Caregiving of children with intellectual disabilities in China--an examination of affiliate stigma and the cultural thesis.

BACKGROUND: While caregivers of children with intellectual disabilities are burdened in every part of the world, it is suspected that particular contexts may make the situation worse. There is little literature on caregivers in China, where familial and clan responsibility rather than individual effort is emphasised, and where communal support, while treasured, is often lacking. METHOD: A total of 211 caregivers in two cities, one with and the other without randomised design, participated in a survey study that assessed affiliated stigma, loss of face, anxiety, mental health and empowerment. RESULTS: A proportion of 60.6% of participants were found to be conspicuous cases with mental disturbance of a level which required further professional attention. Participants with better resource appeared to have coped better, enjoying lower psychological distress, lower anxiety and a higher level of personal empowerment. Multiple regression analysis revealed that mental health is related to the affective dimension of affiliated stigma, loss of face and anxiety level. This was found to account for more than half the variance (55%). DISCUSSION: The subjective burden of care occurs not in isolation but in a cultural field. Chinese caregiving is characterised by a lack of formal support, and such cultural concerns as loss of face and strong affiliated stigma. This socio-political context makes caregiving all the more challenging. The situation has to be addressed by both practitioners and policy makers if family caregiving is to be valued and made sustainable.

Clinicopathological significance of survivin expression in patients with hepatocellular carcinoma.

AIMS: Survivin, a newly discovered member of the inhibitor of apoptosis protein family, is suggested to be involved in liver carcinogenesis. The aim was to investigate the clinical significance of survivin expression in resected hepatocellular carcinoma (HCC) and paired adjacent non-tumour tissue. METHODS AND RESULTS: Immunohistochemistry, reverse transcriptase-polymerase chain reaction and Western blots were used to examine survivin mRNA and protein levels in 94 specimens of HCC tissues at different TNM stages and the data were correlated with the clinicopathological profiles. Patients were categorized into those with high tumour survivin protein levels (T-N >or= -1) and those with low levels (T-N < -1). Follow-up data were collected prospectively. mRNA levels of survivin and its splice variants in tumour tissue were significantly higher than in paired non-tumour tissue. However, survivin protein levels in paired non-tumour tissue were significantly higher than in tumour tissue from all three TNM stages. Additionally, high tumour survivin protein levels (T-N >or= -1) correlated with a better prognosis and low levels (T-N < -1) with a worse survival rate. CONCLUSIONS: High cytoplasmic survivin protein levels in HCC tissues seem to be an indicator of better prognosis in HCC patients after resection.

Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene.

The glycine N-methyltransferase (GNMT) gene encodes a protein that not only acts as an enzyme to regulate the ratio of S-adenosylmethionine to S-adenosylhomocysteine, but also participates in the detoxification pathway in liver cells. Previously, we reported that the expression level of GNMT was diminished in human hepatocellular carcinoma. In this study, the human GNMT gene was cloned and characterized. It contains six exons and spans about 10 kb. Instead of a TATA box, it has a transcriptional initiator located 801 bp upstream from the translation start codon. The gene was localized to chromosome 6p12 using fluorescence in situ hybridization. Northern blot analysis of 16 tissues from different human organs showed that GNMT was expressed only in liver, pancreas, and prostate.

Human T-cell leukemia virus type 1 pX-I and pX-II open reading frames are dispensable for the immortalization of primary lymphocytes.

Human T-cell leukemia virus type 1 (HTLV-1) infects and transforms CD4+ T-lymphocytes both in vivo and in vitro. Although the Tax protein of HTLV-1 has been strongly implicated as a transforming agent, other virally encoded proteins may also play a role in the transformation process. In addition to the rex and tax genes, the pX region of the HTLV-1 genome contains two open reading frames (pX-I and pX-II) which encode the putative viral accessory proteins known as p12I, p30II, and p13II. Mutations in the ACH molecular clone of HTLV-1 that are predicted to abrogate the expression of p12I, p13II and p30II were constructed. These mutations had no effect on viral replication or the immortalization of primary lymphocytes. Although these proteins are dispensable for viral replication and immortalization in vitro, it remains possible that they alter infection in vivo.

Breath hydrogen (H2) analysis in southern Chinese children and infants by gas chromatography and a novel automatic sampling system.

Breath hydrogen (H2) analysis was used to study lactose malabsorption in Southern Chinese children and infants. End-expired air was collected in 85 children using a modified anaesthesia bag system; while in infants, a novel automated end-expired sampling device was constructed and tested on 45 term and 27 preterm infants. Hydrogen and other respiratory gases were measured in the expired air using standard gas chromatograph equipped with a thermal conductivity detector. The system was found to have a detection limit of 0.5 ppm for H2. Both sampling methods were found to be reproducible, with intra-individual coefficient variations of less than 10%. Using 5% carbon dioxide as the expected alveolar concentration, the samples obtained by the bag system represented 85% of the end-expired air, while those obtained by the automated machine corresponded to 75%-100% end-tidal air. Taking 20 ppm rise in breath H2 as a cutoff criterion, the incidence of lactose malabsorption in the children was 78%; while in term and preterm infants this was 17.8% and 63% respectively.

Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.

The human T-cell leukemia virus type I Tax protein trans-activates several cellular genes implicated in T-cell replication and activation. To investigate its leukemogenic potential, Tax was targeted to the mature T-lymphocyte compartment in transgenic mice by using the human granzyme B promoter. These mice developed large granular lymphocytic leukemia, demonstrating that expression of Tax in the lymphocyte compartment is sufficient for the development of leukemia. Furthermore, these observations suggest that human T-cell leukemia virus infection may be involved in the development of large granular lymphocytic leukemia.

Construction and characterization of infectious human T-cell leukemia virus type 1 molecular clones.

Molecular clones of human T-cell leukemia virus type 1 (HTLV-1) have been constructed and stably propagated in plasmids in Escherichia coli. Expression of Tax could be demonstrated from these clones in fibroblast and epithelial cell lines. HOS cells stably transfected with HTLV-1 clone ACH produced all three classes of viral transcripts and Gag proteins. Virus-like particles were also produced from ACH transfected HOS cells as demonstrated by sucrose gradient and electron microscopic analyses. Transfection of peripheral blood mononuclear cells with ACH resulted in production of infectious virus particles which induced lymphocyte proliferation. This study describes useful reagents for further examination of the biological properties of HTLV-1.

CD3-dependent lymphocyte activation by human T cell leukaemia virus type I-producing T cells.

Human T cell leukaemia virus type I-(HTLV-I) transformed cells are capable of stimulating the proliferation of normal T lymphocytes, or stimulating interleukin 2 expression in Jurkat T lymphoid cells. This effect is mediated by the CD2/lymphocyte function-associated antigen 3 (LFA-3) adhesion/signalling pathway. The current work demonstrates that CD3 is also required for this effect, suggesting that the T cell receptor (TCR)/CD3 complex is mediating this effect. However, this effect does not appear to be due to a superantigen since no change in TCR expression was found after HTLV-I-mediated proliferation, nor was proliferation inhibited by an antibody against the specific TCR expressed on Jurkat cells (TCR V beta 8).

Expression of multiple oncogenes in human esophageal carcinomas.

To study the oncogenesis of human esophageal carcinoma, the expression of a variety of oncogenes was studied in 10 esophageal carcinoma cell lines and 16 pairs of tumor and nontumor tissues removed from patients with esophageal carcinoma. Northern blot analyses using 11 different oncogene probes revealed that 5 oncogenes, i.e. c-myc, c-H-ras, c-sis, c-raf, and c-fos, were expressed. Among them, a variant c-sis mRNA transcript of 2.7 kilobase (kb) was expressed in 7 of 10 cell lines and in 9 of 16 tumor tissues. Furthermore, an overexpression and an amplification of c-myc gene was observed in some cell lines. These results suggest that multiple oncogene expression may be required for the induction, maintenance, and progression of esophageal carcinoma. The expression of a 2.7-kb transcript, of c-sis and overexpression of c-myc gene may play some role in the carcinogenesis of esophageal carcinoma.

Total and regional bone mineral densities in women with Colles' fractures: a comparative study with normal matched controls.

Total body and regional bone mineral densities (BMDs) were measured in 34 women with past Colles' fracture and 34 age- and sex-matched controls using the Norland XR-26 dual energy X-ray bone densitometer. The results showed that in patients with Colles' fracture affecting the left forearms, the BMD at the ultradistal 2.5 cm region was significantly lower in the right forearm when compared with the left. This difference was not statistically significant among patients with fractures affecting the right or both forearms. The patients were also found to have lower BMDs in the femoral regions (0.600 +/- 0.010 g/cm2 in patients versus 0.655 +/- 0.019 g/cm2 in controls), pelvis (0.679 +/- 0.009 g/cm2 in patients versus 0.728 +/- 0.020 g/cm2 in controls) and spine (0.710 +/- 0.018 g/cm2 in patients versus 0.780 +/- 0.030 g/cm2 in controls) when compared with the controls. No such difference could be demonstrated in the head, trunks or arms. These data suggested that women with past Colles' fracture might be more prone to fractures of spine and femoral regions. Bone mineral densities in the weight-bearing regions, including femur and spine correlated strongly with each other (femoral neck versus lumbar spine, r = 0.64, p < 0.0001). Sites from the same anatomic regions, namely the femoral regions had highly correlated BMD values (femoral neck versus Ward's triangle, r = 0.91, SEE = 0.05, p < 0.0001), while poorer correlation was found among unrelated regions, such as between left ultradistal forearm and femoral neck (r = 0.43, SEE = 0.10, p < 0.05).

Loss of bone mass in patients with Klinefelter's syndrome despite sufficient testosterone replacement.

To determine whether testosterone replacement therapy reverses the detrimental effects of hypogonadism on bone density, we measured the total body, lumbar spine and proximal femur bone mineral density (BMD) by dual-energy X-ray absorptiometry in 14 patients with Klinefelter's syndrome on long-term testosterone replacement therapy and compared the results with 14 age- and sex-matched normal controls. Seven of the patients were receiving oral testosterone undecanoate thrice daily (240 mg/day) and the others were having intramuscular testosterone enanthate injections once every 3 weeks (250 mg/injection). Their serum testosterone levels were maintained within the normal limits (10-40 nmol/l). We showed that patients on testosterone replacement had decreased amount of bone density in the left femoral neck when compared with the controls (p < 0.01). Similar decreases were also observed in the left Ward's triangle (p < 0.01) and in the left trochanter (p < 0.05). There were no significant differences in the total body and the lumbar spine measurements in these two groups of subjects. No correlation was found between the BMD values of femur and the duration of testosterone treatment in the patients with Klinefelter's syndrome. The type of testosterone treatment was also not associated with significant differences in BMD. In conclusion, sufficient testosterone replacement with currently available methods does not reverse the decrease in bone mass associated with hypogonadism in patients with Klinefelter's syndrome.

Absence of genomes of DNA tumor viruses and expression of oncogenes and growth factors in two esophageal carcinoma cell lines of Chinese origin.

To study the oncogenesis of human esophageal carcinoma, the presence of DNA sequences homologous to several DNA tumor viruses and the expression of oncogenes and growth factor genes were examined in two esophageal carcinoma cell lines of Chinese origin, CE48T/VGH and CE81T/VGH. Southern blot analyses failed to detect sequences homologous to hepatitis B virus (HBV), Epstein-Barr virus (EBV), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV) or human papilloma virus (HPV) genomes. Northern blot analyses revealed that c-myc, c-src, c-H-ras, c-abl, c-sis, and p53 genes were expressed. In addition, transcripts of transforming growth factor alpha (TGF alpha), TGF beta, and platelet derived growth factor A (PDGF A) genes were detected. These studies suggest that DNA tumor viruses may not be involved in the carcinogenesis of esophageal carcinoma. However, cooperation among different oncogenes and the production of growth factors may play an important role in that carcinogenesis.

Overexpression of epidermal growth factor and insulin-like growth factor-I receptors and autocrine stimulation in human esophageal carcinoma cells.

The growth-stimulatory effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and insulin-like growth factor-I (IGF-I) on the human esophageal carcinoma cell line CE48T/VGH were evaluated. Under serum-free conditions, EGF, TGF-alpha, and IGF-I promoted 3.6- to 4.1-fold increased cell proliferation. Scatchard analyses and Northern blot hybridization revealed that both the EGF/TGF-alpha receptor and the IGF-I receptor were overexpressed in CE48T/VGH cells. Furthermore, ligand-dependent autophosphorylation of the EGF receptor and the IGF-I receptor was clearly detected using antireceptor and antiphosphotyrosine antibodies. Autocrine regulation was strongly indicated by the following evidence: (a) CE48T/VGH cells were found to express TGF-alpha and IGF-I genes, (b) serum-free conditioned medium promoted the growth of CE48T/VGH cells and stimulated the autophosphorylation of the EGF/TGF-alpha receptor and the IGF-I receptor, and (c) the addition of IGF-I receptor antibodies significantly suppressed CE48T/VGH cell growth under serum-free conditions. Our studies suggest that the overexpression of EGF and IGF-I receptors and autocrine growth regulation may concertedly control the proliferation of esophageal carcinoma cells.

Rapid postmenopausal loss of total body and regional bone mass in normal southern Chinese females in Hong Kong.

Osteoporosis is a major health problem in Hong Kong, affecting about 200,000 patients among a population of 6 million. To evaluate the rate of bone loss and determinants of low bone mass among the Southern Chinese, we measured the total body and regional bone mass with the XR-26 dual-energy X-ray absorptiometry in 90 normal females. The results show that the total and regional bone densities were stable before menopause, with a change of around 0.5% every year. After menopause, a rapid loss is evident for total body and regional bone mass. The rate of bone loss varies from 1.2% for the pelvis to 3.1% for the Ward's triangle per year. Thus, by the age of 70, most Southern Chinese females would have lost at least 25% of their bone. Age, body weight, and skeletal area are important determinants for the total body bone mass. Bone densities in weight-bearing regions, including hip, pelvis, spine and legs correlate strongly with each other (r = 0.68, P less than 0.001). Correlation is poor among unrelated regions, such as between head and arms (r = 0.39, P greater than 0.5). To conclude, normal Chinese women in Hong Kong lose bone rapidly after menopause at a rate of about 2% per year. This may account for the major incidence of osteoporosis-related complications in Hong Kong.

Automatic end-expiratory air sampling device for breath hydrogen test in infants.

An automatic electronically operated end-expiratory air sampler has been developed for use in small infants. Upon expiration, which is detected by a hot-wire sensor, a small portion of the end-expiratory air is automatically collected into a syringe mounted on a syringe driver. The sampler obtained 87% of the end-expiratory air sample. Additionally, highly reproducible and consistent results were obtained for the respiratory gases (O2, N2, CO2). The sampler has been applied for studying breath hydrogen excretion to detect lactose malabsorption. It may also be applicable to study other expiratory gases in infants.

Importance of measurement of bone density in the management of osteoporosis.

Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include radiogrammetry (RG) and radiographic photodensitometry (RD), single and dual photon absorptiometry (SPA and DPA), quantitative computed tomography (QCT), and single and dual-energy X-ray absorptiometry (SEXA and DEXA). These techniques provide bone mass quantitation at the spine, wrist, hip and total body skeletal sites that are the principal areas usually involved in osteoporosis. The evaluation of the aetiology, progression, and treatment of osteoporosis has been clearly improved with the use of these methods. It is the intent of this review to discuss the pros and cons of these techniques, in particular their applications to the detection and management of osteoporosis.

25-Hydroxycholecalciferol and insulin-like growth factor I are determinants of serum concentration of osteocalcin in elderly subjects with and without spinal fractures.

Osteocalcin is one of the major proteins in the osseous matrix. To evaluate the determinants and thus the physiological control of osteocalcin production in normal and osteoporotic subjects, the serum levels of osteocalcin, 25-hydroxycholecalciferol (25-OH-D3), and insulin-like growth factor I (IGFI) were measured by radioimmunoassay in 44 subjects over 60 years old. Circulating osteocalcin, 25-OH-D3, and IGFI were 0.28 +/- 0.10 nmol/L (1.65 +/- 0.96 ng/mL), 70.5 +/- 25.1 nmol/L (28.3 +/- 10.1 ng/mL), and 23.8 +/- 12.0 nmol/L in 27 healthy controls respectively, as compared with 0.09 +/- 0.09 nmol/L (0.52 +/- 0.52 ng/mL), 48.2 +/- 19.9 nmol/L (19.35 +/- 7.91 ng/mL), and 16.56 +/- 6.96 nmol/L in 17 patients with spinal fractures. Significant correlation was found between osteocalcin and 25-OH-D3 level, as well as between osteocalcin and IGFI. The results show that IGFI and 25-OH-D3 are important determinants for serum concentration of osteocalcin in elderly subjects with and without spinal fractures.

Eight-month longitudinal study of urinary excretion of albumin and tubular proteins in diabetic subjects.

To evaluate the importance of tubular proteinuria in diabetic nephropathy, we studied the serial changes of micro-albuminuria, microproteinuria and protein patterns by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in 38 diabetic patients over 8 months. There was a significant correlation between the amount of micro-albuminuria measured by radio-immunoassay and the amount of microproteinuria quantitated by the Coomassie brilliant blue dye binding method (r = 0.976; p less than 0.0001). Micro-albuminuria of 50 mg/day was equivalent to microproteinuria of 190 mg/day. Among the 38 diabetic patients, 26 had micro-albuminuria above 50 mg/day, while 12 had micro-albuminuria below this level. There was a significant correlation between the amount of microproteinuria and haemoglobin A1, showing that the quantity of microproteinuria was affected by metabolic control. Diabetic patients with micro-albuminuria of above 50 mg/day have a significantly higher diastolic blood pressure than those below this level. Among the diabetic patients with micro-albuminuria of less than 50 mg/day, the amount of micro-albuminuria and microproteinuria remained constant, whereas progressive increases in micro-albuminuria and microproteinuria were observed among the 12 diabetic subjects with micro-albuminuria above 50 mg/day. These support the prognostic importance of this quantity of micro-albuminuria. The protein patterns as revealed by SDS-PAGE with Coomassie blue staining show a significant loss of low-molecular-weight proteins in 7 patients, which may therefore suggest tubular damage. The loss of tubular proteins persisted over a period of 8 months in all 7 subjects, and the amount gradually increased over this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D status among patients with fractured neck of femur in Hong Kong.

Vitamin D deficiency leads to secondary hyperparathyroidism initially and then to mild osteomalacia, both of which conditions may be aymptomatic and may predispose to bone fracture. To assess the importance of vitamin D deficiency in predisposing to fractured neck of femur, we studied the vitamin D status, dietary intake and socio-economic characteristics in 69 patients with fractured neck of femur (group A), 28 normal subjects with age above 60 (group B), and 101 normal volunteers (group C). Patients with fractured neck of femor had significantly lower levels of serum 25-hydroxy-cholecalciferol compared with subjects of groups B and C. There is no statistically significant difference in other biochemical parameters, including calcium, phosphate, and alkaline phosphatase. Patients with fractured neck of femur and with 25-hydroxycholecalciferol below 20 ng/mL were characterized by a home-bound and/or institutionalized life-style, smaller living place, and limited access to open space. To conclude, hypovitaminosis D is a common problem among elderly patients with fractured neck of femur in Hong Kong. The fact that such vitamin D deficiency is associated with muscle weakness may contribute to falls, and thus indirectly account for an increased rate of hip fractures over the normal control.

Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD.

This double-blind crossover study compared the efficacy of two methods of delivery (MDI-spacer and nebulizer) of inhaled albuterol to patients hospitalized for an acute exacerbation of COPD. Within 24 h of admission, 20 subjects (mean age, 69 years) with severe airflow obstruction (mean FEV, 0.69 L) were subjected to a treatment with an MDI-spacer (0.36 mg of albuterol or placebo) followed by treatment with a nebulizer (2.5 mg of albuterol or placebo). Active drug was given by only one device (randomly assigned in a double-blind manner), and the entire sequence was repeated in 4 h, with active drug given in the alternate device. Spirometric data and the Borg dyspnea score were obtained before and 1 h after each sequence of treatments. Treatment resulted in significant improvements in the FEV1, FVC, and Borg score. The percent improvement in the FEV1 was slightly larger after treatment with the nebulizer (16.7 percent vs 13.4 percent). Improvements in the Borg score were slightly larger after treatment with the MDI-spacer (-1.08 vs -0.73). However, these differences were not statistically significant. This study suggests that the MDI-spacer system is an effective method of sympathomimetic delivery in this setting, provided patients are able to master the technique.