Pesticide Sales in Low-Income, Minority Neighborhoods

The US EPA has phased-out residential use of two organophosphate pesticides commonly used to control cockroaches-retail sales of chlorpyrifos were scheduled to end on 12/31/01, and diazinon on 12/31/02. In light of recent findings highlighting the associations between pests, pesticides and health, we surveyed stores in low-income, minority neighborhoods in New York City to determine whether the phase-outs have been effective and to assess the availability of alternatives to spray pesticides. In summer 2002, when sales of chlorpyrifos were illegal and diazinon still legal, we surveyed 106 stores selling pesticides. Four percent sold products containing chlorpyrifos and 40 percent sold products containing diazinon. One year later, when sales of both pesticides were to have ended, we surveyed 109 stores selling pesticides in the same neighborhoods and found chlorpyrifos in only one store and diazinon in 18 percent of stores, including 80 percent of supermarkets surveyed. At least one form of lower toxicity pesticides, including gels, bait stations and boric acid was available in 69 percent of stores in 2002. However sprays were most widely available, found in 94 percent of stores in 2002 and less expensive than lower toxicity baits and gels. In a separate survey of storekeeper recommendations conducted in 2002, storekeepers recommended lower toxicity pesticides as the best way to control cockroaches 79% of the time. The EPA's phase-outs have nearly eliminated sales of chlorpyrifos, but the diazinon phase-out appears to be less effective.     

Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters

Several of the ATP-binding cassette (ABC) transporters confer resistance to anticancer agents and/or antiviral agents when overexpressed in drug-sensitive cells. Recently a MRP1 (ABCC1) tricyclic isoxazole inhibitor, LY475776 was shown to be a glutathione-dependent photoaffinity label of human MRP1 and showed poor labeling of murine mrp1, an ortholog that does not confer anthracycline resistance. In the present study, the specificity of LY475776 was examined for its ability to modulate or photolabel orthologs of MRP1 and several other drug efflux transporters of the ABC transporter family. LY475776 modulated MRP1 and Pgp-mediated resistance (MDR, ABCB1) in, respectively, HeLa-T5 and CEM/VLB(100) cells to both vincristine and doxorubicin. LY475776 photolabeled 170kDa Pgp and was inhibited by the potent Pgp inhibitor LY335979 (Zosuquidar.3HCl). The labeling of the 190kDa MRP1 protein in membranes of HeLa-T5 cells was inhibited by substrates of MRP1 such as leukotriene C(4), vincrisine, and doxorubicin and by the inhibitor, MK571. LY475776 did not photolabel human MRP2 (ABCC2), MRP3 (ABCC3), MRP5 (ABCC5) or breast cancer resistance protein (ABCG2). Because LY475776 photolabels murine mrp1 less well than human MRP1 and binds to a region believed important for anthracycline binding, studies were conducted with monkey and canine MRP1 which also show a reduced ability to confer resistance to anthracyclines. Unlike murine mrp1, both orthologs were photolabeled well by LY475776. These studies indicate that the specificity of LY475776 is fairly limited to Pgp and MRP1 and further studies will help to define the binding regions.     

Cortical spreading depression augments kynurenate levels and reduces malonate toxicity in the rat cortex

Cortical spreading depression (CSD) is characterized by slowly propagating neuronal and astrocytic depolarization, resulting in transient, heightened resistance to subsequent neuronal injury. This study was designed to examine a possible role of the endogenous neuroprotective agent kynurenate (KYNA) in this phenomenon. Unilateral, consecutive CSDs, induced by topical application of 2 M KCl to the cortical surface of adult male rats, resulted in an ipsilateral increase (201-222% compared to controls) in KYNA levels, which was observed in the frontal, parietal and occipital cortex but not in other brain areas. This effect peaked on day 3 after CSD, and KYNA levels returned to normal on day 7. In separate rats, the lesion caused by an intracortical microinjection of the indirect excitotoxin malonate (500 nmol/0.5 microl) on days 1, 3 or 7 after CSD was reduced by 56-75% in the ipsilateral hemisphere. In normal rats, single or multiple injections of the kynurenine 3-hydroxylase inhibitor 4,5-dichlorobenzoylalanine (PNU 156561; 50 mg/kg, i.p.), which results in selective increases in brain KYNA levels, failed to protect cortical neurons against a focal malonate injection. Taken together, these findings indicate that the observed increase in brain KYNA is not responsible for CSD-induced tolerance to malonate-induced neuronal damage.     

Oxygenation prevents sudden death in seizure-prone mice

PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is a significant health problem for some with epilepsy, but no preventive therapy has been developed for high-risk patients. Sudden death in mice, after sound-induced (audiogenic) seizures, can model the seizure-associated respiratory arrest that contributes to SUDEP in some humans and may be useful for evaluating potential SUDEP therapies. This study evaluated the effects of oxygenation on sudden fatal audiogenic seizures (AGSs) in three mouse strains, DBA/2J (D2), B6SAS, and primed C57BL/6J (B6) that differ in genetic background and seizure etiology (idiopathic or acquired). METHODS: The incidence of fatal AGSs was measured in (a) a normal air environment; (b), an oxygen-rich environment; (c) a normal air environment 24 h after a nonfatal AGS; (d) an oxygen-rich environment 24 h after a nonfatal AGS; and (e) a normal air environment 60 s after exposure to an oxygen-rich environment. RESULTS: Sudden, fatal AGS occurred in 100%, 100%, and 58% of the D2, B6SAS, and primed-B6 mice, respectively, in the air environment. Oxygenation completely prevented fatal AGSs in each strain, but had no effect on seizure incidence or severity. Furthermore, the protective effect of oxygenation against fatal seizures occurred only when the mice were in an oxygen-rich environment. CONCLUSIONS: These findings indicate that oxygenation prevents sudden death in seizure-prone mice and suggest that oxygenation may protect some seizure-prone humans at risk for SUDEP.     

Small pulmonary nodules: detection at chest CT and outcome

PURPOSE: To determine the outcome of pulmonary nodules less than 1 cm in diameter detected at chest computed tomography (CT). MATERIALS AND METHODS: Reports of chest CT performed during 6 months were reviewed to find patients with pulmonary nodules smaller than 1 cm in long axis for which repeat CT was recommended. Records were studied to determine whether follow-up had been performed, the initial nodules had changed in size, or nodules had been resected. RESULTS: A total of 3,446 chest CT examinations were performed, with 334 patients meeting inclusion criteria. Three patients underwent nodule resection and had pathologic examination results positive for cancer; 185 underwent follow-up, of whom 13 had results excluded as indeterminate. In the remaining 172 patients, 88 had incomplete characterization because of follow-up of less than 2 years, which left 84 with nodule characterization at follow-up. When these 84 patients were combined with the three patients with nodule resection, the number yielded was 87 patients. Seventy-seven of 87 had benign nodules because of resolution or 2-year stability, and 10 of 87 had malignant nodules because of growth or positive histologic examination results. Nine of 10 with malignant nodules had a known primary neoplasm. CONCLUSION: CT commonly helped identify small nodules. Increase in size occurred infrequently and almost exclusively in patients with a known malignancy.     

Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease

OBJECTIVE: Discrete morphologic, enzymatic and functional changes in skeletal muscle mitochondria have been demonstrated in patients with peripheral arterial disease (PAD). We examined mitochondrial respiration in the gastrocnemius muscle of nine patients (10 legs) with advanced PAD and in nine control patients (nine legs) without evidence of PAD. METHODS: Mitochondrial respiratory rates were determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Muscle samples were obtained from the anteromedial aspect of the gastrocnemius muscle, at a level 10 cm distal to the tibial tuberosity. Mitochondria respiratory rate, calculated as nanoatoms of oxygen consumed per minute per milligram of noncollagen protein, were measured at baseline (V(0)), after addition of substrates (malate and glutamate; (V(SUB)), after addition of adenosine diphosphate (ADP) (V(ADP)), and finally, after adenine nucleotide translocase inhibition with atractyloside (V(AT)). The acceptor control ratio, a sensitive indicator of overall mitochondrial function, was calculated as the ratio of the respiratory rate after the addition of ADP to the respiratory rate after adenine nucleotide translocase inhibition with atractyloside (V(ADP)/ V(AT)). RESULTS: Respiratory rate in muscle mitochondria from patients with PAD were not significantly different from control values at baseline (0.31 +/- 0.06 vs 0.55 +/- 0.12; P =.09), but V(sub) was significantly lower in patients with PAD compared with control subjects (0.43 +/- 0.07 vs 0.89 +/- 0.20; P <.05), as was V(ADP) (0.69 +/- 0.13 vs 1.24 +/- 0.20; P <.05). Respiratory rates after atractyloside inhibition in patients with PAD were no different from those in control patients (0.47 +/- 0.07 vs 0.45 +/- P =.08). Compared with control values, mitochondria from patients with PAD had a significantly lower acceptor control ratio (1.41 +/- 0.10 vs 2.90 +/- 0.20; P <.001). CONCLUSION: Mitochondrial respiratory activity is abnormal in lower extremity skeletal muscle in patients with PAD. When considered in concert with the ultrastructural and enzymatic abnormalities previously documented in mitochondria of chronically ischemic muscle, these data support the concept of defective mitochondrial function as a pathophysiologic component of PAD.     

Can noise reduction filters improve low-radiation-dose chest CT images? Pilot study

Effect of noise reduction filters on chest computed tomographic (CT) images acquired with 50% radiation dose reduction was evaluated. Two sets of images were acquired with multi-detector row CT at standard (220-280 mA) and 50% reduced (110-140 mA) tube current at the level of the carina. After postprocessing with six noise reduction filters, images were compared with baseline standard-dose images for noise, sharpness, and contrast in lungs, mediastinum, and chest wall. Quantitative image noise was measured in descending thoracic aorta. Modulation transfer functions were calculated from CT images of 50-microm wire. Noise reduction filters reduced image noise on low-radiation-dose chest CT images, with some compromise in image sharpness and contrast assessed qualitatively, and slightly altered modulation transfer function at higher spatial frequencies.     

COX-2 inhibitors as radiation sensitizers for upper GI tract cancers: esophagus,stomach, and pancreas

Cancers of the esophagus, stomach, and pancreas have been successfully treated recently with combinations of radiosensitizing chemotherapy and irradiation. New approaches building onto 5-fluorouracil chemoradiation include capecitabine (Xeloda) and irradiation. Capecitabine is an oral 5-fluorouracil (5-FU) prodrug that is more convenient than using infusional 5-FU, appears to have a similar therapeutic profile, and can be combined with daily irradiation. The addition of a cyclooxygenase-2 (COX-2) inhibitor is being investigated in upper gastrointestinal cancer sites because there is a high degree of overexpression of COX-2 in these cancers.     

Treatment planning for stereotactic radiosurgery with photon beams

Stereotactic Radiosurgery (SRS) has evolved as a unique discipline that combines aspects of both surgery and radiation oncology. Technological developments in the past few decades have provided a wide array of treatment techniques, including (i) the Gamma Knife; (ii) Linac-based stereotactic techniques using circular collimators or using micro multileaf collimators (mMLCs); (iii) the Cyber Knife, using an x-band linac mounted on a robotic arm; and (iv) serial and spiral tomotherapy. This paper provides a review of the treatment planning methods for stereotactic radiosurgery. Because of the differences in planning strategies used for each SRS technique, this paper will provide both a general review of the pre-requisites and common features of SRS treatment planning and the planning techniques specific to each of the SRS techniques.     

Gender,hyperlipidemia, and coronary artery disease

The importance of statins for the prevention and treatment of coronary artery disease (CAD), the recent paradoxical effects of hormone replacement therapy on prevention of CAD, and the role of nontraditional risk factors in CAD in women are examined.