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Biomedical subjects

P Y Wu

Publications and source records attributed to P Y Wu.

At least 19 recordsLinked to original sources

Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge.

OBJECTIVE: At hospital discharge, preterm infants may have low body stores of nutrients, deficient bone mineralization, and an accumulated energy deficit. This double-blind, randomized study evaluated the growth of premature infants with birth weights <1800 g who were fed a 22 kcal/fl oz nutrient-enriched postdischarge formula (PDF) or a 20 kcal/fl oz term-infant formula (TF) from hospital discharge to 12 months' corrected age (CA). METHODS: Infants were randomized to PDF or TF a few days before hospital discharge with stratification by gender and birth weight (<1250 g or >/=1250 g). The formulas were fed to 12 months' CA. Growth was evaluated using analysis of variance controlling for site, feeding, gender, and birth weight group. Interaction effects were also assessed. Secondary analyses included a repeated measures analysis and growth modeling. RESULTS: One hundred twenty-five infants were randomized; 74 completed to 6 months' CA and 53 to 12 months' CA. PDF-fed infants weighed more than TF-fed infants at 1 and 2 months' CA, gained more weight from study day 1 to 1 and 2 months' CA, and were longer at 3 months' CA. There were significant interactions between feeding and birth weight group-among infants with birth weights <1250 g, those fed PDF weighed more at 6 months' CA, were longer at 6 months' CA, had larger head circumferences at term 1, 3, 6, and 12 months' CA, and gained more in head circumference from study day 1 to term and to 1 month CA. The repeated measures and growth modeling analyses confirmed the analysis of variance results. The PDF formula seemed to be of particular benefit for the growth of male infants. Infants fed the PDF consumed less formula and had higher protein intakes at several time points. Energy intakes, however, were not different. CONCLUSIONS: Growth was improved in preterm infants fed a nutrient-enriched postdischarge formula after hospital discharge to 12 months' CA. Beneficial effects were most evident among infants with birth weights <1250 g, particularly for head circumference measurements.

Aftercare↗

Enhanced antitumor immunity by fusion of CTLA-4 to a self tumor antigen.

The idiotypic determinant (Id) of the immunoglobulin expressed by a B-cell malignancy can serve as an effective tumor-specific antigen but is only weakly immunogenic. This study demonstrates that the immunogenicity of the tumor Id protein can be dramatically increased by directing it to antigen-presenting cells (APCs). Cytotoxic T-lymphocyte antigen 4 (CTLA-4) present on activated T cells has a strong binding affinity to both B7-1 and B7-2 molecules, which are primarily expressed on APCs. After construction of a fusion protein consisting of Id and CTLA-4 (Id-CTLA4), mice immunized with the fusion protein induced high titers of Id-specific antibody and T-cell proliferative responses without adjuvants and were protected from lethal tumor challenge. The Id-CTLA4 fusion protein was so potent that even low doses (down to 0.1 microg) of the immunogen were able to elicit strong antibody responses. By using an Id-CTLA4 mutant protein, the ability to bind B7 molecules on APCs was shown to be required for the enhanced immunogenicity of Id-CTLA4. These findings demonstrate that fusing CTLA-4 to a potential tumor antigen represents an effective approach to prime antitumor immunities in vivo and may be applicable to the design of vaccines for a variety of other diseases. (Blood. 2000;96:3663-3670)

Abatacept↗

The management of patients with advanced motor neuron disease.

BACKGROUND: There is no specific treatment for motor neuron disease (MND) except hospice or palliative care to improve patients' quality of life and decrease complications. This topic is seldom discussed in Taiwan. METHODS: A retrospective study was conducted of patients with terminal MND who were treated and died at the Veterans General Hospital-Taipei from March 1986 through April 1996. Patients' characteristics, management, length of survival and cause of death were analyzed. RESULTS: Twenty-three patients (M/F, 17/6) were included. The median age of onset was 59 years (range, 24-69). The median interval from onset of symptoms to diagnosis was nine months (range, 2-36). Seventeen patients received mechanical ventilation for an average median of six months. Nineteen patients had dysphagia, 17 received long-term nasogastric tube feeding, one had gastrostomy and one was treated with cricopharyngeal myotomy. Pain over the neck, trunk or limbs was reported by 18 patients; none received narcotics. Only two patients received respiratory exercise training and two had a cervical collar for stabilization. Electronic communication aids were not available. The median survival from onset of symptoms was 36 months (range, 7-99). The causes of death included sepsis (n = 13), respiratory failure (n = 7), heart disease (n = 2) and MND-related cachexia (n = 1). Cardiopulmonary resuscitation was performed for 12 patients. CONCLUSIONS: In Taiwan, management of patients with advanced MND is mainly hospital-based and most of the effort is focused on life-sustaining. More attention needs to be paid to improvement of the quality of life and dignity of the patient.

Adult↗

Poly(ethylene glycol) modification of beta-glucuronidase-antibody conjugates for solid-tumor therapy by targeted activation of glucuronide prodrugs.

Methoxypoly(ethylene glycol) (PEG) modification of Escherichia coli beta-glucuronidase (betaG) was examined as a method to improve the stability and pharmacokinetics of antibody-betaG conjugates for the targeted activation of glucuronide prodrugs at tumor cells. Introduction of 3 PEG molecules did not affect betaG activity whereas higher degrees of PEG modification produced progressively greater loss of enzymatic activity. The enzyme was found to be stable in serum regardless of PEG modification. PEG-modified betaG was coupled via a thioether bond to mAb RH1, an IgG2a antibody that binds to the surface of AS-30D hepatoma cells, to produce conjugates with 3 (RH1-betaG-3PEG), 5.2 (RH1-betaG-5PEG) or 9.8 (RH1-betaG-10PEG) PEG molecules per betaG with retention of 75%, 45% and 40% of the combined antigen-binding and enzymatic activity of the unmodified conjugate RH1-betaG. In contrast to the rapid serum clearance of RH1-betaG observed in mice, the PEG-modified conjugates displayed extended serum half-lives. RH1-betaG-3PEG and RH1-betaG-5PEG also exhibited reduced spleen uptake and greater tumor accumulation than RH1-betaG. BHAMG, the glucuronide prodrug of p-hydroxyaniline mustard (pHAM), was relatively nontoxic in vivo. Injection of 6 mg/kg or 12 mg/kg pHAM i.v. depressed white blood cell numbers by 46% and 71% whereas 80 mg/kg BHAMG reduced these levels by 22%. Although the tumor/blood ratio of RH1-betaG-5PEG was adversely affected by slow clearance from serum, combined therapy of small solid hepatoma tumors with this conjugate, followed 4 and 5 days later with i.v. injections of BHAMG, cured all of seven mice with severe combined immunodeficiency. Combined treatment with a control antibody-betaG conjugate and BHAMG delayed tumor growth and cured two of six mice while treatment with pHAM or BHAMG alone was ineffective.

Aniline Mustard↗

Effects of the callipyge phenotype on serum creatinine, total cholesterol, low-density lipoproteins, very-low-density lipoproteins, high-density lipoproteins, and triacylglycerol in growing lambs.

The goals of this study were to investigate the effects of the callipyge (CLPG) phenotype on serum creatinine and lipid profiles of growing lambs. Preliminary studies in our laboratories indicated that creatinine may have utility in distinguishing the CLPG phenotype and that expression of the CLPG gene altered concentrations of serum total cholesterol (TC). As a result, in this study, we examined the influence of the CLPG gene on concentrations of creatinine, TC, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triacylglycerol (TG) at varying stages of maturity in lambs. Ten homozygous (c/c) Polypay ewes were crossed with Dorset rams heterozygous for the CLPG gene (C/c). From this cross, 20 lambs (13 females and 7 males) were born, of which 11 were homozygotic (c/c) and 9 were heterozygotic (C/c; CLPG) based on muscle weights and longissimus dorsi (LD) area at slaughter. Blood samples were taken at monthly intervals and serum lipid constituents were assayed. At 1 mo of age, no differences (P > .05) in plasma lipids were detectable between phenotypes. However, at 2 mo age, CLPG lambs had higher (P < .01) concentration of TG, TC, HDL, and VLDL compared to homozygotic (c/c) lambs. Triglycerides and VLDL were elevated (P < .05) in CLPG lambs at 3 mo of age. By slaughter, no differences (P > .05) in serum lipid constituents were detectable between genotypes. Hence, the increase in serum TC is due to elevated levels of HDL and VLDL. These observations indicate that creatinine may be used to distinguish CLPG lambs and that the CLPG gene alters serum lipid profiles during the postnatal period.

Aging↗

Use of fetal ultrasound to select metabolic therapy for pregnancies complicated by mild gestational diabetes.

OBJECTIVE: To determine whether fetal ultrasound early in the third trimester can identify Latina with mild gestational diabetes mellitus (GDM) whose fetuses are at risk for macrosomia and, if so, whether maternal insulin therapy can reduce that risk. RESEARCH DESIGN AND METHODS: Study subjects included 303 consecutive women with GDM and a fasting serum glucose level < 5.8 mM on diet therapy who had a fetal ultrasound between 29 and 33 weeks gestation. Of the women, 98 (32%) had a fetal AC > or = 75th percentile for gestational age, and 59 women completed a randomized trial of diet therapy (n = 29) or diet plus twice daily insulin (n = 30). Maternal nutrient levels were assessed by meal tolerance testing (MTT) before and during therapy and by capillary glucose monitoring four to seven times a day. Birth weights corrected for gestational age and neonatal glycemia and skin folds were the primary outcome variables compared between treatment groups. RESULTS: Diet and diet-plus-insulin groups were well matched for maternal age, prepregnancy relative weight, weight gain during pregnancy, and glycemia at entry. Insulin therapy reduced maternal capillary (P < 0.005) and MTT (P < 0.001) glucose levels and prevented a diet-associated rise in MTT triglyceride levels (P < 0.002). Gestational age at delivery was similar in insulin- and diet-treated groups (39.6 +/- 0.2 vs. 39.5 +/- 0.2 weeks). Birth weights (3,647 +/- 67 vs. 3,878 +/- 84 g; P < 0.02), the prevalence of large-for-gestational age infants (13 vs. 45%, P < 0.02), and neonatal skin-fold measurements at three sites (P < 0.005) were reduced in the insulin-treated group. Rates of transient neonatal hypoglycemia were low in both treatment groups (14 and 18%, respectively) and did not differ significantly between groups. CONCLUSIONS: Fetal ultrasound early in the third trimester identified women with mild GDM whose infants were at high risk for fetal macrosomia in the absence of standard glycemic criteria for insulin therapy. Insulin treatment reduced the macrosomia, indicating that fetal ultrasound can be used to guide metabolic therapy in pregnancies complicated by mild GDM.

Analysis of Variance↗

Benzodiazepines increase preprocholecystokinin messenger RNA levels in rat brain.

Using in situ hybridisation, the effects of acute and chronic diazepam administration and diazepam withdrawal on preprocholecystokinin (CCK) mRNA levels in discrete regions of rat brain were determined. In cerebral cortex and a subpopulation of hippocampal neurones, CCK mRNA levels were increased after a single injection of diazepam and 24 h after withdrawal from chronic diazepam treatment, but not after chronic diazepam treatment. These results show that, in some neuronal groups, CCK mRNA expression is regulated by benzodiazepines, although there is no clear link between CCK mRNA levels and anxiety state.

Animals↗

Transient and sustained components of the pupillary responses evoked by luminance and color.

That the pupil reacts to changes in luminance and color, as well as to spatial features in the retinal image raises questions about whether phasic and tonic and/or color and luminance visual pathways project to the pretectal pupillomotor neurons. The present study compares pupillary responses evoked by heterochromatic and achromatic luminance increments to investigate whether the pupillary responses evoked by color and by luminance are independent of one another. Principal component analysis is used to examine the constituents of the pupil responses. The results support the belief that the visual input to the pupillomotor system is organized into phasic and tonic (but not necessarily independent color and luminance) pathways.

Adult↗

Gastrointestinal tolerance, fat absorption, plasma ketone and urinary dicarboxylic acid levels in low-birth-weight infants fed different amounts of medium-chain triglycerides in formula.

This study was conducted to evaluate the effect of medium-chain triglycerides (MCT) in a formula for low-birth-weight (LBW) infants on gastrointestinal tolerance, fat absorption, plasma ketone levels, and urinary dicarboxylic acid (DCA) excretion. At the start of enteral feedings, 64 LBW infants (< or = 1500 g) were randomly assigned to one of four experimental formulas. The formulas contained either 0, 17, 34, or 50% of the total fat as MCT oil. The nonfat constituents of all four formulas were the same and identical to Similac Special Care 24 (SCF). Infants were studied from the start of enteral feeding until approximately 7 days after reaching full feeds. Growth and tolerance were assessed in all infants over the entire feeding period. A 48-h balance study was conducted after enteral intake exceeded 100 kcal/kg/day for 3 days. Stool fat, plasma D-(-)-3-hydroxybutyrate (3HB) and carnitine, serum glucose, and urinary DCA levels were determined. Groups did not differ in growth, formula intake, fat absorption (76-84%), serum glucose, or plasma carnitine levels. Gastrointestinal tolerance was excellent and did not differ among groups. Plasma 3HB was significantly different (p < 0.05) only between the 0 and 50% MCT groups, 50 +/- 10 versus 120 +/- 20 microM, respectively. The excretion of urinary DCAs increased with increasing amounts of MCT in the formula. In conclusion, fat absorption and gastrointestinal tolerance were not affected by different MCT levels (0 to 50% of the total fat), but higher levels of plasma 3HB and urinary DCAs were associated with higher levels of MCT in the LBW formulas studied.

Analysis of Variance↗

A comparison of rat brain amino acid and monoamine content in diazepam withdrawal and after exposure to a phobic stimulus.

1. The content of amino acids (taurine, glycine, glutamic acid, gamma-aminobutyric acid (GABA) and aspartic acid) and monoamines (5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline) in homogenates of rat cortical and hippocampal tissue were measured by high performance liquid chromatography (h.p.l.c.) with fluorescent and electrochemical detection respectively, after two anxiogenic treatments: exposure to a phobic stimulus (cat odour) and withdrawal from chronic diazepam treatment. 2. In neither of the two anxiogenic situations was there a significant change in any amino acid content, in either brain area. 3. In the group withdrawn from chronic diazepam, cortical 5-HT and 5-HIAA levels and hippocampal 5-HT levels were significantly increased. Noradrenaline content was significantly decreased in the hippocampus. 4. The changes in 5-HT and 5-HIAA levels following cat odour exposure were area-specific in that they decreased in the hippocampus, but increased in the cortex. 5. Following cat odour exposure, noradrenaline levels appeared not to change in either area studied. However during exposure to cat odour, it was found that half the animals avoided the odour source and half were indifferent. The animals showing marked avoidance had significantly higher cortical noradrenaline content and this was significantly different from control, whereas hippocampal noradrenaline levels were not dependent upon the differences in avoidance of the odour source. 6. The results show clearly different neurochemical changes in the rat following exposure to a phobic stimulus and withdrawal from diazepam. It is hoped comparative studies such as this will enable better understanding of anxiety states in the rat which could parallel the different classes of anxiety recognised in the clinic

Amino Acids↗

The role of 5-HT in the anxiogenic effects of acute ethanol withdrawal and in the long-lasting cognitive deficits.

There was a significant increase in potassium-stimulated release of 3H-[5-HT] from hippocampal slices taken from rats withdrawn from chronic ethanol treatment, compared with control-treated rats. The anxiogenic behaviour observed 12 h after ethanol withdrawal was inhibited by the 5-HT1A partial agonist, buspirone (200 micrograms/kg s.c.), indicating that the increased 5-HT release might underlie the anxiogenic response. The ex-ethanol treated rats showed impaired habituation of motor activity in the holeboard and a reduced exploratory response. The latter, but not the former, were reversed by the 5-HT3 receptor antagonist, ondansetron (0.01 microgram/kg i.p.). Ondansetron was without effect on working memory errors, but significantly increased the number of reference memory errors made by the ex-ethanol group. It also had a significantly anxiogenic effect in this group. These results suggest that the chronic ethanol treatment changes the 5-HT system and has long-lasting effects on the function of 5-HT3 receptors.

Animals↗

An object-based approach to medical process automation.

The medical events of providers rendering services for patient care are necessarily interrelated. A clinical information system must reliably record these events and relate the information about their inter-dependency. The quality of clinical information therefore depends crucially on the proper coordination and tracking of these events according to established protocols. We introduce an object-based approach to define medical processes for their automation. For each medical process, we capture in one logical unit, an event-driven mechanism to coordinate of inter-dependent medical events of the process, and the data relevant to the process. We call the encapsulated unit a form object. Moreover, the form object may contain sub-objects each of which also encapsulates its own protocol knowledge and relevant information. In contrast to other approaches, the form object facilitates for administering medical processes due to its locality of definition, and its event-driven paradigm reflects medical events more naturally.

Computer Simulation↗

Modification of chlordiazepoxide's behavioural and neurochemical effects by handling and plus-maze experience.

The purpose of the present experiment was to determine how a rat's prior history (of repeated gentle handling and/or of the elevated plus-maze apparatus) modified the behavioural and neurochemical response to chlordiazepoxide. In handled animals one previous exposure to the plus-maze rendered the rats insensitive to the anxiolytic effects of chlordiazepoxide in this test. This phenomenon of 'one-trial tolerance' was not seen in unhandled rats and thus both prior handling and prior maze experience were necessary to abolish the behavioural response to chlordiazepoxide. The effects of chlordiazepoxide on K(+)-evoked [14C]GABA (gamma-aminobutyric acid) release were also modified by the rat's past history. The drug-induced reduction of GABA release in the cortex was abolished by prior plus-maze experience; whereas handling modified chlordiazepoxide's effects on GABA release in the hippocampus (the drug decreased release in unhandled rats and increased release in those given repeated gentle handling). Thus an anxiolytic response to chlordiazepoxide in the plus-maze was accompanied by reduced GABA release in both cortex and hippocampus. The 5-HT system (5-hydroxytryptamine) also proved sensitive to the rats' past history. The effects of chlordiazepoxide on K(+)-evoked [3H]5-HT release from the hippocampus depended on both prior handling and plus-maze experience and could be predicted from the undrugged level of evoked release; when this was low, chlordiazepoxide increased it, when it was high, chlordiazepoxide reduced it. These results raise the possibility that the beneficial effects of a benzodiazepine may depend on the baseline condition of the animals.

Animals↗

Effect of nasolacrimal occlusion on timolol concentrations in the aqueous humor of the human eye.

We studied the effect of manual nasolacrimal occlusion on the concentration of timolol in the aqueous humor of eyes of patients undergoing cataract extraction. Aqueous humor samples were obtained at various times after timolol maleate instillation from patients with or without 5 min of nasolacrimal occlusion; aliquots were assayed by HPLC. In patients receiving occlusion treatment, average timolol concentrations were statistically greater than those in control patients both between 15 and 90 min after instillation and also at 180 min. Pharmacokinetic analysis indicated that occlusion increased the concentration of timolol in the aqueous humor 1.7 times. In both groups, timolol concentrations were highest approximately 1 h after instillation. The decline in aqueous humor timolol concentrations occurred at similar rates in both groups.

Aged↗

[The interrelationship between the O2-dependent bactericidal mechanism and hyperbilirubinemia of newborn].

In order to investigate the influence of indirect bilirubin to O2-dependent bactericidal mechanism in adult and newborn phagocytes we use the NBT reduction activity of granulocytes and monocytes as index, by infiltrated granulocytes and monocytes in different concentration of indirect bilirubin with or without latex stimulator. The NBT reduction activity of granulocytes infiltrated in 20 mg/dl indirect bilirubin will increase slightly, compared to uninfiltrated; but with latex stimulator, the increment will decrease significantly, this change is reversible, when indirect bilirubin be washed, the stimulating capacity by latex stimulator in granulocyte will be stronger; there were no such change pattern in monocytes. Since there were a big difference in NBT reduction activity of granulocytes and monocytes between newborns, with or without latex stimulator, we can't get a satisfied result. Indirect bilirubin in cells will increase NBT reduction activity of monocytes, but not in granulocytes.

Adult↗

Aqueous humor pilocarpine and timolol levels after instillation of the single drug or in combination.

Aqueous humor levels of pilocarpine and timolol in rabbits after administration of either 2% pilocarpine or 0.5% timolol in single-drug solutions were compared with the concentrations found after instillation of a fixed combination of 0.5% timolol and 2% pilocarpine drops. Time intervals considered were 15 min, 30 min, 1 hr, 4 hr, and 8 hr after application. Drug concentrations were analyzed in individual aqueous samples by high-performance liquid chromatography. No statistically significant differences in either pilocarpine or timolol concentrations in aqueous humor were found at any time tested between the single-drug preparations and the combination.

Administration, Topical↗

Oxygenation index in patients with meconium aspiration: conventional and extracorporeal membrane oxygenation therapy.

The use of the alveolar-arterial oxygen difference P(A-a)O2 and the oxygenation index (mean airway pressure [Paw] FIO2 x 100/PaO2) have been proposed for selecting infants who will require extracorporeal membrane oxygenation (ECMO) therapy. However, the use of the oxygenation index (OI) in conjunction with Paw in an exclusive population of patients with meconium aspiration syndrome (MAS) has not been reported. Fourteen patients born in our facility and managed with conventional therapy and five infants treated with ECMO were enrolled in the study. All patients had clinical and x-ray evidence of MAS. Infants who received conventional treatment required mechanical ventilation greater than 48 h, FIO2 1.0, and were under the care and supervision of one neonatologist. Management was directed to minimize barotrauma by avoidance of routine hyperventilation, use of lower Paw, and sufficient expiratory time. One patient died before ECMO and 13 infants survived. Six survivors had an OI greater than 25 (three had an OI greater than 40), six had a Paw greater than or equal to 12 cm H2O (12 to 15 cm H2O in five infants) and six patients had a P(A-a)O2 greater than or equal to 610 torr. One surviving infant was transferred for ECMO therapy (OI 67, Paw 20 cm H2O). The five patients treated with ECMO survived (OI 48 to 92, Paw 20 to 29.5 cm H2O P(A-a)O2 627 to 650 torr). One patient in each group developed chronic lung disease with evidence of resting tachypnea. Our findings indicate that an OI greater than 40 in association with a Paw greater than or equal to 20 cm H2O may be helpful in predicting which infants with MAS need ECMO, whereas patients requiring a Paw less than or equal to 15 cm H2O can be managed with conventional therapy. An OI greater than or equal to 25 but less than 40 is not associated with high mortality in these patients. The predictive value of Paw of 16 to 20 cm H2O and the duration of an OI greater than 40 in patients with MAS need further investigation.

Airway Resistance↗