Palliative care in gynaecological oncology

Gynaecological malignancy accounts for significant patient morbidity and mortality. Clinical aims focus upon palliative management and supportive care when potentially curative treatment options are exhausted. Patients with recurrent, advancing or terminal disease may suffer severe and distressing physical and psychological effects associated with both cancer diagnosis and treatments. It is of paramount importance that patients, families and carers are provided with the assistance they need to have as high a quality of life as possible.This review focuses upon the provision of relief from pain and other distressing symptoms commonly associated with gynaecological malignancy. In addition, we highlight some of the important aspects of psychosocial care.     

Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy

Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca²⁺ concentration inside pancreatic acinar cells ([Ca²⁺]_i), due to excessive release of Ca²⁺ stored inside the cells followed by Ca²⁺ entry from the interstitial fluid. The sustained [Ca²⁺]_i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca²⁺ release-activated Ca²⁺ channels (CRAC) would prevent sustained elevation of [Ca²⁺]_i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca²⁺ ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca²⁺. Ca²⁺ entry then occurred upon admission of Ca²⁺ to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca²⁺ entry in a concentration-dependent manner within the range of 1 to 50 μM (IC₅₀ = 3.4 μM), but had little or no effect on the physiological Ca²⁺ spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 μM), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca²⁺]_i, which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca²⁺]_i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis.     

A Peer-Educator Network HIV Prevention Intervention Among Injection Drug Users: Results of a Randomized Controlled Trial in St. Petersburg, Russia

We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74–35.65) and 7.76 (95 % CI 3.51–17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15–1.08) without a statistically significant difference between the two groups (log rank test statistic X² = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs.     

Quantitative 3D elemental microtomography of Cyclotella meneghiniana at 400-nm resolution

X-ray fluorescence tomography promises to map elemental distributions in unstained and unfixed biological specimens in three dimensions at high resolution and sensitivity, offering unparalleled insight in medical, biological, and environmental sciences. X-ray fluorescence tomography of biological specimens has been viewed as impractical—and perhaps even impossible for routine application—due to the large time required for scanning tomography and significant radiation dose delivered to the specimen during the imaging process. Here, we demonstrate submicron resolution X-ray fluorescence tomography of a whole unstained biological specimen, quantifying three-dimensional distributions of the elements Si, P, S, Cl, K, Ca, Mn, Fe, Cu, and Zn in the freshwater diatom Cyclotella meneghiniana with 400-nm resolution, improving the spatial resolution by over an order of magnitude. The resulting maps faithfully reproduce cellular structure revealing unexpected patterns that may elucidate the role of metals in diatom biology and of diatoms in global element cycles. With anticipated improvements in data acquisition and detector sensitivity, such measurements could become routine in the near future.     

The Roll of Toll-like Receptors in the Antiphospholipid Syndrome

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis, recurrent fetal loss, and the presence of antiphospholipid antibodies (aPL). Recent data support the idea that the thrombotic activity in APS patients is attributed to enhanced cytokine release via activation of certain Toll-like receptors. To investigate these mechanisms more precisely, different experimental approaches were used to investigate this connection in detail. IgG fractions and/or monoclonal aPL, either generated from murine or human B cells were intensely used for stimulation experiments of monocytes, endothelial cells, or dendritic cells. All these stimuli induced an enhanced expression and secretion of cytokines, especially tumor necrosis factor (TNF)-α, caused by specific regulation or activation of Toll-like receptors. Using specific agonists or inhibitors could confirm the causal connection of these stimulatory effects. This review focuses on these recent developments, connecting the binding of aPL with the activity of Toll-like receptors, especially in monocytes, endothelial cells, and dendritic cells.     

Impaired cerebral autoregulation in primary biliary cirrhosis: implications for the pathogenesis of cognitive decline

Background: Cognitive impairment is recognised in the early stages of primary biliary cirrhosis (PBC). Aims: To determine the mechanisms that underlie the cognitive dysfunction that can occur in early‐stage PBC, with a particular focus on the role of autonomic dysfunction and altered cerebral autoregulation. Patients: Early‐stage PBC patients, and age‐ and sex‐matched controls. Interventions and main outcome measures: Brain magnetic resonance imaging to determine the relationship between structural brain abnormalities (T₂) and cerebral vasculature responsiveness assessed using the Valsalva manoeuvre. Dynamic assessment of cerebral vascular flow using transcranial Doppler was also performed in PBC subjects to derive the pulsatility index (a marker of cerebral resistance) and the autoregulatory slope index [ASI; ratio between the cerebral blood flow velocity and blood pressure (BP)]. Results: Cerebral resistance was increased (P=0.04), and cerebral autoregulation in response to the Valsalva was significantly impaired in the PBC group with markedly lower mean ASI values compared with the controls (7.8±7.0 vs ?8.5±8.4; P=0.002). All controls had normal cerebral autoregulation compared with only 20% of the PBC group. Indicators of sympathetic failure (BP change between Valsalva phases III–IV and low‐frequency heart rate variability) correlated with increasing globus pallidus (GP) T₂ values (P<0.05), beyond the effect of age. Conclusion: This study demonstrates the presence of increased cerebral vascular resistance and abnormal cerebral autoregulation in PBC patients, and identifies a potentially important association between the degree of abnormality in structural changes in the GP. These findings suggest that organic brain injury in PBC is directly related to autonomic dysfunction.     

Relationship Between Fear of Falling and Outcomes of an Inpatient Geriatric Rehabilitation Population—Fear of the Fear of Falling

OBJECTIVES: To examine the effects of various risk factors on three functional outcomes during rehabilitation. SETTING: Geriatric inpatient rehabilitation unit. DESIGN: Observational longitudinal study. PARTICIPANTS: One hundred sixty‐one geriatric rehabilitation inpatients (men, women), mean age 82, who were capable of walking at baseline. MEASUREMENTS: Functional status was assessed weekly between admission and discharge and at a follow‐up 4 months later at home using the function component of the Short Form—Late Life Function and Disability Instrument, the Barthel Index, and Habitual Gait Speed. Various risk factors, such as falls‐related self‐efficacy (Falls Efficacy Scale–International), were measured. Associations between predictors and functional status at discharge and follow‐up were analyzed using linear regression models and bivariate plots. RESULTS: Fear of falling predicted functioning across all outcomes except for habitual gait speed at discharge and follow‐up. Visual comparison of functional trajectories between subgroups confirmed these findings, with different levels of fear of falling across time in linear plots. Thus, superior ability of this measure to discriminate between functional status at baseline across all outcomes and to discriminate between functional change especially with regard to the performance‐based outcome was demonstrated. CONCLUSION: Falls‐related self‐efficacy is the only parameter that significantly predicts rehabilitation outcome at discharge and follow‐up across all outcomes. Therefore, it should be routinely assessed in future studies in (geriatric) rehabilitation and considered to be an important treatment goal.