[Expert consensus on early prediction and diagnosis of diabetic kidney disease].

Diabetic kidney disease (DKD) is a type of chronic kidney disease (CKD) caused by diabetes. The clinical diagnosis of DKD is usually based on the presence of increased albuminuria and/or decreased estimated glomerular filtration rate (eGFR), and exclusion of other causes of CKD. The clinical features of DKD are proteinuria, gradual decline in renal function, and severe renal failure in the later stages, which is one of the main causes of death in patients with diabetes. Any single biomarker might be insufficient to evaluate renal injury; thus, multiple methods and markers are needed. In addition, diabetic patients should be paid more attention to the kidney, and kidney damage should be evaluated with standardized assessment aimed at strengthening the early prediction and diagnosis of DKD.

[Using of ¹8F-FDG to evaluate the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway: a PET-MRI pilot study].

Objective:This study evaluated the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway via the instillation of ¹8F-FDG at the olfactory cleft. Method:Seven healthy volunteers and 5 patients with traumatic dysosmia were enrolled in the study. Subjects were all instilled with ¹8F-FDG on each side of the olfactory cleft under endoscopy. After 12 hours, a PET/MR scan was performed to track the metabolism pathway of ¹8F-FDG. Then, we compared the diameter of the olfactory bulb and the olfactory bulb intake between normal volunteers and patients with traumatic olfactory disorders. Result:In healthy volunteers, there was a significant difference in ¹8F-FDG uptake between the regions of interest in which ¹8F-FDG was or was not in contact with the cribriform plate（P=0.012 7）; this difference also existed in patients with traumatic olfactory disorders（P=0.038 1）. Patients with traumatic olfactory disorders did not exhibit significant differences in ¹8F-FDG uptake in the region of interest compared with healthy volunteers（P=0.937 2）. Conclusion:The olfactory bulb is obviously atrophied in patients with traumatic olfactory dysfunction, and the uptake of ¹8F-FDG in the olfactory bulb region of interest is also reduced. The administration of ¹8F-FDG via olfactory fissure area can enter olfactory bulb and parafrontal tissues through the nasal brain pathway,¹8F-FDG can enter the central nervous system through the nasal-brain pathway, which is not affected by olfactory nerve transection injury.

[MicroPET-CT study of the association between odor stimulation and olfactory related brain activation in rats].

Objective: Using (18)F-fluorodeoxyglucose ((18)F-FDG) and microPET-CT to test the feasibility of (18)F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of (18)F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of (18)F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat's brain after PEA stimulation included bed nucleus and insula. Activation regions of rat's brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions: Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat's brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.

Morphologic and molecular alteration during tibia fracture healing in rat.

OBJECTIVE: To monitor morphological feature and related osteogenic and bone metabolic change during healing of tibia fracture in a rat model. MATERIALS AND METHODS: Tibia density and trabecular thickness were evaluated. Histopathology was examined by HE staining. Serous inflammatory factors IL-4, IL-6, TNF-α and metabolic biomarkers ALP, ß-CTX, P1NP, were determined by ELISA. The expression of RUNX2, TGF-ß1, VEGF-α, BMP-2, BMP-4, and BMP-7 in callus tissue were qualified by RT-PCR. RESULTS: Bone density decreased until week 4 and then increased post-operation. Trabeculae in callus were thickened over time with active osteogenesis. ELISA indicated the most severe inflammation at week 2, with the highest level of TNF-α, IL-6, and the lowest level of IL-4. After 4 weeks, the inflammation was alleviated accompanying with the decline of TNF-α and IL-6, while there was the elevation of IL-4. Bone metabolism showed active osteogenesis and resorption at week 6 with high P1NP and ß-CTX. The expression of RUNX2, TGF-ß1, VEGF-α, BMP-2, BMP-4, and BMP-7 increased progressively from week 1 to 6. The major lesions at week 2 in sham were tissue necrosis, periosteal reactive hyperplasia, inflammatory cell infiltration, capillary hyperplasia and slight fibro-blast cytopoiesis. At week 4, proliferation was greatly activated, fibrous callus shaped and chondrogenesis and some osteogenesis occurred at week 8. CONCLUSIONS: In rat model, bone density started to increase at week 6 after fracture, accompanied with trabeculae thickening, serous inflammatory factors decline, and peaked bone morphogenetic protein/growth factors, which indicated active osteogenesis was conforming to the classical phase of secondary fracture healing.

Potent antitumor activity of Oct4 and hypoxia dual-regulated oncolytic adenovirus against bladder cancer.

Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor-selective replication of oncolytic adenoviruses may be hindered by oxygen deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus, retaining its antitumor activity even in a hypoxic environment. We have previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven by nine copies of the Oct4 response element (ORE) for specifically killing Oct4-overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual-regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2α and Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF-2α was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells, while sparing normal cells. AdLCY exerted potent antitumor effects in mice bearing human bladder tumor xenografts and syngeneic bladder tumors. It could target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4 is expressed in various cancers, AdLCY may be further explored as a broad-spectrum anticancer agent.

Time- and dose-dependent effect of psyllium on serum lipids in mild-to-moderate hypercholesterolemia: a meta-analysis of controlled clinical trials.

OBJECTIVES: Evidences from randomized clinical trials and meta-analysis have claimed an association between the use of soluble dietary fiber from psyllium and a cholesterol-lowering effect. However, there is still uncertainty as to the dose-response relationship and its long-term lipid-lowering efficacy. This meta-analysis was primarily conducted to address the dose-response relationship between psyllium and serum cholesterol level and time-dependent effect of psyllium in mild-to-moderate hypercholesterolemic subjects. METHODS: Twenty-one studies, which enrolled a total of 1030 and 687 subjects receiving psyllium or placebo, respectively, were included in the meta-analysis. The studies were randomized placebo-controlled trials, double blinded or open label, on subjects with mild-to-moderate hypercholesterolemia. The dose of psyllium was between 3.0 and 20.4 g per day and intervention period was more than 2 weeks. Any type of diet background was permitted. Diet lead-in period was between 0 and 8 weeks. RESULTS: Compared with placebo, consumption of psyllium lowered serum total cholesterol by 0.375 mmol/l (95% CI: 0.257-0.494 mmol/l), and LDL cholesterol by 0.278 mmol/l (95% CI: 0.213-0.312 mmol/l). With random-effect meta-regression, a significant dose-response relationship were found between doses (3-20.4 g/day) and total cholesterol or LDL cholesterol changes. Regression model of total cholesterol was -0.0222+0.2061 x log (dose+1), and that of LDL cholesterol was 0.0485+0.1390 x log (dose+1). There was a time effect of psyllium on total cholesterol (equation: 6.3640-0.0316 x treatment period) and on LDL cholesterol (equation: 4.3134-0.0162 x treatment period), suggesting that psyllium reduced serum total cholesterol more quickly than LDL cholesterol. CONCLUSIONS: Psyllium could produce dose- and time-dependent serum cholesterol-lowering effect in mild and moderate hypercholesterolemic patients and would be useful as an adjunct to dietary therapy for the treatment of hypercholesterolemia.

Comparison of ibuprofen and indometacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial.

BACKGROUND: To date there is no firm conclusion as to the efficacy and safety of ibuprofen compared with indometacin for patent ductus arteriosus (PDA) closure in extremely premature infants. OBJECTIVE: To conduct a randomised controlled trial to better address this problem. METHODS: 119 infants (gestational age < or =28 weeks) with respiratory distress syndrome and PDA confirmed by echocardiography were randomly assigned to receive either indometacin (0.2 mg/kg) or ibuprofen (10 mg/kg), starting at <24 hours of life, followed by half these first doses within 48 hours at 24-hour intervals if indicated by echocardiographic PDA flow pattern. RESULTS: The PDA closure rate and the doses of drug (mean (SD)) were similar in both groups: 53/60 (88.3%) and 1.9 (1.5) mg/kg in infants given ibuprofen, and 52/59 (88.1%) and 1.9 (1.7) mg/kg in infants given indometacin. No significant difference was found in the numbers of infants requiring surgical ligation, and the levels of post-treatment serum creatinine and urea nitrogen between the two groups. Although not significantly different, more infants (9/59 (15.3%)) treated with indometacin tended to develop oliguria (<1 ml/kg/h) than those treated with ibuprofen (4/60 (6.7%)). There were no significant differences in side effects or complications between the two groups. CONCLUSIONS: Ibuprofen is as effective as indometacin for the early-targeted PDA treatment in extremely premature infants, without increasing the incidence of complications. When the echocardiographic PDA flow pattern was used as a guide for PDA treatment, fewer doses of drugs were needed to achieve acceptable closing rates.

Meta-analysis: the efficacy of nootropic agent Cerebrolysin in the treatment of Alzheimer's disease.

To determine the therapeutic effect of nootropic agent Cerebrolysin on patients with mild to moderate Alzheimer's disease (AD), we searched the Cochrane Library, Medline, PubMed, and Chinese Biomedical Literature Analysis and Retrieval System for Compact Disc (CBMDISC), and communicated with EBEWE Pharmaceutical Ltd, for randomized trials comparing Cerebrolysin with placebo in AD. Available data on clinical global impression, cognitive performance and activities of daily living were extracted from 6 randomized double-blind placebo-controlled clinical trials and combined with standard meta-analysis methods. An infusion with Cerebrolysin for 4 weeks (30 ml Cerebrolysin daily on five consecutive days of each week) led to a significant improvement of the clinical global impression. Compared with placebo, log(OR) was 1.1799, and 95% confident interval was 0.7463-1.6135 (P < 0.05), indicating that Cerebrolysin could significantly improve the clinical global impression in patients with mild to moderate AD. However, more convincing evidences are needed for the efficacy of Cerebrolysin on the cognitive performance and activities of daily living.

Peripheral B lymphocyte beta1,3-galactosyltransferase and chaperone expression in immunoglobulin A nephropathy.

PURPOSE: Aberrant O-glycosylation of serum IgA(1) is presumed to be one of the main pathogenesis of immunoglobulin A nephropathy (IgAN). beta1,3-galactosyltransferase (beta1,3GT), whose activity requires coexistence of a specific chaperone, is the main enzyme which participate in the glycosylation process. The current study was carried out to elucidate the expression level of beta1,3GT (C1GALT1) and its chaperone (Cosmc) in IgAN, and their relationships with clinical features as well as IgA glycosylation level. DESIGN, SETTING AND SUBJECTS: Forty-one patients with IgAN, 21 patients with non-IgAN glomerulonephritis and 26 normal controls were included in the present study. Peripheral B lymphocytes were isolated, and then expression level of C1GALT1 and Cosmc were quantitatively measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Serum IgA level and glycosylation level were determined by enzyme-linked immunosorbent assay (ELISA) and VV lectin-binding method. Correlation analysis was performed between C1GALT1/Cosmc expression levels and clinical manifestations (severe proteinuria, renal dysfunction, gross haematuria). RESULTS: B-lymphocyte Cosmc gene expression level was significantly lower in IgAN patients than that of normal control and non-IgAN patients (P<0.05), whilst no apparent disparity was observed in C1GALT1 expression level. Cosmc expression showed a negative correlation with IgA O-glycosylation level indicated by VV lectin-binding assay. Statistical analysis also indicated that the level of Cosmc expression was negatively correlated with severe proteinuria (P<0.05) instead of gross haematuria (P>0.05). CONCLUSION: These data suggested that the aberrant IgA O-glycosylation in IgAN was resulted from a downregulation of beta1,3GT chaperone (Cosmc) expression in B lymphocyte, which is closely associated with clinical characteristics of the disease. This downregulation might be one of the fundamental pathogenic abnormalities in IgAN.

Tricuspid regurgitation in patients with beta-thalassemia major.

Although cardiac complications remain the main causes of death in thalassemic patients, right heart dysfunction has been little studied and the mechanism is still unclear. Echocardiography was performed in 39 patients with beta-thalassemia major and 35 aged-matched controls. The gender, age, heart rate, blood pressure, left ventricular ejection fraction (LVEF), acceleration time (AcT) of right ventricular outflow and right ventricular ejection time (RVET), AcT/RVET, and the presence of tricuspid regurgitation (TR) were compared between the two groups. We also compared the gender, age, age at first blood transfusion, serum ferritin level, alanine aminotransferase (ALT), the presence of antibodies to hepatitis C virus, liver fibrosis, splenectomy, platelet counts, diabetes mellitus, arrhythmia, cardiomegaly, LVEF, AcT, RVET, AcT/RVET, and signal intensity ratio (SIR) of myocardial magnetic resonance imaging (MRI) between thalassemic patients with and without TR. The incidence of TR in thalassemic patients was significantly higher than that in the control group (30.8 vs 11.4%, p=0.03). The incidences of splenectomy (p=0.03), platelet counts (p=0.01), and SIR of myocardial MRI (p=0.03) in thalassemic patients with TR were significantly higher than in those without TR. The AcT was shorter and the AcT/RVET ratio was smaller, suggesting higher pulmonary pressure in the thalassemic patients with TR. Occurrence of TR in patients with beta-thalassemia major may be a consequence of cardiac iron deposit, thrombocytosis, splenectomy, or pulmonary hypertension.

Glucose-insulin infusion for the early treatment of non-oliguric hyperkalemia in extremely-low-birth-weight infants.

In order to investigate the status of non-oliguric hyperkalemia and to evaluate glucose-insulin infusion treatment among extremely-low-birth-weight (ELBW) infants, 161 infants weighting less than 1000 gm at birth were enrolled for this study. They were divided into two groups: a hyperkalemic group and a non-hyperkalemic group. Hyperkalemia was defined here as a serum potassium level of greater than 6 mEq/L in a non-hemolyzed arterial blood sample. A glucose-insulin infusion was administered to the patients when hyperkalemia was detected in them during the first few days after birth. The infusion was discontinued when the serum potassium levels had been less than 6 mEq/L and stabilized for 6 hours. The incidence of non-oliguric hyperkalemia among ELBW infants in this study was 58% (93/161). The mean gestational age of neonates was 25.7 +/- 1.8 weeks (hyperkalemic) and 26.6 +/- 1.7 weeks (non-hyperkalemic). The mean rate of increases in serum potassium levels was 0.32 +/- 0.29 mEq/L/hr (hyperkalemic) and 0.13 +/- 0.12 mEq/L/hr (non-hyperkalemic). The incidence of severe intraventricular hemorrhage (IVH) was 19% (18/93) (hyperkalemic) and 4.4% (3/68) (non-hyperkalemic). The incidence of cardiac arrhythmia was 12% (11/93) (hyperkalemic) and 0% (non-hyperkalemic) respectively. Neonates with fewer weeks of gestation at birth and faster increases in serum potassium levels were associated with a more prominent tendency toward hyperkalemia. Hyperkalemia markedly increases the risk of severe IVH and arrhythmia for ELBW infants. A higher glucose infusion rate should be maintained to prevent hypoglycemia following insulin treatment.

Persistent pulmonary hypertension of the newborn: echocardiographic assessment.

Twenty seven newborn infants with persistent hypoxemia in the first 3 days after birth were enrolled for hemodynamic assessment using echocardiography. Measurements included pulmonary arterial pressure (peak velocity of tricuspid regurgitation (TR), patent ductus arteriosus (PDA) flow pattern, interatrial shunting flow pattern and pulmonary flow velocity ratio (the time to peak velocity/right ventricle ejection time ratio (TPV/RVET)) and left ventricular ejection fraction. The estimated systolic pulmonary arterial pressure and the systemic arterial pressure determined via an indwelling arterial line were recorded at the time of echocardiographic examination, and pulmonary arterial pressure/systemic arterial pressure was calculated. Nineteen infants (70.4%) had a TR sufficient to estimate systolic pulmonary arterial pressure. The median value of pulmonary arterial pressure/systemic arterial pressure was 1.02 (range, 0.68 to 1.78). Twenty two infants (81.5%) had a PDA and flow patterns indicating pulmonary arterial pressure above or approaching systemic arterial pressure. All infants had a foramen ovale and flow patterns were bi-directional or pure right-to-left. TPV/RVET had a wide range of values (0.23 to 0.55), and only 44.5% of infants had high pulmonary arterial pressure as reflected by low TPV/RVET ratio. Eleven infants (40.7%) had an ejection fraction below the normal range. Results of 17 survivors were compared with 8 deceased infants (2 infants of birth weight less than 1000 gm were excluded who died of massive pulmonary hemorrhage). There were no significant differences for any parameter of pulmonary arterial pressure, but ejection fraction was significantly lower in deceased infants. This study has demonstrated that it is possible to evaluate pulmonary arterial pressure noninvasively by using echocardiography in most newborn infants with clinical evidence of persistent pulmonary hypertension of the newborn (PPHN). Ejection fraction is an echocardiographic parameter which can significantly predict mortality.

Risk factors of pulmonary hemorrhage in very-low-birth-weight infants: a two-year retrospective study.

Pulmonary hemorrhage is a serious complications in very-low-birth-weight (VLBW) infants with respiratory distress syndrome (RDS). We undertook a 2-year retrospective study to investigate the predisposing factors and the incidence of pulmonary hemorrhage in VLBW infants. From January 1997 through December 1998, twenty infants were diagnosed with massive pulmonary hemorrhage (MPH) according to the following criteria: active bleeding from the endotracheal tube, acute drop in hematocrit (> or = 10%), and the development of multilobar infiltration on chest radiograph. The mean gestational age was 26.9 +/- 2.5 weeks, the mean birth weight was 909 +/- 290 g. Twenty historic controls with similar gestational age and birth weight were retrospectively identified during the study period. The incidence of MPH in VLBW infants was 5.9%(20/340). A lack of prenatal corticosteroid administration, surfactant replacement therapy for RDS, and a patent ductus arteriosus (PDA) with cardiovascular dysfunction requiring dopamine support were the significantly predisposing factors of MPH in the acute stage (< or = 7th day of life). To avoid MPH and decrease mortality and morbidity in the acute stage, prenatal corticosteroid administration, evaluation of the necessity of surfactant therapy, and early recognition and aggressive treatment of hemodynamically significant PDA were necessary.

Chronic lung disease in extremely low birth weight infants: a two-year retrospective analysis.

To determine the incidence and classification of chronic lung disease (CLD) in extremely low birth weight (ELBW) infants, a 2-year retrospective analysis was performed. From January 1997 to December 1998, 117 infants weighing less than 1000 g were enrolled. The survival rate beyond 28 days was 60.7% (71/117). CLD was defined as a supplemental oxygen requirement at 28 days of age, with symptoms of persistent respiratory distress and chest radiograph showing characteristic appearance. In addition to the common finding of CLD, infants with bronchopulmonary dysplasia (BPD) had history of respiratory distress syndrome (RDS), infants with Wilson-Mikity syndrome (WMS) had no RDS but had early appearance of bubbly lung on chest x-ray, and infants with chronic pulmonary insufficiency of prematurity (CPIP) had only hazy appearance on chest x-ray. The incidence of CLD in infants who survived beyond 28 days was 50.7% (36/71). Among the 36 infants with CLD, 17 (47%) had BPD, 4 (11%) had WMS and 15 (42%) had CPIP. The median (min, max) days of mechanical ventilation were 45 (9, 112), 45.5 (45, 50) and 7.5 (0, 40) days in BPD, WMS and CPIP groups, respectively. The median (min, max) days of oxygen requirement were 73 (28, 120), 149 (70, 211) and 52.5 (38, 90) days, respectively. The infants still requiring oxygen at post-conceptional age of 36 weeks are significantly more in BPD (14 (82.4%)) and in WMS (4 (100%)) than in CPIP (3 (20%)). Two (1 BPD, 1 WMS) were discharged and received oxygen therapy at home. Four infants with BPD died of respiratory failure. CLD includes a wide range of conditions, from BPD or WMS with severe respiratory morbidity and mortality to no residual problems. Such information is important for design of appropriate strategies to prevent CLD.

Partial liquid ventilation in normal rabbits: comparison of three kinds of perfluorocarbon.

Perfluorocarbon liquids have been used in liquid ventilation studies and considered an effective technique of gas exchange with less barotrauma when compared with gas ventilation. We compared the effects of partial liquid ventilation (PLV) using 3 kinds of perfluorocarbon liquids (Fluorinert FC 43, FC 77 and FC 84) available in Taiwan in normal rabbits. We were able to achieve adequate oxygenation and ventilation during a 2-hour-duration of PLV using FC 43, FC 77 or FC 84. There was no significant difference in hemodynamic status or laboratory findings between control group and PLV groups. There were also no significant differences before LV and after 2 hours of PLV among PLV groups. Histological study of lung tissue revealed intact and well expanded alveoli, and no significant pathological change after 2 hours of PLV. These results show that PLV using FC 43, FC 77 or FC 84 is an effective technique for maintaining adequate pulmonary gas exchange in normal rabbits.

Echocardiographic flow pattern of patent ductus arteriosus: a guide to indomethacin treatment in premature infants.

AIM: To compare the efficacy and safety of an indomethacin treatment strategy based on serial echocardiographic measurement of patent ductus arteriosus (PDA) flow pattern with a standard protocol. METHODS: Neonates weighing less than 1500 g at birth, who required respiratory support, and who had developed symptomatic PDA, were studied. PDA was confirmed in all infants using colour Doppler echocardiography, and serial observations of the ductal flow pattern were made. Infants randomly assigned to receive conventional indomethacin treatment (protocol group) were given an initial dose of 0.2 mg/kg, followed by 0.1 or 0.2 mg/kg, depending on age, 12 hourly for two further doses, and were eligible for a second course. Those randomly assigned to the ductal flow pattern assessment (ECHO group) received further doses of indomethacin after 24 hours, only if their flow pattern was "pulsatile" or "growing." RESULTS: There was no significant difference in the primary outcome measures between the two groups. The closure rate was 89.1% and 87.2%, respectively, in the protocol and ECHO groups. The mean (SD) doses of indomethacin were significantly higher in the protocol group: 3.2 (1.4) doses compared with 1.6 (0.9) doses. There was a significantly higher incidence of hypoglycaemia, impaired urine output, and gastrointestinal bleeding in the protocol group. CONCLUSIONS: An indomethacin treatment strategy for PDA based on measurement of the ductal flow pattern is associated with a reduction in the total doses of indomethacin administered, and a reduced rate of complications, compared with a conventional protocol. There is no difference in closure rate.

Dynamics of reactive oxygen intermediate production in human glioma: n-6 essential fatty acid effects.

BACKGROUND: Reactive oxygen intermediates (ROIs) are important signals controlling cell growth and cell death. Local essential fatty acid (EFA) deficiencies in tumour cells may limit tumour ROI generation. This deficiency may be rectified by the addition of exogenous EFA. MATERIALS AND METHODS: The n-6 EFA effects on tumour ROIs were analysed in terms of kinetics, dose-response and individual cell type responses using flow cytometry of intracellular 2',7'-dichlorofluorescin oxidation. ROI formation in 30 gliomas and five paired samples of normal brain tissue, > 500 000 cells per specimen, was analysed every 10 s for 0-25 min. RESULTS: Tumour cell basal ROI was lower than normal brain tissue ROI from the same subjects (P < 0.00002). Normal and tumour cell ROIs were stimulated by 4-40 micromol L-1 n-6 EFAs, arachidonic acid (AA) and gamma-linolenic acid (GLA). The stimulated ROI rate was exponential, with the maximum dependent on EFA concentration and tumour grade. CONCLUSIONS: EFAs stimulated tumour cells more than normal cells (P < 0.0000017, n = 71) and increased ROIs in glial fibrillary acidic protein-positive cells in tumours. This indicated high sensitivity of glioma cell ROIs to n-6 EFAs.

Glucose and insulin infusion versus kayexalate for the early treatment of non-oliguric hyperkalemia in very-low-birth-weight infants.

Forty very low birth weight (VLBW) infants with non-oliguric hyperkalemia in the first few days after birth were enrolled in this study. They were randomly divided into 2 groups, regular insulin (RI) infusion group and kayexalate resin enema group. Therapy was administered when serum potassium level was greater than 6 mEq/L. None of these infants received blood transfusion during this study course. In RI group (n = 20), the ratio of infusion glucose to regular insulin was 10-15 gm glucose to 1 unit RI, and the glucose infusion rate was maintained at least 6 mg/Kg/min. In Kayexalate group (n = 20), the dose of Kayexalate was 1 gm/Kg body weight given rectally every four hours. All treatment discontinued after the serum potassium level returned to normal for 6 hours. The mean gestational ages were 27.4 +/- 1.8 weeks in RI group and 28.4 +/- 2.4 weeks in Kayexalate group, respectively. Mean birth weights were 935 +/- 259 gm (RI) and 1065 +/- 214 gm (Kayexalate). The ages at onset of hyperkalemia were 24.6 +/- 8.2 (RI) and 22.2 +/- 8.1 (Kayexalate) hours after birth. The mean urine outputs during the 8-hour interval prior to development of hyperkalemia were 5.4 +/- 1.3 (RI) and 5.5 +/- 0.9 (Kayexalate) ml/kg/min. The durations of hyperkalemia were 26.4 +/- 14.9 (RI) and 38.6 +/- 13.3 (Kayexalate) hours. The peak serum potassium levels during therapy were 7.3 +/- 0.9 and 7.4 +/- 0.6 mEq/L. The incidences of grade II and above intraventricular hemorrhage (IVH) were 15% (3/20) and 50% (10/20). The incidences of cardiac dysrhythmia were 5% (1/20) and 10% (2/20). Significantly shorter duration of non-oliguric hyperkalemia and lower incidence of IVH were noted in RI group, but there were no differences in the peak potassium level or the incidence of cardiac dysrhythmia between these two groups. We conclude that to use early continuous regular insulin infusion therapy for the treatment of non-oliguric hyperkalemia in VLBW infants is more effective than kayexalate in decreasing the duration of hyperkalemia and reducing the incidence of intraventricular hemorrhage.

Influence of perinatal factors on limit of viability in extremely low birth weight infants.

This retrospective study investigated the influence of perinatal factors on the limit of viability in extremely low birth weight (ELBW) infants. From January 1997 to May 1998, all infants weighing less than 1000 gm admitted to NICU of China Medical College Hospital were enrolled in this study. Still-born infants and infants with congenital anomaly were excluded. The end outcome was survival of the infants (defined as alive at discharge). Eighty-four infants were included in this study. Their mean gestational age (GA) was 25.8 +/- 1.76 weeks, mean birth weight (BW) was 772 +/- 114 gm, and overall survival rate was 48.8%. The smallest intact survival was a female infant of GA 23 weeks and BW 530 gm. Early neonatal mortality rate (< 7 days) was 26.2% (23/84). The cut off levels, below which mortality significantly increased, were GA < 24 weeks and BW < 700 gm (odds ratio, 6.11, confidence interval, 2.01 to 18.63 for GA; odds ratio, 2.65, confidence interval, 1.09 to 6.39 for BW). The two most significant factors which independently affected neonatal survival were GA < 24 weeks and early neonatal dexamethasone treatment for the prevention of chronic lung disease (odds ratio, 9.24, confidence interval, 2.53 to 33.76 for GA; odds ratio, 35.83, confidence interval, 7.03 to 183 for dexamethasone treatment). We conclude that in order to further reduce neonatal mortality, efforts should be made in the areas of prenatal care and women's health to prevent extreme prematurity and low birth weight infants. In the case of an impending delivery of an ELBW infant, an active plan of management for all gestations > or = 24 weeks seems appropriate. Finally, unless it is proven to be safe, early neonatal dexamethasone treatment for prevention of chronic lung disease should not be routinely used in ELBW infants.

Effect of erythromycin on feeding intolerance in very low birth weight infants: a preliminary observation.

To investigate the effect of erythromycin on feeding intolerance in very low birth weight infants, from February 1997 to December 1997 twenty infants weighing less than 1500 g, with prolonged intolerance of enteral feeding, were enrolled in this study. The protocol for erythromycin treatment was: a loading dose of 30 mg/kg/day, divided into three portions given every eight hours intravenously for 1 hour over a three day period; then a maintenance dose of 3-5 mg/kg intravenously for one hour once a day was given until full feeding was well established. The assessment of erythromycin effect was the daily net orogastric balance (volume of orogastric tube feeding minus volume of orogastric aspirates). The mean gestational age was 27.1 +/- 2.0 weeks (mean +/- SD) and the mean birth weight was 1025 +/- 196 g. The mean age when erythromycin started was 19.5 +/- 14 days; the mean days after the initiation of erythromycin when orogastric tube feeding could be started and full feeding established were 2.4 +/- 1.1 days and 15.1 +/- 2.2 days, respectively. At the beginning of erythromycin treatment, the net balance of tube aspirates was -4.8 +/- 4.1 ml. The net balance rose significantly to 30.6 +/- 15.3 ml, 92.6 +/- 25.4 ml and 125.3 +/- 18.1 ml at 7, 14 and 21 days after erythromycin treatment, respectively. In conclusion, erythromycin treatment is a safe method to improve intolerance of enteral feeding in very low birth weight infants. It is suggested that the effect of erythromycin on gastrointestinal motility in these infants should be further investigated in the context of a randomized, controlled trial before widespread clinical implementation of this treatment.