Impact of UVA on pruritus during UVA/B phototherapy of inflammatory skin diseases: a randomized double-blind study.

BACKGROUND: Narrowband (TL-01) UVB phototherapy (UVB nb) is effective in treating inflammatory skin disease. The addition of UVA is traditionally advocated to reduce pruritus, but lacks evidence for this recommendation. OBJECTIVES: The aim of this study was to assess the effect of UVB nb and UVA phototherapy in combination compared against UVB nb monotherapy on pruritus, disease activity and quality of life. METHODS: In this double-blind randomized clinical trial, 53 patients suffering from inflammatory skin diseases with pronounced itching (Visual Analogue Scale (VAS) for pruritus ≥5) were randomized into two treatment groups. One group received UVB nb (311 nm) phototherapy alone and another group received a combination of UVB nb and UVA (320-400 nm) phototherapy. UV therapy was performed three times per week over 16 weeks. Pruritus (VAS and 5-D itch score), disease activity and quality of life (Dermatology Life Quality Index, DLQI) were assessed at baseline and weeks 4, 8, 12 and 16. RESULTS: In both treatment groups, there was a reduction in pruritus scores, disease activity and DLQI. No difference in pruritus score, disease activity and quality of life could be detected between the group receiving UVB nb alone and those receiving UVB nb combined with UVA. CONCLUSIONS: Phototherapy with UVB nb alone, and UVB nb combined with UVA are equally effective in treating inflammatory skin disease and indifferent in reducing disease-associated pruritus. Given this non-inferiority for UVB nb monotherapy, the recommendation of adding UVA to UVB nb phototherapy for pruritic inflammatory skin disease should be abandoned.

[Leg swelling following inguinal and ilioinguinal dissection of melanoma metastases]. / Beinschwellungen nach inguinaler und ilioinguinaler Dissektion von Melanommetastasen.

BACKGROUND: With respect to survival and local disease control, the adequate extent of lymph node dissection for melanoma metastasis to the groin is controversial. Since the methods for accurate quantification of leg oedemas are not well standardised, it remains also unclear whether the iliac part of a radical ilioinguinal lymph node dissection contributes to postoperative lymphoedema. PATIENTS AND METHODS: Using a questionnaire and clinical examinations, we prospectively studied 65 persons for the presence of leg swellings (11 with inguinal lymph node dissection (sCLND), 23 with ilioinguinal dissection (rCLND), and 31 without nodal surgery and without signs of venous insufficiency). Exact volumetry of the legs was performed using the Image 3 D method. RESULTS: The mean interval between the lymphadenectomy and the examination for swellings was 24 ±â€†30 months. Compared with sCLND, the amount of postoperative drainage fluid was significantly higher after rCLND (1960 ±â€†1390 mL versus (vs.) 898 ±â€†578 mL). Patients with rCLND perceived more frequently leg swellings (83 % vs. 55 %, p = 0.09), however, also 23 % of the control persons perceived leg swellings. Clinical signs of swelling were found slightly more frequently in the rCLND group (52 % vs. 45 %). After rCLND, the gain in volume of the ipsilateral thigh was significantly higher than after sCLND (7.01 ±â€†4.83 % vs. 1.29 ±â€†6.12 %, p = 0.01). Patients with rCLND more frequently needed manual lymph drainage (70 % vs. 45 %). In the control persons, the volumes of the right (mostly dominant) and the left legs did not differ significantly. CONCLUSIONS: Our results suggest that the iliac part of an ilioinguinal lymph node dissection significantly contributes to lymphoedema. Because of the multitude of reasons for swellings of the lower leg, volumetry of the thigh seems to be most adequate for quantifying the amount of postoperative lymphoedema.

Ambient habitat noise and vibration at the Georgia Aquarium.

Underwater and in-air noise evaluations were completed in performance pool systems at Georgia Aquarium under normal operating conditions and with performance sound tracks playing. Ambient sound pressure levels at in-pool locations, with corresponding vibration measures from life support system (LSS) pumps, were measured in operating configurations, from shut down to full operation. Results indicate noise levels in the low frequency ranges below 100 Hz were the highest produced by the LSS relative to species hearing thresholds. The LSS had an acoustic impact of about 10 dB at frequencies up to 700 Hz, with a 20 dB re 1 µPa impact above 1000 Hz.

Thrombophilia in patients with chronic venous leg ulcers-a study on patients with or without post-thrombotic syndrome.

BACKGROUND: Chronic venous leg ulcers (CVU) cause considerable burden of disease for the patients as well as enormous costs for health care systems. The pathophysiology of CVU is complex and not entirely understood. So far reliable pathogenic and/or prognostic parameters have not been identified. OBJECTIVES: We studied the role of thrombophilia in patients referred to a University dermatology department for treatment of CVU. PATIENTS AND METHODS: A cohort of 310 patients with active chronic venous leg ulcers (CEAP 6) was stratified into two comparably large groups according to the presence or absence of post-thrombotic syndrome (PTS+; PTS-) as determined using duplex scan and/or phlebography. In addition, several thrombophilia parameters were assessed. RESULTS: The prevalence of protein S deficiency and factor V Leiden mutation was significantly higher in PTS+ patients compared with the PTS- group. However, patients in both subgroups revealed high prevalences of thrombophilia (antithrombin deficiency, protein C deficiency, protein S deficiency, activated protein C resistance, factor V mutation or elevated homocysteine). CONCLUSION: Based on these data, it is conceivable that thrombophilia contributes to the pathogenesis of CVU, possibly through induction of microcirculatory dysregulations.

The volume of postoperative drainage fluid as a potential early predictor of lymphedema after lymph node excision for metastatic melanoma.

Lymphedema (LE) following lymph node dissection is a major problem for cancer patients, and radiation therapy, extended surgery, groin dissection, obesity, and older age are well-established risk factors of LE. We studied whether these risk factors are further associated with high volumes of postoperative drainage fluid after complete lymph node dissection (CLND) for melanoma metastases. Moreover, we examined whether a high amount of drainage fluid after sentinel lymph node biopsy (SLNB) can predict a high amount of drainage fluid after subsequent CLND. Using descriptive statistics and regression analyses, we analyzed the cumulative volumes of postoperative drainage fluid for 836 melanoma patients with lymph node excision in the axilla or groin. In multiple regression analyses, the well-established risk factors of LE, i.e., increased body mass index, older age, and ilioinguinal versus inguinal versus axillary dissection predicted a high drainage volume after CLND. Of note, a high drainage fluid volume after SLNB also predicted a high drainage volume after subsequent CLND. In patients with groin dissections, who are particularly susceptible to swelling, extended iliac dissection, age above 60, and a cumulative drainage volume of more than 100 ml in the preceding SLNB were predictors of the cumulative drainage volume. We find that common risk factors predict the volume of postoperative drainage fluid after CLND and postoperative LE. Further, high postoperative drainage volume may therefore function as a potential early predictor of LE following CLND.

Sentinel lymphonodectomy does not increase the risk of loco-regional cutaneous metastases of malignant melanomas.

With regard to malignant melanoma, the impact of lymph node surgery on the development of loco-regional cutaneous metastases (LCM) has not yet been adequately addressed. However, this aspect is of interest, since sentinel lymphonodectomy (SLNE) has been suspected of causing LCM by inducing entrapment of melanoma cells. We analysed 244 patients with SLNE and compared the data with 199 patients treated with delayed lymph node dissection (DLND) for clinically palpable metastases. Analysis of both groups commenced at the time of excision of the primary tumour, using the Kaplan-Meier method. LCM that appeared as a first recurrence, as well as the overall probability of developing LCM, were recorded. For sentinel-negative patients with a primary melanoma >1mm thick, the 5-year probability of developing LCM as a first recurrence was 6.9 +/- 0.02% (+/-standard error of the mean (SEM)). The probability was 17.6 +/- 0.03% in the DLND group. Comparing the two node-positive subgroups, the probability of developing LCM as a first recurrence was significantly higher in patients with positive SLNE (27.3 +/- 0.05%, P = 0.03). However, the 5-year overall probability of developing LCM did not differ significantly in the node-positive groups (33.3% in the DLND group vs. 33.7% in patients with positive sentinel lymph nodes (SLNs)). Since early excision of lymphatic metastases by SLNE avoids nodal recurrences, thereby prolonging the recurrence-free interval, the chance of LCM to manifest as a first recurrence should inevitably increase. However, the overall in-transit probability is not increased after SLNE.

Dynamic lymphoscintigraphy and image fusion of SPECT and pelvic CT-scans allow mapping of aberrant pelvic sentinel lymph nodes in malignant melanoma.

To date, there are no reliable criteria to identify those patients with melanoma-infiltrated sentinel lymph nodes (SLNs) of the groin who might benefit from an extended lymphadenectomy, including the pelvic lymph nodes. We hypothesised that there are pelvic lymph nodes that receive lymph directly from the primary tumour, thus being at an increased risk for metastasis. In order to determine the frequency of radioactively labelled pelvic lymph nodes and the kinetics of their appearance, we introduce here a combination of dynamic lymphoscintigraphy, single photon emission computed tomography (SPECT) and image fusion of SPECT and pelvic Computed Tomography (CT)-scans. By dynamic lymphoscintigraphy and intraoperative gamma probe detection, superficially located inguinal SLNs (median 2 nodes) could be identified in all of the 51 patients included in this analysis. The histological search for micrometastases was positive in 16 patients (median Breslow thickness of the primary melanoma 2.5 mm). In 29 patients, SPECT and the image fusion technique were additionally performed. Radioactively labelled pelvic lymph nodes were detected in 20 individuals, 6 of them presenting aberrant pelvic SLNs that, on dynamic lymphoscintigraphy, had appeared simultaneously with the superficial SLN(s). Of the 6 patients in whom radioactive pelvic lymph nodes were excised together with the superficial SLN(s), only one had positive superficial SLNs. In this patient, the aberrant pelvic SLN proved to be tumour-positive. In 9 patients, there was no radiotracer uptake in the pelvic lymph nodes at all. Image fusion of SPECT and pelvic CT-scans is an excellent tool to localise exactly the pelvic tumour-draining nodes. The significance of radioactively labelled pelvic lymph nodes for the probability of pelvic metastases should be analysed further.

Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease.

Early versus delayed excision of lymph node metastases is still being assessed in malignant melanoma. In the present retrospective, multicentre study, the outcome of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with the outcome of 623 patients with delayed lymph node dissection (DLND) of clinically enlarged lymph node metastases. In order to avoid the lead-time bias, survival was generally calculated from the excision of the primary tumour. Survival curves were constructed using the Kaplan-Meier product-limit estimate. Cox's proportional hazards model was used to perform a multivariate analysis of factors related to overall survival. Compared with SLNE and early performed complete lymph node dissection, DLND yielded a significantly higher number of lymph node metastases. Median and mean tumour thickness were nearly identical in the two therapy groups. The estimated 3-year overall survival rate was 80.1+/-2.8% (+/-standard error of the mean (SEM)) in patients with positive SLNs, and 67.6+/-1.9% in patients with DLND (5-year survival rates 62.5+/-5.5 and 50.2+/-5.4%, respectively). The difference between the two survival curves was statistically significant (P=0.002). Using multifactorial analysis, SLNE (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent predictors of overall survival. The location of the primary tumour (P=0.59) was non-significant. Considering only those centres with sufficient data for epidermal ulceration, this risk factor was also significant. In cutaneous malignant melanoma, early excision of lymphatic metastases, directed by the sentinel node procedure, provides a highly significant overall survival benefit.

Locoregional cutaneous metastasis in patients with therapeutic lymph node dissection for malignant melanoma: risk factors and prognostic impact.

In patients with lymph node metastasis of malignant melanoma, the incidence of additional locoregional cutaneous metastases has not been well documented. More importantly, the prognostic impact of locoregional cutaneous metastases appearing prior to therapeutic lymphadenectomy is unclear. Using Kaplan-Meier estimations and a Cox proportional hazards model, we addressed these questions in 224 patients with palpable lymph node metastases to the axilla or the groin. The 10 year overall probability to develop regional cutaneous metastasis, calculated from primary tumour excision, was 38.7%. Using univariate and multivariate analysis, Breslow thickness was a significant risk factor of in-transit disease in node-positive patients. In 24 patients (10.7%) locoregional cutaneous metastases had appeared before therapeutic lymphadenectomy, but this was not associated with a survival disadvantage. In conclusion, locoregional cutaneous metastases amenable to surgical excision do not significantly influence the survival prognosis after therapeutic lymphadenectomy. In the subpopulation of patients with lymph node metastasis, Breslow thickness predicts the probability of additional locoregional cutaneous metastasis.

Prognostic factors of overall survival in patients with delayed lymph node dissection for cutaneous malignant melanoma.

To date, no study of melanoma patients who have undergone delayed lymph node dissection (DLND) has focused on the independent prognostic factors of overall survival, as calculated from surgery on the primary. Using Kaplan-Meier estimates and Cox's proportional hazard model, the significance of prognostic factors was evaluated in 173 patients who developed clinically apparent regional lymph node metastases. When calculated from excision of the primary tumour (median Breslow thickness 3.0 mm), the median survival was 38 months. When calculated from DLND, the median survival was 19 months. Multifactorial analysis revealed that the number of nodes involved at the time of DLND significantly affected both survival calculated from primary tumour excision (P = 0.0002) and survival calculated from DLND (P < 0.0001). In contrast, the well-known risk factors of primary melanoma did not significantly influence overall survival or survival after DLND. However, the remission duration between surgery on the primary and DLND clearly depended on epidermal ulceration (P = 0.001), Breslow thickness (P = 0.009) and the site of the primary melanoma (P = 0.048). Thus, in patients submitted to DLND, the risk factors of primary melanoma influence the early period of the disease, until metastatic lymph nodes become palpable. With regard to overall survival, only the extent of nodal disease determines the prognosis of these patients.

Inefficacy of vindesine monotherapy in advanced stage IV malignant melanoma patients previously treated with other chemotherapeutic agents.

The anti-melanoma activity of vindesine as a single or polychemotherapeutic agent has been reported previously in adjuvant and first-line melanoma treatment. In this study, we investigated the usefulness of vindesine monotherapy as salvage therapy in stage IV melanoma patients after failure of other chemotherapies. Thirteen patients with progressive disease were treated with 3 mg/m2 vindesine every 2 weeks (median age, 61 years). Previous systemic treatment consisted of polychemotherapy or combined chemo-immunotherapy. All 13 patients suffered from visceral metastases (three lung, one liver, one adrenal gland and eight multiple visceral metastases). A median of three vindesine treatments was administered. Despite the various pre-treatments, the toxicity of vindesine was mild. In all 13 patients, vindesine treatment was stopped due to disease progression. The median survival after primary tumour diagnosis was 42 months (8-151 months), the survival after entering stage IV was 11 months (3-35 months), and the survival after starting vindesine therapy was 4 months (1-22 months). We conclude that vindesine monotherapy is ineffective in stage IV melanoma patients previously treated with other chemotherapeutic agents.

Effects of occupational exposure to organic solvents and noise on hearing.

This study explored the effects of occupational exposure to solvents and noise on hearing. Interviews and hearing tests were conducted for printing and paint manufacturing workers. The experimental groups included unexposed (N = 50) workers and workers exposed to noise (N = 50), noise and toluene (N = 51), or an organic solvent mixture (N = 39). The risk of hearing loss was greater for the exposed groups than for the unexposed group. The adjusted relative risk estimates were four times greater [95% confidence interval (95% CI) 1.4-12.2] for the noise group, 11 times greater (95% CI 4.1-28.9) for the noise and toluene group, and five times greater (95% CI 1.4-17.5) for the solvent-mixture group. The findings suggest that exposure to the studied solvents had a toxic effect on the auditory system and that an interaction between noise and toluene took place. The audiological results of the noise and toluene group suggest a central auditory pathway involvement in the hearing losses observed.

[Painful cutaneous leiomyosarcoma]. / Schmerzhaftes kutanes Leiomyosarkom.

Leiomyosarcomas are derived from smooth muscles and only rarely involve the skin. A 73-year-old male presented with progressive tumor painful on the chest which had been present for 3 years and was tender to palpation, a finding more often associated with benign leiomyomas. immunohistochemical staining demonstrated multiple nerve fibers entrapped by atypical myofibrils, perhaps explaining the tenderness. Since 1996, we have excised five painless cutaneous leiomyosarcomas, in which entrapped nerves could not be demonstrated.

[Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases]. / Dronabinol zur supportiven Therapie metastasierter maligner Melanome mit Lebermetastasen.

BACKGROUND: Loss of appetite and nausea can reduce the quality of life of patients with malignant melanoma and liver metastases. Often established antiemetic drugs fail to bring relief. Tetrahydrocannabinol (THC, Marinol), which is the active agent of Indian hemp, has been used successfully in this situation for other malignant tumors. PATIENTS AND METHODS: We treated 7 patients with hematogenous metastatic melanoma and liver metastases suffering from extensive loss of appetite and nausea supportively with dronabinol (Marinol. All of these patients had previously received standard antiemetic therapy without adequate relief. Dronabinol is a synthetic Delta-tetrahydrocannabinol. The drug was administered in capsule form. We evaluated the palliative effects of dronabinol with a special patient evaluation form, which was filled out at the beginning of the therapy and again after 4 weeks. RESULTS: The majority of patients described a significant increase in appetite and decrease in nausea. These effects remained for some weeks, but then decreased as metastases progressed and the general condition worsened. All of the patients experienced slight to moderate dizziness, but it was not sufficiently troubling to cause interruption or termination of therapy. CONCLUSION: Loss of appetite and nausea due to liver metastases of malignant melanoma can be treated in individual cases supportively with Dronabinol.

Interactions between aortic pressure and inotropic responses in the carotid sinus baroreflex of the rabbit.

The isolated left carotid sinus of rabbit was stimulated with 20 kPa pressure steps. By means of an intraaortic balloon catheter the arterial blood pressure could be either fixed against reflex changes (pressure clamp) or adjusted to any value desired. The passive pressure dependence of the left ventricular systolic pressure LVSP is observed to be linear, and the enddiastolic pressure LVEDP is hardly affected. The LV contractility index CI = (d log P/dt)max has a nonlinear dependence on the aortic pressure. Its slope, the so-called coefficient of pressure-induced inotropy CPI, is high in the lower pressure range and vice versa. In the paced heart inotropic reflex responses to 20 kPa intrasinus pressure steps, expressed in percent attenuation of the CI, were firstly elicited at freely variable arterial pressure and, thereupon, at pressure clamp conditions. In the latter case the inotropic effects are significantly lower (14.5%) than at free running pressure (34.6%). A mean of CPI = 2.32% . kPa-1 is obtained from the inotropic effect differences and the concomitant pressure drops. When subdividing the effects with respect to initial diastolic pressure, we could obtain a CPI = 3.7% . kPa-1 in the pressure range below 14.5 kPa, and a CPI = 1.53% . kPa-1 for higher pressures. The primary inotropic effects at pressure clamp conditions do not depend on the arterial pressure.