Association of Frailty with Healthcare Costs Using Claims Data in Korean Older Adults Aged 66.

OBJECTIVE: To explore the association of frailty and its eight components with claims-based healthcare costs among South Korean older adults aged 66 from 2009 to 2012. DESIGN: A cross-sectional design. SETTING: Data were obtained from administrative claims, Regular Biennial General and Cancer Screening Examinations, and the 66-year Lifetime Transitional Period Health Examination. PARTICIPANTS: South Korean older adults aged 66 (N = 818,337). MEASUREMENTS: Frailty was measured using eight components (i.e., hospital admission, self-assessed health status, polypharmacy, weight loss, depressed mood, incontinence, visual and auditory problems, and performance on the Timed Up and Go test). Healthcare costs included those associated with inpatient and outpatient care and pharmaceuticals. Multiple Tobit regression was used to assess the association between frailty and healthcare costs before and after propensity score matching. RESULTS: The mean annual total healthcare cost was $1,403.24 in robust participants, $2,364.78 in pre-frail participants, and $3,655.13 in frail participants. Among participants after propensity score matching, total healthcare costs were higher by $959.58 in the pre-frail (P < 0.001) and by $2,249.70 in the frail group (P < 0.001) compared to the robust group. The presence of each of the eight frailty components was significantly associated with higher total healthcare costs. CONCLUSION: By comparing the variables of interest using claims data, our study showed that frailty and each of its eight symptoms was associated with increased healthcare costs. This provides evidence of the need for identifying and managing frailty to reduce healthcare costs among South Korean older adults.

Measuring the burden of disease due to climate change and developing a forecast model in South Korea.

OBJECTIVES: Climate change influences human health in various ways, and quantitative assessments of the effect of climate change on health at national level are becoming essential for environmental health management. STUDY DESIGN: This study quantified the burden of disease attributable to climate change in Korea using disability-adjusted life years (DALY), and projected how this would change over time. METHODS: Diseases related to climate change in Korea were selected, and meteorological data for each risk factor of climate change were collected. Mortality was calculated, and a database of incidence and prevalence was established. After measuring the burden of each disease, the total burden of disease related to climate change was assessed by multiplying population-attributable fractions. Finally, an estimation model for the burden of disease was built based on Korean climate data. RESULTS: The total burden of disease related to climate change in Korea was 6.85 DALY/1000 population in 2008. Cerebrovascular diseases induced by heat waves accounted for 72.1% of the total burden of disease (hypertensive disease 1.82 DALY/1000 population, ischaemic heart disease 1.56 DALY/1000 population, cerebrovascular disease 1.56 DALY/1000 population). According to the estimation model, the total burden of disease will be 11.48 DALY/1000 population in 2100, which is twice the total burden of disease in 2008. CONCLUSIONS: This study quantified the burden of disease caused by climate change in Korea, and provides valuable information for determining the priorities of environmental health policy in East Asian countries with similar climates.

The rate of decline of glomerular filtration rate is a predictor of long-term graft outcome after kidney transplantation.

BACKGROUND: To improve the long-term outcome of kidney transplantation (KT), it is important to identify and take active steps to reduce the number or severity of novel risk factors. We investigated whether changes in estimated glomerular filtration rate over the first year after KT (ΔeGFR12-3) was associated with long-term renal allograft function and survival. METHODS: Four hundred twenty-eight allograft recipients transplanted between 1990 and 2001 underwent ΔeGFR12-3 calculation using the equation: ΔeGFR12-3 = ([eGFR at 12 months post-KT - eGFR at 3 months post-KT]/[eGFR at 3 months post-KT]) × 100%. Recipients were divided into 3 groups according to their ΔeGFR12-3: group I (n = 150), ΔeGFR12-3 ≥ 10%; group II (n = 151), 10 > ΔeGFR12-3 ≥ -10%; and group III (n = 127), ΔeGFR12-3 < -10%. Multiple linear regression analysis was used to adjust for confounding variables that may affect long-term renal allograft function, and Kaplan-Meier analysis, to compare allograft survival. RESULTS: At a mean follow-up of 120 ± 58 months, we observed 112 renal allograft losses. The ΔeGFR over 10 years post-KT (ΔeGFR120-3) was significantly associated with the serum uric acid levels at 3 months post-transplantation and ΔeGFR12-3. Group III showed poor renal allograft survival; group I, 194 ± 8 months; group II, 197 ± 7 month and; group III, 163 ± 4 months; (log-rank test, P < .05). A Cox proportional hazard model revealed ΔeGFR12-3 to be independently associated with future renal allograft loss (hazard ratio, 0.981; 95% confidence interval, 0.974-0.992). CONCLUSION: Our results suggested that ΔeGFR12-3 may be an independent predictor of kidney allograft survival. Routine application of eGFR is strongly recommended to identify patients at risk for chronic allograft dysfunction.

Clinical impact of methicillin-resistant Staphylococcus aureus bacteremia based on propensity scores.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen not only in nosocomial infections, but also in community-associated infections. The aim of this study was to evaluate the impacts of methicillin resistance on mortality, length of hospitalization, and hospital costs via propensity score matching in S. aureus bacteremia. PATIENTS AND METHODS: A propensity-matched case-control study was conducted in a tertiary hospital in Korea from 2003 to 2008. RESULTS: A total of 266 patients who had clinically significant S. aureus bloodstream infections were investigated. Fifty-three propensity-matched case-control pairs with MRSA bacteremia were likely to have stayed in the hospital longer before developing bacteremia (mean 25.0 vs. 6.1 days; P = 0.01). However, after developing bacteremia, the differences in the mean duration of hospital stay was not significant (mean 35.0 vs. 28.7 days; P = 0.33). Similar numbers of MRSA and methicillin-susceptible S. aureus (MSSA) patients died (P = 0.48). The mean total hospital costs after S. aureus bacteremia increased more for MRSA patients compared to MSSA patients. However, this difference was not statistically significant ($9,369.6 vs. $8,355.8; P = 0.62). CONCLUSIONS: This study indicates that MRSA bacteremia is not associated with higher risks of mortality or hospital costs. It is, however, associated with a substantial increase in the length of hospital stay as compared to MSSA bacteremia. This information may help clinicians and policymakers derive methods to control the impacts of MRSA infection.

Direct and indirect antitumor effects by human peripheral blood lymphocytes expressing both chimeric immune receptor and interleukin-2 in ovarian cancer xenograft model.

Human peripheral blood lymphocytes (PBLs) electroporated with RNA encoding anti-Her-2/neu-specific chimeric immune receptor (CIR) have been reported to elicit potent immune responses against SKOV3 tumors in a nude mouse model. However, CIR-electroporated PBL (CIR-PBL) did not proliferate, and the cell number rapidly decreased in the absence of exogenous interleukin-2 (IL-2). In this study, PBLs electroporated with both CIR and IL-2 RNA (CIR/IL-2-PBL) were studied to determine whether antitumor effects could be improved by adoptive immunotherapy. CIR and IL-2 were expressed in CIR/IL-2-PBL at levels similar to PBLs electroporated, with IL-2 RNA (IL-2-PBL) or CIR-PBL. Transfer of IL-2 RNA induced proliferation and prolonged survival of PBLs in vitro. In a xenograft model, both IL-2-PBL and CIR/IL-2-PBL showed significantly higher antitumor effects than CIR-PBL. The number of tumor-infiltrating natural killer (NK) cells was significantly increased in IL-2-PBL and CIR/IL-2-PBL. After NK cell depletion, IL-2-PBL showed significantly lower antitumor effects than CIR/IL-2-PBL. These results suggest that transfer of IL-2 RNA to CIR-PBL can promote NK cell infiltration of tumors and prolong survival of infused PBLs in vivo. RNA electroporated PBLs may represent efficient tools for delivery of functional molecules to tumors by multiple gene transfer.

Genetic associations of IL1RN polymorphisms with metabolic syndrome in a Korean population.

Metabolic syndrome (MetS) is rapidly growing into one of the major public health issues worldwide. Interleukin 1 receptor antagonist (IL1Ra) functions as a competitor of proinflammatory cytokines and has an important role in metabolic functions, including insulin secretion. To identify the relationship between the interleukin 1 receptor antagonist gene (IL1RN) and MetS, we genotyped nine single nucleotide polymorphisms (SNPs) in the gene using direct sequencing in 66 MetS patients and 346 normal subjects in the Korean population. Among the nine polymorphisms, after adjusting for age and sex, rs928940 (G>T) showed a significant association with MetS in the codominant ( P= 0.023) and recessive models ( P= 0.011). Also, rs315952 (C>T) exhibited a significant association with MetS in the codominant model ( P= 0.046). The results suggest that the IL1RN polymorphisms may be associated with MetS in the Korean population.

Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice.

Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.

IL-10-transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation.

Recent data suggest that adult mesenchymal stem cells (MSCs) might enhance allogeneic hematopoietic engraftment and prevent graft-versus-host disease (GVHD) owing to their immunosuppressive nature. Using a murine model of acute GVHD, this study examined whether or not the immunosuppressive properties of MSCs could reduce the severity of experimental GVHD. The early injection of MSCs after transplant did not attenuate the severity of acute GVHD. Therefore, this study investigated whether or not the use of IL-10-transduced MSCs (IL-10 MSCs) could reduce the severity of acute GVHD. Lethally irradiated recipients were transplanted and injected with IL-10 MSCs, the MSC-expressing vector alone (vector MSCs), or the diluent (controls), respectively, on day +1. Compared with the vector MSCs or controls, there was a significantly lower mortality in the recipients of the IL-10 MSCs at day 50 after the transplant (percent survival, 0 or 10 vs 70%, P=0.0004 or 0.0064, respectively). The decrease in mortality was confirmed by the semi-quantitative GVHD score (P<0.05), and was associated with decreased serum levels of the pro-inflammatory cytokines, IFN-gamma, on day +7 (P=0.015). Therefore, beneficial effects on GVHD were observed when MSCs were engineered to express the anti-inflammatory cytokine, IL-10.

Structural phase transition and hydrogen ordering of TlH2PO4 at low temperature.

The crystal structure of TlH(2)PO(4) (TDP) has been studied at low temperature. The lattice parameters were derived from high-resolution X-ray powder diffraction in the temperature range between 8 and 300 K. A detailed crystal structure analysis of the antiferroelectric low-temperature phase TDP-III has been performed based on neutron diffraction data measured at 210 K on a twinned crystal consisting of two domain states. The structure model in the triclinic space group P\bar 1 is characterized by a complete ordering of all the H atoms in the asymmetric O-H...O hydrogen bonds. The phase transition from the ferroelastic TDP-II to the antiferroelectric TDP-III phase at 229.5 +/- 0.5 K is only slightly of first order and shows no detectable hysteresis effects. Its mechanism is driven by the hydrogen ordering between the partially ordered TDP-II state and the completely ordered TDP-III state. The polymorphism of TDP and the fully deuterated TlD(2)PO(4) (DTDP) is presented in the form of group-subgroup relations between the different space groups.

During ontogeny primitive (CD34(+)CD38(-)) hematopoietic cells show altered expression of a subset of genes associated with early cytokine and differentiation responses of their adult counterparts.

Comparison of gene expression profiles in closely related subpopulations of primitive hematopoietic cells offers a powerful first step to elucidating the molecular basis of their different biologic properties. Here we present the results of a comparative quantitative analysis of transcript levels for various growth factor receptors, ligands, and transcription factor genes in CD34(+)CD38(-) and CD34(+)CD38(+) cells purified from first trimester human fetal liver, cord blood, and adult bone marrow (BM). In addition, adult BM CD34(+)CD38(-) cells were examined after short-term exposure to various growth factors in vitro. Transcripts for 19 of the 24 genes analyzed were detected in unmanipulated adult BM CD34(+)CD38(-) cells. Moreover, the levels of transforming growth factor beta (TGF-beta), gp130, c-fos, and c-jun transcripts in these cells were consistently and significantly different (higher) than in all other populations analyzed, including phenotypically similar but biologically different cells from fetal or neonatal sources, as well as adult BM CD34(+) cells still in G(0) after 2 days of growth factor stimulation. We have thus identified a subset of early response genes whose expression in primitive human hematopoietic cells is differently regulated during ontogeny and in a fashion that is recapitulated in growth factor-stimulated adult BM CD34(+)CD38(-) cells, before their cell cycle progression and independent of their subsequent differentiation response. These findings suggest a progressive alteration in the physiology of primitive hematopoietic cells during development such that these cells initially display a partially "activated" state, which is not maximally repressed until after birth. (Blood. 2000;96:4160-4168)

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G(2)/M transit and do not reenter G(0).

An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G(1) fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G(0)/G(1) and S/G(2)/M. Interestingly, the G(0) cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle-associated change in in vivo stem cell homing, the cultured G(0)/G(1) and S/G(2)/M CD34(+) CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor beta(1) that increased the G(0)/G(1) fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle-associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo-manipulated grafts. (Blood. 2000;96:4185-4193)

Efficient retrovirus-mediated gene transfer to transplantable human bone marrow cells in the absence of fibronectin.

The low frequency of transplantable hematopoietic stem cells in adult human bone marrow (BM) and other differences from cord blood stem cells have impeded studies to optimize the retroviral transduction of stem cells from adult sources. To address this problem, first a cytokine combination was defined that would both maximize the kinetics of adult BM CD34(+)CD38(-) cell mitogenesis and minimize the period of prestimulation required for the transduction of these cells by a MSCV-GFP/neo(r) virus in tissue culture dishes in the absence of fibronectin. Three days of stimulation with flt3-ligand, Steel factor, interleukin (IL)-3, and hyper-IL-6 proved both necessary and sufficient to obtain 83% +/- 2% GFP(+) CD34(+)CD38(-) cells, 75% +/- 10% G418-resistant clonogenic progenitors, and 50% +/- 20% transduced long-term culture-initiating cells as recovered 48 hours after a single exposure to virus. Moreover, this was accompanied by a several-fold increase in viral receptor (pit-1) messenger RNA transcripts in the target cells. Using this prestimulation protocol, repeated daily exposure to new virus (3x) did not alter the proportion of transduced cells over that obtained with a single exposure. Adult human BM cells able to engraft immunodeficient (NOD/SCID-beta(2)M(-/-)) mice were also efficiently transduced (10%-20% GFP(+) human lymphoid and myeloid cells present 6-8 weeks after transplant) using a 6-day prestimulation and infection protocol. A clinically useful efficiency of retrovirus-mediated gene transfer to transplantable adult human BM stem cells can thus be obtained with a protocol that allows their semisynchronous activation into cycle and concomitant increased expression of virus receptor transcripts before virus exposure.

The myb gene family in cell growth, differentiation and apoptosis.

The myb gene family consists of three members, named A, B and c-myb which encode nuclear proteins that function as transcriptional transactivators. Proteins encoded by these three genes exhibit a tripartate structure with an N-terminal DNA-binding domain, a central transactivation domain and a C-terminal regulatory domain. These proteins exhibit highest homology in their DNA binding domains and appear to bind DNA with overlapping sequence specificities. Transactivation by myb gene family varies considerably depending on cell type and promoter context suggesting a dependence on interaction with other cell type specific co-factors. While the C-terminal domains of A-Myb and c-Myb proteins exert a negative regulatory effect on their transcriptional transactivation function, the C-terminal domain of B-Myb appears to function as a positive regulator of this activity. One or more of these proteins interact with other transcription factors such as Ets-2, CEBP and NF-M. In addition, expression of these genes is cell cycle-regulated and inhibition of their expression with antisense oligonucleotides has been found to affect cell cycle-progression, cell division and/or differentiation. Members of the myb gene family exhibit different temporal and spatial expression patterns suggesting a distinctive function for each of these genes. Gene knockout experiments show that these genes play an essential role in development. Loss of c-myb function results in embryonic lethality due to failure of fetal hepatic hematopoiesis. A-myb null mutant mice, on the other hand are viable but exhibit growth abnormalities, and defects in spermatogenesis and female breast development. While the role of c-myb in oncogenesis is well established, future experiments are likely to provide further clues regarding the role of A-myb and B-myb in tumorigenesis.

The C-terminal domain of B-Myb acts as a positive regulator of transcription and modulates its biological functions.

The myb gene family consists of three members, named A-, B-, and c-myb. All three members of this family encode nuclear proteins that bind DNA in a sequence-specific manner and function as regulators of transcription. In this report, we have examined the biochemical and biological activities of murine B-myb and compared these properties with those of murine c-myb. In transient transactivation assays, murine B-myb exhibited transactivation potential comparable to that of c-myb. An analysis of deletion mutants of B-myb and c-myb showed that while the C-terminal domain of c-Myb acts as a negative regulator of transcriptional transactivation, the C-terminal domain of B-Myb functions as a positive enhancer of transactivation. To compare the biological activities of c-myb and B-myb, the two genes were overexpressed in 32Dcl3 cells, which are known to undergo terminal differentiation into granulocytes in the presence of granulocyte colony-stimulating factor (G-CSF). We observed that c-myb blocked the G-CSF-induced terminal differentiation of 32Dcl3 cells, resulting in their continued proliferation in the presence of G-CSF. In contrast, ectopic overexpression of B-myb blocked the ability of 32D cells to proliferate in the presence of G-CSF and accelerated the G-CSF-induced granulocytic differentiation of these cells. Similar studies with B-myb-c-myb chimeras showed that only chimeras that contained the C-terminal domain of B-Myb were able to accelerate the G-CSF-induced terminal differentiation of 32Dcl3 cells. These studies show that c-myb and B-myb do not exhibit identical biological activities and that the carboxyl-terminal regulatory domain of B-Myb plays a critical role in its biological function.

Successful treatment with cyclosporine in a case of hemophagocytic syndrome manifesting as severe liver dysfunction.

Forms of hemophagocytic syndrome, which affects mainly children, vary from mild to very severe and often fatal. We describe an adult patient with hemophagocytic syndrome in whom severe liver dysfunction developed. The condition continued to deteriorate despite treatment with plasma exchange, high-dose gamma globulin, and corticosteroid therapy. Treatment with cyclosporine (2.3 mg/kg/day) dramatically improved the condition and normalized liver function. Cyclosporine reduced the serum levels of ferritin, interferon-tau, interleukin-6, and soluble interleukin-2 receptor. These findings suggest that hemophagocytic syndrome accompanied with severe liver dysfunction results from hypercytokinemia, and cyclosporine is useful in preventing a fatal outcome during the acute phase.

Murine A-myb gene encodes a transcription factor, which cooperates with Ets-2 and exhibits distinctive biochemical and biological activities from c-myb.

The myb gene family consists of three members, named A-, B-, and c-myb, which encode nuclear proteins that bind to DNA and function as regulators of transcription. Our results show that murine A-myb is a poor transactivator of transcription compared with murine c-myb. Deletion of the COOH-terminal domain of A-Myb, or co-expression with Ets-2 resulted in increased transactivation potential. While ectopic overexpression of c-myb in 32Dcl3 cells results in a block to the ability of these cells to undergo terminal differentiation resulting in indefinite growth in granulocyte-colony-stimulating factor (G-CSF), similar overexpression of A-myb results in growth arrest and concomitant terminal differentiation of 32D cells into granulocytes. Co-expression of A-myb and ets-2 in these cells results in the restoration of the proliferative activity of the cells in G-CSF, but fails to induce a block to G-CSF-induced terminal differentiation. However, overexpression of the COOH-terminal deletion mutant of A-myb results in a block to G-CSF-induced differentiation of 32D cells, suggesting that the distinctive biological phenotypes produced by A-myb and c-myb genes are mediated by their COOH-terminal domains.

Transcriptional activation potential of normal and tumor-associated myb isoforms does not correlate with their ability to block GCSF-induced terminal differentiation of murine myeloid precursor cells.

The myb gene has been shown to be an important regulator of hematopoietic cell proliferation, differentiation and apoptosis. Activation of the myb gene into an oncogenic form has involved structural alterations to the coding sequences. Thus, the v-myb gene encoded by the Avian Myeloblastosis Virus, is truncated at both the 5' and 3' ends. Additionally, tumor cells containing rearrangements in the myb locus, such as the ABPL tumors or NFS60 tumor cell line have recently been shown to display a heterogeneity of structure. In this study, we examined the growth and differentiation properties of clonal cell lines derived from 32Dcl3 which harbor myb transgenes; derived from v-myb, and the ABPL-1, ABPL-2, ABPL-4 and NFS-60 cell lines. Retroviral vectors containing the appropriate myb cDNAs were produced, transfected into packaging cell lines, and the viruses were used to generate the 32D derivative cell clones. Abrogation of IL-3 dependence was never observed in any cell line. Expression of c-myb, ABPL-1-myb and ABPL-2-myb isoforms in 32D cells resulted in a block to their ability to terminally differentiate into granulocytes at the pro-myelocytic stage. However, expression of ABPL-4-myb or NFS60-myb in these cells failed to result in a similar effect. These cells differentiated into granulocytes in the presence of G-CSF, albeit more slowly than control 32Dcl3 cells. We also examined the ability of various Myb-isoforms to transactivate transcription of reporter genes containing Myb-binding elements in their promoter/enhancer sequences, to determine whether the phenotypic effects produced by these various isoforms correlate with their ability to transactivate transcription. Our results show that while v-myb and c-myb transactivated transcription equally well, the NFS60-myb exhibited the highest levels of transcriptional transactivation. The ABPL-1, ABPL-2 and ABPL-4-myb isoforms showed very low levels of transcriptional transactivation potential with the same reporter genes. These results suggest that the ability of various Myb-isoforms to transactivate transcription does not by itself correlate with their ability to induce a block to G-CSF-induced terminal differentiation of myeloid precursor cells.

Reductive cleavage of glycosides with borane complexes in the presence of boron trifluoride etherate.

Mixtures consisting of five equivalents each of borane.methyl sulfide and boron trifluoride etherate per equivalent of acetal or five equivalents of various amine-borane complexes and 10 equivalents of boron trifluoride etherate readily accomplished reductive cleavage of the glycosidic linkages of several per-O-methylated monosaccharides and polysaccharides. In all cases, the expected products were obtained in the expected molar proportions and no artifactual products were observed. Reductive-cleavage analysis using these reagents is particularly convenient because the reagents themselves are easy to handle and because subsequent acetylation of the products is accomplished in situ.

Is an abnormal Doppler umbilical artery waveform ratio a risk factor for poor perinatal outcome in the non-small for gestational age fetus?

To determine if abnormal umbilical artery velocimetry is associated with a higher rate of perinatal morbidity in pregnancies in which the outcome is not manifested by a small for gestational age (SGA) fetus, perinatal outcome was compared according to the results of Doppler umbilical artery velocimetry. Doppler study was performed in 328 singleton pregnancies with non-SGA fetuses within 7 days of delivery. The prevalence of abnormal Doppler studies was 10%. Patients with abnormal umbilical artery velocimetry had a significantly higher rate of complications, including cesarean section for fetal distress, preterm delivery, low Apgar scores, congenital anomalies, admission to the neonatal intensive care unit, and perinatal death, than patients with a normal umbilical artery velocimetry. Ten perinatal deaths were associated with major congenital anomalies. Moreover, in the absence of congenital anomalies patients with abnormal Doppler results also had a significantly higher incidence of adverse perinatal outcome compared with patients with normal umbilical artery velocimetry. Our data suggest that even the non-SGA fetus with an abnormal Doppler umbilical artery waveform ratio is at increased risk for poor perinatal outcome.