Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

BACKGROUND: Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. OBJECTIVES: To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. METHODS: Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. RESULTS: Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. CONCLUSIONS: Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.

Patients with soft tissue sarcoma comprise a higher probability of comorbidities than cancer-free individuals. A secondary data analysis.

Soft tissue sarcoma comprises a heterogeneous group of solid malignant tumours. Comorbidities are important prognostic factors for survival and adversely impact quality of life. We examined the complex relationship between soft tissue sarcoma and comorbidities over time in a large population-based sample. The study uses routine data from the German statutory healthcare system (n = 2,615,865). Case identification of soft tissue sarcoma and comorbid diseases was based on ICD-10 codes and diagnostic modifiers. Uni- and multivariate regression models were used to obtain risk estimates for chronic somatic and mental comorbidities in soft tissue sarcoma patients compared to a cancer-free control group. At diagnosis, patients with soft tissue sarcoma were significantly more likely to be affected with prevalent bronchial asthma, ≥1 cardiovascular risk factor (hypertension, angina pectoris, heart failure, peripheral arterial disease and thrombosis), back pain, depression, anxiety disorder and adjustment disorder than cancer-free controls. During the course of disease, sarcoma patients were at a significantly higher risk to develop incident depression, anxiety disorder and adjustment disorder. Comorbidities need to be considered in clinical decision making regarding the treatment of soft tissue sarcoma patients. Psycho-oncological treatment should be incorporated into medical care of patients with sarcoma.

Effects of the German skin cancer screening programme on melanoma incidence and indicators of disease severity.

BACKGROUND: In Germany a nationwide melanoma screening programme for adults aged ≥ 35 years was introduced in July 2008. Evidence on utilization and effects is limited. OBJECTIVES: To examine the uptake and effects of the German nationwide screening programme. METHODS: This analysis is based on pseudonymized outpatient routine data of a German health insurance company covering data of > 2 million individuals from Saxony for the years 2005-2012. Cases of melanoma and nonmelanoma skin cancer (NMSC) were identified using an algorithm based on the International Classification of Diseases, 10th Revision. Cross-sectional and longitudinal analyses were applied to determine the utilization of the screening programme and effects on skin cancer incidence and disease severity as a proxy for prognosis. RESULTS: Overall, 38·0% of eligible persons (≥ 35 years) were screened at least once between July 2008 and December 2012. The annual participation rate was 12·4%. Out of 533 393 persons screened, melanoma and NMSC were diagnosed in 0·3% and 2·5%, respectively. The 6-month melanoma incidence per 100 000 insured persons decreased from 12·8 before screening introduction (January to June 2008) to 10·2 after introduction (July to December 2008). NMSC incidence increased from 173·8 to 175·5 per 100 000. The numbers of screening participants receiving interferon alpha and/or being diagnosed with lymph node and/or distant metastasis (8·6%, 5·9%, 1·5%, respectively) were lower than in nonparticipants (11·2%, 8·5%, 3·5%). These differences were not significant. CONCLUSIONS: The results suggest that the introduction of a generic skin cancer screening programme in Germany was not associated with significant changes in incidence. No firm conclusions regarding the effects of skin cancer screening on prognosis can be drawn. Longer follow-up and linkage with clinical registry data are necessary to clarify the effect of screening participation on incidence and prognosis.

A systematic review of the outcomes reported in multimodal pain therapy for chronic pain.

BACKGROUND AND OBJECTIVE: There are no recommendations provided for the outcome domains of chronic pain that should be explicitly considered in each clinical trial to describe the efficacy and effectiveness of multimodal pain therapy (MPT). Our aims were to summarize all reported outcome domains in studies assessing the effects of MPT for chronic pain, and to subsequently inform a consensus-based development of a core outcome set of domains in this field. DATABASE AND DATA TREATMENT: Medline, Embase and AMED were searched for studies reporting on chronic pain for at least 3 months that applied MPT and investigated outcome domains. All reported outcome domains were extracted from eligible articles. The patient-reported outcome measurement information system (PROMIS) was applied for conceptual classification. RESULTS: From 3626 potentially relevant titles, 70 studies were included. The median and maximal numbers of outcome domains were 8 and 34, respectively. Although most studies (n = 45/70) assessed a combination of all three core health areas, i.e. physical, mental and social health, there was great variation in the specific domains chosen to address these core health areas. No outcome domain was measured consistently in all studies. After selection of all outcome domains which were reported in at least 10% of all studies included, we identified 14 different outcome domains, mostly operationalized through the domains pain intensity (n = 56/70) and depressive symptoms (n = 42/70). CONCLUSIONS: The current lack of standardization of outcome domains in MPT studies hinders to readily compare interventions from different trials and is a barrier towards evidence-based decision making. Based on these results, the development of a core outcome set of domains for MPT has been initiated.

12 S small nuclear ribonucleoprotein-associated acidic-and pyrimidine-specific endoribonuclease from calf thymus and L5178y cells.

12 S ribonucleoprotein (RNP) particles were separated from a 45 S RNP complex (Bachmann, M., Zahn, R. K. and Müller, W. E. G. (1983) J. Biol. Chem. 258, 7033-7040) isolated from calf thymus and L5178y cells. The particles were determined to be associated with an acidic endoribonuclease (pI 4.1; pH optimum 6.2). the enzyme requires Mg2+ and is sensitively inhibited by higher NaCl concentrations. The nuclease specifically degrades poly(U) and poly(C) in an endonucleolytic manner; the end-products are 3'-UMP (85%) and 2',3'-cyclic UMP (12%). Poly(A) strongly inhibits the pI 4.1 endoribonuclease activity. The Michaelis constant (for poly(U)) was determined as 82 microM and the maximal reaction velocity was 0.54 mumol/microgram per h. The endoribonuclease is distinguished from the known pyrimidine-specific ribonucleases (pancreatic ribonuclease and endoribonuclease VII) by further criteria, e.g., resistance to thiol reagents, inhibition by EDTA, Mg2+ requirement, pI and pH optimum. Using the techniques of counterimmunoelectrophoresis and immunoaffinity column chromatography it was shown that the pI 4.1 endoribonuclease-associated 12 S RNP particles display antigenicity to anti-Sm and anti-(U1)-RNP antibodies. An RNA component, isolated from the 12 S-45 S hypercomplex, was identified as U1-snRNA.

Recent advances in the morphology of myositis.

Myositis in man may be divided into infectious and non-infectious forms. The myopathologist more often deals with the latter forms which comprise dermatomyositis/polymyositis, inclusion body myositis, mixed connective tissue disease/collagenoses, and granulomatous myopathies. Modern morphological techniques as enzyme-histochemistry, electron microscopy, immunohistology, and morphometry are of different value in various forms of myositis, but are often indispensable techniques in up-to-date diagnostic work up of a myositis.

[L-tryptophan-associated chronic eosinophilia-myalgia syndrome treated with cyclosporin]. / L-Tryptophan-assoziiertes chronisches Eosinophilie-Myalgie-Syndrom behandelt mit Ciclosporin.

After 2 weeks of ingestion of 130 g L-Tryptophan a 52 year old female develops an Eosinophilia Myalgia Syndrome with acute onset of deep venous thrombosis of forearm and possible initial cardiac manifestation featuring intermittent sinustachykardia. This is followed by a severe chronic disease (follow-up 15 months) with diffuse scleroderma and sensomotoric polyneuropathia. The deep muscle biopsy-specimen shows mononuclear infiltration of fascia and interstitial myositis with rare eosinophils. A blood eosinophilia (900/ul) occurs only in the initial acute onset of the illness. Plasma level of Kynurenine is significantly high (4000 pmol/ml), collagenneosynthesis is activated (Procollagen type III peptid 0.927 U/ml). No significant clinical improvement was seen with Acathioprine (100 mg/d) and Prednisolon (40-60 mg/d), after treatment with Ciclosporin scleroderma regresses completely, polyneuropathy is persisting.

Pathomechanism of brain oedema in experimental intracerebral mass haemorrhage.

The prognosis of intracerebral haemorrhage is extremely poor when arterial hypertension is present. We investigated elastance of the brain tissue and brain hydraulic conductivity in normotensive (MAP approximately 110 mmHg) and hypertensive (MAP approximately 170 mmHg/angiotensin infusion) cats following a stereotactically produced intracerebral haemorrhage. For 12 hours after the onset of haemorrhage we registered the course of ICP, subsequently the water content of cortex, white matter and basal ganglia as well as the interstitial concentration of serum proteins in the corresponding regions were determined (Evans-Blue, immunofluorescence). Hypertension was associated with a slight increase in ICP and tissue water content but with a 3 fold more elevated content of interstitial serum proteins. Immunofluorescence analysis showed the oedema in the hypertensive group to be vasogenic in nature and in the normotensive cats to originate from the haematoma itself. The generally poor outcome of intracerebral mass haemorrhage in hypertensive subjects could be ascribed to the nature of the concomitant brain oedema, as described in this study.

[Antimitochondrial antibodies against the M2-antigen with immune vasculitis and discoid lupus erythematosus without proof of liver disease]. / Antimitochondriale Antikörper gegen das M2-Antigen mit Immunvaskulitis und diskoidem Lupus erythematodes ohne Nachweis einer Lebererkrankung.

We have seen a 54-year-old patient with discoid lupus erythematosus and biopsy-proven vasculitis with granular deposits of complement and immunoglobulins in small subcutaneous vessels of clinically normal skin. Serologically, neither antinuclear antibodies nor antibodies against double-stranded DNA, Sm-Ag nor ribonucleoprotein could be demonstrated whereas the immunofluorescence test for antimitochondrial antibodies was positive during the whole observation period of 15 months. The further characterisation of the antimitochondrial antibodies by a newly described radio-immuno-assay demonstrated that the antibodies are directed against the primary biliary cirrhosis specific M2-antigen of mitochondria. So far, the patient, however, does not show any clinical or laboratory signs of primary biliary cirrhosis and a liver biopsy showed no evidence of that disease. It is discussed whether there is a coincidence of different autoimmunopathies or if the findings are symptoms of a single disease. Follow-up study might solve this open question.

Association of a polyuridylate-specific endoribonuclease with small nuclear ribonucleo-proteins which had been isolated by affinity chromatography using antibodies from a patient with systemic lupus erythematosus.

Immunoglobulins, containing antibodies against U1-snRNP, have been prepared from a patient with systemic lupus erythematosus. After coupling these antibodies to a Sepharose matrix, U-snRNPs have been isolated and purified from rat liver nuclei by use of immunoaffinity chromatography. The resulting RNPs had the typical protein pattern of U-sn RNPs and a sedimentation coefficient of 12 S. The U-snRNP preparation was associated with an endoribonuclease which required Mg2+ for optimal activity. The enzyme, with an pH optimum of 6.2, degraded only poly(U). Other single-stranded polyribo- and polydeoxyribonucleotides, tRNA, as well as double-stranded RNA and DNA were not digested. The products of a terminal digestion are (U)6-12 with 3'-OH and 5'-P termini. The possible involvement of this endoribonuclease in the splicing of hnRNA is discussed.

Rare association of herpes simplex virus IgM-specific antibodies and Guillain-Barré syndrome successfully treated with plasma exchange and immunosuppression.

Herpes simplex virus (HSV) has been associated with various neurological disorders. In contrast, HSV infection is very rarely found in acute polyneuroradiculitis. In this report, a patient is described with a severe course of Guillain-Barr¿ syndrome (GBS). HSV IgM-specific antibodies and a rise of complement-fixation antibodies were detected. During the acute phase of neurologic syndrome, a nerve biopsy showed myelin damage and IgM deposits on the inner layer of the perineurium. Plasma exchange, in combination with immunosuppression, was successfully applied as a treatment in the relapsing course of GBS. Finally, after recovery, HSV-specific IgM antibodies disappeared.

[Systemic lupus erythematosus. Brown-Sequard syndrome, spinal ataxia and peripheral polyneuropathy as the sole manifestations]. / Systemischer Lupus erythematodes. Brown-Séquard-Syndrome, spinale Ataxie und periphere Polyneuropathie als einzige Manifestationen.

Neurologic manifestations were the sole symptoms of disease in three patients with systemic lupus erythematodes (SLE): one case presented with Brown-Séquard's syndrome, a second with spinal ataxia and polyneuropathy, and a third with polyneuropathy. In all three patients there was a considerable delay in making the diagnosis after onset of neurological symptoms. The diagnosis was established either by demonstration of antinuclear antibodies in combination with antibodies against dsDNA or by the demonstration of antibodies against dsDNA alone. In two patients perivascular deposits of IgG and C3 were seen in skin-muscle biopsies from the calf region.

A case of Sjögren's syndrome with severe anemia due to myelitis.

An unusual case of Sjögren's syndrome presenting with severe anemia as the predominant clinical feature is described. Histological examination of a bone marrow biopsy specimen demonstrated that the patient's anemia was caused by myelitis and vasculitis of the small intraosseous vessels. Our report might stimulate a more thorough investigation of bone marrow in patients with connective tissue diseases and anemia.

Nodular nonsuppurative panniculitis in association with primary biliary cirrhosis and Hashimoto's thyroiditis.

Recurrent episodes of livid, painful, subcutaneous nodules on both lower extremities with consecutive soft tissue atrophy developed in a 57-year-old woman with previously undiagnosed primary biliary cirrhosis (PBC) and Hashimoto's thyroiditis. Histological examination of a biopsy taken from an active area of the skin showed nodular nonsuppurative panniculitis. Immunosuppressive therapy with prednisone was necessary to control disease activity. The etiology and pathogenesis of nodular nonsuppurative panniculitis is still unknown. Frequently, the disease occurs in patients with autoimmune disorders. The association with PBC and Hashimoto's disease as described herein reinforces the view that nodular nonsuppurative panniculitis may be the response of the subcutaneous adipose tissue to an unknown autoimmune stimulus.

Processes and outcomes of training on rapid assessment and response methods on injecting drug use and related HIV infection in the Russian Federation.

In September 1997, Médecins Sans Frontières-Holland (MSF-H) began a project to provide training and support for HIV/AIDS prevention among injecting drug users (IDUs) in the Russian Federation, focusing on the use of the World Health Organization Rapid Assessment and Response Guide on Injecting Drug Use, and the European Peer Support Manual. As part of the training, participants are asked to carry out a rapid situation assessment (RSA) in their city or region as a major step towards designing and implementing an effective program to prevent HIV transmission among IDUs. This paper focuses on the first four training cycles of the programme (from January 1998 to January 1999), in which 89 health professionals and others from 32 Russian cities took part. A total of 28 rapid situation assessments were completed or almost completed by participants during these four cycles. The paper provides an overview of the methods used and major problems faced by participants undertaking these assessments, as well as summarising the 14 harm reduction programmes which resulted.