Synopsis The New England Journal of Medicine features a review of the treatment of infections associated with a variety of surgical implants. The article describes the clinical and economic effects, addresses diagnostic challenges, discusses the general principles of medical and surgical treatment, and analyses implant-specific therapeutic approaches prosthetic heart valves, vascular grafts, pacemakerdefibrillator systems, left ventricular assist devices, joint prostheses, fracture-fixation devices, ventricular shunts, mammary implants and inflatable penile implants!

Epirubicin is an anthracycline newly approved by the FDA with orphan status ; that is currently used in more than 80 countries to treat a variety of cancers. It is a semisynthetic derivative of daunorubicin and epimer of doxorubicin. Indications: Epirubicin is indicated as a component of adjuvant therapy for patients showing evidence of axillary lymph node involvement following resection of a primary breast cancer. Pharmacology: Epirubicin molecules form a complex with molecules of DNA by intercalating between nucleotide bases and thereby inhibiting synthesis of DNA, RNA, and proteins. Indeed, such intercalation promotes cleavage of DNA by the enzyme topoisomerase II. While these effects may be responsible for the cytotoxicity of epirubicin, there may also be other mechanisms. Efficacy: FDA approval was based on randomized, openlabel, multicenter trials that evaluated the use of epirubicin 110-120 mg m2 ; , in combination with cyclophosphamide and fluorouracil, for the adjuvant therapy of 1, 281 patients with axillary node-positive breast cancer but without evidence of distant metastases. All patients were pre- or perimenopausal. When compared with another triple therapy in which methotrexate replaced epirubicin ; , the groups receiving epirubicin showed significantly better outcome measures over the latter two or more years of the five-year study--a higher five-year relapse-free rate and a higher overall five-year survival rate. Contraindications: Epirubicin should not be used to treat patients who have any of the following conditions: severe myocardial insufficiency or a recent myocardial infarction; prior use of anthracyclines up to a maximum cumulative dose; baseline neutrophil count of less than 1500 cells mm3.
Mechanisms against allergens. Current strategies for drug development and allergen-specific immunotherapy exploit these observations. GPCRs are the most prominent targets for drug discovery and according to estimations, up to half of all modern drugs are targeted at GPCRs Gudermann et al. 1995, Flower 1999 ; . In addition, several ligands for GPCRs are found in the top-100 selling pharmaceutical products. 200-500 orphan GPCRs may still exist in the human genome providing many opportunities for drug discovery Howard et al. 2001 ; . Pharmacological agents that block or stimulate GPCR action are commonly utilized in the treatment of allergic diseases. 3.1 The GPCR superfamily: classification The superfamily of GPCRs is evolutionary highly conserved and one of the largest groups of proteins in animals Lander et al. 2001, Venter et al. 2001 ; . The structural characteristics of GPCRs show a topology of seven transmembrane TM ; -helices connected by three intracellular loops and three extracellular loops Baldwin et al. 1993 ; . The human genome contains more than 800 genes for GPCRs, which may represent up to 2-3 % of all protein coding genes Fredriksson et al. 2003 ; . GPCRs play important roles both in the major peripheral organ systems and in the central nervous system. The receptors can be classified by several ways based e.g. on their amino acid similarities Vassilatis et al. 2003 ; , ligand binding sites, receptor function and ligand structure Bockaert and Pin 1999 ; as well as homology in the human genome Fredriksson et al. 2003 ; . According to the phylogenetic analysis of GPCRs in the human genome, the receptors can be divided into five main families, Glutamate, Rhodopsin, Adhesion, Frizzled Taste2 and Secretin Fredriksson et al. 2003 ; . Rhodopsin, Secretin and Glutamate families correspond to A, B and C clans in the traditional A-F classification of GPCRs, respectively, where the subclans are defined using roman number nomenclature Attwood and Findley 1994, Kolakowski 1994 ; . The A-F classification covers all GPCRs in both vertebrates and invertebrates, and some families of the system do not exist in humans. The Rhodopsin family is by far the largest of the five human GPCR families and most of the current drug targets among GPCRs are found within this family, which contains 15, 241, 24, and 15 non-olfactory receptors, respectively Attwood and Findley 1994 ; . The rhodopsin family has several characteristics such as the Asn-Ser-x-x-Asn-Pro-x-x-Tyr motif in TMVII, the Asp-Arg-Tyr DRY ; motif or the Asp Glu ; -Arg-Tyr Phe ; sequence at the border between TMIII and the second intracellular loop. The ligands for most of the rhodopsin family receptors bind within a cavity between the TM regions Baldwin et al. 1993 ; except for the glycoprotein binding receptors such as luteinizing hormone, follicle stimulating hormone and thyroid-stimulating hormone receptors, where the ligand-binding domain is in the amino terminus. In addition to hormones, rhodopsin family GPCRs can be activated by biogenic amines, peptides, nucleosides and nucleotides as well as lipids and eicosanoids. The large group of olfactory receptors belongs to this family but two thirds of the 900 genes in the subgroup represent pseudogenes in humans, for instance, dramamine dosage for dogs. 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Historically, Bhutan had some of the world's most severe iodine deficiency. A survey in 1983 described a mean national goiter prevalence of 64.5%. The government responded with a vigorous IDD elimination program. A recent publication Iodine Deficiency Disorders: The Bhutan Story, 1992, published by the Directorate of Health Services, Ministry of Social Services, Royal Government of Bhutan ; describes the progress on follow-up to that year. The present article offers some highlights. The severity of IDD in Bhutan has been described previously in the Newsletter 1 ; : 12, 1985 and 5 2 ; : 9, 1989 ; . The overall goiter prevalence was around 60%, ranging from 41% to 85% among different areas. In the western region, nearly 50% of those surveyed had urinary iodine levels less than 25 mg iodine per gram creatinine, and the incidence of elevated TSH's on screening for neonatal hypothyroidism was around 10%. All districts had cretins, and in some the incidence reached 10%. All of Bhutan's salt is imported, chiefly from India. Iodized salt had been tried in the 1960's but had been found unacceptable to the population. In 1985 a salt iodization plant was opened at Phuntsholing on the border with India. All salt reaching the country is processed in this plant. The IDD control program consists of components, as follows: Salt iodization - The Food Cooperation of Bhutan is responsible for distribution of salt throughout the country. The government regulates the distribution and requires that all salt pass through the iodization plant. Iodized oil administration - Fifty-four thousand injections were administered during 1988-91 along the southern border because competing non-iodized salt was available to the population. It is not anticipated that further oil injections will be necessary as the community has now been educated to the importance of iodized salt. Monitoring - Salt is required to contain 60 ppm of iodine at the factory, 25 ppm at retail, and at least 15 ppm at the household or consumption level. Field kits are used in the primary health care system and all basic health units are required to test a minimum of 60 samples quarterly and send reports to headquarters. Evaluation - Regular impact evaluations are carried out. Education - Community education is recognized as essential to a successful program and is a major area of government focus. The 1991 92 nationwide survey Thirty clusters in the north and an additional 30 in the south were included, as recommended by WHO ICCIDD UNICEF methodology. A total of 1581 women and 1443 children about 50 women and 45 children per cluster ; were examined in the northern area and 988 women and 992 children about 30 of each per cluster ; in the south. Total goiter prevalences among women were 18.5% in the north and 45.9% in the south. Among children aged 6-11, they were 18.4 in the north and 33.5 in the south and enalapril.

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Cocaine Cocaine became quite popular during the 19th century. Vin Mariani, a combination of coca leaf extract and wine, was quite popular in Europe. Coca-Cola at the end of the century actually contained coca leaf extract for a short time. Cocaine was isolated in 1860 and attracted many advocates. Freud recommended the use of cocaine before discovering the negative effects of long-term use. By the end of the 1800's in the U.S., cocaine was available in many patent medicines and other preparations. Although physicians were aware of the dangers of addiction, there were no nationwide controls until the 1900's.