Cancer pain management: long-term maintenance therapy.

This is a case report regarding a patient on maintenance therapy with methadone wth cancer pain. Minimal increase in methadone dose and a better modulation of administration intervals were effective, allowing the achievement of an optimal analgesia in a short time. This effect was maintained at home after discharge up the last follow-up 3 weeks after discharge. Existing literature is discussed and it is suggested to use the same drug, methadone, in increased doses.

Home palliative medicine: an audit of weekend and public holiday telephones on-call.

OBJECTIVES: To report the on-call activity of a well-established home care programme. METHODS: The charts of consecutive phone calls recorded in the weekend or public holidays were reviewed. RESULTS: The principal reason to call were based on caregivers' uncertainty, for the need of information or just to be reassured. The other more frequent reason to call was related to technical problems with peripheral intravenous central catheters. CONCLUSIONS: An integrated system of 'on call' allows to select the interventions, covering most of the patients' needs.

Opioids in advanced cancer: use, storage and disposal in the home.

OBJECTIVES: To determine the patterns of storing, using and disposing of opioids among patients with advanced cancer followed at home. METHODS: Patients who were prescribed opioids were selected. Prescribed opioids and their doses used for background pain and breakthrough pain were collected, as well as CAGE (cut down, annoyed, guilty and eye opener) for alcohol and drugs, smoking and history of illicit substance use. Questions regarding the opioid use, storage and disposal were posed. RESULTS: 100 patients were surveyed. Fifty-one patients had unused opioids at home, 25 patients did not throw away the drugs, 40 patients saved opioids for future use and 35 patients were unaware of proper opioid disposal methods. A total of 28 patients reported unsafe use by sharing or losing their opioids; 12 patients were unaware that their opioid could be fatal when taken by others. Most patients acknowledged that pain medications could be dangerous when taken by others. Patients with a partner and who were married were more likely to keep their opioids locked (p=0.028 and p=0.025, respectively). CONCLUSION: A large number of patients with advanced cancer followed at home do not store, use and dispose of opioids safely. Patient education programmes should be incorporated to decrease the availability of opioids at home for abuse, diversion, and accidental poisoning.

The use of complementary alternative medicines in advanced cancer patients followed at home.

OBJECTIVES: To assess the use of complementary alternative medicines (CAM) in advanced cancer patients followed at home. METHODS: A consecutive sample of advanced cancer patients admitted to a home palliative care program was invited to participate in the study in a period of two months. Demographic characteristics, religious belief, education level, diagnosis, and socio-economic condition were recorded. Patients were asked about the use of CAM, considered to be a health-related treatment practiced outside the established health services. Information about CAM indications and those who prescribed or suggested CAM were also collected. RESULTS: Two hundred and eighty-three advanced cancer patients followed at home were surveyed. Twelve patients (4.2%) were receiving CAM. The indication and type of CAM were variable, as well as the costs. Given the low number of patients taking CAM, no further analysis was performed. CONCLUSION: A limited number of advanced cancer patients followed at home were using CAM. Further multicenter studies with a larger sample should be performed to provide information about such therapies, also including eventual benefits.

Epidemiology and Characteristics of Episodic Breathlessness in Advanced Cancer Patients: An Observational Study.

CONTEXT: Episodic breathlessness is a relevant aspect in patients with advanced cancer. OBJECTIVES: The aim of this study was to assess the different aspects of this clinical phenomenon. METHODS: A consecutive sample of patients with advanced cancer admitted to different settings for a period of six months was surveyed. The presence of background breathlessness and episodic breathlessness, their intensity (numerical scale 0-10), and drugs used for treatment were collected. Factors inducing episodic breathlessness and its influence on daily activities were investigated. RESULTS: Of 921 patients, 29.3% (n = 269) had breathlessness and 134 patients (49.8%) were receiving drugs for background breathlessness. In the multivariate analysis, the risk of breathlessness increased with chronic obstructive pulmonary disease, although it decreased in patients receiving disease-oriented therapy and patients with gastrointestinal tumors. The prevalence of episodic breathlessness was 70.9% (n = 188), and its mean intensity was 7.1 (SD 1.6). The mean duration of untreated episodic breathlessness was 19.9 minutes (SD 35.3); 41% of these patients were receiving drugs for episodic breathlessness. The majority of episodic breathlessness events (88.2%) were triggered by activity. In the multivariate analysis, higher Karnofsky Performance Status levels were significantly related to episodic breathlessness, although patients receiving disease-oriented therapy were less likely to have episodic breathlessness. CONCLUSION: This study showed that episodic breathlessness frequently occurs in patients with breathlessness in the advanced stage of disease, has a severe intensity, and is characterized by rapid onset and short duration, which require rapid measures.

How does glycerol enhance the bioprotective properties of trehalose? Insight from protein-solvent dynamics.

We present Raman investigations on lysozyme/trehalose/glycerol solutions at low water content, from room temperature up to the occurrence of the protein thermal denaturation. We studied the Amide I band and the low-frequency spectrum as a function of the glycerol content. The former allows us to monitor the protein unfolding; the latter probes the protein and solvent dynamics in anharmonic and quasi-harmonic regimes. It was shown that adding a small amount of glycerol to trehalose stiffens the dry matrix in which proteins are embedded, thus improving their stability. The analysis of the Amide I band reveals that glycerol enhances the stabilization effect of trehalose on proteins for low water content, but still liquid, systems. Data show that the protein unfolding temperature has a maximum value around 5% Glyc/TRE g/g. The overlapping low-frequency contributions, corresponding to fast anharmonic and quasi-harmonic motions, respectively, related to the mean square displacement ⟨u(2)⟩ and the vibrational density of states (VDOS) usually determined by neutron scattering experiments, have been carefully analyzed to understand the effect of glycerol. The intensity of the quasi-elastic scattering (QES) peak reveals a dynamical-like transition at high temperatures, close to the denaturation temperature. This one, as well as the low-frequency vibrational modes, reflects the same enhanced trend of the Amide I band with respect to the glycerol concentration, but at lower temperatures. A linear correlation is found among the transition temperatures of both the dynamical-like transition and the low-frequency modes, as well as the temperature dependent change of the Amide I frequency. This confirms the solvent dynamics as a necessary precursor to promote protein unfolding. Glycerol anti-plasticizes the matrix with respect to the trehalose by enhancing the stability of the protein in a more rigid trehalose/water/glycerol matrix. As expected from the analysis of the Amide I band, the maximum effect of glycerol on trehalose is determined for 5% Glyc/TRE content.

Adherence, compliance and persistence to oral antineoplastic therapy: a review focused on chemotherapeutic and biologic agents.

INTRODUCTION: To date, orally administered chemotherapy and biologic agents represent a significant percentage of all antineoplastic treatments in several types of cancer, which are most likely to increase in the near future. In this scenario, the issue of adherence and persistence to oral therapy is a key issue since poor compliance to oral antineoplastic treatments may negatively influence patients' clinical outcomes and, in turn, cause an increase in costs, number of hospitalizations and time spent in the hospital. AREAS COVERED: The issue of adherence to new oral chemotherapeutic and/or biologic agents has not been deeply evaluated and data published in medical literature are quite scarce. Adherence is a multidimensional phenomenon, which may be influenced by patient- and health-care provider-related factors, anticancer therapy itself, education and socioeconomic aspects. Patients' selection plays, therefore, a key role in maximizing adherence and persistence to oral therapies. Treating health-care practitioners should first evaluate patient reliability to avoid prescribing oral treatments to patients with socioeconomic and medical conditions, which may predict poor adherence. EXPERT OPINION: Adherence and persistence to new oral biologic agents, which are linked to several side effects and whose use is constantly widening, should represent a main endpoint of clinical research in the nearest future.

Protein thermal denaturation and matrix glass transition in different protein-trehalose-water systems.

Biopreservation by saccharides is a widely studied issue due to its scientific and technological importance; in particular, ternary amorphous protein-saccharide-water systems are extensively exploited to model the characteristics of the in vivo biopreservation process. We present here a differential scanning calorimetry (DSC) study on amorphous trehalose-water systems with embedded different proteins (myoglobin, lysozyme, BSA, hemoglobin), which differ for charge, surface, and volume properties. In our study, the protein/trehalose molar ratio is kept constant at 1/40, while the water/sugar molar ratio is varied between 2 and 300; results are compared with those obtained for binary trehalose-water systems. DSC upscans offer the possibility of investigating, in the same measurement, the thermodynamic properties of the matrix (glass transition, T(g)) and the functional properties of the encapsulated protein (thermal denaturation, T(den)). At high-to-intermediate hydration, the presence of the proteins increases the glass transition temperature of the encapsulating matrix. The effect mainly depends on size properties, and it can be ascribed to confinement exerted by the protein on the trehalose-water solvent. Conversely, at low hydration, lower T(g) values are measured in the presence of proteins: the lack of water promotes sugar-protein interactions, thus weakening the confinement effect and softening the matrix with respect to the binary system. A parallel T(den) increase is also observed; remarkably, this stabilization can reach ∼70 K at low hydration, a finding potentially of high biotechnological relevance. A linear relationship between T(g) and T(den) is also observed, in line with previous results; this finding suggests that collective water-trehalose interactions, responsible for the glass transition, also influence the protein denaturation.

Thermal denaturation of myoglobin in water--disaccharide matrixes: relation with the glass transition of the system.

Proteins embedded in glassy saccharide systems are protected against adverse environmental conditions [Crowe et al. Annu. Rev. Physiol. 1998, 60, 73-103]. To further characterize this process, we studied the relationship between the glass transition temperature of the protein-containing saccharide system (T(g)) and the temperature of thermal denaturation of the embedded protein (T(den)). To this end, we studied by differential scanning calorimetry the thermal denaturation of ferric myoglobin in water/disaccharide mixtures containing nonreducing (trehalose, sucrose) or reducing (maltose, lactose) disaccharides. All the samples studied are, at room temperature, liquid systems whose viscosity varies from very low to very large values, depending on the water content. At a high water/saccharide mole ratio, homogeneous glass formation does not occur; regions of glass form, whose T(g) does not vary by varying the saccharide content, and the disaccharide barely affects the myoglobin denaturation temperature. At a suitably low water/saccharide mole ratio, by lowering the temperature, the systems undergo transition to the glassy state whose T(g) is determined by the water content; the Gordon-Taylor relationship between T(g) and the water/disaccharide mole ratio is obeyed; and T(den) increases by decreasing the hydration regardless of the disaccharide, such effect being entropy-driven. The presence of the protein was found to lower the T(g). Furthermore, for nonreducing disaccharides, plots of T(den) vs T(g) give linear correlations, whereas for reducing disaccharides, data exhibit an erratic behavior below a critical water/disaccharide ratio. We ascribe this behavior to the likelihood that in the latter samples, proteins have undergone Maillard reaction before thermal denaturation.

Staurosporine-induced apoptosis in Chang liver cells is associated with down-regulation of Bcl-2 and Bcl-XL.

A potent inhibitor of serine/threonine kinases, staurosporine exerts antiproliferative and apoptotic effects in many cancer cells, although the exact mechanism of its action is still unclear. This study examines the effects of staurosporine on Chang liver cells, an immortalized non-tumor cell line, in comparison with those caused in HuH-6 and HepG2 cells, two human hepatoma cell lines. Our results provide evidence that staurosporine promotes apoptosis in Chang liver cells as observed by flow cytometric analysis and acridine orange/ethidium bromide staining. The effect appeared already after 8 h of treatment and increased with treatment time and dose. After 48 h of exposure to 200 nM staurosporine clear apoptotic signs were observed in about 50% of the cells. Western blotting analysis showed that in Chang liver cells staurosporine induced a marked decrease in the levels of the antiapoptotic factors Bcl-2 (-75%) and Bcl-XL (-50%). Staurosporine also caused loss of mitochondrial transmembrane potential, release of cytochrome c from mitochondria and activation of caspase-3. The involvement of caspases in staurosporine-induced cell death was also suggested by the observation that the addition of z-VAD-fmk, a general inhibitor of caspases, suppressed apoptosis. In HuH-6 and HepG2 cells treatment with staurosporine induced the arrest of cells in G2/M phase of cell cycle. This effect was not modified by z-VAD-fmk and was not accompanied by the appearance of biochemical signs of apoptosis. We conclude that staurosporine induced apoptosis in Chang liver cells by a mitochondria-caspase-dependent pathway which was closely correlated with a decrease in Bcl-2 and Bcl-XL levels, while in HuH-6 and HepG2 hepatoma cells the drug caused only an antiproliferative effect.