Does labelling a rare cancer diagnosis 'good' affect the patient's experience of treatment and recovery?

Doctors sometimes tell patients with rare but highly treatable cancers that they have 'good' cancer which some patients have found unhelpful, but this has been little explored. The aim of this study was to explore how patients reacted to being told they had a 'good' cancer. Qualitative interviews were carried out with 25 people with rare but prognostically favourable cancers who had received treatment at two hospitals within a cancer network. Results showed that despite good treatment outcomes, patients are still very shocked to hear the word cancer and react in similar ways to those with other forms of cancer. The potential effects of treatment should be recognised as having a detrimental effect on patient well-being whatever the prognosis. We should therefore avoid using 'good' and 'cancer' in the same sentence. In addition, the impact on all family members should not be underestimated. The data can be used to improve clinical practice and improve support for people affected by cancer.

Jugular Venous Flow Abnormalities in Multiple Sclerosis Patients Compared to Normal Controls.

BACKGROUND: To determine if extracranial venous structural and flow abnormalities exist in patients with multiple sclerosis (MS). METHODS: Magnetic resonance imaging was used to assess the anatomy and function of major veins in the neck in 138 MS patients and 67 healthy controls (HC). Time-of-flight MR angiography (MRA) was used to assess stenosis while 2-dimensional phase-contrast flow quantification was used to assess flow at the C2/C3 and C5/C6 levels. Venous flow was normalized to the total arterial flow. The MS patients were divided into stenotic (ST) and nonstenotic (NST) groups based on MRA assessment, and each group was compared to the HC group in anatomy and flow. RESULTS: The MS group showed lower normalized internal jugular vein (IJV) blood flow (tIJV/tA) than the HC group (P < .001). In the MS group, 72 (52%) were classified as ST while 66 (48%) were NST. In the HC group, 11 (23%) were ST while 37 (77%) were NST. The ST-MS group had lower IJV flow than both HC and NST-MS groups. CONCLUSION: After categorizing the MS population into two groups based upon anatomical stenosis, as determined from an absolute quantification of IJV cross section, clear differences in IJV flow between the ST-MS and HC samples became evident. Despite the unknown etiology of MS, abnormal venous flow was noted in a distinct group of MS patients compared to HC.

A comparative study of magnetic resonance venography techniques for the evaluation of the internal jugular veins in multiple sclerosis patients.

BACKGROUND AND PURPOSE: The use of magnetic resonance imaging (MRI) to assess the vascular nature of diseases such as multiple sclerosis (MS) is a growing field of research. This work reports on the application of MR angiographic (MRA) and venographic (MRV) techniques in assessing the extracranial vasculature in MS patients. MATERIALS AND METHODS: A standardized MRI protocol containing 2D TOF-MRV and dynamic 3D contrast-enhanced (CE) MRAV was run for 170 MS patients and 40 healthy controls (HC). The cross-sectional area (CSA) of the internal jugular veins (IJVs) was measured at three neck levels in all subjects for both MRV techniques to determine the presence of venous stenoses. All data were analyzed retrospectively. RESULTS: For the values where both methods showed signal, the 3D method showed larger CSA measurement values compared to 2D methods in both IJVs, in both MS and HC subjects which was confirmed with student paired t-tests. Of the 170 MS patients, 93 (55%) in CE-MRAV and 103 (61%) in TOF-MRV showed stenosis in at least one IJV. The corresponding numbers for the 40 HC subjects were 2 (5%) and 4 (10%), respectively. Carotid ectasias with IJV stenosis were seen in 26 cases (15%) with 3D CE-MRAV and were not observable with 2D TOF-MRV. Carotid ectasias were not seen in the HC group. In the 2D TOF-MRV data, banding of the IJVs related to slow flow was seen in 58 (34%) MS cases and in no HC cases. MS patients showed lower average CSAs than the HC subjects. CONCLUSION: The 3D CE MRAV depicted the vascular anatomy more completely than the 2D TOF-MRV. However, the 3D CE MRAV does not provide any information about the flow characteristics which are indirectly available in the 2D TOF-MRV in those cases where there is slow flow.

TorsinB expression in the developing human brain.

Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. The majority of cases are caused by a 3-bp deletion (GAG) in the coding region of the DYT1 (TOR1A) gene. The cellular and regional distribution of torsinA protein, which is restricted to neuronal cells and present in all brain regions by the age of 2 months has been described recently in human developing brain. TorsinB is a member of the same family of proteins and is highly homologous with its gene adjacent to that for torsinA on chromosome 9q34. TorsinA and torsinB share several remarkable features suggesting that they may interact in vivo. This study examined the expression of torsinB in the human brain of fetuses, infants and children up to 7 years of age. Our results indicate that torsinB protein expression is temporarily and spatially regulated in a similar fashion as torsinA. Expression of torsinB protein was detectable beginning at four to 8 weeks of age in the cerebellum (Purkinje cells), substantia nigra (dopaminergic neurons), hippocampus and basal ganglia and was predominantly restricted to neuronal cells. In contrast to torsinA, torsinB immunoreactivity was found more readily in the nuclear envelope. High levels of torsinB protein were maintained throughout infancy, childhood and adulthood suggesting that torsinB is also needed for developmental events occurring in the early postnatal phase and is necessary for functional activity throughout life.

Effect of nebulized albuterol on blood glucose in patients with diabetes mellitus with and without cystic fibrosis.

Over 90% of cystic fibrosis (CF) patients are treated with bronchodilators, and 6% have diabetes. Some with asthma also have diabetes, and most are treated with bronchodilators. Systemic administration of adrenergic agents can cause increases in blood glucose, but the effect of inhaled agents is unclear. A double-blind study was performed on 10 patients with type 1 diabetes mellitus (DM) without CF (3 male, 7 female, mean age 25.5 years) and 9 patients with insulin-dependent CF-related diabetes (CFRD) (8 male, 1 female, mean age 21.9 years). On 2 separate days before 9 AM fasting and the morning dose of insulin, 2.5 mg of albuterol or nebulized placebo were given. Blood glucose was measured by finger stick with a glucose reflectance meter before and 15, 30, 45, and 60 min after treatment. No significant changes from baseline or differences between placebo and albuterol occurred in either group. The mean maximum increase from baseline in DM was 20 mg/dl on placebo, and 38 mg/dl on albuterol; in the CFRD, the respective changes were 7 and 7 mg/dl. Two DM patients had a > 50 mg/dl increase on albuterol vs. placebo; no CFRD patients had differences of such magnitude. DM patients had greater increases from baseline than CFRD patients on placebo and albuterol. Differences reached statistical significance at 30 and 45 min on placebo, and 45 min on albuterol. Albuterol 2.5 mg by nebulizer causes no clinically significant increases in blood glucose in DM or CFRD patients. Diabetes patients without CF have a significantly greater increase of glucose with time (placebo or albuterol) than CFRD patients.

TorsinA expression is detectable in human infants as young as 4 weeks old.

Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. The majority of cases are caused by a 3-bp deletion (GAG) in the coding region of the DYT1 (TOR1A) gene. The cellular and regional distribution of torsinA protein and its message has been described previously in several regions of normal adult human and rodent brain. This study examines the expression of torsinA in the developing human brain of fetuses, infants and children up to 7 years of age in four selected brain regions. Expression of torsinA protein was detectable beginning at 4 to 8 weeks of age postnatally in the cerebellum (Purkinje cells), substantia nigra (dopaminergic neurons), hippocampus and basal ganglia. Prominent torsinA immunoreactivity was not seen before 6 weeks of age postnatally, a period associated with synaptic remodeling, process elimination and the beginning of myelination. Our results indicate that torsinA protein expression is temporally and spatially regulated and is present in all brain regions studied by the age of 2 months on into adulthood.

Leptin expression in breast nipple aspirate fluid (NAF) and serum is influenced by body mass index (BMI) but not by the presence of breast cancer.

While obesity is a known risk factor for postmenopausal breast cancer, the molecular mechanisms involved are unclear. Systemic levels of leptin, the product of the ob (obesity) gene, are increased in obese individuals (body mass index, BMI, over 25) and are higher in women than men. Leptin has been found to stimulate the growth of breast cancer cells in vitro. Our goal was to determine whether leptin was 1) present in nipple aspirate fluid (NAF), and 2) whether NAF leptin levels were associated with a) levels in serum, b) obesity, and c) breast cancer. We collected and evaluated NAF specimens from 83 subjects and serum specimens from 49 subjects. NAF leptin was detectable in 16/41 (39 %) of premenopausal and 21/42 (50 %) postmenopausal subjects. NAF leptin was significantly lower (p = 0.042) in premenopausal than postmenopausal women with a BMI < 25, but not in those with a higher BMI. NAF leptin was significantly associated with BMI in premenopausal (p = 0.011) but not in postmenopausal women. Serum leptin was associated with BMI in both premenopausal and postmenopausal women (p = 0.0001 for both). NAF and serum leptin were associated in premenopausal (p = 0.02) but not postmenopausal women. Neither NAF nor serum leptin was associated with premenopausal or postmenopausal breast cancer. Our findings include that 1) leptin is present in the breast and detectable in a subset of NAF samples, 2) NAF leptin in premenopausal but not postmenopausal women parallels serum leptin levels, and 3) neither NAF nor serum levels of leptin were associated with premenopausal or postmenopausal breast cancer.

A prospective investigation of the impact of smoking bans on tobacco cessation and relapse.

BACKGROUND AND OBJECTIVES: To examine the long term impact of workplace smoking bans on employee smoking cessation and relapse. Over three years we studied a total of 1033 current or former smokers (intervention group) employed in smoke-free hospitals and 816 current or former smokers (comparison group) employed in non-smoke-free workplaces. The design of this natural experiment is a prospective cohort study. We randomly selected both hospitals and employees from 12 strata based on hospital size and state tobacco regulations, and sampled employees in the same communities. Main outcome measures were post-ban quit ratio and relapse rate. RESEARCH DESIGN: Between groups comparisons were conducted using the Cochran-Mantel-Haenszel statistic for general association, stratified Cox proportional hazards models, and the CMH analysis of variance statistic based on ranks. McNemar's test and the sign test were used to test for changes over time within each group. RESULTS: Differences in the post-ban quit ratio were observed between intervention and comparison groups (p < or = 0.02). For employees whose bans were implemented at least seven years before survey, the post-ban quit ratio was estimated at 0.256, compared with 0.142 for employees in non-smoke-free workplaces (p = 0.02). After controlling for a variety of factors, time to quit smoking was shorter for the hospital employees (p < 0.001), with an overall relative risk of quitting of 2.3. Contrary to expectations, relapse rates were similar between the groups. CONCLUSION: Employees in workplaces with smoking bans have higher rates of smoking cessation than employees where smoking is permitted, but relapse is similar between these two groups of employees. The results of this investigation have international applicability for policy makers, clinicians, employers, and employees. Countries should review smoking policies in workplaces in light of their own smoking patterns and efforts to deal with environmental tobacco smoke.

Differential modulation of prostaglandin H synthase-2 by nitric oxide-related species in intact cells.

Nitrogen monoxide (NO) has been reported to both activate and inhibit prostaglandin (PG) biosynthesis. This apparent paradox might be explained by the production/action of distinct NO-related species formed as a result of the prevailing redox states of different cellular systems. As such, the effect of NO donors with different redox characteristics on the modulation of prostaglandin H synthase-2 (PGHS-2) in primary mouse cortical astrocytes and COS-7 cells engineered to overexpress PGHS-2 was assessed. In general, compounds that released NO(*) or NO(-) enhanced, while a peroxynitrite (OONO(-)) generator inhibited, PGHS-2-dependent prostaglandin production. While the possibility of altered gene transcription was eliminated in the COS-7 system as PGHS-2 was maximally expressed, in primary astrocytes where PGHS-2 expression was induced by lipopolysaccharide (LPS), effects on protein expression were detected. Compounds that released NO(*) synergistically enhanced LPS-mediated PGHS-2 protein synthesis. None of these effects were mediated by cGMP. All donors lost their ability to modulate PGHS-2 expression and function when decayed. These results indicate that the ultimate effect of NO on PGHS-2 enzyme activity and expression is dictated by the prevalent NO-related species formed, suggesting that important interactions which may exist between NO and prostanoid pathways in vivo will be highly dependent on the inherent redox environment.

A close association of torsinA and alpha-synuclein in Lewy bodies: a fluorescence resonance energy transfer study.

TorsinA, a novel protein in which a mutation causes dominant, early onset torsion dystonia, may serve as a chaperone for misfolded proteins that require refolding or degradation. It has been hypothesized that misfolded alpha-synuclein, a protein in which two mutations cause autosomal dominantly inherited Parkinson's disease, serves as a nidus for the development of a Lewy body. We hypothesized that torsinA plays a role in the cellular processing of alpha-synuclein. We demonstrate that anti-torsin antibodies stain Lewy bodies and Lewy neurites in the substantia nigra and cortex. Using sensitive fluorescent resonance energy transfer (FRET) techniques, we find evidence of a close association between torsinA and alpha-synuclein in Lewy bodies.

Phase I and pharmacokinetic study of the novel MDR1 and MRP1 inhibitor biricodar administered alone and in combination with doxorubicin.

PURPOSE: To evaluate the safety, tolerability, and pharmacokinetics of biricodar (VX-710), an inhibitor of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP1), alone and with doxorubicin in patients with advanced malignancies. The effect of VX-710 on the tissue distribution of (99m)Tc-sestamibi, a P-gp and MRP1 substrate, was also evaluated. PATIENTS AND METHODS: Patients with solid malignancies refractory to standard therapy first received a 96-hour infusion of VX-710 alone at 20 to 160 mg/m(2)/h. After a 3-day washout, a second infusion of VX-710 was begun, on the second day of which doxorubicin 45 mg/m(2) was administered. Cycles were repeated every 21 to 28 days. (99m)Tc-sestamibi scans were performed before and during administration of VX-710 alone. RESULTS: Of the 28 patients who enrolled, 25 patients were eligible for analysis. No dose-limiting toxicity (DLT) was observed in the nine assessable patients who received 120 mg/m(2)/h or less. Among seven patients receiving VX-710 160 mg/m(2)/h, two DLTs were seen: reversible CNS toxicity and febrile neutropenia. All other adverse events were mild to moderate and reversible. Plasma concentrations of VX-710 in patients who received at 120 and 160 mg/m(2)/h were two- to fourfold higher than concentrations required to fully reverse drug resistance in vitro. VX-710 exhibited linear pharmacokinetics with a harmonic mean half-life of 1.1 hours. VX-710 enhanced hepatic uptake and retention of (99m)Tc-sestamibi in all patients. CONCLUSION: A 96-hour infusion of VX-710 at 120 mg/m(2)/h plus doxorubicin 45 mg/m(2) has acceptable toxicity in patients with refractory malignancies. The safety and pharmacokinetics of VX-710 plus doxorubicin warrant efficacy trials in malignancies expressing P-gp and/or MRP1.

Criminals' explanations of their criminal behavior, III: the effects of time and context.

The authors looked at the explanations for their index of violent crimes as given by 69 incarcerated violent male offenders, respectively. We then examined the extent to which those explanations changed with the passing of time and with change in context. We found that explanations of impaired internal control increased with the passing of time, and that such explanation was given more often to mental health professionals rather than law enforcement professionals. Finally, we found that our subjects tended to give mental health professionals fewer explanations involving external control with the passing of time.

The application of a compact multispectral imaging system with integrated excitation source to in vivo monitoring of fluorescence during topical photodynamic therapy of superficial skin cancers.

A novel, compact and low-cost multispectral fluorescence imaging system with an integrated excitation light source is described. Data are presented demonstrating the application of this method to in vivo monitoring of fluorescence before, during and after topical 5-aminolevulinic acid photodynamic therapy of superficial skin cancers. The excitation source comprised a fluorescent tube with the phosphor selected to emit broadband violet light centered at 394 nm. The camera system simultaneously captured spectrally specific images of the fluorescence of the photosensitizer, protoporphyrin IX, the illumination profile and the skin autofluorescence. Real-time processing enabled images to be manipulated to create a composite image of high contrast. The application and validation of this method will allow further detailed studies of the characteristics and time-course of protoporphyrin IX fluorescence, during topical photodynamic therapy in human skin in vivo.

Effects of stress management on pain behavior in rheumatoid arthritis.

OBJECTIVE: To examine the effects of stress management training on pain behavior exhibited by persons with rheumatoid arthritis (RA) and the relationship of change in pain behavior with certain patient characteristics as well as change in self-reported levels of pain. METHODS: Patients with RA (n = 131) were randomly assigned to 1 of 3 groups: a stress management group, an attention control group, or a standard care control group. The stress management and attention control groups received a 10-week intervention followed by a 15-month maintenance phase. RESULTS: The 3 groups did not differ significantly in the change in pain behavior at any of the assessment periods. However, persons with RA who had less disease activity tended to exhibit positive changes in pain behavior over time. Changes in self-reported pain were not significantly related to changes in pain behavior. CONCLUSION: The results indicate that stress management interventions do not reduce total pain behaviors exhibited by persons with RA. Changes in pain behaviors appear to be related to disease activity, age, and disease duration, but not to changes in self-reported measures of pain.

Implications of depression in rheumatoid arthritis: do subtypes really matter?

OBJECTIVE: To examine depressive disorders and health status in patients with rheumatoid arthritis (RA), controlling for potential confounds. METHOD: Subjects (n = 426) completed measures of depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D]) and health status (Arthritis Impact Measurement Scales 2 [AIMS2]), via cross-sectional survey. Subjects (n = 299) with few depressive symptoms (CES-D < or = 10) were not evaluated further. Subjects with CES-D > or = 11 were interviewed using the Primary Care Evaluation of Mental Disorders to diagnose major depressive disorder (MDD; n = 46), dysthymic disorder (DD; n = 21), or minor depressive disorder (MND; n = 18). RESULTS: Regression analyses examined differences between the depressive disorders on AIMS2 subscales. Health status scores were similar between the depressive disorder subcategories; significant differences were found between MDD and MND on AIMS2 Physical scores and MDD and DD on AIMS2 Symptom scores. CONCLUSION: Regarding health status, presence of depression itself seems to overshadow differences between depression subtypes; antidepressant treatments/referrals for persons with concomitant RA and any depressive disorder subtype appear warranted.

Mutant torsinA, responsible for early-onset torsion dystonia, forms membrane inclusions in cultured neural cells.

Early-onset torsion dystonia is a hereditary movement disorder thought to be caused by decreased release of dopamine into the basal ganglia, without apparent neuronal degeneration. Recent cloning of the gene responsible for this disease, TOR1A (DYT1), identified the encoded protein, torsinA, as a member of the AAA+ superfamily of chaperone proteins and revealed highest levels of expression in dopaminergic neurons in human brain. Most cases of this disease are caused by a deletion of one glutamic acid residue in the C-terminal region of the protein. Antibodies generated against torsinA revealed expression of a predominant immunoreactive protein species similar to the predicted size of 37.8 kDa in neural, glial and fibroblastic lines by western blot analysis. This protein is N-glycosylated with high mannose content and not, apparently, phosphoryl-ated. Overexpression of torsinA in mouse neural CAD cells followed by immunocytochemistry, revealed a dramatically different pattern of distribution for wild-type and mutant forms of the protein. The wild-type protein was found throughout the cytoplasm and neurites with a high degree of co-localization with the endoplasmic reticulum (ER) marker, protein disulfide isomerase. In contrast, the mutant protein accumulated in multiple, large inclusions in the cytoplasm around the nucleus. These inclusions were composed of membrane whorls, apparently derived from the ER. If disrupted processing of the mutant protein leads to its accumulation in multilayer membranous structures in vivo, these may interfere with membrane trafficking in neurons.

Cyclooxygenase-2 contributes to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical cell culture.

Cyclooxygenase isozymes (COX-1 and COX-2) are found to be constitutively expressed in brain, with neuronal expression of COX-2 being rapidly induced after numerous insults, including cerebral ischemia. Because overactivation of N-methyl-D-aspartate (NMDA) receptors has been implicated in the cell loss associated with ischemia, we characterized the expression of the COX isozymes in murine mixed cortical cell cultures and used isozyme-selective inhibitors to determine their relative contribution to NMDA receptor-stimulated prostaglandin (PG) production and excitotoxic neuronal cell death. Immunocytochemical analysis of mixed cortical cell cultures revealed that COX-2 expression was restricted to neurons, whereas COX-1 was expressed in both neurons and astrocytes. Brief exposure to NMDA (5 min; 100 microM) elicited a time-dependent accumulation of PGs in the culture medium that preceded neuronal cell death and correlated with the induction of COX-2 mRNA. COX-1 expression remained unchanged. Flurbiprofen, a nonselective COX-1/COX-2 inhibitor, blocked NMDA-stimulated PG production and attenuated neuronal death in a concentration-dependent manner. Similar results were obtained with the specific COX-2 inhibitor NS-398 (10-30 microM) but not with the selective COX-1 inhibitor valeryl salicylate (10-300 microM). Inhibition of total constitutive COX activity with aspirin (100 microM, 1.5 h) before NMDA exposure did not prevent subsequent NMDA-mediated neuronal cell death. However, neuronal injury in aspirin-pretreated cultures was attenuated by flurbiprofen administration after NMDA exposure. Finally, the protection afforded by COX-2 inhibition was specific for NMDA because neither flurbiprofen nor NS-398 protected neurons against kainate-mediated neurotoxicity. Together, these results support the conclusion that newly synthesized COX-2 protein contributes to NMDA-induced neuronal injury.

Stress management in rheumatoid arthritis: what is the underlying mechanism?

OBJECTIVE: To test whether change in cognitive-behavioral variables (such as self-efficacy, coping strategies, and helplessness) is a mediator in the relation between cognitive behavior therapy and reduced pain and depression in persons with rheumatoid arthritis (RA). METHODS: A sample of patients with RA who completed a stress management training program (n = 47) was compared to a standard care control group (n = 45). A path analysis testing a model including direct effects of comprehensive stress management training on pain and depression and indirect effects via change in cognitive-behavioral variables was conducted. RESULTS: The path coefficients for the indirect effects of stress management training on pain and depression via change in cognitive-behavioral variables were statistically significant, whereas the path coefficients for the direct effects were found not to be statistically significant. CONCLUSION: Decreases in pain and depression following stress management training are due to beneficial changes in the arenas of self-efficacy (the belief that one can perform a specific behavior or task in the future), coping strategies (an individual's confidence in his or her ability to manage pain), and helplessness (perceptions of control regarding arthritis). There is little evidence of additional direct effects of stress management training on pain and depression.