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Title: Pharmacology / [edited by] Karen Whalen ; collaborating editors buy discount levitra soft alcohol and erectile dysfunction statistics, Carinda Feild order levitra soft without a prescription impotence support group, Rajan Radhakrishnan. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Healthcare professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. Harvey, PhD 1936–2017 Co-creator and series editor of the Lippincott Illustrated Reviews series, in collaboration with Pamela C. Illustrator and co-author of the first books in the series: Biochemistry, Pharmacology, and Microbiology and Immunology. Klinker Chapter 30: Protein Synthesis Inhibitors Jacqueline Jourjy Chapter 31: Quinolones, Folic Acid Antagonists, and Urinary Tract Antiseptics Kenneth P. Overview Pharmacokinetics refers to what the body does to a drug, whereas pharmacodynamics (see Chapter 2) describes what the drug does to the body. Four pharmacokinetic properties determine the onset, intensity, and duration of drug action. Distribution: Second, the drug may reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids. Metabolism: Third, the drug may be biotransformed through metabolism by the liver or other tissues. Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces. Using knowledge of pharmacokinetic parameters, clinicians can design optimal drug regimens, including the route of administration, dose, frequency, and duration of treatment. Routes of Drug Administration the route of administration is determined by properties of the drug (for example, water or lipid solubility, ionization) and by the therapeutic objectives (for example, the need for a rapid onset, the need for long-term treatment, or restriction of delivery to a local site). Major routes of drug administration include enteral, parenteral, and topical, among others. Enteral Enteral administration (administering a drug by mouth) is the most common, convenient, and economical method of drug administration. The drug may be swallowed, allowing oral delivery, or it may be placed under the tongue (sublingual) or between the gums and cheek (buccal), facilitating direct absorption into the bloodstream. Oral drugs are easily self-administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes, such as activated charcoal. However, the pathways involved in oral drug absorption are the most complicated, and the low gastric pH inactivates some drugs. A wide range of oral preparations is available including enteric-coated and extended-release preparations. Enteric-coated preparations An enteric coating is a chemical envelope that protects the drug from stomach acid, delivering it instead to the less acidic intestine, where the coating dissolves and releases the drug. Enteric coating is useful for certain drugs (for example, omeprazole) that are acid labile, and for drugs that are irritating to the stomach, such as aspirin. For example, the half-life of oral morphine is 2 to 4 hours, and it must be administered six times daily to provide continuous pain relief. Sublingual/buccal the sublingual route involves placement of drug under the tongue. Parenteral the parenteral route introduces drugs directly into the systemic circulation. Parenteral administration is also used for patients unable to take oral medications (unconscious patients) and in circumstances that require a rapid onset of action. Parenteral administration provides the most control over the dose of drug delivered to the body. However, this route of administration is irreversible and may cause pain, fear, local tissue damage, and infections. The four major parenteral routes are intravascular (intravenous or intra- arterial), intramuscular, subcutaneous, and intradermal. It is useful for drugs that are not absorbed orally, such as the neuromuscular blocker rocuronium. When injected as a bolus, the full amount of drug is delivered to the systemic circulation almost immediately. Depot preparations often consist of a suspension of drug in a nonaqueous vehicle, such as polyethylene glycol. As the vehicle diffuses out of the muscle, drug precipitates at the site of injection. The drug then dissolves slowly, providing a sustained dose over an extended interval. This route should not be used with drugs that cause tissue irritation, because severe pain and necrosis may occur. Agents for diagnostic determination and desensitization are usually administered by this route. Oral inhalation and nasal preparations Both the oral inhalation and nasal routes of administration provide rapid delivery of drug across the large surface area of mucous membranes of the respiratory tract and pulmonary epithelium. Drugs that are gases (for example, some anesthetics) and those that can be dispersed in an aerosol are administered via inhalation. This route is effective and convenient for patients with respiratory disorders such as asthma or chronic obstructive pulmonary disease, because drug is delivered directly to the site of action, thereby minimizing systemic side effects. The nasal route involves topical administration of drugs directly into the nose, and it is often used for patients with allergic rhinitis. When local, rapid effects are needed, it is necessary to introduce drugs directly into the cerebrospinal fluid. Transdermal This route of administration achieves systemic effects by application of drugs to the skin, usually via a transdermal patch. The rate of absorption can vary markedly, depending on the physical characteristics of the skin at the site of application, as well as the lipid solubility of the drug. Rectal Because 50% of the drainage of the rectal region bypasses the portal circulation, the biotransformation of drugs by the liver is minimized with rectal administration. This route is also useful if the drug induces vomiting when given orally, if the patient is already vomiting, or if the patient is unconscious. Rectal absorption is often erratic and incomplete, and many drugs irritate the rectal mucosa. Absorption of Drugs Absorption is the transfer of a drug from the site of administration to the bloodstream. The rate and extent of absorption depend on the environment where the drug is absorbed, chemical characteristics of the drug, and the route of administration (which influences bioavailability). Routes of administration other than intravenous may result in partial absorption and lower bioavailability.

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I I Observe the sudden increase in the airway pressure at the end of inspiration (arrow) order genuine levitra soft on-line erectile dysfunction treatment yoga, caused by expiratory effort from the patient buy generic levitra soft 20mg on-line erectile dysfunction after prostate surgery. This can often be ameliorated by raising the flow threshold for breath termination, especially in patients with airflow obstruction. Furthermore, these consequences could worsen respiratory mechanics and potentiate further dyssynchrony, perpetuating this pathologic process. Macroscopic injury consists of the presence of extra-alveolar air, and it is commonly referred as barotrauma. It includes pneumothorax, pneumomediastinum, pneumoperitoneum, subcutaneous emphysema, and cystic lung spaces. In addition, the release of intracellular mediators from injured cells in response to those forces may promote further damage to the lungs directly or indirectly by activating epithelial, vascular and inflammatory cells that release more injurious molecules (biotrauma). In conditions where the pleural pressure is nonsignificant (chest wall elastance is normal and the patient is passively ventilated), the transpulmonary pressure relates mainly to the alveolar pressure at the end of inspiration when the airflow is zero (plateau pressure). Thus, restricting plateau pressure is a commonly used strategy to limit the transpulmonary pressure and avoid alveoli overdistention. Unfortunately, there are insufficient data to support the application of these strategies in routine clinical practice. Permissive hypercapnia may be a necessary consequence of lung protective ventilation, although it should probably be avoided in patients with intracranial hypertension and perhaps in pregnancy. One of the mechanisms of weaning failure appears to be an inability of the circulatory system to handle the increased demands of spontaneous ventilation [58]. These changes can be dramatic, especially when breathing effort is high or the chest wall compliance is greatly reduced. Because these effects are usually least at end expiration, all vascular pressures should be measured then. Patients with airflow obstruction often recruit expiratory muscles, artifactually raising end-expiratory Ppl. However, the lack of adequate data from human studies precludes the use of these strategies in current clinical practice [70–74]. The principles underlying ventilator management differ between these groups so that initial settings should be individualized. Subsequently, the clinician should adjust these initial settings according to the patient–ventilator interaction and the respiratory system mechanical properties as revealed by pressure and flow waveform analysis. In addition, a “ventilator bundle,” consisting of head-of-bed elevation; daily sedative interruption; readiness testing for spontaneous breathing; and other preventive steps should generally be provided to all ventilated patients. Normal Gas Exchange and Mechanics Patients with normal lungs may be ventilated in the perioperative setting; for drug overdose; in the setting of brain injury; or for other neuromuscular crises. Principles include achieving relatively normal arterial blood gas tensions and reducing the risk of complications, such as by using the ventilator bundle. This appears to be well tolerated in adequately sedated patients, although it may be less safe in pregnancy, with intracranial hypertension, and during active myocardial ischemia. Airflow Obstruction the most important guideline for ventilating patients with severe airflow obstruction is to avoid dangerous degrees of hyperinflation. Some clinicians prefer2 pressure-targeted modes because these intrinsically limit the degree of hyperinflation (because hyperinflation tends to reduce V ), but flow-T targeted modes allow control over minute ventilation. Chest Wall Restriction Chest wall restriction is seen among patients with severe kyphoscoliosis, abdominal compartment syndrome, large ascites, circumferential burns, and massive obesity. The crucial challenge in these patients is that, during passive ventilation, the inspiratory rise in Ppl is proportional to chest wall elastance and V. Although high values for Pplat may not signal lung overdistention, they are best avoided nevertheless to prevent cardiovascular effects. Simpler, modular circuits facilitate interhospital transfer; transport for diagnostic testing or to the operating room; and mobilization for physical therapy and rehabilitation. This device has a semipermeable membrane separating blood and its cellular elements from the gas phase, while allowing diffusion of oxygen and carbon dioxide. Newer hollow-fiber, polymethylpentene membranes are highly efficient gas exchangers, have a large surface area for diffusion, and present low resistance to blood flow. These characteristics allow rapid blood flow rates using simple, centrifugal pumps, while being compact and reliable. Gas is supplied from wall oxygen or a gas cylinder, through a blender that regulates the fraction of oxygen, directed into the hollow fibers of the membrane, then out an exit port. Vascular Cannulae Blood exits and rejoins the circulation through vascular cannulae placed into large, central vessels. Cannulae can be inserted by three different methods: (1) extrathoracic percutaneous approach by the Seldinger technique, (2) open surgical technique, usually used for cannulation of central arterial vessels, and (3) semiopen cutdown approach, which is a variation of the percutaneous technique, but with direct visualization of the vessel cannulation [30,59]. Dual-lumen cannulae allow both withdrawal and return of blood through a single access site, but fluoroscopic or echocardiographic guidance is recommended for insertion to reduce the risk of major vessel or right ventricular injury. Blood Pump Centrifugal pumps have largely replaced roller pumps, a major safety advantage afforded by the low blood resistance of modern membrane lungs. Sensors may show blood gas tensions and other biochemical data and are used to detect bubbles within the circuit or signal other potential crises. Access points are provided for giving fluids and blood products; sampling blood for laboratory testing; removing air inadvertently introduced into the circuit; infusing heparin; or incorporating renal replacement therapies. Blood is withdrawn from a large central vein, directed by the pump into the extracorporeal circuit, and returned to the venous circulation. Vascular access can be provided by a two-site approach in which a drainage cannula (23 to 29 Fr) is placed in a central vein, usually the femoral vein, extending to the vena cava. The return cannula (21 to 23 Fr) resides in another central vein (internal jugular or contralateral femoral vein) extending into the right atrium. Even though the cannulae are in separate locations, turbulence in the venous circulation may allow some oxygenated blood to be withdrawn again and sent to the extracorporeal circuit. The single-site approach utilizes a dual-lumen cannula usually placed through the internal jugular vein and extended across the right atrium to the inferior vena cava. Blood is withdrawn through ports situated in both inferior and superior vena caval portions of the cannula, sent to the extracorporeal circuit, and returned through the second lumen into the right atrium where a jet is directed toward the tricuspid valve. Some degree of recirculation is seen nevertheless, especially if the cannula is positioned poorly or when blood flow rates are high. Other advantages of single-site cannulation are simplicity, fewer sites for vascular injury, and ease of getting the patient out of bed to sit, stand, or walk. Arterial saturations are often in the mid-80s to low 90s, which is adequate for maintaining oxygen transport. Blood is withdrawn from the venous system, passed through the extracorporeal circuit for gas exchange, and returned to the patient’s arterial system using the pump to produce sufficient pressure. The drainage cannula (23 to 29 Fr) is usually inserted into the femoral vein extending to the inferior vena cava. The cannula for blood return (17 to 19Fr) is inserted into the femoral artery (ipsilateral or contralateral) extending to the distal abdominal aorta. The returning blood will generate retrograde blood flow in the aorta which can increase the cardiac afterload with negative consequences for the failing heart. There are two peculiarities, however: (a) the systemic blood pressure lacks normal pulsatility unless there is residual native pump function; (b) oxygen saturation varies along the aorta (and its branches) as desaturated blood ejected from the dysfunctional heart mixes with highly oxygenated blood returned to the distal aorta.

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Peterson A Clinical Guide for Contraception believed that lower microorganisms might possess the same enzymes used by adrenal glands to make cortisone discount levitra soft 20mg otc erectile dysfunction treatment food, especially the difcult step of introduc- ing an oxygen molecule to the structure buy levitra soft 20mg without a prescription erectile dysfunction drugs from himalaya. This they acquired, a fungus of the Rhizopus species, by leaving an agar plate on the window sill of the “oldest and dirti- est laboratory at the Upjohn Company. Teir method used Rhizopus nigricans to covert progesterone to 11-hydroxyprogesterone, that could in turn be processed into hydrocortisone, also called cortisol, the major corticosteroid secreted by the adrenal cortex. By 1955, Upjohn had become the market leader, and Searle shut down its perfusion cells and quit the race. Upjohn’s commercialization of the methods developed by Peterson and Murray led to popular and successful products. But the Searle people had gained valuable experience that would eventually pay of with other synthesized hormones and products. The Upjohn method used progesterone as the starting point, available in the early 1950s only from Syntex. George Rosenkranz’s laboratory at Syntex was also pursuing the industrial synthesis of cortisone, and in July 1951, Syn- tex was about to sign a contract with a large chemical frm to begin produc- tion. Rosenkranz told the story: “I received a phone call from Upjohn asking me whether we would be able to accept an order for 10 tons of progesterone at 48 cents a gram. Rosenkranz accepted the order, and Syn- tex found itself as the key supplier of progesterone to other companies. The Synthetic Progestational Drugs, Norethindrone and Norethynodrel Djerassi and other Syntex chemists turned their attention to the sex steroids. Tey discovered that the removal of the 19-carbon from yam-derived pro- gesterone increased the progestational activity of the molecule. The clue for this work came from Maximilian Ehrenstein at the University of Pennsyl- vania, who reported in 1944 that a potent progestational compound he had produced appeared to be progesterone without its carbon at the 19 posi- tion; henceforth, the 19-nor family of compounds indicated steroid chem- ical structures without the carbon atom at the 19 position. The ethinyl testosterone prod- uct was known as ethisterone, marketed in 1941, and the Syntex chemists reasoned that removal of the 19-carbon would increase the progestational potency of this orally active compound. Oral Contraception On October 15, 1951, norethindrone was synthesized at Syntex; the fnal steps were performed by Luis Miramontes, working on his undergraduate thesis in chemistry under Djerassi’s supervision. Searle & Company, fled a patent for norethynodrel, a compound closely related to norethindrone, difering only in the position of the double bond, on August 31, 1953. From 1949 to 1951, he was a research fellow working with Edward Kendall at the Mayo Foundation on the synthesis of cortisone. Colton joined Searle in 1951, along with Byron Riegel, to develop steroid drugs, succeeding with Nilevar, the frst commercial anabolic agent marketed in 1956 and Aldac- tone, the antialdosterone antihypertensive agent introduced in 1959. Norethynodrel was the result of a deliberate and planned program to cre- ate orally active agents with progestational activity. Later, Colton pointed out that although the Syntex and Searle chemists followed a similar path, they were independently pursuing the trail blazed by previous scientists. Norethindrone was tested as a contraceptive by Edward Tyler in Los Angeles and Joseph Goldzieher in San Antonio, Texas, but Parke- Davis chose not to pursue government approval, probably fearing religious reactions. By 1964, Ortho, Parke-Davis, and Syntex (now in California) were marketing oral contraceptives containing norethindrone or its acetate. The creation of norethindrone and norethynodrel by the chemists was essential in the development of oral contraception because the natural hor- mone progesterone is relatively impotent given orally, requiring very large doses that even then do not achieve a uniform response. The synthetic A Clinical Guide for Contraception progestational agents are very active when administered orally, producing reliable efects with small doses. A Wall Street entrepreneur, Charles Allen, acquired Syntex in 1956 for $2 million cash and a loan of $2 million to be paid from future profts. Carl Djerassi, who had lef for an academic position at Wayne State University, was recruited back to the company. The growth of the company was meteoric, with blockbuster hits like Synalar, a topical corticoidsteroid for the treatment of psoriasis, and Naproxen, a nonsteroid, anti-infam- matory drug. Much of this success was to an innovative philosophy in the pharmaceutical business, “patent and publish. Djerassi eventually lef Syntex to become a full-time professor at Stanford University, and is now a playwright and novelist living in San Francisco. Gregory Pincus Gregory Goodwin (Goody) Pincus was born in 1903 in New Jersey, the son of Russian Jewish immigrants who lived on a farm colony founded by a Jew- ish philanthropic organization. Crozier’s hero was Jacques Loeb who discovered artifcial parthenogenesis working with sea urchin eggs. Tus, Crozier, infuenced by Loeb, taught Pin- cus, Hoagland, and Skinner (in reproductive biology, neurophysiology, and psychology, respectively) to apply science to human problems. Oral Contraception Hoagland, afer a short stay at Harvard, spent a year in Cambridge, England, and then moved to Clark University in Worcester, Massachu- setts, to be the chair of biology at the age of 31. Pincus performed pioneering studies of meiotic maturation in mamma- lian oocytes, in both rabbit and human oocytes. In 1934, Pincus reported the achievement of in vitro fertilization of rabbit eggs, earning him a head- line in the New York Times that alluded to Haldane and Huxley. By 1936, Harvard had cited Pincus’s work as one of the university’s outstanding scientifc achievements of all time, but Harvard denied him reappointment in 1937. At Clark University, Hudson Hoagland was in constant confict with the president of the university, Wallace W. In 1931, the Department of Biology consisted of one faculty member and his graduate student, and their chair, Hudson Hoagland. Hoagland, upset and angry over Harvard’s refusal to grant reap- pointment to his friend (suspecting that this was because of anti-Semitism), invited Pincus to join him. Hoagland secured funds for Pincus from philan- thropists in New York City, enough for a laboratory and an assistant. This success impressed the two men, especially Hoagland, planting the idea that it would be possible to support research with private money. In 1933, he earned a bachelor’s degree in animal psychology from the Tsing Hua University in Peking and stayed at the university as a teacher. Afer 1 year, he was pleased to receive an invitation from Arthur Walton to study the physi- ology of sheep sperm at The University of Cambridge, and he promptly accepted. He wrote three letters to American scientists, and only Pin- cus answered, ofering a fellowship at Clark University. Chang mistakenly assumed that a fellowship in the United States was the same as at the Uni- versity of Cambridge where a Fellow was assured of a lifetime income. Years later, Chang would direct the testing of new progestins to efectively inhibit ovulation in animals. Soon Hoagland had put together a group of outstanding scientists, but because of his ongoing antagonism with President Atwood, the group was denied faculty status. A Clinical Guide for Contraception Frustrated by the politics of academia, Hoagland and Pincus (who both enjoyed stepping outside of convention) had a vision of a private research center devoted to their philosophy of applied science. Indeed, the establish- ment of the Worcester Foundation for Experimental Biology, in 1944, can be attributed directly to Hoagland and Pincus, their friendship for each other, and their confdence, enthusiasm, ambition, and drive. It was their spirit that turned many members of Worcester society into fnancial supporters of biologic science.

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A randomized clinical study apy purchase levitra soft australia erectile dysfunction questions, contraception and treatment in peri during one year order levitra soft 20 mg overnight delivery erectile dysfunction treatment non prescription, Acta Obstet Gynecol and postmenopausal women, Maturitas Scand 76:449, 1997. Wildemeersch D, Pylyser K, De Wever Multicenter Trial, Contraception 52:77, N, Dhont M, Treatment of non atypical 1995. Van Kets H, Van der Pas H, Thiery and belief, Stud Fam Plann 20: M, Wildemeersch D, Vrijens M, Van 355, 1989. Inki P, Hurskainen R, Palo P, Ekholm mode of action of intrauterine contra- E, Grenman S, Kivela A, Kujansuu ceptive devices in women, Fertil Steril E, Teperi J, Yliskoski M, Paavonen J, 49:768, 1988. Milsom I, Andersson K, Andersch B, device users: Detection with a highly Rybo G, A comparison of flurbiprogen, specific and sensitive assay, Fertil Steril tranexamic acid, and a levonorgestrel- 47:265, 1987. Hurskainen R, Teperi J, Rissanen P, after use of the levonorgestrel 20 mcg/ Aalto A-M, Grenman S, Kivelä A, day or copper T 380Ag intrauterine Kujansuu E, Vuorma S, Yliskoski M, device, Contraception 34:261, 1986. Paavonen J, Clinical outcomes and costs Intrauterine Contraception with the levonorgestrel-releasing intra- 87. Grigorieva V, Chen-Mok M, Tarasova intrauterine system and mefenamic acid M, Mikhailov A, Use of a levonorgestrel- for the treatment of idiopathic menor- releasing intrauterine system to treat rhagia: a multiple analysis using total bleeding related to uterine leiomyomas, menstrual fluid loss, menstrual blood Fertil Steril 79:1194, 2003. Mercorio F, De Simone R, Di Spiezio charts, Br J Obstet Gynaecol 112:1121, Sardo A, Cerrota G, Bifulco G, Vancore 2005. Soysal S, Soysal M, the efficacy of trauterine system and thermal balloon levonorgestrel-releasing intrauterine ablation for heavy menstrual bleeding, Br device in selected cases of myoma-related J Obstet Gynaecol 113:257, 2006. Baldszti E, Wimmer-Puchinger B, releasing intrauterine system: effects on Loschke K, Acceptability of the long- ovarian function and uterus, Arch Gyne- term contraceptive levonorgestrel- col Obstet 280:39, 2009. Hidalgo M, Bahamondes L, Perrotti M, intrauterine system at hysterectomy, Int J Diaz J, Dantas-Monteiro C, Petta C, Gynecol Pathol 27:74, 2008. Fedele L, Bianchi S, Raffaelli R, of the levonorgestrel-releasing intrauterine Portuese A, Dorta M, Treatment of system (Mirena) up to two years, Contra- adenomyosis-associated menorrhagia ception 65:129, 2002. Kilic S, Yuksel B, Doganay M, Bardakci estrel-releasing intrauterine system on H, Akinsu F, Uzunlar O, Mollamahuto- serum lipids and the endometrium in glu L, the effect of levonorgestrel-releas- breast cancer patients taking tamoxifen, ing intrauterine device on menorrhagia Climacteric 11:252, 2008. Abu J, Brown L, Ireland D, Endometrial and the copper T 380Ag intrauterine adenocarcinoma following insertion of devices: a five-year randomized study, the levonorgestrel-releasing intrauterine Contraception 42:361, 1990. United Nations Development Pro- Latin American centers, Contraception gramme/United Nations Population 50:17, 1994. Sivin I, Dose- and age-dependent ectopic Development and Research Training in pregnancy risks with intrauterine contra- Human Reproduction, Task Force on the ception, Obstet Gynecol 78:291, 1991. Farr G, Amatya R, Contraceptive Koskenvuo M, Pregnancy during the use efficacy of the copper T 380A and copper of levonorgestrel intrauterine system, T 200 intrauterine devices: results from Am J Obstet Gynecol 190:50, 2004. Backman T, Huhtala S, Blom T, Luoto from 1966 to 1985 in Turku, Finland, R, Rauramo I, Markku K, Length of Am J Obstet Gynecol 160:642, 1989. Backman T, Rauramo I, Jaakkola K, devices and pelvic inflammatory disease: Inki P, Vaahtera K, Launonen A, Ko- an international perspective, Lancet skenvuo M, Use of the levonorgestrel- 339:785, 1992. Lundström E, Söderqvist G, Svane G, ine contraception in diabetic women, Azavedo E, Olovosson M, Skoog L, von Fertil Steril 42:568, 1984. Kimmerle R, Weiss R, Bergert M, assessment of mammographic breast Kurz K, Effectiveness, safety, and density in patients who received low- acceptability of a copper intrauterine dose intrauterine levonorgestrel in con- device (Cu Safe 300) in type I diabetic tinuous combination with oral estradiol women, Diabetes Care 16:1227, 1993. Suri V, Aggarwal N, Kaur R, the intrauterine contraceptive device vs Chaudhary N, Ray P, Grover A, Safety hormonal contraception in women who of intrauterine contraceptive device are infected with the human immuno- (copper T 200 B) in women with cardiac deficiency virus, Am J Obstet Gynecol disease, Contraception 78:315, 2008. Proceedings and Actinomyces detection on cervical from the Fourth International Confer- smear, Obstet Gynecol 87:142, 1996. Persson E, Holmberg K, Dahlgren associated with the copper-T intrauterine S, Nielsson L, Actinomyces Israelii in contraceptive device, Am J Obstet Gyne- genital tract of women with and without col 127:869, 1976. Suhonen S, Haukkamaa M, Jakobsson of intrauterine contraceptive devices in T, Rauramo I, Clinical performance of pregnancy, Obstet Gynecol 72:961, 1988. Lewit S, Outcome of pregnancy with system and oral contraceptives in young intrauterine device, Contraception 2:47, nulliparous women: a comparative study, 1970. Assaf A, Gohar M, Saad S, El-Nashar A, Eur J Contracept Reprod Health Care Abdel Aziz A, Removal of intrauterine 10:82, 2004. United Kingdom Family Planning a Wilson’s disease patient with chronic Research Network, Pregnancy outcome liver disease, Contraception 56:241, 1997. Doll H, Vessey M, Painter R, Return of Copper-T-200, Acta Obstet Gynecol fertility in nulliparous women after dis- Scand 63:261, 1984. Andersson K, Batar I, Rybo G, Return Contraceptive effectiveness of immedi- to fertility after removal of a levonorg- ate compared with delayed insertion of estrel-releasing intra-uterine device and intrauterine devices after abortion: a de- Nova T, Contraception 46:575, 1992. Anteby E, Revel A, Ben-Chetrit A, uterine contraception, Adv Contracept Rosen B, Tadmor O, Yagel S, Intrauter- 6:207, 1990. Celen S, Möröy P, Sucak A, Aktulay A, cacy of prophylactic doxycycline at inser- Danisman N, Clinical outcomes of early tion, Br J Obstet Gynaecol 97:412, 1990. A new need for sexual safety has brought modern respect and new developments to the condom, while the other barrier methods continue to serve well for appropriate couples. How- ever, the diaphragm and the cervical cap were not invented until the late 1800s, the same time period that saw the beginning of investigations with spermicidal agents. The Japanese used balls of bamboo paper, Islamic women used willow leaves, and the women in the Pacifc Islands used seaweed. Ref- erences can be found throughout ancient writings to sticky plugs, made of gumlike substances, to be placed in the vagina prior to intercourse. In pre- literate societies, an efective method had to have been the result of trial and error, with some good luck thrown in. The social and technical circumstances of ancient times conspired to make communication of information very difcult. Hence, the widespread use of potions, body movements, and amulets; all of which can be best described as magic. The descriptions of contraceptive techniques by Soranus are viewed as the best in history until modern times. Soranus gave explicit directions regarding how to make concoctions that probably combined a barrier with spermicidal action. He favored making pulps from nuts and fruits (probably very acidic and spermicidal) and advo- cated the use of sof wool placed at the cervical os. In 1564, Gabriello Fallopius, one of the early authori- ties on syphilis, described a linen condom that covered the glans penis. The linen condom of Fallopius was followed by full covering with animal skins and intestines, but use for contraception cannot be dated to earlier than the 1700s. Vulcanization of rubber dates to 1844, and, by 1850, rubber con- doms were available in the United States. The introduction of liquid latex and automatic machinery ultimately made reliable condoms both plentiful and afordable. Some blame the more prudish attitude toward sexuality as an explanation for why American women had difculty learning self-insertion techniques. By the 1950s, more than 90 diferent spermicidal products were being marketed, and some of them were used in the frst eforts to control fertility in India.

M. Thorus. Siena Heights University.

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