An evidence-based review of important issues concerning neonatal hyperbilirubinemia

This article is adapted from a published evidence report concerning neonatal hyperbilirubinemia with an added section on the risk of blood exchange transfusion (BET). Based on a summary of multiple case reports that spanned more than 30 years, we conclude that kernicterus, although infrequent, has at least 10% mortality and at least 70% long-term morbidity. It is evident that the preponderance of kernicterus cases occurred in infants with a bilirubin level higher than 20 mg/dL. Given the diversity of conclusions on the relationship between peak bilirubin levels and behavioral and neurodevelopmental outcomes, it is apparent that the use of a single total serum bilirubin level to predict long-term outcomes is inadequate and will lead to conflicting results. Evidence for efficacy of treatments for neonatal hyperbilirubinemia was limited. Overall, the 4 qualifying studies showed that phototherapy had an absolute risk-reduction rate of 10% to 17% for prevention of serum bilirubin levels higher than 20 mg/dL in healthy infants with jaundice. There is no evidence to suggest that phototherapy for neonatal hyperbilirubinemia has any long-term adverse neurodevelopmental effects. Transcutaneous measurements of bilirubin have a linear correlation to total serum bilirubin and may be useful as screening devices to detect clinically significant jaundice and decrease the need for serum bilirubin determinations. Based on our review of the risks associated with BETs from 15 studies consisting mainly of infants born before 1970, we conclude that the mortality within 6 hours of BET ranged from 3 per 1000 to 4 per 1000 exchanged infants who were term and without serious hemolytic diseases. Regardless of the definitions and rates of BET-associated morbidity and the various pre-exchange clinical states of the exchanged infants, in many cases the morbidity was minor (eg, postexchange anemia). Based on the results from the most recent study to report BET morbidity, the overall risk of permanent sequelae in 25 sick infants who survived BET was from 5% to 10%.     

Evaluation of a patient education tool to reduce the incidence of incontinence post-prostate surgery

A pelvic floor muscle exercise program can reduce the incidence of incontinence post-prostate surgery. The purpose of this study was to validate a new education tool, a refrigerator magnet, in comparison to a paper copy with the same information, to determine if patient compliance with the exercises increased.     

Cdk5: mediator of neuronal death and survival

Cdk5 (cyclin-dependent kinase 5) is a serine/threonine kinase implicated to play pivotal roles in neuronal development. Recently, its potential involvement as a regulator of neuronal death and survival has attracted considerable interests. Importantly, increasing evidence has linked Cdk5 to the etiopathology of neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. Here we summarize the recent findings on Cdk5 not only as an important participant in neuronal death, but also a key player in neuronal survival. Elucidating the mechanisms of regulation of Cdk5 and its downstream signaling might prove to be crucial in the therapeutic treatment of neurodegenerative diseases.     

Hepatoprotective effect of Sabina przewalskii against menadione-induced toxicity

Sabina przewalskii is a Tibetan medicinal plant. Pretreatment with an ethyl acetate-soluble fraction of the plant suppressed the plasma alanine aminotransferase activity in menadione-intoxicated mice. In vitro studies showed that the Sabina extract could inhibit NADH-induced superoxide production in isolated hepatocytes as indicated by a decrease of lucigenin-amplified chemiluminescence. In addition, the extract inhibited tert-butyl hydroperoxide-induced lipid peroxidation in isolated hepatocytes dose-dependently. These results suggested that the protective action of the Sabina extract against menadione-induced hepatotoxicity is associated with its antioxidant activities including the scavenging of superoxide anion radicals and inhibition of lipid peroxidation.     

Lung cancer susceptibility and polymorphisms of glutathione-S-transferase genes in Hong Kong

OBJECTIVE: To study the potential role of genetic polymorphisms of glutathione-S-transferases GSTM1, GSTT1 and GSTP1 in susceptibility to lung cancer in Hong Kong Chinese. METHODS: 229 consecutive incident patients with a histological diagnosis of lung cancer from a regional hospital and 197 healthy population-based controls were recruited for this study between July 1999 and June 2001. Genetic polymorphisms of GSTT1 and GSTM1 were determined using PCR-based technique. RESULTS: The frequencies of GSTT1 and GSTM1 null genotypes were 51.8 and 59.4% in healthy controls and 63 and 54.7%, respectively, in lung cancer patients. GSTP1 Val105/Val105 genotype was found in only 1% of healthy controls. The risk for lung cancer with GSTT1 null genotype was significantly higher, adjusted odds ratio (OR) 1.69, 95% confidence interval (CI) 1.12-2.56, compared with those with the GSTT1 genotype; the increase in risk was found only in non-smokers. GSTM1 null genotype, combined GSTT1 and GSTM1 null genotype and GSTP1 Val105/Val105 genotype did not confer any increase risk for lung cancer. CONCLUSION: GSTT1 null genotype is associated with an increased risk for lung cancer in non-smoking Chinese in Hong Kong.     

Activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB in tumour necrosis factor-induced eotaxin release of human eosinophils

The CC chemokine eotaxin is a potent eosinophil-specific chemoattractant that is crucial for allergic inflammation. Allergen-induced tumour necrosis factor (TNF) has been shown to induce eotaxin synthesis in eosinophils. Nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK) have been found to play an essential role for the eotaxin-mediated eosinophilia. We investigated the modulation of NF-kappaB and MAPK activation in TNF-induced eotaxin release of human eosinophils. Human blood eosinophils were purified from fresh buffy coat using magnetic cell sorting. NF-kappaB pathway-related genes were evaluated by cDNA expression array system. Degradation of IkappaBalpha and phosphorylation of MAPK were detected by Western blot. Activation of NF-kappaB was determined by electrophoretic mobility shift assay. Eotaxin released into the eosinophil culture medium was measured by ELISA. TNF was found to up-regulate the gene expression of NF-kappaB and IkappaBalpha in eosinophils. TNF-induced IkappaBalpha degradation was inhibited by the proteasome inhibitor N-cbz-Leu-Leu-leucinal (MG-132) and a non-steroidal anti-inflammatory drug sodium salicylate (NaSal). Using EMSA, both MG-132 and NaSal were found to suppress the TNF-induced NF-kappaB activation in eosinophils. Furthermore, TNF was shown to induce phosphorylation of p38 MAPK time-dependently but not extracellular signal-regulated kinases (ERK). Inhibition of NF-kappaB activation and p38 MAPK activity decreased the TNF-induced release of eotaxin from eosinophils. These results indicate that NF-kappaB and p38 MAPK play an important role in TNF-activated signalling pathway regulating eotaxin release by eosinophils. They have also provided a biochemical basis for the potential of using specific inhibitors of NF-kappaB and p38 MAPK for treating allergic inflammation.     

Effect of torsion on microarterial anastomosis patency

All kinds of technical faults must be prevented in microvascular anastomosis for successful reconstructive microsurgery. Torsion at the anastomosis site is one of the most basic technical errors. In this study, we investigate the effect of different degrees of microarterial torsion on patency and its physical changes on anastomosis in a rat model. A total of 144 microanastomosis were performed in 72 Sprague-Dawley rats. They were divided into 9 groups. The anastomosis was performed at 0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, 225 degrees, 270 degrees, 315 degrees, and 360 degrees of torsion randomly. Patency rates and the narrowest point of the artery after the anastomosis were recorded after 1 hour for each group. In the second stage of the study, the 9 groups were divided into 2 groups for patency rates and histopathological sampling at the second and seventh days postoperatively. The femoral arteries in all groups were all patent at the end of 1 hour. Only 5 microanastomosis were thrombosed (one in the 45 degrees group, one in the 225 degrees group, one in the 270 degrees group, and two in the 315 degrees group) at the second day of exploration. Only two arteries were thrombosed (one in the 45 degrees group and one in the 315 degrees group) at the seventh day of exploration. The patency rate was 96.8% in experimental groups excluding the control group. Different degrees of torsion had no statistically significant effect on the patency rates of microvascular anastomosis. Torsional repair of the femoral artery in the rat has no significant histopathologic changes, but alternately, endothelial integrity was affected by excessive degrees of torsion. Different degrees of torsion at the anastomosis site do not affect patency rates and cross sectional histology of rat femoral arteries. In clinical practice, minor torsion can be tolerated, however, factors affecting patency such as tension, diameter disproportion, and tight closure can affect the final result of anastomosis. We observed that torsional force of the vessel is distributed along the artery to the weakest point.     

Effect of torsion on microvenous anastomotic patency in a rat model and early thrombolytic phenomenon

Torsion at the microanastomosis site is a basic fault and should be avoided. In this study, we investigate the effects of different degrees of microvenous torsion on patency and its physical changes on anastomoses in a rat model. One hundred anastomoses were performed at different degrees of torsion, using femoral veins of Sprague-Dawley rats. Anastomoses were performed at 0 degrees, 45 degrees, 90 degrees, 135 degrees, and 180 degrees of torsion randomly. Patency tests immediately, 1 h, and 1 week after the anastomoses were checked, using the refill test. Measurements of external diameter were recorded at three points: one at the anastomosis site, and the others 2 mm proximal and distal to the anastomotic site. Finally, histopathologic and scanning electron microscopy studies were performed. Subsequently, because of the peculiar phenomenon of early recannulation of the thrombosed vessels, 20 vessels were also explored on the first and the third days postoperatively. The data demonstrate that torsion at 180 degrees, compared with 0 degrees, 45 degrees, and 90 degrees, impaired patency significantly (P < 0.005). In the subsequent study of 20 veins that were thrombosed on the first day, all became patent on the third day and remained so. In conclusion, rotation of a microvenous anastomosis begins to affect the patency rate at 90 degrees of torsion, and at 180 degrees has a patency rate of only 25%. However, all become patent again from the third day onwards. Thrombosis of rat femoral veins without chronic obstruction results in rapid lysis of thrombus and transient proliferative changes.