Biomedical subjects
K Wolff
Publications and source records attributed to K Wolff.
Identification and characterization of specific sequences encoding pathogenicity associated proteins in the genome of commensal Neisseria species.
The distribution of distinct sequences in pathogenic and commensal Neisseria species was investigated systematically by dot blot analysis. Probes representing the genes of Rmp, pilin and IgA1 protease were found to hybridize exclusively to the chromosomal DNA of the pathogenic species, Neisseria gonorrhoeae and/or Neisseria meningitidis. In contrast, specific sequences for the genes of the porin protein Por and the opacity protein (Opa) were also detected in a panel of commensal Neisseria species such as N. lactamica, N. subflava, N. flava, N. mucosa and N. sicca. Using opa-specific oligonucleotides as probes in chromosomal blots, the genomes of the commensal Neisseria species show a totally reduced repertoire of cross-hybridizing loci compared to the complex opa gene family of N. gonorrhoeae. DNA sequence analysis of one opa-related gene derived from N. flava and N. sicca, respectively, revealed a large degree of homology with previously described gonococcal and meningococcal genes, e.g., a typical repetitive sequence in the leader peptide and the distribution of the hypervariable and conserved regions. This observation, together with the finding, that the gene is constitutively transcribed, leads to the assumption that some of the commensal Neisseria species may have the potential for the expression of a protein harboring similar functions as the Opa proteins in pathogenic Neisseriae.
Autoantibodies to desmoplakin I and II in patients with erythema multiforme.
Erythema multiforme (EM) represents a syndrome of chronic recurrent inflammatory skin disease. Depending on the severity and extent of skin and mucosal involvement, it is defined either as EM minor or EM major. In this study we demonstrate the presence of autoantibodies (aAbs) against desmoplakin I and II, two major proteins of the desmosomal plaque, in six of six patients with the severe variant of EM, EM major. Light microscopic studies of lesional skin and mucous membranes localized in vivo bound immunoglobulin G (IgG) in a dotted desmosomal pattern along the cytoplasmic membranes of keratinocytes. By immunoelectronmicroscopy, in vivo bound IgG was confined to the desmosomal plaques. These findings were confirmed by indirect immunolocalization studies that demonstrated the presence of IgG aAbs in the serum of patients during active disease. These aAbs did not only bind to desmosomal plaques of epithelial cells where they colocalized with defined murine monoclonal antibodies directed against desmoplakin I and II, but also labeled the intercalated discs of myocardial cells. Biochemical characterization of circulating IgG aAbs revealed desmoplakin I and II as actual target autoantigens. By passive transfer of serum into newborn mice, in vivo binding of serum aAbs to keratinocytes was shown. The findings presented in this study imply a humoral immune response in certain patients with EM major and indicate a potential pathogenetic role of aAbs against desmoplakin I and II in this disease.
Epiluminescence microscopy. A useful tool for the diagnosis of pigmented skin lesions for formally trained dermatologists.
BACKGROUND AND DESIGN: Epiluminescence microscopy (ELM) is a noninvasive technique that, by employing the optical phenomenon of oil immersion, makes subsurface structures of the skin accessible for in vivo examination and thus provides additional criteria for the clinical diagnosis of pigmented skin lesions. At present, almost all studies about the value and clinical importance of ELM are based on data derived from ELM experts (ie, dermatologists specifically trained in this technique). In the present study, we attempt to determine whether the clinical diagnosis of pigmented skin lesions is significantly improved using ELM and whether ELM-trained individuals and dermatologists not trained in this technique profit equally from this technique. Randomly selected histologically proven pigmented skin lesion specimens, photographed with (ELM) and without oil immersion (surface microscopy) were presented by slide projection to six ELM experts and 13 ELM nonexperts (ie, dermatologists not formally trained in ELM) for diagnosis. To evaluate the diagnostic performance of ELM experts and nonexperts with and without the oil immersion technique (ie, ELM vs surface microscopy), the following parameters were obtained: intraobserver and interobserver agreement by kappa statistics and sensitivity and specificity of diagnostic performance. RESULTS: Our results show that by using the ELM technique the ELM experts reach a substantially better intraobserver agreement than nonexperts (median kappa, 0.56 vs 0.36). The interobserver agreement was markedly increased in the ELM experts group (average gain, 7%) but decreased in the ELM nonexperts group (average loss, 6%). The sensitivity of diagnosis was significantly increased in the ELM experts group (average gain, 10%), but decreased in the nonexperts group (average loss, 10%). Finally, the specificity of diagnosis was excellent in the ELM experts group, both with and without oil immersion (0.91) and was somewhat improved by ELM in the nonexperts group (0.77 vs 0.85). CONCLUSIONS: We conclude that the ELM technique increases sensitivity in formally trained dermatologists, but may decrease the diagnostic ability in dermatologists not formally trained in the ELM technique. Consequently, formal broad-based training in ELM should be offered to the dermatologic community.
Microdialysis in cutaneous pharmacology: kinetic analysis of transdermally delivered nicotine.
Direct measurements of cutaneous drug levels and kinetics have long been hampered by lack of appropriate methods. Recently, studies have indicated that microdialysis, a method of continuous in vivo sampling of extracellular fluid, may also be performed in human skin. The present study was designed to evaluate this technique for kinetic analyses of cutaneous drug levels. Using a transdermal nicotine delivery system with 35 mg of nicotine as a model, nicotine levels were determined in the dialysate of human skin by means of high performance liquid chromatography. In vitro studies demonstrated that nicotine levels in the dialysate strictly correlated with nicotine concentrations in the dialyzed medium. In nine healthy male volunteers receiving nicotine by transdermal delivery, nicotine was detectable within 90-180 min, and peak levels of approximately 1000 ng/ml were detected within 240-360 min of patch application. Correlation analyses of the individual data from our subjects revealed that nicotine kinetics were independent of skin barrier function, as assessed by transepidermal water loss, but indicated that the detectable maximum nicotine levels may depend on the location of the probe. In summary, the present study demonstrates that microdialysis may be a novel, powerful tool to study cutaneous pharmacology in vivo.
Generalized herpes simplex infection complicating bullous pemphigoid.
Explore the source record for details and available documents.
Varicose vein stripping--a prospective study of the thrombotic risk and the diagnostic significance of preoperative color coded duplex sonography.
Insufficiency of epifascial veins promotes venous ulceration and increases thromboembolic risk in general surgery patients. Epifascial varicose vein stripping is therefore considered the most effective prophylactic procedure. Thromboembolic risk of patients undergoing this surgical procedure has not yet been prospectively evaluated but appears to be lower than in general surgery patients. The gold standard of preoperative assessment of varicose surgery patients is ascending pressure phlebography, but this technique is invasive, time consuming and costly. We prospectively investigated 100 consecutive varicose vein surgery patients for postoperative thrombosis. Ascending pressure phlebography (APP) and colour coded duplex sonography (CCDS) were performed before and 10 to 21 days after the stripping operation in 100 and 70 patients, respectively. APP revealed no postoperative deep vein thrombosis in all 100 limbs investigated (0 percent; 95 percent confidence interval: 0 to 2.95). With regard to epifascial vein reflux there was good agreement between APP and CCDS (quadratic weighted kappa: 0.76). In 67 out of 73 superficial veins investigated excellent agreement of diagnostic accuracy was found for both diagnostic procedures (91.78 percent; 95 percent confidence interval: 82.96 to 96.92). We conclude that thrombotic risk of varicose vein surgery is low in properly selected patients. CCDS provides a high degree of accuracy in diagnosis of reflux and regular vein morphology and should therefore replace APP; however, APP does remain essential in the preoperative workup of atypical anatomical variants.
[Endoparasite infection in stray and abandoned dogs in southern Switzerland].
At their entry into the animal domicile, "La Stampa", in Lugano (canton Tessin), 217 stray dogs and 154 unwanted dogs were examined for infections with intestinal parasites, filariae, Babesia and Leishmania. The following techniques were used for detection of intestinal parasites: combined sedimentation-flotation, MIFC technique and scotch tape adherence test. Prevalences of helminth egg excretion in stray dogs and in unwanted dogs, respectively, were as follows: 34% and 22% for Trichuris, 17% and 14% for Toxocara, 3% and 5% for hookworms, 4% and 0% for taeniids. Dipylidium, Toxascaris and Capillaria were diagnosed sporadically. Samples positive for taeniids were further tested for the presence of Echinococcus coproantigens in a sandwich ELISA: one of 9 dogs was strongly positive. This dog was euthanized for security reasons and upon dissection, 11 Taenia hydatigena and more than 10,000 gravid Echinococcus granulosus worms were found. Microfilariae were detected in the blood of 3 stray dogs and one unwanted dog by the Difil-test. In all 4 cases the infective species was Dirofilaria immitis as confirmed by morphology, acid phosphatase activity analysis of microfilariae and by detection of specific antigens in blood plasma by ELISA. Specific antibodies against antigen of Leishmania infantum could not be detected in any of these dogs by ELISA. However, 3 stray dogs had specific antibodies against antigen of Babesia canis as demonstrated by IFAT.
Plasma methadone monitoring with methadone maintenance treatment.
Explore the source record for details and available documents.
Effects of isradipine on endothelin-induced constriction of myometrial arteries in normotensive pregnant women.
The results of our previous studies suggested that endothelin-1 (ET-1) might be contributory to the impaired uteroplacental blood flow seen in preeclampsia. The aim of this study was to investigate the in vitro influence of isradipine on ET-1-induced contraction of myometrial resistance arteries from pregnant women, as these vessels are partly responsible for the regulation of uteroplacental blood flow in preeclampsia. Small myometrial arteries were dissected from myometrium obtained from 20 normotensive term pregnant women undergoing elective cesarean section and mounted in a tissue chamber. Tension was recorded isometrically. When ET-1 (10(-8) mol/L)-contracted vessels were exposed to increasing concentrations (10(-6), 10(-5), and 10(-4) mol/L) of isradipine, the myometrial arteries demonstrated essentially no relaxation. A significant mean relaxation of 31% was seen only with the highest isradipine concentration of 10(-3) mol/L. Pretreatment with isradipine attenuated ET-1-induced contraction by 26% at 3 x 10(-4) mol/L and by up to 80% at 10(-3) mol/L. Preincubation with lower concentrations of isradipine did not significantly reduce subsequent ET-1 contraction. The present study has thus shown that isradipine at high concentrations counteracts ET-1-induced constriction of myometrial arteries in term pregnant women. Pretreatment with isradipine at high concentrations attenuates the ET-1 contraction.
Application of an artificial neural network in epiluminescence microscopy pattern analysis of pigmented skin lesions: a pilot study.
In vivo epiluminescence microscopy (ELM) is a non-invasive technique which improves the clinical diagnosis of naevi and malignant melanoma by providing diagnostic criteria that cannot be appreciated by the naked eye. The present study investigated whether ELM criteria pattern analysis can be employed in an objective, observer-trained, computer-aided diagnostic system, and whether artificial neural networks (ANN) can be applied to the diagnosis of pigmented skin lesions (PSL). The ELM criteria patterns of 200 PSL oil immersion images (60 common naevi, 60 dysplastic naevi, and 80 malignant melanomas) were analysed using a standardized questionnaire. One hundred randomly assigned PSL were used as a training set for an ANN, the remaining 100 PSL serving as the test set. The ANN was trained by backward propagation according to the histological diagnosis, and its performance was compared with that of human investigators. Out of the test set the human investigators correctly diagnosed 88% of PSL and the ANN 86%. In a dichotomized model comparing common, compound, and dysplastic naevi vs. malignant melanoma, i.e. benign vs. malignant PSL, the sensitivity and specificity of human diagnosis was 95 and 90%, respectively, whereas the sensitivity and specificity of the ANN diagnosis was 95 and 88%. Our data indicate that artificial neural networks can be trained to diagnose PSL at a human expert level, based on patterns provided by ELM criteria. We suggest that this technique offers a new approach to the diagnosis of PSL.
[Therapy of cutaneous T-cell lymphomas].
Cutaneous T-cell lymphomas (CTCL) show a wide clinical spectrum of cutaneous diseases caused by a clonal proliferation of malignant T-helper cells. In the early stages of CTCL diagnosis is challenging and may require a combination of clinical, pathological, immunomorphologic and molecular findings. The identification of early disease is crucial for the rapid implementation of adequate treatment, which may even be curative as has been reported with psoralen photochemotherapy (PUVA), total skin electron beam (TSEB) irradiation and topical chemotherapy. The combination of these treatment modalities with each other and, in addition, with management by synthetic retinoids and interferons has increased the therapeutic potential. Systemic (poly)-chemotherapy has been used so far exclusively for advanced stages of CTCL and may result in partial remission. Extracorporeal photochemotherapy (photopheresis) has been shown to be the most efficient mode of treatment for the Sézary syndrome.
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)
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.
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.
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.
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.
Immediate effects of a public education campaign on prognostic features of melanoma.
Explore the source record for details and available documents.