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Biomedical subjects

K Wolff

Publications and source records attributed to K Wolff.

At least 109 records · Page 6Linked to original sources
PubMed1997

Quantification of vascularity in nodular melanoma and Spitz's nevus.

Spitz's nevi are acquired benign melanocytic skin tumors. Usually they are differentiated from nodular melanoma by clinical and histopathological criteria. Since Spitz's nevi are one of the most common simulators of nodular melanomas their bizarre histopathology may cause diagnostic confusion and make it difficult to differentiate these two melanocytic tumors. One of the histologic features shared by Spitz's nevus and nodular melanoma is prominent vascularity. The ability of malignant melanoma to induce angiogenesis is well established whereas benign melanocytic tumors do not have a prominent overall vascularity. The purpose of this study was to find out whether the degree of vascularity of nodular melanomas differs significantly from that of benign Spitz's nevi. In this study the number of microvessels and the vessel area were determined in 23 Spitz's nevi and 16 nodular melanomas. The number of microvessels and the vessel area were determined on Ulex Europaeus agglutinin I-stained sections by computer-assisted image analysis. Two methods of measurement were used, namely systematic and selective sampling. Measurement of the whole tumor specimen (systematic sampling) revealed a vessel count of 10.83/field (SD +/-5.97) for Spitz's nevi whereas nodular melanomas exhibited a significantly lower (p=0.04) vessel count of 6.44/field (SD +/-3.85). This difference was even more pronounced when the vessel area (Spitz's nevi: 17.85x10-4mm2, SD +/-10.32; nodular melanomas: 7.88x10-4mm2, SD +/-5.23) was investigated (p < 0.001). The difference in vessel area and vessel count was insignificant for areas exhibiting the greatest vascularity (selective sampling). Measurement of vessel count and vessel area lead us to conclude that Spitz's nevi have a significantly higher vascularity than do nodular melanomas. Our results thus indicate that angiogenesis in these pigmented lesions is not correlated with malignancy.

Humans↗
PubMed1997

Juvenile hyaline fibromatosis: impaired collagen metabolism in human skin fibroblasts.

Juvenile hyaline fibromatosis (JHF) is inherited as a fatal autosomal recessive disorder characterised by multiple tumorous mucocutaneous proliferations. In this paper a 14 month old girl with JHF is described. For this condition, a malfunction of collagen synthesis is considered as the pathogenetic cause. Recently published data have revealed an absent band for type III collagen (TIIIC) chain in western blot studies of clinically unaffected JHF skin. Therefore supernatants of skin fibroblast cell cultures, obtained from normal human skin, were analysed for type 1 collagen (TIC) and TIIIC metabolites by radioimmunoassays. Besides the typical morphological connective tissue changes in the skin lesions, TIC synthesis and degradation were found increased in JHF fibroblasts compared with control fibroblasts. In contrast, TIIIC overall metabolism was significantly reduced by 36% compared with controls.

Cell Culture Techniques↗
PubMed1997

Micro-extraction of commonly abused benzodiazepines for urinary screening by liquid chromatography.

We have developed a micro-extraction procedure for the analysis of seven commonly prescribed benzodiazepines (chlordiazepoxide, diazepam, lorazepam, nitrazepam, nordiazepam, oxazepam, and temazepam) in urine using liquid chromatography. The method is reliable and sensitive, uses small volumes (100 microL) of urine and is suitable for the detection and quantification of low concentrations of benzodiazepines. The micro-extraction procedure allowed rapid sample processing, which is important for routine sample handling. The limit of detection for the seven benzodiazepines ranged from 0.10-0.71 mg/L and recovery of the different benzodiazepines was good, ranging from 70-105%. Between- and within-assay coefficients of variation ranged from 6.3% to 13.8%, and 2% to 3.5%, respectively. Chlordiazepoxide chromatographed poorly (between assay coefficient of variation 35.4%, within-assay 7%), and we set the cut-off value for this compound at 5.0 mg/L.

Benzodiazepines↗
PubMed1997

Benzodiazepine misuse by drug addicts.

Using a high-performance liquid chromatography method, we measured seven commonly prescribed benzodiazepines (chlordiazepoxide, nitrazepam, nordiazepam, oxazepam, lorazepam, temazepam and diazepam) in 100 urine samples obtained from patients attending the Leeds Addiction Unit. All of the urines selected for investigation were positive for benzodiazepines using an EMIT (Enzyme Immunoassay) screen. Forty-four of the urines contained a range of benzodiazepines, none of which had been prescribed. Nitrazepam was detected most frequently (61 urine samples), but had not been prescribed to any of the patients in this study. Chlordiazepoxide was detected in 49 urine samples, although it had been prescribed to only five patients. Temazepam was detected in 28 urine samples. Fourteen patients providing 21 urine samples had been prescribed temazepam for treatment. However, temazepam was detected in only 14 of these samples. Multiple benzodiazepine abuse was evident from the high rate of detection of unrelated benzodiazepines.

Alcoholism↗
PubMed1997

Plasma endothelin in normal and diabetic pregnancy.

OBJECTIVE: To examine endothelin-1 (ET-1) concentrations longitudinally throughout pregnancy in healthy and insulin-dependent diabetic women and to evaluate the relationship between ET-1 and big ET-1 in normal pregnancy. RESEARCH DESIGN AND METHODS: Venous blood samples were obtained consecutively in gestational weeks 18, 28, and 38 from 40 healthy women with uneventful pregnancies and 24 pregnant women with IDDM. By radioimmunoassay, plasma ET-1 and big ET-1 were analyzed in the healthy women and plasma ET-1 in the diabetic women. RESULTS: In the diabetic pregnant women, plasma ET-1 levels were significantly higher than in healthy pregnant women during the entire observation period (P < 0.001), but did not change with advancing gestational age. Five of the diabetic, but none of the healthy pregnant women, developed preeclampsia. ET-1 levels did not differ between the diabetic women who developed preeclampsia and those who did not. Plasma ET-1 levels in healthy pregnant women were within the range of those in healthy nonpregnant women and did not change during pregnancy. The big ET-1 levels increased and the ET-1/big ET-1 ratio decreased significantly during the observation period. CONCLUSIONS: Plasma ET-1 levels do not change with advancing gestational length. During normal pregnancy, the ET-1/big ET-1 ratio decrease, indicating a suppressed converting enzyme activity or altered clearance of ET-1. Pregnant women with IDDM have markedly elevated ET-1 levels. Although diabetic women with and without preeclampsia did not differ with respect to endothelial dysfunction, as reflected by elevated ET-1 concentration, we cannot exclude that altered endothelial function may be of importance for the increased frequency of preeclampsia in pregnant IDDM patients.

Adult↗
PubMed1997

Intestinal helminths and their influence on the indicators of iron status in the elderly.

The intestinal helminthiasis and hematological status was assessed in 100 elderly residents of two low-land communities, one at sea-level and the other at 61; m, equally representative of men and women. These are beth low-income communities. The population showed a 48% helminth infection rate which consisted of hookworm, Trichuris, and Ascaris infection. The prevalence of each of the individual parasites was considered light to moderate and the intensity of infection was generally low in this population. A strong inverse association between intensity of hookworm infection and hemoglobin levels was observed but only at intensities greater than 2,000 eggs/gram feces. Lower intensities of infection had no apparent influence on hematological status. The evaluation of hematological status using hematocrit and hemoglobin showed different prevalences of risk of anemia of 14.1% and 43.8%, respectively. These differences may reflect the chosen cut-off values. Iron deficiency does not appear to be a major problem in this population with only 5% or 11% having absent stores using the low and high cut-off values of circulating serum ferritin, respectively.

Aged↗
PubMed1997

Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis of the palms.

We performed a randomized double-blind study within-group comparison in 11 patients to study the effect of subcutaneous injections of botulinum A toxin in focal hyperhidrosis of the palms. A total dose of 120 mU (mouse units) of botulinum A toxin (Dysport) was injected into six different sites on one palm, whereas the other was injected with sterile saline. Objective quantification of sweat production was performed using digitized ninhydrin-stained sheets. Three weeks after treatment, the mean reduction of sweat production in the botulinum A toxin-treated palms was 26% (P < 0.001), after 8 weeks 26% (P = 0.002) and after 13 weeks 31% (P < 0.001). Subjective assessment of sweat production by the patients using a visual analogue scale showed a 38% improvement in the botulinum A toxin-treated palms at 3 weeks (P = 0.002), 40% at 8 weeks (P = 0.002) and 38% at 13 weeks (P = 0.002). Neither the objective measurement nor the subjective rating showed a statistically significant reduction of sweating in the placebo-treated palms. Three patients reported reversible minor weakness of powerful handgrip after injection at the toxin-treated site, lasting between 2 and 5 weeks.

Adult↗
PubMed1996

Endothelin-1 and big endothelin-1 levels in normal term pregnancy and in preeclampsia.

To study the concentrations of endothelin-1 (ET-1) and its precursor, big ET-1, in samples of amniotic fluid, fetal urine, umbilical arterial and venous blood, retroplacental blood and maternal uterine and brachial venous blood obtained from normal and preeclamptic women. Samples were collected from 31 healthy pregnant women (16 in labor and 15 undergoing elective cesarean section) and 35 preeclamptic women (9 in labor and 26 undergoing cesarean section). Big ET-1 and ET-1 were measured by radioimmunoassay and the ET-1 to big ET-1 ratios were calculated. In preeclamptic women there was a significant elevation of ET-1 in the maternal brachial and uterine veins and of big-ET-1 in the brachial vein. The ET-1 concentrations and the ET-1/big ET ratios were significantly higher on the fetal side (i.e., in the umbilical vein and amniotic fluid) than in maternal blood, but in these sampling locations there was no difference between the normal pregnancy and preeclampsia group. A significant negative correlation (r = -0.67, P < 0.01) was found between plasma ET-1 in the umbilical vein and birth weight in the preeclamptic group. ET-1 was significantly higher in amniotic fluid than in the first neonatal urine of corresponding pregnancies (15.0 +/- 2.0 vs. 3.0 +/- 2.9 pmol/l, P < 0.05). The ET-1 and big ET-1 concentrations are significantly higher in fetal plasma and amniotic fluid than in maternal plasma, indicating increased endothelin converting enzyme activity and increased ET-1 production in utero. The elevated ET-1 concentration in maternal blood in preeclamptic compared with normal pregnant women and the negative correlation between ET-1 in the umbilical vein and birth weight suggest that ET-1 plays a pathophysiological role in preeclampsia and other conditions with intrauterine growth restriction.

Adult↗
PubMed1996

N-ras oncogene expression changes the growth characteristics of human melanoma in two independent SCID-hu mouse models.

Fifteen percent of all human melanomas carry mutations in ras genes, the majority of which are located in codon 61 of the N-ras gene. However, the biological significance of these mutations is as yet unknown. In this study, we investigated the influence of N-ras oncogene products mutated in codon 61 on the growth characteristics of human melanoma in vivo by establishing 2 SCID-hu mouse xenotransplantation models. Tumors grown in SCID mice injected with human melanoma carrying activated N-ras genes were significantly larger (p < 0.004) than tumors grown in animals injected with the appropriate control transfectants. Additionally, tumors with N-ras point mutations clearly showed a more pleomorphic phenotype than the control groups. Our results, obtained in 2 independent SCID-hu xenotransplantation models, suggest that mutated N-ras oncogene expression may be an important factor influencing growth characteristics of human melanoma without altering metastatic potential. These novel in vivo model systems provide a tool for further study of the biology of mutated ras in melanoma and should also prove useful for testing new and improved treatment strategies for human melanoma carrying mutated ras genes.

Animals↗
PubMed1996

Dermal microvascular endothelial cells express CD32 receptors in vivo and in vitro.

Immune complexes are thought to be the major cause of cutaneous necrotizing vasculitis, but the mechanism of immune complex targeting to specific vessels is largely unknown. In myelomonocytic cells, immune complex binding and receptor-mediated endocytosis are mediated by Fc gamma R. We asked whether dermal microvascular endothelial cells (DMEC) express Fc gamma Rs. In cryostat sections of normal human skin, mAb IV.3 or AT10, both recognizing CD32 (Fc gamma RII), localizes to the luminal surface of DMEC of the superficial but not of the deep vascular plexus. All DMEC do not express CD16 (Fc gamma RIII) or CD64 (Fc gamma RI) molecules. Adult skin-derived DMEC in culture express CD32 (Fc gamma RII) molecules, as measured by FACS, but are negative for CD16 or CD64. HUVEC, tested for comparison, do not express CD16, 32, or 64 proteins. By reverse-transcriptase PCR and subsequent Southern blot analysis, the isoform of the CD32 molecule expressed on DMEC is determined as Fc gamma RIIa. HUVEC do not contain Fc gamma RIIa or Fc gamma RIIb mRNA. In DMEC, Fc gamma RIIa cross-linking results in immediate intracellular free Ca2+ ([Ca2+]i) concentration fluxes and in rapid internalization of the occupied receptors. We conclude that DMEC are equipped with fully functional Fc gamma RIIa molecules.

Adult↗
PubMed1996

Endothelin receptor type A and B gene expression in human nonpregnant, term pregnant, and preeclamptic uterus.

OBJECTIVE: The aim of this study was to quantify the gene expression of ETA and ETB receptors within the different uterine segments of nonpregnant, normal pregnant, and preeclamptic women. STUDY DESIGN: Biopsy samples from the cervix, isthmus, and corpus uteri were obtained from eight nonpregnant, nine term pregnant, and seven preeclamptic women. The concentration of ETA and ETB receptor messenger ribonucleic acid were determined by a solution hybridization technique with complementary ribonucleic acid probes. Results are presented in counts per minute per microgram of total nucleic acid as mean +/- SEM. RESULTS: The expression of messenger ribonucleic acid encoding the ETA receptor was generally higher in the upper than in the lower uterine segment in nonpregnant, normal pregnant, and preeclamptic myometrium, whereas the opposite pattern was seen with regard to ETB. During normal pregnancy the concentrations of ETA receptor messenger ribonucleic acid in the corpus and ETB receptor messenger ribonucleic acid in the isthmus were significantly elevated compared with those in nonpregnant women. This enhanced gene expression was, however, not observed in the preeclamptic group. CONCLUSION: Our finding of segmentally differentiated endothelin receptor gene expression is compatible with a role for endothelin-1 in stimulating uterine contractions through ETA receptors during spontaneous labor and suggests a relaxing effect of the ETB receptor on the myometrium.

Adult↗
PubMed1996

Accuracy of contrast-enhanced magnetic resonance angiography in chronic thromboembolic disease.

RATIONALE AND OBJECTIVES: We evaluated the accuracy of contrast-enhanced magnetic resonance (MR) angiography in demonstrating the findings of chronic pulmonary thromboembolism (CPTE) compared with conventional pulmonary angiography. METHODS: We examined 18 patients with CPTE proved by conventional pulmonary angiography and 16 healthy control patients. T1-weighted and single-breathhold, two-dimensional multiplanar spoiled gradient-recalled pulmonary images were obtained after injection of gadopentetate dimeglumine. Images were interpreted independently by two radiologists. RESULTS: All patients with CPTE were identified on MR angiography images by both readers. Sensitivity and specificity for MR angiography in diagnosing abnormal segments were 76% and 95% for reader 1 and 68% and 93% for reader 2, respectively. Sensitivity and specificity for MR angiography in depicting abnormal lobes were 83% and 96% for reader 1 and 82% and 93% for reader 2, respectively. Interobserver agreement was high; kappas for abnormal segments and abnormal lobes were .72 and .84, respectively. The T1-weighted spin-echo images demonstrated a mosaic signal intensity pattern in all patients with CPTE. CONCLUSION: Contrast-enhanced MR angiography accurately depicts abnormal segments and lobes in occlusive vascular disease and clearly distinguishes between patients with CPTE and those with healthy lungs.

Chronic Disease↗
PubMed1996

Limitations of high frequency ultrasound in determining the invasiveness of cutaneous malignant melanoma.

Preoperative assessment of melanoma invasion by sonometry has been reported to exhibit a high correlation with postoperative histometry based on the determination of a regression coefficient. We believe that this approach is not adequate and that it can be misleading. We therefore applied an appropriate statistical approach to our data to re-examine this issue. Preoperative measurements by sonometry were compared with postoperative histometry in 71 consecutive patients with the clinical diagnosis of malignant melanoma. Patients with the histological diagnosis of melanoma in situ (n = 13) were excluded from this comparison, as sonometry cannot distinguish structures restricted to the epidermis and Breslow thickness is not routinely determined in Clark level I melanomas. The agreement between sonometry and histometry was analysed by plotting the mean of the two methods against their difference. By linear regression analysis the correlation coefficient (r) in the invasive melanomas (n = 58) was found to be 0.92. The median thickness of the invasive tumours by sonometry was 1.36 mm, and by histometry 0.89 mm. In 95% of the cases sonometry differed by 37% above to 48% below the values obtained by histometry. Thus, we conclude that the accuracy of sonometry in predicting preoperative tumour thickness- and tumour invasiveness-is far lower than previously reported.

Adult↗
PubMed1996

Autoantibodies against desmoplakin I and II define a subset of patients with erythema multiforme major.

In a previous report, we described autoantibodies against the desmosomal plaque proteins desmoplakin I and II (dp I and II) in patients with erythema multiforme (EM) major. In the present study we investigated ten EM major and eight EM minor patients for circulating autoantibodies and performed clinical and immunomorphological evaluations. Seven out of ten EM major patients revealed anti-dp I and II autoantibodies. Antigens were biochemically characterized by Western blotting and immunoprecipitation of epithelial-cell-derived protein extracts. These autoantibodies bind in vivo to lesional skin/mucosa in a pemphigus-type dotted pattern along the cytoplasmic membranes of keratinocytes. Ultrastructural immunolocalization studies confine in vivo bound autoantibodies to the cytoplasmic desmosomal plaque. Autoantibody binding studies with the sera of such patients demonstrate that the target antigens are not restricted to squamous epithelia but are also expressed in simple and transitional epithelia, on hepatocytes, and on cells of mesenchymal origin, e.g., myocardial cells. Comparing the clinicopathological features of ten patients with EM major, we could not define any discriminating clinical symptoms among patients with or without autoantibodies. Histopathological examination, however, revealed that only patients with EM major and autoantibodies against dp I and II show suprabasal acantholysis in lesional skin and mucous membranes, suggesting a potential role of the humoral immune response in the pathogenesis of this disease. These findings suggest that these autoantibodies define a subset of patients within the clinical spectrum of EM.

Adult↗
PubMed1996

Increased nuclear volume in metastasizing "thick" melanomas.

Tumor invasion is the most reliable prognostic factor for primary stage I melanoma. "Thick" melanomas, with a Breslow thickness of more than 4 mm, tend to have a poor prognosis. Exceptions occur: some patients have no further recurrence of tumor. In an attempt to determine prognostic markers for "thick" clinical stage I melanomas, we investigated the volume-weighted mean nuclear volume of primary melanomas with tumor invasions > or = 4.0 mm in 32 patients. Seventeen of these patients developed melanoma metastases within a follow-up period of 60 mo; 15 patients who did not developed metastases and were comparable with regard to clinical and histological criteria were selected as a comparison group. Volume-weighted mean nuclear volume (Vv) is determined by a technique that permits an unbiased, efficient, shape- and orientation-independent, 3-dimensional estimation of nuclear size in tissues. This technique has been employed successfully in the prognostic assessment of stage I and II melanomas and was recently proven to be a sensitive marker for thin, high-risk melanomas. In our patients, Vv was determined by computer-assisted image analysis on Feulgen-stained sections by stereologic estimation of the Vv. The mean Vv (+/-SD) of primary melanomas with subsequent metastatic course was 794.99 +/- 209.18 micron3 (range: 409.48-1161.9 micron3), whereas primary melanoma lesions without subsequent metastases exhibited a mean Vv 640.54 +/- 205.07 micron3 (range: 206.7-927.48 micron3). This difference was found to be statistically significant (p = 0.0439). "Thick" melanomas with subsequent metastases thus exhibited a significantly higher Vv than did melanomas that did not metastasize.

Adult↗