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Cytotoxicity of the bioreductive agent RH1 and its lack of interaction with radiation.

BACKGROUND AND PURPOSE: RH1 is a new bioreductive agent that was developed as a cytotoxic agent with selectivity for tumour cells expressing high levels of the enzyme DT-diaphorase (DTD). The aim of the present study was to investigate the cytotoxicity of RH1 in relation to cellular levels of reducing enzymes and any interaction of RH1 with ionizing radiation under oxic and hypoxic conditions. PATIENTS AND METHODS: The MB-MDA231 human breast cancer cell line (WT) and WT cells transfected with the NQO1 gene encoding DTD (the D7 cell line) were used to examine the dependency of RH1's cytotoxicity on cellular DTD activity. The role of the 1-electron reducing enzyme P450 reductase was also studied using a P450 reductase-transfected isogenic cell line (R4). A clonogenic assay was used to investigate the cytotoxicity of RH1 with and without irradiation in air and in nitrogen. In all cases drug exposure was for 3 h. RESULTS: DTD levels were around 300-fold higher in D7 compared to WT and R4 cells. RH1 was cytotoxic at nanomolar concentrations to all the cell lines, and was 2-3 times more toxic in the D7 cells with high DTD than in the other two cell lines. Doses of RH1 was around 2-fold more effective in hypoxic than in oxic WT cells, but not by as much in D7 cells. RH1 did not radiosensitise the cells but showed an additive effect when combined with irradiation under oxic and hypoxic conditions. CONCLUSIONS: RH1 shows high clonogenic cytotoxicity to MDA231 cells with high DTD activity but its selectivity based on the presence of DTD is much less than as shown in previous reports. RH1 showed an additive cell killing effect when combined with irradiation under both oxic and hypoxic conditions.

Antineoplastic Agents↗

Prostate-specific antigen (PSA) in the monitoring of prostate cancer after radical prostatectomy and external beam radiation.

BACKGROUND: During the last few years, prostate-specific antigen (PSA) has been established as the most important tumor marker for prostate cancer. The aim of our study was to evaluate the response of PSA after surgery and radiotherapy of prostate cancer. PATIENTS AND METHODS: From 1/1995 to 9/1997, 32 patients were treated by radical prostatectomy and subsequent radiotherapy. Radiation therapy was carried out using a linear accelerator to the prostate bed, a total dose of 60 Gy was given. PSA values were measured immediately before irradiation, weekly during radiation therapy and every three months thereafter in the usual follow-up pattern. RESULTS: 21 of 32 patients had no measurable PSA after surgery. In the remaining 11 patients the median PSA half-life was reached 3 months after irradiation, the nadir after 15 months. 5 patients with increasing PSA levels suffered from a relapse (15.6%). CONCLUSIONS: We found that PSA monitoring is a useful marker for treatment outcome and that adjuvant radiotherapy after surgery improves local control as well as biochemical failure rate. If PSA is still detectable after surgery the risk for biochemical failure is significantly higher (45.5%).

Aged↗

Video display terminals: risk of electromagnetic radiation.

BACKGROUND: Technologic advances have led to increased use of computers at home and in the workplace. It is estimated that more than 100 million workers in the United States and Canada will be using computers daily by the year 2000. Anecdotal reports have suggested a link between video display terminals (VDTs) and disease. This has generated much concern about whether electromagnetic radiation (EMR) emitted by VDTs cause illness among users. METHODS: We reviewed pertinent articles in the literature. RESULTS: Several studies have addressed the role of VDTs in disease causation, specifically whether EMR causes skin or ocular disease or obstetric complications. The data reviewed were inconsistent or methodically flawed. Therefore, a definitive conclusion cannot be drawn to support the hypothesis that EMR produced by VDTs causes disease. CONCLUSIONS: We believe continued research should be done to further define and elucidate the risk of EMR produced by VDTs.

Computer Terminals↗

Safety studies of topical imiquimod 5% cream on normal skin exposed to ultraviolet radiation.

BACKGROUND: Imiquimod 5% topical cream is an immune response modifier that induces interferon alpha and interleukin-12, and exhibits antiviral and tumor-inhibiting properties. It is currently available for treatment of genital and perianal warts. Three randomized, open-label or assessor-blinded, placebo-controlled studies were carried out to assess its safety on normal white skin exposed to ultraviolet radiation (UVR). METHODS: Healthy white volunteer adult subjects between the ages of 18 and 60 years with skin types I, II or III (Fitzpatrick Scale, US Federal Register 43:38260, 1978) were invited to participate. Imiquimod 5% cream (each dose approximately 0.1-0.2 ml) was compared with placebo cream. Two preliminary studies assessed the potential photosensitizing properties of the drug, and the third study added measurement of sunburn cell counts (SBC) and deoxyribonucleic acid (DNA) pyrimidine dimer (PD) formation. The three studies were: a 6-week standard photocontact allergenicity bioassay; a 4-day standard phototoxicity bioassay; and a 4-week photodamage study using biopsy sample analyses to determine SBC or PD frequency. RESULTS: Imiquimod had no detectable potential for inducing either photocontact allergy (n=115) or phototoxicity (n=20). The final study further assessing photodamage potential of imiquimod included 44 subjects. There were no significant differences between imiquimod vs. the control (no drug+UVB) for SBC counts (mean 0.88 vs. 0.93), or PD frequency (mean 60.86 vs. 70.03). CONCLUSIONS: Results from the two preliminary safety studies suggest that imiquimod 5% cream does not possess a detectable photosensitizing potential in humans. Furthermore, topical imiquimod did not enhance UVR-induced damage to epidermal cells or DNA.

Administration, Topical↗

Visualization of penetrating transmural arteries in situ by monochromatic synchrotron radiation.

BACKGROUND: Penetrating transmural arteries with a diameter of < 500 microns are considered to be a critical vascular component that causes a transmural variation of myocardial blood flow under various pathophysiological conditions. However, the conventional coronary angiographic system is not oriented to the visualization of such small arteries as these. METHODS AND RESULTS: We magnified and monochromatized the inherently narrow beam (3 mm along the vertical direction) of synchrotron radiation by using an asymmetrically cut silicon crystal with 311 reflecting planes to obtain a monochromatic x-ray with relatively large beam size (60 x 25 mm) and with an energy of just above (+130 eV) the K-absorption edge of the contrast materials (33.17 and 37.41 ke V for iodine and barium, respectively). We irradiated dogs or excised hearts with the monochromatic x-ray and obtained coronary angiograms using an image intensifier and video system with a spatial resolution of 170 microns. In the anesthetized dog experiments, we visualized the transmural penetrating arteries (5 to 15 mm in length) arising every 4 to 7 mm from the epicardial branch. Visualization of these arteries filled with heavy element-loaded microspheres (15 microns in diameter) in the excised-heart experiments, in which the monochromatic x-ray was irradiated to the hearts through a 10- to 20-cm acrylic plate, indicated that this system could be used for human patients, in whom body absorption of x-ray is substantial. CONCLUSIONS: Coronary angiogram by means of monochromatic x-ray is useful for a precise evaluation of coronary circulation, both in clinical setting and in physiological animal experiments.

Animals↗

Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation.

BACKGROUND: Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men. The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer. METHODS: Because the major source of vitamin D is casual exposure to ultraviolet (UV) radiation, the authors examined the geographic distributions of UV radiation and prostate cancer mortality in 3073 counties of the contiguous United States using linear regression and trend surface analyses. RESULTS: The geographic distributions of UV radiation and prostate cancer mortality are correlated inversely (P < 0.0001). Prostate cancer mortality exhibits a significant north-south trend, with lower rates in the South. These geographic patterns are not readily explicable by other known risk factors for prostate cancer. CONCLUSIONS: These data lend support to the hypothesis that UV radiation may protect against clinical prostate cancer. Viewed in conjunction with other recent data, including those demonstrating a differentiating effect of vitamin D on human prostate cancer cells, these findings suggest that vitamin D may have an important role in the natural history of prostate cancer.

Dose-Response Relationship, Radiation↗

Soluble levels of CD-95, CD 95-L and various cytokines after exposing human leukocytes to ionizing radiation.

BACKGROUND: Local radiotherapy induces systemic effects and influences the immune system. Some of these effects can hardly be explained by direct cellular reactions, but might be triggered by humoral factors. MATERIALS AND METHODS: In seminoma patients we measured the influence of radiotherapy on various lymphocyte subsets by FACS-analysis. We analysed the release of cytokines, CD95 (Apo-1/Fas) and CD 95-L (Fas-Ligand) of human blood cells after exposure to ionizing radiation in vitro and in vivo by ELISA-technique. RESULTS: Although radiation leads to a differential and sustained reduction of all lymphocytes subsets in vivo no increase of cytokine levels, or of levels of CD95 or CD 95-L could be detected by ELISA in vivo or in vitro. On the contrary mitogen-induced cytokine production in vitro was inhibited by radiation. CONCLUSIONS: Local radiation induced a significant systemic decrease of all lymphocyte subsets, but neither a systemic release of cell death mediators like CD95 or various cytokines, nor a release in the extracellular space in vitro were detectable.

Adult↗

Estimation of radiation dose received during treatment of in-stent restenosis using ionizing radiation.

BACKGROUND: Angioplasty is a widely accepted procedure for the treatment of coronary artery disease. However, restenosis of the treated vessel occurs in 30% of patients within 6 months. Intravascular brachytherapy (IVB) is used to inhibit the formation of new tissue growth at the vessel treatment site. IVB protocols using either gamma ray or beta particle emitting isotopes have been tested and approved. However, very little data are available on resultant whole-body dose and the potential for long-term radiation effects. METHODS: Using thermoluminescence dosimetry (TLD) devices, specifically lithium fluoride (LiF) doped with Mg, Cu, and P, the radiation dose on the surface of patients undergoing IVB was measured. The TLDs were positioned on the body to obtain a measure of the gamma dose at selected anatomic locations. Additionally, the skin dose from fluoroscopy was estimated. RESULTS: Measurements indicate that the average body dose on the skin surface from all TLDs, clinical requirements, and gamma source configurations varies from 0.95 mSv (95 mrem) at the head to 27.06 mSv (2706 mrem) at the sternal notch. For beta sources, the dose varied from 0.11 mSv (11.4 mrem) at the head to 0.49 mSv (49.5 mrem) at the sternal notch. The fluoroscopy contribution of dose to the body dose (15-min exposure time) was 0.10 mSv (10 mrem) at the head and 2.57 mSv (257 mrem) to the sternal notch. CONCLUSIONS: The results suggest that surface skin exposures from gamma sources used in IVB pose acceptable risks considering the medical benefits of the procedures.

Brachytherapy↗

Storage of apheresis platelets after gamma radiation.

BACKGROUND: There are conflicting data on the effect of irradiation and subsequent storage on the quality of platelet components. STUDY DESIGN AND METHODS: The retention of platelet properties during storage of gamma-irradiated apheresis suspensions was studied in 22 apheresis components obtained on a cell separator with a specialized centrifugation chamber. Immediately after collection, each suspension was divided equally into two 1-L polyolefin containers. On Day 1 (n = 12) and Day 3 (n = 10) one of each pair of suspension containers was gamma radiated with 2500 cGy. All platelet suspensions were stored for 5 days at 20 to 24 degrees C. Samples were drawn on Day 5 from each of the 22 pairs of containers for evaluation of an array of in vitro properties. Samples were taken from 10 pairs of containers for platelet labeling with either 51Cr or 111In for subsequent transfusion and concurrent in vivo measurement of recovery and survival. Posttransfusion samples were drawn after 24 hours for ex vivo whole blood aggregation. RESULTS: Comparable in vitro and in vivo properties were measured in irradiated and control platelets, whether irradiation was performed on Day 1 or Day 3. The mean +/- 1 SD in vivo recovery and survival time for controls and platelets irradiated on Day 1 was 52 +/- 14 percent and 146 +/- 34 hours and 51 +/- 7 percent and 147 +/- 36 hours, respectively. For Day 3 irradiation, the values were 46 +/- 12 percent and 150 +/- 60 hours and 47 +/- 9 percent and 151 +/- 53 hours, respectively. A small, but measurable adverse effect of irradiation on ex vivo platelet aggregation was present. CONCLUSION: These data indicate that storage of apheresis platelets after gamma radiation is without clinically significant, demonstrably adverse effects on platelet quality.

Blood Platelets↗

Generation of interleukin 8 in stored apheresis platelet concentrates and the preventive effect of prestorage ultraviolet B radiation.

BACKGROUND: Several recent studies have reported both the generation of cytokines, including interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and IL-8, in the supernatants of stored platelet concentrates (PCs) and the implications of this generation in febrile nonhemolytic transfusion reactions. Prestorage filtration is regarded as highly effective in the prevention of cytokine generation. STUDY DESIGN AND METHODS: Studies evaluated 1) the levels of these cytokines in apheresis PCs during storage, 2) the effects of white cell inactivation by ultraviolet B or gamma-radiation on the generation of cytokines, and 3) the effects of poststorage filtration on cytokine levels. The apheresis PCs were treated by either ultraviolet B radiation (20,000 J/m2), gamma-radiation (30 Gy), or filtration. Samples were collected sequentially on various days after storage. Cytokines were determined by enzyme-linked immunosorbent assay. RESULTS: The average white cell count in 15 PCs tested was 2.58 +/- 0.7 x 10(6) per mL (range, 0.7-10 x 10(6)/mL). A detectable level of IL-8 was found at 3 days of storage, and the levels of this cytokine increased progressively with increasing storage time, ranging from 1.6 to 35,280 pg per mL on Day 5 and from 2.7 to 83,601 pg per mL on Day 8. Reverse transcriptase-polymerase chain reaction analysis showed that the level of IL-8 paralleled the expression of IL-8 transcripts. The levels of IL-1 beta, IL-6, TNF-alpha, and monocyte chemotactic protein-1 were very low, even on Day 8. Ultraviolet B-radiated PCs failed to generate IL-8, even at 8 days of storage, whereas levels of IL-8 in gamma-radiated PCs were similar to those in nonirradiated PCs. Poststorage filtration of PCs with a negatively charged polyester filter, but not with a positively charged one, markedly reduced the levels of IL-8. CONCLUSION: Of the cytokines tested, IL-8 had the most evident generation in apheresis PCs during storage. Prestorage inactivation of white cells by ultraviolet B radiation, but not by gamma-radiation, was effective in preventing the generation of cytokines during the storage of PCs.

Anaphylatoxins↗

The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation.

BACKGROUND: If cancer arises and is maintained by a small population of cancer-initiating cells within every tumor, understanding how these cells react to cancer treatment will facilitate improvement of cancer treatment in the future. Cancer-initiating cells can now be prospectively isolated from breast cancer cell lines and tumor samples and propagated as mammospheres in vitro under serum-free conditions. METHODS: CD24(-/low)/CD44+ cancer-initiating cells were isolated from MCF-7 and MDA-MB-231 breast cancer monolayer cultures and propagated as mammospheres. Their response to radiation was investigated by assaying clonogenic survival and by measuring reactive oxygen species (ROS) levels, phosphorylation of the replacement histone H2AX, CD44 levels, CD24 levels, and Notch-1 activation using flow cytometry. All statistical tests were two-sided. RESULTS: Cancer-initiating cells were more resistant to radiation than cells grown as monolayer cultures (MCF-7: monolayer cultures, mean surviving fraction at 2 Gy [SF(2Gy)] = 0.2, versus mammospheres, mean SF(2Gy) = 0.46, difference = 0.26, 95% confidence interval [CI] = 0.05 to 0.47; P = .026; MDA-MB-231: monolayer cultures, mean SF(2Gy) = 0.5, versus mammospheres, mean SF(2Gy) = 0.69, difference = 0.19, 95% CI = -0.07 to 0.45; P = .09). Levels of ROS increased in both mammospheres and monolayer cultures after irradiation with a single dose of 10 Gy but were lower in mammospheres than in monolayer cultures (MCF-7 monolayer cultures: 0 Gy, mean = 1.0, versus 10 Gy, mean = 3.32, difference = 2.32, 95% CI = 0.67 to 3.98; P = .026; mammospheres: 0 Gy, mean = 0.58, versus 10 Gy, mean = 1.46, difference = 0.88, 95% CI = 0.20 to 1.56; P = .031); phosphorylation of H2AX increased in irradiated monolayer cultures, but no change was observed in mammospheres. Fractionated doses of irradiation increased activation of Notch-1 (untreated, mean = 10.7, versus treated, mean = 15.1, difference = 4.4, 95% CI = 2.7 to 6.1, P = .002) and the percentage of the cancer stem/initiating cells in the nonadherent cell population of MCF-7 monolayer cultures (untreated, mean = 3.52%, versus treated, mean = 7.5%, difference = 3.98%, 95% CI = 1.67% to 6.25%, P = .009). CONCLUSIONS: Breast cancer-initiating cells are a relatively radioresistant subpopulation of breast cancer cells and increase in numbers after short courses of fractionated irradiation. These findings offer a possible mechanism for the accelerated repopulation of tumor cells observed during gaps in radiotherapy.

Biomarkers, Tumor↗

Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

BACKGROUND: One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. RESULTS: Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. CONCLUSION: Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

DNA Damage↗

Systematic errors in the measurement of emissivity caused by directional effects.

Accurate knowledge of surface emissivity is essential for applications in remote sensing (remote temperature measurement), radiative transport, and modeling of environmental energy balances. Direct measurements of surface emissivity are difficult when there is considerable background radiation at the same wavelength as the emitted radiation. This occurs, for example, when objects at temperatures near room temperature are measured in a terrestrial environment by use ofthe infrared 8-14-microm band.This problem is usually treated by assumption of a perfectly diffuse surface or of diffuse background radiation. However, real surfaces and actual background radiation are not diffuse; therefore there will be a systematic measurement error. It is demonstrated that, in some cases, the deviations from a diffuse behavior lead to large errors in the measured emissivity. Past measurements made with simplifying assumptions should therefore be reevaluated and corrected. Recommendations are presented for improving experimental procedures in emissivity measurement.

Journal Article↗

A comparative study of the long term psychosocial functioning of childhood acute lymphoblastic leukemia survivors treated by intrathecal methotrexate with or without cranial radiation.

BACKGROUND: Although previous research has delineated medical, cognitive, and neuropsychologic late effects of central nervous system (CNS) prophylaxis for childhood acute lymphoblastic leukemia (ALL), it has been difficult to draw conclusions about the long term psychosocial sequelae of these treatments due to methodologic problems that led to inconclusive results in past studies. In the current study, the authors examined the long term psychosocial functioning of childhood ALL survivors who had been treated on a Phase III clinical protocol (Cancer and Leukemia Group B [CALGB] 7611) between 1976 and 1979, in which they were randomized to receive either 2400 centigray of cranial radiation (CRT) with intrathecal methotrexate (IT-MTX) or intermediate dose systemic methotrexate (IV-MTX) with IT-MTX. METHODS: One hundred ten survivors of childhood ALL (mean age, 20.8 years) treated on CALGB 7611 who were age 14 years or older and disease free for at least 1 year were studied a mean of 14.7 years after their entry on CALGB 7611. In a telephone interview, a psychosocial assessment battery was administered to the patients, consisting of measures that assessed psychologic, sexual, social, and vocational functioning as well as any delayed physical effects. RESULTS: Survivors who had received CRT + IT-MTX had significantly poorer academic achievement (P = 0.0001), poorer self-images with regard to their bodies (P = 0.001), and greater psychologic distress (P = 0.005). CONCLUSIONS: Cranial radiation used to treat children with ALL has significant long term sequelae in terms of poorer academic achievement and psychosocial functioning. These data add weight to the conclusion that CRT prophylaxis should only be used to treat children who are at high risk of CNS relapse.

Achievement↗

Modern therapy of chronic wounds with respect to radiation.

BACKGROUND: Descriptions of wound care techniques have been found in some of the oldest archeological findings and chronic wounds have been threaded man thousands of years. However, only in the last few decades substantial progress has been made in understanding the cellular and biochemical processes relevant in normal healing. PATHOPHYSIOLOGY: Wound healing is a complex process involving a variety of different cells, proteins, chemoattractants, proteinases and growth factors. The normal repair process is a coordinated cellular and biochemical event and can be characterized by 3 different healing phases (inflammatory, proliferative, and remodeling phase). Certain pathophysiologic conditions and metabolic disorders alter this preprogrammed course, leading to delayed healing or chronic non-healing wounds. DISTURBANCE OF WOUND HEALING AFTER RADIATION: Especially irradiation can complicate tissue repair and surgical wound healing. Therefore this article will review the basic understanding of the wound healing process and the knowledge of modern surgical and conservative wound therapy from a surgical point of view, which is essential to surpass pathophysiological situations and avoid chronic wounds.

Chronic Disease↗

Endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy without the use of radiation.

BACKGROUND: Biliary disease in pregnancy is a relatively uncommon condition; the diagnosis of this condition is not standardized. Furthermore, the use of radiographic imaging studies and therapeutic approaches in pregnancy is limited because of the possibility of fetal exposure. STUDY DESIGN: During a 2-year interval of 2001 to 2002, we successfully performed endoscopic retrograde cholangiopancreatography (ERCP) studies in 6 pregnant women between 6 and 30 weeks of gestation with symptomatic acute cholangitis or pancreatitis without irradiation exposure or major maternal complications. Five of the women had classic symptoms of severe right upper quadrant abdominal pain, gallbladder stones, jaundice, and dilated bile ducts on ultrasonic evaluation. One woman had severe recurrent pancreatitis during early pregnancy 4 years after a cholecystectomy. The cases are compiled to provide a descriptive review of ERCP without the use of radiation imaging treatment for these conditions. RESULTS: Maternal outcome: After ERCP, jaundice resolved in all cases. No further episodes of pancreatitis occurred during the 1 affected pregnancy. No post-ERCP complications occurred during this series. Two patients required cholecystectomy later, one in the postpartum period and the other 5 weeks post-ERCP. Fetal outcome: Two infants were born at term without complications. Two infants were born prematurely at 35 weeks, 1 with significant growth retardation and pulmonary complications and 1 without developmental problems or complications. Two mothers were lost to follow-up; the outcomes of their pregnancies are unknown. CONCLUSION: The use of ERCP in pregnancy is limited because of the undesirable effects of radiation exposure to the fetus.

Adult↗

Early detection of Richter's transformation: stable disease with dose-reduced gemcitabine and local radiation.

BACKGROUND: The occurrence of Hodgkin's lymphoma (HL) as a second aggressive lymphoid malignancy (known as Hodgkin's disease variant of Richter's transformation) is rarely observed. Response rates, even with highly aggressive therapy such as stem cell transplantation, are limited, ranging from 4 to 43%, and the medium survival time ranges from 5 to 8 months. CASE REPORT: A 72-year-old patient with a history of chronic lymphatic leukemia (CLL) was admitted with thoracic back pain and assumed progression of the CLL. The patient showed no fever, night sweats or weight loss. A computed tomography (CT) scan confirmed the progression of axillary and cervical lymph nodes. In addition, an intraspinal infiltration at the 8th thoracic vertebra (Th8) was detected. Surprisingly, histology of an extirpated lymph node demonstrated the existence of 2 tumors in the same lymph node. Infiltrates of small lymphocytes representing the pre-existing CLL (CD5-, CD20-, CD23-positive) coexisted with Reed-Sternberg Hodgkin's cells (CD30-, CD15-positive). Chemotherapy was started, combined with palliative radiation of vertebrae Th7-Th10. 12 months after diagnosis of Richter's transformation the patient is still alive without any progression of the underlying disease. CONCLUSION: We present a unique case of a Hodgkin's disease variant of Richter's transformation and CLL in the same lymph node, which was detected early because of spinal infiltration and was subsequently stabilized with reduced-dosage gemcitabine and local radiation. Additionally, we show unique pictures of 2 tumors coexisting in the same lymph node.

Aged↗

Photokeratitis from subablative 193-nanometer excimer laser radiation.

BACKGROUND: Photokeratitis is a side effect of UV light exposure whereby the corneal epithelium is photochemically injured in a time delayed fashion. UV light exposure in the far ultraviolet wavelength range has not previously been observed. This study addresses the concern of photokeratitis from subablative 193-nanometer excimer laser light. METHODS: Dutch belted rabbit corneas were irradiated with subablative 193-nanometer excimer laser light over a wide range of total energy exposures, and examined by slit lamp biomicroscope for signs of photokeratitis. Photokeratitis was identified by epithelial haze and stippling, and rose bengal and fluorescein staining at varied time intervals between 1/2 to 26 hours post exposure. RESULTS: At threshold energy exposures of 1.0 to 1.5 J/cm2, an immediate superficial epithelial haze was seen which disappeared within several hours. At higher energy exposures of 10 J/cm2, a delayed photokeratitis with deep rose bengal and even fluorescein staining was seen. This latter delayed photokeratitis resembles that of longer UV wavelengths and is due to excimer laser fluorescence, whereas the former is a direct response of the 193-nanometer light. The percentage of excimer laser light undergoing fluorescence is calculated as less than 1%. CONCLUSIONS: The potential side effects and hazards of scattered 193-nanometer radiation during excimer laser surgery are extremely limited because of the shorter penetration depth of direct excimer radiation and the minimal fluorescent emission of longer UV wavelengths for energy exposures within the realm of clinical use.

Animals↗