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R. Iomar, M.B. B.CH., M.B.B.Ch., Ph.D.

Vice Chair, Alabama College of Osteopathic Medicine

Phenindione It produces more serious nonhaemorrhagic toxic effects: should not be used. This is more likely if therapy is not properly monitored or interacting drugs/contraindications are present. Cutaneous necrosis is a rare complication that can occur with any oral anticoagulant. Phenindione produces serious toxicity; should not be used (though still available). Factors which enhance the effect of oral anticoagulants (see above) should also be taken into consideration. Warfarin given in early pregnancy increases birth defects, especially skeletal abnormalities: foetal warfarin syndrome-hypoplasia of nose, eye socket, hand bones, and growth Chapter 44 retardation. Drug interactions A large number of drugs interact with oral anticoagulants at pharmacokinetic or pharmacodynamic level, and either enhance or depress their effect. These interactions are clinically important (may be fatal if bleeding occurs) and may involve more than one mechanism; the exact mechanism of an interaction is not always definable. Newer cephalosporins (cefamandole, moxalactam, cefoperazone) cause hypoprothrombinaemia by the same mechanism as warfarin -additive action. Chloramphenicol, erythromycin, celecoxib, cimetidine, allopurinol, amiodarone and metronidazole: inhibit warfarin metabolism. Barbiturates (but not benzodiazepines), rifampin and griseofulvin induce the metabolism of oral anticoagulants. The dose of anticoagulant determined during therapy with these drugs would be higher: if the same is continued after withdrawing the inducer- marked hypoprothrombinemia can occur- fatal bleeding is on record. Heparin is utilized for rapid and short-lived action, while oral anticoagulants are suitable for maintenance therapy. Deep vein thrombosis and pulmonary embolism Because venous thrombi are mainly fibrin thrombi, anticoagulants are expected to be highly effective. The best evidence of efficacy of anticoagulants comes from treatment and prevention of venous thrombosis and pulmonary embolism. Prophylaxis is recommended for all high risk patients including bedridden, old, postoperative, postpartum, poststroke and leg fracture patients. When deep vein thrombosis/ pulmonary embolism has occurred, immediate heparin followed by warfarin therapy should be instituted. Three months anticoagulant therapy (continued further if risk factor persists) has been recommended by American College of Chest Physicians (2001). Introduction of low dose heparin prophylaxis for patients undergoing elective surgery has considerably reduced the incidence of leg vein thrombosis and pulmonary embolism in the postoperative period. It is based on the premise that inhibition of small amount of activated factor X prevents further amplification of active products-particularly thrombin. This is the regimen of choice: does not need laboratory monitoring; spontaneous bleeding does not occur. It was hoped that anticoagulants will prevent extension of the thrombus and ward off a recurrent attack. For secondary prophylaxis against a subsequent attack- anticoagulants are inferior to antiplatelet drugs. Vascular surgery, prosthetic heart valves, retinal vessel thrombosis, extracorporeal circulation, haemodialysis Anticoagulants are indicated along with antiplatelet drugs for prevention of thromboembolism. The coagulation factors get consumed for the formation of intravascular microclots and blood is incoagulable. They are curative rather than prophylactic; work by activating the natural fibrinolytic system.

Pts can be asymptomatic or can present with fever, cough, chest discomfort, hemoptysis, and shortness of breath. Aspergillus disseminates from lung to brain, skin, thyroid, bone, and other organs. Cerebral aspergillosis: Single or multiple lesions, hemorrhagic infarction, and cerebral abscess are common. The presentation can be acute or subacute, with mood changes, focal signs, seizures, and a decline in mental status. Chronic pulmonary aspergillosis is characterized by one or more cavities expanding over months to years, with pulmonary symptoms, fatigue, and weight loss. The overall mortality rate is ~50% with treatment, but the disease is uniformly fatal without therapy. Pathogenesis Most cases are acquired via inhalation, with consequent pulmonary infection. Early: headache, fever, lethargy, cranial nerve paresis, visual deficits, meningismus. Usually asymptomatic but can present as cough, increased sputum production, and chest pain. If azole prophylaxis fails, it is unclear whether a class change is required for therapy. No evidence indicates whether or not therapy modifies progression to bronchiectasis/fibrosis. Note: the oral dose is usually 200 mg bid for voriconazole and itraconazole and 400 mg bid for posaconazole. Caspofungin is given as a single loading dose of 70 mg, followed by 50 mg/d; some authorities use 70 mg/d for patients weighing >80 kg, and lower doses are required with hepatic dysfunction. Micafungin is given as 50 mg/d for prophylaxis and as at least 150 mg/d for treatment; this drug is not yet approved by the U. Lipidassociated amphotericin B is given at 3 mg/kg (AmBisome) or 5 mg/kg (Abelcet). Lesions can be papules, plaques, purpura, vesicles, tumor-like lesions, or rashes. If antiretroviral therapy results in immunologic improvement, it may be possible to stop fluconazole. Mucorales appear as broad, usually nonseptate hyphae with branches at right angles; organisms are described as ribbon-like. Epidemiology Mucorales are ubiquitous in the environment, and spores of these fungi are likely to be inhaled daily. Pts may present with typical symptoms of sinusitis: low-grade fever, dull sinus pain, nasal congestion, and thin bloody nasal discharge. The disease may progress to hypesthesia or numbness of the face overlying the infection, headache, bloody nasal discharge, and altered mental status. Orbit involvement causes double vision, blindness, reduction of ocular motion, proptosis, and ptosis. Diagnosis Biopsy of sites of infection for histology and culture is critical for an accurate diagnosis; as much tissue as possible should be submitted for examination. Mucormycosis Three factors are key to successful outcomes: reversal of underlying predisposing condition, if possible; aggressive surgical debridement; and aggressive antifungal treatment.

Those same values that he carried throughout his career in Delaware and into the Vice Presidency. Through thick and thin, he trusted me to be his partner in so many fights, and I will be forever grateful to him. So when he asked me to help organize women for his 1988 Presidential campaign, I was all in. I cherished our time serving in Congress together, and I was so honored that he asked me to carry the Violence against Women Act in the House. Well, if I am being honest, it was his then 8-year-old daughter, Ashley, who got him involved. Schoolchildren across the country were boycotting their tuna fish sandwiches after learning that dolphins could be killed as tuna was caught, and Ashley was begging her father to take action. Our bill became law in 1992, and it is estimated that it saves tens of thousands of dolphins every year. I thought he was very courageous to point out a better way to solve the civil war in Iraq, and I was so proud to stand with him. Who could ever forget how he shepherded the Recovery Act through Congress-a near impossible feat in this polarized political climate Who could ever forget his long history of fighting for community policing and to strengthen the bonds between police officers and their communities When he talks about his incredible wife, children, and grandchildren, you know they are his guiding star. He likes to tell the advice that his father gave him as a child: ``Champ, when you get knocked down get up. President, I join my colleagues today in honoring you and thanking you for the incredible devotion you have shown to the U. Senate and to express my deep respect for you-respect that I know the people of Michigan share. One thing we have always had in common: our parents were both in the automobile industry. As of course you know, your dad was a car salesman, and my father owned an Oldsmobile dealership. So we have both known, from the very beginning, how critically important American manufacturing is for so many people in Michigan and across the country. We worked together, both when you were the Senator from Delaware and then as the Vice President of the United States, to save the auto industry back in 2008. There are countless instances over your 40 years of service when you were on the right side of history: when you led the passage of the Violence Against Women Act; in your work as the chair of the Judiciary and Foreign Relations Committee; through your wise counsel as Vice President and your ability to work with us to get so much done over the last 8 years; with Dr. Early on in your career, you said that the work that we do here allows us to ``literally have the chance to shape the future-to put our own stamp on the face and character of America, to bend history just a little bit. There is a great quote from a poet I know that you admire very much, William Butler Yeats. President-understood that the best way to reach people is by appealing to their heart, meeting them where they are. In return, he gave his life to the Senate, serving the people of Delaware for more than three decades. He served also as the chairman of the Foreign Relations Committee, facing down dictators and championing nuclear nonproliferation. He is, of course, recognized in Senate lore as a particularly strong speaker and debater. If the Chamber was empty of Senators, he would even turn and deliver his speeches to the captive audience in the staff gallery behind him. Not long ago, he was in my home State of Rhode Island to tout needed infrastructure projects. Now, Rhode Island has one of the highest rates of structurally deficient bridges in the Nation, and my senior Senator, Jack Reed, and I have worked hard to bring Federal resources to bear in addressing that need. A personal relationship is what allows you to go after someone hammer and tongs on one issue and still find common ground on the next.

The disease has three stages that are characterized by marked changes in skin color. Diagnosis Diagnosis is based on clinical presentation, dark-field microscopy of scrapings from lesions, and serologic testing (as for venereal syphilis). Diagnosis A high index of suspicion prompting elicitation of a detailed exposure history is critical and guides confirmatory testing. Most other serologic tests use a saprophytic leptospire as the antigen and provide nonspecific results. From a pragmatic viewpoint, severe leptospiral disease frequently requires empirical initiation of broadspectrum parenteral therapy before the diagnosis is confirmed. Clinical Manifestations Symptoms are similar, although not identical, in the two types of relapsing fever. Relapsing febrile episodes are typically of shorter duration than the first episode. Diagnosis Laboratory confirmation is made by the detection or isolation of spirochetes from blood during a febrile episode. Microscopic examination of Wright- or Giemsastained thick or thin blood smears or buffy coat analysis is most common. Monitoring the pt for a Jarisch-Herxheimer reaction (an acute exacerbation of symptoms including hypotension, tachycardia, and marked elevation of body temperature) for the first 12 h after the first dose of antibiotic is recommended. Clinical Manifestations the clinical manifestations of all the acute rickettsial presentations are similar during the first 5 days and consist of nonspecific symptoms: fever, headache, and myalgias with or without nausea, vomiting, and cough. As the course progresses, clinical manifestations-including occurrence of a macular, maculopapular, or vesicular rash; eschar; pneumonitis; and meningoencephalitis-vary from one disease to another. Pathogenesis Rickettsiae are inoculated by the tick after 6 h of feeding, spread lymphohematogenously, and infect numerous foci of contiguous endothelial cells. After 3 days of nonspecific symptoms, half of pts have a rash characterized by macules appearing on the wrists and ankles and subsequently spreading to the rest of the extremities and the trunk. Bleeding is a rare but potentially lifethreatening consequence of severe vascular damage. Diagnosis Within the first 3 days, diagnosis is difficult, since only 3% of pts have the classic triad of fever, rash, and known history of tick exposure. Recognized principally in New York City, rickettsialpox has been reported in other urban and rural locations in the United States as well as in Ukraine, Croatia, Mexico, and Turkey. Clinical Manifestations A papule forms at the site of the mite bite and develops a central vesicle that becomes a painless black-crusted eschar surrounded by an erythematous halo. The diagnosis can be based on serology, immunohistochemistry, or detection of the organism in a louse found on a pt. It is endemic in eastern and southern Asia, northern Australia, and the Pacific islands. Clinical Manifestations Clinical findings are nonspecific and include fever (96%), headache (72%), myalgia (68%), and malaise (77%). Clinical Manifestations Given high seroprevalence rates in endemic areas, it appears that most people develop subclinical infections. Cattle, sheep, and goats are responsible for most cases of human infection; many other animals can serve as vectors of transmission or as reservoirs of disease. Clinical Manifestations the specific presentation of acute Q fever differs geographically (e. The vegetations differ from those in bacterial endocarditis of other etiologies and manifest as endothelium-covered nodules on the valve. The combination of rifampin (300 mg once daily) plus doxycycline (100 mg bid) or ciprofloxacin (750 mg bid) has been used with success. Genome sequence data from many different Mycoplasma species have helped define the minimal set of genes necessary for cellular life. Lacking a cell wall and bounded only by a plasma membrane, mycoplasmas colonize mucosal surfaces of the respiratory and urogenital tracts.