Maintaining normal temperature immediately after birth in late preterm and term infants: A systematic review and meta-analysis.

AIM: Prevention of hypothermia after birth is a global problem in late preterm and term neonates. The aim of this systematic review and meta-analysis was to evaluate delivery room strategies to maintain normothermia and improve survival in late preterm and term neonates (≥34 weeks' gestation). METHODS: Medline, Embase, CINAHL, CENTRAL and international clinical trial registries were searched. Randomized controlled trials (RCTs), quasi-RCTs and observational studies were eligible for inclusion. Risk of bias for each study and GRADE certainty of evidence for each outcome were assessed. RESULTS: 25 RCTs and 10 non-RCTs were included. Room temperature of 23 °C compared to 20 °C improved normothermia [Risk Ratio (RR), 95% Confidence Interval (CI): 1.26, 1.11-1.42)] and body temperature [Mean Difference (MD), 95% CI: 0.30 °C, 0.23-0.37 °C), and decreased moderate hypothermia (RR, 95% CI: 0.26, 0.16-0.42). Skin to skin care (SSC) compared to no SSC increased body temperature (MD, 95% CI: 0.32, 0.10-0.52), reduced hypoglycemia (RR, 95% CI: 0.16, 0.05-0.53) and hospital admission (RR, 95% CI: 0.34, 0.14-0.83). Though plastic bag or wrap (PBW) alone or when combined with SSC compared to SSC alone improved temperatures, the risk-benefit balance is uncertain. Clinical benefit or harm could not be excluded for the primary outcome of survival for any of the interventions. Certainty of evidence was low to very low for all outcomes. CONCLUSIONS: Room temperature of 23 °C and SSC soon after birth may prevent hypothermia in late preterm and term neonates. Though PBW may be an effective adjunct intervention, the risk-benefit balance needs further investigation.

Association of Pharmacist-led Deprescribing Intervention with the Functional Recovery in Convalescent Setting.

So far, no studies investigated the association between pharmacist intervention and rehabilitation outcomes. The aim of study was to establish whether the pharmacist-led deprescribing intervention affects rehabilitation outcomes. This retrospective, observational, single-center, cohort study included consecutive geriatric patients (n = 448) with pharmacist-led intervention between 2017 and 2019. Participants were divided based on pharmacist-led deprescribing and non deprescribing interventions during hospitalization. Demographic data, laboratory data, the Functional Independence Measure were (FIM) analyzed between the groups. Multiple linear regression analysis was performed to analyze the relationship between pharmacist-led deprescribing and FIM total gain. The primary outcome was FIM total gain. The rate of pharmacist intervention during the study period was 92.4%. A multiple linear regression analysis of FMI-T gain, adjusting for confounding factors, revealed that the pharmacist-led deprescribing intervention was independently correlated with FMI-T gain. Particularly, the use of dyslipidemia drugs, antipsychotic drugs, hypnotics, and nonsteroidal anti-inflammatory drugs significantly decreased during hospitalization. The pharmacist-led deprescribing intervention was independently and significantly associated with FIM-T gain. The pharmacist-led deprescribing intervention improved functional recovery in a rehabilitation setting.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

One-time umbilical cord milking after cord cutting has same effectiveness as multiple-time umbilical cord milking in infants born at <29 weeks of gestation: a retrospective study.

OBJECTIVE: To compare two strategies to potentiate the effects of placental transfusion in infants born at <29 weeks of gestation. STUDY DESIGN: Twenty infants who received one-time umbilical cord milking after umbilical cord cutting were compared with 20 infants from a previous study group who received multiple-time umbilical cord milking. The primary outcome measurements were the probability of not needing a red blood cell (RBC) transfusion during the hospital stay and the total number of RBC transfusions within 21 days after birth. RESULT: There was no significant difference in the probability of not needing a transfusion during the hospital stay (P=0.75) and the mean number of RBC transfusions given within the first 21 days of life (1.1±1.8 for the one-time umbilical cord-milking group vs 0.7±1.2 for the multiple-time umbilical cord-milking group, P=0.48). CONCLUSION: One-time umbilical cord milking after umbilical cord cutting had similar beneficial effects to multiple-time umbilical cord milking before umbilical cord cutting in very premature infants.

Time to first cigarette and lung cancer risk in Japan.

BACKGROUND: Cigarette smoking is the major cause of lung cancer (LC). Although the time to first cigarette (TTFC) of the day is a distinct indicator of nicotine dependence, little information is available on its possible relation to LC. PATIENTS AND METHODS: This case-control study includes a total of 1572 incident LC cases and 1572 non-cancer controls visiting for the first time the Aichi Cancer Center Hospital between 2001 and 2005. We estimated the odds ratio (OR) and 95% confidence interval (CI) for TTFC using a logistic regression model after adjustment for several potential confounders. RESULTS: TTFC was inversely associated with the risk of LC. This association was consistent across histological subtypes of LC. For all LCs considered among ever smokers and after accurate allowance for smoking quantity and duration, besides other relevant covariates, compared with TTFC >60 min, the adjusted ORs were 1.08 (95% CI, 0.73-1.61) for TTFC of 31-60 min, 1.40 (0.98-2.01) for 6-30 min and 1.86 (1.28-2.71) for within 5 min (Ptrend, < 0.001). Statistically marginally significant heterogeneity by histological subtype was observed (Pheterogeneity, 0.002). CONCLUSIONS: Nicotine dependence, as indicated by the TTFC, is associated with increased risk of LC and is therefore an independent marker of exposure to tobacco smoking.

Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants.

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.

Reproductive and hormonal risk factors for luminal, HER2-overexpressing, and triple-negative breast cancer in Japanese women.

BACKGROUND: Although the clinical relevance of the molecular subtypes of breast cancer is evident, etiological differences among subtypes have not been well established, especially among Asian. Here, we evaluated the hypothesis that the etiologic impact of reproductive and hormonal features differs among molecular subtypes. MATERIALS AND METHODS: We conducted a case-control study in pre- and postmenopausal Japanese. We examined 706 breast cancer patients and 1412 age- and menopausal status-matched noncancer controls. Immunohistochemical stains for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were used to classify the cases into 554 luminal (hormone receptor positive), 84 HER2-overexpressing (hormone receptor negative, HER2 positive), and 68 triple-negative cases (hormone receptor negative, HER2 negative). Associations were evaluated using multivariate polytomous logistic regression models. RESULTS: A significant association was observed between early age at menarche and risk of luminal disease (odds ratios = 1.67, 95% confidence interval: 1.22-2.29; P trend = 0.001). No significant differences in association with parity, age at first live birth, breastfeeding history, age at menopause, or synthetic hormonal use were seen across molecular subtypes of breast cancer. CONCLUSIONS: These findings indicate that reproductive events in adolescence have differential impact on the risk of breast cancer molecular subtypes in Japanese.

Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma.

BACKGROUND: The association between dietary folate intake, two polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS), and survival in head and neck squamous cell carcinoma (HNSCC) patients is not clarified. PATIENTS AND METHODS: We conducted a retrospective cohort study of 437 HNSCC patients treated at Aichi Cancer Center. We evaluated the survival impact of pretreatment dietary folate intake, which was estimated using a food-frequency questionnaire, and two polymorphisms, MTHFR C677T and a 6-bp insertion/deletion in the 3'-untranslated region of TYMS, using multivariate proportional hazard models. RESULTS: Patients with high folate intake (≥320 µg/day; n=144) had significantly higher survival than patients with low or medium folate intake (<320 µg/day; n=278; 79.1% versus 68.2%, respectively, P=0.020). This association was consistent with multivariate analyses adjusted for established prognostic factors (hazard ratio 0.56; 95% confidence interval 0.37-0.84). MTHFR and TYMS polymorphisms did not show significant association with survival, although the TYMS 6-bp insertion allele showed potential association with a reduced risk of death. Notably, no significant interaction was observed between folate intake and the two examined polymorphisms. CONCLUSIONS: High pretreatment dietary folate intake was identified as an independent prognostic factor associated with improved clinical outcomes in HNSCC patients. Further study is warranted.

Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy.

BACKGROUND: To our knowledge, no reports have evaluated the effects of genetic polymorphisms of insulin-like growth factor-I (IGF-I) on clinical outcomes of gastric cancer patients. METHODS: We retrospectively analyzed the impact of IGF-I polymorphisms on recurrence-free survival (RFS) in 430 patients with gastric cancer who underwent curative gastrectomy between 2001 and 2005 in our institution. RESULTS: Among the 430 gastric cancer patients, 345 were pathological stage I or II, while 85 were stage III or IV. The median 5-year RFS rate was 85.3% (95% confidence interval [CI] 81.4-88.5). In a multivariate Cox model (adjusted for age, gender, histology, pathological stage, adjuvant chemotherapy, and history of diabetes), two IGF-I polymorphisms, rs1520220 and rs2195239, were significantly associated with RFS (hazard ratio [HR] 0.60, 95% CI 0.40-0.91; and HR 0.60, 95% CI 0.41-0.89, respectively, in a per-allele model). When stratified by stage (I-II versus III-IV), rs1520220 in particular was associated with RFS in patients with stage III-IV disease, with a P-value for interaction of 0.01. CONCLUSIONS: Our findings indicate that genetic polymorphisms of IGF-I may have a substantial effect on recurrence for gastric cancer patients who have undergone curative gastrectomy. This information may help identify population subgroups that could benefit from IGF-I-targeting agents.

Inverse association between soy intake and non-Hodgkin lymphoma risk among women: a case-control study in Japan.

BACKGROUND: Non-Hodgkin lymphoma (NHL) is one of the common malignant tumors worldwide. Environmental factors, such as diet have an important association with the risk of cancer. Although soy intake has been associated with a reduced risk of several cancers, its association with NHL is not known. PATIENTS AND METHODS: We evaluated the association between soy consumption and risk of NHL by conducting a hospital-based case-control study in 302 patients with NHL and 1510 age- and sex-matched control subjects. Odds ratio (OR) and 95% confidence intervals (CIs) for groups with moderate (27-51 g/day) to high (>51 g/day) relative to low (<27 g/day) intake were calculated using multivariate conditional logistic regression model. RESULTS: Soy intake was significantly associated with a reduced risk of NHL in women but not in men (OR [95% CI] for moderate and high intake: women, 0.64 [0.42-1.00] and 0.66 [0.42-1.02], respectively; men, 1.40 [0.87-2.24] and 1.33 [0.82-2.15], respectively; P-interaction = 0.02). This finding appeared consistent across NHL subtypes. CONCLUSION: These results indicate the potential importance of certain ingredients in soy for lymphomagenesis. Further studies to evaluate the mechanism behind the association between soy intake and lymphomagenesis are warranted.

Association between dietary calcium and vitamin D intake and cervical carcinogenesis among Japanese women.

BACKGROUND/OBJECTIVES: To examine the association between dietary calcium and vitamin D intake and cervical neoplasia risk, we conducted a case-control study. SUBJECTS/METHODS: We selected 405 incident cervical neoplasias (333 invasive carcinomas and 72 cervical intraepithelial neoplasias grade III (CIN3)) and 2025 age-matched non-cancer controls. Dietary information was collected using a semiquantitative food-frequency questionnaire (FFQ). The effect on cervical neoplasia risk was evaluated using conditional logistic regression models. RESULTS: The inverse association between invasive carcinoma and milk, yogurt and fish was observed. On the other hand, the marginally significant inverse association between CIN3 and tofu and green leafy vegetables was observed. Compared with the lowest quartile (Q1) of calcium intake, adjusted odds ratios (ORs) for each of the three upper quartiles (Q2, Q3 and Q4) on invasive carcinoma risk were 0.86 (95% confidence interval (CI) 0.63-1.17), 0.50 (95% CI 0.34-0.73) and 0.68 (95% CI 0.48-0.97), respectively (P for trend=0.004). However, no association between calcium and cancer risk was evident among CIN3 cases (P for trend=0.528). Vitamin D intake showed a similar inverse association (Q2: OR 1.03, 95% CI 0.74-1.44; Q3: OR 0.80, 95% CI 0.56-1.15; and Q4: OR 0.64, 95% CI 0.43-0.94; P for trend=0.013). Similar to calcium, no association between vitamin D intake among CIN3 was evident (P for trend=0.109). An inverse association with calcium was evident in women whose vitamin D intake was low. However, this combined effect was not significant (invasive carcinoma: interaction P=0.819; and CIN3: interaction P=0.101). CONCLUSION: We found an inverse association between dietary calcium and vitamin D intake and cervical neoplasia risk among a group of Japanese women.

Association between serum lipoprotein lipase mass concentration and subcutaneous fat accumulation during neonatal period.

BACKGROUND/OBJECTIVES: Subcutaneous adipose tissue grows rapidly during the first months of life. Lipoprotein lipase (LPL) has a quantitatively important function in adipose tissue fat accumulation and insulin-like growth factor-I (IGF-I) is a determinant of neonatal growth. Recent studies showed that LPL mass in non-heparinized serum (LPLm) was an index of LPL-mediated lipolysis of plasma triacylglycerol (TG). The objective was to know the influence of serum LPL and IGF-I on neonatal subcutaneous fat growth, especially on catch-up growth in low birth weight infants. SUBJECTS/METHODS: We included 47 healthy neonates (30 males, 17 females), including 7 small for gestational age. We measured serum LPLm and IGF-I concentrations at birth and 1 month, and analyzed those associations with subcutaneous fat accumulation. RESULTS: Serum LPLm and IGF-I concentrations increased markedly during the first month, and positively correlated with the sum of skinfold thicknesses both at birth (r=0.573, P=0.0001; r=0.457, P=0.0035) and at 1 month (r=0.614, P<0.0001; r=0.787, P<0.0001, respectively). In addition, serum LPLm concentrations correlated inversely to very low-density lipoprotein (VLDL)-TG levels (r=-0.692, P<0.0001 at birth; r=-0.429, P=0.0052 at 1 month). Moreover, the birth weight Z-score had an inverse association with the postnatal changes in individual serum LPLm concentrations (r=-0.639, P<0.0001). CONCLUSIONS: Both serum LPLm and IGF-I concentrations were the determinants of subcutaneous fat accumulation during the fetal and neonatal periods. During this time, LPL-mediated lipolysis of VLDL-TG may be one of the major mechanisms of rapid growth in subcutaneous fat tissue. Moreover, LPL, as well as IGF-I, may contribute to catch-up growth in smaller neonates.

Blood pressure and urine output during the first 120 h of life in infants born at less than 29 weeks' gestation related to umbilical cord milking.

OBJECTIVE: To investigate the effects of umbilical cord milking on cardiopulmonary adaptation in very low birth weight infants. PATIENTS AND METHODS: This study was the secondary analysis of a randomised control study of the effect of umbilical cord milking in premature infants. Forty singleton infants born between 24 and 28 weeks' gestation were randomly assigned to groups in which the umbilical cord was clamped either immediately after birth (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Blood pressure, heart rate, urine output, fluid intake, and ventilatory index values in both groups were measured during the first 120 h after birth. RESULTS: There were no significant differences in gestational age or birth weight between the two groups. The initial haemoglobin value was higher in the milked group (mean (SD) 16.5 (1.4) g/dl in the milked vs 14.1 (1.6) g/dl in the control; p<0.01). During the first 12 h, blood pressure was significantly higher in the milked group. Urine output in the milked group was higher than that in the control group during the first 72 h. There were no significant differences in heart rate, water intake, or ventilatory index values between the groups. CONCLUSION: Umbilical cord milking may facilitate early stabilisation of both blood pressure and urine output in very low birth weight infants.

Low-density lipoprotein profile changes during the neonatal period.

OBJECTIVE: To investigate natural change of low-density lipoprotein (LDL) profile during the neonatal period and the impact of gestational age and birth weight on those changes. STUDY DESIGN: We measured lipid composition in LDL fraction, LDL particle size and apolipoprotein B (apoB) concentration at birth, 5 days of age and 1 month of age in 63 healthy neonates that had 37 to 41-week gestational age. RESULT: Low-density lipoprotein cholesterol and apoB concentrations increased from birth to 5 days of age, and the concentration persisted at 1 month in breast-fed and mixed-fed infants. However, in formula-fed infants, the concentration decreased at 1 month. At 5 days of age, neonates had larger and more triglyceride (TG)-rich LDL particles than at birth. At 1 month of age, LDL particles were smaller and more cholesterol rich than at 5 days of age. Single regression analyses showed that gestational age had influenced the LDL profile at birth and 5 days of age, while at 1 month milk determined the profile. CONCLUSION: The number of LDL particles increased rapidly during the first 5 days of life, and the composition of LDL particles is modulated by TG content throughout the neonatal period. Gestational age and milk, rather than birth weight, determine postnatal changes in LDL profile.

Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born at less than 29 weeks' gestation: a randomised controlled trial.

OBJECTIVE: To investigate the effects of umbilical cord milking on the need for red blood cell (RBC) transfusion and morbidity in very preterm infants. PATIENTS AND METHODS: 40 singleton infants born between 24 and 28 weeks' gestation were randomly assigned to receive umbilical cord clamped either immediately (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Primary outcome measures were the probability of not needing transfusion, determined by Kaplan-Meier analysis, and the total number of RBC transfusions. Secondary outcome variables were haemoglobin value and blood pressure at admission. RESULTS: There were no significant differences in gestational age and birth weight between the two groups. The milked group was more likely not to have needed red cell transfusion (p = 0.02) and had a decreased number (mean (SD)) of RBC transfusions (milked group 1.7 (3.0) vs controls 4.0 (4.2); p = 0.02). The initial mean (SD) haemoglobin value was higher in the milked group (165 (14) g/l) than in the controls (141 (16) g/l); p<0.01). Mean (SD) blood pressure at admission was significantly higher in the milked group (34 (9) mm Hg) than in the controls 28 (8) mm Hg; p = 0.03). There was no significant difference in mortality between the groups. The milked group had a shorter duration of ventilation or supplemental oxygen than the control group. CONCLUSION: Milking the umbilical cord is a safe procedure, reducing the need for RBC transfusions, and the need for circulatory and respiratory support in very preterm infants.

Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients.

Twist is a transcription factor that regulates the expression of tumour suppressors such as E-cadherin. We examined the distribution and expression of Twist in human epithelial ovarian carcinoma (EOC) to examine its clinical significance. Paraffin sections from EOC tissues (n=82) were immunostained with Twist antibody, and the staining intensity was evaluated. The clinicopathological factors examined were age, International Federation of Gynecology and Obstetrics staging, histological type, tumour grade, preoperative value of CA125, peritoneal cytology, volume of ascites and residual tumour after cytoreductive surgery. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Of the 82 carcinomas, 49 (59.8%) cases were negative for Twist immunoexpression, and 33 (40.2%) were positive immunoexpression. When categorized into negative vs positive expression, Twist was not associated with any of the clinicopathological parameters examined. However, positive Twist expression significantly predicted poorer OS and PFS when compared with negative expression (P<0.0001). In the multivariate analyses, positive Twist expression was the only independent prognostic factor for survival in this study (P<0.0001). Positive Twist expression seems to be a useful marker in patients with EOC likely to have an unfavourable clinical outcome.

Preventive management of hypoglycemia in very low-birthweight infants following indomethacin therapy for patent ductus arteriosus.

BACKGROUND: To evaluate the effects of an increase in glucose infusion rate of 2 mg/kg per min from the basal infusion rate on the prevention of hypoglycemia in very low-birthweight (VLBW) infants, following indomethacin therapy for patent ductus arteriosus (PDA). METHODS: Forty VLBW infants with PDA were given indomethacin 0.2 mg/kg intravenously up to three doses. In 15 of the 40 infants (supplemented group: between April 1995 and March 1996) the glucose infusion rate was increased in 2 mg/kg per min increments from the basal rate just before the initial indomethacin administration, compared with 25 historical control infants who received a fixed glucose infusion rate during the first 12 h after the initial dose. We evaluated the changes in blood glucose levels and glucose infusion rates in both groups. RESULTS: In the control group 11 of 25 (44%) infants had a blood glucose value below 40 mg/dL between 12 and 60 h (mean 32.7 h). In contrast only two out of 15 infants in the supplemented group reached the glucose level below 40 mg/dL between 72 and 96 h but both two were light-for-dates infants (defined as birthweight below the 10th percentile for gestational age on the standard intrauterine growth curve). Blood glucose values in the supplemented group were significantly higher than those in the control group between 12 and 96 h. However, glucose infusion rates were similar before and between 72 and 96 h. CONCLUSIONS: This retrospective study shows that an increase in glucose infusion rate of 2 mg/kg per min, in addition to the pre-existing stable maintenance glucose intake, might prevent against the occurrence of unexpected hypoglycemia in VLBW infants following indomethacin therapy.

High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the foundation of powerful complex trait and pharmacogenomic analyses. The availability of large SNP databases, however, has emphasized a need for inexpensive SNP genotyping methods of commensurate simplicity, robustness, and scalability. We describe a solution-based, microtiter plate method for SNP genotyping of human genomic DNA. The method is based upon allele discrimination by ligation of open circle probes followed by rolling circle amplification of the signal using fluorescent primers. Only the probe with a 3' base complementary to the SNP is circularized by ligation. RESULTS: SNP scoring by ligation was optimized to a 100,000 fold discrimination against probe mismatched to the SNP. The assay was used to genotype 10 SNPs from a set of 192 genomic DNA samples in a high-throughput format. Assay directly from genomic DNA eliminates the need to preamplify the target as done for many other genotyping methods. The sensitivity of the assay was demonstrated by genotyping from 1 ng of genomic DNA. We demonstrate that the assay can detect a single molecule of the circularized probe. CONCLUSIONS: Compatibility with homogeneous formats and the ability to assay small amounts of genomic DNA meets the exacting requirements of automated, high-throughput SNP scoring.

Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapy.

BACKGROUND: The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy. METHODS: Fifty-eight infants (gestational age 39.4 +/- 1.4 weeks; birth weight 3,245 +/- 435 g) were given phototherapy with similar light energy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given human albumin at 1 g/kg bodyweight, i.v., during the first 2 h of phototherapy. RESULTS: When comparing changes in total and unbound bilirubin values 0, 2, 6 and 24 h after entering the study between the albumin-treated group and the control group, there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However, there was no significant reduction in total serum bilirubin values during the study period. In the albumin-treated group, the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40 +/- 0.19, 0.41 +/- 0.20 and 0.43 +/- 0.20 microg/dL, respectively. CONCLUSIONS: The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values, the fraction that is potentially neurotoxic.

Effect of vibration on auditory organ systems in low-birth weight infants treated with high-frequency oscillatory ventilation: 5 year outcome.

BACKGROUND: To determine the effects of vibration exposure caused by high-frequency oscillatory ventilation (HFOV) on the auditory organ systems in low-birth weight (LBW) infants. METHODS: Between 1989 and 1990, 30 LBW infants who received assisted ventilation with HFOV (n = 14) or conventional mechanical ventilation (CMV; n = 16) in the level III neonatal intensive care unit at Tokyo Metropolitan Ohtsuka Hospital were enrolled in this study. The effects of vibration exposure on the auditory system structures were investigated with auditory brainstem responses (ABR) at 37-41 weeks of postconceptional age and at 6, 12, 18 and 24 months of age until they passed and follow-up studies were performed at least until 5 years of age. RESULTS: All infants enrolled in the study survived at discharge and one (7.1%) infant in the HFOV group and two (12.5%) in the CMV group failed the initial ABR test, but there were no significant differences between the two groups. Auditory brainstem response abnormalities were still observed in one infant in the HFOV group at 6 months of age, but this child died at 9 months of age because of meningitis. In contrast, in the CMV group, one patient passed the ABR test at 6 months of age, but another remained abnormal at 5 years of age. One of three infants with ABR abnormalities at 6 months of age had neurologic sequelae at 5 years of age and one of 28 infants who passed the initial ABR test was detected with cerebral palsy. No patients with hearing loss were clinically detected at 5 years of age. CONCLUSIONS: The results of the serial ABR examinations and the 5 year follow-up studies suggest that vibration exposure caused by HFOV may not increase the adverse effects on the auditory system in LBW infants.