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Biomedical subjects

K Wolff

Publications and source records attributed to K Wolff.

At least 91 records · Page 5Linked to original sources

Route of drug use and its implications for drug effect, risk of dependence and health consequences.

Route of administration has a profound, but often overlooked, influence on the actual experience of the drug use itself, on the risk of resulting development of dependence, and on the nature of the harms to which drug users are exposing themselves. These three areas are reviewed. The influence of route of administration on drug effect is considered first with regard to overall effectiveness of absorption, and also with regard to speed of onset of effect. The implications for risk of dependence cover animal and human laboratory studies of reinforcement schedules, epidemiological studies, the attitudes of drug users themselves to the different routes of possible drug use and associated dependence risk and the postulated influences on progression to dependence. Finally, the relationship between route of drug use and health sequelae is explored for the three most widely used routes of administration of illicit drugs-snorting, smoking and injecting.

Journal Article↗

Estimation of the volume-weighted mean nuclear volume discriminates keratoacanthoma from squamous cell carcinoma.

Keratoacanthoma (KA) is a fairly common neoplasm that in the past has been considered by many to be benign. Keratoacanthoma is usually differentiated from squamous cell carcinoma (SCC) by histopathologic criteria. However, the cytologic features of KA and SCC are often similar. Hence, KA may be confused with SCC at the histopathologic level. Volume-weighted mean nuclear volume (Vv) is determined by a technique that permits an unbiased and efficient estimation of nuclear volumes in tissues without any assumptions regarding nuclear shape. In this study, the volume-weighted mean nuclear volume was determined in 18 KAs and 19 SCCs 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 employing stereologic estimation of the volume-weighted mean nuclear volume. The mean Vv of KA was 704.5 microm3 (SD +/-170.5), whereas SCC exhibited a significantly lower Vv of 533.9 microm3 (SD+/-164.9) (p = 0.006). The sensitivity and specificity of Vv for the discrimination between KA and SCC was 0.80 and 0.78, respectively. We found that KAs show a significantly larger Vv than SCCs and thus, the estimation of the volume-weighted mean nuclear volume may be regarded as a helpful tool for the differential diagnosis of KA and SCC.

Aged↗

Diagnostic informativeness of compressed digital epiluminescence microscopy images of pigmented skin lesions compared with photographs.

Epiluminescence microscopy (ELM) is a useful method for improved diagnostic accuracy in early cutaneous melanoma. Conventional photographs of ELM images are commonly used for clinical research and documentation. Electronic images have advantages compared with photographs and are essential for medical informatics, computerized learning and telemedicine. Compression of electronic images allows a reduction in volume of data, but significant image deterioration may occur at high compression rates. We sought to study the diagnostic informativeness of compressed digital ELM images compared with conventional photographs. Fifty photographs of pigmented skin lesions, including 23 melanomas, were presented to eight dermatologists as photographic slides and as digital images with 30:1 Joint Photographic Experts Group (JPEG) compression. The diagnostic performance of the media and the readers was described in terms of sensitivity, specificity and areas under receiver operating characteristic curves (AUC). Agreement between the readings of the two types of media regarding the presence or absence of ELM criteria was assessed using kappa (kappa) statistics. The mean AUC was 0.81 (95% confidence interval [CI] = 0.73-0.90) for slides and 0.81 (95% CI = 0.72-0.90; P = 0.89) for digital images. Agreement between the readings of the two types of media regarding the presence or absence of ELM criteria ranged from kappa = 0.55 (95% CI = 0.22-0.88) for grey-blue area to kappa = 0.89 (95% CI = 0.74-1.00) for radial streaming. In conclusion, digital ELM images with 30:1 JPEG compression appear to be as informative as photographic slides when used to differentiate between melanoma and non-melanoma.

Area Under Curve↗

Epiluminescence microscopy-based classification of pigmented skin lesions using computerized image analysis and an artificial neural network.

Epiluminescence microscopy (ELM) is a non-invasive technique for in vivo examination which can provide additional criteria for the clinical diagnosis of pigmented skin lesions (PSLs). In the present study we attempt to determine whether PSLs can be automatically diagnosed by an integrated computerized system. This system should recognize the PSL, automatically extract features and use these features in training an artificial neural network, which should--if sufficiently trained--be capable of recognizing and classifying a new PSL without human aid. One hundred and twenty images of randomly selected histologically proven PSLs (33 common naevi, 48 dysplastic naevi and 39 malignant melanomas) were used in this study. The images were digitally obtained and the morphological features of the PSLs were extracted electronically without human assistance. The numerical data were then divided into learning and testing cases and linked to an artificial neural network for training and for further classification of lesions that the system had not been trained on. Our results show that the computerized system was able to automatically identify 95% of the PSLs presented. The sensitivity and specificity of the computerized system were 90% and 74% respectively. In contrast, when differentiating between individual types of lesions, the system performed at true positive rates of only 38% for malignant melanoma, 62% for dysplastic naevi and 33% for common naevi. Our data indicate that (1) ELM images of PSLs provide an excellent source for digital image analysis; (2) the vast majority of PSLs can be correctly identified by a relatively simple (and thus not "intelligent") application of digital image analysis; (3) automatic feature extraction based mainly on ABCD rules provides reliable data on the distinction between benign and malignant PSLs; and (4) there is evidence that artificial neural networks can be trained to adequately discriminate between benign and malignant PSLs.

Dysplastic Nevus Syndrome↗

Lactate compared with pH analysis at fetal scalp blood sampling: a prospective randomised study.

OBJECTIVE: Fetal scalp blood sampling is a widely used method for assessing fetal condition in the event of ominous fetal heart rate patterns. The purpose of this randomised trial was to compare the value of fetal scalp blood lactate and pH management in cases of abnormal intrapartum fetal heart rate tracings. METHODS: Of 341 cases of ominous fetal heart rate patterns, 169 were randomly assigned to pH analysis, and 172 to lactate measurements. Lactate was measured using a lactate card requiring 5 microL of blood and yielding the result within 60 seconds. pH analysis was performed with an ABL 510 acid-base analyser requiring 35 microL of blood and yielding the results within 47 seconds. RESULTS: Unsuccessful fetal blood sampling procedures (no result or an unreliable result) occurred significantly more often in the pH subgroup than in the lactate subgroup (OR 16.1 with 95% CI 5.8-44.7). In the pH subgroup the failure rate was inversely related to the degree of cervical dilatation. Compared with the pH subgroup, the lactate subgroup was characterised by fewer fetal scalp incisions per blood sampling attempt (median 1.0 [interquartile range (IQR) 1-1] vs 2.0 [IQR 1-2]), and significantly less time required for the sampling procedure (median 120 s [IQR 90-147] vs 230 s [IQR 180-300]). The groups did not differ in mode of delivery, neonatal outcome and umbilical artery acid-base balance and lactate levels. CONCLUSION: This trial showed the levels of lactate and pH in fetal scalp blood to be comparable in predicting perinatal outcome, but the procedure to measuring lactate was more successful than that for pH. Owing to its simplicity of performance, lactate analysis is an attractive alternative for intrapartum fetal monitoring.

Female↗

Balloon catheter for induction of labor in nulliparous women with prelabor rupture of the membranes at term. A preliminary report.

The balloon catheter method has been described as an effective method for cervical ripening hitherto used exclusively before rupture of the membranes. We found it of interest to perform a pilot study of the balloon catheter method after rupture of the membranes. In 18 nulliparous women, with an unripe cervix (Bishop score < or = 5) 48 h after prelabor rupture of the membranes at term, cervical ripening was performed using a 26-gauge balloon catheter. Seventy six percent of these women delivered vaginally. Clinical and neonatal outcome data did not differ as compared with term pregnant women who entered labor spontaneously or had a ripe cervix (Bishop score >5) and labor induced with oxytocin within 48 h after prelabor rupture of the membranes. Despite visualization of a pool of amniotic fluid in the vagina on speculum examination on admission, there was a high proportion of patients with an intact forebag observed during the birth process. This preliminary report indicates that the balloon catheter method might be a well-tolerated, safe, and effective method for induction of labor after rupture of the membranes at term.

Adult↗

Micro-extraction of chlordiazepoxide and its primary metabolites, desmethylchlordiazepoxide and demoxepam, from plasma and their measurement by liquid chromatography.

We have developed a micro-extraction procedure for the analysis of chlordiazepoxide and its two unique metabolites, demoxepam and desmethylchlordiazepoxide, in plasma, using liquid chromatography. The method is both reliable and sensitive for the quantitation of low plasma concentrations of these three compounds. The extraction procedure allows rapid sample processing, which, together with the small sample volume (100 microL), makes it ideal for routine sample handling. The limit of detection for the three compounds ranged from 0.075 to 0.125 mg/L and recovery of the three different benzodiazepines ranged from 87 to 94%. Within- and between-assay coefficients of variation ranged from 3.1-4.5% and from 4.7 to 7.6%, respectively.

Anti-Anxiety Agents↗

Immunoelectron microscopic characterization of human dermal lymphatic microvascular endothelial cells. Differential expression of CD31, CD34, and type IV collagen with lymphatic endothelial cells vs blood capillary endothelial cells in normal human skin, lymphangioma, and hemangioma in situ.

We performed a comparative investigation of the immunomorphological characteristics of lymphatic and blood microvascular endothelial cells in normal human skin, cutaneous lymphangiomas, and hemangiomas, employing a pre-embedding immunogold electron microscopic technique. We stained for cell membrane proteins that are commonly used for light microscopic characterization of blood endothelial cells. With blood microvascular endothelial cells, we observed uniform labeling of the luminal cell membranes with monoclonal antibodies (MAbs) JC70 (CD31), EN-4 (CD31), BMA120, PAL-E, and QBEND-10 (CD34), and strong staining of the vascular basal lamina for Type IV collagen under normal and pathological conditions. In contrast, lymphatic microvascular endothelial cells in normal human skin and in lymphangiomas displayed, in addition to a luminal labeling, pronounced expression of CD31 and CD34 along the abluminal cell membranes. Moreover, CD31 was preferentially detected within intercellular junctions. The expression of CD34 was mostly confined to abluminal endothelial microprocesses and was upregulated in lymphangiomas and hemangiomas. Type IV collagen partially formed the luminal lining of initial lymphatics and occasionally formed bridges over interendothelial gaps. Our findings suggest a function of transmigration protein CD31 in recruitment of dendritic cells into the lymphatic vasculature. CD34 labeling may indicate early endothelial cell sprouting. The distribution of Type IV collagen also supports its role as a signal for migration and tube formation for lymphatic endothelial cells.

Antigens, CD34↗

Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.

PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS: Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.

Adjuvants, Immunologic↗

Endothelial cell tube formation depends on cadherin 5 and CD31 interactions with filamentous actin.

Capillary tube formation represents a specialized endothelial cell function and is a prerequisite for the establishment of a continuous vessel lumen. Tube formation is thought to depend on cell-cell adhesion molecules, but whereas cadherins, Ig superfamily proteins, and integrins have been considered as potential candidates, the specific proteins subserving this function are unknown. We identified cadherin 5 and CD31 as two molecules critical for endothelial cell tube formation. Using human dermal microvascular endothelial cells or human umbilical vein endothelial cells for an in vitro capillary tube formation assay or, for comparison, an in vivo wound healing model in SCID mice, we show that tube formation in vivo and in vitro were prevented by adhesion-blocking mAbs to both proteins when used in conjunction but not by either mAb alone. In addition, both mAbs but not each individual mAb blocked cytoplasmic filamentous actin (F-actin) reorganization that resulted in cytoplasmic F-actin clumps similar to those induced by cytochalasin D, suggesting that cadherin 5 and CD31 tune tube formation in concert with F-actin. Indeed, cytochalasin D blocked capillary tube formation but colchicine did not, the latter inhibiting microtubule but not F-actin assembly. Using immunoprecipitation methods, we show for the first time that not only cadherin 5 but also a portion of CD31 connects to beta-catenin, which is part of the adherens junction complex known to be linked to F-actin. In conclusion, we provide evidence that cadherin 5, CD31, beta-catenin, and F-actin shape a functional complex that controls endothelial cell tube formation.

Actin Cytoskeleton↗

Activated N-ras contributes to the chemoresistance of human melanoma in severe combined immunodeficiency (SCID) mice by blocking apoptosis.

Activation of the N-ras gene by point mutations occurs in about 15 % of all human melanomas. Using recently established melanoma severe combined immunodeficiency-human mouse xenotransplantation models, here we further investigate the biological significance of these mutations. We demonstrate that activated N-ras significantly contributes to the chemoresistance of human melanoma both in vitro and in vivo by blocking apoptosis. Overexpression of wild-type N-ras had no such effects. With antisense oligonucleotides and farnesyltransferase inhibitors, tools capable of blocking Ras function on the therapeutic horizon, our observation that activated N-ras is not a bystander but a factor worth targeting to improve therapeutic outcome in melanoma gains additional importance.

Animals↗

Epiluminescence microscopy of small pigmented skin lesions: short-term formal training improves the diagnostic performance of dermatologists.

BACKGROUND: Epiluminescence microscopy (ELM) makes subsurface structures of the skin accessible for in vivo examination and provides additional criteria for the clinical diagnosis of pigmented skin lesions (PSLs). We demonstrated that ELM increases diagnostic sensitivity in dermatologists formally trained in the use of this technique but decreases diagnostic ability in dermatologists not formally trained in its application. OBJECTIVE: Our purpose was to determine the effects of short formal ELM training on the diagnostic performance of 11 previously untrained dermatologists. METHODS: One hundred image-pairs of randomly selected histologically proven PSLs, photographed with (ELM) and without oil immersion (surface microscopy), were presented by slide projection to the testees. To evaluate the effects on diagnostic performance before and after short-term training, we used the receiver-operator characteristics technique. RESULTS: Without training the use of ELM did not enhance diagnostic accuracy, but rather decreased it in 8 of 11 testees. In contrast, after 9 hours of formal training in ELM the diagnostic performance of the testees was significantly enhanced with an average gain of 8.4%. CONCLUSION: Our data confirm that formal training is required for the useful application of the ELM technique.

Austria↗

Lymph node sonography versus palpation for detecting recurrent disease in patients with malignant melanoma.

The aim of this study was to examine the efficacy of lymph node palpation versus high resolution lymph node sonography for the detection of lymph node metastases in patients with malignant melanoma. We retrospectively evaluated 2256 pairwise lymph node examinations of the cervical, axillary and inguinal region by palpation and sonography in 264 patients with resected melanomas greater than 0.75 mm of invasion thickness. Lymph node metastases occurred in 50 patients (19%) which were detected in 38 (76%) by both methods in agreement. In 7 cases (14%) palpation failed, in 3 cases (6%) sonography failed and in 2 cases both methods failed to identify metastases. The overall sensitivity of detecting metastatic disease was 82% for palpation and 90% for sonography which was statistically not different. The overall specificity by sonography (99%) was significantly better than for lymph node palpation (88%). Taking into account the results of this analysis, we conclude that patients with a negative result by lymph node palpation do not need further sonography for verification. However, any suspect result by palpation should be additionally evaluated by lymph node sonography in order to rule in or out metastatic disease.

Adolescent↗

The pharmacokinetics of methadone in healthy subjects and opiate users.

AIMS: There is some evidence that monitoring methadone plasma concentration may be of benefit in dosage adjustment during methadone maintenance therapy for heroin (opiate) dependence. However, the kinetics of oral methadone are incompletely characterized. We attempted to describe the latter using a population approach combining intensive 57 h sampling data from healthy subjects with less intensive sparse 24 h data from opiate users. METHODS: Single oral doses of rac-methadone were given to 13 drug-naive healthy subjects (7 men and 6 women) and 17 opiate users beginning methadone maintenance therapy (13 men and 4 women). Plasma methadone concentrations were measured by h.p.l.c. Kinetic analysis was performed using the P-Pharm software. RESULTS: Comparison of kinetic models incorporating mono- or biexponential disposition functions indicated that the latter best represented the data. The improvement was statistically significant for the data from healthy subjects whether the full 57 h or truncated 24 h profiles were used (P<0.031 and P<0.024, respectively), while it was of borderline significance for the more variable data from opiate users (P=0.057) or for pooled (healthy subjects and opiate users) data (P=0.066). The population mean oral clearance of methadone was 6.9+/-1.5 s.d. l h(-1) (5.3+/-1.2 s.d. l h(-1) using 0-24 h data) in the healthy subjects. The results of separate analyses of the data from opiate users and healthy subjects were in contrast with those obtained from pooled data analysis. The former indicated a significantly lower clearance for opiate users (3.2+/-0.3 s.d. l h(-1), P<0.001); 95% CI for the difference = -3 to -6 l h(-1) and no difference in the population mean values of V/F (212+/-27 s.d. l and 239+/-121 s.d. l, P=0.15), while according to the latter analysis addiction was a covariate for V/F but not for oral clearance. A slower absorption of methadone in opiate users was indicated from the analysis of both pooled and separate data. The median elimination half-life of methadone in healthy subjects was 33-46 h depending on the method used to calculate this parameter. CONCLUSIONS: Estimates of the long terminal elimination half-life of methadone (33-46 h in healthy subjects and, possibly, longer in opiate users) indicated that accurate measurement of this parameter requires a duration of sampling longer than that used in this study. Our analysis also suggested that parameters describing plasma concentrations of methadone after a single oral dose in healthy subjects may not be used for predicting and adjusting dosage in opiate users receiving methadone maintenance therapy unless coupled with feedback concentration monitoring techniques (for example Bayesian forecasting).

Adolescent↗

Statistical evaluation of epiluminescence microscopy criteria in the differential diagnosis of malignant melanoma and pigmented basal cell carcinoma.

Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the differential diagnosis of MM. Fifty histologically verified pigmented skin lesions (25 PBCCs and 25 MMs) were investigated using ELM for the presence of ELM criteria; their significance was determined by calculating the odds ratios. We found that individual ELM criteria have different weights of significance in the differential diagnosis of PBCC (leaf-like distribution of diffuse pigmentation, gradual thinning at the periphery and telangiectasia) and MM (pigment network, black and grey pigmentation, radial streaming, pseudopods, brown globules and black dots). Selected patterns of ELM criteria adjusted to the distinct types of pigmented skin lesions are characteristic features for preoperative diagnosis. The prevalence of distinct ELM criteria in PBCC and MM is of critical value in differentiating between the two types of lesions.

Basal Cell Carcinoma↗

HECA-452+ T cells migrate through superficial vascular plexus but not through deep vascular plexus endothelium.

The skin is nourished by two interconnected vascular systems, the superficial vascular plexus coursing just beneath the epidermis and the deep vascular plexus located above the subcutaneous tissue. Skin inflammatory T cells in diseases, such as psoriasis or dermatitis, strikingly aim for the superficial vascular plexus without involving the deep vascular plexus, and the infiltrating T cells bear a distinct phenotype expressing the cutaneous lymphocyte-associated antigen, which is recognized by mAb HECA-452. We wanted to know whether HECA-452+ lymphocytes indeed are able to distinguish between superficial and deep vascular plexus homing sites. Employing the hu-SCID mouse model grafted with human skin and human T cells, as described previously, we developed a new skin-grafting strategy providing superficial and deep vascular plexus skin specimens placed separately onto the same mouse. Fourteen days after allogeneic human T cell grafting, both human skin sites were densely infiltrated by human T cells, but only T cells within the superficial vascular plexus, but not within the deep vascular plexus, expressed the cutaneous lymphocyte-associated antigen. IL-2 and IFN-gamma expression and allogeneic vessel destruction were present within both superficial and deep vascular plexus skin. This model provides direct evidence that expression of a specific homing receptor is indeed able to direct lymphocyte traffic, not only to a distinct organ but also to a distinct vascular bed within one organ.

Animals↗