Follow-up care for survivors of lymphoma who have received curative-intent treatment.

OBJECTIVE: This evidence summary set out to assess the available evidence about the follow-up of asymptomatic survivors of lymphoma who have received curative-intent treatment. METHODS: The medline and embase databases and the Cochrane Database of Systematic Reviews were searched for evidence published between 2000 and August 2015 relating to lymphoma survivorship follow-up. The evidence summary was developed by a Working Group at the request of the Cancer Care Ontario Survivorship and Cancer Imaging programs because of the absence of evidence-based practice documents in Ontario for the follow-up and surveillance of asymptomatic patients with lymphoma in complete remission. RESULTS: Eleven retrospective studies met the inclusion criteria. The proportion of relapses initially detected by clinical manifestations ranged from 13% to 78%; for relapses initially detected by imaging, the proportion ranged from 8% to 46%. Median time for relapse detection ranged from 8.6 to 19 months for patients initially suspected because of imaging and from 8.6 to 33 months for those initially suspected because of clinical manifestations. Only one study reported significantly earlier relapse detection for patients initially suspected because of clinical manifestations (mean: 4.5 months vs. 6.0 months, p = 0.042). No benefit in terms of overall survival was observed for patients depending on whether their relapse was initially detected because of clinical manifestations or surveillance imaging. SUMMARY: Findings in the present study support the importance of improving awareness on the part of survivors and clinicians about the symptoms that might be associated with recurrence. The evidence does not support routine imaging for improving outcomes in this patient population.

Prolonged clinical remissions in patients with relapsed or refractory follicular lymphoma treated with autologous stem cell transplantation incorporating rituximab.

Three sequential phase II trials were conducted with different immunotherapy approaches to enhance the outcome of autologous transplant (high-dose therapy and autologous stem cell transplantation (HDT/ASCT)) for recurrent follicular lymphoma. Seventy-three patients were enrolled from 1996 to 2009. Patients received HDT/ASCT combined with (1) interferon-α 3 MU/m(2) subcutaneously (SC) three times per week (TIW) for 2 years post-ASCT, (2) rituximab (R) 375 mg/m(2) for in vivo purging 3-5 days pre-stem cell collection and 2 × 4 weekly R at 2 and 6 months post-ASCT, respectively, or (3) three infusions of R pre-stem cell collection followed by 6× R weekly and interferon-α 3 MU/m(2) SC TIW. Although not statistically significant, progression-free survival (PFS) for patients who received rituximab was 56.4 and 49.1% at 5 and 10 years compared to 36 and 21% in those who did not receive rituximab. Molecular relapse post-HDT/ASCT was the strongest predictor of PFS in a multivariate analysis. Molecular relapse was coincident with or preceded clinical relapses in 84% of patients who relapsed­median of 12 months (range 0-129 months). Adverse events included secondary malignancy, transformation to diffuse large B cell lymphoma, prolonged mostly asymptomatic hypogammaglobulinemia, and pulmonary fibrosis. The long-term toxicity profile must be considered when selecting patients for this treatment.

The meaning and process of pain acceptance. Perceptions of women living with arthritis and fibromyalgia.

BACKGROUND: Within the past 10 years, cognitive-behavioural pain management models have moved beyond the traditional focus on coping strategies and perceived control over pain, to incorporate mindfulness- and acceptance-based approaches. Pain acceptance is the process of giving up the struggle with pain and learning to live life despite pain. Acceptance is associated with lower levels of pain, disability and psychological distress. Relatively little is known, however, about how patients arrive at a state of acceptance without the aid of therapy. OBJECTIVES: To explore personal definitions of acceptance and the factors that facilitate or hinder acceptance. METHODS: Eleven focus groups, involving a total of 45 women with arthritis and fibromyalgia, were conducted. RESULTS: The qualitative analysis revealed that, while the women rejected the word 'acceptance', they did agree with the main components of existing research definitions. The women's responses revealed that acceptance was a process of realizations and acknowledgements, including realizing that the pain was not normal and help was needed, receiving a diagnosis, acknowledging that there was no cure and realizing that they needed to redefine 'normal'. Diagnosis, social support, educating self and others, and self-care were factors that promoted acceptance. Struggling to retain a prepain identity, negative impacts on relationships, others not accepting their pain and the unspoken message that the pain was 'all in their head' were barriers to acceptance. CONCLUSION: The implications of these findings, distinctions between the diagnostic groups and recommendations regarding how health professionals can facilitate the process of acceptance are discussed.

Modified milk fat reduces plasma triacylglycerol concentrations in normolipidemic men compared with regular milk fat and nonhydrogenated margarine.

BACKGROUND: A modified milk fat with reduced cholesterol was developed by fractionation technology. OBJECTIVE: The effect of this modified milk fat on the lipoprotein profile of 21 normolipidemic men was compared with that of regular milk fat and nonhydrogenated margarine. DESIGN: A crossover design was used for the administration of the 3 experimental diets, which provided 13240 kJ as 16% protein, 51% carbohydrates, 33-34% lipids, and 21 g fiber/d. The ratio of polyunsaturated to saturated fat was 1.3:1 for the margarine diet and 0.3:1 for the milk-fat diets. The cholesterol content of the modified milk-fat and margarine diets was similar (248 and 254 mg/d, respectively), but was significantly higher (428 mg/d) for the regular milk-fat diet. RESULTS: Modified and regular milk fats did not change plasma total and LDL cholesterol significantly, but margarine did (P < 0.01). Furthermore, modified milk fat maintained initial HDL(2)-cholesterol concentrations, but margarine reduced this variable significantly (P < 0.05). These results can be explained by the lower ratio of polyunsaturated to saturated fat in the modified and regular milk-fat diets than in the margarine diet. Men who ingested modified milk fat had significantly (P < 0.05) lower total and VLDL-triacylglycerol and VLDL-cholesterol concentrations than did those who ingested either regular milk fat or margarine. This may have been, in part, because of the lower intestinal fat absorption with modified milk fat than with regular milk fat and margarine arising from changes in the melting properties of milk fat with fractionation. CONCLUSION: A reduction in plasma triacylglycerol concentrations after the consumption of modified milk fat may prevent the onset of hypertriacylglycerolemia.

Comparison of simulated driving performance in narcolepsy and sleep apnea patients.

Many patients with obstructive sleep apnea (OSA) or narcolepsy have difficulty driving and increased automobile accidents. Previously we have shown that OSA patients perform poorly on a laboratory-based divided-attention driving test (DADT). Patients with narcolepsy may be as sleepy as OSA patients, so we compared performance on the DADT of OSA patients with that of narcolepsy patients. Twenty-one male OSA patients [age 49.3 +/- 12.7 (SD) years; apnea-hypopnea index (AHI) 73 +/- 29] 21 age- and sex-matched controls, and 16 narcoleptics (12 males, four females; age 39.6 +/- 15.2 years) underwent polysomnography followed by daytime sleep latency testing (MSLT). Following a practice session, all subjects were given the DADT for 20 minute prior to each daytime nap of the MSLT. Narcolepsy patients were younger than OSA or controls and more sleepy than OSA patients. Tracking error was much worse in patients than controls (228 +/- 145 cm for OSA vs. 196 +/- 146 for narcolepsy vs. 71 +/- 31 for controls; p < 0.001), although half of either patient group performed as well as controls. There was only a weak relationship between MSLT and tracking in either patient group. We conclude that impairment in laboratory driving performance skills is seen in both groups of sleepy patients but the degree of impairment is difficult to predict from sleepiness alone.

Regiospecific analysis of fractions of bovine milk fat triacylglycerols with the same partition number.

Bovine milk fat was fractionated using preparative reversed-phase high-performance liquid chromatography. The conditions consisted of two successive linear gradients of acetonitrile and tert-butylmethylether, followed by a final isocratic mixture of the two eluants, leading to triacylglycerols grouped by their partition number (PN). Fractions corresponding to partition numbers 32 to 50 were isolated and analyzed for fatty acid distribution between sn-1,3 and sn-2 positions by Grignard degradation. Results showed that the fatty acid distribution in milk fat triacylglycerols is nonrandom. The distribution of short-chain fatty acids, stearic (predominantly at sn-1,3 position) and palmitic (predominantly sn-2 position), did not change with triacylglycerol size. Medium-chain fatty acids were predominantly located at sn-2 position, but their proportion at this position decreased with triacylglycerol size. Oleic acid distribution was also size-dependent in that it was located in high proportions at sn-2 position in smaller triacylglycerols and vice versa. Results also showed that the sn-2 position was more unsaturated than sn-1,3 position in the PN range from 32 to 40, but it was more saturated in triacylglycerols with higher PN.

Bisphenol A induces differentiation of human preadipocytes in the absence of glucocorticoid and is inhibited by an estrogen-receptor antagonist.

BACKGROUND: Obesity is a major health concern in the developed world, and increasing evidence suggests that exposures to common environmental substances may enhance the risk for the development of this disease. OBJECTIVES: The current study examines the effect of the ubiquitous plastic monomer bisphenol A (BPA) on the differentiation of primary human preadipocytes in vitro and the role of the estrogen and glucocorticoid receptors. METHODS: In this study, the mechanism of BPA-induced adipogenesis in preadipocytes from donors with healthy body mass index in the absence of exogenous glucocorticoid was evaluated. The effects of estradiol, the estrogen-receptor (ER) antagonist ICI and the glucocorticoid receptor (GR) antagonist RU486 on BPA-induced adipogenesis were examined. The expression levels of key adipogenic factors were assessed. RESULTS: Treatment of preadipocytes with 1-50 µM BPA induced a dose-dependent increase in differentiation and lipid accumulation as determined by lipid staining and triacylglyceride quantification. BPA also induced expression of the adipogenic markers aP2, adipsin, peroxisome proliferator-activated receptor γ and the CCAAT-enhancer-binding proteins α and ß. Co-treatment of cells with ICI inhibited the BPA-induced increase in aP2 levels, while treatment with ICI or estradiol alone had no effect. Treatment of cells with the GR antagonist RU486 had no effect on BPA-induced differentiation as evaluated by aP2 levels. CONCLUSIONS: This study is one of the first to show that BPA induces human adipocyte differentiation in the absence of exogenous glucocorticoid through a non-classical ER pathway rather than through GR activation. These studies add to the growing evidence that endocrine-disrupting chemicals such as BPA have the potential to modulate adipogenesis and impact human biology.

Rituximab purging and maintenance combined with auto-SCT: long-term molecular remissions and prolonged hypogammaglobulinemia in relapsed follicular lymphoma.

We enrolled 23 patients with relapsed follicular lymphoma (FL) in a prospective single-arm study of auto-SCT combined with in vivo rituximab graft purging and post transplant rituximab maintenance. Minimal residual disease was monitored with quantitative PCR testing. With a median follow-up of 74.2 months, neither median overall survival (OS) nor PFS has been reached. Here, 5-year OS and 5-year PFS are 78% (95% confidence interval (CI) 61-95%) and 59% (95% CI 38-80%), respectively. Time to progression (TTP) with the experimental regimen was significantly improved compared with TTP with the last prior treatment (P<0.001). Durable molecular remissions occurred in 11 of 13 assessable patients. PFS was significantly longer in patients who achieved a molecular remission by 3 months post-auto-SCT (P=0.001). Prolonged hypogammaglobulinemia occurred in most patients; however, no increase in major infections was observed.

Analysis of Gamma Radionuclides in Selected Farm Produce of Oka, Quebec - A Niobium Mining Community.

An investigation of the gamma emitting radionuclides present in selected farm produce of Oka, Quebec, was conducted. In the three categories of foodstuffs, such as cheese, apple and maple sugar, obtained from the immediate vicinity of niobium mill tailings piles, distinguishable radioactivity from natural sources and worldwide fallout was evident. Except for lead-214 and radium-226, the tailings spectrum showed a typical pattern of natural background value. With the exception of lead-212, uranium-235, thallium-208 and actinium- 228, all radionuclides in farm produce were near or below levels of detection. There was no significant difference in the radiation level of food samples grown in control areas.

Describing and analyzing constipation in acute care.

Many patients in acute care hospitals experience constipation, yet the literature on constipation focuses on long-term care and does not provide tools for describing and analyzing bowel management from the perspective of health care professionals or patients. The article describes the development of a bowel management task force at one acute care hospital and the initial steps taken to improve clinical quality in this area. A multifaceted approach was used to collect baseline data on practice, expectations, and problems related to bowel management. Valuable data were obtained from both patients and health care providers that have provided direction for improving clinical outcomes and patient satisfaction.

Effects of nasal CPAP on simulated driving performance in patients with obstructive sleep apnoea.

BACKGROUND: Many patients with obstructive sleep apnoea (OSA) have difficulty in driving and experience increased automobile accidents. It has previously been shown that patients with OSA perform poorly on a laboratory based divided attention driving test (DADT). METHODS: Seventeen men with OSA of mean (SD) age 49.7 (11.2) years and an initial apnoea/hypopnoea index (AHI) of 73.0 (28.9) were restudied from one to 12 (mean (SD) 9.2 (4.2)) months after initiating treatment with nasal continuous positive airway pressure (CPAP) to examine the effects of treatment on DADT performance. Eighteen age and sex matched controls were also retested 8.4 (3.4) months after their initial tests. Following a practice session, all subjects were given the DADT for 20 minutes before each daytime nap of the standard multiple sleep latency test (MSLT). RESULTS: Untreated patients with OSA, who performed much worse than controls in all measures, improved significantly on all measures of performance, particularly in tracking error which returned to the level of controls in all but one patient. Changes in performance were much greater for patients with OSA than for controls in tracking error (mean difference 106 (95% CI 75 to 135) cm), sleep latency/ MSLT (5.3 (95% CI 2.7 to 8.0) min), number of correct responses (1.2 (95% CI 0.4 to 1.9)), number of missed responses (1.7 (95% CI 0.9 to 2.3)), and number out of bounds (10.0 (95% CI 7.9 to 13.6)), but not for response time (0.1 (95% CI -0.3 to 0.2) s). Improvement in tracking error was highly correlated with improvement in sleepiness (r = 0.65). CONCLUSIONS: Impairment in laboratory driving performance skills in patients with OSA is reversed by successful treatment with nasal CPAP. Changes in daytime sleepiness account for some but not all of the improvement.

Simulated driving performance in patients with obstructive sleep apnea.

To assist in determining ability to drive in patients with obstructive sleep apnea (OSA), we developed a divided attention driving test (DADT) based on the work of Moskowitz and Burns (6). We first examined its ability to detect impaired performance by testing normal subjects both sober and impaired by alcohol (mean blood alcohol level, 95 +/- 25 mg/dl). Subsequently, 21 male patients with OSA (age 49.3 +/- 12.7 [SD] yr; apnea hypopnea index [AHI] 73 +/- 29) and 21 age- and sex-matched control subjects underwent polysomnography followed by daytime sleep latency testing (MSLT). Before each day-time nap, subjects were given the DADT for 20 min. Patients who performed much worse than control subjects in all measures, with the largest difference noted in tracking error (OSA, 228 +/- 145 cm versus control 71 +/- 31 cm, p < 1 x 10(-9)). Half of the patients were worse than any control subject, with some showing performance worse than control subjects impaired by alcohol. However, MSLT and AHI explained less than 25% of the variance in tracking error, making individual prediction problematic. We concluded that in laboratory driving performance skills are markedly impaired in over half our group with sleep apnea. Further testing and comparing on-road performance should aid in predicting ability to drive.

Stimulation of poly(ADP-ribose) synthesis by free radicals in C3H10T1/2 cells: relationship with NAD metabolism and DNA breakage.

We have studied the effect of H2O2 and O2- produced by xanthine and xanthine oxidase on NAD catabolism, poly(ADP-ribose) synthesis, and production of DNA single-strand breaks in C3H10T1/2 cells. The results show a correlation between the induction of DNA single-strand breaks, the decrease of NAD pool, and the accumulation of polymer. New techniques, based on affinity chromatography and reversed-phase high pressure liquid chromatography, have allowed an accurate determination of polymer contents and showed a 20-fold stimulation of polymer biosynthesis induced by active oxygen species. Inhibition experiments performed with 3-aminobenzamide have shown that the decrease in NAD levels after exposure of cells to active oxygen species was caused by stimulation of poly(ADP-ribosyl)ation and of another cellular process.

Distribution of cholesterol in milk fat fractions.

Milk fat was fractionated into liquid (m.p. congruent to 12 degrees C), intermediate (m.p. congruent to 21 degrees C) and solid (m.p. congruent to 39 degrees C) fractions by three different processes--melt crystallization, short-path distillation and supercritical CO2 extraction--and the cholesterol content of these fractions determined. Cholesterol was enriched in the liquid fractions from all three processes, in particular about 80% of the cholesterol being found in the liquid fraction obtained by short-path distillation. The basis of migration of cholesterol into various milk fat fractions was explained by its affinity to various triglycerides (melt crystallization) and by vapour pressure and molecular weight (short-path distillation). It was more complex in the supercritical CO2 extraction process; the interplay of cholesterol affinity toward CO2 and its molar volume, and its vapour pressure enhancement under applied pressure play a role.

Clinical use of immunoassays in assessing exposure to fungi and potential health effects related to fungal exposure.

OBJECTIVE: To review and summarize current evidence regarding the proper role of immunoassays in clinical assessments of exposure to fungi and health effects related to fungal exposure. DATA SOURCES: We reviewed relevant scientific investigations and previously published reviews concerning this topic. STUDY SELECTION: The authors' clinical, laboratory, and public health experiences were used to evaluate relevant data for scientific merit. RESULTS: Testing to determine the presence of IgE to specific fungi may be a useful component of a complete clinical evaluation in the diagnosis of illnesses that can be caused by immediate hypersensitivity such as allergic rhinitis and asthma. Detection of IgG to specific fungi has been used as a marker of exposure to agents that may cause illnesses such as hypersensitivity pneumonitis. However, the ubiquitous nature of many fungi and the lack of specificity of fungal antigens limit the usefulness of these types of tests in the evaluation of potential building-related illness and fungal exposure. Specific serologic tests (such as tests for cryptococcal antigen, coccidioidal antibody, and Histoplasma antigen) have been shown to be useful in the diagnosis of some fungal infections, but these are the exception not the rule. CONCLUSIONS: There is currently not enough scientific evidence to support the routine clinical use of immunoassays as a primary means of assessing environmental fungal exposure or health effects related to fungal exposure. Health care providers who care for persons expressing concerns about the relationship of symptoms to potential exposure to fungi are advised to use immunoassay results with care and only as an adjunct to a comprehensive approach to patient care.