Too tall for the tape: the weight of schoolchildren who do not fit the Broselow tape.

BACKGROUND: In paediatric resuscitation, for a rapid and accurate estimate of children's weight, the Broselow tape can be used in children who are 46-144 cm tall. The Broselow tape has previously been found to provide the most accurate estimate of children's weight internationally, but it is not known how many fall outside the range of the tape, or whether such children can be assumed to be of adult weight, or how otherwise to estimate the weight of these children. OBJECTIVES: To determine what proportion of children in different age groups falls outside the limits of the Broselow tape, how their weight compares with that of the adults and what correlates most strongly with weight in these children. METHODS: This was a population-based prospective observational study of Chinese children up to 12 years old, from schools in Hong Kong. Weight was measured to the nearest 0.2 kg, and the height, foot-length and mid-arm circumference (MAC) were measured to the nearest 0.1 cm. RESULTS: 40% of 10-year olds and 70% of 11-year olds were too tall for the tape. Their median weight was 41.9 kg. This was significantly less than the median weight of 18-year olds (55 kg, p<0.0001) in Hong Kong. The strongest correlate with weight in these children was MAC. CONCLUSIONS: The Broselow tape is inappropriate for use in most children over 10 years old. Children too tall for the tape cannot be assumed to be of adult weight; to do so would imply an average overestimate of 30%. Weight estimates in older children could be based on MAC.

Expression of NEDD4L and ENaC in Urinary Extracellular Vesicles in Pre-eclampsia.

OBJECTIVE: To assess changes in expression of renal epithelial sodium channel (ENaC) and NEDD4L, a ubiquitin ligase, in urinary extracellular vesicles (UEV) of pre-eclamptic women compared to normal pregnant controls. METHODS: Urine was collected from pre-eclamptic women (PE, n = 20) or during normal pregnancy (NP, n = 20). UEV were separated by differential ultracentrifugation. NEDD4L, α-ENaC and γ-ENaC were identified by immunoblotting. RESULTS: There was no difference in the expression of NEDD4L (p = 0.17) and α-ENaC (p = 0.10). PE subjects showed increased expression of γ-ENaC by 6.9-fold compared to NP (p < 0.0001). CONCLUSION: ENaC expression is upregulated in UEV of pre-eclamptic subjects but was not associated with changes in NEDD4L.

The normal ranges of cardiovascular parameters in children measured using the Ultrasonic Cardiac Output Monitor.

OBJECTIVE: The Ultrasonic Cardiac Output Monitor is a noninvasive method of hemodynamic assessment and monitoring in critically ill patients. There are no published reference ranges for normal values in children for this device. This study aimed to establish normal ranges for cardiovascular indices measured using Ultrasonic Cardiac Output Monitor in children aged 0-12 yrs old and to assess interobserver reliability. DESIGN: This was a population-based cross-sectional observational study. SETTING: Schools and kindergartens in Hong Kong. SUBJECTS: Chinese children aged up to 12 yrs old. INTERVENTIONS: Two operators performed Ultrasonic Cardiac Output Monitor scans on each child together with standard oscillometric measurement of blood pressure and heart rate. Software intrinsic to the Ultrasonic Cardiac Output Monitor device produces values for stroke volume, cardiac output, and systemic vascular resistance. For each parameter, normal ranges were defined as lying between the 2.5th and 97.5th percentiles. Interobserver reliability was assessed with Bland-Altman plots, coefficients of variation, and intraclass correlation. MEASUREMENTS AND MAIN RESULTS: A total of 1,197 Chinese children (55% boys) were scanned. Normal ranges of values for cardiac output, stroke volume, and systemic vascular resistance indices are presented. Interobserver reliability for Ultrasonic Cardiac Output Monitor was superior to that for standard blood pressure and heart rate measurement. CONCLUSIONS: This large study presents normal values for cardiovascular indices in children using the Ultrasonic Cardiac Output Monitor with good interobserver reliability.

Cost minimization analysis of capecitabine versus 5-fluorouracil-based treatment for gastric cancer patients in Hong Kong.

BACKGROUND: EOX (epirubicin, oxaliplatin, Xeloda; capecitabine) and FOLFOX4 (5-fluorouracil (5-FU), leucovorin, oxaliplatin) are the common chemotherapy regimens used in the treatment of advanced gastric cancer (aGC) in Hong Kong. This study aimed to compare the costs of these therapies for aGC patients from both the healthcare and societal perspectives. It should be noted that, while FOLFOX4 is routinely administered in an outpatient setting in North America and Europe, inpatient setting is adopted in Hong Kong instead, incurring hospitalization cost as a result. METHODS: Fifty-eight patients were identified from the electronic records in two public tertiary hospitals, with 45 and 13 receiving EOX and FOLFOX4 regimens, respectively. Healthcare cost was direct medical costs including drugs, clinic follow-up, hospitalization, diagnostic laboratories, and radiographs. Societal cost refers to indirect costs such as patient time and travel costs. Cost items were further classified as "expected" or "unexpected". All cost data was expressed in US dollars. RESULTS: Patients in the EOX and FOLFOX4 arm received an average of 5.3 and 7.8 cycles of treatment, respectively. The capecitabine-based regimen group had a higher expected medication cost per cycle when compared to the 5-FU-based treatment group (US$290.3 vs US$66.9, p < .001), but lower expected hospitalization costs (US$76.9 vs US$1,269.2, p < .001). The total healthcare cost and total societal cost per patient was reduced by 67.2% (US$5,691.9 vs US$17,357.4, p < .001) and 25.3% (US$3,090.5 vs US$4,135.1, p = .001), respectively, in the capecitabine-based regimen group. Sensitivity analyses based on full cycle regimen costs and net capecitabine or 5-FU/leucovorin costs still showed EOX to be less costly than FOLFOX4. CONCLUSION: The capecitabine-based regimen, EOX, was found to generate significant cost saving from both the healthcare and societal perspectives in regions in which FOLFOX4 is given in an inpatient setting.

The normal ranges of cardiovascular parameters measured using the ultrasonic cardiac output monitor.

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18-60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18-60 years; (2) combine these data with those for healthy children (aged 0-12), adolescents (aged 12-18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM-derived variables according to both weight and age. This was a population-based cross-sectional observational study of healthy Chinese subjects aged 0.5-89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5-89; 52% male). From previous studies, 1197 children (aged 0-12, 55% male), 590 adolescents (aged 12-18, 49% male), and 77 elderly (aged 60-89, 55% male) were included. New data were collected from 354 adults aged 18-60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly.

The angiosuppressive effects of 20(R)- ginsenoside Rg3.

Aberrant angiogenesis is an essential step for the progression of solid tumors. Thus anti-angiogenic therapy is one of the most promising approaches to control tumor growth. In this study, we examined the ability of 20(R)-ginsenoside Rg3 (Rg3), one of the active compounds present in ginseng root, to interfere with the various steps of angiogenesis. Rg3 was found to inhibit the proliferation of human umbilical vein endothelial cells (HUVEC) with an IC50 of 10 nM in Trypan blue exclusion assay. Rg3 (1-10(3) nM) also dose dependently suppressed the capillary tube formation of HUVEC on the Matrigel in the presence or absence of 20 ng/ml vascular endothelial growth factor (VEGF). The VEGF-induced chemoinvasion of HUVEC and ex vivo microvascular sprouting in rat aortic ring assay were both significantly attenuated by Rg3. In addition, Rg3 (150 and 600 nM) remarkably abolished the basic fibroblast growth factor (bFGF)-induced angiogenesis in an in vivo Matrigel plug assay. The Matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, which play an important role in the degradation of basement membrane in angiogenesis and tumor metastasis present in the culture supernatant of Rg3-treated aortic ring culture were found to decrease in their gelatinolytic activities. Taken together, these data underpin the anti-tumor property of Rg3 through its angiosuppressive activity.

Apolipoprotein epsilon-4 allele and the two-year progression of cognitive function in Chinese subjects with late-onset Alzheimer's disease.

BACKGROUND: Although the significance of apolipoprotein E4 (Apo E4) in Alzheimer's disease (AD) has been well established in Caucasian populations, its role in determining the rate of cognitive decline in other ethnic groups has yet to be determined. This study examined the two-year progression of cognitive decline and its association with Apo E4 allelic status in a group of Chinese elderly subjects with AD. METHOD: One hundred and four Chinese subjects with mild and moderate AD as assessed by the Clinical Dementia Rating (CDR 1 and 2) were followed up at a mean (SD) duration of 22.53 (5.21) months. The rate of cognitive decline and its association with Apo E4 allelic status was evaluated RESULTS: At follow-up, 74 (73 percent) subjects were reassessed. Forty-nine remained stable at the same CDR and 25 had deteriorated. The mean (SD) deterioration in the Mini-Mental State Examination (MMSE) was 2.52 (4.38) and in the Mattis Dementia Rating Scale (DRS) was 9.03 (14.98) (paired t-test, p < 0. 001). There was no significant difference in the baseline MMSE and DRS scores between the "stable", "deteriorated", or "deceased" groups. Mildly demented subjects with the Apo E4 allele were more likely to have deteriorated to a more severe CDR than subjects without the Apo E4 allele (Pearson chi2 = 5.72, df 1, p = 0.017, Odds ratio = 6.3, CI 1.3 to 30.53). CONCLUSION: The presence of the Apo E4 allele may influence the rate of cognitive deterioration, particularly in subjects with mild AD.

Electrogenic ion transport in the mouse endometrium: functional aspects of the cultured epithelium.

A primary culture of mouse endometrial epithelium grown on permeable supports was established and the electrogenic ion transport across the endometrial epithelium was studied using the short-circuit current (I(SC)) technique. Enzymatically isolated mouse endometrial cells were immunostained with epithelial cells markers, cytokeratins, indicating an epithelial origin of the culture. Mouse endometrial epithelial cells grown on Millipore filters formed polarized monolayers with junctional complexes as revealed by light and electron microscopy. The cultured monolayers exhibited an average basal I(SC) of 4.6 +/- 0.3 microA/cm2, transepithelial voltage of 2.7 +/- 0.2 mV and transepithelial resistance of 599 +/- 30 omega cm2. The basal current was reduced by 85% in Na+-free solution and 13% in Cl(-)-free solution. The basal current could also be substantially (57.7%) blocked by an apical Na+ channel blocker, amiloride (10 microM), suggesting that Na+ absorption largely contributed to the basal current. Apical addition of Cl- channel blocker, DPC (2 mM), also exhibited an inhibitory effect, 19.4%, on the basal I(SC), indicating minor involvement of Cl- secretion as compared to that of Na+ absorption. The cultured endometrial epithelium also responded to a number of secretagogues including adrenaline and forskolin with increases in the I(SC), which could involve substantial Cl- secretion. The present study has established a culture of mouse endometrial epithelium exhibiting predominantly Na+ absorption under unstimulated condition, and Cl- secretion in response to various secretagogues. This culture may be useful for studying various regulatory mechanisms of electrogenic ion transport across the endometrial epithelium.

The role of calcitonin gene-related peptide in the regulation of anion secretion by the rat and human epididymis.

A study was carried out to investigate the role of the calcitonin gene-related peptide (CGRP) in the regulation of electrolyte transport in the rat and human epididymis. In monolayer cultures derived from the rat cauda epididymal cells, CGRP stimulated the short-circuit current (SCC) in a dose-dependent manner with the EC50 (concentration required to produce 50% of the response) at 15 nmol/l. This effect of CGRP was seen when the peptide was added to the basolateral aspect of the cells; apical addition having negligible effect. The CGRP-induced rise in the SCC was dependent on the presence of chloride in the bathing solution. Calcitonin had no effect on the SCC and did not affect the CGRP-induced rise in the SCC. The effect of CGRP on secretion was inhibited in a competitive fashion by the CGRP receptor antagonist CGRP(8-37). In contrast to bradykinin, angiotensin II and endothelin I, the effect of CGRP was independent of prostaglandin synthesis. Measurement of intracellular adenosine 3':5'-cyclic monophosphate showed a time- and dose-dependent increase upon stimulation with CGRP. CGRP also stimulated the SCC in monolayers grown from the human epididymis. The current could be inhibited by apical application of the chloride channel blocker, diphenylamine-2-carboxylate. Immunoreactive CGRP was found in the epithelia of rat and human cauda epididymidis. It is suggested that CGRP may regulate the electrolyte and fluid secretion in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of spermatozoa.

Localization and distribution of angiotensin II in the rat epididymis.

The localization and distribution of angiotensin II (Ang II) in the rat epididymis was studied using immunohistochemical and RIA techniques. The immunohistochemical results showed that Ang II-like immunoreactivity progressively increased along the length of the rat epididymis (cauda > corpus >> caput) and was predominately localized in the basal region of the epididymal epithelium. Occasionally, immunostaining of lighter intensity was also found in the apical region. The concentration of Ang II in cultured rat cauda epididymal epithelial cells was further measured by RIA. In addition to that found in cultured epithelial cells, Ang II activity was also detected in the culture medium, suggesting a secretory role of the epithelium. These findings suggest that Ang II could be derived locally from epididymal epithelium and that it could play a role in local regulation of epithelial transport and, possibly, in the maintenance of sperm function as well, by exerting its paracrine and/or autocrine effect in various regions of the epididymis.

Understanding the spatial clustering of severe acute respiratory syndrome (SARS) in Hong Kong.

We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease "hot spots." Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated.

CGRP-immunoreactivity in Merkel cells and nonmyelinated nerve plexuses of dog skin.

In dog skin Merkel cells, calcitonin gene-related peptide (CGRP) immunoreactivity was consistently encountered at the subcellular dense-core granule region. The immunogold particles used as a marker for CGRP, were located specifically in and around the dense-core granules. They were also found in the surrounding cytoplasm close to the dense-core granules. Nerve terminals supplying the Merkel cell were CGRP-negative. CGRP-immunoreactive nonmyelinated nerve fibres were also found in the same specimen. These nonmyelinated nerve fibres were ensheathed by Schwann cell cytoplasm. The gold particles were only located in the dense-core granules of the axis cylinders. It is concluded that a CGRP-like substance predominantly accumulates in the dense-core granules of dog Merkel cells as well as in cutaneous nonmyelinated fibres.

Cytotoxic effect of ascorbate and its derivatives on cultured malignant and nonmalignant cell lines.

The effect of L-ascorbate and its derivatives on the growth of malignant and nonmalignant cell lines has been examined. L-Ascorbate and its oxidative product dehydroascorbate were cytotoxic or lethal to the fast-growing malignant cells, but they were less toxic to nonmalignant cells. Two isomers of ascorbate, D-ascorbate and D-isoascorbate, both with 5% of the antiscorbutic potency and very high turnover rate, had similar activities. The cytotoxic effect of ascorbate was apparently not related to the metabolic or vitamin activities of ascorbate at the cellular level. Furthermore, studies on the viability of treated cells indicated that the observed effect on cell growth was not cytostatic in nature but was the result of a direct cell-killing action of ascorbate. Several groups of ascorbate derivatives were also tested; many of them were toxic to these cells. The results support the hypothesis that the cytotoxic activity of ascorbate was due to its chemical properties and that certain oxidation and degradation products of ascorbate were cytotoxic agents.

Microwave fixation of nuclear matrix in tumor cells.

Microwave irradiation provides good fixation of human and animal tissues for light and electron microscopy. In this study, microwave irradiation was used for the fixation of cytoplasmic and nuclear matrix in tumor cells. The nuclear matrix appears well preserved and exhibits a network formed by thick and thin filaments. Hence microwave fixation can be used as a quick and effective method for the study of the morphology of nuclear matrix.

Methionine-enkephalin immunoreactivity in Merkel cell dense-core granules of nude mice sinus hair. A post-embedding immunogold electron-microscopic study.

The ultra-immunocytochemical technique applied in the present study revealed the occurrence of methionine-enkephalin (met-enkephalin)-like substance in the dense-core granules of Merkel cells of nude mice sinus hair. Incubation of ultra-thin sections of sinus hair with met-enkephalin antisera conjugated with gold particles showed specific association of gold particles on the dense-core granules of the Merkel cells. Gold particles were heavily and specifically located on the dense-core granules as well as in the adjacent cytoplasm. Dense-core granules of degenerating Merkel cells also exhibit met-enkephalin immunoreactivity. The nerve terminals associated with the Merkel cell did not show met-enkephalin immunoreactivity. Therefore, it is concluded that a met-enkephalin-like substance is present and stored in nude mice Merkel cell dense-core granules and it might act as a neurotransmitter or neuromodulator which could be involved in the functioning of the cell. Non-osmicated tissue should be used to locate this substance because of the possibility of cross-linkage of the amino acid sequence with osmium tetroxide.

Ascorbic acid with cupric ions as a chemotherapy for human lung tumor xenografts implanted beneath the renal capsule of immunocompetent mice.

The growth of human lung carcinoma xenografts implanted beneath the renal capsule of immunocompetent mice was investigated (the six-day subrenal capsule assay) by using combinations of ascorbic acid and cupric ions. A maximum suppression of growth of this human lung tumor, LX-1, was observed at an estimated consumption level by the mice of 6 to 8 g ascorbic acid and 2 to 5 mg cupric ions per day per kg body weight. The data suggest that more than one oxidative or degradative product of ascorbic acid or of some copper compounds may be responsible for the observed antitumor activities, and that the chemotherapeutic effect is being produced at some stoichiometric ratios of ascorbic acid to cupric ions. When such a combination of the two substances was consumed by the mice, optimal therapeutic effect was exerted on the implanted xenografts.

In vivo antineoplastic activity of ascorbic acid for human mammary tumor.

The effect of ascorbic acid on the growth of human mammary tumor xenografts was investigated using the 6-day subrenal capsule assay method. The results showed that ascorbic acid (1 or 5 g/liter) administered in the drinking water significantly inhibited the growth of tumor fragments implanted beneath the renal capsule of immunocompetent mice. The results agree with other work carried out in animal experiments with animal tumors. Administration of ascorbic acid in the mouse diet did not affect the growth of the human mammary tumor fragments within the 6-day experimental period. Tumor growth was inhibited when mice were fed a diet containing ascorbic acid (50g/kg diet) together with cupric sulfate (18 or 90 mg/liter) in the drinking water. The results support the hypothesis that certain oxidation and degradation products of ascorbic acid are active antineoplastic agents for the human mammary carcinoma studied.

An immuno-electron microscopic study on the relationship between nuclear matrix and DNA in rat spermatocytes.

The nucleus of the mammalian spermatid undergoes a series of changes in its chromatin and nucleoprotein composition during transport from testis to epididymis. The sperm DNA is very tightly packaged by protamines instead of histones in somatic cells. However, the nuclear matrix and its association with DNA have not yet been definitively scrutinized with the electron microscope. The present study reveals that the protamine-depleted sperm nuclear matrix appears as a network of thick and thin filaments with glodular structures attached the these fibers. Monoclonal antibody to single- and doublestranded DNA was used to localize remnant DNA after extraction. By immunofluorescence microscopy, monoclonal antibody against DNA was localized outside the nucleus as a halo. Immuno-electron microscopy showed that gold particles were mainly associated with nuclear matrix surrounding the sperm head. Our results suggest a specific structural organization of sperm DNA with its matrix.

Ultrastructural study on the development of the rat [correction of mouse] spermatocyte nuclear matrix during epididymal maturation.

The rat sperm nucleus, after sequential extraction with detergents, nuclease and ammonium sulfate, consists of a skeletal structure that resembles the original nuclear shape. This chromatin-depleted skeleton is formed by thick and thin fibers as well as globular structures of different sizes. These fibers form anastomosis. The sperm nuclei obtained from testis and caput epididymis exhibits a loose fibrous network with thin fibers at the center. The entire nucleus of the sperm in the caudal epididymis is formed by a dense network of thick and thin fibers. These highly branched matrix fibers had diameters of 35 and 12 nm. It is concluded that the increase in density of the matrix fibers is related to the condensation of the chromatin in the maturation of the spermatozoa.

Fine structural observations on the human sperm nuclear matrix.

The nucleus of the mammalian sperm is formed after a series of morphological and biochemical changes during spermatogenesis. The human sperm nucleus, after sequential extraction with detergents, nuclease and ammonium sulfate, consists of a fibroskeletal structure which maintains the original nuclear shape. The chromatin-depleted skeleton is formed by thick and thin fibers as well as electron-dense patches of different sizes. These highly branched matrix fibers had average diameters of 35 and 12 nm. Polarization of the fibroskeletal structure is apparent and can be used as a good model to study the function of nuclear matrix in nuclear compartmentation in germ cells.