Affordable measurement of human total energy expenditure and body composition using one-tenth dose doubly labelled water.

BACKGROUND: The doubly labelled water (DLW) method is the technique of choice for measurement of free-living total energy expenditure (TEE) in humans. A major constraint on the clinical applicability of the method has been the expense of the (18)O isotope. METHOD: We have used a reduced-dose (one-tenth of the currently recommended standard dose) of DLW for the measurement of TEE and body composition in nine healthy adult male volunteers. RESULTS: TEE measured by reduced-dose DLW was positively correlated with resting energy expenditure measured by metabolic cart (r=0.87, P<0.01). Isotope-derived fat mass and body mass index were strongly correlated (r=0.86, P<0.01). In four subjects in whom we performed a complementary evaluation using standard-dose isotope enrichment, the TEE measurements were satisfactorily comparable (mean+/-s.d.: reduced dose 2586+/-155 kcal/day vs standard dose 2843+/-321 kcal/day; mean difference 257+/-265 kcal/day). CONCLUSION: These data indicate that DLW measurements of human energy expenditure and body composition can be performed at a substantially reduced dose (and cost) of isotope enrichment than is currently employed.

Centenary of tele-electrocardiography and telephonocardiography.

In the history of electrocardiography the names of two physiologists stand out: Augustus Waller (1865-1922) and Willem Einthoven (1860-1927). Waller was the first to show that the beating heart produces a weak electric potential, which can be registered by a measuring device connected to electrodes attached to the skin. Einthoven developed a 'string' galvanometer, which was much faster and more sensitive than the system used by Waller. Einthoven's electrocardiograph was ready for use in 1903. To facilitate investigations of patients Einthoven connected his instrument to the Academic Hospital in Leyden, by a telephone line, as suggested by his engineering colleague Johannes Bosscha in Delft. The first successful tele-electrocardiogram was transmitted on Sunday 22 March 1905. The heart tones were registered by wiring a specially developed microphone placed on the subject's chest to another string galvanometer. The event was therefore a first both for tele-electrocardiography and for telephonocardiography. We are still awaiting the full-scale implementation of these achievements, 100 years later.

Benefits and drawbacks of telemedicine.

Telemedicine is a vast subject, but as yet there are limited data on the clinical effectiveness and cost-effectiveness of most telemedicine applications. As a result, objective information about the benefits and drawbacks of telemedicine is limited. This review is therefore based mainly on preliminary results, opinions and predictions. Many potential benefits of telemedicine can be envisaged, including: improved access to information; provision of care not previously deliverable; improved access to services and increasing care delivery; improved professional education; quality control of screening programmes; and reduced health-care costs. Although telemedicine clearly has a wide range of potential benefits, it also has some disadvantages. The main ones that can be envisaged are: a breakdown in the relationship between health professional and patient; a breakdown in the relationship between health professionals; issues concerning the quality of health information; and organizational and bureaucratic difficulties. On balance, the benefits of telemedicine are substantial, assuming that more research will reduce or eliminate the obvious drawbacks.

Social capital, gold for telemedicine?

Value norms within an interactive social network, social capital, can improve many aspects of the quality of life including health. Effective means of communication are key to making the social capital available. Telemedicine is therefore well placed to playing an important role in providing social capital to many groups in a society, which are at present deprived of this resource for maintaining health.

Wiring a medical school and teaching hospital for telemedicine.

The planning and installation of a telemedicine system for communication within a teaching hospital and its academic and hospital units with a capacity for accommodation of up to 400 video-stations is described. The system is intended for improving the communication between patients and health professionals, and between the health professionals themselves. It also provides the basis for improving pre-graduate teaching, especially problem-based learning, and all aspects of postgraduate teaching.

Human liver regeneration: hepatic energy economy is less efficient when the organ is diseased.

Recovery of liver cell mass following hepatectomy requires a metabolic compromise between differentiated function and organ regrowth. Clinical experience has shown that hepatic failure after resection is more common when the organ is diseased. We have evaluated intracellular hepatic biochemistry in patients with normal and cirrhotic livers undergoing partial hepatectomy, using 31-phosphorus magnetic resonance spectroscopy ((31)P MRS). Eighteen patients were studied, half with normal liver architecture (normal group, n = 9) and half with cirrhotic parenchyma (cirrhosis group, n = 9). Magnetic resonance examinations were performed preoperatively and on postoperative days 2, 4, 6, 14, and 28. Hepatic volume (estimated by magnetic resonance imaging [MRI]) and blood chemistries were measured at the same intervals. Following a comparable reduction in parenchymal volume, the cirrhotic group demonstrated a more sustained fall in adenosine triphosphate (ATP) energy state. Disturbance of membrane phospholipid metabolism and duration of acute-phase reaction were more marked when the liver was diseased. The pattern of derangement of hepatic function, however, was similar in the two groups. Overall, the recovery process was less efficient in the cirrhotic organ, and culminated in a diminished rate and extent of the regenerative response. These outcomes indicate that liver regeneration after partial hepatectomy involves modulation of hepatic energy economy in response to changing work demands. The efficiency of this process is influenced by the histopathologic state of the organ, and in turn governs the physiologic reserve. These findings may explain the mechanism of posthepatectomy liver failure, and offer a rational basis for the assessment of novel hepatic support strategies.

Moving with the sun.

A global 24-hour telemedicine conference entitled, "Moving with the Sun" was successfully completed on June 30 and July 1 1997 between participants from Hong Kong and China, as well as with sixteen major international medical centres around the globe. In addition to celebrating the return of Hong Kong to the People's Republic of China, the conference also signified the establishment of the Chinese University of Hong Kong, and Hong Kong as a bridge between Western countries and the PRC.

Telemedicine in China.

Telemedicine has been shown to have a considerable impact in medical education, conferencing and consultation. As a result, the People's Republic of China has been keen to develop telemedicine. In her attempts to further the development of telemedicine, China has looked to the progress of medical services in Western countries such as Europe and North America. The United States of America, however, has exceeded the rest in exchange of health-care information and telemedicine technologies with China. Although China has been enthusiastic about the exchange, telemedicine in China requires development in the technical infrastructure and professional infrastructure.

Wiring a medical school and teaching hospital for telemedicine.

The planning and installation of a telemedicine system for communication within a teaching hospital and its academic and hospital units with a capacity for accommodation of up to 400 video-stations is described. The system is intended for improving the communication between patients and health professionals, and between the health professionals themselves. It also provides the basis for improving pre-graduate teaching, especially problem-based learning, and all aspects of postgraduate teaching.

The role of telenursing in the provision of geriatric outreach services to residential homes in Hong Kong.

A residential nursing home in Hong Kong was linked to the community geriatric assessment team based in a regional hospital using videoconferencing equipment operating at 384 kbit/s. The feasibility of providing nursing services and their acceptability to users were evaluated over 12 months. There were 198 occupants of the nursing home and their mean age was 82 years (range 60-101). Services included patient education regarding the use of a metered dose inhaler, wound management and a falls prevention programme, together with assessment of clients' need for infirmary care and the risk of aspiration. The acceptability of the system to the clients and nursing home staff was also assessed. It was found that 89% of such services could be carried out via telemedicine, and only 11% required on-site visits. There was an increase in the proportion of patients correctly using inhalers as well as a reduction in the number of falls. More consultations were conducted by the nurse (an increase of 76% per month) and an additional 8.4 patients per month could be attended to by the nurse compared with 5 patients when on-site visits were used. Acceptability to clients and nursing home staff was good. The problem of lack of resources to support elderly residential care institutions makes service delivery via telemedicine appear economically attractive, as well as facilitating improvements in the quality of long-term care.

Structures of disease-specific serum alpha-fetoprotein isoforms.

Alpha-fetoprotein (AFP) is widely used as a serological marker in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT). By application of isoelectric focusing (IEF) disease-specific AFP isoforms can be identified. Three major bands are apparent: + 1 (associated with 'benign' liver disease), + II (associated with HCC) and +III (associated with NSGCT). Recently, we have characterized the predominant glycans of human serum AFP and now report the application of these findings and electrospray ionization-mass spectrometry (ESI-MS) to the determination of the glycan composition of the isoforms present in the sera of 12 patients with HCC and of one patient with NSGCT. ESI-MS allowed simultaneous identification of various AFP glycoforms in purified serum AFP. Seven glycoforms were identified, but with different abundance in the sera of the HCC patients, whereas six glycoforms were identified in the serum from the NSGCT patient. The glycan structures of these glycoforms were deduced from their observed masses. AFP glycoforms carrying a single biantennary complex-type N -glycan appeared as the predominant glycoforms, whereas those carrying both N -glycan and O -glycan appeared as minor glycoforms. Correlation between the abundance of the AFP glycoforms and the IEF band intensity suggested that different degrees in sialylation cause the formation of isoforms. This contention was subsequently supported by the ESI-MS and kinetic in vitro desialylation studies on purified Bands + l and + lI AFPs. Our findings indicate that HCC-associated isoforms (Band + II) represent a group of glycoproteins whose carbohydrate structures are all characterized by being mono-sialylated, whereas those associated with benign liver disease and NSGCT are di- and a-sialo species, respectively. Knowledge of the structure of the tumour-specific isoforms should form an important basis for clinically useful assays.

Expression of p19INK4d, CDK4, CDK6 in glioblastoma multiforme.

Deregulation of the G1/S checkpoint is a frequent event in the development of glioblastoma multiforme (GBM). Previous studies have shown more than 50% of primary GBM tumours contain either complete loss of the p16INK4a locus or amplification of the CDK4 gene. Moreover, many heterozygosity studies have shown deletion on human chromosome 19p13.2, where the p19INK4d gene has been localized. We examined the expression of p19INK4d and its two CDK substrates in a series of glioma-derived cell lines and tumours. No gene rearrangement or deletion was observed in the p19INK4d gene in these cell lines; however, expression of CDK4 and CDK6 was elevated relative to matched normal brain tissue in eight of 18 GBM tumours (44%). Furthermore, CDK6 expression level was increased in 12/14 glioblastomas, but undetectable in tumour samples of a previous lower grade tumour from the same patient. These data attest to the functional importance of both CDK4 and CDK6 in astrocytic tumourigenesis, particularly during the later stages of tumour progression.

Establishment and characterization of a human cell line from paediatric cerebellar glioblastoma multiforme.

Permanent glioma cell lines are invaluable tools in understanding the biology of glioblastomas. The present study reports the establishment of a clonal human cell line, GBM6840, derived from a biopsy of paediatric cerebellar glioblastoma multiforme. GBM6840 had a doubling time of 32 h and grew as a monolayer of large round cells that retained immunopositivity for glial fibrillary acidic protein and vimentin. Karyotypic analysis revealed a modal chromosome number of 68 and polysomies of chromosomes 3, 5 and 20, as well as the presence of 3-4 marker chromosomes. GBM6840 also showed anchorage-independent growth in soft agar and tumour formation in nude mice. The p16(CDKN2A) gene was transcriptionally silenced by hypermethylation, consistent with the lack of protein expression observed in the original tumour and cultured cells. Western blot analysis revealed normal protein expression of pRb and CDK4. It appears that p16 is the major component altered in the cell cycle pathway and may confer these cells unrestrained proliferation potential. Neither EGFR gene amplification nor over-expression of the protein was detected in the cultured cells. Over-expression of the p53 protein was observed in the majority of cells, despite undetectable mutation (exons 5-8) in the gene. One allele of the PTEN gene was found to be mutated during in vitro cultivation. Telomerase activity was demonstrated in the cultured cells but not in the original tumour, supporting the hypothesis that telomerase is required for the in vitro immortalization process.

Plasma DNA as a prognostic marker in trauma patients.

BACKGROUND: Recently, much interest has developed in the potential use of plasma DNA as a diagnostic and monitoring tool. We hypothesized that plasma DNA is increased in patients with trauma and may be prognostic in such patients. METHODS: We studied 84 patients who had sustained an acute blunt traumatic injury. We measured plasma DNA by a real-time quantitative PCR assay for the beta-globin gene. Blood samples were collected at a median time of 60 min following injury. Blood samples were also obtained from 27 control subjects. RESULTS: The median plasma DNA concentrations in the control, minor/moderate trauma (Injury Severity Score <16; n = 47), and major trauma (Injury Severity Score > or =16; n = 37) groups were 3154 kilogenome-equivalents/L, 13 818 kilogenome-equivalents/L, and 181 303 kilogenome-equivalents/L, respectively. Plasma DNA concentrations in patients with adverse outcomes, including acute lung injury, acute respiratory distress syndrome, and death, had 11. 6- to 12-fold higher plasma DNA concentrations than those who did not develop these complications. At a cutoff of 232 719 kilogenome-equivalents/L, the sensitivities of plasma DNA analysis for the prediction of acute lung injury, acute respiratory distress syndrome, and death were 100% (95% confidence interval, 100-100%), 100% (95% confidence interval, 100-100%), and 78% (95% confidence interval, 40-97%), respectively. The respective specificities were 81% (95% confidence interval, 71-89%), 80% (95% confidence interval, 70-88%), and 82% (95% confidence interval, 71-90%). CONCLUSIONS: Plasma DNA is increased after trauma and may be a potentially valuable prognostic marker for these patients.

Sodium salicylate-induced apoptosis of human peripheral blood eosinophils is independent of the activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase.

BACKGROUND: It has been shown that the inhibition of eosinophilic apoptosis is an important mechanism for the development of blood and tissue eosinophilia in allergic diseases. Considerable attention has recently been focused on the role played by different intracellular kinase cascades in the control of apoptosis. In the present study, we investigated the effect of sodium salicylate (NaSal), a nonsteroidal anti-inflammatory drug, on mitogen-activated protein kinases (MAPK) and apoptosis of human eosinophils. METHODS: Human blood eosinophils were purified from buffy coat. NaSal-induced apoptosis of eosinophils was assessed by morphological changes and Annexin-V binding assay. Changes of MAPK activity upon treatment with NaSal were measured by kinase activity assay and Western blot. RESULTS: NaSal could induce apoptosis of human blood eosinophils in a dose- and time-dependent manner. It could also activate c-Jun N-terminal kinase (JNK) and p38 MAPK but not extracellular signal-regulated protein kinase (ERK) activity within 1 h. Pretreatment of eosinophils with p38 MAPK and JNK anti-sense (AS) phosphorothioate oligodeoxynucleotides (ODN) or specific p38 MAPK inhibitor SB 203580 did not have any significant effect on NaSal-induced apoptosis. However, ERK AS ODNs could trigger the apoptosis of normal eosinophils. CONCLUSION: There is no direct relationship between the activation of JNK and p38 MAPK pathways and NaSal-induced apoptosis in human peripheral blood eosinophils.