Intensity-modulated radiation therapy (IMRT) for meningioma

To assess the safety and efficacy of intensity-modulated radiation therapy (IMRT) in the treatment of intracranial meningioma.

Forty patients with intracranial meningioma (excluding optic nerve sheath meningiomas) were treated using IMRT with the NOMOS Peacock system between 1994 and 1999. Twenty-five patients received IMRT after surgery either as adjuvant therapy for incomplete resection or for recurrence, and 15 patients received definitive IMRT after presumptive diagnosis based on imaging. Thirty-two patients had skull base lesions, and 8 had nonskull base lesions. The prescribed dose ranged from 40 to 56 Gy (median 50.4 Gy) at 1.71 to 2 Gy per fraction, and the volume of the primary target ranged from 1.55 to 324.57 cc (median 20.22 cc). The mean dose to the target ranged from 44 to 60 Gy (median 53 Gy). Follow-up ranged from 6 to 71 months (median 30 months). Acute and chronic toxicity were assessed using Radiation Therapy Oncology Group (RTOG) morbidity criteria and tumor response was assessed by patient report, examination, and imaging. Overall survival, progression-free survival, and local control were calculated using the Kaplan-Meier method.

Cumulative 5-year local control, progression-free survival, and overall survival were 93%, 88%, and 89%, respectively. Two patients progressed after IMRT, one locally and one distantly. Each was treated with IMRT after multiple recurrences of benign meningioma over many years. Both were found to have malignant meningioma at the time of relapse after IMRT, and it is likely their tumors had already undergone malignant change by the time IMRT was given. Defined normal structures generally received a significantly lower dose than the target. The most common acute central nervous system (CNS) toxicity was mild headache, usually relieved with steroids. One patient experienced RTOG Grade 3 acute CNS toxicity, and 2 experienced Grade 3 or higher late CNS toxicity, with one possible treatment-related death. No toxicity was observed with mean doses to the optic nerve/chiasm up to 47 Gy and maximum doses up to 55 Gy.

IMRT is a promising new technology that is safe and efficacious in the primary and adjuvant treatment of intracranial meningiomas. A history of local aggression may indicate malignant degeneration and predict a poorer outcome. Toxicity data are encouraging, but the potential for serious side effects exists, as demonstrated by one possible treatment-related death. Larger cohort and longer follow-up are needed to better define efficacy and late toxicity of IMRT.     

Neurite outgrowth can be modulated in vitro using a tetracycline-repressible gene therapy vector expressing human nerve growth factor

The delivery of neurotrophic factors to the adult nervous system has potential applications for the treatment of neurodegenerative diseases and trauma. In vivo and ex vivo gene therapy offer a means of delivering growth factors and other therapeutic substances to the central nervous system (CNS) in an intraparenchymal, accurately targeted, and regionally restricted manner. Ideally, gene therapy delivery systems should also be regulatable, allowing exogenous control of amount of gene product delivery. In the present experiment, a tetracycline-regulatable gene expression system was generated to determine whether controllable release of nerve growth factor (NGF) and green fluorescent protein (GFP) from primary rat fibroblasts could modulate biological responses (neurite outgrowth) in vitro. Using a tetracycline-repressible construct, it was found that NGF mRNA, NGF protein, and NGF-induced neurite outgrowth could be tightly regulated within a 24 hour period, and in a dose-dependent fashion, by exposure to the tetracycline analog doxycycline. Similarly, levels of green fluorescence could be regulated in GFP-transfected cells. These findings in a neurobiological system lay the framework for future studies using regulated neurotrophin delivery in in vivo models of neurodegenerative diseases and CNS injury.     

Clinical and molecular biologic characteristics of early-onset versus late-onset colorectal carcinoma in Filipinos

A case-control study of Filipino patients who underwent surgical resection for colorectal cancer (CRC) during a 1-year period was undertaken. Thirty-five patients under age 40 years were identified. Paraffin blocks of these and 35 randomly selected patients over age 40 underwent histologic and immunohistochemical evaluation. Markers chosen for evaluation included the apoptosis-associated gene products (p53 and bcl-2), a tumor proliferation activity-related factor (Ki-67), and the markers (MLH1 and MSH2) of DNA microsatellite instability (MSI). Results were correlated with age and the stage and location of the tumor. The average age of the early-onset group was 30.7 years compared to the late-onset group at 67.0 years; and the male/female ratio was equivalent. The younger patients had a significantly higher Dukes stage, the tumors were more poorly differentiated, and they were more frequently of the mucinous and signet ring cell histopathologic type. Expression of p53 was higher in the younger patients (p < 0.001) and was independent of the degree of differentiation or the stage of the tumor. No differences of expression were noted for the other markers measured. The increased frequency of CRC in Filipino patients less than 40 years of age offers a unique opportunity to gain a better understanding of carcinogenesis, which might be exploited during diagnosis and management. The differences noted between the early- and late-onset CRC are provocative and provide an impetus for increased screening in Filipinos.     

Performance of the neonatal pig heart subjected to oxygen insufficiency

Isolated, paced, isovolumically beating, neonatal pig (n = 32) hearts underwent retrograde aortic perfusion with a solution containing insulin (100 microU/ml), glucose (5.5 mM), and palmitate (0.55 mM). Glycolysis, lactate release, glucose oxidation, palmitate oxidation, and oxygen consumption were assessed. The hearts were perfused during three periods: (1) baseline, pO(2) approximately 500 mm Hg, heart rate 150 bpm; (2) hypoxia, pO(2) approximately 60-80 mm Hg, heart rate 150 bpm, or tachycardia, pO(2) approximately 500 mm Hg, heart rate 300 bpm, and (3) recovery, return to baseline conditions. For hypoxia and tachycardia, the oxygen supply-demand ratio was comparable ( approximately 1 nmol O(2)/mm Hg/g(dry)). During baseline, the left ventricular peak systolic pressure (PSP) averaged 126 +/- 6 mm Hg, the end-diastolic pressure (EDP) 5 mm Hg, and the relaxation time constant (Tau) 34 +/- 2 ms; the coronary flow was 36 +/- 2 ml/min/g(dry). During hypoxia, the PSP decreased to 70 +/- 2 mm Hg, while EDP, Tau, and coronary flow increased to 26 +/- 2 mm Hg, 104 +/- 14 ms, and 70 +/- 2 ml/min/g(dry), respectively; palmitate oxidation and oxygen consumption decreased well below baseline. During tachycardia, the PSP decreased to 88 +/- 1 mm Hg, and the EDP increased to 11 +/- 1 mm Hg, while Tau and coronary flow did not change significantly; palmitate oxidation and oxygen consumption increased above baseline. For both stressors, the predicted lactate release underestimated the measured values by a factor of approximately 2, but were comparable during baseline and recovery. Upon recovery, PSP returned to approximately 80% of baseline, while EDP remained elevated, for both stressors. Glucose oxidation returned to baseline, but palmitate oxidation became accelerated. We conclude for neonatal pig hearts subjected to oxygen insufficiency: (1) that PSP decreases and (2) that EDP and Tau increase with hypoxia, whereas EDP increases, while Tau remains unchanged with tachycardia. Following both stressors, palmitate oxidation becomes enhanced and dissociated from mechanical activity.     

Urinary 8-hydroxy-2'-deoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to fine particulates

Residual oil fly ash (ROFA) is a chemically complex mixture of compounds, including metals that are potentially carcinogenic because of their ability to cause oxidative injury. In this study, we investigated the association between exposure to particulate matter with an aerodynamic mass median diameter 相似文献   

Inhalation and dermal exposure among asphalt paving workers

The primary objective of this study was to identify determinants of inhalation and dermal exposure to polycyclic aromatic compounds (PACs) among asphalt paving workers. The study population included three groups of highway construction workers: 20 asphalt paving workers, as well as 12 millers and 6 roadside construction workers who did not work with hot-mix asphalt. During multiple consecutive work shifts, personal air samples were collected from each worker's breathing zone using a Teflon filter and cassette holder connected in series with an XAD-2 sorbent tube, while dermal patch samples were collected from the underside of each worker's wrist. All exposure samples were analyzed for PACs, pyrene and benzo[a]pyrene. Inhalation and dermal PAC exposures were highest among asphalt paving workers. Among paving workers, inhalation and dermal PAC exposures varied significantly by task, crew, recycled asphalt product (RAP) and work rate (inhalation only). Asphalt mix containing high RAP was associated with a 5-fold increase in inhalation PAC exposures and a 2-fold increase in dermal PAC exposure, compared with low RAP mix. The inhalation PAC exposures were consistent with the workers' proximity to the primary source of asphalt fume (paver operators > screedmen > rakers > roller operators), such that the adjusted mean exposures among paver operators (5.0 microg/m3, low RAP; 24 microg/m3, high RAP) were 12 times higher than among roller operators (0.4 microg/m3, low RAP; 2.0 microg/m3, high RAP). The dermal PAC exposures were consistent with the degree to which the workers have actual contact with asphalt-contaminated surfaces (rakers > screedmen > paver operators > roller operators), such that the adjusted mean exposures among rakers (175 ng/cm2, low RAP; 417 ng/cm2, high RAP) were approximately 6 times higher than among roller operators (27 ng/cm2, low RAP; 65 ng/cm2, high RAP). Paving task, RAP content and crew were also found to be significant determinants of inhalation and dermal exposure to pyrene. The effect of RAP content, as well as the fact that exposures were higher among paving workers than among millers and roadside construction workers, suggests that the PAC and pyrene exposures experienced by these paving workers were asphalt-related.     

Clinical diagnosis and assessment of severity of confirmed dengue infections in Vietnamese children: is the world health organization classification system helpful?

Classification of dengue using the current World Health Organization (WHO) system is not straightforward. In a large prospective study of pediatric dengue, no clinical or basic laboratory parameters clearly differentiated between children with and without dengue, although petechiae and hepatomegaly were independently associated with the diagnosis. Among the 712 dengue-infected children there was considerable overlap in the major clinical features. Mucosal bleeding was observed with equal frequency in those with dengue fever and dengue hemorrhagic fever (DHF), and petechiae, thrombocytopenia, and the tourniquet test differentiated poorly between the two diagnostic categories. Fifty-seven (18%) of 310 with shock did not fulfill all four criteria considered necessary for a diagnosis of DHF by the WHO, but use of the WHO provisional classification scheme resulted in considerable over-inflation of the DHF figures. If two separate entities truly exist rather than a continuous spectrum of disease, it is essential that some measure of capillary leak is included in any classification system, with less emphasis on bleeding and a specific platelet count.     

Detection and false-positive rates of maternal serum markers for Down syndrome screening according to maternal age in women over 35 years of age. A study of the agreement of eight dedicated software packages

Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women > or =35 years in an attempt to reduce the need for invasive procedures and thereby avoid their side effects. Our objective was to compare, in women > or =35, eight different software packages dedicated to second trimester MSS, thus providing reliable data for patient counselling. A simulation study was carried out on 189 sera from women with Down syndrome fetuses and 11 962 sera from mothers of unaffected babies. The first step was to estimate the joint distribution of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG). The second step was to calculate trisomy 21 detection and false-positive rates for each software according to maternal age (35-45 years), using the usual 1:250 risk threshold. Agreement between software packages was measured using 2 x 2 kappa coefficients. Detection rates and false-positive rates increased with maternal age. Depending on the software, 57-71% detection rates were achieved at 35 years with 12-18% false-positive rates. At 45 years, 61-100% detection rates were achieved with 66-95% false-positive rates. Up to 39 years, all softwares were concordant (kappa coefficients >0.75). In the range 35-45 years, false-positive and detection rates increased substantially with maternal age and differences between software packages are observed.