Associations of fatigue to work-related stress, mental and physical health in an employed community sample.

BACKGROUND: While work-related fatigue has become an issue of concern among European employees, the relationship between fatigue, depression and work-related stressors is far from clear. The purposes of this study were (1) to determine the associations of fatigue with work-related stressors, severe medical disease, health behavior and depression in the working population and (2) to determine the unique impact of work-related stressors on fatigue. METHODS: We used cross-sectional data of N = 7,930 working participants enrolled in the Gutenberg Health Study (GHS) from 2007 to 2012 filled out the Personal Burnout Scale (PBS) of the Copenhagen Psychosocial Questionnaire (COPSOQ), the PHQ-9, and a list of work-related stressors. RESULTS: A total of 27.5% reported increased fatigue, esp. women, younger persons with a lower social status and income, smokers, severely medically ill, previously and currently depressed participants. Fatigue was consistently associated with severe medical disease, health behavior and depression, which need to be taken into account as potential confounders when analyzing its relationship to work-related strains. Depression was consistently associated with work-related stressors. However, after statistically partialling out depression, fatigue was still significantly associated with work-related stress. CONCLUSIONS: Fatigue as an indicator of allostatic load is consistently associated with work-related stressors such as work overload after controlling for depression. The brief Personal Burn-out Scale is suitable for assessing work-related fatigue in the general population.

Coping patterns in special school staff: demographic and organizational factors.

BACKGROUND: Teachers' mental health is commonly discussed in organizational health studies, but studies in special schools are rare. Work-related coping and experience patterns (WCEPs) have been shown to be associated with mental health and intentions to leave. The influence of organizational factors on coping patterns has not been examined. AIMS: To assess the distribution of WCEPs in special school staff and to identify potential influencing factors. METHODS: We surveyed a sample of teachers and educational staff in 13 German special schools using the WCEP questionnaire and COPSOQ (Copenhagen Psychosocial Questionnaire). RESULTS: Of 245 teachers and 417 educational staff contacted, 114 teachers (47%) and 252 educational staff (60%) responded, an overall response rate of 55% (366/662). Coping patterns of special school staff were classified as unambitious (30%), excessively ambitious (7%), resigned (17%), healthy-ambitious (12%) or unclassifiable (34%). Furthermore we found several significant relations with demographic and organizational factors. For example, the resigned pattern is associated with age [Exp(B) 1.12; 95% CI 1.05-1.19], emotional demands [Exp(B) 1.07; 95% CI 1.01-1.12], work-family conflict [Exp(B) 1.07; 95% CI 1.03-1.10] and bullying [Exp(B) 1.04; 95% CI 1.00-1.08]. CONCLUSIONS: Since emotional and social factors are associated with risky (excessively ambitious or resigned) and unambitious coping patterns in special school teachers and educational staff, interventions should focus on them. Further research could explore causal relations and observe the development of coping styles over time.

Effects of an acute exposure to toluene on the DNA repair activity of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) in healthy subjects.

The structure and previous studies on the biotransformation of toluene lead to the suspicion that metabolites may be formed which preferentially react with strongly nucleophilic partners such as sulfhydryl groups of cysteines in proteins. Human 8-oxoguanine DNA glycosylase 1 removes the major oxidative DNA damage and possesses eight cysteines. Its potential inactivation may lead to accumulation of DNA damage by reactive oxygen species formed by exogenous agents or by ubiquitous endogenous processes. The goal of the present investigation was to study the in vivo effect in humans of an acute toluene exposure on hOGG1 activity. Twenty healthy, non-smoking males were exposed to 50 ppm toluene and to filtered air in an exposure chamber for 270 min, using a cross-over design. Before and 30 min after the end of exposure, blood samples were taken and toluene concentrations and the hOGG1 activity were measured. hOGG1 activity was determined in peripheral mononuclear blood cells. Thirty minutes after exposure to toluene, we found a median blood concentration of 0.25 mg toluene/l. Compared with the activity before exposure, upon exposure to toluene a statistically insignificant median increase of hOGG1 activity by +0.4% and upon exposure to air by +2.3% was determined. Thus, no reduction of the hOGG1 repair activity after acute exposure to 50 ppm toluene was observed.

Focal femoral osteolysis after revision hip replacement with a cannulated, hydroxyapatite-coated long-stemmed femoral component: a new route for particulate wear debris.

We describe a case of symptomatic focal femoral osteolysis around a screw hole distal to the hydroxyapatite-coated portion of a cannulated femoral component in a revision hip replacement. No locking screw had been inserted into this, the most proximal of the three distal holes for locking screws. The presence of polyethylene wear debris in the tissue excised from the lesion suggested that it had passed through the cannulated portion of the stem and out of the proximal unfilled distal locking hole, initiating an osteolytic reaction in an otherwise well-fixed stem. This case highlights an important design characteristic of such cannulated, uncemented femoral components. We recommend that the proximal aperture of these cannulated stems be occluded at implantation.

Leukocyte transglutaminase 2 expression limits atherosclerotic lesion size.

OBJECTIVE: Transglutaminase 2 (TG2), a broadly expressed regulator of protein cross-linking, wound healing, and tissue fibrosis, mediates apoptotic cell ingestion and transforming growth factor-beta release by macrophages and thereby can limit leukocyte-mediated inflammation. In atherosclerosis, oxidative stress and accumulation of unesterified cholesterol stimulate atherosclerotic lesion cell apoptosis. Cell death in advanced atherosclerotic lesions promotes lesion expansion and vulnerable plaques prone to rupture. Hence, we tested the hypothesis that leukocyte TG2 expression limits atherosclerosis. METHODS AND RESULTS: We transplanted TG2-/- or TG2+/+ bone marrow into lethally irradiated low-density lipoprotein receptor (LDLR)-/- mice and evaluated diet-induced atherosclerosis after 16 weeks. We subsequently studied cultured TG2-/- and congenic TG2+/+ mouse macrophages for selected atherogenesis regulatory functions. Atherosclerotic aortic valve lesions in LDLR-/- recipients of TG2-/- bone marrow were larger and more subintimal lesional macrophage penetration than in TG2+/+ marrow recipients. Lesion intimal TG2 expression appeared robust in TG2+/+ but not TG2-/- marrow recipients. Cultured TG2-/- macrophages demonstrated diminished phagocytosis of apoptotic leukocytes, unaltered endocytosis, and degradation of oxidized LDL but decreased retinoic acid induction of the reverse cholesterol transport and apoptotic cell uptake mediator ABCA1. CONCLUSIONS: We conclude that macrophage TG2 expression promotes both apoptotic cell clearance and ABCA1 expression in vitro and limits atherosclerotic lesion size in vivo.

[Socio-legal evaluation of UV-induced skin tumors]. / Sozialrechtliche Bewertung UV-induzierter Hauttumoren.

The present work deals with insurance and legal issues on the prevention of UV-induced skin tumors. We are convinced that squamous cell carcinoma of the skin fulfils the socio-legally required conditions according to paragraph 9 Abs. 2 SGB VII for approval as an occupational disease. In malignant melanoma evidence also exists for its induction through UV exposure and increased risk for occupational UV exposure, thus, making approval as an occupational disease possible in individual cases. According to the currently available medical knowledge on basal cell carcinoma and malignant melanoma, there is no sufficient basis for the approval of these as occupational disorders. Therefore, significant actions should not only be taken in the context of primary disease prevention, but also within the framework of secondary and tertiary disease prevention in occupational UV exposure.

Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival?

BACKGROUND: Patients with distant melanoma metastases have median survivals of 4 to 8 months. Previous studies have demonstrated improved survival after complete resection of pulmonary and hollow viscus gastrointestinal metastases. We hypothesized that patients with metastatic disease to intra-abdominal solid organs might also benefit from complete surgical resection. METHODS: A prospectively acquired database identified patients treated for melanoma metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of these from 1971 to 2000. The primary intervention was complete or incomplete surgical resection of intra-abdominal solid-organ metastases, and the main outcome measure was postoperative overall survival (OS). Disease-free survival (DFS) was a secondary outcome measure. RESULTS: Sixty patients underwent adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was significantly improved after complete versus incomplete resections, but median OS after complete resection was not significantly different for single-site versus synchronous multisite metastases. The 5-year survival in the group after complete resection was 24%, whereas in the incomplete resection group, there were no 5-year survivors. Median DFS after complete resection was 15 months. Of note, the 2-year DFS after complete resection was 53% for synchronous multi-site metastases versus 26% for single-site metastases. CONCLUSIONS: In highly selected patients with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at complete surgical resection may improve OS. It is important that the number of metastatic sites does not seem to affect the OS after complete resection.

Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding.

alpha4 integrins are essential for embryogenesis, hematopoiesis, inflammation, and immune response possibly because alpha4 integrins have distinct signaling properties from other integrins. Specifically, the alpha4 cytoplasmic domain binds tightly to paxillin, a signaling adaptor protein, leading to increased cell migration and an altered cytoskeletal organization that results in reduced cell spreading. The alpha4 tail contains potential phosphorylation sites clustered in its core paxillin binding region. We now report that the alpha4 tail is phosphorylated in vitro and in vivo. Furthermore, Ser(988) is a major phosphorylation site. Using antibodies specific for Ser(988)-phosphorylated alpha4, we found the stoichiometry of alpha4 phosphorylation varied in different cells. However, >60% of alpha4 was phosphorylated in Jurkat T cells. Phosphorylation at Ser(988) blocked paxillin binding to the alpha4 tail. A phosphorylation-mimicking mutant of alpha4 (alpha4S988D) blocked paxillin binding and reversed the inhibitory effect of alpha4 on cell spreading. Consequently, alpha4 phosphorylation is a biochemical mechanism to modulate paxillin binding to alpha4 integrins with consequent regulation of alpha4 integrin-dependent cellular functions.

Surgical resection for metastatic melanoma to the liver: the John Wayne Cancer Institute and Sydney Melanoma Unit experience.

HYPOTHESIS: Metastatic melanoma to the liver is not incurable; complete surgical resection can achieve long-term survival in selected patients. BACKGROUND: Metastases to the liver are diagnosed in 10% to 20% of patients with American Joint Committee on Cancer stage IV melanoma. Surgical resection has not been generally accepted as a therapeutic option, as most patients will have other sites of disease that limit their survival to a median of only 4 to 6 months. However, there is little information on outcomes following resection in those patients with disease limited to the liver. PATIENTS AND METHODS: Review of the prospective melanoma databases at the John Wayne Cancer Institute, Santa Monica, Calif, and the Sydney Melanoma Unit, Sydney, Australia, identified 1750 patients with hepatic metastases, of whom 34 (2%) underwent exploration with intent to resect the metastases. Prognostic factors within the group of patients who underwent resection were examined by univariate and multivariate analysis, and median disease-free survival (DFS) and overall survival (OS) were calculated. RESULTS: Of 34 patients undergoing exploratory celiotomy, 24 (71%) underwent hepatic resection and 10 (29%) underwent exploration but not resection. Eighteen patients (75%) underwent complete surgical resection, while the remaining 6 underwent palliative or debulking procedures with incomplete resection. The operative resections included lobectomy (n=14), segmentectomy (4), nonanatomic resection (5), and extended lobectomy (1). The median number of resected lesions was 1, and median lesion size was 5 cm (range, 0.7-22 cm). The median disease-free interval between initial diagnosis of melanoma and development of hepatic metastases was 58 months (range, 0-264 months). Median DFS and OS estimates in the 24 patients who underwent surgical resection were 12 months (range, 0-147 months) and 28 months (range, 2-147 months), respectively. Five-year DFS and OS in this group were 12% and 29%. Macroscopically, complete resection of disease (P =.001) and histologically negative resection margins (P =.03) significantly improved DFS by univariate analysis. Patients rendered surgically free of disease also tended to have improved OS (P =.06). Median OS was 28 months for patients who underwent surgical resection compared with 4 months for patients who underwent exploration only (P<.001). CONCLUSIONS: Resection of metastatic melanoma to the liver may improve DFS and OS in selected patients, similar to resection of other metastatic sites. Therefore, patients with limited metastatic sites, including the liver, who can be rendered free of disease should be considered for complete surgical resection, as their prognosis is otherwise dismal.

The affinity of integrin alpha(4)beta(1) governs lymphocyte migration.

The interaction of integrin alpha(4)beta(1) with endothelial VCAM-1 controls the trafficking of lymphocytes from blood into peripheral tissues. Cells actively regulate the affinity of alpha(4)beta(1) for VCAM-1 (activation). To investigate the biological function of alpha(4)beta(1) activation, we isolated Jurkat T cell lines with defective alpha(4)beta(1) activation. Using these cells, we found that alpha(4)beta(1)-stimulated alpha(L)beta(2)-dependent cell migration was dramatically reduced in cells with defects in alpha(4)beta(1) activation. These cells required 20 times more VCAM-1 to promote alpha(L)beta(2)-dependent cell migration. This defect was at the level of alpha(4)beta(1) affinity as an activating alpha(4)beta(1) Ab rescued alpha(4)beta(1)-stimulated alpha(L)beta(2)-dependent migration. In contrast, migration of alpha(4)beta(1) activation-defective cells on VCAM-1 alone was enhanced at higher VCAM-1 densities. Thus, alpha(4)beta(1) activation determines a set point or threshold at which VCAM-1 can regulate alpha(L)beta(2)-dependent as well as alpha(4)beta(1)-dependent cell migration. Changes in this set point may specify preferred anatomical sites of integrin-dependent leukocyte emigration from the bloodstream.

Laparoscopic radiofrequency ablation of unresectable hepatic malignancies. A phase 2 trial.

BACKGROUND: Radiofrequency ablation (RFA) of hepatic malignancies has been performed successfully via a percutaneous route or at laparotomy. We analyzed the efficacy and utility of laparoscopic intraoperative ultrasound and RFA in patients with unresectable hepatic malignancies. METHODS: Between November 1997 and November 1999, 27 patients with unresectable hepatic malignancies and no evidence of extrahepatic disease were entered in a phase 2 trial of laparoscopic intraoperative ultrasound and RFA. Real-time ultrasonography was used to guide RFA, and lesions were ablated at a temperature of 100 degrees C for 10 min. Overlapping ablations were performed for larger lesions. RESULTS: Additional tumors were identified in 10 (37%) of the 27 study patients by laparoscopy and laparoscopic intraoperative ultrasound despite extensive preoperative imaging. Radiofrequency ablation of 85 hepatic tumors yielded no mortality and only one case of postoperative bleeding. During a mean follow-up period of 14 months, four tumors (4.7%) locally recurred. Of the 27 patients, 11 (41%) remain free of disease at this writing; (22%) are alive with disease; and 10 (37%) have died with disease. CONCLUSION: Laparoscopic RFA and intraoperative ultrasound constitute a safe and accurate method for ablation of unresectable hepatic tumors.

Long-term management and outcome of parathyroidectomy for sporadic primary multiple-gland disease.

HYPOTHESIS: For a specific subset of patients with sporadic primary multiple-gland parathyroid disease, subtotal parathyroidectomy results in long-term normocalcemia in the majority of patients, with a minimal complication rate. DESIGN: Retrospective analysis of outcomes in patients undergoing parathyroidectomy performed by a single surgeon (A.E.G.) between 1984 and 1999. SETTING: A multidisciplinary endocrine service based at a tertiary referral center. PATIENTS: Patients undergoing subtotal parathyroidectomy for primary hyperparathyroidism due to sporadic multiple-gland disease identified from a single surgeon's operative records (A.E.G.). MAIN OUTCOME MEASURES: Data analyzed included demographic factors, operative and pathologic findings, and postoperative and long-term clinical and laboratory results, including calcium and intact parathyroid hormone levels. RESULTS: Of 379 patients undergoing parathyroidectomy for hyperparathyroidism between 1984 and 1999, 49 (13%) had sporadic multiple-gland disease. Median preoperative calcium and intact parathyroid hormone (iPTH) levels were 2.7 mmol/L (10.8 mg/dL) and 11.79 pmol/L, respectively. Postoperative calcium and iPTH levels were available in 39 patients, and median values were 2.28 mmol/L (9.1 mg/dL) and 2.84 pmol/L, respectively. Long-term follow-up was available for 36 patients (73%), and duration ranged from 6 to 180 months (median, 44 months). Median calcium and iPTH levels at follow-up were 2.3 mmol/L (9.2 mg/dL) and 3.26 pmol/L, respectively, with 3 (8%) of 36 patients having evidence of persistent or recurrent hyperparathyroidism. No patient had biochemical evidence of hypoparathyroidism at long-term follow-up. Five patients (14%) had persistent elevated iPTH levels (range, 8.11-10.95 pmol/L) and normal calcium levels. CONCLUSIONS: Subtotal parathyroidectomy for sporadic primary multiple-gland disease resulted in a long-term normocalcemia rate of 92%, with minimal complications. Selective subtotal parathyroidectomy can yield excellent long-term results in patients with multiple-gland disease.

No effects of pulsed radio frequency electromagnetic fields on melatonin, cortisol, and selected markers of the immune system in man.

There is growing public concern that radio frequency electromagnetic fields may have adverse biological effects. In the present study eight healthy male students were tested to see whether or not radio frequency electromagnetic fields as used in modern digital wireless telecommunication (GSM standard) have noticeable effects on salivary melatonin, cortisol, neopterin, and immunoglobulin A (sIgA) levels during and several hours after exposure. In a specifically designed, shielded experimental chamber, the circularly polarized electromagnetic field applied was transmitted by an antenna positioned 10 cm behind the head of upright sitting test persons. The carrier frequency of 900 MHz was pulsed with 217 Hz (average power flux density 1 W/m2). In double blind trials, each test person underwent a total of 20 randomly allotted 4 hour periods of exposure and sham exposure, equally distributed at day and night. The results obtained show that the salivary concentrations of melatonin, cortisol, neopterin and sIgA did not differ significantly between exposure and sham exposure.

Increased filamin binding to beta-integrin cytoplasmic domains inhibits cell migration.

Multicellular animal development depends on integrins. These adhesion receptors link to the actin cytoskeleton, transmitting biochemical signals and force during cell migration and interactions with the extracellular matrix. Many integrin-cytoskeleton connections are formed by filamins and talin. The beta7 integrin tail binds strongly to filamin and supports less migration, fibronectin matrix assembly and focal adhesion formation than either the beta1D tail, which binds strongly to talin, or the beta1A tail, which binds modestly to both filamin and talin. To probe the role of filamin binding, we mapped the filamin-binding site of integrin tails and identified amino acid substitutions that led to selective loss of filamin binding to the beta7 tail and gain of filamin binding to the beta1A tail. These changes affected cell migration and membrane protrusions but not fibronectin matrix assembly or focal adhesion formation. Thus, tight filamin binding restricts integrin-dependent cell migration by inhibiting transient membrane protrusion and cell polarization.

Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5-fluorouracil.

Most colorectal cancers metastatic to the liver are resistant to chemotherapy and are not amenable to surgical resection. This study evaluated our 6-year experience (July 1992-July 1998) in treating patients with unresectable hepatic colorectal metastases refractory to systemic 5-fluorouracil (5-FU). One hundred fifty-three patients underwent cryosurgical ablation (CSA) of 5-FU-resistant hepatic metastases. The patients then received either hepatic arterial floxuridine (FUDR), systemic CPT-11, or no postoperative adjuvant chemotherapy. Number, size, and location of hepatic metastases, carcinoembryonic antigen (CEA) levels, and type of postoperative treatment were analyzed. One to 15 lesions were frozen (median number, 3; median size, 6 cm), for a total of 73 synchronous and 80 metachronous lesions. Overall median survival was 28.4 months from the date of diagnosis of liver metastases and 16.1 months from the time of CSA. After cryosurgery alone, median survival was 13 months, which was significantly shorter than the post-CSA survival of 23.6 months with adjuvant CPT-11 and 21.2 months with hepatic FUDR (P = 0.007). Predictors of survival included preoperative CEA, postoperative reduction in CEA, and adjuvant chemotherapy (P < 0.05). Neither size, number of lesions, nor tumor location impacted survival. At a median follow-up of 13 months, 67% of patients have recurred (35% hepatic, 16% extrahepatic, and 49% both). Twenty percent of the recurrences were in the lobe of the CSA site. The 25 patients who underwent a second CSA had a median survival of 28.4 months from CSA and 40 months from the date of diagnosis of liver metastases. These data indicate that CSA offers an effective alternative for unresectable patients resistant to 5-FU. Systemic CPT-11 or regional FUDR may further prolong survival after CSA.

Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications.

BACKGROUND: Radiofrequency ablation (RFA) is increasingly used for the local destruction of unresectable hepatic malignancies. There is little information on its optimal approach or potential complications. METHODS: Since late 1997, we have undertaken 91 RFA procedures to ablate 231 unresectable primary or metastatic liver tumors in 84 patients. RFA was performed via celiotomy (n = 39), laparoscopy (n = 27), or a percutaneous approach (n = 25). Patients were followed with spiral computed tomographic (CT) scans at 1 to 2 weeks postprocedure and then every 3 months for 2 years. RESULTS: Intraoperative ultrasound (IOUS) detected intrahepatic disease not evident on the preoperative scans of 25 of 66 patients (38%) undergoing RFA via celiotomy or laparoscopy. In 38 of 84 patients (45%), RFA was combined with resection or cryosurgical ablation (CSA), or both. RFA was used to treat an average of 2.8 lesions per patient, and the median size of treated lesions was 2 cm (range, 0.3-9 cm). The average hospital stay was 3.6 days overall (1.8 days for percutaneous and laparoscopic cases). Ten patients underwent a second RFA procedure (sequential ablations) and, in one case, a third RFA procedure for large (one patient), progressive (seven patients), and/or recurrent (three patients) lesions. Seven (8%) patients had complications: one skin burn; one postoperative hemorrhage; two simple hepatic abscesses; one hepatic abscess associated with diaphragmatic heat necrosis following sequential percutaneous ablations of a large lesion; one postoperative myocardial infarction; and one liver failure. There were three deaths, one (1%) of which was directly related to the RFA procedure. Three of the complications, including one RFA-related death, occurred after percutaneous RFA. At a median follow-up of 9 months (range, 1-27 months), 15 patients (18%) had recurrences at an RFA site, and 36 patients (43%) remained clinically free of disease. CONCLUSIONS: Celiotomy or laparoscopic approaches are preferred for RFA because they allow IOUS, which may demonstrate occult hepatic disease. Operative RFA also allows concomitant resection, CSA, or placement of a hepatic artery infusion pump, and isolation of the liver from adjacent organs. Percutaneous RFA should be reserved for patients at high risk for anesthesia, those with recurrent or progressive lesions, and those with smaller lesions sufficiently isolated from adjacent organs. Complications may be minimized when these approaches are applied selectively.

Changes in cellular proliferation rate of lymphocytes after long-distance flights as a possible risk for patients with HIV-infection.

OBJECTIVES: Several studies showed that long-distance flights can influence cellular immunity. This might be due to a cortisol- and catecholamin- induced change in immunity with an impairment of T-lymphocyte dependent cellular immunity and an enhancement of B-lymphocyte dependent humoral immunity. Similar results can be found in patients with HIV. It is also known that progress of this disease and affection of T-helper-cells by the virus are induced by stimulation of the immune system, a phenomenon that also occurs during long distance flights. Therefore, a possible interaction between long-distance flights and the progression of HIV-infection should be discussed. METHODS: Cell cultures of 22 subjects after long-distance flights with and without rapid time zone shifts and of 16 patients with HIV (stage 2 3) were investigated. Mononuclear blood cells were stimulated with different lectins in culture and proliferation was measured by incorporation of bromodesoxyuridine. Moreover, all cultures were titrated with chromate concentrations between 0 to 700 ng/ml to measure the tolerance of the cells against chromate (VI) in vitro as a marker of the functional efficiency of the cellular part of the immune system. Maximal proliferation rate and tolerance against chromate were compared in both groups. RESULTS: After long distance flights tolerance against chromate decreased significantly during the first 24 h after flight. After 48 h levels were similar to those 1 week after flights. The decrease was similar to the results found in the stage 2 group of HIV-patients, but by far less to the decrease in stage 3 patients. Maximal proliferation rate dropped significantly during the second day after arrival compared to 1-week control values. CONCLUSION: Changes in the cellular immune system in healthy subjects after long-distance flights have been similar to the results of patients with stage 2 of HIV-infection. Mechanisms of changes in both groups are comparable in influencing T-cell-induced immunity. This could point to an additive effect on cellular immunity of HIV-patients by long distance-flights. Rosen neopterin concentrations and increases of apoptotic T-cells in both groups support this assumption. Therefore, further studies are urgently needed to investigate the interactions between HIV-infection and long-distance flights.

Principles of sentinel lymph node identification: background and clinical implications.

The management of clinically negative regional lymph nodes in early-stage melanoma has been controversial for many years. While some advocate wide excision of the primary with elective node dissection (ELND), others recommend excision of the primary alone and therapeutic node dissection (TLND) for recurrences in the nodal basin. ELND is based on the concept that metastases occur by passage of the tumor from the primary to the regional nodes and distant sites, in which case early dissection of regional nodes will disrupt metastatic progression and prevent the spread of disease. Advocates of the "wait and watch" approach suggest that regional node metastases are markers for disease progression and that distant disease can occur without node metastases. Four randomized prospective studies comparing ELND and TLND have not demonstrated overall survival advantage for ELND, but suggest that patients with early regional metastases may benefit from ELND. As an alternative, Morton et al., from UCLA and the John Wayne Cancer Institute, devised intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL). These minimally invasive operative procedures allow identification of the first and key (sentinel) lymph node (SN). The technique accurately maps the lymphatics by lymphoscintigraphy, and vital blue dye leads the surgeon to the SN. The pathologist then concentrates on seeking metastases in the nodes most likely to contain metastases. Patients with tumor-positive SN undergo completion lymph node dissection (CLND), while those without SN metastases avoid the complications and costs associated with this procedure. Morton et al., in a report on their initial experience of LM/SL, performed CLND in all cases regardless of SN tumor status and demonstrated the precise staging capacity of the procedure. Since this initial report, numerous studies have validated the accuracy and low morbidity of the procedure. Each center must master a learning phase. The procedure is dependent on the close cooperation of nuclear medicine physicians, surgeons, and pathologists. While LM/SL is now almost standard practice in the US, the results of clinical trials are awaited to determine whether LM/SL can replace ELND and TLND in the management of early-stage melanoma.