Present work has been focused on the importance of the products of the heme catabolic pathway, in particular under conditions of unconjugated hyperbilirubinemias (neonatal jaundice and Crigler-Najjar syndrome (CNS)). The second part of the project was focused on the improvement of some pharmacological approaches used in the treatment of these diseases, as well as on studies of bilirubin products that are formed during the treatment by phototherapy (PT). Neonatal jaundice is one of the most common complications in neonates. Currently, there is no efficient pharmacotherapy and the treatment with blue light is used as a gold standard for severe neonatal jaundice. However, the absolute safety of PT has still not been confirmed. In this context, it is important to note that some neonatologists start the PT before serum bilirubin levels reach the recommended values and that patients with CNS type I (CNSI) are forced to be on life-long PT (unless undergoing liver transplantation). The focus of the present project was to study biological effects of bilirubin photoisomers (PI) in an in vitro model of the human neuroblastoma SH-SY5Y cells that are used for studies of the neuronal metabolism. In further studies performed on animal model of hyperbilirubinemic rats and mice, we investigated a suitable gene...

Eine Erhöhung des Bilirubins über 2 mg/dl betrifft 90 % aller Neugeborenen. Sie ist meist physiologisch und tritt optisch sichtbar bei 60-70 % dieses Kollektivs auf. In der pathologischen, exzessiv erhöhten Form ist sie der häufigste Grund für eine stationäre Wiederaufnahme während der ersten sieben Lebenstage. Ihre schwerste Komplikation, der Kernikterus, scheint - trotz allgemein verfügbarer, preiswerter und sicherer Therapiemöglichkeiten - wieder vermehrt aufzutreten. Die Gründe liegen im Überwachungsdefizit bei früher Entlassung von schlecht aufgeklärten Eltern, Nichtbeachtung der Besonderheiten der Neugeborenen ≤ 38 Schwangerschaftswochen und der zunehmenden Tendenz zum Stillen bei häufig unzureichender Anleitung. Ferner werden ikterische Kinder nur zu oft lediglich visuell bezüglich des Grades der Bilirubinämie eingeschätzt und die Therapie somit erheblich verzögert. Gegenstand dieser Arbeit ist die Frage, ob aus der Dynamik des Serumbilirubinspiegels von der Geburt bis zum 3. Lebenstag die Wahrscheinlichkeit des Auftretens einer phototherapiepflichtigen Hyperbilirubinämie abgeschätzt werden kann. Dazu wurde der Serumbilirubinspiegel direkt postnatal aus dem Nabelschnurblut, bzw. am 3. Lebenstag gleichzeitig mit dem Stoffwechselscreening ermittelt und der Phototherapiebedarf im Verlauf festgehalten. Um die Aussage zu präzisieren, wurde die Studienpopulation aus 2573 Kindern weiter unterteilt in 2180 reife tAGA- (hier Eu- und Hypertrophe), 267 reife tSGA-Kinder (Hypotrophe) und 126 FG (Frühgeborene). In allen 3 Gruppen korrelierten das Nabelschnurbilirubin und der Serumbilirubinwert vom 3. Lebenstag positiv mit der Entwicklung einer Hyperbilirubinämie. Anhand dieser Ausgangswerte konnten Grenzen für Hoch-, Mittelhoch-, Mittelniedrig- und Niedrigrisikogruppen definiert werden, welche die Entwicklung einer Hyperbilirubinämie mit einer Wahrscheinlichkeit von ≥ 20 %, 5-20 %, 0 < x <5 % und 0 % voraussagen. Damit kann man bereits früh eine Vorabselektion entsprechend dem Gefährdungspotential treffen und die Verlaufskontrollen entsprechend terminieren. Als Risikofaktoren einer therapiepflichtigen Hyperbilirubinämie wurden außerdem Frühgeburtlichkeit, seltener tSGA, geringes Geburtsgewicht und niedriges Gestationsalter (in der vorliegenden FG-Gruppe nicht signifikant) gefunden. Im Falle einer Sectiogeburt und bei Zuhilfenahme von Hilfsmitteln im Rahmen einer vaginalen Entbindung nahm der Bedarf an Phototherapie in der tAGA- und tSGA-Gruppe zu.:Bibliographische Beschreibung……………………………………………………………………….1 Abkürzungsverzeichnis………………………………………………………………………………..2 1. Einleitung…………………………………………………………………………………...3 1.1. Geschichtliche Entwicklung……………………………………………………………………...3 1.2. Wandel der Anschauungen zu den Therapiegrenzen…..…………………………….................4 1.3. Hyperbilirubinämie……………………………………………………………………………….7 1.4. Kernikterusregister………………………………………………………………………………..8 1.5. Problemstellung…………………………………………………………………………………...9 2. Patienten und Methoden………………………………………………………………..11 2.1. Patientenkollektiv………………………………………………………………………………...11 2.2. Ausschlusskriterien………………………………………………………………………………11 2.3. Datenerfassung………………………………………………………………………………...…11 2.4. Phototherapie (PT)………………………………………………………………………………12 2.5. statistische Analyse………………………………………………………………………………13 2.5.1. konkrete Fragestellung………………………………………………………………………………...…13 2.6. Signifikanzniveau……………………………………………………..………………………….13 3. Ergebnisse………………………………………………………………………………..14 3.1. Gesamtpopulation…………………………………………………………….………………….14 3.2. Charakteristika der Studienpopulation…………………………….…………………………..14 3.3. tAGA (reife eu- und hypertrophe Neugeborene)………………………………………………16 3.4. tSGA (reife hypotrophe Neugeborene).……….……………………………………………….18 3.5. Frühgeborene (FG)………………………………..…………………………….……………….20 3.6. direkter Vergleich der 3 Untergruppen (tAGA, tSGA und FG)…………………………...…22 3.7. Charakteristika der Population der zweiten Studienphase…………………………………...28 3.8. tAGA-Kinder in der zweiten Studienphase (TSB3-tAGA)……………………………………30 3.9. tSGA in der zweiten Studienphase (TSB3-tSGA)….…………………………………………..32 3.10. Frühgeborene in der zweiten Studienphase (TSB3-FG)……………….…………………….35 3.11. direkter Vergleich der drei Untergruppen der zweiten Studienphase…………….………..37 3.12. Vergleich der retro- und prospektiven Teile der Studie…….……………………………….43 3.13. Die Phototherapiegruppe………………………………………………………………………45 3.13.5. Zusammenhang zwischen Phototherapie und Geburtsmodus………………………………………..47 3.13.6. Zusammenhang zwischen Phototherapie und Nabelschnurbilirubin………………………………..48 3.13.7. Zusammenhang zwischen Phototherapie und Serumbilirubin vom 3.LT (TSB3)…………………..51 3.14. Vorhersage der therapiepflichtigen Hyperbilirubinämie anhand der Nabelschnurbilirubin-Werte…..………………………………………………….…………………………………….……..54 3.14.1. statistische Begriffe………………………………………………………………………………………54 3.14.2. Vorhersage der therapiepflichtigen Hyperbilirubinämie anhand der Nabelschurbilirubin-Werte.54 3.15. Vorhersage der therapiepflichtigen Hyperbilirubinämie anhand TSB3 (Serumbilirubin vom 3. Lebenstag)……………………...………………………………………..……………………56 3.16. Zusammenhang zwischen NS-Bili und TSB3(Serumbilirubin vom 3. Lebenstag)…………58 3.17. Regressionsanalyse…………………………………...…………………………………………59 3.17.1. univariate Regressionsanalyse………………………………………………………………………….59 3.17.2. multivariate Regressionsanalyse………………………………………………………………………..59 3.18. Odds Ratio einer therapiepflichtigen Hyperbilirubinämie………………………………….61 3.19. Beginn und Dauer der Phototherapie…………………………………………………………62 4. Diskussion……………………………………….…………………………………..…….64 Nabelschnurbilirubin und Phototherapie………………………………………………….……….64 Serumbilirubin vom 3. Lebenstag und Phototherapie….………………………………………….67 Kombination aus Nabelschnurbilirubin und Serumbilirubin vom 3.Lebenstag…………………71 Phototherapiegruppe…………………………………………………………………………………73 Schlussfolgerung…………………………...…………………………………………………………76 5. Zusammenfassung der Arbeit……………………………………………………………78 6. Literaturverzeichnis………………………………………………………………………82 7. Abbildungsverzeichnis……………………………………………………………………98 8. Tabellenverzeichnis……………………………………………………………………….99 Erklärung über die eigenständige Abfassung der Arbeit…………………………..……101 Danksagung…………………...…………………………………………………..………..102 Lebenslauf……………………………………………………………………………………………103

La photothérapie dynamique (PTD) est un traitement alternatif du cancer qui nécessite l’utilisation de chromophores (photosensibilisateurs) capables d’induire la mort cellulaire suite à une irradiation lumineuse. Les nanoparticles d’or (AuNP), grâce à leur phénomène de résonance plasmon localisée, peuvent exalter les propriétés photophysiques des chromophores localisés à leur surface. L’utilisation d’une excitation biphotonique, dans le proche infrarouge, peut être utilisée pour améliorer l’action thérapeutique (PTD) ou diagnostique (imagerie de fluorescence) des chromophores en augmentant la profondeur de pénétration dans les tissus et la résolution tridimensionnelle de la microscopie biphotonique.Lors de ce travail, l’élaboration de nouvelles nanoparticules hybrides est proposée, présentant des applications potentielles en bioimagerie (sondes brillantes) et comme photosensibilisateurs pour la PTD. Ces nanoparticules sont composées d’un cœur d’or sur lequel sont greffés des conjugués polymère-chromophores biphotoniques. La stratégie de synthèse a consisté à : i) synthétiser des conjugués polymère-chromophores biphotoniques solubles dans l’eau ; ii) les greffer de manière orientée à la surface des AuNP. La synthèse des conjugués polymère-chromophores hydrosolubles on été synthétisés via le couplage efficace de chromophores hydrophobes en position latérale des copolymères P(NAM-co-NAS) bien-définis, obtenus par la techniques de polymérisation radicalaire contrôlée RAFT. Cette stratégie permet le contrôle à la fois de la longueur des chaînes polymère formées (2 000 g.mol-1 < Mn plus < 37 000 g.mol-1) et du nombre de chromophores couplés par chaîne (de 1 à 21). Le greffage orienté de ces conjugués à la surface des AuNP a été mis en évidence (TEM, ATG) et les densités de greffage se sont avérées élevées (~0.5chaîne/nm²). Un des rôles de la chaîne polymère étant de contrôler la distance entre les chromophores et la surface des AuNP. Il a été mis en évidence que l’augmentation de la longueur de chaine des conjugués induisait, outre une augmentation de la couronne greffée (par MET) sur les AuNP, une augmentation de l’émission de fluorescence de ces conjugués polymère-chromophores. Enfin, les propriétés biologiques des conjugués avant et après greffage sur les AuNP ont été évaluées in cellulo, mettant en valeur leur potentiel pour des applications thérapeutiques et diagnostiques. / Photodynamic therapy (PDT) is an alternative treatment of cancer requiring the use of chromophore molecules (photosensitizers), which can induce cell death after light excitation. Gold nanoparticles (AuNP), exhibiting localized Surface Plasmon Resonance, can enhance the photophysical response of chromophores located in their vicinity, and thus improve their therapeutic action. Moreover, the use of highly localized two-photon chromophores (photosensitizers and fluorophores), capable to undergo a localized excitation by light in the Near InfraRed region, should increase the penetration depth into tissues, thus improve the treatment efficiency (by PDT) and the imaging (by fluorescence microscopy) of cancer tissues.In this work, we describe the elaboration of water-soluble hybrid nano-objects for PDT and fluorescence bioimaging applications, composed of two-photon chromophore-polymer conjugates grafted onto gold nanoparticles. In order to obtain these nano-objects we follow a multistep strategy: i) the synthesis of a well-defined water-soluble chromophore-polymer conjugates; ii) the end-group oriented grafting of chromophore-polymer conjugates onto 20 nm AuNP. The coupling of hydrophobic two-photon chromophores on linear water-soluble copolymer chains (poly(N-acryloylmorpholine-co-N-acryloxysuccinimide)), obtained by controlled/living RAFT polymerization, resulted in well-defined water-soluble chromophore-polymer conjugates, with different polymer lengths (2 000 g.mol-1 < Mn < 37 000 g.mol-1) and architectures (random or block), and a controlled number of chromophores per chain (varying between 1 and 21). Their grafting onto 20 nm AuNP gave water-soluble hybrid nano-objects with high grafting densities (~0.5 chains/nm²). The role of the polymer chain being to tune the distance between chromophores and AuNP surface, we have evidenced the increase in the polymer corona thickness of grafted AuNP (estimated by TEM) with the increasing polymer Mn, corroborating with the corresponding distance-dependent fluorescence properties of those. Finally, the in cellulo biological properties of two-photon chromophore-polymer conjugates, before and after grafting onto AuNP, have been investigated, highlighting their potential for two-photon bioimaging and PDT applications.

Indiana University-Purdue University Indianapolis (IUPUI) / Introduction: Microbial biofilms have been shown to be a cause of persistent endodontic infections. It is more resistant than planktonic bacteria to host immune defenses and antimicrobials. Studies indicate that photodynamic light therapy (PDT), which involves using light at specific wavelengths, has a potent antibacterial effect on bacterial biofilm. PDT is an antimicrobial strategy that involves the use of a nontoxic photosensitizer (PS) along with a light source. The excited PS reacts with molecular oxygen to produce highly reactive oxygen species, which induce injury or death to microorganisms. PSs have a high degree of selectivity for inhibiting microorganisms without negatively affecting host mammalian cells. PDT has been suggested as an adjuvant to conventional endodontic treatment. Studies at IUSD have shown that blue light at 380 nm to 440 nm has the ability to inactivate Streptococcus mutans biofilm without any exogenous PS. Objective: The objective of this study was to determine the effectiveness of blue light at 380 nm to 440 nm to reduce adherence of Enterococcus faecalis biofilm after NaOCl irrigation at various concentrations. Materials and Methods: E. faecalis biofilm was established for 72 hours in 96- well flat-bottom microtiter plates using Tryptic Soy Broth supplemented with 1.0-percent sucrose (TSBS). Biofilm was irradiated with blue light for 5 minutes before exposure to various concentrations of NaOCl for 30 seconds. A crystal violet biofilm assay was used to determine relative density of the biofilm. Data were analyzed with two-way ANOVA and Sidak-adjusted multiple comparisons using a 5.0-percent significance level. Null Hypothesis: Blue light and NaOCl will not have an effect against E. faecalis biofilm adherence. Results: Overall, there was a significant effect (p < 0.05) for NaOCl and a significant effect for blue light. The effects of the combination of NaOCl and blue light were also significant. Conclusion: We reject the null hypothesis and accept the alternative hypothesis that blue light when used in conjunction with NaOCl will reduce adherence of E. faecalis biofilm.

No description available.

Much of the research on differential hemispheric activation as a function of age or the presence of depression suggests that a relative decrease in left hemisphere activation is associated with depression, while a decrease of right hemisphere activation is associated with age. Recent research, however, has demonstrated the role of the right hemisphere in maintaining general behavioral arousal. Pilot data suggest that elderly people experience behavioral over-arousal when presented with stressful or novel environmental stimuli. Equally interesting is the finding in a single-case study that ambient light and noise have a differential effect on behavior presumed to be representative of the left and the right cerebral hemispheres. The left hemisphere appears to be more responsive to ambient light level, with the right hemisphere being more responsive to ambient noise level. The present study sought to provide further support of selective hemispheric activation to bright light, and to examine the relationships among hemi-activation, age and depression by using behavioral measures of lateral anterior (finger tapping rate) and posterior (dichotic listening) cortical functioning. Two identical experiments were employed to evaluate old and young, and depressed and non-depressed sUbjects. Direct evidence of right herni-aging effects on laterality was not significant in the first experiment, but data suggested the possibility of a ceiling effect for behavioral arousal in the older group which was not seen in younger subjects. The second experiment yielded no significant results between depressed and non-depressed groups. Hypotheses of under and over arousal in subjects are proposed to explain findings. Possible implications for treatment and recommendations for further research are proposed. / Ph. D.

碩士 / 國立臺灣大學 / 護理學研究所 / 102 / Hyperbilirubinemia is the most common health problem in the neonatal phase. Around 1% to 4% of newborns will be hospitalized again due to this problem in the first week after birth. The research is to explore the effects of nursing interventions on newborn with hyperbilirubinemia within 14 days after being discharged from hospital. These factors includes the characteristics of newborns and their mothers, newborns’ admission body weight, discharge body weight, bilirubin value at admission, bilirubin value at discharge, days of phototherapy, length of hospital stay, feeding pattern, times of output, amount of breast milk feeding, breastfeeding time, amount of formula milk feeding. Data were collected by the researcher herself through chart review. Research tools include self-developed checklists for the demographic characteristics of both newborns and their mothers and the clinical manifestationof newborn babies. All the data were recored in a laptop computer. Investigation period ranged from 2013.10.07 to 2013.11.09. Control group from Jan, 2008 to Dec, 2009. There are 61 newborns in total which got hyperbilirubinemia and need readmitted, Experimental group, in between Jan, 2010 and Dec, 2011, there are 30 newborns who suffered the same symptoms. The SPSS20.0 software was used for the statistics analysis, including methods like description statistics, Chi-square test, independent sample t-test and Fisher’s exact test, and Scheffe test. We found that by providing mothers with complete instructions for taking care of a baby with hyperbilirubinemia during the nursing intervening, it helps reducing the readmission rate of the newborns with hyperbilirubinemia from 3.86% to 2.16%. Decrease infant formula from 465.12 ± 224.34 ml to 323.86 ± 172.75 ml (t = -2.98, p = .004). Comparing the status of readmission, the experimental group was heavier in both admission body weight（2876.27 ± 463.65gm vs 3123.98 ± 551.37gm, t = -2.12, p =.037）and discharge body weight（2951.87 ± 487.13 gm vs 3284.82 ± 559.93 gm, t = -2.78, p = .007）, had higher value in discharge bilirubin（11.50 ± 1.41 mg / dL vs 10.74 ± 1.37 mg / dL, t = 2.47, p = .015）, and has less intake of formula milk (323.86 ± 172.75 ml vs 465.12 ± 224.34 ml, t = -2.98, p = .004) significantly than in the control group. In addition, we found that the older age of the mother, the lenth of hospital stay of the newborn baby is shorter （7.50 ± 0.70 vs 3.79 ± 1.65 vs 3.44 ± 1.59, t＝5.407, p＝.011）. The higher level of mother’s education was, both length of hospital stay （8.00 ± 0.00 vs 3.80 ± 2.04 vs 3.33 ± 1.52 vs 3.50 ± 1.54 vs 6.00 ± 1.00天, t＝3.312, p＝.026）and days of phototherapy were shorter（8.00 ± 0.00 vs 2.60 ± 1.82 vs 2.33 ± 1.53 vs 2.44 ± 1.38 vs 4.33 ± 2.08, t＝3.941, p＝.013）. Mothers with the degree of university had more amount of breast milk feeding than both mothers with high school deploma and graduate degree (192.57 ± 80.59 vs 60.00 ± 0.00, 51.33 ± 10.26 respectively, t = 5.031, p = .038). Based on the concept of family-centered care, the nursing education with complete instruction of taking care of a newborn baby indeed contribute a mother to improve their understanding about correct feeding pattern and observation. Current study support the effect on increasing breast feeding, decreasing formula milk feeding, and reducing the rate of readmission for the infant with hyperbilirubinemia. These findings provide nursing staffs a good reference for nursing care of the newborns.

碩士 / 義守大學 / 電子工程學系 / 101 / Recently, light emitting diode (LED) phototherapy has attracted attention for reducing pain and inducing tissue repair through several mechanisms. The LED has a longer life, is more economically accessible and can be efficient as laser light. Despite increased basic and clinical researches and improved understanding of pathologic mechanisms, optimal post-surgical pain therapy remains a challenge for physicians. The analgesic effect of LED on incisional wound has not been examined. The effect of pro- and anti-inflammatory cytokine, COX-2 and PGE2 in pain treatment has been demonstrated by previous report. Thus, in this study, we will examine the analgesic effect of LED therapy and the role of pro- and anti-inflammatory cytokine, COX-2 and PGE2 in incisional skin after LED therapy or not. The rats were randomly divided into four groups. Rats received 940nm LED therapy 6 days before incision over left hind planta (group L-I) or 6 days after incision (group I-L) or from 3 days before incision to 3 days after incision (group L-I-L), skin incision only (group I). Thermal withdrawal latency was tested before and after treatment, skin tissues were collected for IL-1β, IL-10, COX-2 and PGE2 protein analysis (n=5 each group) by western blot after behavior test. Thermal withdrawal latency was significant decreased in incision wound but not in incision wound treated with LED. The IL-1β, COX-2 and PGE2 were significant decreased after LED treatment compared with incision wound with no LED treatment group (P<0.05). The IL-10 was significant increased after LED treatment compared with incision wound with no LED treatment group (P<0.05). Thus, the analgesic effect of LED was associated with the decrease of IL-1β, COX-2 and PGE2 and the increase of IL-10, and confirmed that the LED therapy on cut pain relief has a positive effect.

博士 / 國立臺灣大學 / 臨床醫學研究所 / 102 / Pruritus is the dominant symptom of skin disease and a frequent manifestation of systemic disease. It causes serious discomfort, anxiety, depression, sleeping disorders, considerable skin damagend and has substantial effects on quality of life. We conducted a cross-sectional study to investigate the association of glycemic control with generalized pruritus in type 2 diabetes. A total of 385 patients with type 2 diabetes who attended the diabetes care system underwent cutaneous examination by a dermatologist. A detailed interview questionnaire including visual analogue scale was used to assess various characteristics and the intensity of pruritus. Generalized pruritus was noted in 27.5% of the diabetic patients. As a result of pruritus, 24.5% of the patients had difficulties in falling asleep, 15.1% had disturbance of sleep, and 9.5% needed soporifics. Patients who had a higher postprandial glucose level had a higher probability of having generalized pruritus [OR=1.41 (95% C.I.: 1.05–1.90), P=0.02] in type 2 diabetic patients. We found generalized pruritus in patients with type 2 diabetes mellitus is associated with PC glucose control. This finding arouses the physicians to pay more attention to pruritus in diabetic patients and to motivate the patient for better blood glucose control. Uremic pruritus is also one of the most common and bothersome symptoms in patients with chronic kidney disease, with approximately 40-90% of patients on long-term maintenance dialysis suffering from this problem. To date, the mechanisms of uremic pruritus remain poorly characterized. We conducted a prospective cohort study of patients with maintenance hemodialysis in the hemodialysis center. Patient demographic and clinical characteristics, laboratory parameters, dialysis adequacy (assessed by Kt/V), and pruritus intensity were recorded at baseline and follow-up. Change score analysis of the difference score of VAS between baseline and follow-up was performed using multiple linear regression models. A total of 111 patients completed the study. Linear regression analysis showed that lower Kt/V and use of low-flux dialyzer were significantly associated with the aggravation of pruritus after adjusting for the baseline pruritus intensity and a variety of confounding factors. The optimal threshold value of Kt/V for pruritus was 1.5 suggested by both generalized additive models and receiver operating characteristic analysis. The cut-off value of 1.5 for Kt/V suggested by our study for pruritus is slightly above the target levels reducing mortality recommended in clinical practice guidelines, which not only implies that a Kt/V higher than the current standard may not further improve survival but may improve the quality of life, but also indicates that the clearance of pruritogenic substances could influence the intensity of pruritus. The therapeutic options for uremic pruritus are limited and unsatisfactory. Broad band ultraviolet B phototherapy has been demonstrated to be effective in the treatment of uremic pruritus in previous studies. Recently there is a trend of replacing BB-UVB phototherapy units with narrowband ultraviolet B (NB-UVB) units, as studies have demonstrated that NB-UVB is more efficacious in the treatment of psoriasis. However, studies regarding NB-UVB phototherpy for uremic pruritus are rare. A single blinded, randomized control trial was conducted to investigate the efficacy of NB-UVB phototherapy in uremic pruritus. Eligible participants were adults older than 18 years old, with CKD stage 3 to 5 and 5D. Patients with pruritus of visual analogue scale score over 5, itching duration of more than 2 months, and refractory to oral antihistamines and topical emollients were enrolled. The treatment group received NB-UVB phototherapy 3 times per week for 6 weeks. The dose of NB-UVB started from 210 mJ/cm2 and was increased by 10% at each time. The control group received time-matched exposures to long-wave ultraviolet light (UVA).Visual analogue scale score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6-week phototherapy. Both NB-UVB and control groups have significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared to control group, the NB-UVB group showed a significant improvement in the involved body surface area affected by pruritus (p = 0.006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity at week 6, week 10, and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal. NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared to control group for refractory uremic pruritus. This finding may imply that although NB-UVB has been demonstrated to be more effective than BB-UVB for the treatment of psoriasis, its superior effect should not be directly extrapolated to other potential phototherapy-responsive dermatoses, such as uremic pruritus in this study.

博士 / 國立臺灣大學 / 臨床醫學研究所 / 102 / Neonatal hyperbilirubinemia is a common problem with the incidence around 60~70%. The peak serum levels of unconjugated bilirubin in full-term Asian and American Indian neonates are almost double as those in Caucasian and black populations. The finding suggests that genetic factors are involved in the development of neonatal hyperbilirubinemia. Breastfeeding jaundice is common in exclusively breastfed neonates, but its pathogenesis is still unclear. The uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphism was shown to contribute to the development of neonatal hyperbilirubinemia. We hypothesize that the variation of UGT1A1 gene may contribute to neonatal breastfeeding jaundice. 211 G to A Variation of UDP-Glucuronosyl Transferase 1A1 Gene and Neonatal Breastfeeding Jaundice We prospectively enrolled 688 near term &; term infants who were exclusively breast-fed (BF group) or were supplemented by infant formula partially (SF group) before onset of hyperbilirubinemia. Genotyping of the promoter and exon1 of UGT1A1 was performed in all neonates. Neonates in BF group had a significantly higher maximal body weight loss ratio, peak bilirubin level, and a greater incidence of hyperbilirubinemia than those in SF group. Neonates with nucleotide 211 GA or AA variation in UGT1A1 genotypes had higher peak serum bilirubin levels and higher incidence of hyperbilirubinemia than wild types (GG). This phenomenon was only seen in BF group but not in SF group when we do subset analysis. This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice. Prediction of Severe Neonatal Hyperbilirubinemia Using Cord Blood Hydrogen Peroxide: A Prospective Study Given the relationship between bilirubin and hydrogen peroxide, which is one of reactive oxygen species, we hypothesized that cord blood hydrogen peroxide could be utilized to predict the severity of neonatal hyperbilirubinemia. We prospectively enrolled 158 term or near-term healthy neonates. Cord blood and capillary blood at three and five days of age were measured for hydrogen peroxide and bilirubin concentrations. Newborns were divided into severe or less severe hyperbilirubinemic groups. The rising patterns were similar among bilirubin concentrations and hydrogen peroxide levels during the first few days of life. There was a strong positive correlation between bilirubin concentrations and hydrogen peroxide levels after correlation analysis. It revealed that a cord blood hydrogen peroxide signal level of 2500 counts/10 seconds was an appropriate cut-off for predicting severe hyperbilirubinemia. Sensitivity and the negative predictive value were 76.2% and 93.3%, respectively. Our findings confirm that hydrogen peroxide levels and bilirubin concentrations in cord and neonatal blood are closely related. A cord blood hydrogen peroxide level above 2500 counts/10 seconds associated with a high predictive value for severe hyperbilirubinemia. Other factors associated with neonatal hyperbilirubinemia To evaluate the impact of breast-feeding promotion on the incidence of hyperbilirubinemia, on peak bilirubin level and on mean days of hospitalization. Total 1273 healthy full-term newborns born before and after the Baby Friendly Hospital Initiative Program was launched in July 2000. There was a significant association between monthly rates of breast-feeding and the incidence of hyperbilirubinemia, BW loss ratio, the bilirubin level on the third or fourth day, the peak bilirubin level, the mean hospital days, the mean days of phototherapy, as well as the frequencies of urination and defecation. A total of 874 neonates were exclusively breastfed and subsequently enrolled in this study. We analyzed the association between weight loss percentage and hyperbilirubinemia and investigated the best weight loss percentage cut-off value for prediction of subsequent hyperbilirubinemia before two weeks of age. Neonates with lower gestational age (GA) and greater weight loss percentage were associated with hyperbilirubinemia. By using weight loss > 8% of BBW after 48 hours and weight loss > 11% of BBW after 72 hours as the cut-off values for prediction of subsequent hyperbilirubinemia, respectively. We also retrospectively collected exclusively breast-feeding healthy term and near-term newborns born in our nursery between May 1 2002 to June 30 2005. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during 4th to 10th day of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the AUROC curve of 0.788. Model validation in the separate study (N=209) showed similar discrimination capability (AUROC=0.8340). Gestational age, maximal body weight loss percentage and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia.