Factors associated with lower quality of life among patients receiving palliative care

Title.  Factors associated with lower quality of life among patients receiving palliative care.
Aim.  This paper is a report of a study conducted to (1) assess the quality of life (QoL) and physical functioning status of patients diagnosed with advanced cancer and receiving palliative care; (2) determine if there was a statistically significant relationship between their physical functioning and QoL and (3) identify the demographic and disease-related variables related to their QoL.
Background.  Achieving the best possible QoL is a major goal in palliative care. However, research findings about the relationship between QoL and demographic variables have been inconsistent.
Method.  Three hundred patients with advanced cancer were recruited from four district hospitals in Hong Kong between February 2005 and July 2006. Their QoL and physical functioning status were assessed by face-to-face interview, using the McGill Quality of Life Questionnaire (Hong Kong version) and the Palliative Performance Scale respectively.
Results.  Participants reported reduced ambulation, inability to perform hobbies or housework, and the need for occasional assistance in self-care (mean: 64·6 out of 100, sd : 19·3, range: 20–100). QoL was fair (mean: 6·2 out of 10, sd : 1·5, range: 0·9–10). There was a weak positive association between physical functioning and QoL scores. Multiple regression analysis showed that patients who were older, female, had ever been married, or had higher physical functioning tended to have better QoL.
Conclusion.  More could be done in symptom and psychosocial management to improve patients' QoL, in particular for those who are younger, male or single, or who have lower physical functioning.     

Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin.

PURPOSE: Angiogenesis inhibitors have strong therapeutic potential as antitumor agents in suppressing tumor growth and metastatic progression. Vasostatin, the N-terminal domain of calreticulin, is a potent angiogenesis inhibitor. In this study, we determined the effectiveness of vasostatin delivered by recombinant pseudotype adeno-associated virus 2/5 (rAAV2/5-VAS) as a gene therapy approach for lung cancer treatment. EXPERIMENTAL DESIGN: We used rAAV2/5 to deliver vasostatin intratumorally or systemically in different mouse lung tumor models--subcutaneous, orthotopic xenograft, and spontaneous metastasis lung tumor models. The therapeutic efficacy of rAAV2/5-VAS was determined by monitoring tumor volume, survival rate, and degree of neovascularization after treatment in these models. RESULTS: Mice bearing subcutaneous tumor of rAAV2/5-VAS pretreated Lewis lung carcinoma cells showed >50% reduction in primary tumor volume and reduced spontaneous pulmonary metastases. The tumor-suppressive action of rAAV2/5-VAS in subcutaneous human lung tumor A549 xenograft correlated with a reduced number of capillary vessels in tumors. In the orthotopic xenograft model, rAAV2/5-VAS suppressed metastasis of A549 tumors to mediastinal lymph nodes and contralateral lung. Furthermore, treatment of immunocompetent mice in the spontaneous lung metastases model with rAAV2/5-VAS after primary tumor excision prolonged their median survival from 21 to 51.5 days. CONCLUSION: Our results show the effectiveness of rAAV2/5-VAS as an angiogenesis inhibitor in suppressing tumor growth during different stages of tumor progression, validating the application of rAAV2/5-VAS gene therapy in treatment against lung cancer.     

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

Diagnosis of nasopharyngeal carcinoma

The diagnosis of nasopharyngeal carcinoma rests on perceptive symptom analysis, a careful clinical examination, and the selection of appropriate clinical investigations. A high index of suspicion is required. When mirror examination fails to provide a satisfactory view of the nasopharynx, flexible or rigid nasopharyngeal endoscopy is mandatory. Serologic examination of IgA antibodies to Epstein-Barr virus early antigen and viral capsid antigen is helpful in identifying high-risk patients. Biopsy material should be sent fresh to the laboratory for analysis so that special staining can be carried out in cases of doubtful diagnosis.     

Optimal serological tests for the detection of Helicobacter pylori infection in the Chinese population

BACKGROUND: Numerous serological tests for the detection of Helicobacter pylori infection have been developed. However, many perform poorly when evaluated in the Chinese population. AIM: To search for optimal serological tests for the detection of H. pylori infection in Chinese patients. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, gastric biopsies were taken for the CLOtest and histological examination. Patients were then given a 13C-urea breath test. Sera were used to test for H. pylori infection, employing three commercial enzyme-linked immunosorbent assay kits (pylori DTect, HP IgG and GAP IgG). Results were compared with the gold standard defined by the CLOtest, histology and 13C-urea breath test. RESULTS: Among the 142 patients (47 male, 95 female; mean age, 49 years) recruited, 81 (57%) were H. pylori-positive, 57 (40%) were H. pylori-negative and four (3%) were defined to be indeterminate. Using a self-defined cut-off value after calculation, the best accuracies for the pylori DTect, HP IgG and GAP IgG tests were 97%, 91% and 80%, respectively. CONCLUSIONS: The pylori DTect test is an optimal serological test for the detection of H. pylori infection in Hong Kong Chinese patients. The HP IgG test may be used as an alternative.     

Effects of pharmacological preconditioning with U50488H on calcium homeostasis in rat ventricular myocytes subjected to metabolic inhibition and anoxia

1. The effects of pharmacological preconditioning with U50488H (U(50)), a selective kappa-opioid receptor agonist, on Ca(2+) homeostasis in rat ventricular myocytes subjected for 9 min to metabolic inhibition (MI) and anoxia (A), consequences of ischaemia, were studied and compared with those of preconditioning with brief periods of MI/A. 2. Precondition with 30 micro M of U(50) for three cycles of 1 min each cycle separated by 3 min of recovery (UP) significantly increased the percentage of non-blue cells following MI/A. The effect of UP is the same as that of preconditioning with an inhibitor of glycolysis and an oxygen scavenger for three 1-min cycles separated by three-minute recovery (MI/AP). The results indicate that like MI/AP, UP also confers cardioprotection. 3. MI/A increased intracellular Ca(2+) ([Ca(2+)](i)) and reduced the amplitude of caffeine-induced [Ca(2+)](i) transients, an indication of Ca(2+) content in the sarcoplasmic reticulum (SR). MI/A also reduced the electrically-induced [Ca(2+)](i) transient, that indicates Ca(2+)-release during excitation-contraction coupling, and Ca(2+) sparks in unstimulated myocytes, that indicates spontaneous Ca(2+)-release from SR. It also prolonged the decline of the electrically-induced [Ca(2+)](i) transient and slowed down the recovery of the electrically-induced [Ca(2+)](i) transient after administration of caffeine. In addition, MI/A prolonged the decline of caffeine induced [Ca(2+)](i) transient, an indication of Na(+)-Ca(2+) exchange activity, and UP prevented it. So UP, that confers cardioprotection, prevented the changes induced by MI/A. With the exception of Ca(2+)-spark, which was not studied, the effects of MI/AP are the same as those of UP. 4. It is concluded that pharmacological preconditioning with U(50), that confers immediate cardioprotection, prevents changes of Ca(2+) homeostasis altered by MI/A in the rat heart. This may be responsible, at least partly, for the cardioprotective action. 5. The study also provided evidence that MI/A causes mobilization of Ca(2+) from SR to cytoplasm causing Ca(2+)-overload which may be due to reduced Ca(2+)-uptake by SR. MI/A also reduces spontaneous and electrically induced Ca(2+) release from SR.     

Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation

The synthesis and structure-activity relationship study of a series of compounds with heterocycles in place of the cis double bond in combretastatin A-4 (CA-4) are described. Substituted tosylmethyl isocyanides were found to be the key intermediates in construction of the heterocycles. Cytotoxicities of the heterocycle-based CA-4 analogues were evaluated against NCI-H460 and HCT-15 cancer cell lines. 3-Amino-4-methoxyphenyl and N-methyl-indol-5-yl were the best replacements for the 3-hydroxy-4-methoxyphenyl in CA-4. 4,5-Disubstituted imidazole was found to be the best for the replacement of the cis double bond in CA-4. Medicinal chemistry efforts led to the discovery of compounds 24h and 25f that were found to be 32 and 82% bioavailable, respectively, in rat. Evaluation of 24h and 25f against murine M5076 reticulum sarcoma in mice revealed that both compounds were orally efficacious with an increase in life span of 38.5 and 40.5%, respectively.     

Healing of root resorption: a case report

External resorption is sequelae of necrotic periodontal membrane over a large area of root following an injury to the tooth. This usually occurs after severe dental injuries such as intrusion, severe luxations or exarticulation injuries complicated by a prolonged extra oral period. This case report presents a clinical and radiographic follow up (13 months) of treatment of inflammatory external root resorption on maxillary central incisor using Vitapex. Gradual healing of resorption was observed radiographically with no tenderness or pathological mobility.     

Epidermal growth factor improves nutritional outcome in a rat model of short bowel syndrome

Background/Purpose: This study investigates the effect of epidermal growth factor (EGF) on nutrient absorption in a rat model of short bowel syndrome (SBS). Methods: Male juvenile rats underwent either transection (Sham) or ileocecal resection leaving a 20-cm jejunal remnant. Animals underwent follow-up for 10 days, and resected animals were treated with placebo or recombinant human EGF (1-53). Animals were pair fed; in vivo nutrient absorption, intestinal permeability, morphology, and total intestinal DNA and protein content were measured. Results: Resected EGF-treated animals lost significantly less weight than those in the placebo group ([minus ]4.2 [plusmn] 3 v [minus ]13.7 [plusmn] 6.9%), absorbed significantly more 3-0 methylglucose (76.8 [plusmn] 6.6 v 64.9 [plusmn] 10.1%), and had reduced permeability (lactulose/mannitol ratio, 0.35 [plusmn] 0.19 v 0.60 [plusmn] 0.20; P [lt ] .05 for all comparisons). Conclusions: These findings show that treatment of short bowel syndrome animals with EGF reduced weight loss and improved carbohydrate absorption and intestinal permeability. These findings suggest that enteral EGF may be a useful therapy for short bowel syndrome; further studies are indicated.