Plasma levels of natriuretic peptides and year-by-year blood pressure variability: a population-based study.

Augmented blood pressure (BP) variability over various time periods has been recognized as a risk factor for cardiovascular diseases. Both atrial and B-type natriuretic peptides (ANP and BNP) are secreted in response to volume or pressure overload to the heart, exerting natriuretic and vasodilator actions. In this study, we examined the relationships between year-by-year BP variability and plasma levels of ANP and BNP in the general population. Study subjects were local residents receiving an annual heath checkup, who had an estimated glomerular filtration rate of >30 ml min-1 per 1.73 m2 and no history of heart disease. Of those, we selected 314 subjects that received checkups at least five times over the past 6 years. BP variability year-by-year was retrospectively evaluated by s.d., coefficient of variation, average real variability and variation independent of the mean of BP values of 6 or 7 time points. The four parameters of BP variability were each found to significantly correlate with logarithmically transformed ANP and BNP levels by simple regression. When classified by quartiles of s.d. of systolic BP, the highest quartile group showed significantly higher levels of the natriuretic peptides compared with other groups. Multivariate analyses revealed that BP variability was an independent determinant for the ANP and BNP levels. In conclusion, augmented year-by-year BP variability over the past 6 years was associated with elevation of plasma levels of ANP and BNP, suggesting a possible relationship between the BP variability and cardiac load, in the general population.

Magnesium sulphate and perinatal mortality and morbidity in very-low-birthweight infants born between 24 and 32 weeks of gestation in Japan.

OBJECTIVE: Maternal exposure to magnesium sulphate has a neuroprotective effect in premature infants. This study aimed to examine this neuroprotective effect and the dose-response relationship in very-low-birthweight infants born between 24 and 32 weeks of gestation. STUDY DESIGN: A retrospective cohort study compared the rates of mortality and brain damage between three groups: no magnesium sulphate, low-dose (<50g) magnesium sulphate and high-dose (≥50g) magnesium sulphate. RESULTS: Japanese maternal and neonatal databases were linked using six key parameters from 2003 to 2007. Of 298,514 deliveries, 9101 were very-low-birthweight infants. Among these, full matching was possible for 5562 infants. Of the fully-matched infants, 3763 were born between 24 and 32 weeks of gestation, and 1813 (48%) were followed-up beyond 18 months. A multivariate analysis of the data, including gestational age, sex, fetal growth restriction, antenatal steroids and low pH (<7.1), showed that the low-dose group had no beneficial effects in terms of a reduction in mortality or incidence of brain damage (cerebral palsy or mental retardation). The high-dose group showed a significantly higher mortality rate [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.2-2.9]. A stratified subgroup analysis of infants born between 28 and 32 weeks of gestation showed that survivors in the low-dose group had significantly lower rates of cerebral palsy (OR 0.4, 95% CI 0.2-0.98) and brain damage (OR 0.2, 95% CI 0.1-0.9), while the high-dose group did not show any significant changes. CONCLUSION: This study found that antepartum exposure to magnesium sulphate did not reduce the infant mortality rate or influence neurological outcomes. However, among infants born between 28 and 32 weeks of gestation, rates of cerebral palsy and brain damage were found to be significantly lower among survivors in the low-dose group.

Non-destructive evaluation of ATP content and plate count on pork meat surface by fluorescence spectroscopy.

The potential of fluorescence spectroscopy was investigated for the non-destructive evaluation of ATP content and plate count on pork meat surface stored aerobically at 15 °C during three days. Excitation (Ex) Emission (Em) Matrix of fluorescence intensity was obtained and fluorescence from tryptophan (Ex=295 nm and Em=335 nm) and NADPH (Ex=335 nm and Em=450 nm) was detected. Because tryptophan and NADPH fluorescence changed along with the growth of microorganisms, microbial spoilage on meat could be detected from fluorescence. By applying PLSR (Partial Least Squares Regression) analysis, ATP content and plate count were predicted with good determination coefficient (0.94-0.97 in calibration and 0.84-0.88 in validation).

Ezetimibe reduces urinary albumin excretion in hypercholesterolaemic type 2 diabetes patients with microalbuminuria.

OBJECTIVE: This study investigated the effects of ezetimibe, an inhibitor of intestinal cholesterol absorption, on early phase diabetic nephropathy. METHODS: A total of 32 hypercholesterolaemic type 2 diabetes patients with microalbuminuria, defined as a urinary albumin excretion (UAE) 30 but < 300 mg/g creatinine, were enrolled. Various clinical and laboratory parameters were determined at baseline and after 6 months of treatment with 10 mg/day ezetimibe. RESULTS: Ezetimibe treatment significantly decreased glycated haemoglobin (HbA(1c)), low-density lipoprotein-cholesterol (LDL-C), triglycerides and UAE, and significantly increased high-density lipoprotein-cholesterol and albumin. It also decreased the serum level of monocyte chemoattractant protein-1 (MCP-1), but this difference was not statistically significant. Univariate analyses showed a correlation between UAE and body mass index, systolic and diastolic blood pressures, HbA(1c), LDL-C, estimated glomerular filtration rate (inverse), creatinine and MCP-1. Since these parameters may be closely correlated with each other, multiple stepwise regression analysis was performed and demonstrated that HbA(1c) and MCP-1 were independent determinants of UAE. CONCLUSIONS: Ezetimibe may be a promising therapeutic strategy for improving albumin excretion, partly through its anti-inflammatory properties, and for reducing LDL-C in hypercholesterolaemic type 2 diabetes patients with microalbuminuria.

Rapid detection of Escherichia coli contamination in packaged fresh spinach using hyperspectral imaging.

A rapid method based on hyperspectral imaging for detection of Escherichia coli contamination in fresh vegetable was developed. E. coli K12 was inoculated into spinach with different initial concentrations. Samples were analyzed using a colony count and a hyperspectroscopic technique. A hyperspectral camera of 400-1000 nm, with a spectral resolution of 5 nm was employed to acquire hyperspectral images of packaged spinach. Reflectance spectra were obtained from various positions on the sample surface and pretreated using Sawitzky-Golay. Chemometrics including principal component analysis (PCA) and artificial neural network (ANN) were then used to analyze the pre-processed data. The PCA was implemented to remove redundant information of the hyperspectral data. The ANN was trained using Bayesian regularization and was capable of correlating hyperspectral data with number of E. coli. Once trained, the ANN was also used to construct a prediction map of all pixel spectra of an image to display the number of E. coli in the sample. The prediction map allowed a rapid and easy interpretation of the hyperspectral data. The results suggested that incorporation of hyperspectral imaging with chemometrics provided a rapid and innovative approach for the detection of E. coli contamination in packaged fresh spinach.

Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy.

Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.

Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis.

AIMS: Focal glomerulosclerosis (FGS) and minor glomerular abnormalities are kidney diseases characterized by massive proteinuria. Urinary liver-type fatty acid-binding protein (L-FABP), an intracellular carrier protein of free fatty acids, is expressed in proximal tubules of the human kidney. Patients with FGS show significant improvement with low-density lipoprotein (LDL) apheresis. The aim of the present study was to determine whether urinary L-FABP levels differ between patients with FGS and those with minor glomerular abnormalities and whether levels are altered by LDL apheresis. PATIENTS AND METHODS: There were 24 patients with minor glomerular abnormalities (nephrotic stage, n = 14, remission stage, n = 10), 17 patients with FGS, and 20 healthy age-matched subjects were included in the present study. Urinary L-FABP levels were measured by enzyme-linked immunosorbent assay and compared. All patients with minor glomerular abnormalities at the nephrotic stage received prednisolone for 6 months, and all FGS patients received some form of immunosuppression therapy with prednisolone, cyclophosphamide or mizoribine for 12 months. LDL apheresis was performed in eight FGS patients with drug-resistant nephrotic syndrome. RESULTS: Urinary L-FABP levels were significantly higher in the 17 FGS patients (82.0 +/- 44.4 microg/g.Cr) than in the 24 patients with minor glomerular abnormalities (10.2 +/- 8.4 microg/g.Cr) (p < 0.01) and in the 20 healthy subjects (7.4 +/- 4.2 microg/g.Cr) (p < 0.01). Urinary L-FABP levels differed little between nephrotic stage and remission stage in patients with minor glomerular abnormalities. Urinary L-FABP levels were significantly higher in the eight drug-resistant FGS patients (122.6 +/- 78.4 microg/g.Cr) than in the nine drug-sensitive FGS patients (45.9 +/- 32.0 microg/g.Cr). Urinary L-FABP levels did not correlate with levels of other clinical markers including serum creatinine, urinary protein, and urinary N-acetyl-beta-D- glucosaminidase. In the eight drug-resistant FGS patients, LDL-apheresis significantly reduced urinary protein excretion (p < 0.01) and urinary L-FABP levels (p < 0.01). CONCLUSIONS: Urinary L-FABP may be a useful diagnostic indicator for differentiation between FGS and minor glomerular abnormalities. LDL apheresis may be effective in ameliorating tubulointerstitial lesions associated with FGS.

Low-density lipoprotein apheresis in a patient with arteriosclerosis obliterans and light chain deposition disease.

A 49-year-old women with arteriosclerosis obliterans (ASO) complicated with light chain deposition disease (LCDD) is described. Renal biopsy showed a diffuse mesangial nodular lesion and tubulointerstitial changes. Congo red and lambda light chain staining were negative; however, the kappa light chain was positive in both glomeruli and tubular basement membranes by immunostaining. Using electron microscopy, electron-dense materials were found within glomerular basement membrane, mesangium and tubular basement membrane. The patient had renal dysfunction and nephrotic syndrome with progressive skin ulcers in the left leg. The patient was diagnosed as ASO with LCDD. She received low-density lipoprotein (LDL) apheresis once weekly for 10 consecutive weeks. Serum total cholesterol and phospholipid levels were decreased, and serum creatinine and blood urea nitrogen levels also tended to decline after treatment. Urinary protein excretion was reduced markedly, and hypoalbuminemia was also improved. Ischemic symptoms including leg pain and leg coldness and numbness improved after apheresis. The walking distance increased on a treadmill. The skin temperature was increased from 33.8 degrees C to 35.5 degrees C after apheresis and the skin ulcers were also improved. Plasma nitric oxide (NO) levels were increased from 66.0 microM/l to 88.0 microM/l and plasma endothelin (ET)-1 levels were decreased from 14.5 pg/ml to 5.8 pg/ml after apheresis. LDL apheresis was effective in ameliorating hyperlipidemia, massive proteinuria, hypoalbuminemia and high serum creatinine levels in an LCDD patient with nephrotic syndrome. Furthermore, we showed beneficial effects of LDL apheresis on skin ulcers due to ischemia in an ASO patient complicated with LCDD.

Adaptation of cardiovascular responses to repetitive umbilical cord occlusion in the late gestation ovine fetus.

1. The impact of repeated umbilical cord occlusion on the normal maturation of fetal heart rate (FHR) and mean arterial pressure (MAP) and the cardiovascular responses to successive umbilical cord occlusion was investigated over a 21 day period in the latter part of gestation. 2. Fifteen chronically instrumented sheep (control group n = 6; occlusion group n = 9) were studied for 21 days (113-133 days of gestation, term = 145 days) with umbilical cord occlusions (90 s duration) performed every 30 min for 1-4 h each day. On days 1, 9 and 18, FHR, FHR variation and MAP were monitored continuously and fetal arterial blood gases, pH and metabolites were measured at predetermined intervals. The baroreflex response to 75-100 microg phenylephrine (I.V.) was tested on days 1 and 18. 3. Basal FHR decreased (DeltaFHR: control, 34.6 +/- 3.6 beats x min(-1); occlusion, 36.9 +/- 2.7 beats x min(-1)) and MAP increased (DeltaMAP: control, 3.1 +/- 1.7 mmHg; occlusion, 5.2 +/- 2.1 mmHg) to a similar extent in control and occlusion groups between days 1 and 21 of the study. There was a small decline in FHR variation over the 21 day study in occlusion, but not control, group fetuses. 4. The magnitude of the fall in FHR decreased and the rise in MAP increased, despite similar changes in blood gases in response to umbilical cord occlusion, over the course of the 21 day study. Despite a significant decline in the ratio of DeltaFHR to DeltaMAP on days 9 and 18 compared to day 1, there was no difference between control and occlusion groups in baroreflex sensitivity. However DeltaFHR/DeltaPO2, an index of chemoreceptor sensitivity, had decreased by day 9 and 18 compared to day 1. 5. The cardiovascular responses to umbilical cord occlusion are altered with repetitive occlusions during the latter part of gestation, with a decrease in DeltaFHR/DeltaMAP, which does not involve changes in baroreflex sensitivity, but may involve changes in chemoreceptor sensitivity. However, repeated umbilical cord occlusion appears to have no impact on baseline cardiovascular control since there was no change in the normal maturational decrease in FHR and rise in MAP.

Intermittent umbilical cord occlusion in the ovine fetus: effects on blood glucose, insulin, and glucagon and on pancreatic development.

OBJECTIVE: To determine whether repetitive umbilical cord occlusion resulting in fetal hypoxemia but not cumulative acidosis also affects fetal glucose levels and the levels of the regulatory hormones insulin and glucagon, by altering glucose delivery and with repetitive insults by inducing fetal glucose production, thus possibly affecting pancreatic development. METHODS: Fifteen chronically catheterized fetal sheep were studied over 21 days. Umbilical cord occlusions (UCOs) (duration 90 seconds) were performed every 30 minutes for 3-4 hours each day. Fetal arterial blood was sampled at predetermined times on days 1, 9, and 18 for blood gases, pH, glucose, lactate, insulin, and glucagon. When animals were sacrificed, fetal pancreatic tissues were collected for insulin immunostaining. RESULTS: Blood glucose decreased acutely with each UCO but showed a cumulative increase of approximately 30% over the course of each sampling day. Although plasma insulin levels also increased over the course of sampling on days 9 and 18, plasma glucagon levels remained unchanged throughout the study. The percentage of pancreatic islet cells immunopositive for insulin, which averaged 67%, was also unchanged in experimental compared with control animals. CONCLUSION: Umbilical cord occlusion during the latter part of pregnancy, which caused severe but limited hypoxemia, also resulted in acute decreases in blood glucose levels because of reduced exogenous glucose delivery and a cumulative increase in glucose in response to repetitive insults, possibly by inducing fetal glucose production, enhancing glucose delivery, or both. However, repetitive UCO as studied had minimal effect on plasma insulin levels and no effect on glucagon levels or on pancreatic immunostaining for insulin, and thus had no evident effect on pancreatic development.

The experimental herbicide CGA 325'615 inhibits synthesis of crystalline cellulose and causes accumulation of non-crystalline beta-1,4-glucan associated with CesA protein.

Developing cotton (Gossypium hirsutum) fibers, cultured in vitro with their associated ovules, were used to compare the effects of two herbicides that inhibit cellulose synthesis: 2,6-dichlorobenzonitrile (DCB) and an experimental thiatriazine-based herbicide, CGA 325'615. CGA 325'615 in nanomolar concentrations or DCB in micromolar concentrations causes inhibition of synthesis of crystalline cellulose. Unlike DCB, CGA 325'615 also causes concomitant accumulation of non-crystalline beta-1,4-glucan that can be at least partially solubilized from fiber walls with ammonium oxalate. The unusual solubility of this accumulated glucan may be explained by its strong association with protein. Treatment of the glucan fraction with protease changes its size distribution and leads to precipitation of the glucan. Treatment of the glucan fraction with cellulase digests the glucan and also releases protein that has been characterized as GhCesA-1 and GhCesA-2--proteins that are believed to represent the catalytic subunit of cellulose synthase. The fact that cellulase treatment is required to release this protein indicates an extremely tight association of the glucan with the CesA proteins. In addition, CGA 325'615, but not DCB, also causes accumulation of CesA protein and a membrane-associated cellulase in the membrane fraction of fibers. In addition to the effects of CGA 325'615 on levels of both of these proteins, the level of both also shows coordinate regulation during fiber development, further suggesting they are both important for cellulose synthesis. The accumulation of non-crystalline glucan caused by CGA 325'615 mimics the phenotype of the cellulose-deficient rsw1 mutant of Arabidopsis that also accumulates an apparently similar glucan (T. Arioli, L. Peng, A.S. Betzner, J. Burn, W. Wittke, W. Herth, C. Camilleri, H. Hofte, J. Plazinski, R. Birch et al. [1998] Science 279: 717).

[The role of cardiac catheterization for diagnosis and treatment of pulmonary hypertension].

The role of the cardiac catheterization for diagnosis and treatment of pulmonary hypertension (PH) is very important. When mean pulmonary artery pressure increased more than 25 mmHg, then PH is defined. But this is measured accurately only by the catheterization. And we can discriminate the etiology of PH clearly by pulmonary capillary wedge pressure (Ppcw) or intra-cardiac shunt (L to R) by blood oxygen saturation step-up, and both parameters are obtained by this method. The etiology of PH is diagnosed as left sided heart failure, if Ppcw is increased more than 13 mmHg. PH is produced by congenital heart disease (ASD, VSD, PDA etc.), when the oxygen saturation step-up is recognized. And PH is induced by any pulmonary disease or pulmonary thrombo-embolism or collagen disease or liver cirrhosis or PPH, if Ppcw is normal and no oxygen step-up is recognized.

The effect of intermittent umbilical cord occlusion on insulin-like growth factors and their binding proteins in preterm and near-term ovine fetuses.

Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (128-131 days of gestation) ovine fetuses, we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animals (preterm n=7; near term n=7) UCOs were carried out by complete inflation of an occluder cuff (duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 mmHg), and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1.5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and kidney (22%, P<0.01), but hig! her in the heart (72%, P<0.01), while IGFBP-4 (2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-term group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.

Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus.

OBJECTIVE: To determine whether repeated hypoxic insults with umbilical cord occlusion over 4 days will lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine fetus. METHODS: Umbilical cord occlusions of 90 seconds duration were performed every 30 minutes for 3 to 5 hours each day (experimental group n = 7, control group n = 7; at 112-116 days' gestation, term = 147 days). Arterial blood was sampled at predetermined times for blood gases and pH, plasma ACTH, and cortisol. Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also were localized and quantified by in situ hybridization. RESULTS: During umbilical cord occlusions fetal arterial oxygen pressure (approximately 17 mmHg) and pH (approximately 0.05) decreased, and carbon dioxide pressure increased (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood gas or pH change over successive occlusions for any of the 4 study days. Plasma ACTH increased, as measured after cord occlusion and over the course of successive cord occlusions on days 1 and 4, and returned to control values by the next day. The cumulative increase in ACTH was much less on day 4 than day 1 (15 +/- 3 compared with 101 +/- 25 pg/mL, P <.05). Plasma cortisol increased, as measured after cord occlusion and over the course of successive cord occlusions on day 4 only (2.7 +/- 0.4 to 4. 7 +/- 0.3 ng/mL, P <.05). POMC mRNA increased 2.5-fold in the pars distalis of the pituitaries from cord occlusion compared to control fetuses, but was unchanged in the pars intermedia. GR mRNA, which was detected in the pars distalis only, was unaltered. CONCLUSION: Repetitive umbilical cord occlusion in the preterm ovine fetus resulted in the activation of the HPA axis, with increased adrenocortical responsiveness over time, and involved differential regulation of POMC mRNA expression in the pars distalis and pars intermedia of the pituitary, but with no change in GR.

Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation.

We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.

Intermittent umbilical cord occlusion in the ovine fetus near term: effects on behavioral state activity.

OBJECTIVE: The purpose of this study was to determine the effects on fetal behavioral state activity of intermittent umbilical cord occlusion resulting in repetitive severe short-term hypoxemia. STUDY DESIGN: Fifteen near-term fetal sheep (experimental group, n = 8; control group, n = 7) were studied during 4 days while behavioral and cardiovascular parameters were monitored. Each day after a 2-hour control period, cord occlusions were performed in the experimental group animals by complete inflation of an occluder cuff (duration, 90 seconds) every 30 minutes for 3 to 5 hours. Results are presented as group mean +/- SEM. RESULTS: During umbilical cord occlusions fetal arterial PO(2) (change of 12 mm Hg), oxygen saturation (change of 40%), and glucose concentration (change of 0.3 mmol/L) fell and PCO(2) (change of 7 mm Hg) rose, but all returned toward control values after release of occlusion. Fetal behavioral state activity was markedly disrupted by 90 seconds of cord occlusion, with animals showing an abrupt flattening of the electrocorticogram. In >90% of instances the first identifiable state after cord release was the high-voltage non-rapid-eye-movement state. There was no apparent change in this response through the 4 days of the study. For experimental group animals the mean percentages of time spent in low-voltage electrocortical state (from 53 +/- 2 to 36 +/- 2), electro-ocular state (from 45 +/- 3 to 28 +/- 3), and fetal breathing activity (22 +/- 4 to 12 +/- 3) were significantly decreased (P <.001) during occlusion hours with respect to nonocclusion hours. CONCLUSION: Intermittent umbilical cord occlusion with severe but limited hypoxemia and no cumulative acidosis in the near-term ovine fetus disrupts behavioral state activity, with a flattening of the electrocortical activity during occlusions and an overall decrease in the prominence of the low-voltage rapid-eye-movement state. If such insults are frequent and severe enough, they might have an effect on growth and development of the brain during the perinatal period.

Low efficiency of oxygen utilization during exercise in hyperthyroidism.

STUDY OBJECTIVE: The mechanism of exercise intolerance in hyperthyroidism has not been fully elucidated. This study was undertaken to determine if hyperthyroidism reduced the efficiency of sub-maximal exercise. STUDY DESIGN: We measured cardiorespiratory variables up to the anaerobic threshold (AT) during ramp-loading cycle ergometry in 12 patients (New York Heart Association functional class II or III). Studies were performed in the hyperthyroid state and repeated in the euthyroid state after 10 months of medical treatment. In 10-W steps from rest to the AT, we measured oxygen uptake (VO2) as a measure of total body work rate, and pressure rate product (PRP) as a measure of cardiac work rate. Loading watts at AT divided by the increment of Vo2 from rest to the AT (delta Watt/delta VO2) was calculated as an index of work efficiency (where delta means the increment of each value from rest to the AT). RESULTS: VO2 and PRP at the AT were not significantly different between hyperthyroid and euthyroid states (VO2, 16.6 +/- 3.0 vs 17.5 +/- 2.3 mL/min/kg; PRP, 229 +/- 41 vs 218 +/- 28 x 10(2) mm Hg/min). However, loading watts at the AT were significantly lower in the hyperthyroid than the euthyroid state (28 +/- 22 vs 60 +/- 14 W: p < 0.01). VO2 and PRP while hyperthyroid were significantly higher than when euthyroid at every 10-W step during ramp-loading exercise. Furthermore, delta Watt/delta VO2 was significantly lower in hyperthyroid than euthyroid states (p < 0.001). There was a significant inverse correlation-ship between triiodothyronine and delta Watt/delta Vo2 (r = -0.654, p < 0.001). CONCLUSION: Hyperthyroidism causes low work efficiency, which may limit exercise tolerance.

Higher plants contain homologs of the bacterial celA genes encoding the catalytic subunit of cellulose synthase.

In spite of much effort, no one has succeeded in isolating and characterizing the enzyme(s) responsible for synthesis of cellulose, the major cell wall polymer of plants. We have characterized two cotton (Gossypium hirsutum) cDNA clones and identified one rice (Oryza sativa) cDNA that are homologs of the bacterial celA genes that encode the catalytic subunit of cellulose synthase. Three regions in the deduced amino acid sequences of the plant celA gene products are conserved with respect to the proteins encoded by bacterial celA genes. Within these conserved regions, there are four highly conserved subdomains previously suggested to be critical for catalysis and/or binding of the substrate UDP-glucose (UDP-Glc). An overexpressed DNA segment of the cotton celA1 gene encodes a polypeptide fragment that spans these domains and binds UDP-Glc, while a similar fragment having one of these domains deleted does not. The plant celA genes show little homology at the N- and C-terminal regions and also contain two internal insertions of sequence, one conserved and one hypervariable, that are not found in the bacterial gene sequences. Cotton celA1 and celA2 genes are expressed at high levels during active secondary wall cellulose synthesis in developing cotton fibers. Genomic Southern blot analyses in cotton demonstrate that celA forms a small gene family.

Hyperinflation with intrinsic PEEP and respiratory muscle blood flow.

Increased end-expiratory lung volume and intrinsic positive end-expiratory pressure (PEEP) are common in obstructive lung disease, especially during exacerbations or exercise. This loads the respiratory muscles and may also stress the circulatory system, causing a reduction or redistribution of cardiac output. We measured the blood flow to respiratory muscles and systemic organs using colored microspheres in 10 spontaneously breathing anesthetized tracheotomized dogs. Flows during baseline breathing (BL) were compared with those during hyperinflation (HI) induced by a mechanical analogue of airway closure and with those during an inspiratory resistive load (IR) that produced an equivalent increase in inspiratory work and time-integrated transdiaphragmatic pressure. Cardiac output was unchanged during IR (3.19 +/- 0.27 l/min at BL, 3.09 +/- 0.34 l/min during IR) but was reduced during HI (2.14 +/- 0.29 l/min; P < 0.01). Among the organs studied, flow was unaltered by IR but decreased to the liver and pancreas and increased to the brain during HI. For the respiratory muscles, flow to the diaphragm increased during IR. However, despite a 1.9-fold increase in inspiratory work per minute and a 2.5-fold increase in integrated transdiaphragmatic pressure during HI, blood flow to the diaphragm was unchanged and flow to the scalenes and sternomastoid fell. The only respiratory muscle to which flow increased during HI was the transversus abdominis, an expiratory muscle. We conclude that the circulatory effects of hyperinflation in this model impair inspiratory muscle perfusion and speculate that this may contribute to respiratory muscle dysfunction in hyperinflated states.