data. Statistical analysis showed that the kinetics of oral methadone at steady-state were described using a single compartment model. Analysis of the plasma concentration-time curves gave estimates of the variance of methadone clearance and apparent volume of distribution, and indicate that methadone is rapidly absorbed (mean Ka, 1.7 h-1) with a detectable increase in the plasma drug concentration 15 to 30 min after dosing. The elimination of methadone from plasma was found to occur slowly (mean t1/2 26.8 h) beginning soon after the administration of the daily oral prescription. The apparent volume of distribution-assuming the oral bioavailability (f) of methadone to be 0.95--was large (mean 6.7 l.kg-1). The slow clearance of this drug from the body (mean 3.1 ml.min-1.kg-1) confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval.

Adult↗

Nonbullous pemphigoid: prodrome of bullous pemphigoid or a distinct pemphigoid variant?

We describe two patients with pruritic, mainly urticarial or eczematous lesions associated with peripheral blood eosinophilia. No vesicles or blisters developed in either patient throughout the course of the disease (29 and 38 months, respectively). To characterize the clinicopathologic features of these patients we performed histopathologic studies, direct and indirect immunofluorescence, immunoelectron microscopy (patient 2), and immunoprecipitation of both patients' serum. Histopathologic examination revealed a moderate eosinophilic infiltrate partly arranged along the basement membrane zone and focally invading the epidermis. Linear deposits of immunoglobulin and C3 along the dermoepidermal junction were localized within the lamina lucida and over the hemidesmosomal plaques. Immunoprecipitation revealed the presence of circulating autoantibodies against the 230 kd bullous pemphigoid antigen. These findings suggest that our patients had a distinct, nonbullous variant of the pemphigoid spectrum.

Aged↗

Statistical evaluation of epiluminescence microscopy criteria for melanocytic pigmented skin lesions.

BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive technique by which the clinical diagnosis of pigmented skin lesions (PSL) can be improved. Many ELM criteria have been described, but their significance in the differential diagnosis of PSL has not yet been established. OBJECTIVE: The purpose of this study was to determine the value of ELM criteria in the differential diagnosis of PSL. METHODS: Two hundred one melanocytic PSL (61 common nevi, 60 dysplastic nevi, and 80 melanomas) were investigated with ELM for the presence of certain ELM criteria; their significance was determined by calculating the odds ratios. RESULTS: Individual ELM criteria have different weights of significance in the differential diagnosis of melanocytic PSL. Selected patterns of ELM criteria adjusted to the distinct types of PSL considerably improve the diagnostic accuracy of melanocytic PSL. CONCLUSION: The prevalence of certain distinct ELM criteria in a given melanocytic PSL has statistical value in differential diagnosis.

Confidence Intervals↗

Rapid detection of genetic variability in chrysanthemum (Dendranthema grandiflora Tzvelev) using random primers.

Genetic variation in chrysanthemum (Dendranthema grandiflora) was studied using a recently developed technique generating Random Amplified Polymorphic DNAs (RAPDs). It appeared that variation between cultivars was high and that the cultivars used could be distinguished from each other by using only two different primers. A family of cultivars, derived from one original cultivar by vegetative propagation, had identical fragment patterns. Because of the high level of polymorphism and clonal stability RAPD fragments are useful for cultivar identification. Genetic variability among related Dendranthema species was too high to study genetic distances either among cultivars within chrysanthemum or among species related to chrysanthemum.

Base Sequence↗

MCP-1 mRNA expression in basal keratinocytes of psoriatic lesions.

In addition to hyperproliferation of keratinocytes, psoriasis is characterized by pronounced leukocytic infiltration. In contrast to the epidermal localization of neutrophils and T lymphocytes, macrophages are almost exclusively restricted to the dermal compartment. By immunohistologic analysis, these dermal macrophages were mainly encountered in the papillary dermis and arranged along the rete ridges in close proximity to proliferating keratinocytes. Monocyte chemoattractant protein (MCP-1) anti-sense RNA probes yielded abundant signals over the proliferating basal keratinocytes of the tips of the rete ridges, and, to a lesser extent, in cells in the papillae. Thus, the strongest MCP-1 message in psoriatic lesions is found above the dermal-epidermal junction and this may explain the characteristic sub-basal distribution of dermal macrophages. These results suggest that MCP-1 is important in regulating the interaction between proliferating keratinocytes and dermal macrophages in psoriasis pathogenesis.

Antigens, CD↗

CD68 positive epidermal dendritic cells.

In a pilot study designed to investigate immunopathologic events in the evolution of cutaneous lesions in pemphigus foliaceus, we found that in this condition the epidermis is replete with CD68+ dendritic cells. The present study was designed to investigate the nature of this novel intraepidermal CD68+ cell population. For that purpose lesional skin of five patients with PF and, for comparison, of patients with another acantholytic autoimmune disease, pemphigus vulgaris, were examined using a panel of monoclonal antibodies in a three-step immunoperoxidase technique, in an immunofluorescence double-labeling technique, and by immunoelectron microscopy. We found epidermal CD1a+ Langerhans cells significantly decreased in pemphigus foliaceus compared to pemphigus vulgaris, but pemphigus foliaceus and not pemphigus vulgaris epidermis harbored large amounts of bone marrow-derived (CD45+) cells that expressed CD68, HLA-DR, and beta 2-integrin antigens, the most pronounced expression being observed for CD11c and CD18. These epidermal CD68+ cells were of dendritic shape, were CD1a-, and lacked Birbeck granules (BG); however, a small portion of CD68+ cells was also CD1a+ and exhibited BG as revealed by immunoelectron microscopy. These findings demonstrate that in certain conditions, i.e., in pemphigus foliaceus but not in pemphigus vulgaris, there is a shift from CD1a+/CD68- epidermal Langerhans cells towards CD1a-/CD68+ dendritic epidermal cells. The detection of a small number of CD1a+/CD68+/BG+ dendritic epidermal cells may identify these cells as a link between the CD1a+/CD68+/BG+ Langerhans cells and the CD1a-/CD68+/BG- cell population and suggests that these cells represent a transitional form of myelomonocytic cells during their phenotypic and morphologic transformation into resident epidermal Langerhans cells.

Adolescent↗

In vivo epiluminescence microscopy: improvement of early diagnosis of melanoma.

The majority of pigmented skin lesions can be diagnosed correctly on the basis of clinical criteria; however, there remain a surprisingly high number of small pigmented lesions in which the distinction between melanocytic and non-melanocytic and benign and malignant lesions, and thus between melanoma and non-melanoma, is difficult or impossible to make with the naked eye. Epiluminescence microscopy is a non-invasive technique that, by use of oil immersion, makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented lesions. The technique of epiluminescence microscopy is reviewed, and the significant improvement in the clinical diagnosis of pigmented skin lesions and, in particular, melanoma by this technique is documented.

Humans↗

Contractile effects of endothelin 1 and endothelin 3 on myometrium and small intramyometrial arteries of pregnant women at term.

This in vitro study was undertaken to investigate the effects of endothelin 1 (ET-1) and endothelin 3 (ET-3) on intramyometrial arteries and myometrial tissue of the uterus from pregnant women at term. Segments of small myometrial arteries (outer diameter 100-500 microns) obtained at cesarean section were isolated and mounted in tissue chambers. The effect of ET-1 and ET-3 on isometric tension was compared with the action of noradrenaline. In similar experiments on myometrial strips, the effect of ET-1 and ET-3 was studied in comparison with oxytocin. ET-1 and ET-3 both produced contractions of arteries and myometrial strips, ET-1 being the most potent. The response of ET-1 was more powerful than the effect of the reference compounds, i.e. noradrenaline with regard to myometrial arteries and oxytocin with regard to the myometrium. It is concluded that endothelins are powerful constrictors of myometrial arteries from pregnant women and possess strong oxytocic effects. In particular, ET-1 could be involved in the regulation of myometrial contractility and/or uteroplacental blood flow.

Adult↗

An evaluation of the measurement of drugs of abuse by commercial and in-house horizontal thin layer chromatography.

We have compared an in-house horizontal thin layer chromatography (TLC) method with a commercial TLC screening kit (Toxi-Lab) to find the most suitable method for screening urine for opioid drugs. The in-house TLC procedure is cheaper and more efficient than the commercial TLC method and is ideal as a confirmatory method when used in conjunction with other established laboratory methods. The in-house TLC method is useful for one-off requests and is able to differentiate between small quantities (0.1-0.5 mg/L) of the different, commonly abused opioids and their metabolites, which means that it is well suited for use at a local Drug Addiction Unit as a routine screening service.

Chromatography, High Pressure Liquid↗

Early recognition and prognostic markers of melanoma.

Malignant melanoma can be cured if the tumour is recognized at an early phase. Therefore, early recognition is of critical importance and cannot be overemphasized. Epiluminescence microscopy is a non-invasive technique that makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented skin lesions. Thereby preoperative clinical diagnosis can be improved. In order to assess the prognosis of a melanoma patient and to predict the outcome of the disease a number of morphological and immunological parameters these will be reviewed, are helpful.

DNA↗

Pigmented Spitz nevi: improvement of the diagnostic accuracy by epiluminescence microscopy.

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.

Diagnosis, Differential↗

Fotemustine plus dacarbazine in advanced stage III malignant melanoma.

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.

Adult↗

Isolation of human immunodeficiency virus type 1 from human epidermis: virus replication and transmission studies.

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.

Cell Line↗