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EDITORIAL STAFF Joseph H. Friedman, MD Editor-in-Chief Joan M. Retsinas, PhD Managing Editor Stanley M. Aronson, MD, MPH Editor Emeritus EDITORIAL BOARD Stanley M. Aronson, MD Jay S. Buechner, PhD John J. Cronan, MD James P. Crowley, MD Edward Feller, MD John P. Fulton, PhD Peter A. Hollmann, MD Anthony Mega, MD Marguerite A. Neill, MD Frank J. Schaberg, Jr., MD Fred J. Schiffman, MD Lawrence W. Vernaglia, JD, MPH Newell E. Warde, PhD William J. Waters, Jr., PhD OFFICERS Frederic V. Christian, MD President Barry W. Wall, MD Vice President Kathleen Fitzgerald, MD President-Elect Diane R. Siedlecki, MD Secretary Francis Basile, MD Treasurer Tilak K. Verma, MD, MBA Immediate Past President DISTRICT & COUNTY PRESIDENTS Geoffrey R. Hamilton, MD Bristol County Medical Society Herbert J. Brennan, DO Kent County Medical Society Jayanthi Parameswaran, MD Newport County Medical Society Martin R. Papazian, MD Pawtucket Medical Association Patrick J. Sweeney, MD, PhD, MPH Providence Medical Association Nitin S. Damie, MD Washington County Medical Society Naeem M. Siddiqi, MD Woonsocket District Medical Society, for example, weight gain.
Hydrolysing activity. This is in contrast to the results of a previous study suggesting that M. tuberculosis H37Ra produces an additional minor b-lactamase with predominant cephalosporinase activity Voladri et al., 1998 ; . This discrepancy may be due to strain differences, as we have used the strain H37Rv for our work and Voladri et al. 1998 ; used the strain H37Ra. Alternatively, the previous study used purified b-lactamase preparations and consequently may have been more sensitive than our study, which used whole-cell lysates. In addition, the aforementioned study harvested b-lactamase activities from the supernatants of 34-week-old cultures. If a minor b-lactamase is produced at a much slower rate and is subsequently secreted or released into the medium due to cell lysis, a 34-week-old culture could yield larger amounts of the minor b-lactamase. Our study used whole-cell lysates of younger, lateexponential-phase cultures; the studies in M. fortuitum Fattorini et al., 1991 ; , M. tuberculosis Zhang et al., 1992 ; and our own data not shown ; indicate that the majority of b-lactamase activity at this stage is cell-associated. Alternatively, it has been proposed that this minor cephalosporinase of M. tuberculosis is not a b-lactamase per se, but is D, D-carboxypeptidase, capable of hydrolysing b-lactam antibiotics Voladri et al., 1998 ; . BlaS, the major b-lactamase of M. smegmatis described here, shows a high degree of homology to the molecular class A b-lactamase enzymes Ambler, 1980; Ambler et al., 1991 ; . This same classification has been previously suggested based on N-terminal sequencing of a purified b-lactamase from M. smegmatis mc2155 Quinting et al., 1997 ; . The analysis of the coding region for the enzyme reported in this study supports its molecular class A b-lactamase classification. Previous biochemical studies suggested that the M. smegmatis major b-lactamase hydrolyses penicillins and cephalosporins in an equally efficient manner. These biochemical data support the class A designation indicated by protein homology!
Copies of the booklet, "Cannabis and Mental Functions" may be obtained from the author: David Copestake, 22 Meadow View, Banbury, Oxon, OX16 9SR, England Issam Rashid Walid, Iraq's ex-Chief of Protocol and a former aid of Saddam Hussein, says Saddam frequently used drugs such as cannabis and heroin. "Saddam was heavily into drugs. He began in 1959, with cannabis, and then, when he seized power in 1979, he used heroin at times." ".drugs made him lose his mind." UK News: Ananova: February 12, 2004, for example, lactic acidosis.
Depending on one's faith in the market, one might have more or less confidence that private actors would consolidate all patents within a group and only within a group ; . Imagine if one were to overcome those hurdles. Table 7.1 summarizes policy proposals for addressing resistance externalities across hypothetical antibiotics by three types of patent status. Yet what are we to do about resistance externalities across antibiotics of different patent statuses? The answer is the same as in the previous paragraph. Extending either sui generis rights or future patents over all antibiotics regardless of patent status would entail a takings that would require just compensation. The alternative is to rely on licensing agreements that consolidate rights over all antibiotics from a functional resistance group, regardless of patent status, in one company last row of Table 7.1 ; . Consolidation, however, raises antitrust questions, to which we now turn.
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Problems with dyslipidemia and glucose sugar ; metabolism continue to plague HIV + people. But is it the HIV meds causing the problems or the HIV itself? A study in HIV Medicine 6, p. 114, 2005 ; examined 419 HIV + people who had never taken HIV meds before. Researchers found that patients with more advanced HIV disease lower T-cell counts, higher viral loads, or a history of having an AIDSdefining illness ; were more likely to show signs of dyslipidemia and insulin resistance, a condition associated with the development of diabetes. These findings indicate that the HIV disease itself can lead to many of the metabolic problems seen in HIV + patients and omeprazole.
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Absent or defective IP protection. One way to prevent the sale of unauthorised copies of medicines is to enable companies to register and enforce trademarks. These enable vendors to signal the quality of their product to potential purchasers. Trademark owners have strong incentives to ensure that the quality of their product is maintained because their reputation and hence future profitability depend upon it.In many LDCs, it is difficult to enforce trademarks even for local companies. Where trademarks cannot be enforced, cheaply produced poor quality copies will typically crowd out good quality drugs. Lack of adequate civil liability. Civil law protects the consumer against mis-sold or defective goods. By enabling consumers or their relatives ; to obtain redress from the manufacturer or supplier of a harmful product, such liability both compensates those who are harmed and discourages manufacturers and suppliers from selling counterfeits. In many LDCs, however, civil law is either poorly defined or difficult to enforce. Inability to resolve disputes over property rights and contracts in independent courts. Underlying the lack of civil liability and weak IP protection are costly and inefficient legal systems As a result, it can often take years for cases to be heard. Many courts in LDCs are hampered by a lack of basic things such as.
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Disease and presence of human papillomavirus after conization. Oncology 1998; 55 6 ; : 517-20. Paraskevaidis E, Arbyn M, Sotiriadis A et al. The role of HPV testing in the follow up period after treatment for CIN: a systematic review of the literature. Cancer Treat Rev 2004; 30 2 ; : 205-11. Zielinski GD, Bais AG, Helmerhorst TJ et al. HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis. Obstet Gynecol Surv 2004; 59 7 ; : 543-53. Petry KU, Menton S, Menton M et al. Inclusion of HPV testing in routine cervical cancer screening for women above 29 years in Germany: results for 8466 patients. Br J Cancer 2003; 88 10 ; : 1570-7. Prendiville W, Cullimore J, Norman S. Large loop excision of the transformation zone LLETZ ; . A new method of management for women with cervical intraepithelial neoplasia. Br J Obstet Gynaeco 1989; 96 9 ; : 1054-60. Kyrgiou M, Koliopoulos G, Martin-Hirsch P et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive lesions: a systematic review and meta-analysis of the literature. Lancet 2006; 367 9509 ; : 489-98. Bruinsma F, Lumley J, Tan J, Quinn M. Pre-cancerous changes in the cervix and risk of subsequent preterm birth. BJOG 2007; 114 1 ; : 70-80. Clifford GM, Smith JS, Aguado T, Franceschi S. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer 2003; 89 1 ; : 101-5. Harper DM, Franco EL, Wheeler C et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364 9447 ; : 1731-2. Villa LL, Costa RL, Petta CA et al. Prophylactic quadrivalent human papillomavirus types 6, 11, 16, and 18 ; L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 2005; 6 5 ; : 271-8. Harper DM, Franco EL, Wheeler CM et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367 9518 ; : 1247-55 and
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Department of Nuclear Medicine, St. Vincent's University Hospital, Dublin, Department of Surgery, Conway Institute of Biomolecular and Biomedical Research, University College Dublin and Dublin Molecular Medicine Centre, Dublin 4, Ireland. Address for correspondence: Department of Nuclear Medicine, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. Fax 353-1-2696018; e-mail Michael.J.Duffy ucd.ie. Received July 5, 2004; accepted December 2, 2004. Previously published online at DOI: 10.1373 clinchem.2004.046227 and
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COST ANALYSIS The cost of antithyroid medication varies widely depending on retailer and brand. Out-of-pocket expenses vary additionally with one's prescription plan. Prescribed at the usual ratio MMI-to-PTU, 1: 10 ; , MMI is more expensive than PTU $43 month for a daily dose of MMI 30 mg compared with $26 month for a daily dose of PTU 300 mg, according to destinationrx ; , but when administered at a ratio closer to equipotency MMI-to-PTU, 1: 30 ; , MMI becomes the less costly choice $15 month for a daily dose of MMI 10 mg compared with $26 month for a daily dose of PTU 300 mg ; . COMPLIANCE CONSIDERATIONS Because Graves' disease may cause poor concentration and memory impairment, one could hypothesize that compliance rates would be especially poor in patients with hyperthyroidism. Therefore, a drug that can be given in a single daily dose would be preferred. Since the serum half-life and duration of action of MMI is longer t1 2 4-6 h ; than that of PTU t1 2 60 min ; , 29, 30 MMI can be given as a single daily dose to most patients, whereas PTU generally must be given every 6 to 8 hours, at least initially. Ease of administration logically translates into improved compliance. In the only prospective randomized trial looking at compliance, the compliance rate defined as taking 80% of prescribed pills ; was significantly higher for MMI 83% ; than for PTU 53% ; .10, for example, rosiglitazone.
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Tion, whereas 270 82.3% ; had no signs of dehydration. Of the 328 acute episodes of diarrhoea, 300 91.5% ; patients were on pharmacological intervention, and six 1.8% ; were on non-pharmacological interventions assurance, education, dietary advice, fluid intake ; . In 22 6.7% ; cases, patients' management was not specified. The prescribing patterns for the treatment of 300 episodes of diarrhoea are shown in Table 2. In a sample of 300 patients, ORS was prescribed to 89.3% n 268 12.3% received ORS alone, whereas 77% received ORS in combination with symptomatic drugs and or intravenous fluids. The mean number of drugs per prescription was 2.2 + 0.9, whereas the mean number of drugs per.
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Check with your doctor as soon as possible if any of the following side effects occur: sudden or severe abdominal pain pounding heartbeat increased or decreased heart rate irregular heartbeat sensation of burning, warmth, heat, numbness, tightness, or tingling stop taking the medication and seek immediate medical attention if any of the following occur: heart attack symptoms include pain, pressure, tightness or heaviness in the chest, jaw, neck or shoulder, sweating, or shortness of breath ; severe allergic reaction symptoms include swelling of the face, or throat; hives; or difficulty breathing ; stroke symptoms include sudden numbness or weakness, especially on one side of the body; sudden confusion or problems with speech; sudden vision problems in one or both eyes; sudden dizziness or loss of coordination; sudden severe headache, especially if it seems different from your usual headaches ; some people may experience side effects other than those listed.
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Technology Perimetry FDT ; N-30, a visual function specific test targeting magnocellular ganglion cells. Design: Cross-sectional analysis of an observational cohort study. Participants : One eye of 259 participants was evaluated: 51 normals, 56 ocular hypertensives OHT ; , 118 eyes with glaucomatous optic neuropathy GON ; and 34 with progressive GON PGON ; , a more stringent criteria to increase probability that glaucoma is present. Methods : Cross-sectional analysis. Visual fields were not used to classify groups. PGON, the best gold standard currently available for evaluation of functional tests, was documented by evidence of progressive change in optic disc appearance on masked review of simultaneous stereophotographs by two experts. Main outcome measures : Areas under the ROC for FDT indices and number of defective locations at various probabilities on the pattern and total deviation plots using area under the ROC. ROC results were then used to establish criteria for abnormality at different specificities. Results: Results are shown in Table 1 for parameters with largest ROC areas. Also shown are sensitivities at set specificities along the ROC curve for the PGON group Table 2 ; . Within a diagnostic group, no significant differences were found in areas under the ROC for the parameters evaluated. Conclusions : When comparing visual function specific tests with each other, with standard perimetry, or with measures of optic nerve structure it is important to utilize the best criteria for abnormality for each type of test. It is also important to take into account the trade-off in sensitivity vs. specificity for the particular use in question. The FDT N-30 test performs well in separating normal and glaucomatous eyes using a variety of parameters as evidenced by the large area under the ROC. Support: Grants NEI EY 08208 PAS ; and EY11008 LMZ ; References : 1. Burnstein Y, Ellish, NJ, Magbalon M, Higginbotham EJ: Comparison of frequency doubling perimetry with humphrey visual field analysis in a glaucoma practice. J Ophthalmol, 2000. 129 3 ; : p. 328-33. 2. Cello KE, Nelson-Quigg JM, Johnson CA: Frequency doubling technology perimetry for detection of glaucomatous visual field loss. J Ophthalmol, 2000. 129 3 ; : p. 314-22. 3. Johnson CA, Samuels SJ: Screening for glaucomatous visual field loss with frequency-doubling perimetry. Invest Ophthalmol Vis Sci, 1997. 38 2 ; : 413-25. Medeiros FA, Sample PA, Weinreb RN: Frequency doubling technology perimetry abnormalities as predictors of glaucomatous visual field loss. J Ophthalmol, 2004. 137 5 ; : p. 86371. 4. Paczka JA, Friedman DS, Quigley HA, Barron Y, Vitale S: Diagnostic capabilities of frequency-doubling technology, scanning laser polarimetry, and nerve fiber layer photographs to distinguish glauocmatous damage. J Ophthalmol, 2001. 131: p. 188-197. 5. Sample PA, Bosworth CF, Blumenthal EZ, Girkin C, Weinreb RN: Visual function-specific perimetry for indirect comparison of different ganglion cell populations in glaucoma. Invest Ophthalmol Vis Sci, 2000. 41 7 ; : 1783-90. 6. Wu LL, Suzuki Y, Kunimatsu S, Araie M, Iwase A, Tomita G: Frequency doubling technology and confocal scanning ophthalmoscopic optic disc analysis in open-angle glaucoma with hemifield defects. J Glaucoma, 2001. 10 4 ; : 256-60. P094 SENSITIVITY OF A NEW BLUE-ON-YELLOW SPARSE MVEP IN THE DETECTION OF GLAUCOMATOUS VISUAL FIELD DEFECTS. A. Klistorner, A. Martins, S. Graham, J. Grigg, I. Goldberg, F. Billson Sydney University, Sydney, Australia.
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Created through molecular manipulation. It has a similar spectrum of antitumor activity. However, it has a more favorable toxicity profile, is easier to administer, and is associated with improved quality of life in cancer patients Tighe & Goodman, 1988 ; . Carboplatin has the particular advantage of not requiring intensive intravenous ; hydration before and after administration to avoid kidney toxicity. This enables the agent to be given on an outpatient basis, thereby saving the cost of hospitalization. As a result, although carboplatin is about 10 times more expensive than cisplatin, the overall costs of treatment are about one third less Tighe & Goodman, 1988 ; . Despite their positive activities in a variety of cancers, cisplatin and carboplatin are both ineffective in colorectal cancer, the second-leading cause of death in North America, claiming 56, 000 lives annually. But a third anticancer platinum compound, oxaliplatin, has shown promising activity in advanced colorectal cancer when given alone or in combination with other chemotherapies, even in patients refractory to standard agents Giacchetti et al., 2000; de Gramont et al., 2000 ; . Even small improvements in colorectal cancer treatment outcomes can have potentially large economic benefits, although these have not yet been quantified. Second-Generation Diabetes Drugs: Improved Glycemic Control Without Increased Costs Second-generation sulfonylurea agents used in the treatment of diabetes have several advantages over the first-generation agents in this class see Sulfonylurea Agents, above ; . In 1987 California added the second-generation agents to the Medi-Cal formulary, thereby allowing Medicaid recipients to receive these drugs. A study of more than 5000 Medi-Cal patients determined the clinical and economic effects of this addition after 6 months Sclar et al., 1990 ; . Addition of the new agents was correlated with an overall improvement in the outcome of drug therapy and a corresponding decrease in hospital and nursing home costs for diabetic patients. However, drug expenditures rose for patients prescribed the new agents, since these drugs are more expensive than the firstgeneration agents. As a result, total expenditures were unchanged. Although overall costs were not reduced, the addition of these incremental improvements resulted in a higher level of glycemic control without increasing costs.
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National Osteoporosis Foundation Guidelines The practicing physician needs to determine which patients are at risk for an osteoporotic fracture and when treatment should be initiated. The NOF has developed guidelines for selecting patients who should receive treatment to reduce the risk of fracture and these are based primarily on BMD i.e., T-scores ; together with other risk factors in addition to 10 low BMD. The NOF guidelines with are based on DXA-derived T-scores determined at the hip ; recommend treatment in the following clinical situations: Women with T-scores below -2.0 with no risk factors Women with T-scores below -1.5 with one or more risk factors for fractures Women with a prior vertebral or hip fracture The presence of a vertebral fracture significantly increases the lifetime risk of subsequent fractures and there are data to show that women who develop a vertebral fracture are at 26 substantial risk for additional fracture within the next year. American Association of Clinical Endocrinologists The American Association of Clinical Endocrinologists AACE ; also has guidelines for prevention and treatment of postmenopausal osteoporosis and its recommendations are consistent with those of the NOF regarding those women with T-scores of -1.5 and 9 lower if risk factors for fracture Table 1 ; are present. However, AACE guidelines use a T-score reference of -2.5 and lower which is the WHO criteria for the diagnosis of osteoporosis ; , instead of -2.0, for treatment in postmenopausal women without risk factors. AACE recommends treating women with low-trauma fractures who have low BMD defined as T-scores less than -1.0 or any postmenopausal woman in whom nonpharmacologic preventive measures are ineffective i.e., bone loss continues or low-trauma fractures occur ; . It is this group of patients with T-scores less than -1.0 that require particular attention since they are at substantial 27 risk and constitute most of those who sustained fractures. Management of Postmenopausal Women with Low BMD without Fractures In postmenopausal women with T-scores above -1.5 and no fractures, preventive measures should continue with calcium and vitamin D supplements, together with appropriate exercise. BMD would be rechecked in 2 years or as clinically indicated. There are those who argue for a more aggressive therapeutic intervention in this group of postmenopausal women to 28 prevent osteoporosis from occurring, with the rationale that and
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