Ultraviolet exposure and risk of melanoma and basal cell carcinoma in Ulm and Dresden, Germany.

BACKGROUND: There is a perpetuating increase in melanoma and basal cell carcinoma (BCC) incidence in Europe. Few studies are evaluating various risk factors for both tumours. OBJECTIVES: This pre-planned additional analysis directly compared occupational and past-time ultraviolet exposure behaviour, and examined the effects of sun sensitivity between melanoma and sporadic BCC, and assessed its importance for the two entities. PATIENTS/METHODS: The study included 503 patients (melanoma, n = 291 and BCC, n = 212), and 329 controls from Germany. In all, 244 (49%) of the cases and 165 (50%) of the controls were male (median age melanoma, 55 years; BCC, 69 years; and controls, 57 years). Selection of important risk factors was performed by backward elimination in a polytomous logistic regression. RESULTS: When directly comparing melanoma and sporadic BCC, actinic elastosis (OR 48.83; 95% CI 17.87, 133.40) and site were associated with a higher risk of melanoma, whereas mountaineering in childhood, sunburn 20 years before diagnosis, farming full time, sunbed use in general, seborrheic keratosis, actinic cheilitis, actinic keratosis and age were associated with a higher risk of sporadic BCC. Gardening 20 years before melanoma, hair colour and solar lentigo were risk factors for both entities. A re-evaluation of the data excluding lentiginous melanoma entities (i.e. acro-lentiginous and lentigo-maligna melanoma) resulted in selection of the same factors. However, compared to controls, atopy evolved as a protective factor for melanoma (OR 0.29; 95% CI 0.15, 0.57) and BCC (OR 0.41; 95% CI 0.17, 0.99), respectively, but was associated with a higher risk of sporadic BCC compared to melanoma. CONCLUSION: The odds for having clinical actinic elastosis was lower in BCC compared to melanoma. In contrast, various factors associated with chronic UV exposure and age had higher odds for sporadic BCC, rather than melanoma. Further research is required to set the context for these findings, especially regarding, atopy in non-lentiginous vs. lentiginous forms of melanoma, and possible molecular pathways involved.

Improved patient safety with a simplified operating room to pediatric intensive care unit handover tool (PATHQS).

Introduction: Patient handover is a crucial transition requiring a high level of coordination and communication. In the BC Children's Hospital (BCCH) pediatric intensive care unit (PICU), 10 adverse events stemming from issues that should have been addressed at the operating room (OR) to PICU handover were reported into the patient safety learning system (PSLS) within 1 year. We aimed to undertake a quality improvement project to increase adherence to a standardized OR to PICU handover process to 100% within a 6-month time frame. In doing so, the secondary aim was to reduce adverse events by 50% within the same 6-month period. Methods: The model for improvement and a Plan, Do, Study, Act method of quality improvement was used in this project. The adverse events were reviewed to identify root causes. The findings were reviewed by a multidisciplinary inter-departmental group comprised of members from surgery, anesthesia, and intensive care. Issues were batched into themes to address the most problematic parts of handover that were contributing to risk. Intervention: A bedside education campaign was initiated to familiarize the team with an existing handover standard. The project team then formulated a new simplified visual handover tool with the mnemonic "PATHQS" where each letter denoted a step addressing a theme that had been noted in the pre-intervention work as contributing to adverse events. Results: Adherence to standardized handover at 6 months improved from 69% to 92%. This improvement was sustained at 12 months and 3 years after the introduction of PATHQS. In addition, there were zero PSLS events relating to handover at 6 and 12 months, with only one filed by 36 months. Notably, staff self-reporting of safety concerns during handover reduced from 69% to 13% at 6 months and 0% at 3 years. The PATHQS tool created in this work also spread to six other units within the hospital as well as to one adult teaching hospital. Conclusion: A simplified handover tool built collaboratively between departments can improve the quality and adherence of OR to PICU handover and improve patient safety. Simplification makes it adaptable and applicable in many different healthcare settings.

Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.

In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway activated in response to infections is based on degradation of IkappaB inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show that IKKalpha is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-kappaB target genes, and processing of the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF-kappaB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation.

Interlaboratory evaluation of a new reverse transcriptase polymerase chain reaction-based enzyme-linked immunosorbent assay for the detection of circulating melanoma cells: a multicenter study of the Dermatologic Cooperative Oncology Group.

PURPOSE: Reverse transcription-polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is the most frequently used laboratory method for the detection of circulating tumor cells in melanoma patients. However, previously published results showed considerable variability in the PCR positivity rates. MATERIALS AND METHODS: We designed a collaborative study to assess the sensitivity, specificity, and clinical relevance of a new standardized RT-PCR-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating melanoma cells. Blood samples of healthy donors mixed with cells of a melanoma cell line were prepared in a blinded fashion, and aliquots were sent to seven participating laboratories experienced in RT-PCR. RESULTS: The results demonstrate a high sensitivity (1 melanoma cell/mL blood) and specificity (no false-negatives and 7.4% [2 of 28] false-positives) of the assay and a satisfactory rate of interlaboratory reproducibility. The analysis of aliquots of blinded samples derived from 60 melanoma patients identified tyrosinase mRNA in 17 of 60 (28.3%): three (20%) of 15 stage I patients, two (13.3%) of 15 stage II patients, five (35.7%) of 14 stage III patients, and seven (43.8%) of 16 stage IV patients. The interlaboratory reproducibility of positive samples, however, was extremely low and indicates the presence of low amounts of target mRNA. CONCLUSION: Reverse transcriptase-PCR ELISA has a high sensitivity and specificity for the detection of tyrosinase mRNA in peripheral blood cells. The low interlaboratory reproducibility for the detection of tumor cells in blood samples of melanoma patients, however, raises the question of relevance of this assay for clinical use.

Chromosome 7 aneusomy. A marker for metastatic melanoma? Expression of the epidermal growth factor receptor gene and chromosome 7 aneusomy in nevi, primary malignant melanomas and metastases.

Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) play an important role in a variety of malignant neoplasias, making the search for aberrations in the relevant chromosomes an important issue. Differential expression of the EGFR gene was investigated by reverse transcriptase (RT)-PCR on tissue samples of normal skin, nevi, primary melanomas, and melanoma metastases. The EGFR gene is located on chromosome 7p12.3-p12.1. To determine the number of chromosomes 7 in cell nuclei of the mentioned tissue samples we performed fluorescence in situ hybridization (FISH) on touch preparations, using a DNA probe that hybridizes specifically to the centromeric region of chromosome 7. Additionally, chromosome 7 number in interphase nuclei was determined in short-term primary cell cultures of nevi, primary melanomas, and metastases. The highest EGFR gene expression frequency was found in melanoma metastases. By FISH we detected the highest fraction of cell nuclei with more than two chromosomes 7 in the group of metastases. Our results suggest that overexpression of the EGFR gene might play an important role in metastasis of malignant melanoma. This is well reflected by polysomy 7, possibly accounting for an increased EGFR gene copy number.

Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer.

The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), HER2, HER3 and HER4 are involved in the pathogenesis of multiple human malignant neoplasias. However, their role in the carcinogenesis of basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) remains to be elucidated. In order to further define the role of these RTKs, 56 human skin tissue samples of normal skin, BCC and SCC were studied by conventional and differential and quantitative reverse transcriptase-polymerase chain reaction (rtPCR). EGFR and HER3 were predominantly expressed in the BCCs and SCCs, while HER2 was ubiquitously expressed. HER4 was not expressed in any sample. Since in vitro studies have provided compelling evidence that heterodimer formation of these receptors are associated with different signal transduction processes, coexpression patterns might be decisive for the induction and maintenance of a malignant phenotype. These results confirm this concept: isolated HER2 expression and EGFR/HER2 were predominantly found in normal skin, while HER2/HER3 and the triple expression of EGFR/HER2/HER3 were seen more frequently in the BCCs and SCCs compared with normal skin (50% and 40% compared with 26%, respectively). The activation of HER3, in addition to EGFR and HER2, might therefore be associated with the malignant phenotype. However, due to the small numbers in this study, further confirmation of the patterns is needed.

Interferon gamma in survivors of the Chernobyl power plant accident: new therapeutic option for radiation-induced fibrosis.

BACKGROUND: One of the remarkable clinical consequences of the Chernobyl accident was skin involvement, leading to extensive cutaneous fibrosis. Apart from surgery, no established treatment is available. METHODS: A group of survivors, working in or present at the accident site on April 26, 1986, and a few days thereafter, were examined, treated, and followed-up in 6-month intervals from September 1991 to November 1995. Eight individuals were identified as suffering from excessive cutaneous fibrosis. Skin thickness was measured with high-frequency (20 MHz) ultrasound in a clinically well-defined target skin lesion, in addition to histologic confirmation of radiation fibrosis. Interferon gamma was scheduled for all patients on a low-dose regimen (3 x 50 microg/week s.c.). In 2 patients, interferon was discontinued after the first injection, due to withdrawal of consent. In 6 patients, interferon was continued for 30 months, with 1 injection weekly for a further 6 months. Treatment was discontinued in November 1994. Four patients in the treated group and 1 of the 2 patients treated only once ("untreated patients") were reexamined 1 year later. RESULTS: In all individuals treated for 36 months, a significant (p < 0.005) reduction of radiation fibrosis could be determined, in contrast to a significant (p < 0.005) increase in the 2 untreated patients. Follow-up 1 year after discontinuation of the interferon treatment demonstrated significant (p < 0.005) recurrence of fibrosis. CONCLUSION: Low-dose interferon appears to be a safe and effective treatment of cutaneous radiation fibrosis following accidental exposure to high doses of ionizing radiation. Long-term supportive therapy may be required.

Are there good ways to give 'bad news'?

There has been considerable speculation about the inevitability of parental dissatisfaction with being informed about their child's disability. Mothers and fathers of 24 infants with a recently diagnosed disability were interviewed regarding their preferences for how to be told the "bad news." Qualitative analyses revealed nine themes of parental preferences for how to communicate difficult information. Parents affirmed communication themes previously discussed in the literature, such as being told early and together, and identified new ones, such as affective tone and physical contact with their baby. The importance of these themes is presented for this sample. Recommendations for how to present "bad news" can be concisely drawn from these findings. Results suggest that parental dissatisfaction with the process of telling is not inevitable.

Radiation lentigo. A distinct cutaneous lesion after accidental radiation exposure.

BACKGROUND: Accidental exposure of skin to ionizing radiation leads to long-term alterations such as fibrosis, keratosis, and teleangiectasias. Also, noncharacteristic hyperpigmentation and hypopigmentation may be noted. OBSERVATIONS: A distinct lesion is described on the calves of a white male survivor of the 1986 nuclear accident at Chernobyl, Ukraine. Several years after the accident at Chernobyl, characteristic pigmented macules developed in the areas of skin that had previously been exposed to ionizing radiation: there was a marked, sharply demarcated lentiginous hyperpigmentation of epidermal and basal keratinocytes and melanocytes, as well as an increase in the number of melanocytes. No cellular atypia was noted. CONCLUSIONS: This case demonstrates the potential of high single doses of ionizing radiation to induce pigmented lesions with similar clinical and histological features as they have been described after exposure to natural UV radiation or radiation from a tanning bed or sunlamp or after therapy with oral psoralen with long-wave UV-A radiation (PUVA), described as solar, tanning bed, and PUVA lentigines. The absence of cellular atypia may account for a favorable prognosis and enables clear distinction from more serious diagnoses such as lentigo maligna melanoma.

Parent-child interactions in families with alcoholic fathers.

Adolescent offspring (N = 121) of alcoholic, depressed, and nondistressed fathers were observed during problem-solving discussions with their fathers, mothers, and with both parents together. Assessments were conducted when parents were and were not drinking alcohol. Nondistressed father-child dyads differed from both clinical samples in showing higher rates of congeniality and problem solving, whereas the impact of alcohol consumption on father-child, mother-child, or triadic interactions was not related to diagnostic status of father. Results are discussed in terms of the nonspecific effects of parental disturbance on family relationships and reasons for the absence of alcoholism specific effects on parent-child interaction.

Soluble p185/her2 and S100 in yolk sac blood from human melanoma metastases xenotransplanted to chick embryo chorioallantoic membrane.

BACKGROUND: The chorionallantoic membrane (CAM) of the chick embryo has been used as an experimental model for studying tumor invasion and metastasis of human malignant melanoma. In search for a model to show graft-host-interactions in vivo, tumor markers in peripheral blood of the host were investigated. MATERIALS AND METHODS: Before collecting melanoma metastasis xenografts, blood samples were taken from CAM and a control group. S100 and sp185/her2 in peripheral blood were evaluated in a blinded manner. RESULTS: 23/28 samples deriving from successfully performed human melanoma metastasis CAM xenografts were positive for S100 versus 2/22 samples for sp185/her2. CONCLUSION: Regarding melanoma, in this model sp185/her2 gave no additional information. S100 levels corresponded to clinical and immunohistological findings concerning adherence of tumors and extravasation of human melanoma cells. Based on these data S100 levels in the peripheral blood could help to determine the effect of exogenous stimuli such as radiation and therapeutic agents on metastatisation of the xenografts.

S100 beta is a more reliable tumor marker in peripheral blood for patients with newly occurred melanoma metastases compared with MIA, albumin and lactate-dehydrogenase.

Lactate-dehydroxynase (LDH) has been described as a leading blood parameter in patients with melanoma metastases. However, recent data indicates that levels of S100 as well as melanoma inhibiting activity (MIA) in peripheral blood, correlate with melanoma progression. The aim of this study was to evaluate tumor markers S100, MIA, LDH and albumin in peripheral blood of 373 melanoma patients. 284 patients presented with in-situ or UICC stage I/II, and 89 with stage III/IV (54 tumor-free, 29 with newly occurred metastases). For newly occurred metastases, sensitivity was highest for S100 in peripheral blood (0.86), followed by MIA (0.80), LDH (0.48), and albumin (0.15). Specificity for albumin (0.99) and LDH (0.98) was higher than for S100 (0.91) and MIA (0.62). This data indicate that S100 in peripheral blood as compared to MIA, LDH and albumin appears to be the most appropriate tumor marker for newly occurred melanoma metastases.

Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma.

Apoptosis is an important cofactor in the pathogenesis of a plethora of malignancies. However, little is known about modulation of the expression of bcl gene family in melanocytic tumors. To determine the role of bcl-2, bcl-x and bax in melanocytic tumors we investigated the differential expression of these genes via RT-PCR in tissue samples from human benign nevi, primary melanomas and melanoma metastases in comparison with normal skin. Bcl-2 was strongly expressed in 14/16 metastases (87.5%), whereas only 7/13 primary melanomas (53%), 7/15 nevi (46%) and 7/16 normal tissue samples (43%) showed expression of bcl-2 (P < 0.05). There was a strong indication of a correlation between tumor thickness and bcl-2 expression in nodular malignant melanomas. Expression of bcl-x was found in 16/16 melanoma metastases (100%), 11/13 primary melanomas (84%), 12/15 nevi (80%) and 10/16 normal tissue samples (62%) (P < 0.05). Bcl-xL expression increased from primary melanoma to melanoma metastases, whereas bcl-xS showed a decreasing expression level during melanoma progression. No differences in bax expression were seen between melanoma metastases, primary melanoma, nevi and normal tissue. Immunohistochemical investigations of another 53 tissue samples showed similar results. Our results strongly indicate that bcl-2 and bcl-xL gene expression increases with progression of malignant melanoma. Bcl-2 and bcl-xL expression could reflect an increased malignant potential caused by an inhibition of apoptosis and growth advantage for metastatic melanoma cells.

Continuous central venous oxygen saturation monitoring under varying physiological conditions in an animal model.

We compared saturations from a paediatric central venous oximetry catheter with co-oximetry values with changes in drug infusions, intravascular blood volume and hypoxia in an animal model. Piglets (large white) were anaesthetised, intubated and mechanically ventilated. PediaSat oximetry catheters were placed in the superior vena cava via jugular vein cut-down and in the inferior vena cava percutaneously via the femoral vein. A carotid arterial catheter was placed via cut-down for blood sampling and pressure monitoring. Anaesthesia was maintained with continuous thiopentone and supplemental morphine. Haemodynamics (heart rate, mean arterial blood, central venous pressure), fibreoptic ScvO2 (ScvO2-inferior) from inferior vena cava, fibreoptic ScvO2 (ScvO2-superior) from superior vena cava and blood gas oximetry (ScvO2-co-ox) were measured simultaneously at predetermined intervals during increasing adrenaline and sodium nitroprusside infusions and during increasing hypoxia and hypovolaemia. There was good agreement of both superior vena cava and inferior vena cava ScvO2 catheters with co-oximetry during adrenaline and sodium nitroprusside infusions. During the hypoxia study there was good agreement between the co-oximeter to ScvO2-superior catheter but poor agreement with to the inferior vena cava catheter samples. In the hypovolaemic phase of the experiment there was good agreement between the measured co-oximetry value and ScvO2-superior catheter until the mean blood pressure reached 43 mmHg. The oximetry catheter is capable of identifying changes in ScvO2 under physiological conditions usually encountered in clinical medicine but was less accurate at the extremes of physiology and when placed in the inferior vena cava catheter especially during hypovolaemia and hypoxia.

Acute renal failure in children undergoing cardiopulmonary bypass.

OBJECTIVE: To investigate the incidence, implicating factors and outcome of acute renal failure after cardiopulmonary bypass in patients admitted to a paediatric intensive care unit. DESIGN: Prospective observational pilot study. SETTING: A 14 bed paediatric intensive care unit in a university affiliated, tertiary care referral children's hospital. PATIENTS: One hundred and one children (less than sixteen years of age) admitted to the Pediatric Intensive Care Unit following cardiopulmonary bypass between June 2003 and May 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PRISM-III score was calculated on admission. Baseline admission urea (mmol/L) and creatinine (micromol/L) serum levels and highest urea and creatinine levels were measured. Urine output (mL/kg/hour) and frusemide dose (mg/kg/day) were also noted. A baseline inotrope score was calculated on admission and the highest inotrope score was noted based on maximum infused doses of inotrope in the first 36 hours. The surgical procedure was used to determine a Jenkins score. Eleven (11%) children developed acute renal injury (doubling of creatinine), one child (1%) developed acute renal failure (tripling of creatinine) and one child died (1%). No child required dialysis for acute renal failure and none developed chronic renal impairment. Low cardiac output was the only significant risk factor identified for developing acute renal injury or failure. CONCLUSIONS: Acute renal injury is common and occurred in 11% of our children following congenital cardiac surgery, but acute renal failure requiring dialysis is uncommon.

Conceptualizing social support in families of children with special health needs.

The concept of social support is used increasingly to understand families and their functioning. While conceptualization of the support process is regrettably absent for much research on families, earlier models developed for examining social support of individuals can enlighten research on families. The history of the social support concept is presented along with an overview of current typologies of social support and models of how it impacts physical and mental health. Research on the social support of families with children with special needs is reviewed relative to these issues. Greater recognition of a comprehensive model of support is advocated. Recommendations are made for longitudinal research on temporal patterns of utilization and satisfaction with support, and for consideration of cultural contexts in interpreting social supports.

[Two superficially spreading malignant melanomas on nevus spilus]. / Zwei superfiziell spreitende maligne Melanome auf Naevus spilus.

A case of a 49-year-old patient with two superficial spreading melanomas arising from a naevus spilus is presented. Although opinions differ on the potential for malignant transformation in naevi spili, they should be carefully watched, and if changes are found these lesions should be subjected to histopathologic examination.