Bio-nanotechnology and photodynamic therapy--state of the art review.

Photodynamic therapy (PDT) and bio-nanotechnology (NT) show striking similarities in clinical design and mechanistics. The PDT paradigm of photosensitizer application, light activation and singlet oxygen generation does in fact occur on the nanoscale level as does the resultant outcomes. NT has the ability to explain as well as modify each of the critical steps of PDT particularly photosensitizer design and delivery, light source miniaturization and optimization, location and intensity of the photodynamic reaction as well as offering a far greater insight into dosimetry and mechanisms of action. This review will explore the current and potential future interactions and modifications NT may have on PDT.

Determination of absorbed dose in water at the reference point d(r0, theta0) for an 192Ir HDR brachytherapy source using a Fricke system.

A ring-shaped Fricke device was developed to measure the absolute dose on the transverse bisector of a 192Ir high dose rate (HDR) source at 1 cm from its center in water, D(r0, theta0). It consists of a polymethylmethacrylate (PMMA) rod (axial axis) with a cylindrical cavity at its center to insert the 192Ir radioactive source. A ring cavity around the source with 1.5 mm thickness and 5 mm height is centered at 1 cm from the central axis of the source. This ring cavity is etched in a disk shaped base with 2.65 cm diameter and 0.90 cm thickness. The cavity has a wall around it 0.25 cm thick. This ring is filled with Fricke solution, sealed, and the whole assembly is immersed in water during irradiations. The device takes advantage of the cylindrical geometry to measure D(r0, theta0). Irradiations were performed with a Nucletron microselectron HDR unit loaded with an 192Ir Alpha Omega radioactive source. A Spectronic 1001 spectrophotometer was used to measure the optical absorbance using a 1 mL quartz cuvette with 1.00 cm light pathlength. The PENELOPE Monte Carlo code (MC) was utilized to simulate the Fricke device and the 192Ir Alpha Omega source in detail to calculate the perturbation introduced by the PMMA material. A NIST traceable calibrated well type ionization chamber was used to determine the air-kerma strength, and a published dose-rate constant was used to determine the dose rate at the reference point. The time to deliver 30.00 Gy to the reference point was calculated. This absorbed dose was then compared to the absorbed dose measured by the Fricke solution. Based on MC simulation, the PMMA of the Fricke device increases the D(r0, theta0) by 2.0%. Applying the corresponding correction factor, the D(r0, theta0) value assessed with the Fricke device agrees within 2.0% with the expected value with a total combined uncertainty of 3.43% (k=1). The Fricke device provides a promising method towards calibration of brachytherapy radiation sources in terms of D(r0, theta0) and audit HDR source calibrations.

Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization.

A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

(HP)Ge Measurement of spectra for diagnostic X-ray beams.

The X-ray spectra applied in diagnostic radiology to the energy range between 50 and 125 kVp, were experimentally determined using a high-purity germanium detector, (HP)Ge, coupled to a multichannel analyser. A simple stripping procedure was implemented, according to that described by Seelentag and Panzer, to correct the pulse height distribution and then to determine the photon spectra. The measurements were performed for those conditions where the X-ray beam is transmitted through Pb filters 0.2-0.7 mm thick. It was necessary to estimate the effective dose in the same way that it is done for radiology diagnosis room shielding projects. The spectra were also determined to the X-ray qualities recommended by the IEC for primary diagnostic X-ray and for X-ray beams attenuated by aluminium filters 2.5-42.5 mm thick. The spectra obtained were compared with data derived from the literature presenting good agreement.

Clinical PD/PDT in North America: An historical review.

The healing properties of light have been appreciated for thousands of years. However, the harnessing of light energy to create a rigorous and reliable means to diagnose and treat human disease is only a relatively recent phenomenon. Despite outstanding results from ancient history and subsequent reemergence and refinement of this knowledge over the last 100 years, it took again the hand of serendipity to open the modern age of Photodiagnosis and Photodynamic Therapy. Based on the prescience and perseverance of a handful, the under appreciated observations of tumor fluorescence and photodynamic action have been brought to a worldwide audience. This review highlights the development of clinical Photodiagnosis and Photodynamic Therapy, emphasizing the significant events and milestones taking place in North America.

[Primary immunodeficiency secondary to ZAP-70 deficiency]. / Imunodeficiência primária por défice de ZAP-70.

The authors present the case of a child with recurrent infections since the age of 4 months, including bilateral pneumonia by Pneumocystis carinii and protracted varicella. Serum immunoglobulin values (when 10 months old), and B cell values were normal. There was persistent lymphocytic leucocytosis, near absence of CD8+ cells, and an increased CD4/CD8 ratio. The percentage of activated T cells and the expression of HLA class I were normal. Proliferation, activation and IL-2 synthesis studies in T cells showed a TCR/CD3-associated signal transduction deficit. ZAP-70 cDNA sequencing showed a mutation, and no ZAP-70 protein was detected in T cells. ZAP-70 deficiency is associated with a rare immune deficiency with absence of CD8+ T cells as well as a functional deficiency in T cells. Seven months after bone marrow transplantation the child is clinically well and immunologically recovered.

[My history of pediatrics]. / A minha história da pediatria.

In an attempt to discern the paradigms underlying our medical practice (more specifically paediatrics) over the last 30 years, it was found that these are rather similar to the ones prevailing at the beginning of this period--all wrong-doings were attributed to outside forces which had to be neutralized; the obsession to standardise the internal milieu; the compulsion to always do something, little attention being paid to collateral effects; the ends justifying the means and the charm of technology.

Absence of lysozyme (muramidase) in the intestinal Paneth cells of newborn infants with necrotising enterocolitis.

AIM: To determine immunocytochemically whether preterm and newborn infants with necrotising enterocolitis (NEC) show differences in numbers of lysozyme positive Paneth cells compared with normal controls, and to relate the findings to the possibility that lysozyme deficiency may facilitate the bacterial infections thought to be associated with this condition. METHODS: Tissues from 10 infants with NEC and from 11 matched controls were sectioned and stained immunocytochemically for lysozyme. Differences in the numbers of Paneth cells and degree of lysozyme positivity in the tissues were assessed. RESULTS: Tissues from NEC patients showed no, or very few, lysozyme positive Paneth cells, whereas controls showed strong positive staining. CONCLUSIONS: A deficiency or developmental defect in Paneth cells, resulting in an absence of lysozyme, may render the intestine more susceptible to bacterial infection, allowing organisms to adhere and translocate across the mucosa. Such enhancement of infection may contribute to the pathogenesis of NEC.

Neurobrucellosis in children.

UNLABELLED: Neurobrucellosis is an uncommon disease in children. The authors present two cases of brucellar meningo-encephalitis. Headache and vomiting were the main complaints and one child had also some behavioural disturbance as well as papilloedema and sixth cranial nerve palsy. The clinical diagnosis was suggested by epidemiological data in both cases. Blood and CSF cultures confirmed brucellar aetiology in one of the cases and positive serum and CSF specific antibodies in both. Clinical course was favourable after treatment with doxycycline, rifampicin and streptomycin. No relapse occurred and there were no sequelae. CONCLUSION: Neurobrucellosis should be considered in the differential diagnosis of neurobehavioural disturbance of children living in areas where brucellosis is endemic.

Influence of detector size in photon beam profile measurements.

Correction is necessary to account for the detector size in clinical dosimetry of photon and electron beams. This correction is due to the absorbed dose gradient present in a finite-size detector. Further corrections are necessary when the detector and phantom materials are not the same. These corrections are due to the perturbation in the charged-particle fluence. Generally these corrections are applied to measurements along the central axis of the beam. Cross beam profile measurements, however, are not usually corrected for detector size. The ionization profile is also usually assumed to be equivalent to the absorbed dose profile. We have corrected the ionization chamber size effect by two approaches: extrapolation of measurements to zero detector size and deconvolution of measurements using a simple model for the detector response function. We have measured absorbed dose profiles to water using a small water-equivalent plastic scintillation detector. Film profile measurements were also studied. The ionization profile corrected for detector size and absorbed dose profile were not equal, probably due to loss of charged-particle equilibrium in the beam edges. For ionization chamber measurements, knowledge of the charged-particle spectrum is needed to convert ionization to absorbed dose to water. This is not necessary for relative absorbed dose measurements under charged-particle equilibrium. Film has been shown to be a straightforward and reliable method for cross beam profile measurements.

Influence of hip prostheses on high energy photon dose distributions.

Radiotherapy treatment of patients having a hip prosthesis is a common problem facing dosimetrists and physicists when the treatment plan requires irradiation of the pelvic area. To quantify the perturbation of these devices, attenuation studies were done with 6 and 18 MV photon beams using various hip prostheses models with varying size and composition. These studies have shown that an attenuation of as much as 50% can be found in a single beam profile under the prosthesis. We have studied the capability of a dose planning system to predict the transmission of these devices as compared with measurements.

[Body height of Portuguese school children. Evolution in the last half century]. / Estatura de Portugueses de idade escolar. Evolução no último meio século.

The height values of 122 boys and 124 girls, 7 to 11 years old, from 19 primary schools of the central area of Portugal were evaluated in 1988. The values from boys of all ages and girls younger than 9 years were normally spread, according to american (NCHS-USA 1976) standards. Girls older than 9 years were relatively shorter which could be related to the late puberty of these country girls. These figures are about 4 cm higher than those collected from portuguese school children born in 1964.