ABSTRACT
A previous phase III clinical trial failed to show significant therapeutic benefit of repeated subcutaneous nerve growth factor (NGF) administration in the treatment of diabetic neuropathy. Animal studies have since shown that site-specific viral-mediated expression of NGF in the lumbar dorsal root ganglia prevents peripheral nerve dysfunction associated with chemically induced neuropathy. Using a Herpes simplex virus expression vector, we have investigated the effect of localized NGF expression in a genetic mouse model of progressive diabetic neuropathy, the +/+ Leprdb mouse. We found that site-specific delivery of NGF initially delayed the appearance of hypoalgesia, assessed by the Hargreaves test, by 1 month and effectively attenuated this deficit for 2 months over the approximately 10 months normal life-span of these animals. Once the disease progressed into its more severe stages, NGF, although still capable of altering the electrophysiological profile of the sensory A- and C-fibers and influencing the expression of p75 and substance P in the dorsal root ganglia, could no longer maintain normal nociception. These data suggest that maximal therapeutic benefit in future NGF-based gene therapy trials will be gained from early applications of such viral-mediated neurotrophin delivery.
Subject(s)
Diabetic Nephropathies/genetics , Diabetic Nephropathies/therapy , Genetic Therapy , Nerve Growth Factors/physiology , Simplexvirus/physiology , Action Potentials/physiology , Age Factors , Animals , Behavior, Animal , Blotting, Northern/methods , Cell Count/methods , Disease Models, Animal , Dose-Response Relationship, Radiation , Electric Stimulation/methods , Ganglia, Spinal/physiopathology , Genetic Vectors/physiology , Immunohistochemistry/methods , Male , Mice , Mice, Inbred C57BL , Nerve Fibers/physiology , Nerve Fibers/radiation effects , Pain Measurement/methods , RNA, Messenger/metabolism , Reaction Time , Receptor, Nerve Growth Factor/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods , Substance P/metabolismABSTRACT
STUDY OBJECTIVE: To assess emergency physician knowledge of and effect on clinical practice of the ACEP "Clinical Policy for Management of Adult Patients Presenting With a Chief Complaint of Chest Pain, With No History of Trauma." METHODS: We conducted a written survey of attending physicians by mail and in person at emergency medicine meetings. Residents were surveyed at their academic departments. The survey recipients were emergency physicians and residents from university, community teaching, urban, and rural hospitals. RESULTS: Of the 338 surveyed physicians, 163 (48%; 95% confidence interval [CI], 43% to 54%) said that they were aware of the policy. Fifty-four percent of ACEP members said they were aware of the policy, compared with 24% of nonmembers. Of the physicians who said they were aware of the policy, 63% did not know that the policy contains rules. Seventy-one percent of the physicians who were aware of the policy incorrectly believed the policy requires treatment with thrombolytic therapy in certain cases of myocardial infarction. Physicians said they learned about the policy by reading it (42%), by word of mouth (16%), or in department/quality assurance meetings (13%). Twelve percent of physicians believe the policy has changed their clinical practice. CONCLUSION: Fewer than half the emergency physicians we surveyed were aware of the policy. Of the physicians who said they had been aware of the policy, most did not know important specifics of the policy.
Subject(s)
Chest Pain/diagnosis , Emergency Medicine/standards , Health Knowledge, Attitudes, Practice , Medical Staff, Hospital , Practice Guidelines as Topic , Practice Patterns, Physicians' , Academic Medical Centers , Adult , Chest Pain/etiology , Emergency Medicine/methods , Humans , Medical Staff, Hospital/education , Medical Staff, Hospital/psychology , Societies, Medical , Surveys and Questionnaires , United StatesABSTRACT
A simple and rapid method for the simultaneous determination of 11 metals (As, Be, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, and Zn) in urine by inductively coupled argon plasma-atomic emission spectrometry is presented. Acidification of the urine was the only sample preparation required. Background correction was applied to ensure accuracy. Analytical calibration was based on matrix matching using a "simulated urine" solution. Detection limits in the low mg/L range and linearity over three orders of magnitude were obtained for all 11 metals. In the Occupational Health Laboratory, this procedure has been applied for routine screening of workers for occupational exposure to toxic metals.
Subject(s)
Environmental Monitoring/methods , Metals/urine , Spectrometry, X-Ray Emission/methods , Calibration , Environmental Exposure , Humans , Spectrometry, X-Ray Emission/standardsABSTRACT
A simple, sensitive, and specific method for measuring the concentration of platinum in urine is reported. Urine specimens for this study were collected from laboratory staff and from patients who received treatment with cisplatin as a chemotherapeutic agent for cancer. The concentration of platinum was determined by inductively coupled plasma atomic emission spectrometry. The entrance slit of the simultaneous spectrometer, normally used for correction of optical alignment, was moved by the micrometer to shift the emission line of platinum onto the detector originally assigned to tellurium. Background correction was applied to compensate for spectral interference and thus enhance accuracy. The analytical detection limit was 0.05 mg Pt/L. At 10.0 mg Pt/L in spiked urines the recovery was 93.3% with a relative standard deviation of 6.6%. Storage for 10 days at 4 degrees C did not affect the recovery.
