Migration of phthalates on culture plates – an important challenge to consider for in vitro studies

Phthalates are endocrine disruptors of the reproductive system and suspected to influence many other organ and hormone systems. They are also semi-volatile organic compounds present in the gas phase in the environment. Their mode of action has been investigated in numerous in vitro studies. Multi-well culture plates are typically used to study phthalates in cell cultures. In a pilot study, we observed evidence of phthalate migration in 24-well culture plates. As this has not previously been described, we investigated the phenomenon in more detail. Primary human thyroid epithelial cell cultures (n?=?8 cultures) were exposed to either di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), mono-n-butyl phthalate (MnBP) or di-(2-ethylhexyl) phthalate (DEHP). Measurement of phthalate metabolites by mass spectrometry demonstrated that the short-branched DEP was able to migrate to adjacent wells when added to cell culture plates. DnBP also seemed to be able to migrate, unlike the long-branched DEHP or the monoester MnBP which did not seem to have this ability. High background levels of phthalate metabolites were also observed, which might compromise results from low dose phthalate studies. In conclusion, the migration of phthalates which is probably caused by their volatile properties might lead to false interpretation of study results.     

Observations on muscle activity in REM sleep behavior disorder assessed with a semi-automated scoring algorithm

Objectives

Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent.

Polymethylmethacrylate bone cements and additives: A review of the literature

Polymethylmethacrylate (PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950s to the recent advent of nanoparticle additives. Additives have been trialed to address problems with modern bone cements such as the loosening of prosthesis, high post-operative infection rates, and inflammatory reduction in interface integrity. This review aims to assess current additives used in PMMA bone cements and offer an insight regarding future directions for this biomaterial. Low index (< 15%) vitamin E and low index (< 5 g) antibiotic impregnated additives significantly address infection and inflammatory problems, with only modest reductions in mechanical strength. Chitosan (15% w/w PMMA) and silver (1% w/w PMMA) nanoparticles have strong antibacterial activity with no significant reduction in mechanical strength. Future work on PMMA bone cements should focus on trialing combinations of these additives as this may enhance favourable properties.     

Progressive trichodysplasia spinulosa in a patient with chronic lymphocytic leukaemia in remission

A 70-year old Caucasian man with chronic lymphocytic leukaemia developed trichodysplasia spinulosa 2 months after ceasing chemotherapy. Histological features characteristic to this condition include dilated and enlarged hair follicles, hyperplastic hair bulbs, hyperplasia of inner root sheath cells with numerous large, eosinophilic, trichohyaline granules, and hypercornification. Although he was in remission for chronic lymphocytic leukaemia, lesions were slowly progressive 15 months after cessation of chemotherapy. We also describe a painless pull-test where spicules can be easily plucked and assessed microscopically for inner root sheath keratinization, or observed with surface microscopy in a clinic setting.     

Occult risk factor for the development of cerebral edema in children with diabetic ketoacidosis: possible role for stomach emptying

The incidence of cerebral edema during therapy of diabetic ketoacidosis (DKA) in children remains unacceptably high—this suggests that current treatment may not be ideal and that important risk factors for the development of cerebral edema have not been recognized. We suggest that there are two major sources for an occult generation of osmole‐free water in these patients: first, fluid with a low concentration of electrolytes that was retained in the lumen of the stomach when the patient arrived in hospital; second, infusion of glucose in water at a time when this solution can be converted into water with little glucose. In a retrospective chart review of 30 patients who were admitted with a diagnosis of DKA and a blood sugar > 900 mg/dL (50 mmol/L), there were clues to suggest that some of the retained fluid in the stomach was absorbed. To minimize the likelihood of creating a dangerous degree of cerebral edema in patients with DKA, it is important to define the likely composition of fluid retained in the stomach on admission, to look for signs of absorption of some of this fluid during therapy, and to be especially vigilant once fat‐derived brain fuels have disappeared, because this is the time when glucose oxidation in the brain should increase markedly, generating osmole‐free water.     

No effect on survival of home psychosocial intervention in a randomized study of Danish colorectal cancer patients

Objective: We investigated whether regular home visits to persons with newly diagnosed colorectal cancer influenced their overall survival and selected immune parameters. Methods: A total of 249 Danish colorectal cancer patients undergoing abdominal surgery were randomly assigned to a control or an intervention group. The intervention group received 10 home visits from a project nurse or a medical doctor during the first 2 years after discharge. The home visits aimed at providing emotional support and information. A subgroup of 55 patients provided blood samples 3, 12 and 24 months after discharge for measurement of immune parameters. Survival was assessed 6.5–9.5 years after the first operation. Results: A total of 148 patients died during follow‐up. The intervention was not significantly associated with survival (p=0.68) after adjustment for Dukes' stage, radicality of the operation, age, sex, family social class and marital status. Likewise, no significant interactions were found between group and these covariates (all p?0.08). In the substudy of the possible effect of the intervention on immune parameters, there were no differences between the two groups with respect to lymphocyte proliferation (all p?0.078) or natural killer cell activity (all p?0.33) and no consistent effect on the number of specific subsets of cells (phenotypes) during follow‐up. Conclusion: The study failed to provide evidence that the psychosocial intervention provided as home visits significantly affected the prognosis or selected immune parameters of patients who had undergone surgery for colorectal cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

Accuracy of self-reported family history of cancer in a large case–control study of ovarian cancer

OBJECTIVE: To evaluate the reliability of self-reported family history of cancer in first-degree female relatives and to examine possible determinants of accurate reporting. METHODS: Women with ovarian cancer and controls were recruited between 1995 and 1999 and interviewed. The study comprised 579 cases and 1,564 controls with 6,265 first-degree female relatives. Self-reported familial cancer diagnoses were validated from registry data. Sensitivity, specificity, and kappa were calculated, and possible determinants were examined by logistic regression. RESULTS: The sensitivity of self-reporting ranged from 0.78 to 0.90 for all cancers but was lower for self-reporting of most site-specific cancers, ranging from 0.29 to 0.94. The specificity of self-reporting ranged from 0.91 to 0.99 for cancer in general and from 0.99 to 1.00 for site-specific cancers. Type of relative, age at interview, and length of education influenced the sensitivity and specificity significantly. The odds ratio for ovarian cancer was higher when based on registry data than on self-reported data and was significant (OR = 2.58 vs. 1.56). CONCLUSIONS: Cancer diagnoses in first-degree relatives are not always accurately reported by patients with ovarian cancer or by controls. The results indicate that studies of associations with family cancer history should validate self-reported family cancer diagnoses as carefully as possible.     

Social inequalities in stage at diagnosis of rectal but not in colonic cancer: a nationwide study

We investigated stage at diagnosis in relation to socioeconomic status (SES) among 15 274 patients with colorectal adenocarcinoma diagnosed in 1996-2004 nationwide in Denmark. The effect of SES on the risk of being diagnosed with distant metastasis was analysed using logistic regression models. A reduction in the risk of being diagnosed with distant metastasis was seen in elderly rectal cancer patients with high income, living in owner-occupied housing and living with a partner. Among younger rectal cancer patients, a reduced risk was seen in those having long education. No social gradient was found among colon cancer patients. The social gradient found in rectal cancer patients was significantly different from the lack of association found among colon cancer patients. There are socioeconomic inequalities in the risk of being diagnosed with distant metastasis of a rectal, but not a colonic, cancer. The different risk profile of these two cancers may reflect differences in symptomatology.     

Risk of solid cancer,cardiovascular disease,anaphylaxis, osteoporosis and fractures in patients with systemic mastocytosis: A nationwide population‐based study

In patients with systemic mastocytosis (SM), several aspects of morbidity remain poorly understood. We assessed the risk of solid cancers, cardiovascular disease, anaphylaxis, osteoporosis, and fractures in SM patients. Using Danish medical registries, we conducted a nationwide population‐based cohort study including 687 adult (≥15 years) SM patients diagnosed during 1997–2012. A comparison cohort of 68,700 subjects from the general Danish population who were alive and without SM at the given SM subject's diagnosis were age‐ and gender‐matched. Outcomes were a new diagnosis of solid cancer, venous thromboembolism (VTE), myocardial infarction (MI), stroke, anaphylaxis, osteoporosis, or fracture. For solid cancers the hazard ratio (HR) was 2.4 (95% confidence interval [CI] 1.9–2.8) with a 10‐year absolute risk (AR) in the SM‐cohort of 12.6% (95% CI 9.4–16.3). Specifically, we found a HR of 7.5 (95% CI 4.4–13.0) for melanoma and a HR of 2.5 (95% CI 1.7–3.5) for non‐melanoma skin cancers (NMSCs). For VTE we found a HR of 1.9 (95% CI 1.2–3.0), with a 10‐year AR of 3.9% (95% CI 2.3–6.1); for MI a nonsignificant increased HR of 1.4 (95% CI 0.9–2.3), with a 10‐year AR of 1.8% (95% CI 0.9–3.2); and for stroke a HR of 1.6 (95% CI 1.1–2.3) with a 10‐year AR of 4.6% (95% CI 2.8–6.9). The HR for anaphylaxis was 7.2 (95% CI 5.3–9.9), and the 10‐year AR was 3.1% (95% CI 1.9–4.9). For osteoporosis the HR was 3.6 (95% CI 2.7–4.6) with a 10‐year AR of 7.2% (95% CI 5.2–9.8). For fractures the HR was 1.2 (95% CI 0.9–1.6) and the 10‐year AR was 5.9% (95% CI 3.9–8.4). SM patients are at increased risk of solid cancers – especially melanoma and NMSC—and cardiovascular disease. The risk of anaphylaxis and osteoporosis is clearly increased in SM, though absolute risk was low in this population‐based study. The fracture‐risk was only slightly increased. Am. J. Hematol. 91:1069–1075, 2016. © 2016 Wiley Periodicals, Inc.     

A nationwide study of serous “borderline” ovarian tumors in Denmark 1978–2002: Centralized pathology review and overall survival compared with the general population

Objective

To describe the study population and estimate overall survival of women with a serous “borderline” ovarian tumor (SBT) in Denmark over 25 years relative to the general population.

Methods

The Danish Pathology Data Bank and the Danish Cancer Registry were used to identify 1487 women diagnosed with SBTs from 1978 to 2002. The histologic slides were collected from Danish pathology departments and reviewed by expert pathologists and classified as SBT/atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Associated implants were classified as noninvasive or invasive. Medical records were collected from hospital departments and reviewed. Data were analyzed using Kaplan–Meier and relative survival was estimated with follow-up through September 2, 2013.

Results

A cohort of 1042 women with a confirmed SBT diagnosis was identified. Women with stage I had an overall survival similar to the overall survival expected from the general population (p = 0.3), whereas women with advanced stage disease had a poorer one (p < 0.0001). This was evident both in women with noninvasive (p < 0.0001) and invasive implants (p < 0.0001). Only among women with advanced stage, overall survival of women with SBT/APST (p < 0.0001) and noninvasive LGSC (p < 0.0001) was poorer than expected from the general population.

Conclusions

To date this is the largest nationwide cohort of SBTs where all tumors have been verified by expert pathologists. Only in women with advanced stage SBT, overall survival is poorer than in the general population which applies both to women with noninvasive and invasive implants as well as to women with SBT/APST and noninvasive LGSC.