Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

PURPOSE: Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. METHODS: English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. RESULTS: Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. CONCLUSION: Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

Incorporating spirituality in psychosocial group intervention for women undergoing in vitro fertilization: a prospective randomized controlled study.

OBJECTIVES: This study examined the efficacy of a group intervention, the Integrative Body-Mind-Spirit (I-BMS) intervention, which aims at improving the psychosocial and spiritual well-being of Chinese women undergoing their first IVF treatment cycle. DESIGN: The I-BMS intervention facilitates the search of meaning of life in the context of family and childbearing, as well as the letting go of high IVF expectations. A randomized controlled study of 339 women undergoing first IVF treatment cycle in a local Hong Kong hospital was conducted (intervention: n= 172; no-intervention control: n= 167). METHODS: Assessments of anxiety, perceived importance of childbearing, and spiritual well-being were made at randomization (T(0) ), on the day starting ovarian stimulations (T(1)), and on the day undertaking embryo transfer (T(2)). RESULTS: Comparing T(0) and T(2), interaction analyses showed women who had received the intervention reported lower levels of physical distress, anxiety, and disorientation. They reported being more tranquil and satisfied with their marriage, and saw childbearing as less important compared to women in the control group. CONCLUSIONS: These findings suggest that I-BMS intervention was successful at improving the psychosocial and spiritual well-being of women undergoing their first IVF treatment cycle. This study highlights the importance of providing integrative fertility treatment that incorporates psychosocial and spiritual dimensions.

The relationships of social support, uncertainty, self-efficacy, and commitment to prenatal psychosocial adaptation.

AIMS: To report a study of the relations of prenatal psychosocial adaptation, social support, demographic and obstetric characteristics, uncertainty, information-seeking behaviour, motherhood normalization, self-efficacy, and commitment to pregnancy. BACKGROUND: Prenatal psychosocial assessment is recommended to identify psychosocial risk factors early to prevent psychiatric morbidities of mothers and children. However, knowledge on psychosocial adaptation and its explanatory variables is inconclusive. DESIGN: This study was non-experimental, with a cross-sectional, correlational, prospective design. METHODS: The study investigated Hong Kong Chinese women during late pregnancy. Convenience sampling methods were used, with 550 women recruited from the low-risk clinics of three public hospitals. Data was collected between January-April 2007. A self-reported questionnaire was used, consisting of a number of measurements derived from an integrated framework of the Life Transition Theory and Theory of Uncertainty in Illness. Explanatory variables of psychosocial adaptation were identified using a structural equation modelling programme. RESULTS: The four explanatory variables of the psychosocial adaptation were social support, uncertainty, self-efficacy, and commitment to pregnancy. In the established model, which had good fit indices, greater psychosocial adaptation was associated with higher social support, higher self-efficacy, higher commitment to pregnancy, and lower uncertainty. CONCLUSION: The findings give clinicians and midwives guidance in the aspects to focus on when providing psychosocial assessment in routine prenatal screening. Since there are insufficient reliable screening tools to assist that assessment, midwives should receive adequate training, and effective screening instruments have to be identified. The explanatory role of uncertainty found in this study should encourage inquiries into the relationship between uncertainty and psychosocial adaptation in pregnancy.

Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus.

The serological hallmark of systemic lupus erythematosus (SLE) is the presence of antibodies against double-stranded DNA. However, several studies have suggested that it is not DNA itself, but nucleosomes that are the immunogenic particles involved both in the induction of anti-DNA antibodies, and in the pathophysiology of SLE. Meanwhile, It has been demonstrated that there is an accelerated in vitro apoptosis of lymphocytes from patients with SLE. Therefore, one can postulate that the process of apoptosis may provide a source of nuclear antigens to drive the autoantibody response seen in SLE. Our study has demonstrated that hydroxychloroquine exhibits an anti-apoptotic action and this anti-apoptotic effect is dependent on monocyte coexistence. We used both morphology assessment and fluorescent antibody cell sorter (FACS) analysis to measure the apoptotic percentage of lymphocytes from 25 SLE patients in medium alone (control) or with the addition of different concentrations of hydroxychloroquine. Our results have shown that there is a significant decrease in the percentage of apoptosis at the therapeutic concentration (10(-6) M) as compared with the control (p < 0.05). It has been reported that the anti-rheumatic properties of hydroxychloroquine result from its interference with antigen processing in macrophages and other antigen-presenting cells. We propose that this results in decreased stimulation of autoreactive lymphocytes reactive with self-peptides, and consequently diminution of activation-induced cell death (apoptosis) of mature peripheral lymphocytes.

Pulmonary actinomycosis in Korea.

Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces, a Gram-positive, microaerophilic bacterium. Pulmonary involvement, other than cervicofacially or abdominopelvically, is uncommon and often leads to a misdiagnosis of pulmonary tuberculosis or lung cancer. In order to investigate the clinical, radiological, diagnostic and therapeutic characteristics of pulmonary actinomycosis, we reviewed a total of 25 cases reported in Korea. Thirteen were diagnosed at our hospital between 1985 and 1997 and 12 were reported in Korean publications. The condition occurred most frequently in middle-aged males, the most common symptom being haemoptysis, followed by cough and sputum. The main radiological features were peripherally located mass or nodule and consolidation, with central low attenuation. Complications such as empyema, sinus fistula or mediastinitis did not occur. Diagnosis was confirmed by percutaneous needle aspiration (n = 8), bronchoscopic biopsy (n = 3) or thoracotomy (n = 13). Eleven of 25 cases were treated medically and in nine others, surgical resection was followed by treatment with antibiotics. In conclusion, when a middle-aged male patient presents with haemoptysis and cough, together with radiologic findings of a peripheral mass or nodule with/without central low attenuation, pulmonary actinomycosis should be suspected.

The effect of allergen immunotherapy on in vitro IL-4 and IFN-gamma production by peripheral mononuclear cells in house dust-sensitive Chinese patients with bronchial asthma.

The IFN-gamma produced by Th1 cells and IL-4 produced by Th2 cells are two most important cytokines in the regulation of IgE production. House dust immunotherapy has been tried in the treatment of house dust-sensitive Chinese asthmatic patients with good results. We examined the influence of such treatment on in vitro IL-4 and IFN-gamma production by peripheral blood mononuclear cells in house dust-sensitive asthmatic patients. Allergen immunotherapy in house-dust sensitive asthmatic patients can significantly decrease IL-4 production from peripheral mononuclear cells (p<0.05). The production levels of IL-4 in patients without treatment had higher levels than those in patients with hyposensitization (p<0.01). Such therapy also have some effect on promotion of IFN-gamma production in asthmatic patients. In conclusion, immunotherapy with house dust may have the potential ability to shift the Th1/Th2 balance of immune response to allergens and to create a favorable cytokine microenvironment to suppress the allergic reaction in the asthmatic airway.

Measurement of synovial tumor necrosis factor-alpha in diagnosing emergency patients with bacterial arthritis.

Because of the high morbidity and mortality in patients with bacterial arthritis, rapidly and correctly diagnosing this critical condition is a challenge to emergency clinicians. Synovial fluid samples were obtained from 75 patients with arthritis disorders who presented to an emergency service, and levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured. Twenty patients with culture-proven bacterial arthritis had higher levels of synovial TNF-alpha than patients with osteoarthritis or with inflammatory arthritis, including gouty arthritis, rheumatoid arthritis, reactive arthritis, and lupus arthritis. There was a good sensitivity for synovial TNF-alpha level in diagnosing patients with bacterial arthritis. Nearly 100% of patients with bacterial arthritis had elevated synovial TNF-alpha levels. However, synovial IL-1 beta and IL-6 levels failed to discriminate bacterial arthritis from other inflammatory arthritis. Measurement of synovial TNF-alpha level may be useful as a diagnostic aid in emergency patients with bacterial arthritis disorders.

CT-guided percutaneous insertion of interstitial radiotherapy catheters in head and neck tumors.

We describe a new method of placing interstitial radiation therapy catheters in patients with head and neck tumors. In three patients with recurrent inoperable head and neck tumors CT guidance was utilized to insert interstitial radiation therapy catheters percutaneously. This method enabled palliative radiation therapy to be administered without the need for surgical placement of seeds or catheters. The detailed anatomical localization of tumor and vascular structures provided by CT enabled precise percutaneous placement of afterloading catheters while ensuring safety. Pain was reduced and tumor size was decreased in all three patients. The CT-guided percutaneous insertion of afterloading catheters is a simple yet effective method of providing interstitial radiation therapy for head and neck tumors.

The study of anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with systemic lupus erythematosus and central nervous system involvement.

Anticardiolipin (ACL) antibodies and interleukin-6 (IL-6) in cerebrospinal fluid (CSF) may be involved in the mechanism of lupus patients with central nervous system (CNS) involvement. ACL antibodies of 3 isotypes and IL-6 were measured in paired CSF and serum samples from 14 lupus patients with CNS involvement, 5 lupus patients without CNS involvement and 7 patients with non-inflammatory neurological diseases. ACL antibodies, IgG and IgM isotypes, and IL-6 were significantly increased in CSF from lupus patients with CNS involvement as compared with other 2 groups of patients. Both ACL antibodies and IL-6 decreased after neurological activity subsided. These results suggest increased ACL antibodies and IL-6 in CSF are involved in immune responses within CNS in lupus patients. Quantitation of CSF ACL antibodies may be helpful in evaluating neurological activity of lupus patients with CNS involvement.

Measurement of anti-endothelial and anti-cardiolipin autoantibodies and intercellular adhesion molecules-1 in patients with systemic and cutaneous vasculitis.

Two types of autoantibodies and intercellular adhesion molecule-1 (ICAM-1) were measured in patients with vasculitis. There were 13 patients with systemic vasculitis, and 12 with cutaneous vasculitis. The measured antibodies included antiendothelial cell antibodies (AECA) and anti-cardiolipin (ACL) antibodies of three isotypes. Results showed that patients with systemic vasculitis had elevated levels of ICAM-1 and IgG isotype ACL antibodies. Higher levels of ICAM-1 and IgG isotype ACL antibody were found in patients with systemic vasculitis than in those with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement, and for following the disease course.

Monoclonal gammopathies and the related autoimmune manifestations in Taiwan.

A total of 50,000 patients were surveyed for the presence of monoclonal immunoglobulins during the past two decades. There were 411 cases of monoclonal gammopathies including 243 cases of plasma cell neoplasms and 168 cases of secondary plasma-cell dyscrasia. Among the 227 cases of multiple myeloma and Waldenström's macroglobulinemia, there were 49.3% IgG class, 22.9% IgA class, 9.7% IgM class and 13.2% light chain type. In addition, there were 1.3% of nonexcretory myeloma including an IgM type. A relatively high frequency (4.8%) of IgD M-proteins was detected but heavy chain disease was not encountered in the present series. Purified M-components from patients with possible autoimmune manifestations were subjected to immunofluorescence studies. Autoimmune activity of M-proteins was found in a patient of Waldenström's macroglobulinemia with peripheral neuropathy, and another patient of cryofibrinogenemia with recurrent purpura and gangrene. In conclusion, a high frequency of IgD myeloma is found in Chinese patients of this area. M-components may have autoimmune activity resulting in unusual clinical manifestations.

Pancreatitis related to antiphospholipid antibody syndrome in a patient with systemic lupus erythematosus.

A 39-year-old woman was admitted with abdominal pain and dyspnea, and a diagnosis of systemic lupus erythematosus with renal involvement was established. Laboratory tests revealed highly elevated anticardiolipin antibody, thrombocytopenia and false positive VDRL. Generalized thrombus formation and Libman-Sacks endocarditis were found at postmortem examination. The pancreas showed chronic inflammation with thrombi in pancreatic arteries, but no vasculitic change was observed. Lowering of pancreatic blood flow because of arterial thrombi was a possible cause of pancreatitis in this patient. The spectrum of antiphospholipid antibody associated diseases may be extended to include pancreatitis as a thrombotic complication.

Immunochemical characterization and therapeutic effect of house dust extract in bronchial asthma.

The immunochemical characteristics of house dust extract used in hyposensitization were studied by SDS-polyacrylamide gel, isoelectrofocusing, counterimmunoelectrophoresis and Western blot. The gel electrophoregram and isoelectrofocusing plate demonstrated a complex mixture of acid proteins with molecular weights ranging from 56 to 12 KD and isoelectric point distributing from 4.6 to 5.6. The counterimmunoelectrophoresis revealed as many as five precipitating bands in sera from 60% asthmatic patients after hyposensitization. The Western blot showed heterogeneous IgE reaction bands varied from 45 to 22 KD, including a strong 27 KD reaction band found in 40% of the asthmatic patients not receiving hyposensitization. The efficacy of house dust extract hyposensitization was evaluated in 102 asthmatic patients, followed up at the Allergic Clinic since 1980. There were 42 malea and 60 females with a mean age of 30.8 (16 to 60), and the total follow-up patient-year was 512.6 with a mean of 5.0 year per patient (1 to 11). Complete remission of asthmatic symptoms and medication was found in 5% patients, and 12% patients had little or no improvement. The majority of patients (83%) had improvement in asthmatic symptoms and medication dosage. The average serum IgE levels and total eosinophil count dropped significantly after hyposensitization (p < 0.001). In conclusion, the immunochemical characteristics of house dust extract were analyzed and mite allergens, especially Group I antigens, may be the important constituents. Good therapeutic effect, both clinically and with laboratory evaluation, was obtained with more than 80% of the asthmatic patients achieving improvement under house dust hyposensitization.

Biclonal gammopathy--report of a case with primary gastrointestinal lymphoma.

A 61-year-old female patient had had abdominal pain for two months; primary gastrointestinal lymphoma of diffuse, large cell type histology was diagnosed. Bone marrow study was negative. Bimodal gamma globulin was found on serum protein electrophoresis. Immunoelectrophoresis and immunofixation confirmed the nature of biclonal gammopathy with a fast-migrating IgM-kappa band and a slow-migrating IgG-kappa band. Biclonal gammopathy is unusual, and only rarely have cases been reported. The immunologic and molecular implications of biclonal gammopathy are discussed.

Anticardiolipin antibodies in patients with acute myocardial infarction.

Fifty-six consecutive patients, 53 males and 3 females aged from 36 to 83 with a mean age of 61.0, all with acute myocardial infarction (AMI), were screened for anticardiolipin antibodies (ACA) by single sampling at time of admission to the medical intensive care unit; results were compared with those for age-matched, healthy controls. IgM and IgG-ACA were measured by an enzyme-linked immunosorbant assay technique. IgG-ACA were detected in 9 patients (16.1%); IgM-ACA were detected in 9 patients (16.1%). Only one of the patients had raised ACA of both isotypes. There was on difference in either ACA levels or frequency of ACA elevation between patients and controls. Risk factors of coronary artery disease showed no significant difference between patients with and without ACA. Low titer of IgG-ACA was found in one of ten patients with reinfarction and/or previous cerebral infarction. In conclusion, single measurements of anticardiolipin antibodies in general AMI patients are unlikely to yield diagnostically important information. The implication of occasional significant elevation of such antibodies in a general AMI population remains to be speculated.

Continuous methacholine inhalation provocation with resistance monitoring in asthmatic patients.

Continuous methacholine inhalation with simultaneous bronchial resistance monitoring was performed in 15 controls and 26 asthmatic patients. The subjects were in quiet tidal breathing, and the airway resistance measured by forced oscillation method were continuously recorded with X-Y recorder. The mean airway resistance of the asthmatic patients was higher than that of the control group, so was the conductance of the asthmatics lower than that of the control. All the asthmatics were responsive to the methacholine test, while only two controls had the response. No correlation could be obtained between bronchial reactivity and sensitivity, but the bronchial sensitivity was correlated with serum total IgE (r = 0.448; p less than 0.05), and suggest that the higher the IgE is, the more sensitive the asthmatic patients respond to methacholine. Continuous methacholine provocation is useful in the diagnosis of bronchial asthma and is more safe and time-saving compared with conventional intermittent method.

Serum interleukin-2 receptor in systemic lupus erythematosus and rheumatoid arthritis.

Interleukin-2 receptor (IL-2R) is expressed on activated lymphocyte after stimulation with antigen or interleukin-2 (IL-2), meanwhile soluble form of the receptor is released. Using enzyme-linked immunosorbent assay, serum IL-2R levels were determined in 34 healthy controls, 61 patients with systemic lupus erythematosus (SLE) and 32 patients with rheumatoid arthritis (RA), yielding mean +/- SD values of 355 +/- 89, 807 +/- 453 and 567 +/- 210 U/ml respectively. In both SLE and RA patients, the active disease group had more markedly elevated serum IL-2R levels compared with those of the inactive group. In patients with SLE, elevated serum IL-2R is associated with lymphopenia, renal disorders, decreased C3 level and increased anti-DNA, thus make it a good parameter to monitor disease activity in SLE.

Characteristics of the cytotoxic effects of the phenothiazine class of calmodulin antagonists.

We have characterized the antiproliferative effects of the phenothiazines, a group of antipsychotic drugs possessing a wide range of pharmacological actions. The phenothiazines inhibited both the proliferation and clonogenicity of L1210 leukemic lymphocytes. This effect was dependent on both time of exposure and concentration of drug. Clonogenicity of cells in the logarithmic phase of growth was inhibited by greater than 99% at a concentration of drug that had no effect on cells in the plateau phase of growth. Human and murine cell lines, grown either in suspension or in monolayers, were equally susceptible. Calmodulin (CaM), purified from L1210 cells by preparative polyacrylamide gel electrophoresis, had sensitivity to inhibition by phenothiazines similar to that reported for CaM prepared from brain. The order of potency was trifluoperazine greater than or equal to fluphenazine greater than chlorpromazine greater than chlorpromazine-sulfoxide. As a class, these drugs were less potent antagonists of CaM than was the bee venom polypeptide, melittin. The antiproliferative effects of phenothiazines were similar to the anticalmodulin effects. Thus, the same order of potencies was seen for both effects; the shapes of the dose-response curves were similarly steep and the effects of excess calcium on the inhibition of both were identical. These studies add pharmacological support for CaM being a potential intracellular target for the antiproliferative effect of the phenothiazines.

Inhibition of growth of C6 astrocytoma cells by inhibitors of calmodulin.

We evaluated the effect of several classes of calmodulin inhibitors on the activity of calmodulin prepared from C6 astrocytoma cells and studied the activity of these drugs as inhibitors of the growth of C6 cells in tissue culture. There was a good correlation between the activity of the drugs as inhibitors of calmodulin and their activity as inhibitors of cell growth. The most potent compounds were calmidazolium and melittin as compared to the phenothiazines, trifluoperazine, chlorpromazine, chlorpromazine-sulfoxide or the diphenylbutylpiperidine, pimozide. The mechanism by which the inhibition of calmodulin leads to the death of cells could not be attributed entirely to inhibition of the calmodulin-sensitive cyclic nucleotide phosphodiesterase. Calmodulin is a heat stable, calcium-binding protein involved in numerous biological processes. Recent evidence indicates that calcium and calmodulin may be important for cellular proliferation. For example, this protein changes in concentration during the cell cycle; is involved in the disassembly of the mitotic apparatus; is increased in concentration in rapidly growing hepatomas and in transformed fibroblasts. Weiss and co-workers demonstrated that phenothiazines and structurally similar drugs are capable of binding to and inhibiting the activity of calmodulin. It has been recently observed that certain drugs that inhibit the activity of calmodulin also inhibit the growth of malignant cells in vitro and in vivo. In these studies, however, there was no direct correlation of the effect of the drugs on the calmodulin from the cell type under investigation with cytotoxicity. To learn more about the relationship between a drug's ability to inhibit calmodulin and its antiproliferative activity, we correlated the effect of drugs on the activity of calmodulin prepared from the C6 astrocytoma cell line with their effect on cellular proliferation. Since many inhibitors of calmodulin readily cross the blood-brain barrier and since no acceptable treatment for malignancies of the central nervous system exist, we chose this cell line as a model for elucidating the potential antineoplastic effects of calmodulin inhibitors.