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Biomedical subjects

Birgit Kahle

Publications and source records attributed to Birgit Kahle.

9 recordsLinked to original sources

Tight junctions and compression therapy in chronic venous insufficiency.

Tight junctions (TJs) provide a barrier function, inhibiting solute and water flow through the paracellular space. There had been no analysis until now as to how tight junction molecules could be involved in the pathology of patients with chronic venous insufficiency. The aim of the study was to analyse the expression pattern of TJ-molecules occludin (OCLN), claudin-1 (CLDN-1), claudin-3 (CLDN-3) and claudin-5 (CLDN-5) on mRNA and protein level in patients with edema, venous leg ulcers and healthy controls. Biopsy specimens were taken in healthy individuals and in patients before, and four weeks after compression therapy. mRNA-expression was determined by using reverse-transcriptase and polymerase chain reaction (RT-PCR) and the protein-expression was determined by Western blotting from tissue specimens. Quantification performed determining the expression for TJ-molecules displayed diminished expression for CLDN-1 (p<0.01) and CLDN-5 (p<0.01) in patients with chronic venous insufficiency in comparison with healthy controls on mRNA as well as protein level. No statistical differences were detected for OCLN and CLDN-3 between the edema group and healthy controls. There was a significantly elevated expression (p<0.01) on mRNA and protein level between the leg ulcer group and healthy controls for OCLN and CLDN-3. Densitometric evaluation revealed a more significantly elevated expression (p<0.01) for CLDN-1 and CLDN-5 on mRNA and protein level after four weeks of compression therapy in comparison with prior to treatment for the edema as well as the leg ulcer group. Compression therapy tightens the paracellular barrier via elevated expression of specific TJs and prevents thereby the progression of chronic venous insufficiency due to inhibited permeability of fluid into the perivascular tissue.

Bandages↗

Efficacy of sclerotherapy in varicose veins-- prospective, blinded, placebo-controlled study.

OBJECTIVE: The objective of this study was to investigate the efficacy of sclerotherapy for varicose veins in a randomized blinded study. METHODS: Twenty-five patients with varicose veins (C(2-4), E(P), A(SP), P(R)) were included. Fourteen subjects received polidocanol (Aethoxysklerol) and 11 patients received normal saline injections. Compression was applied for 1 week. One, 4, and 12 weeks later controls were performed using duplex ultrasonography. The quotient of venous by arterial volume flow was used as quantitative hemodynamic pattern. Patients and the examiner were unaware of which liquid had been injected. RESULTS: In comparison to group 2, 76.8% of the veins treated with polidocanol were completely occluded (p<0.0001). In group 1 the venoarterial flow index decreased from 1.45+/-0.66 to 1.06+/-0.2 (p=0.05). In 11 occluded veins of 14 (group 1), the venoarterial flow index decreased from 1.5+/-0.07 to 0.98+/-0.12 (p<0.05), which is a level found in competent veins. In group 2, the venoarterial flow index remained stable increased. CONCLUSIONS: Injection sclerotherapy using polidocanol (Aethoxysklerol) is efficient to obliterate varicose veins and to improve venous hemodynamics.

Female↗

Somatic mitochondrial mutations in melanoma resection specimens.

As epidemiological data suggest ultraviolet (UV) radiation to be the major environmental factor for the development of melanoma, we screened this malignancy for UV-specific C right curved arrow T and CC right curved arrow TT DNA mutations as described in squamous and basal cell carcinomas of the skin. Mitochondrial (mt) DNA was addressed which is known to be highly more susceptible for mutations than nuclear DNA. In the mt genome we chose part of the non-coding displacement-loop (D-loop) containing two hypermutable (C)n tracts especially prone for C right curved arrow T and CC right curved arrow TT changes. A total of 69 melanoma resection specimens was investigated by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) electrophoresis, followed by DNA cloning and sequencing. We detected alterations of the mt D-loop fragment in 4/34 (12%) melanoma primary tumours and in 7/35 (20%) cutaneous and subcutaneous metastases which was no statistically higher proportion upon Fisher's exact test (p=0.17). Among these 11 positive cases, 9 exhibited alterations in the (C)n microsatellite sequences indicating microsatellite instability (MSI) of mtDNA (C)n tracts. Besides 7 insertions and 2 deletions of nucleotides, 11 mutations occurred including only 4 UV-specific C right curved arrow T mutations in a nodular melanoma of the skin and in two subcutaneous metastases. CC right curved arrow TT mutations were not detected in any tissue sample. As (C)n tract alterations occurred in 2/9 primary melanomas with subsequent metastasis, whereas all 20 non-metastasizing cutaneous melanomas were not affected, these somatic changes may reflect genomic imbalance during tumour progression and may be useful for the assessment of patients' prognosis.

Base Sequence↗

Expression of the heat shock cognate protein HSP73 correlates with tumour thickness of primary melanomas and is enhanced in melanoma metastases.

Seeking to identify melanoma-associated genes by comparing gene expression in uncultured primary melanoma specimens with those in nevi, from which melanomas often are known to arise, we applied subtractive suppression hybridization. Generating a subtracted library of candidate genes up-regulated in primary melanomas, this library contained cDNA fragments of the genes encoding heat shock cognate protein (HSP73) and major histocompatibility complex (HLA-DR) which were overexpressed in further 19 independent melanoma resection specimens on cDNA Southern blots when compared to 19 acquired melanocytic nevi. Upon immunohistochemistry, HSP73 protein expression was detected in the cytoplasm of melanoma cells in primary tumours and metastases. In primary melanomas, the proportion of HSP73 protein expressing cells correlated with tumour thickness according to Breslow which was statistically significant. HSP73 immunostaining was stronger in melanoma metastases when compared with acquired melanocytic nevi which was statistically significant. In addition to melanoma, gastric and uterus cancer tissues exhibited higher HSP73 mRNA expression on a matched tumour/normal cDNA array than their normal counterparts which was statistically significant. Participating in the regulation of folding, assembly and degradation of proteins and protecting cellular proteins from the damage caused by cellular stress like hypoxia or changes in cellular pH, elevated HSP73 expression possibly confers proliferative advantage on melanoma cells.

Gene Expression Regulation, Neoplastic↗

Preoperative ultrasonographic identification of the sentinel lymph node in patients with malignant melanoma.

BACKGROUND: Dissection of the "sentinel lymph node" (SLN) as identified by lymphoscintigraphy is becoming increasingly important in the treatment of patients with malignant melanoma. The purpose of the current study was to determine whether the SLN also could be identified by ultrasound. METHODS: Sixty-seven patients with malignant melanoma (40 females and 27 males, with an average age of 48.8 years) in whom extirpation of the SLN was indicated underwent ultrasonography of the regional lymph nodes prior to preoperative lymphoscintigraphy. The location of the melanoma was the legs in 30 patients, the arms in 14 patients, and the trunk in 23 patients. During regional ultrasonography, the location of the lymph nodes that differed in the cortex/medulla ratio from the surrounding lymph nodes was marked on the skin corresponding to the planes of insonation (M1) when the probe was held vertically to the skin surface. After lymphoscintigraphy using technetium-99m, the position of a gamma probe at which the highest count rate vertical to the skin surface was recorded also was marked (M2). RESULTS: In the inguinal region, the agreement between M1 and M2 was found to be 100% (40 of 40 SLNs) and was 72.5% in the axilla (29 of 40 SLNs). In patients with melanomas located on the leg, the location of M1 and M2 agreed in 97% of cases (36 of 37 lymph nodes in 30 patients); in patients with melanomas located on the arms, the agreement was 76% (13 of 17 lymph nodes in 14 patients) and in patients with melanomas located on the trunk, the agreement was 75% (21 of 28 lymph nodes in 23 patients). The position documented by ultrasound relative to the neighboring structures of the SLN was confirmed intraoperatively in all cases. CONCLUSIONS: The results of the current study indicate that the SLN in patients with melanoma located on the limbs, especially the legs, are characterized by a specific sonomorphologic pattern. Preoperative sonography might constitute an important addition to lymphoscintigraphy in the planning of SLN biopsy.

Female↗

Quantitative venous severity scoring using the venous arterial flow index by duplex sonography.

BACKGROUND: Volume flow, as the product of the mean blood flow velocity by the cross sectional area, means an interesting hemodynamic pattern that can be calculated by duplex. OBJECTIVE: To quantify the severity of venous insufficiency using the correlation between the volume flow in the common femoral vein (VFV) and artery (VFA), called the venous arterial flow index (VAFI). METHODS: A total of 163 consecutive patients were included: 46 patients with postthrombotic syndrome (PTS, group 1), 38 patients with complete varicosity of the greater saphenous vein (group 2), 40 patients with only segmental or truncal varicosity (group 3), and 39 patients with competent veins (group 4). Under standardized conditions, duplex sonography was performed to calculate volume flow in the common femoral vein and artery as a product of mean blood flow velocity (vm) and precise diameter (d = 2pir) of the vessel due to the formula VF = vmxpir2 (L/min). Division of the venous and arterial volume flow data calculated the VAFI. RESULTS: Significant differentiation of VFV (P <.001) and VAFI (P <.0001) between varicose veins and healthy limbs were found. In PTS the mean VFV was 0.50 L/min and the mean VAFI was 1.465. In the complete varicosity group, mean VFV was 0.46 L/min and mean VAFI was 1.48. In group 3, the mean VFV was 0.41 L/min and the mean VAFI was 1.31. In healthy persons, mean VFV was 0.36 L/min and mean VAFI was 0.87. CONCLUSION: The VAFI can be used to quantify the hemodynamic severity in venous insufficiency.

Blood Flow Velocity↗

Lymphangioma circumscriptum of the vulva following surgical and radiological therapy of cervical cancer.

BACKGROUND: Lymphangioma circumscriptum of the vulva rarely develops after postoperative pelvic irradiation. GOAL: The goal was to describe two cases of lymphangioma circumscriptum and their treatment and present a brief review of the literature. STUDY: Two female patients, aged 75 years and 46 years, presented with persistent edema, papules, and vesicles of the labia majora, which had developed 15 and 9 years after hysterectomy, lymph node dissection, and subsequent irradiation of cervical cancer. The external diagnosis was genital warts. RESULTS: In both cases histology revealed lymphangioma circumscriptum of the vulva. Whereas the older woman's condition responded well to laser treatment, keloids developed in the second patient at the site of carbon dioxide laser vaporization. CONCLUSION: CO2 laser treatment recently has been recommended for vulvar lymphangioma circumscriptum and is effective in vaporizing the communicating vessels to deeper cisterns. To our knowledge this is the first description of keloid development after laser therapy for vulvar lymphangioma circumscriptum, and such an effect should be considered before CO2 laser surgery is applied for this particular entity.

Aged↗