The ellagic acid metabolites urolithin A and B differentially affect growth, adhesion, motility, and invasion of endometriotic cells in vitro.

STUDY QUESTION: What are the effects of plant-derived antioxidant compounds urolithin A (UA) and B (UB) on the growth and pathogenetic properties of an in vitro endometriosis model? SUMMARY ANSWER: Both urolithins showed inhibitory effects on cell behavior related to the development of endometriosis by differentially affecting growth, adhesion, motility, and invasion of endometriotic cells in vitro. WHAT IS KNOWN ALREADY: Endometriosis is one of the most common benign gynecological diseases in women of reproductive age and is defined by the presence of endometrial tissue outside the uterine cavity. As current pharmacological therapies are associated with side effects interfering with fertility, we aimed at finding alternative therapeutics using natural compounds that can be administered for prolonged periods with a favorable side effects profile. STUDY DESIGN, SIZE, DURATION: In vitro cultures of primary endometriotic stromal cells from 6 patients subjected to laparoscopy for benign pathologies with histologically confirmed endometriosis; and immortalized endometrial stromal (St-T1b) and endometriotic epithelial cells (12Z) were utilized to assess the effects of UA and UB on endometriotic cell properties. Results were validated in three-dimensional (3D) in vitro co-culture spheroids of 12Z and primary endometriotic stroma cells of one patient, and organoids from 3 independent donors with endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The effects on cell growth were measured by non-radioactive colorimetric assay to measure cellular metabolic activity as an indicator of cell viability (MTT assay) and flow cytometric cell cycle assay on primary cultures, St-T1b, and 12Z. Apoptosis analyses, the impact on in vitro adhesion, migration, and invasion were evaluated in the cell lines. Moreover, Real-Time Quantitative Reverse Transcription polymerase chain reaction (RT-qPCR) assays were performed on primary cultures, St- T1b and 12Z to evaluate a plausible mechanistic contribution by factors related to proteolysis (matrix metalloproteinase 2, 3 and 9 -MMP2, MMP3, MMP9-, and tissue inhibitor of metalloproteinases -TIMP-1-), cytoskeletal regulators (Ras-related C3 botulinum toxin substrate 1 -RAC1-, Rho-associated coiled-coil containing protein kinase 2 -ROCK2-), and cell adhesion molecules (Syndecan 1 -SDC1-, Integrin alpha V-ITGAV-). Finally, the urolithins effects were evaluated on spheroids and organoids by formation, viability, and drug screen assays. MAIN RESULTS AND THE ROLE OF CHANCE: 40 µM UA and 20 µM UB produced a significant decrease in cell proliferation in the primary endometriotic cell cultures (P < 0.001 and P < 0.01, respectively) and in the St-T1b cell line (P < 0.001 and P < 0.05, respectively). In St-T1b, UA exhibited a mean half-maximum inhibitory concentration (IC50) of 39.88 µM, while UB exhibited a mean IC50 of 79.92 µM. Both 40 µM UA and 20 µM UB produced an increase in cells in the S phase of the cell cycle (P < 0.01 and P < 0.05, respectively). The same concentration of UA also increased the percentage of apoptotic ST-t1b cells (P < 0.05), while both urolithins decreased cell migration after 24 h (P < 0.001 both). Only the addition of 5 µM UB decreased the number of St-T1b adherent cells. TIMP-1 expression was upregulated in response to treating the cells with 40 µM UA (P < 0.05). Regarding the 12Z endometriotic cell line, only 40 µM UA decreased proliferation (P < 0.01); while both 40 µM UA and 20 µM UB produced an increase in cells in the G2/M phase (P < 0.05 and P < 0.01, respectively). In this cell line, UA exhibited a mean IC50 of 40.46 µM, while UB exhibited a mean IC50 of 54.79 µM. UB decreased cell migration (P < 0.05), and decreased the number of adherent cells (P < 0.05). Both 40 µM UA and 20 µM UB significantly decreased the cellular invasion of these cells; and several genes were altered when treating the cells with 40 µM UA and 10 µM UB. The expression of MMP2 was downregulated by UA (P < 0.001), and expression of MMP3 (UA P < 0.001 and UB P < 0.05) and MMP9 (P < 0.05, both) were downregulated by both urolithins. Moreover, UA significantly downregulated ROCK2 (P < 0.05), whereas UB treatment was associated with RAC1 downregulation (P < 0.05). Finally, the matrix adhesion receptors and signaling (co)receptors SDC1 and ITGAV were downregulated upon treatment with either UA or UB (P < 0.01 and P < 0.05, respectively in both cases). Regarding the effects of urolithins on 3D models, we have seen that they significantly decrease the viability of endometriosis spheroids (80 µM UA and UB: P < 0.05 both) as well as affecting their area (40 µM UA: P < 0.05, and 80 µM UA: P < 0.01) and integrity (40 µM UA and UB: P < 0.05, 80 µM UA and UB: P < 0.01). On the other hand, UA and UB significantly inhibited organoid development/outgrowth (40 and 80 µM UA: P < 0.0001 both; 40 µM UB: P < ns-0.05-0.001, and 80 µM UB: P < 0.01-0.001-0.001), and all organoid lines show urolithins sensitivity resulting in decreasing viability (UA exhibited a mean IC50 of 33.93 µM, while UB exhibited a mean IC50 of 52.60 µM). LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was performed on in vitro endometriosis models. WIDER IMPLICATIONS OF THE FINDINGS: These in vitro results provide new insights into the pathogenetic pathways affected by these compounds and mark their use as a potential new therapeutic strategy for the treatment of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded EU MSCA-RISE-2015 project MOMENDO (691058). The authors have no conflicts of interest to declare.

Similar autobiographical memory impairment in long-term secondary progressive multiple sclerosis and Alzheimer's disease.

BACKGROUND: Memory disturbance is a common symptom of multiple sclerosis (MS), but little is known about autobiographical memory deficits in the long-term course of different MS subtypes. Inflammatory activity and demyelination is pronounced in relapsing-remitting multiple sclerosis (RRMS) whereas, similar to Alzheimer's disease, neurodegeneration affecting autobiographical memory-associated areas is seen in secondary progressive multiple sclerosis (SPMS). OBJECTIVE: In light of distinct disease mechanisms, we evaluated autobiographical memory in different MS subtypes and hypothesized similarities between elderly patients with SPMS and Alzheimer's disease. METHODS: We used the Autobiographical Memory Interview to assess episodic and semantic autobiographical memory in 112 education- and gender-matched participants, including healthy controls and patients with RRMS, SPMS, amnesic mild cognitive impairment (aMCI) and early Alzheimer's dementia (AD). RESULTS: Patients with SPMS, AD, and aMCI, but not with RRMS, exhibited a pattern of episodic autobiographical memory impairment that followed Ribot's Law; older memories were better preserved than more recent memories. In contrast to aMCI and AD, neither SPMS nor RRMS was associated with semantic autobiographical memory impairment. CONCLUSION: Our neuropsychological findings suggest that episodic autobiographical memory is affected in long-term patients with SPMS, possibly due to neurodegenerative processes in functional relevant brain regions.

Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma.

BACKGROUND AND PURPOSE: Radiotherapy constitutes an essential element in the multimodal therapy of Ewing's sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing's sarcoma in vitro. MATERIAL AND METHODS: An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing's sarcoma cell lines with and without irradiation. RESULTS: Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation. CONCLUSION: Survivin is a radiation-inducible protein in Ewing's sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing's sarcoma.

Does dye laser treatment with higher fluences in combination with cold air cooling improve the results of port-wine stains?

BACKGROUND AND OBJECTIVE: The use of cold air cooling (CAC) and cryogen spray cooling during dye laser treatment of port-wine stains (PWS) has become a standard in recent years. Still unsolved is the question of which fluences are necessary in combination with CAC in order to achieve an optimum clearance and the lowest possible rate of side-effects. STUDY DESIGN: In a prospective study, we treated 11 patients with PWS with pulsed dye laser (Photogenica V, Cynosure, lambda = 585 nm, iota(p) = 0.5 ms, spot size = 7 mm). Each PWS was partitioned into three areas: (area 1) 6 J/cm(2) without CAC, (area 2) 6 J/cm(2) with CAC (level 4), (area 3) 9 J/cm(2) with CAC (level 4). RESULTS: Area 3 (mean, 59%) showed a slightly better clearance than area 1 (mean, 57%); in area 2, we observed a reduced clearance (mean, 45%). Compared with area 1, we achieved a reduction of pain through CAC in areas 2 and 3. The healing periods as well as the rate of side-effects were comparable in all areas. CONCLUSION: We observed a slight but not statistically relevant increase in clearance with the use of higher fluences and CAC compared with lower fluences without CAC. Because pain is lowered significantly when using CAC, and because this makes the treatment more comfortable for the patients, we tend to recommend the use of higher fluences (9 J/cm(2)) with simultaneous CAC for treating PWS.

Flow-cytometric identification, enumeration, purification, and expansion of CD133+ and VEGF-R2+ endothelial progenitor cells from peripheral blood.

A flow cytometric method for identifying, purifying, and expanding endothelial progenitor cells (EPC) derived from peripheral blood is reported. During our experiments, we found that isolation of viable EPC is not possible by using the standard flow cytometric protocols, since erythrocyte lysing influences cell survival. Furthermore, erythrocyte lysing has a high impact on quantative analysis of EPC with 20% lower numbers compared to no-lyse data. The viability of EPCs was tested with a colony forming test after both lysis based FACS of EPCs and without lysing. CD133 and VEGF-R2 revealed as positive markers for EPC selection and 7-amino actinomycin D (7-AAD) to eliminate dead cells. The few purified CD133+ and VEGF-R2+ cells showed strong colony-forming capacity in a human stem cell methylcellulose based medium (colony assay) when isolated by the no-lyse protocol. The colonies showed the typical shape of early EPC-colonies with round immature cells in the centre and dendritic or spindelcell-shaped peripheral cells, which were also immunologically identified as EPC-derived. Compared to this, erythrocyte lysing reagents destroyed even all sorted EPCs. Summarizing the presented data suggest that the use of erythrocyte lysing reagents is neither suitable for cloning nor for counting of endothelial progenitor cells, and no-lyse protocols should be used.

Electro-optical synergy (ELOS) technology for nonablative skin rejuvenation: a preliminary prospective study.

BACKGROUND AND OBJECTIVES: In this preliminary prospective study, we evaluated the efficacy and safety of nonablative wrinkle treatment using combined radiofrequency (RF) and optical energy (Polaris). The dual energy technology of Polaris, called ELOS, which stands for electro-optical synergy, uses synchronous pulses of bipolar RF current and pulsed visible light (diode laser) delivered in the same pulse. MATERIALS AND METHODS: Twenty-four subjects with periorbital and perioral wrinkles received six treatments at 4-week intervals with the Polaris WR (Syneron, Inc., Israel, 900 nm, max. RF energy 100 J/cm(3), max. laser energy 50 J/cm(2)). Each treatment consisted of two passes over the treatment area using pulsed optical and RF parameters that were determined by the patient's skin phenotype and distribution of target chromophores. The follow-up period was 3 months after the last treatment. RESULTS: Independent scoring of blinded photographs showed a wrinkle score improvement of at least 1 (0 = no improvement, 1 = medium, 2 = good, 3 = excellent improvement) 3 months after the last of six treatment sessions. There was no difference between periorbital and perioral wrinkle reduction. Fifty-eight per cent (14/24) of the subjects reported a notable wrinkle reduction; 16% noted mild to moderate oedema and erythema lasting for no more than 1 day. Scarring or pigmentary changes were not detected. The average pain score was 0.6 (0 = no pain, 5 = intolerable pain). CONCLUSION: Multiple treatments with the Polaris WR produced objective and subjective reduction of periorbital and perioral wrinkles. The occurrence of side-effects and pain was very low. The clinical effect may be caused by matrix coagulation of the deep dermis by the RF and selective thermolysis of blood vessels with the 900 nm diode laser.

[Laser therapy for vascular lesions]. / Laser- und Lichttherapie von vaskulären Hautveränderungen.

The use of lasers to treat vascular lesions began in the late 1960s with the introduction of argon laser. More recently pulsed laser and intense pulsed light techniques have further improved results and reduced side effects. Their function is based on the principle of selective photothermolysis. Simultaneous application of cooling methods (contact cooling, cold air, cryogen spray) has become standard procedure for these types of therapy, whose most important indications are port-wine stain, hemangioma, and telangiectasia. A persistent difficulty is their limited penetration, resulting in limited or no effect on deeper dermal layers. New approaches therefore include combinations with bipolar radio frequency or the use of two different laser systems, e.g., dye and Nd:YAG lasers. The different lasers are described along with their effectivity, limitations and indications.

[Excimer laser. Treatment of iatrogenic hypopigmentation following skin resurfacing]. / Excimerlaser. Behandlung von iatrogenen Hypopigmentierungen nach Skin-Resurfacing.

As skin resurfacing has become more common, the number of patients developing post-treatment hypopigmentation has increased. No effective treatment for this complication has been developed. Some hypopigmented disorders, including vitiligo, have been treated with the excimer laser. We used the XeCl excimer laser to successfully treat a 78-year-old woman with perioral leukoderma following CO(2) laser skin resurfacing. The repigmentation was stable for at least 16 months. Larger prospective studies of this new therapeutic intervention are recommended to evaluate its efficacy and long-term stability.

[Reticulohistiocytoma. Treatment with pulsed-dye laser]. / Retikulohistiozytom. Behandlung durch gepulsten Farbstofflaser.

Reticulohistiocytoma is a rare non-Langerhans-cell histiocytosis. On exposed skin areas it is a cosmetic problem and can cause mechanical irritation due to its prominent nature. We successfully treated a histologically confirmed reticulohistiocytoma on the back of a 60 year old woman with a pulsed dye-laser (wavelength 585 nm, pulse 0.45 msec). The lesion regressed significantly after the first treatment (spot size: 7 mm, fluence 7.8 J/cm(2)). After another laser treatment, the lesion completely disappeared. At 28 month follow-up, no recurrence was seen. Permanent side effects were not observed. In our case report the use of the pumped pulsed dye-laser has proven to be an elegant and low risk treatment option for reticulohistiocytoma. The mechanism of action remains unknown.

[Repigmentation of persistent laser-induced hypopigmentation after tattoo ablation with the excimer laser]. / Repigmentierung persistierender laserinduzierter Hypopigmentierungen nach Tätowierungsentfernung mit dem Excimerlaser.

Hypopigmented skin developed following tattoo removal with the Q-switched Nd:YAG laser. The hypopigmented area remained unchanged for over 4 years, until the use of the 308-nm xenon-chloride excimer laser induced a significant repigmentation in 40 sessions over 14 months. The excimer laser has the potential to influence the reduced activity of the melanocytes, as demonstrated with electron microscopy.

[Diffused traumatic dirt and decorative tattooing. Removal by Q-switched lasers]. / Diffundierte Schmutz- und Schmucktätowierungen. Entfernung durch gütegeschaltete Laser.

BACKGROUND AND OBJECTIVE: Pigment fanning or spread is one complication of decorative tattooing, but is also seen after traumatic tattoos. The reason for this spreading remains unclear. While excision of the diffused pigment was previously considered the treatment of choice, today destruction of the pigment with Q-switched laser systems is the therapy with the highest efficiency and lowest rate of side effects. Therefore areas of pigment spread should be excised only in rare exceptional cases. PATIENTS/METHODS: 4 patients with pigment fanning after permanent make up and traumatic tattooing of the periorbital region were treated with the Q-switched ruby (694 nm) and Q-switched Nd:YAG (1064 nm) lasers. RESULTS: All patients showed a significant (70-80%) clearance of the spread pigment; two had complete clearing. Side effects such as hyper- or hypopigmentation, scarring or ink darkening were not seen. CONCLUSIONS: The Q-switched ruby- and Q-switched Nd:YAG-lasers are a therapeutic modality for pigment fanning with high efficiency and low rate of side effects. Attempts of explanation for pigment spread after tattoos are given, but further histological and electron microscopical investigations are needed to find the pathogenetic mechanism.

[Medical dermatologic laser therapy. A review]. / Medizinische dermatologische Lasertherapie. Eine Ubersicht.

The medical indications for laser therapy have been somewhat overlooked, perhaps because of the success of cosmetic laser therapy. As a result, many effective medical treatments are not covered by insurance companies. Lasers are helpful in many aspects of dermatologic treatment. Examples include pigmented lesions (Becker nevus), benign tumors (organoid nevi, adenoma sebaceum), dyschromias (traumatic tattoos), inflammatory diseases of the skin and subcutaneous tissue (lupus erythematosus, scars), hypertrichosis, premalignant lesions, and vascular lesions (hemangiomas and malformations). The various disorders which can effectively be treated with lasers are reviewed.

Mutagenicity of low-filtered 30 kVp X-rays, mammography X-rays and conventional X-rays in cultured mammalian cells.

PURPOSE: To measure the mutagenic effectiveness of low-filtered 30 kVp X-rays, mammography X-rays and conventional (200 kVp) X-rays in mammalian cells. MATERIALS AND METHODS: Two different cell lines and mutation assays were used. Exponentially growing SV40-transformed human fibroblasts were exposed to graded doses of mammography (29 kVp, tungsten anode, 50 microm Rh filter) or conventional X-rays and the frequency of 6-thioguanine-resistent HPRT-deficient mutants was determined. Exponentially growing hamster A(L) cells, which contain a single human chromosome 11 conferring the expression of the human surface protein CD59, were subjected to magnetic cell separation (MACS) in order to remove spontaneous mutants before irradiation with low-filtered 30 kVp (tungsten anode, 0.5 mm Al filter) or conventional X-rays. Fractions of radiation-induced CD59- mutants were quantified by flow-cytometry after immunofluorescence labelling of CD59 proteins. RESULTS: Mammography X-rays were more effective than conventional X-rays at inducing killing of human fibroblasts, whereas 30 kVp X-rays and conventional X-rays were about equally effective at killing Al. cells. Mutant frequencies were linearly related to dose in both mutation assays. An RBE = 2.7 was calculated for the yield of HPRT mutants in human fibroblasts exposed to mammography relative to conventional X-rays and an RBE = 2.4 was obtained for the CD59 mutant frequency in A(L) cells irradiated with low-filtered 30 kVp relative to conventional X-rays. CONCLUSIONS: Both low-filtered 30 kVp and mammography X-rays are mutagenic in mammalian cells in vitro. It is unknown if and how the enhanced mutagenicity of mammography X-rays measured in human cells in vitro translates into breast cancer risk for predisposed women with an enhanced inherited risk for breast cancer. Although the ICRP guidelines attribute the same relative biological effectiveness to all radiations of low LET, including X- and gamma-radiations of all energies for radiobiological protection purposes including the assessment of risks in general terms, they also state that 'for the estimation of the likely consequences of an exposure of a known population, it will sometimes be better to use absorbed dose and specific data relating to the relative biological effectiveness of the radiations concerned and the probability coefficients relating to the exposed population' (ICRP 1991: 32). This latter statement may apply for the population of familial predisposed women. We hope that the presented data on the enhanced mutagenicity of mammography X-rays may stimulate a re-evaluation of the risk assessment of mammography for familial predisposed women. In the meantime, one should be cautious and avoid early and frequent mammography exposure of predisposed women. Alternative examination methods should be applied for these women with an inherited increased risk for breast cancer.

Mutation induction and neoplastic transformation in human and human-hamster hybrid cells: dependence on photon energy and modulation in the low-dose range.

Mutation induction in the HPRT gene of human fibroblasts after irradiation with mammography-like 29 kVp or 200 kVp x-rays shows radiohypersensitivity for doses smaller than approximately 0.5 Gy. Similarly, mutation induction in the CD 59 gene on human chromosome 11 in A(L) cells shows radiohypersensitivity for doses smaller than approximately 0.5 Gy after exposure to 200 kVp x-rays, but not after irradiation with low-filtered 30 kVp x-rays. The RBE values of 29 and 30 kVp x-rays relative to 200 kVp x-rays are strongly dose dependent. For neoplastic transformation of human hybrid (CGL1) cells after irradiation with 29 or 200 kVp x-rays or 60Co gamma rays a linear-quadratic dose relationship was observed with RBE values of approximately four and eight for mammography relative to 200 kVp x-rays and 60Co gamma rays, respectively.

[CO(2) and Er:YAG lasers in dermatology and aesthetic surgery]. / CO(2)- und Er:YAG-Laser in der Dermatologie und Asthetischen Medizin.

In the past few years, the spectrum of indications for ablative lasers in dermatology and aesthetic medicine has been expanded due to technological innovations. In the following, technical basics, laser-tissue interactions, indications for the CO(2) and Er:YAG laser and laser treatment management are described. In addition, side effects and reactions associated with the use of these laser systems are listed and compared.

["Skin rejuvenation" by non-ablative laser and light systems. Literature research and overview]. / "Skin rejuvenation" durch nichtablative Laser- und Lichtsysteme. Literaturrecherche und Ubersicht.

Currently, ablative laser therapy (with CO2/Er:YAG lasers) and deep chemical peeling are effective and promising methods of skin rejuvenation. The induction of collagen synthesis was observed after peelings with trichloroacetic acid or phenol as well as after treatments with the CO2 laser. In past years, the undesirable side effects and risks of these methods have led to intensified research in the fields of non-ablative facial rejuvenation and subsurfacing by means of ablative laser systems and intense pulsed light systems. The objective is to achieve selective, heat-induced denaturalisation of dermal collagen that leads to subsequent reactive synthesis but does not damage the epidermis. Recently, the results of numerous clinical and histological studies have indicated that these new technologies are successful. After critical review and assessment of current literature, we can say that in terms of their efficacy, non-ablative methods are not a comparable alternative to ablative skin resurfacing.

A novel true volumetric method for the determination of residual leucocytes in blood components.

BACKGROUND AND OBJECTIVES: Accurate determination of residual leucocytes [white blood cells (WBC)] in blood components is of high clinical importance. To date, several labour-intensive, time-consuming or expensive techniques have been used for this purpose. MATERIALS AND METHODS: A method for the determination of residual WBC is described using a novel low-cost flow-cytometric cell counter and analyser (CCA). The DNA in WBC was stained using 4'-6-diamidino-2-phenylindole (DAPI) and WBC were automatically analysed by true volumetric counting of 200-microl samples (prepared from a 20-microl undiluted sample). RESULTS: Dilution experiments over a range of 0.5-50 WBC/microl showed a linearity of r = 0.998. The detection limit of this method was 0.83 WBC/microl of red blood cell concentrate (RCC) and 0.67 WBC/microl of platelet concentrate (PC), with an accuracy of 95.5%. CONCLUSION: Residual WBC (< 1 WBC/microl) can be accurately counted using the CCA within 2 min and at a total cost of less than euro 1 per sample.

Immunoglobulin isotypes reveal a predominant role of type 1 immunity in multiple sclerosis.

IgG, its subclasses and IgE concentrations were measured in cerebrospinal fluid (CSF) and serum of multiple sclerosis (MS) patients and matched controls as surrogate markers for type 1 and type 2 immunity. IgE indices were significantly reduced in MS patients compared to controls. In contrast, IgG1 was elevated in CSF of MS patients and elevated indices indicated intrathecal synthesis. Because isotype switching to IgE and IgG4 is driven by type 2 immunity and occurrence of IgG1 has previously been found in type 1 immunity-dominated diseases, the results underscore a role of type 1 immunity in MS.

Free-floating thrombus in the femoral vein--a challenge in phlebologic diagnostics.

Although thrombophlebitis may be a complication of an incompetent great saphenous vein, it usually has a benign outcome. The risk of embolisation is present especially when ascending progression of superficial venous thrombosis extends to the femoral vein. The proximal extension of the thrombus often precedes clinically visible symptoms. Use of colour duplex sonography is superior to phlebography in assessing the saphenofemoral junction area and thrombus propagation in these cases. Our case report details the difficulties encountered in the diagnosis and therapy of a patient with a free-floating thrombus at the saphenofemoral junction.

Treating REM syndrome with the pulsed dye laser.

BACKGROUND AND OBJECTIVE: REM syndrome (reticular erythematous mucinosis) is a benign but bothersome skin disease that common occurs in middle age and among women. Local and systemic treatment measures are often associated with a high rate of side effects and relapses are common. We evaluated the pulsed dye laser as an alternative method because of its good efficacy in vascular skin diseases. STUDY DESIGN/MATERIALS AND METHODS: We treated two female patients with REM syndrome using the pulsed dye laser. RESULTS: In both patients the erythematous skin changes were almost completely removed after five and three laser sessions, respectively. Other than transient hypopigmentation, no side effects occurred. In one case there is still no evidence of recurrence 6 years after a trial treatment was conducted. In the same patient, clinical success was histologically confirmed. CONCLUSIONS: This is the first report on the successful treatment of REM syndrome of two female patients with the pulsed dye laser.