Ani Aydin, MD

• Department of Emergency Medicine
• Bellevue Hospital, New York University
• Medical Center
• New York, New York

This is accomplished with special equipment like an autoclave or pressure cooker that uses steam under pressure erectile dysfunction treatment herbs cheap cialis sublingual 20mg without a prescription. If the object to be sterilized can withstand high heat impotence tcm 20mg cialis sublingual mastercard, like metal can cialis erectile dysfunction wiki best purchase cialis sublingual, then flaming can be used impotence surgery buy cialis sublingual 20mg visa. With this method erectile dysfunction medications side effects discount cialis sublingual 20mg visa, the object is placed directly into a flame or is first dipped into alcohol that is then ignited erectile dysfunction effects trusted 20mg cialis sublingual. Pasteurization is the heating of things like milk and beer at lower temperatures than what would be needed to sterilize them in order to kill pathogens and lower microbial numbers while still protecting the flavor of the product. Liquid solutions can be sterilized by filtration through a membrane with a pore size smaller than the microbes to be removed. If you want proof of this, just think of how leftovers can spoil in the refrigerator if left for too long. The first example is ionizing radiation such as X-rays and gamma rays that either directly damage cells or indirectly damage them via the production of free radicals. Here are some of them: A type of phenol that comes from coal tar is called a cresol and is the main ingredient in Lysol. A bisphenol called triclosan has been used in the manufacture of kitchen utensils like cutting boards to deter microbial growth. Halogens like iodine and chlorine have been used for centuries and are still used today to treat water (iodine tablets) and in the household disinfectant Clorox. Heavy metals like silver, copper, and mercury are very effective against microorganisms and along with their historical use in medicine and industry have recently been incorporated into sporting equipment and clothing to reduce the microbes that cause odor. Get a glimpse of the early earth and see how the evolution of life on earth began with microorganisms that changed the climate to what it is today. Understand the pathways microbes use to get energy and the ways in which they get the carbon they need to make their cellular material, from either carbon dioxide or organic matter. Examine the many places where microbes live, from the bottom of the sea to inside the human body. Unravel the interconnected communities of microbes and see how they cooperate and compete with one another. As the earth changed, it provided microbes with new opportunities for diversification. Organizing our understanding of microbial diversity involves learning about how to tell microbes apart and how to name them. Measuring the diversity of microorganisms today lets us read the history of microbial evolution, which, as it turns out, is also our evolutionary history. After the oceans formed, the surface of the planet was still extremely volatile, with asteroid crashes and cosmic radiation bombarding the surface. In the mud near hydrothermal vents, energy and elements were likely plentiful and conditions for the first life forms may have been right. Tracing the origins of life Within this ancient mud at the bottom of the ocean, the following processes likely happened: 1. The formation of organic molecules was catalyzed spontaneously and without live cells. Proteins with enzyme activities started catalyzing biochemical reactions, including nucleic acid replication. They encircle things and have embedded within them proteins that can move molecules from one side to the other. Lipidenclosed biochemical processes were protected from the randomness of the outside world and the cell was born! The cell has undergone many improvements in the billions of years since it arose, but it remains fundamentally the same today. In Chapter 14, a discussion of viruses highlights some other exceptions to these steps. Diversifying early prokaryotes Early on, primitive cells diverged in two different directions, eventually giving rise to bacteria and archaea. Each of these branches was likely well suited to different environmental conditions, so each gave rise to different structural and metabolic specializations. Bacteria and archaea would have had to develop processes that were similar to each other to survive, yet the exact details would be different in each. The carbon is used to make the carbon-containing molecules used for cell structure and as energy storage. Different types of metabolism evolved, each with its own substrates and waste products. As early microbes consumed one substrate, others evolved to use a new energy or carbon source. The products of their metabolism built up and had a great impact on the chemical composition of the earth. At first, the oxygen produced merely reacted with all the reduced compounds around. But after a couple hundred million years, oxygen eventually accumulated to levels that were high enough for aerobic microorganisms to evolve. It was another 2 billion years before oxygen levels in the atmosphere would get up to the 21 percent that they are today. It formed a thick layer in the upper atmosphere that still covers many parts of the earth today. Up until that point, the levels of radiation bombarding the surface were too high to allow cells to survive. With protection from the ozone layer, life could now leave the relative protection of the sea to start colonizing the land, leading to an explosion of organisms adapted to terrestrial and freshwater habitats. Why did the presence of oxygen in the atmosphere allow such an explosion of different forms of life The amount of energy gained from reducing O2 to H2O is very high, so aerobic organisms can grow much more quickly than anaerobic organisms, producing many more cells from the same amount of a resource. What the rising oxygen levels meant for anaerobic microorganisms is that their reduced substrates were limited as oxygen spontaneously reacted with them. For many anaerobic microorganisms, oxygen was toxic, so they could either develop mechanisms to deal with it or be restricted to locations without oxygen. It started with algae that diversified extensively in the oceans and eventually gave rise to large multicellular organisms. Within 600 million years, these large multicellular organisms gave rise to the many forms of plants and animals that have lived and are alive today. Hitching a ride: Endosymbiosis the fundamental difference between eukaryotic and prokaryotic cells is the presence of a nucleus and membrane-bound organelles, which made many early microbiologists assume that the two had different evolutionary beginnings. In fact, many aspects of eukaryotic biology are more similar to members of the Archaea than to members of the Bacteria. There is still some question about the exact order in which this happened, but evolutionary biologists generally agree that the following things happened within a common archaea-eukaryote ancestor cell: 1. A cyanobacteria was engulfed to eventually become the chloroplast, giving rise to the algae and eventually plants. The photosynthetic eukaryotes that emerged from this were ancestors to the green and red algae and to the plants. Then, nonphototropic eukaryotic microbes engulfed a green or red algae in a secondary endosymbiosis event, giving rise to some of the other protist forms we see today. Bacteria could give up having to defend themselves from being engulfed and having to acquire their own food. The host cell could use some of the hydrogen and the energy produced by the bacteria for the small price of some substrates and having to carry around extra cargo. Cells at that time were likely experimenting with increased size and could use the extra energy to power cellular processes. Photosynthetic eukaryotes show up in the evolutionary record later so scientists think that this early eukaryotic cell, with mitochondria and a nucleus, engulfed a cyanobacteria so that it could use sunlight for energy as well. Next to the diversification of prokaryotes, the appearance of eukaryotes marks the second major explosion of diversity with much more complex cells that could take advantage of brand new habitats. Understanding Evolution Before we can talk about the study of evolution in microorganisms, we should first describe exactly what evolution is. Evolution is made up of a few parts: the descent of one organism from another, also known as ancestry. The individual habitats with all their specific environmental pressures is called a niche. For evolution to work, there has to also be extinction, where the survival of the more successful organisms provides the stock for the next round of diversification and selection. In this way, over time, lineages become more and more specialized for their niches. Mutations (changes) between generations affect many different characteristics of the species, but only the ones that give it an advantage are kept. Some mutations are deadly or make the individual less successful, other mutations are neutral, and still others provide an advantage. Only the neutral and beneficial mutations remain throughout the evolutionary history of that species. Even the evolution of organisms with short periods between generations is too slow to see in a lifetime. Genetically similar organisms living in the same habitat and having the same environmental pressures are called ecotypes. But if conditions change, different members of one ecotype can continue to exist, each taking advantage of different resources, making them into two new ecotypes. Some take advantage of metabolic differences between microorganisms by using biochemical tests to exclude groups one by one until a single species or strain is left. The first approach, based on looking at the unique aspects of each microbe, is used extensively in medical microbiology and is covered in Chapter 17. The second approach, based on the similarities between microorganisms, is used most often to study evolutionary relationships and is covered here and used in Chapter 18. Other genes, like those for luminescence (the production of light), change more quickly over time because their function is more flexibly controlled. More slowly evolving genes are useful for telling the difference between distantly related microorganisms, whereas more quickly evolving genes are better for distinguishing between closely related species. Vertical gene transfer Vertical gene transfer is the transfer of genetic material from the parent directly to the progeny. Errors during replication of the parent genome are transferred to each of the daughter cells, resulting in mutations that may persist through the next generations. This happens through several mechanisms, including transformation and transfection (see Chapter 6). The impact of horizontal transfer is that genes from completely unrelated species can be present within the same genome. Classifying and Naming Microbes Taxonomy is the science of classifying living organisms for the purpose of Telling them apart Describing an individual Allowing microbiologists to speak a universal language Sorting out their evolution Classification is the formal ranking that all described species are grouped into. Ranks are ordered from the most inclusive at the top to the most specific at the bottom. One helpful unofficial ranking for microbiologists is that of a strain (a subspecies label for bacteria that are within the same species but have different characteristics, called phenotypes). All described species are given a two-part name that is considered its scientific name in contrast to its common name. The two-name system is important for having an accurate record of each individual species described to date. The complete name is made up of the genus and species - for example Escherichia coli in Table 8-2, is always italicized and is often shortened to an initial for the genus and the species name: E. For instance, Escherichia is a Latinized version of the last name of Theodor Escherich, who discovered this bacterium, and coli means "of the colon. Organizing and keeping track of all of the known prokaryotes is a big job, but several resources exist: Guides for identification and classification: these are essential when describing a new strain or species or when trying to identify a strain. Culture collections: Culture collections are an important resource because they keep live cultures of microorganisms that can be bought by microbiologists. Lists of currently described microorganisms: these are easy to browse and search through. With the use of modern phylogenetic techniques, the classification and naming of many microorganisms, especially bacteria, have changed as microbiologists have realized that some species within the same genus were actually distantly related to each other and more closely related to other species. Two important examples are the reclassification of many members of very large genera into their own separate genus. This has proven to be important especially in tracing the origins of a human infection. The concept of reproductive isolation only works for organisms that reproduce sexually, so a different approach had to be taken for prokaryotes. Another approach has been proposed for defining species: the phylogenetic species concept, where several conserved genes are used to build a better evolutionary history for bacteria or archaea. More complex phylogenies are both more useful and harder to make than phylogenies based on a single gene. To date, 7,000 species of bacteria and archaea have been found for certain, with likely tens or hundreds of times more (maybe even a million total! Intuitively, it seems like there is such a variety of life around us that we can observe with our own eyes. Historically, scientists have gone through many versions of the tree of life before coming up with the one we use today. Until the advent of molecular phylogenetics, there were many different classification systems based on methods available at each time.

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If a patient demonstrates only a cataract without capsule rupture erectile dysfunction treatment penile injections order discount cialis sublingual line, a secondary operation of the cataract is a good choice erectile dysfunction kegel buy 20 mg cialis sublingual mastercard. Treatment methods After surgery erectile dysfunction age 80 cheap cialis sublingual 20mg without a prescription, systemic and topical antifungal treatments may be used for 2 weeks routinely (Xie et al erectile dysfunction latest treatments buy 20 mg cialis sublingual. For patients with these risk factors erectile dysfunction shots purchase 20mg cialis sublingual visa, however erectile dysfunction vascular causes cialis sublingual 20 mg discount, prolonged topical and systemic antifungal therapy should be initiated. The extent (or size) and depth of infection are not major relevant risk factors for recurrence. If the infected area is near the limbus, even though the infected area is of a relatively small size, it is considered to have a high risk of recurrence. If the infected area is near the limbus, it is difficult to judge the infiltrated edge by microscopy; consequently, the infected tissue cannot be removed easily in its entirety. Although both slitlamp and confocal microscopy can be used in helping to determine whether the infection has reached the endothelium before surgery, they could not reveal clearly the severity of infection in all patients. The severity of infection in some patients (approximately 20%) can be determined only during the operation (Xie et al. As it is very difficult for antifungal medications to reach the recurrence area, antifungal therapy is very ineffective and surgical treatment is necessary. This type of recurrence occurs because of the incomplete removal of the infected central corneal stroma resulting from surgical inexperience. Additionally, it is possible that some fungal hyphae growing vertically have penetrated through the cornea. The higher rate of recurrence in eyes infected with Aspergillus species may be related to the perpendicular growth of fungal filaments, which allows the infection to penetrate deep into the corneal layers or the anterior chamber in a short time. Appropriate treatment methods can be chosen based on the appearance of different clinical features. Antifungal drugs should be used and administered approximately 5 to 7 days after the procedure. The key to successful treatment is the total eradication of the recurrent infection. In this study, intracameral injections of fluconazole were effective for some patients with anterior chamber recurrence. For recurrence in the posterior segment, for which the cure rate of recurrence is low, intravitreal injection of fluconazole combined with vitreous removal should be performed as soon as possible. Clinical Characteristics and Treatment Results of Keratitis caused by Rare Fungal Pathogens Fungal corneal ulcer associated with Rhizopus spp. A 48-year-old male patient suffers corneal infection for 20 days after removal of an iron foreign body from the eye. All layers of the central cornea are infiltrated with a presence of hypopyon, and corneal scraping examination shows fungal hyphae. Corneal scraping examination and confocal microscopy both show fungal hyphae and spores. A large number of dense and messy typical fungal hyphae are found by corneal scraping examination and confocal microscopy. At 3 days, infiltration occurs on the temporal side of the recipient bed, with fungal recurrence. Subconjunctival injection of fluconazole also could not control the infection, and hypopyon appears again. Histopathology shows a vacuole-like hyphal section of Pythium insidiosum accompanied by a large number of inflammatory cells. The infected recipient bed on the temporal side is excised, and limbal corneal transplantation is performed. At 10 days after the second surgery, the severe corneal and intraocular infection requires eye evisceration. Many typical hyphae and some inflammatory cells are observed in the fungal lesion on the temporal side of the cornea by confocal microscopy. Endogenous fungal infection should be considered while treating deep fungal infection with a clinical history of trauma. For patients with infectious keratitis that cannot be definitely diagnosed, glucocorticoids should be administered with caution to prevent aggravation. Even if recurrence occurs after surgery, an individualized therapeutic method based on the recurrence characteristics can achieve good outcomes. Comparison of efficacy of topical and oral fluconazole treatment in experimental Aspergillus keratitis. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Roles of adherence and matrix metalloproteinases in growth patterns of fungal pathogens in cornea. Infectious keratitis in the corneal graft: treatment with partial conjunctival flaps. Efficacy of fluconazole subconjunctival injection as adjunctive therapy for severe recalcitrant fungal corneal ulcer. Antifungal chemotherapy for fungal keratitis guided by in vivo confocal microscopy. Efficacy and safety of long-term corticosteroid eye drops after penetrating keratoplasty: a prospective, randomized, clinical trial. Analysis of causes for penetrating keratoplasty at Shandong Eye Institute from 1997 to 2002. Hyphal growth patterns and recurrence of fungal keratitis after lamellar keratoplasty. Nursing care for fungal endophthalmitis patients treated with vitrectomy combined with liposomal amphotericin B intraocular injection. Clinical observation of anterior segment reconstruction for severe fungal corneal ulcer (in Chinese). Treatment of vitrectomy combined with Liposomal amphotericin B intraocular injection for fungal endophthalmitis. The other is that the incidence gradually decreases with increased latitude (Shah et al. Chinese patients with fungal corneal ulcers usually have a history of plant or soil trauma, followed by a history of abuse of glucocorticoids and antibiotics. In the past 20 years, the incidence of corneal fungal infection has been increasing year by year. Patients with filamentous fungal infections usually have a history of vegetative matter injury, or have worn contact lens or have undergone eye surgery. Clinical Pathology the growth patterns of fungal pathogens are related to the following clinical features: (1) Keratopathy manifests as an elevated lesion on the cornea like a carpet, covering the underlying inflammatory necrotic tissue and the inner normal corneal tissue. Patients are clinically characterized by a large-area, slowly developed, superficial corneal lesion, with mild corneal stromal edema, and usually without satellite lesions or immune rings. Clinically, it is a single ulcer, often reaching the deep corneal stroma, with lipid-like pus on the surface and marked satellite lesions all around accompanied by pseudopods. The severe inflammation causes coagulative necrosis, whereas the mild inflammatory reaction is displayed as mixture of inflammatory tissue and normal tissue. Patients present with obvious inflammatory reaction and a wide range of lesions, often a full-thickness corneal inflammation. There are distinct satellite lesions and pseudopods around the ulcer, all accompanied by hypopyon, in a short course of disease. The latter is a serious fungal infection with specific pseudopods and satellite lesions, and antifungal medications are often ineffective. However, due to the abuse of antibiotics and antiviral drugs, and more seriously the misuse of steroids, the signs and course of the disease often become atypical, which sometimes leads to fast infiltration and ulceration, and even the involvement of the whole cornea within 1 week. Therefore, the disease course cannot be regarded as a main clinical indicator for determination of fungal infection. Diagnosis and Treatment of Fungal Keratitis 81 (3) A satellite lesion refers to a small round lesion in proximity to but having no connection with the major ulceration. There is a blurry-edged transparent band area between the immune ring and the lesion. Before the cornea perforates, most of the pus in the anterior chamber is reactive, and only 15 to 30% contains fungal hyphae. Diagnosis (1) History: Any trauma to the cornea with plants or soil, long-term local or systemic administration of steroids or broad-spectrum antibiotics, or wearing of contact lenses. If the scraping process is correct, the positivity rate of fungal hyphae can be as high as 90% or more (Xu and Xie 2010). The positivity rate was 33 to 55% for Gram staining and 27 to 66% for Giemsa staining (Xie 2003). A fungal culture is required for fungal strain identification according to the fungal growth speed, colony appearance, and morphology of hyphae, spores or cells. The positivity rate of major media, such as Sabouraud medium, blood agar medium, and chocolate medium, is 52 to 79% (Xie 2003). Moreover, as some primary hospitals lack qualified professionals and necessary equipment for diagnosis of fungus, the corneal scraping and culture cannot be performed and non-invasive examination like confocal microscopy cannot be conducted. Under the situation that suppurative keratitis has not been able to be diagnosed as a fungal infection and Acanthamoeba infection, bacterial infection is often considered first. After antibiotic treatment is found to be ineffective or the disease aggravates and even with perforation, an etiological examination and referral to a higher-level hospital must be considered. However, patients have lost the optimal timing of medication, and keratoplasty is required for control of the infection, which yields not only an increased economic burden of patients but also poor therapeutic results. Elevated lesions (in approximately 20% of patients), pseudopods (68%), satellite lesions (27%), immune rings (9%), and endothelial plaques (11%) (Shi and Wang 2013) do not necessarily appear in a single patient. Doctors should carefully observe the lesions under a slit-lamp microscope so as to obtain adequate first-hand information for correct diagnosis. To improve the positivity rate of the examination, the scraping method and location are important. The necrotic tissue on the ulcer surface should be removed before corneal scraping. Meanwhile, doctors should learn to search for fungal hyphae, especially when the laboratory technician reports a negative result, but clinical signs indicate a highly suspected fungal infection. Gram staining and Giemsa staining can be employed to increase the visibility of hyphae. Hospitals at or above the county level are generally viable for etiological detection. Problems in the treatment (1) Major antifungal eye drops in China Triazoles (azoles), like 0. The local and systemic side effects are small, but the antifungal effect is not as strong as amphotericin B. Diagnosis and Treatment of Fungal Keratitis 83 Amphotericin B, one of the polyene antibiotics, is a broad-spectrum antifungal drug with strong activity and less drug resistance but significant irritation. It can damage the permeability and normal metabolism of fungal cells and inhibit their growth. Eye drops of 5% natamycin, a polyene macrolide antifungal agent, can inhibit both the growth of various molds and yeasts and the production of mycotoxins. The polyene macrolide ring on the molecular structure reacts with the cell wall of fungi (molds and yeasts) or ergosterol on the plasma membrane, causing rupture of the cell wall and plasma membrane, leakage of the cell fluid and cytoplasm, and eventually death. Domestically manufactured natamycin eye drops have just entered the market with a relatively low price. Moreover, voriconazole, a novel azole antifungal drug, has broad-spectrum activity against fungi. With its high oral bioavailability and strong penetrating power, voriconazole can achieve the same concentration in the plasma, aqueous humor, and vitreous body as in the experimental treatment for most fungal pathogens isolated from the eye (Hariprasad et al. Voriconazole can be administered as topical 1% eye drops, injection solution into the corneal stroma (0. For severe cases, particularly children who could not cooperate with topical administration, the subconjunctival injection can be added with 0. Systemic use of amphotericin B has been used less for its side effects; if needed, the general situation should be monitored. Steroid hormones can inhibit the anti-infective ability of tissue and promote the reproduction of fungi. Steroids have been found to prolong the period of tissue repair and aggravate the condition by increasing the proliferative and erosive activity of fungi (Wang et al. Moreover, long-term administration of steroid eye drops may result in fungal intraocular infection due to local immunodeficiency which changes the topical microenvironment. Therefore, it should be emphasized that steroids must be used with caution when there is no clear diagnosis of infectious keratitis. Timing for surgical treatment It is advocated that all fungal corneal ulcers, unless combined with perforation or potential perforation, should be treated with combined topical and systemic antifungal drugs to control infection. Then, according to the outcomes of treatment, size, location, depth of the lesion, and visual acuity, surgical intervention can be considered. If there is no improvement after regular local and systemic application of broad-spectrum and effective antifungal agents for 5 to 7 days, timely selection of surgery and indications becomes imperative. Due to the removal of infected tissue, the permeability of the local antifungal medication is increased, and thus the corneal infection may be quickly controlled. The large and deep corneal wound following the lesion incision needs to be covered by conjunctival flaps, which could be helpful in infection control and wound repair. After removal of the corneal lesion, the remaining ulcer is covered with an amniotic membrane. If any infected tissue remains, the infection will be aggravated, which is different from conjunctival flap covering. Because the conjunctival flap has a blood supply, its antifungal resistance is far stronger than the amniotic membrane.

The main elements that make up all of the major nutrients are carbon erectile dysfunction medication australia order cialis sublingual 20mg without a prescription, oxygen erectile dysfunction and diabetes leaflet cheap cialis sublingual 20mg with mastercard, nitrogen erectile dysfunction 55 years old generic 20mg cialis sublingual overnight delivery, phosphorous erectile dysfunction treatment natural food order 20mg cialis sublingual with mastercard, and sulfur erectile dysfunction drugs and infertility discount cialis sublingual 20 mg. These processes are called biogeochemical processes because cycles are affected not only by biological processes but also by geological and chemical ones cough syrup causes erectile dysfunction generic 20 mg cialis sublingual. Despite their small size, microorganisms have a large impact on biogeochemical processes. As long ago as the 19th century, bacteria were suspected of recycling elements between environments and today we know just how extensive their roles are. For every biogeochemical cycle, there are reservoirs where compounds are stored and active processes that transform and move compounds around. Carbon cycling Organic compounds are carbon-containing compounds that make up all the cellular life on earth. Taking the inorganic carbon in the environment and making organic compounds is the job of the autotrophs that are also called primary producers. The main autotrophs responsible for carbon fixation on earth are plants and photosynthetic microorganisms like algae, cyanobacteria, and other types of phytoplankton. Other nonphotosynthetic microbes fix carbon and contribute a bit more to the global organic material. The main processes of carbon utilization on earth are from heterotrophic microbes that either consume it through respiration (both aerobically and anaerobically) or fermentation. Ocean and land animals also consume a small amount of the organic matter produced. These microbes are found in the sediments of the ocean and belong exclusively to the Archaea. Fossil fuels: Deposits of plant material that have been converted to hydrocarbons over many millions of years. Organisms: Carry a significant amount of organic carbon around with them, which they release back into the environment when they die. Nitrogen cycling In addition to carbon, cells also need nitrogen to build things like proteins and nucleic acids. But unlike carbon, where the different forms are more complex organic molecules, the nitrogen cycle involves only different oxidation states of nitrogen. Aside from fixing it from the air, nitrogen is available from decomposing organic matter. When something dies, microorganisms break down the proteins into amino acids and then into ammonia. Each reaction is catalyzed by different bacteria that live together in neutral soils that are well drained, because flooded soils become anoxic quickly. This happens extensively in soils, especially after fertilizer (natural or chemical) is added. Because nitrogen fixation is so expensive metabolically, it can only happen when a lot of energy is available. Symbiotic nitrogen-fixing bacteria include Rhizobia, Cyanobacteria, and Frankia, all discussed next. Rhizobia live in nodules and produce an oxygen-binding protein called leghemoglobin that keeps free O2 levels low. Others have high rates of oxygen consumption so that there is never a large concentration within the cell. Sulfur cycling the sulfur cycle is about the different oxidation states of sulfur - there are many more states than there are for nitrogen. The major volatile gas hydrogen sulfide (H2S) is the most reduced form of sulfur and is used by many bacteria that oxidize it either to elemental sulfur (S0) or to sulfate. Some bacteria even store S0 in their cells as a source of electrons for later (see Chapter 10). The sulfide produced from sulfate reduction, combines with iron to form insoluble black deposits of iron sulfide minerals (FeS and FeS2). These elements also cycle due to the activities of microorganisms, but unlike the other cycles, there are no volatile forms that can escape. As with the other nutrient cycles, keeping things in balance is very important to ocean and terrestrial life. Organisms that use Ca2+ in their exoskeletons, like Foraminfera and corals, need a more basic ocean pH; otherwise, the calcium carbonate deposits that they make get dissolved. Microbes Socializing in Communities Microbes living together in communities interact with one another in positive, negative, and neutral ways. They compete with the other members of their guild for resources, and they compete with everyone for space. They orchestrate these interactions by communicating with members of their own species and with other species through chemical signaling molecules. Using quorum sensing to communicate Quorum sensing is the process in which regulatory pathways within the cells of a population of bacteria are controlled by the density of cells of their own kind. As the name implies, if a sufficient numbers of cells (a quorum) are present, they can do something that requires more than one cell to accomplish. Quorum sensing controls biofilm formation and toxin production, among many other things, some of which are not fully understood. Cells produce a signal molecule called an autoinducer that is sensed by other cells in the vicinity. When enough cells produce the autoinducer, the concentrations become high enough within cells to trigger gene expression. Some autoinducers are specific for the same species of bacteria, whereas others can signal across species. Living in biofilms Whenever you have a fluid washing over a surface, like the water over rocks in a stream or saliva over the teeth in your mouth, biofilms form. A biofilm is a collection of microbes, usually bacteria but also sometimes archaea, within a sticky matrix attached to a surface. There can be an impressive number of species of microorganisms inside of a biofilm, or it can contain only a small number of species. Here are the main reasons bacteria form biofilms: Forprotection: Biofilms are thought to form in order to protect cells from predators, from environmental stresses, and from being mechanically removed from a surface. Forproximity: When cells are close enough together, they can communicate and exchange genetic material and other molecules. They can become a problem for humans, however, because they tend to clog up pipes and filters, form on medical equipment and devices, and protect human pathogens during an infection. Because biofilms are resistant to antibiotics and protected from phagocytosis by our immune cells, organisms in a biofilm are really hard to get rid of. Current research is aimed at preventing biofilms from forming, as well as biofilm-busting treatments with mechanical means and chemicals. This is where oxygen levels on the surface or near a hole in the biofilm are highest and decrease as you move toward the center of a solid area. These areas of low oxygen are a perfect place for anaerobic bacteria or archaea to colonize. Exploring microbial mats You can think of a microbial mat as an extreme example of a biofilm. When plants arrived and started competing with mats for light, and when predators arrived and started eating the bacteria, the number of mats declined. Mats are still found today, mainly in habitats with extreme temperatures or high levels of salt. Microbial mats are many centimeters thick, made of several layers, each with different species of bacteria. Microbial processes, as well as physical factors, result in each layer having different oxygen concentrations, nutrients, and pH conditions. Filamentous cyanobacteria, as well as filamentous chemolithotrophic (sulfateoxidizing) bacteria are common members of microbial mats. Discovering Microbes in Aquatic and Terrestrial Habitats Everything is not everywhere, so although microbes can be found in every habitat, species have their preferred habitats, along with some less-than-ideal ones that they occupy only occasionally. Most aquatic habitats (saltwater and freshwater) and terrestrial habitats contain plants, animals, invertebrates, and microbes. Aside from the nutrient cycles, a few other things describe a microbial community: membership (who is there), diversity (how many different species are thriving there together), and biomass (how big the populations are). The factors that affect these things are nutrient concentrations, mixing, and oxygen concentrations. Thriving in water the photosynthetic microorganisms are commonly found in both freshwater and saltwater habitats. These include algae and cyanobacteria, which either float in the water column (planktonic) or attach to surfaces (benthic). Oxygen levels in freshwater habitats influence the types of communities that can live there. High rates of carbon fixation by primary producers is a problem for all aquatic habitats because it can lead to spikes in heterotrophic activity that consume all the oxygen. These bursts of oxygen consumption affect rivers and oceans as well, but freshwater lakes in summer are particularly vulnerable because they tend to be stratified without much mixing. The organic material and dead autotrophs from the top layer sink down to the bottom of the lake. Because diffusion rates of oxygen into water are low, heterotrophs at the bottom quickly use up all the available oxygen when consuming the organic matter. This zone lacking oxygen is called the anoxic zone and is unsuitable for fish or invertebrate life, but it can be perfect for anaerobic microorganisms. Coastal oceans and the deep sea are two other aquatic habitats for microorganisms. Oxygenic phototrophs use water (H2O) as an electron donor, whereas anoxygenic phototrophs use other reduced molecules like H2S and H2). The photic zone extends down to 300 meters, where light penetrates the water, providing an energy source for a large variety of phototrophic marine microorganisms like algae, phytoplankton, and bacteria. Immediately below the photic zone, down to 1,000 meters, there is no light but there is still biological activity. Below 1,000 meters is the deep sea, where there is far less biological activity because of the low temperature, low levels of nutrients, and high pressure, which increases with depth. There are some unique microbial habitats in the deep sea for bacteria and archaea able to withstand the great pressure, such as those near hydrothermal vents and in the sediments. Soil is made of minerals, organic matter, water, and microorganisms, with pockets of air mixed in. For instance, dry soil has very little water, compacted soil has less air, mineral soil has little organic matter, and organic soil has a lot. Different parts of a soil particle contain different micro-colonies of bacteria or archaea or have fungal hypha growing through them. Plant roots excrete many compounds into the soil such as organic acids, amino acids, and sugars. These compounds attract and support the growth of many kinds of microbes, including bacteria and fungi. Some of these rhizosphere microbes are beneficial to plants because they compete with pathogens in the soil and produce small molecules that are taken up by the plant and used in maintaining hormone balance. The intensity of the interaction between microbes and their living habitat can be anywhere from very high (where both need each other to live) to low enough that neither really notices the other. Very intimate relationships between organisms are called symbiosis, with the microorganism called the symbiont and the other called the host. The nature of the relationship between organisms can be positive, negative, or neutral. For the most part, only positive and neutral relationships are covered here because negative relationships, such as infections, are discussed in Chapters 15 and 17. Microorganisms can form a symbiotic relationship with one another, as well as with other organisms. Lichen are an example of this where algae or cyanobacteria live in very close association with fungal hypha to the mutual benefit of both of them. The algae or cyanobacteria make organic compounds through photosynthesis, and the fungus provides support and protection. Every surface of a plant - both above ground and below ground - is colonized with microorganisms. Plants form intimate relationships with some microorganisms, like bacteria and fungi, that provide them with fixed nitrogen, small molecules, and protection from pathogens in exchange for sugars. There are many different types of plant-microbe interactions, a few of which are covered here. As mentioned in the earlier section on the nitrogen cycle, plants are limited by a lack of fixed nitrogen and often live in association with nitrogen-fixing bacteria, which occur either in the soil as free-living microbes or within plant root tissues. The term rhizobia refers to the group of nodule-forming rhizobacteria that include species of Rhizobium and Bradyrhizobium, among others. Legumes are extremely important to agriculture because they return some fixed nitrogen to the soil when planted in rotation with other crops. One example is the alder tree, which can associate with the filamentous bacteria Frankia. The partnership generates enough fixed nitrogen that alder trees can grow in nitrogen-poor soils. Frankia is not as picky as the rhizobia and will also colonize other woody plants. Mycorrhizal fungi form important symbiotic relationships with many different plants, some of which are dependent on the fungi for survival. The bacterial genus Agrobacterium forms a parasitic association with plants, called crown gall disease, causing large tumor-like growths on plant tissues.

Diseases

• Cerebellar ataxia infantile with progressive external ophthalmoplegia
• Tuberculous meningitis
• Pseudoaminopterin syndrome
• Congenital hypotrichosis milia
• Sandhaus Ben Ami syndrome
• Vulvovaginitis
• Tibial aplasia ectrodactyly hydrocephalus

It is appropriate for benign lesions as well as metastases and myeloma Wide resection involves removing the entire tumor with surrounding normal tissue relative impotence judiciary generic cialis sublingual 20 mg amex. This is used in sarcoma Amputation is reserved for cases where limb salvage is not possible erectile dysfunction treatment homeopathy purchase genuine cialis sublingual line. This occurs in cases where excision involves critical nerves and blood vessels such that complete excision would leave a nonfunctional limb r Wide resection r Amputation Chemotherapy Radiation Chemotherapy is used with curative intent for sarcoma next generation erectile dysfunction drugs buy cialis sublingual 20mg visa, usually both before and after surgery erectile dysfunction more causes risk factors purchase 20mg cialis sublingual with mastercard, and for palliation in metastatic disease and myeloma Used as an adjunct in most soft tissue sarcomas erectile dysfunction diabetes generic 20mg cialis sublingual with mastercard. It can also be used as a primary treatment modality for metastatic disease and myeloma Prevention/management of complications r Thorough investigation to establish the correct diagnosis prior to surgery minimizes complications such an inappropriate intralesional resection of sarcomas erectile dysfunction main causes cialis sublingual 20 mg with amex, which may jeopardize life and limb. It provides palliation for metastatic lesions and myeloma, and improves local tumor control after surgery. Special populations Children r Bone sarcomas are most common in the young and account for 4% of tumors in children, and r Soft tissue sarcomas make up 7% of tumors in pediatric patients, but are more prevalent in r the most common musculoskeletal malignancies in children are osteosarcoma, Ewing sarcoma, r Expandable prostheses are useful in making up for remaining growth in children as the growth plate is usually resected with sarcoma. Follow-up tests and monitoring r Patients should continue surveillance after treatment for bone or soft tissue sarcomas. Patients should be followed with history and physical examination, and appropriate imaging studies. Sarcoma classification: an update based on the 2013 World Health Organization classification of tumors of soft tissue and bone. Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathologic fractures. The most common primary intraocular tumors are uveal melanoma in adults and retinoblastoma in children. Nearly half of all patients with uveal melanoma will eventually die from metastases, even with early treatment. Background Definition of disease r the field of ophthalmologic oncology encompasses primary and metastatic tumors of the eye and ocular adnexa. Disease classification r Primary intraocular tumors arise from the globe itself, while adnexal tumors develop from the r Metastatic tumors to the eye tend to involve the choroid and most commonly arise from the breast or lungs. Pathology/pathogenesis r Uveal melanoma develops through uncontrolled proliferation of uveal melanocytes, though the molecular pathogenesis of this tumor is still unknown. Proposed mechanisms include constitutive Bcl-2 expression leading to apoptosis resistance or inhibition of the Rb and p53 tumor suppressor pathways causing the development of dormant nevi that either remain as such or undergo malignant degeneration. Hereditary retinoblastoma is bilateral (one-third of cases), while sporadic retinoblastoma is usually unilateral (two-thirds of cases). Screening r Given the rarity of ophthalmologic tumors, there are currently no evidence-based standardized screening methods for uveal melanoma or other less common tumors. Annual ophthalmologic Ophthalmologic Oncology 475 examinations including slit lamp and dilated fundus examination can assist in detecting cancer of the eye and ocular adnexa. Secondary prevention r Plaque brachytherapy has a role in preventing re-occurrence of uveal melanoma, although r Chemoreduction with systemic chemotherapy and focal adjuvant therapy or intra-arterial chemotherapy with melphalan have been shown to prevent reoccurrence of retinoblastoma in children. Visual complaints such as flashes, floaters, or blurry vision as well as systemic symptoms such as anorexia or weight loss should also be inquired about. Retinal examination may reveal melanotic (brown) or amelanotic (yellow) masses in the choroid in uveal melanoma. The differential should include other common causes of leukocoria in children such as congenital cataracts, persistent hyperplastic primary vitreous, Coats disease, and ocular toxocariasis. Differential diagnosis Differential diagnosis Uveal melanoma differential: choroidal nevus Features Pigmented or nonpigmented flat lesions of the choroid that are usually <2 mm thick and can gradually become elevated with age. If symptomatic, patients can present with decreased vision, visual field defects, floaters, light flashes, and, rarely, pain. Clinical diagnosis History r When concerned about uveal melanoma, it is important to ask questions that help to differentiate primary ocular melanoma from metastatic disease. Inquiring about a past medical history of cancer, particularly breast, lung, and cutaneous melanoma, as well as systemic symptoms such as anorexia and weight loss, assists in the diagnosis. It is also important to ask questions that help rule out other conditions that mimic retinoblastoma. Disease severity classification r Spindle-A cell melanomas have the best prognosis and epithelioid cell melanomas have the worst prognosis. Laboratory diagnosis List of diagnostic tests r Laboratory tests are not used in the initial diagnosis of intraocular tumors. Diagnosis of ocular complications of systemic cancer therapy r Systemic cancers and their treatments can have adverse effects on the eye. It is important for medical oncologists to know when to refer patients to an ophthalmologist. A detailed history to determine the onset of ocular symptoms in relation to initiation of chemotherapy is important. A basic eye examination should be performed to assess pupils, near visual acuity, and visual fields before a more extensive investigation by an ophthalmologist. Symptoms of both syndromes include ring scotomas, shimmering photopsias, and nyctalopia, which should prompt referral to an ophthalmologist, as diagnosis involves dilated fundus examination demonstrating very subtle retinal findings. Patients may be asymptomatic or experience nonspecific symptoms such as vision loss, floaters, photopsias, or peripheral field defects. In patients with a known cancer diagnosis, such symptoms should prompt referral to an ophthalmologist for further evaluation. Potential pitfalls/common errors made regarding diagnosis of disease r Significant delays in diagnosis of retinoblastoma are commonly reported in developing countries, where children are diagnosed at advanced stages of the disease and have a poorer prognosis. Those with a delay in diagnosis or misdiagnosis such as benign choroidal nevus or age-related macular degeneration are more likely to need enucleation if diagnosed at an advanced stage. If the initial tumor is too extensive for eye salvage therapy, patients undergo enucleation. Second line treatments include external eye wall resection surgery and transpupillary thermal therapy. Second line therapies include thermotherapy, cryotherapy, laser photocoagulation, plaque brachytherapy, external beam radiotherapy, and systemic chemotherapy for metastases. It is also used when the affected eye has no visual potential Used in patients who develop extensive retinal detachment after radiation therapy or to preserve as much vision as possible when radiation therapy is unlikely to do so (poor plaque candidates). It can be performed when the tumor does not involve the posterior pole and is <15 mm in diameter Comment isolated hepatic perfusion therapy with high dose chemotherapy. It can be used as an adjunct to radiation to reduce tumor recurrence rates Used in patients with marginal recurrences after proton therapy Prevention/management of complications r Nonproliferative and proliferative radiation retinopathy and optic neuropathy are complications of plaque brachytherapy, especially in diabetic patients. The choice of treatment and radioisotope for brachytherapy should be selected very carefully. Special populations Pregnancy r It has been suggested that uveal melanoma development may be accelerated by pregnancy because of increases in melanocyte-stimulating hormone. Treatment with plaque brachytherapy tends to be safer toward the end of pregnancy or after birth, with no reported complications or infant metastases. Children r Though rare (1% of all cases), uveal melanoma can develop in children, particularly at or after puberty, and has a better prognosis with lower risk of metastasis. Natural history of untreated disease r Untreated uveal melanoma has a mortality rate of 31% at 5 years. Liver metastases are most common (87% of patients) and carry the worst prognosis with a median survival time of 7 months. The overall median survival time of patients with metastatic uveal melanoma is less than 1 year. If a child remains recurrence-free after 5 years post-treatment, they are considered cured of the disease. Lifetime screening for secondary malignancies should take place in those with familial retinoblastoma. Retinoblastoma treatment burden and economic cost: impact of age at diagnosis and selection of primary therapy. The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease. Although uncommon, pseudohypopyon can occasionally be the initial presenting sign of diffusely infiltrating retinoblastoma as in this patient. It represents cancer cell infiltration of the anterior chamber of the eye masquerading as a hypopyon or true pus collection. Incidence/prevalence r For cancer survivors free of cardiovascular disease at 50 years of age, more than 50% of men and nearly 40% of women will develop cardiovascular disease during their remaining lifespan. Pre-existing risk factors or underlying disease: r Coronary artery disease and ischemia r Hypertension r Alcohol-related cardiomyopathy r Diabetes r Nutritional deficiencies r Cardiac cachexia r Thyrotoxicosis or hypothyroidism. Pathology/pathogenesis r the exact mechanism of cardiotoxicity is agent specific and not quite clear. Cardio-Oncology 489 Primary prevention the following have been studied for primary prevention of cardiotoxicity in high risk individuals, those undergoing high dose chemotherapy, or stem cell transplant: r Beta blockers such as carvedilol and nebivolol. Emerging data on myeloperoxidase need to be confirmed whereas the role of brain natriuretic peptides and C-reactive protein have not been established. Therefore, if continued surveillance with serial echocardiograms is not carried out after completion of chemotherapy, cases of heart failure can be missed. Enalapril, carvedilol, nebivolol, valsartan, and candesartan have demonstrated the best outcomes when studied in this population. Children r Minimizing anthracycline dosage in pediatric cancer patients is a primary method of cardioprotection. Dexrazoxane and enalapril have also been studied as primary (pre-exposure) and secondary (post-exposure) cardioprotectant agents, respectively, in this population. Elderly r the incidence of cardiotoxicity increases with age >65 years with both anthracyclines and trastuzumab. Follow-up tests and monitoring r Patients with history of anthracycline administration should have surveillance echocardiograms annually up to 5 years if their cumulative dose was <400 mg/m2 and annually up to 10 years if dose was >400 mg/m2. Evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Cardiovascular complications of cancer therapy: incidence, diagnosis, pathogenesis, and management. The figure on the left denotes end-diastole and the one on the right depicts end-systole. As there is a decrease in the longitudinal length, it will be denoted by a negative (-) sign; hence the longitudinal strain will be -25%. In the inset, dexrazoxane was shown to bind to Top2 to prevent anthracycline binding. Validation studies have found that a score of 4 or greater should prompt a second evaluation by a team member to determine the nature of the distress and whether the patient should be referred to a psychiatrist, psychologist, social worker, or chaplain. Clinical management Distress Patients who are most vulnerable to distress are those with: r Prior psychiatric disorder (depression, substance abuse) r Cognitive problems Mount Sinai Expert Guides: Oncology, First Edition. However, olanzapine, an antipsychotic, is also often used off label to treat severe anxiety with good results. Depressive disorders r Sadness and grief are normal reactions to a cancer diagnosis and treatment. Because sadness is common, it is important to distinguish between the normal continuum of sadness and depressive disorders. Because the etiology of vegetative/somatic symptoms can be difficult to determine, researchers recommend more emphasis be placed on psychologic symptoms. Drug Starting dose (mg) Maintenance dose Selective serotonin reuptake inhibitors Escitalopram (Lexapro) Fluoxetine (Prozac) Citalopram (Celexa) Benzodiazepines Alprazolam (Xanax) Clonazepam Diazepam (Klonopin) 0. Overdosing with analgesics and sedatives is the most common method of suicide among persons with cancer. Patients at high risk for suicide: r Active suicidal ideation with intent/plan to die. It is usually reversible and occurs in cancer treatr Delirium is often under-recognized and undertreated as it occurs commonly with fever, drugs, metabolic disturbances, central nervous system metastases, and paraneoplastic disorders. A discussion about suicide does not increase risk Assess level of risk Most patients with cancer have passing thoughts about suicide like, "If it gets bad enough I might do something. Obtain prior history Assess substance abuse Identify bereavement Assess medical predictors of risk (Source: Psycho-Oncology: A Quick Reference on the Psychosocial Dimensions of Cancer Symptom Management. Be prepared Develop a "psychiatric code" procedure for psychiatric emergencies Useful institutional phone numbers should be kept on hand and easily available Hospital security, 911, or police Psychiatrist on call Emergency room Chaplaincy Social work Psychiatric hospital admission Do not leave the patient alone until they can be evaluated and started in treatment In the hospital, call a security officer. If not, call 911 At home, can family bring the patient to clinic or the emergency room If not, call 911 to take the patient to the nearest emergency room Dangerous objects. Infection Metabolic disturbance Fever Hypoxia Hypo- or hyperglycemia Electrolyte disturbance Impaired liver function Impaired kidney function Corticosteroids Sympathomimetics Anticholinergic medications Opioid analgesics Benzodiazepine sedative hypnotics Alcohol or drug intoxication Especially alcohol or benzodiazepines Chemotherapy agents (ifosfamide, methotrexate, cytosine arabinoside) Biotherapy agents. May be better if distressed family members do not stay with the patient, especially overnight 1: 1 monitoring by professional patient aides helps ensure patient safety and allows family members to get needed rest Physical environment Caregiver concerns (Source: Psycho-Oncology: A Quick Reference on the Psychosocial Dimensions of Cancer Symptom Management. Drug Antipsychotics Haloperidola (Haldol) Chlorpromazinea (Thorazine) Risperidone (Risperdol) Olanzapine (Zyprexa) Dosage Comments 0.

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