Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors.

BACKGROUND: Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. PATIENTS AND METHODS: Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. RESULTS: Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. CONCLUSIONS: The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important.

Anatomic distribution of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium infections in men who have sex with men.

BACKGROUND: New cases of gonorrhoea (Neisseria gonorrhoeae) and chlamydia (Chlamydia trachomatis) infections have been steadily increasing in Scandinavian countries over the last decade. There is a particular urgency in reducing new infections as isolation of multiple drug resistant strains of gonorrhoea is becoming more frequent. The aim of this study was to determine the prevalence and sites of infection of common sexually transmissible infections (STIs) in men who have sex with men (MSM). METHODS: We have performed a retrospective analysis of the three major STIs, gonorrhoea, chlamydia and Mycoplasma genitalium in urogenital, anorectal and oropharyngeal samples from MSM that attended two STI clinics in Oslo. RESULTS: One hundred and thirty-six men (6.0%) out of 2289 MSM tested were found to be positive for gonorrhoea using a porA gene targeted nucleic acid amplification test (NAAT). Of these, 106 (77.9%) would not have been identified through testing first-void urine alone. Two hundred and twenty eight (10.0%) patients from 2289 tested were found to be positive for chlamydia, 164 (71.9%) of which were identified through anorectal specimens. Ninety-one (5.1%) patients from 1778 tested were found to be positive for M. genitalium, with 65 (71.4%) identified through testing of anorectal specimens. CONCLUSIONS: Our results supports the European findings that the MSM population carries a high burden of STIs and that testing the anorectum and oropharynx will identify a significantly higher percentage of infected patients and reservoirs of STIs.

The mild inflammatory response in febrile neutropenic lymphoma patients with low risk of complications is more pronounced in patients receiving tobramycin once daily compared with three times daily.

We evaluated inflammatory markers in febrile neutropenic lymphoma patients undergoing high-dose chemotherapy with autologous stem cell support. Based on MASCC scores, our patients had a low risk of serious complications and a perspective of a benign initial clinical course of the febrile neutropenia. We also studied the impact of tobramycin given once versus three times daily on these immune markers. Sixty-one patients participating in a Norwegian multicentre prospective randomized clinical trial, comparing tobramycin once daily versus three times daily, given with penicillin G to febrile neutropenic patients, constituted a clinically homogenous group. Four patients had bacteraemia, all isolates being Gram-positive. Thirty-two patients received tobramycin once daily, and 29 patients received tobramycin three times daily. Blood samples were taken at the onset of febrile neutropenia and 1-2 days later. All samples were frozen at -70 °C and analysed at the end of the clinical trial for C-reactive protein (CRP), procalcitonin (PCT), complement activation products, mannose-binding lectin (MBL) and 17 cytokines. We found a mild proinflammatory response in this series of patients. CRP was non-specifically elevated. Ten patients with decreased MBL levels showed the same mild clinical and proinflammatory response. Patients receiving tobramycin once daily showed a more pronounced proinflammatory response compared with patients receiving tobramycin three times daily. Overall, febrile neutropenic cancer patients with a benign clinical course show a mild proinflammatory immune response.

Age-dependent biochemical quantities: an approach for calculating reference intervals.

OBJECTIVE: A parametric method is often preferred when calculating reference intervals for biochemical quantities, as non-parametric methods are less efficient and require more observations/study subjects. Parametric methods are complicated, however, because of three commonly encountered features. First, biochemical quantities seldom display a Gaussian distribution, and there must either be a transformation procedure to obtain such a distribution or a more complex distribution has to be used. Second, biochemical quantities are often dependent on a continuous covariate, exemplified by rising serum concentrations of MUC1 (episialin, CA15.3) with increasing age. Third, outliers often exert substantial influence on parametric estimations and therefore need to be excluded before calculations are made. MATERIAL AND METHODS: The International Federation of Clinical Chemistry (IFCC) currently recommends that confidence intervals be calculated for the reference centiles obtained. However, common statistical packages allowing for the adjustment of a continuous covariate do not make this calculation. RESULTS: In the method described in the current study, Tukey's fence is used to eliminate outliers and two-stage transformations (modulus-exponential-normal) in order to render Gaussian distributions. Fractional polynomials are employed to model functions for mean and standard deviations dependent on a covariate, and the model is selected by maximum likelihood. Confidence intervals are calculated for the fitted centiles by combining parameter estimation and sampling uncertainties. Finally, the elimination of outliers was made dependent on covariates by reiteration. CONCLUSIONS: Though a good knowledge of statistical theory is needed when performing the analysis, the current method is rewarding because the results are of practical use in patient care.

Protein epitopes in carcinoembryonic antigen. Report of the ISOBM TD8 workshop.

To characterize antigenic sites in carcinoembryonic antigen (CEA) further and to investigate whether there are differences between colon tumor CEA and meconium CEA (NCA-2) that can be detected by anti-CEA monoclonal antibodies (MAb), 19 new anti-CEA MAb were analyzed with respect to specificity, epitope reactivity and affinity. Their reactivities were compared with 10 anti-CEA MAb with known CEA-domain binding specificity that have previously been classified into five nonoverlapping epitope groups, GOLD 1-5. Cross-inhibition assays with antigen-coated microtiter plates and immunoradiometric assays were performed in almost all combinations of MAbs, using conventionally purified CEA (domain structure: N-A1B1-A2B2-A3B3-C) from liver metastasis of colorectal carcinomas, recombinant CEA, meconium CEA (NCA-2), truncated forms of CEA and NCA (CEACAM6) as the antigens. The affinity of the MAbs for CEA was also determined. The new MAbs were generally of high affinity and suitable for immunoassays. Three new MAbs were assigned to GOLD epitope group 5 (N-domain binding), 3 MAbs to group 4 (A1B1 domain), 1 to group 3 (A3B3 domain), 3 to group 2 (A2B2 domain) and 3 to group 1 (also the A3B3 domain). Three MAbs formed a separate group related to group 4, they were classified as GOLD 4' (A1B1 domain binding). The remaining 3 MAbs appear to represent new subspecificities with some relationship to GOLD groups 1, 2 or 4, respectively. Five MAbs, all belonging to epitope group 1 and 3, reacted strongly with tumor CEA but only weakly or not at all with meconium CEA, demonstrating that the two products of the CEA gene differ from each other, probably due to different posttranslational modifications.