Bilirubin photoisomerization products in serum and urine from a Crigler-Najjar type I patient treated by phototherapy.

The relative compositions of the photoisomers of bilirubin-1X alpha (4Z, 15Z-bilirubin) in serum and urine of a patient with Crigler-Najjar type I syndrome treated by phototherapy are reported. High-performance liquid chromatography analysis reveals the presence of high serum levels of the configurational bilirubin photoisomer (4Z,15E-bilirubin) before the beginning of phototherapy (between 12 and 16% of the total bilirubin). The configurational photoisomer value increases during phototherapy with blue fluorescent lamps up to a photoequilibrium of about 25%, similar to that obtained in a bilirubin solution in vitro irradiated by the same lamps. This evidence suggests an inefficient serum excretion of the 4Z,15E-bilirubin. Indeed, its average half-life in serum of the Crigler-Najjar patient is found to be about 8 h. No detectable traces of the bilirubin structural isomer, lumirubin, are found in the serum. On the other hand, lumirubin represents the dominant bilirubin isomer excreted in the urine, as both 15Z and 15E configurations. Smaller amounts of 4Z,15E-bilirubin, 4E,15Z-bilirubin and native 4Z,15Z-bilirubin are observed in urine. The presence in urine of 4Z,15Z-bilirubin is probably due to a fast reversion of the configurational photoisomers to their native form. The half-life of the configurational photoisomers in urine kept at 38 degrees C is found to be of the order of a few minutes. Our study indicates that in Crigler-Najjar type I patients, mechanisms exist to excrete all bilirubin photoisomers. The lumirubin pathway seems to contribute markedly to bilirubin excretion in the urine, as occurs in jaundiced babies under phototherapy. However, the contribution of configurational isomers cannot be neglected.

Fibreoptic phototherapy in the management of jaundice in low birthweight neonates.

A fibreoptic phototherapy device has been compared with conventional white and special blue fluorescent phototherapy lamps to evaluate its efficacy in lowering serum bilirubin levels in low-birthweight neonates. Fibreoptic phototherapy was found to be as effective as white light and less effective than blue light, as assessed by (i) the bilirubin concentration after 24 h of phototherapy and at the end of phototherapy, (ii) the duration of phototherapy, (iii) the percentage daily decline rate and (iv) the overall percentage decline rate (p < 0.05). There were no failures of phototherapy and the need for re-exposure was low (4.7% of the total sample), with no difference between groups. The fibreoptic approach represents a promising way to aggregate synergically the most recent optical technologies and develop a modern, efficient and caring phototherapy system for low-birthweight infants.

Quantum yield and skin filtering effects on the formation rate of lumirubin.

Photocyclization of bilirubin to lumirubin in the skin of jaundiced infants exposed to blue-green light irradiation is considered to be the most important process for bilirubin elimination from the organism. The quantum yield phi LR of the bilirubin-->lumirubin photoreaction has been recently measured and found to vary with the excitation wavelength, with a peak at about 520 nm. The quantum yield phi ZE for the strongly competing reversible configurational photoisomerization of bilirubin has also been recently shown to be wavelength dependent and to decrease significantly in the long-wavelength part of the absorption band of bilirubin. These new data are taken into account to model the bilirubin photochemistry in vivo by using a simplified skin optical model based on the Kubelka-Munk theory. The rate kappa LR of formation of lumirubin has been evaluated for the case of a four-layer skin and for monochromatic and narrow-band coloured fluorescent lamps. The effects of long-wavelength increase in phi LR, decrease in phi ZE and skin optical losses all combine to shift significantly the optimal rate of formation of lumirubin towards the green. These results suggest that a significant improvement in phototherapy might be obtained with the introduction of new lamps emitting in the blue-green spectral region between 490 and 510 nm.

Phototherapy in the management of neonatal hyperbilirubinemia: efficacy with light sources emitting more than 500 nanometers.

The clinical action of green fluorescent lamps, properly filtered to remove wavelengths of less than 500 nm, was investigated in a group of 23 newborns with different initial serum bilirubin concentrations. The serum bilirubin levels were measured at 6, 12, 24, and 48 hours after the beginning of phototherapy. These results are compared with those obtained, under the same experimental conditions, in a group exposed to commercial green lamps. Similar bilirubin decline rates were observed in the two experiments. In general, these data confirm the satisfactory clinical efficacy of the green light in phototherapy and prove, in particular, that the blue component present in the emission spectrum of the commercial green lamps has a negligible effect on the bilirubin degradation process.

Phototherapy for neonatal jaundice: clinical equivalence of fluorescent green and "special" blue lamps.

The relative efficacy of fluorescent green (Sylvania F20T12/G) and "special" blue (Westinghouse F20T12/BB) lamps in the phototherapy of jaundiced neonates was investigated. Two groups of low birth weight infants with a mean gestational age of 35 weeks and mean birth weight of 1930 gm, who developed hyperbilirubinemia within the first 5 days of life, were given green or blue lamp phototherapy under the same irradiation conditions. No statistically significant difference in plasma bilirubin concentrations was found between the two groups after 24 or 48 hours of treatment. Because recent measurements indicate that green lamps are much less efficient than special blue lamps for the production of Z, E isomers of bilirubin in vitro and in vivo, the clinical equivalence of these two types of lamps seems to support the hypothesis that production of structural photoisomers of bilirubin is the main mechanism of phototherapy in humans. Therefore, fluorescent green lamps provide an alternative to special blue lamps for treatment of neonatal hyperbilirubinemia.

Laser investigation of bilirubin-photobilirubin photoconversion.

The reversibility of the configurational photoisomerization process of bilirubin (BR) with laser lines in the blue-green spectral region is investigated. Photoisomerization efficiency of BR is found to depend strongly on wavelength, and to decrease when the excitation wavelength is increased from blue to green. Reversion of BR photoisomers (identical to photobilirubin, PBR) back to native BR is demonstrated for several laser lines by irradiating PBR/BR mixtures with wavelengths greater than the excitation wavelengths. Green lines turn out to be very efficient for PBR----BR reversion. The PBR concentrations at photoequilibrium, obtained from the spectrophotometric data, are in close agreement with the corresponding values measured with the high performance liquid chromatography technique in the case of 10 nm bandwidth filtered light reported in the literature. The 457 nm blue laser line produces 32% PBR concentration at photoequilibrium; only 14, 7, and 3% PBR concentrations are produced by the blue-green lines at 488, 501, 514 nm, respectively. The effect on the photostationary PBR/BR mixture of successive irradiations with different wavelengths, and the influence of the wavelength sequence are reported. In the case of blue lines our results support the assumption of the first-order kinetics for the BR in equilibrium PBR photoreaction. Departures are observed with green-lines (501, 514 nm). The present results, together with the i) good clinical efficiency reported for fluorescent green lamps; and ii) slow elimination of configurational photoisomers in infants, tend to confirm the lumirubin-pathway as the main mechanism for phototherapy, and call for clinical investigation of narrow-spectrum lamps with peak emission wavelength in the (biologically safer) 480 divided by 530 nm range.

Green light in phototherapy.

Photodegradation of bilirubin in vivo has been investigated by using green fluorescent sources according to the suggestions obtained in a previous study in vitro. Two groups of 50 jaundiced low-birth-weight infants were exposed to fluorescent light in phototherapy units under similar irradiant conditions. One group was exposed for 24 h to standard green tubes, the other, to daylight lamps. Newborns of the two groups were similar for gestational age, birthweight, and initial bilirubin concentration. A greater decrease in the serum concentration of bilirubin was found in subjects exposed to the green light when compared with infants exposed to daylight lamps. The use of green light is strongly suggested instead of the white, blue, and special blue lamps, because of the real efficiency, power and range of wave lengths.

Laser photolysis of bilirubin.

Photodegradation of bilirubin in vitro has been investigated by using monochromatic light supplied by an argon ion laser selecting the 457.9, 488.0 and 514.5 nm wavelengths. Bilirubin was examined in chloroform, in aqueous solutions and in human serum under different experimental conditions of concentration, laser power and time of irradiance. Photodecomposition was followed by optical density measurements on the absorption maximum of the electronic band at 460 nm. The rate of degradation of bilirubin was found to be only slightly affected by the wavelength of the exciting lines provided they fall within the absorption band. In particular it was shown that any wavelength, lambda, is equally effective if the corresponding absorbance, A lambda, exceeds a minimum value of 5-10%. In the aqueous solutions, light with lambda greater than 470 nm has been found to be largely effective in the photodegradation of bilirubin in vitro.