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Niten Singh, MD

Chief of Endovascular Surgery
Vascular/Endovascular/Limb Preservation Surgery Service
Department of Surgery
Madigan Army Medical Center
Tacoma, Washington

What was striking in those discussions was how much information trans people are unable to access antibiotics nursing considerations generic ciprofloxacin 1000 mg free shipping. Questions from trans women included the following: Long-term efects and safety of hormones antibiotic resistance paper purchase discount ciprofloxacin on-line, and whether there is any diference between birth control pills and other hormones Efects on libido and fertility Needing to be on hormones before having breast or genital surgery Safe anal douching (See 4 antibiotic gel for acne buy generic ciprofloxacin 250 mg on line. This was particularly noticeable amongst trans men living in communities in which English is not widely spoken or read antibiotics for chest acne purchase generic ciprofloxacin from india. During the consultation antibiotics for sinus infection and bronchitis safe ciprofloxacin 750mg, a group of trans men from one South Asian country discovered what binders were and learnt how these could help fatten their chests bacteria 40x purchase ciprofloxacin with a visa. It is a low-cost, trans-led community project in which predominantly trans women and kathoey provide online sexual health and legal information, and social support to their peers in the Tai language (Chaiyajit, 2014). In some countries in this region, there is very little information to share and, in communities with few visible trans men, no one to ask. Four months before the Transmen Camp, the organiser had started daily diaries on his personal blog about his expe riences as a trans man. In September 2014, he and two other trans men offcially launched the blog as Transhition transhition. The name and logo are a reference to how hard it is to transition as a trans man in Indonesia. Roughly 20 trans men regularly respond to the blog, which receives about three emails per week. It has had about 6,000 visits in the frst six months, between September 2014 and February 2015. This is a part of our strategy to show that trans issues are not merely about physical transition. However, it wants to avoid situations in which young trans men hurry through a physical transition process, ignoring the wider social, economic, psychological, and health impacts. There are English-language resources and online communities for trans men in this region, primarily in Australia and New Zealand. However, the information is not always relevant to the very different experiences of trans men in Asia or an emerging trans masculine community in the Pacific. For this reason, all staf, both clinical and non-clinical, need to be trained to demonstrate respect and consideration towards everyone who accesses the premises. Staf who are encountered frst are key players, since their attitudes will be considered a refection of the overall attitudes and quality of the health service. If trans people perceive an attitude or behaviour as hostile or disrespectful, it may prevent them from utilising the service. Receptionists are the face of a service, and need to be included in any trans sensitivity trainings. Receptionists and other health facility staf can support the creation and enforcement of a trans-inclusive waiting room. This could include developing and posting trans-inclusive non-discrimination policies, enforcing these policies when violated, and engaging trans people and communities in ways to make the waiting room trans friendly. When possible and feasible, clinics could include appropriate restroom/toilet facilities to accommodate clients with a variety of gender identities and expressions. Clinic forms and charts should allow for more than two genders, a preferred or nickname in addition to legal name, a preferred pronoun or title, and a space to indicate what name to use during telephone calls, correspondence, and when calling people from the waiting room. His preferred male name might be confdential, and it may be unsafe for it to be used in correspondence with him. Forms and computer systems need to allow for noting this degree of detail about preferred names. Mechanisms should be in place to prevent misidentifcation of clients due to a discrepancy between preferred and legal name. Laboratories and pharmacies are other places where legal names are ofen used on records, with the result that trans people may avoid testing or accessing medications. Some of the initial questions could include the following: Basic questions about gender identity and expression Preferred name, pronouns, gender and details of their social, medical, and surgical transition. If time permits, it is also useful to gather information on the use of alcohol and other substances. Also assess whether the client has experienced violence, self-harm, or injuries at home. Examinations may need to be deferred to a later visit and not done at the initial encounter. Medical providers should work to build trust and rapport with their clients through the use of appropriate language, including asking the client about their preferences in describing anatomy. Providers should explain all components of the examination and procedures beforehand so the client can be fully informed and decide whether or not to consent to some or all of them. Providers may also wish to discuss the choice of language and medical terms with their trans clients; for example, many trans men prefer that providers refer to chest and not breasts. This diversity includes the impacts of non-surgical body modifcations, such as chest binding by trans men or tucking of testicles by trans women. Trans people need access not only to gender transition-specifc healthcare needs, but also to holistic and gender afrming routine general health services and preventive care. However, the circumstances in which trans people live, including impacts of minority stress resulting from their gender identity, may make it much harder to maintain a healthy lifestyle. Trans men who have not had top surgery may intentionally carry extra weight to obscure the appearance of breasts and hips; others may attempt to stay thin to de-emphasise curves and a feminine appearance. Chest binders designed for trans men may make it easier for some to exercise, particularly for non-contact sports; however, binders that are too tight may restrict chest expansion and make exercise difcult. Conversely, some trans men on testosterone may have difculty in gaining weight or muscle mass. Testosterone intake should be adjusted to appropriate male age and activity levels. Trans women may have eating disorders, such as anorexia, or may intentionally take in fewer calories than necessary to maintain a slight build. Other trans women may prefer to gain weight to promote the growth of breasts and hips, which can lead to overweight and obesity. Some trans women may avoid exercise because it is perceived as a male trait or can result in increased muscle mass and a less feminine appearance. Providers should remind trans women of the importance of exercise to maintain a healthy cardiovascular system and optimal bone density. Most recommended vaccinations are not sex specifc and thus are the same as for any client. For those without access to medical and surgical transition services, the use of sof tissue fllers may be the only permanent body modifcation tool available to them. Using sof tissue fllers can provide a rapid and welcomed transformation to their appearance. Unfortunately these fllers carry risks, including local and systemic infection, embolisation, painful granuloma formation, and a systemic infammatory syndrome that can be fatal. In some countries, health workers have performed sof tissue fller injections, ofen unethically or illegally. Additionally, some laypersons may hold pumping parties, at which trans women are injected with these substances using insufciently sterile techniques. Trans women should be screened for prior or risk of future use of sof tissue fller injections and counselled appropriately. Providers should employ a harm-reduction approach to trans women 78 4 who continue to inject sof tissue fllers. Clients should be advised against sharing needles or participating in pumping parties. Complications resulting from prior injections may require surgery to remove fllers or repair excessive damage. Trans people who have not used cross-sex hormones require the same screening criteria as persons of their natal sex, so national guidelines (if they exist) should be followed. Tere have not been any studies that indicate a higher risk of diabetes amongst trans people receiving cross-sex hormones. In many parts of the world, trans people have higher tobacco prevalence than the general population. It is therefore important to screen and treat for known cardiovascular risk factors. For more information on assessing cardiovascular health and hormone use, see Appendix A 1. Trans women, past or current hormone use: Breast: In the absence of trans-specifc guidelines, some experts recommend that national breast-screening practices be applied to trans women. Despite a theoretical risk, no increase in breast cancer incidence has been found to date among trans women on hormones. Risk factors should be assessed on a case-to case basis and according to current evidence-based algorithms. In trans women who have had a vaginoplasty, the prostate can be palpated in the anterior neovaginal wall. It is therefore important to perform periodic visual inspection with a speculum, looking for genital warts, erosions, and other lesions. Trans men, past or current hormone use: Breast cancer: Annual chest wall/axillary exam; follow breast cancer practices as for natal females (not needed following chest reconstruction, but consider if only a reduction was performed). If oophorectomy is performed, it is important that hormone therapy be maintained to reduce the likelihood of osteoporosis. Follow standard national screening recommendations for other cancers, including anorectal, if possible. Providers should be aware that afer a gonadectomy, if a trans client stops hormones, there could be a risk of osteoporosis. Tere is some early evidence that trans women may have lower bone density before initiation of cross-sex hormones, possibly due to lower involvement in physical exercise (avoidance of exercise to prevent muscle mass). In countries where there are national guidelines for osteoporosis screening, providers should encourage trans clients to participate in such screening. In several locations, including Mumbai, Chennai, Bangalore, and Hyderabad, clinics engaged healthcare providers who were sensitive to the needs of trans clients, and provided hormone care, information about gender transition, laser (hair removal) services, and referrals for gender-affrming surgeries. It also reduces loss to follow-up because clients typically receive a diagnosis and treatment within a single visit. Tus, where resources allow, it is recommended that screening with laboratory testing and aetiological diagnosis be conducted for all sexually active clients. As of May 2015, only three case reports have appeared in the published literature of gonococcal infection of a neovagina. Cross-sex hormone use may reduce fertility; this may be permanent even if hormones are discontinued. Estrogen may have the efect of reducing libido, erectile function, and ejaculation in trans women. Special considerations for trans women: Neovaginal walls are usually skin, not mucosa; when it is mucosa, it is urethral or colon mucosa. Perform periodic visual inspections with a speculum to look for genital warts, erosions, and other lesions. It is important to also check for the presence of urethral discharge and ano-genital discharge (using an anoscope) and genital ulcers. No similar data exist for trans men in this region, and a few studies amongst trans men in the United States show generally low levels of infection (Herbst et al. Research in recent years has documented the lack of interconnectedness between these various intervention components and the resulting losses to follow-up. Tese losses are greater across the cascade for trans people than amongst the general population. They are exacerbated amongst trans subpopulations, including trans sex workers, drug users, and youth. In some places that serve a larger trans community, there could be assistants who are trans persons themselves. Tese assistants may help in the collection of personal data, provide general information about the functioning of the service, and motivate users to take advantage of certain interventions. Tese may include the following: Anal/vaginal intercourse without a condom, including receptive anal/vaginal intercourse for trans men Insertive/receptive anal intercourse for trans women Receptive neovaginal intercourse amongst trans women who have had sex reassignment/gender-afrming surgery Sharing of injection paraphernalia during drug or hormone use, or for sof tissue fller injections Counselling also should take into account that erratic hormone use can result in mood swings, masculinising hormones increase libido, and feminising hormones may impair erections and thus make condom use more difcult (Bockting et al. Trans women and men may feel at a disadvantage in negotiating sexual practices and prevention behaviours because they perceive a shortage of partners willing to enter into a committed relationship. The desire to conform to specifc cultural beliefs and practices around gender roles may also contribute to heightened sexual risk. Like other at-risk populations, research has shown that for trans women, unprotected sex is most likely with non commercial primary partners (Nemoto et al. Programmes may also provide trainings for healthcare providers and assist clients to access social support services, when available, that may cover treatment-related costs. They may not be welcoming to trans participants and may be ill suited to provide for the specifc needs of trans men and women. Whenever possible, social support for trans people should be provided, either ofine or online, by trans peers (Bockting et al. Anxiety and depression, including suicidal ideation and attempts, are prevalent and are associated with stigma and discrimination (Bockting et al. Evidence and data on mental health can be found in Chapter 3: Right to Health (Section 3. A mental health assessment is crucial, with particular emphasis on how the trans client has coped with the social stigma attached to gender variance. It is essential that healthcare providers are alert to manifestations of suicidal ideation.

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From a medical 104 standpoint virus ntl purchase ciprofloxacin uk, those Haitian Voodoo bokors certainly know what they are doing infection gum quality ciprofloxacin 500 mg. For those of us who are fortunate enough to have the technology of modern medicine at our disposal to prevent death antibiotics used for ear infections purchase ciprofloxacin with a visa, why do we have to die The fact of the matter is that human beings antibiotic quiz questions cheap 500mg ciprofloxacin visa, along with all other plants and animals antibiotic names starting with z buy generic ciprofloxacin pills, are genetically programmed to die treatment for dogs dry eye buy ciprofloxacin visa. All organisms that have sex, including single-cell eukaryotes, are condemned to die as a condition of birth, as the biologist William Clark puts it in his book, Sex and the Origin of Death. And in so doing (as Clark explains so well in his book) the parents of this genetically new offspring necessarily consign themselves to senescence and eventual death. They clone themselves and will continue to do so as long as there are adequate nutrients and sufficient space in which to keep on multiplying. In cells that have sex to reproduce new offspring and cant clone themselves, a limited life span is a genetically determined property of the organism. The really important cells in a multicellular organism, like us, are the germ cells, the sperm and ova that mammalian testicles and ovaries produce, respectively. The rest of the cells in a multicellular organism are termed the somatic cells, in us the 100 trillion or so cells that make up a human being. Scrape some skin off a person and these cells, termed fibroblasts, will divide and multiply (like bacterial cells do) when placed in an appropriate nutrient bath at the correct temperature. Take them from a middle-aged person and they will divide and double their number 20 to 30 times and then stop (bacterial cells will keep on dividing and doubling their number forever, if you let them). Take them from a fetus and they will go through about 50 cell divisions before they stop. Take some skin from my ninety-two year old friend George Taylor (he would probably let you do it if you asked, just to see what would happen) and those fibroblasts would probably stop 105 dividing after one or two divisions. There is a rare disease, called the Hutchinson-Gilford progeria syndrome, where due to a little understood genetic abnormality, the genetically controlled human aging process is greatly speeded up. William Clark describes it this way: Children [with progeria syndrome] undergo the entire human aging process, through death, in about fifteen years. Their faces begin to look old, with delicate blue veins criss-crossing their foreheads. A few years later, their hair begins to fall out; what is left soon turns gray They rarely enter puberty, seeming to progress directly into old age. Frail and shriveled, they usually die of cardiovascular disease or stroke 106 before the end of their second decade of life. Somatic cell death is an integral ingredient in the complex recipe for life that is encoded in our genes. We can hope that we will lives as long, and in as good estate as people like George Crosby; like my paternal grandmother, who lived to be 100, and my cousin Sally, who remained quite feisty up until her death at the age of 103; or like my friend George Taylor, who recently underwent quadruple coronary Heart in Hand 166 artery bypass surgery at the age of 93 and continues to remain physically and socially active. The average life expectancy of a person in the United States is now 76 years, and increasing. In 1900, the average life expectancy was only 47, and more than half of those deaths occurred in children less than 14 years old. Cure heart disease and cancer and 107 the majority of the populace would live into, and essentially die of, old age. While only about 1 per cent of deaths in our still relatively peaceful country are due to homicide, human-made death has been a scourge throughout the world in this century that is now ending. A very tiny fraction of the people who were the victims of th this 20 century scourge, some 50,000 young Americans are listed by name, in chronological order of their deaths, on the marble walls of the Vietnam War Memorial in Washington, D. With the letters, poems, flowers, and mementos laid by the etched names of those loved ones who met an untimely death in that far corner of the world, who amongst us who has visited this site has not been moved to tears Consider then, if we are to look starkly at the realities of life, the full scale of th human-made death in the 20 century. One particularly chilling example of human-made death occurred in 1937, in Nanking. My friend George Taylor lived in Nanking, then the capital of China, in the mid-1930s. Recently, a book titled the Rape of Nanking was published, a sobering account of the atrocities that the Japanese committed when they invaded this city in 1937. On the way to Nanking officers in the Japanese Army held contests to see who would be the first to be able to decapitate 100 living Chinese persons with their swords, and the results of such contests were reported back home in the Japanese newspapers. He said that he knew some of the people at the University there whose lives were consumed in this heretofore essentially unreported mini-Holocaust (the Japanese government still officially denies Confronting Death 167 that it happened, despite overwhelming evidence to the contrary). It was very sad for him, indeed for all of us, to finally learn the full truth of the carnage that was inflicted on 108 that city by reputedly civilized people. The Twentieth Century Book of the Dead, published in 1972, describes how an estimated 110 million people, 10 million of them children, died in this century from the violence of war or as a result of other actions of human beings. These human-made deaths occurred as follows: More than 62 million people died in conditions of privation, 20 million in enclosed ghettoes, concentration camps, prisoner-of-war camps, and Russian labor camps, where 12 of these 20 million people died. More than 15 million people died from starvation and/or exposure in cities under siege, occupation, or in the throes of civil war, and 26 million died in a state of privation from dislocation due to war, as refugees. More than 42 million people died directly as a result of the violence of war, 1 million from aerial bombs, 18 million from artillery fire, and 24 million people from small arms fire, of which 10 million were either massacred (six million) or executed in a formal manner (four million). Another 3 million people died from various forms of domestic violence, such as in the Russian bread wars, Chinese anti-bourgeois campaigns, and Indian Partition riots. Also not included in these statistics is the genocide that has occurred in Cambodia, engineered by Pol Pot, and in Rwanda and the Balkans. One hopes that in the next century no new predators of other human beings the likes of a Hitler, Stalin, or Mao will arise and take control of the reins of a nation-state. We must hope that in the next century a more Schopenhaurian view of compassion for other people and other living things will arise, which will help to de-emphasize an overweening interest in self, and power over others, as the ultimate objective of life. Failing that, may we be able to live unmolested by totalitarian dictators, terrorists, or unpoliced street gangs. Heart in Hand 168 Grateful as we may be for being able to maintain our health and live under good circumstances, we are still besieged with this haunting question: What happens to us after death He says, instead of worrying about what happens to us after death, we should ask ourselves this question: Where was I before my birth For it is irrefutably certain that non-existence after death cannot be different from non-existence before birth, and is therefore no more deplorable than that is. An entire infinity ran its course when we did not yet exist, but this in no way disturbs us. On the other hand, we find it hard, and even unendurable, that after the momentary intermezzo of an ephemeral existence, a second infinity should follow in 109 which we shall exist no longer. If our soul, or spirit, did not exist before our physical birth, what claim do we have to such a thing after our physical death The Hindu and Buddhist religions, which Schopenhauer studied closely, answer this most important question this way: Our individual souls did previously exist. They were embodied in other humans, or, they say, indeed, in other animals, now dead. Schopenhauer would say that at death our individualness, our willful personhood, our soul is extinguished once and for all. We die and our physical person merges back into the universal, timeless, undifferentiated Noumenon. And if you are not careful how you conduct yourself in this life, your karma may consign you in the next life to be something you would just as soon not be, like a mole rat. Most people in this culture would prefer a more concrete, individualistic form of immortality. But if our souls were not embodied in past lives and we arose from a void, where do we go One concrete form of immortality that we can hope for is what some observers term biologic immortality. With my th children, who are only 1/32 of them, their biologic immortality has indeed become insignificant. In Exodus 20: 6-7 and 34: 5-6, God tells Moses that the punishment of people who hate him will be also inflicted upon their children out to the fourth generation. Heart in Hand 170 Even from a species standpoint, there is no such thing as biologic immortality. Although some 30 million or so species of living things currently exist on this planet, paleobiologists estimate that 99 per cent of all the species of living things that have existed on the planet are now extinct. Most species live for several million years and then disappear, to be replaced by new ones. Paleobiologists reckon that the combined weight of all organisms that have lived on Earth over only the last 500 million years, not to mention the previous three billion years, equals the total mass of the planet. The two most severe ones that we know about occurred 110 245 and 66 million years ago respectively. There is another kind of immortality that human beings can obtain, one that can last at least as long as our species continues to exist on the planet. Thelonious Monk died in 1982 (at the age of 65), 24 years after I saw him play at the Five Spot. In the last years of his life he refused to perform, remained secluded at home with his wife and refused to receive visitors. Thelonious would be very surprised to learn, if it were possible for him to know now that he is dead, that his music is played daily in operating rooms where patients are undergoing open heart surgery. At Swedish Medical Center in Seattle, refrains from his easily absorbed Riverside Trios of Duke Ellington standards provide a soothing backdrop for the delicate work that we do there. With considerable aplomb he steered his way through the shoals of American racial polarization and has left us an enduring body of work. Near the end of his life Ellington was hospitalized in the Harkness Pavilion of the Columbia-Presbyterian Medical Center. The hospital personnel placed a small upright piano in his room at the foot of his hospital bed. I was a member of the surgical team that took care of him (he had chest surgery for what proved to be an incurable form of cancer), and I would make rounds with the team and see him. One of Confronting Death 171 the residents played the piano and knew a lot of Ellington tunes. Duke Ellington died in 1974, but all over the world people continue to sit down and play, or listen to , his wonderful music. Eventually, the spray-painters gave up (but I still keep looking for it to reappear every time I drive that way). The list of great artists who have achieved some degree of creative immortality, in all of the arts, goes on and on. But as Woody Allen says, I dont want to gain immortality in my work, I want to gain it by not dying. We know what happens to our bodies after we die, our ancient bacterial ancestors feast on them and they become foul smelling and putrefied, if they not are embalmed or burned first. These phenomena include seeing ghosts, reports of out-of-body experiences, receiving messages from the dead, reincarnation memories, and near-death experiences. A lot of people believe that these phenomena provide genuine proof that there is life after death. Indeed, wearing black to a funeral is an ancient custom that was first used by mourners and pallbearers as a protective camouflage to evade recognition and possible possession by the recently deceased. And coffins were nailed shut to prevent the dead from coming back and haunting the living. Reincarnation memories in children also have been 111 extensively studied and the results are mixed. Near-death experiences tell us a great deal about the effects of endorphin and other neurotransmitters in people whose brain cells are suffering from a temporary lack of oxygen but have not reached the point of no return of cell death. Some people even like to reproduce this experience by tying a plastic bag around their head when they have sex. Such experiences may be near death, or occur just before death, but they do not tell us anything about death itself. The evidence derived from these various phenomena for Confronting Death 173 their being a soul that exists separately from the body is inconclusive. Although at one point in my life I thought about becoming a Presbyterian minister, I lost the faith necessary to believe that there is life after death when I went to college and studied biology and philosophy of religion. Can a person whose thoughts and feelings are mediated by countless numbers of interconnected neurons in the brain continue to exist as that person in some sort of spiritual form once those cells cease to function and die Is it possible that we go on to some higher spiritual plane after our death, as many people, including my dear wife, Linda, strongly believe We can circle around the black hole of death and make various observations about it, but we cannot know what lies on the other side until we cross over. And as with an actual cosmic back hole, once you cross its event horizon there is no coming back. I fear that the last memory I have of Heart in Hand 174 my indomitable sister going on a hike with me in the Olympic Mountains of Washington State during a visit after her chemotherapy, bald and wearing a wig, refusing to turn back when she got tired, will have to suffice. Nancy kept a photograph of our maternal grandmother, Mary Ashby Warden Williams, on her dresser. We never knew her because she died in childbirth at the age of 24, when our mother, her first child, was only 18 months old. Nancy said, after her breast cancer was diagnosed following the birth of her second child, pointing to the photograph of Mary Ashby, I feel very close to her.

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Errors and Mutations Errors introduced in copying or storing genetic data are the source of the genetic changes that drive evolution antibiotic 800mg purchase ciprofloxacin 500mg free shipping. Some errors antibiotics for sinus and upper respiratory infections generic 1000mg ciprofloxacin with visa, such as in a sequence which controls basic cell design antibiotics for sinus infection cheap ciprofloxacin 1000mg mastercard, or oxygen transport antibiotic question bank discount 1000mg ciprofloxacin otc, or other crucial process antibiotics for uti kidney infection purchase ciprofloxacin amex, are almost always immediately fatal and so are immediately selected out and do not propagate into the genetic code of descendent organisms antibiotic resistance originates by purchase ciprofloxacin overnight delivery. Humans share some sequences with yeast that both humans and yeast must have received from a common ancestor. An error in such a sequence might only cause slight variation of a parameter and only very mildly affect fitness. Finally, some sequences (possibly more than 90 percent of the human genome) have no apparent biological purpose. Changes in such a sequence generally have no immediate effect on the organism and are putatively not selected against at all, thus apparently freely propagating to future generations. Since larger animals have trillions of cells, there are trillions of opportunities for mutations. However, for a mutation to be inherited it must occur in the sequence of cell division between the original egg cell and the subsequent egg or sperm cell. In modern electronic data systems, it is not unusual for errors to occur more or less frequently depending on the pattern of the data. Errors in both electronic and genetic systems can be caused by substitution of an incorrect letter in a sequence and can also be caused by deletion of a letter or insertion of an extra letter. In the genetic code, which is all about pattern and sequence, it is not surprising that it is also true that the chance for an error is pattern sensitive. Copying errors (insertion/deletion 71 the Evolution of Aging errors) which change the length of these repeats are thought to occur virtually every generation. Because of pattern sensitivity, the probability of particular errors varies enormously and is difficult to predict. Genes in the duplicated sections can have subsequent errors that sometimes result in new, useful genes. Presumably, this is the mechanism whereby a more complex and longer genome can evolve from a simpler one. In human genetic code there is a specific pattern of about 300 bases called the alu element. Alu appears about one million times in the human genome and is thought to have a significant role in affecting duplications, which in turn, have a significant role in genetic diseases as well as in implementing evolution of the genetic code. The human genome contains approximately 30,000 genes but the actual number is still unknown. The structure of the sequence of information representing a gene as seen reading sequentially along a chromosome typically includes regulatory regions at the beginning or end of the gene sequence that determine when and where the gene is activated. The coding region determines which protein will be produced by the gene, that is, the sequence of amino acid molecules which will be constructed to produce a particular protein molecule (often referred to as the gene product). The properties of a protein are determined not only by the number and type of the amino acid molecules used in its construction but also by the particular sequence in which the amino acids are assembled. The long protein molecules tend to fold up in very complex ways depending on the particular sequence. There are therefore an essentially infinite number of possible different proteins. Since there are 20 possible amino acids and 64 possible codons, some errors in the third symbol of a codon have no biological effect. The regulatory regions determine when, where, and how much product will be produced. Although some genes produce proteins used in the construction of tissue, many, probably a majority, produce products that act as signals to activate or inhibit other genes thus allowing the construction of a very complex regulatory logic framework. In connection with anti-aging research, detecting the differences in gene activity between a caloric restricted animal and not, or between a progeria victim, and not (see next chapter) could produce valuable clues regarding aging mechanisms. We can think of a specific gene as a message defining a product that accomplishes a particular biological function. Since all multi-cell organisms have a common basic cell design and function it should be no surprise that there are genes that are common to all such organisms. It is estimated that 99 percent of mouse genes have an equivalent human gene that produces a very similar product. A large proportion of the possible random changes to a gene result in its function being destroyed, that is, inactivation of the gene. The organization of the genes in the genome tends to be very different between even similar species. Mice have a different number of chromosomes from humans and the equivalent genes are generally in a different order on different chromosomes. Some genes are organized in groups or clusters that are conserved between mice and humans. The deletion is caused by patterns at the beginning and end of the intron that match in a particular way. They contain their own synchronization patterns and Figure 17 Genes and Chromosomes operate somewhat independently. The position (or locus) of a gene within a chromosome or on a particular chromosome generally does not appear to affect the functional operation of the gene. Methods for inserting new genes into chromosomes have been developed and are used in genetic engineering. Such a gene would be propagated during cell division and even possibly during reproduction of the organism. All normal humans are thought to have the same genes, specifying the same or nearly the same products, in the same order, on the same chromosomes. Genetic differences between humans are expressed in the exact digital content of their genes, generally minor differences such as single letter substitutions. Mendelian genetics considers that some genes in a particular species can have two different specific data contents or alleles such that two different results occur. Often one allele is represented by a gene that is disabled and therefore produces no functional product, while the other allele is represented by the functioning gene, a binary situation. In practice, some genes can have more than one functioning state and a single gene can therefore have more than two alleles. A complex gene having tens of thousands of bases could possibly have many alleles. An error in the regulatory region or an error that deletes the start codon or adds a stop codon could cause the gene to become disabled and produce no useful product. An insertion or deletion in a coding region is likely to disable the gene because all subsequent data would be misinterpreted. The insertion or deletion of exactly three contiguous letters might well have only a minor effect because it would only cause an extra amino acid molecule to appear in the resulting protein (or a single amino acid to be deleted). Other errors could have more minor effects such as changing the amount of product produced. Many of the more than 1000 known human genetic diseases as well as most of the normal variations between individuals are caused by such single letter differences in the genome. If the genes received from both parents are defective, then the child has the recessive genetic disease. Therefore, by far the most likely possibility in a mutation is a single letter error. It would appear to be ridiculously unlikely that an entire new functioning gene could be produced by a random mutation. Since the sequence of the human genome has been completed, it might seem a simple matter to have a computer program search through the genome, and identify genes by their characteristic data patterns such as start and stop codons, regulatory sequences, and intron patterns. In practice, although the start and stop codes are definite, the patterns involved in regulatory sequences and the patterns that denote the borders of an intron are often quite vague in that many different patterns appear to accomplish the same result. In addition, the genome contains pseudogene patterns that resemble genes but are not functional. A pattern can be definitively considered a gene if a gene with the same or similar exons has been found in 74 the Evolution of Aging another species, or if a genetic disease or other trait has been traced to two different forms of the (otherwise) same pattern. Because of these difficulties, we do not yet know for certain even how many genes are in the human genome and have definitively identified relatively few genes. However, they do have an apparent evolutionary effect in that they influence mechanisms that cause segments of code to be duplicated, copied to another part of the genome, or deleted. The sections of expressed genetic code (exons) between introns appear in some cases to correspond to building blocks or modules that have been used by nature to produce a family of different proteins each of which consists of one or more common modules added to a unique sequence. Although the content and length of introns in a particular gene tends to vary between species, the exons and the number of introns tend to be more nearly conserved. Meiosis and Recombination As mentioned, (haploid) sex cells have only one copy of the chromosomes so that when a sperm and egg cell are united the resulting (diploid) cell and subsequent cells have a normal complement of two sets of chromosomes. In order to do this, half of the genetic material is not used during the creation of a sperm or egg cell. This process, called meiosis, and other aspects of sexual reproduction are extremely complicated as will be summarized below. The purpose of this section is to demonstrate the enormous difficulty nature has endured in order to produce the maximum possible genetically transmitted and structured variation in organisms despite the digital nature of the genetic code. In the process of meiosis, one chromosome from each set of two coming from the two parents is randomly selected for transmission in the sperm or egg cell. Humans have 23 different chromosomes (designated as numbers 1 through 22 in order of decreasing length (as seen in the rod form) and either X or Y). Note that the complex recombination mechanism has to guarantee that exactly one of each set of two chromosomes will be transmitted and that we do not possess three of chromosome 1 and none of chromosome 2, etc. We can illustrate the effect of recombination as follows: Suppose that a single pair of parents could produce 1,000 children. All of the children, (excepting identical twins), would be different from each other, different from their parents, and different from their ancestors. Each child contains two sets of genetic data derived by randomly merging the four sets of genetic data possessed by the parents. Each of the four sets of data possessed by the parents is only very slightly different from the other three. However, because of the cascading effect of combining the data variations in different ways, the range of differences between the 1,000 children will be greater than the differences between the parents. For example, we would expect to find some children that are shorter than either of their parents and we would also expect to find some children that are taller than either of their parents. Recombination, unknown to Darwin, fundamentally alters the process of evolution as will be described. The differences produced by recombination are constrained by the differences in the original four sets of genetic data. If, for example, both parents were tall, blue-eyed, blond, 75 the Evolution of Aging Scandinavians, descended from generations of blond, blue-eyed Scandinavians, we would expect all the children to be relatively tall and blue-eyed. If one of the parents was such a Scandinavian and the other was a short, darker skinned person from a distant geographic origin, we would expect the variations between children to be much greater. Although the twins have identical genetic data, they each have two different sets of data. Their descendants are the result of recombining these two sets in different ways and will therefore be different from each other. If each twin possessed two identical sets of genetic data, then their descendants would be identical. Crossover 23 A random sort of human chromosomes would result in 2 or 8,388,608 different possible combinations. Each parent performs such a random shuffle of the chromosomes received from their parents in producing the sperm and egg cells. However, it was eventually determined through inheritance studies that reality was actually yet more complicated. If only the chromosomes were shuffled, then inheritance of a gene on a chromosome would be tied to inheritance of another gene on the same chromosome. If you inherited one gene from one grandparent, you would have to also inherit the other gene from that same grandparent. However, if genes were on the same chromosomes the inheritance of the respective traits ranged from almost independent (inheritance of one trait was random relative to the other) to nearly totally dependent (inheritance of one trait almost always meant inheritance of the other). As a result, the probability of inheriting any two genes on a single chromosome from one parent is proportional to the physical data distance (number of bases) between the genes on the chromosome. If two genes are physically close, then they almost always would be inherited together, if physically distant, their inheritance would be almost independent. Using this genetic linkage (also sometimes referred to as genetic distance) principal and mind numbingly tedious inheritance studies, geneticists have been able to determine the approximate physical chromosome location (locus) of many genetic disease genes. For example, it was determined that Duchenne muscular dystrophy is caused by defects that disable a gene located near the middle of the short arm of the X chromosome. This gene produces a protein, dystrophin, which is needed for proper muscle function. A crossover could involve exchanging exactly 31,500,354 bases starting at base 15,213,655 on each chromosome as measured from the beginning of the chromosomes. If true, this arrangement would represent a major limitation on the process of evolution. Suppose a mutation to an individual organism caused an insertion or deletion of a single base at position 136. Now remember our earlier discussion regarding merging of digital data and the sorts of errors that are created when attempting to merge data strings of different lengths. An insertion at letter 136 would cause one of the crossed over segments in the above example to start one letter further along the chromosome than the swapped segment, causing what amounts to a deletion of one letter. At the same time an insertion of an extra letter would occur at the end of the swapped segment. Any subsequent mating attempt resulting in crossover between a chromosome that had the insertion/deletion and one that did not would result in at least two additional errors because the beginnings and ends of the swapped segments would not match. Therefore, mutations that caused insertions or deletions would be essentially infeasible under the equal crossover arrangement. Insertions appear to be essential to the creation of more complex genetic data and therefore to the creation of more complex organisms.

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But clinical research continued at the Brusch Clinic antibiotic nebulizer order ciprofloxacin pills in toronto, and in collaboration with herbalist Elmer Grove z-pak antibiotic 7 day order ciprofloxacin without a prescription, Caisse and Brusch added additional herbs antibiotic 4 times daily buy ciprofloxacin now, feeling they had potentiated the 1448 formula to the point it no longer needed to be injected virus hitting schools 750mg ciprofloxacin, but could be taken orally virus morphology buy 500 mg ciprofloxacin mastercard. This test is intended to detect immunotherapeutic effects (indicated by the occurrence of tumor regression) or chemotherapeutic effects (indicated by a diminished tumor growth rate) antibiotics with milk generic 750mg ciprofloxacin. The results of six immunotherapy tests and two chemotherapy tests of Essiac samples using the S-180 system all 1449 showed no activity. These disappointing results led to accusations by Caisse of improperly prepared Essiac and the implantation of animal 1450 rather than human carcinoma in the mice. The controversy around Essiac surfaced publicly again in Canada in 1977 when Homemakers Magazine, a widely read national publication, printed an exhaustively-researched article about Caisse and Essiac describing numerous case histories. The management of the publication also offered to set up a trust for Caisse "to represent her in any dealings she might have with the government, Cancer Institute or any interested pharmaceutical companies," an offer she refused 1451. One of the results of the renewed interest in Essiac was an offer from the Resperin Corporation to open five fully staffed clinics to offer Essiac free of charge to those who could not afford the proposed price of the therapy if she would grant the corporation exclusive rights to the formula. Resperin also offered to test Essiac in formal clinical trials with 1451 human subjects. In 1978, Resperin filed a "preclinical new drug submission" with Health and Welfare Canada which would have allowed clinical trials with human subjects to proceed. No evidence of acute toxicity 1453 was found, although some evidence of subacute toxicity (slight weight loss in treated animal) was observed. Details of such submissions are confidential, so the circumstances of the denial are unavailable. Investigation of the nine remaining cases revealed that the cancer was progressing (four cases) the patient had died (two cases) or that the disease had stabilized (three cases). Of this last group, all the patients had previously undergone some form of cancer treatment which could have stabilized 1457 the disease. It was also noted that some of the patients might have benefitted psychologically or emotionally from the treatment. Few patients reported any serious side effects other than occasional nausea vomiting that was attributed to a "variation 1458 in composition" of the preparation. Critics of this study cite numerous unanswered questions, such as whether the patients who "received no benefit" experienced a reduction in pain or increased appetite, whether the herbs were properly handled and the formula 1459 prepared properly, or whether the formula was given orally or by injection. Though the research using Essiac in animals and humans is inconclusive, some research does exist on the anticancer properties of its various constituent herbs, though many herbalists maintain that it may be the synergistic effect of herbs in combination that is largely responsible for any observed benefit. As we have noted, Caisse did not believe that all the constituent herbs in Essiac acted directly on the tumor, but that some served other functions, such as detoxification and elimination. Burdock (Arctium lappa) Burdock root is a key ingredient in another herbal formula for cancer, the Hoxsey Therapy, as well as a staple in the Japanese and macrobiotic diets. According to the Office of Alternative Medicine report on Unconventional Cancer Treatments, burdock has historically been used against tumors in several countries: China (in a record from 502 A. A related species, lesser burdock, was employed as an antitumor 1462 agent by the Potawatomi Indians in the Midwest. Japanese researchers tested Arctium lappa (burdock) and nine other vegetable juices for their ability to prevent chemically-induced chromosomal mutations in rat bone marrow cells. Significant suppression of the incidence of 1469 mutations was found using the fresh or boiled juice from onion, burdock, egg plant, cabbage and welsh onion. Arctium lappa (burdock) was also found by another team of Japanese researchers to reduce the mutagenicity of chemicals activated by the metabolism, as well as those whose mutagenicity is not dependant upon metabolic activity. Benzaldehyde, which has been isolated from burdock, has also shown anticancer activity in some animal tests, described in the section on laetrile. Arctium lappa seed (Burdock) contains a number of ligands, including arctigenin, which has been shown to induce differentiation in mouse myeloid leukaemia (M1) cells. In their report on their studies of terminal differentiating agents from methanolic extracts of over 200 plants tested, Kaoru Umehara and his colleagues at the University of Shizuoka found that burdock seeds showed a marked differentiation-inducing activity toward M1 cells at very low concentrations, 1471 though they were inactive towards a human promyelocytic leukaemia cell line. Arctigenin has also demonstrated potent cytoxic effects against another human leukaemia cell line while showing no toxicity to normal lymphocytes. Aloe Emodin and Emodin have been isolated from sorrel and have shown antitumor activity in some animal test 1480 systems. In one study, a Japanese researcher found that Rumex acetosa polysaccharide displayed antitumor activity in mice 1481 implanted with Sarcoma 180 solid tumors. Slippery elm contains betasitosterol and a polysaccharide shown to 1482 have antitumor activity in animal models. Another group found Rheum palmatum to be inactive in two 1484 other animal tumor systems. However, some components of Rheum palmatum 1485-1487 (Aloe Emodin, Catechin, Emodin and Rhein) have shown antitumor activity in some animal systems. Rhein is a compound found in a number of purgative herbs that is largely responsible for their activity. Boik discusses research on the antitumor properties of Rhein, which 1486-1487 seems to disrupt protein synthesis in neoplastic cells. Other studies indicate that it may be most effective when the exposure is prolonged, with an exponential relationship between cell kill rate and Rhein concentration up to 20 1488-1490 hours, and a linear relationship thereafter. In other research cited by Boik, Rhein has also shown antitumor activity in vivo, increasing survival time in P388 leukaemia bearing mice in one study and inhibiting melanoma in mice 1491-1492 by 76 percent in another. Today, the situation for the cancer patient interested in using Essiac is bewildering at best. Numerous "competing" formulas are on the market, each manufacturer claiming to have to have the version that Caisse used. They charge that it is missing at least one key ingredient and is drastically off in the ratios of the various herbs. In 1988, Charles Brusch, who claimed to have treated his own cancer using Essiac, entered into a partnership with Elaine Alexander, a Vancouver, British Columbia, radio talk show host who had interviewed him several times, to circumvent the law and market Essiac as a "detoxification tea" under a different name. She also believed 1495 that various "specious facsimiles" of Essiac that are available on the market could be dangerous to patients. The fact remains that there is no information available how Caisse used Essiac for specific cancers or whether all patients received the same formula and dosages. Further, neither Caisse nor her supporters ever published their research on the formula in animals or humans. Although Essiac is unapproved for marketing in Canada, the Canadian government allows Essiac to be manufactured, sold and used by cancer patients under certain circumstances. A cooperative arrangement between Resperin and the Health Protection Bureau authorizes the sale of Essiac to cancer patients on "compassionate grounds" when no other treatment is appropriate. Today, according to the Office of Alternative Medicine, Flora, Resperin, Essiac International, Glum, and Herbal Essence are the major suppliers of Essiac. The annual cost for dry herbs is estimated to be in the range of $100 to $400, making Essiac a relatively inexpensive therapy with a contradictory research record and legions of patients over the years who feel they have received some benefit from it, either in terms of anticancer activity or quality of life benefits. There are also some interesting combinations of about 200 Indian plants and herbs of ancient Vedic, 608-609 Chinese tradition, of Africa and of Sud-America, used today in modern western plant 621,773,793,794 therapy which has revalued their importance. It has been called stone breaker because it has been used for generations by the indigenous peoples of the Amazon as an effective remedy to eliminate gallstones and kidney stones and for other kidney problems. The plant is employed for numerous other conditions, including blennorrhagia, colic, diabetes, dysentery, fever, flu, tumors, jaundice, vaginitis, and dyspepsia. It is little wonder that Phyllantus niruri is used for so many purposes, since the plant has demonstrated antihepatotoxic, antispasmodic, antiviral, antibacterial, diuretic, febrifugal, and hypoglycemic activities. It is also known as an anodyne, aperif, carminative, digestive, emmenagogue, laxative, stomachic, tonic, and vermifuge, based on its long, documented history of uses. Its considered an excellent remedy for removing uric acid from the urine and eliminating stones. Its also used for hydropsy, urinary and bladder infections and blockages, liver ailments, painful joints, cystitis, prostate disorders, kidney disorders, hepatitis, diabetes and as an antispasmodic and muscle relaxant specific to the urinary tract system. In India, its a common household remedy for asthma and bronchitis and is used to treat coughing, extreme thirst, anemia, jaundice, and tuberculosis. The antihepatotoxic (liver-protecting) activity of Phyllantus niruri was attributed to two compounds in the plant, Phyllanthin and Hypophyllanthin, in a 1985 study by Indian researchers. Glycosides found in Phyllantus niruri demonstrated aldose reductase inhibitory activity in studies conducted by a Japanese research group in 1988 and 1989. The analgesic activity of Phyllantus niruri was demonstrated in 1994 and 1995 by another research group in Brazil. The diuretic, hypotensive and hypoglicemic effects of Phyllantus niruri were documented in a small, ope human study conduced in 1995. This study showed a significant diuretic effect, a significant reduction in systolic blood pressure in nondiabetic hypertensives and female subjects, and a significant reduction in blood glucose in diabetic patients taking Phyllantus niruri for 10 days. Preliminary clinicals trials on children with infective hepatitis using an Indian drug containing Phyllantus niruri as the main ingredient showed promising results that fueled the subsequent in vitro and in vivo studies. The in vitro inactivation of hepatitis B by Phyllantus niruri was reported in India in 1982. A study that followed indicated that in vivo Phyllantus niruri eliminated hepatitis B in Mammals within 3 to 6 weeks. Other research, conducted from 1990 to 1995 has indicated that Phyllantus niruri does demonstrate anviral activity against hepatitis B. A Pharmaceutical Institute isolated at least one of the constituents in the plant responsible for this activity, a novel compound that they named niruriside and described in a 1996 study. Hypoxis hemerocallidea (Hypoxidaceae) the African potato comes from the forests of Kwa Zulu Natal and Pondoland. The active principles of this plant include Sitosterol and Sitosteroline, together with an anti-tumoral phenolic component: hypoxide. Sitosterol and Sitosteroline have a proven beneficial effect on the human immune system. Ben Smith, consultant in the oncology department of the Tygerberg Hospital in Cape Town, has treated patients with advanced tumors discovering that this has increased hopes of survival. Patients who suffer from tumors of the pancreas usually die within 4-6 months of diagnosis, but after therapy based on Sterol, taken from the plant, they have survived for a year or more, with relief from the unpleasant side effects of Chemo-Therapy. From other data in literature, it has been reported that after 24 hours of administering this substance, 152 in general, there is an increase in the number and the activity of Natural Killers and the 271 interleuchines, the tumoral Necrosis Factor and the activity of the macrophages increase. Note: Viscum album (mistletoe) can cause orthostatic hypertension and strong bradycardia; it cannot be used in patients who suffer from serious bradycardia or blocks of the sinuatrials or the branchia ventricular atrium. Maytenus krukovit, laevis, macrocarpa, ebenifolia (Chuchuhuasi) There is an extensive bibliography on the action of Maytenus krukovit, laevis, macrocarpa, 793,824-829 ebenifolia. In the 1960s it discovered its potent immune-stimulating properties, finding that it dramatically increased phagocytosis in mice. In the mid-1970s Italian researchers studying a chuchuhuasi extract used effectively to treat skin cancers identified its antitumor properties. Its antiinflammatory properties were discovered in the 1980s by another Italian research group. They discovered that its anti-inflammatory properties, radiation protectant action, and antitumor properties were at least partially linked to triterpenes and antioxidants isolated in the trunk bark. In 1993 a Japanese research group isolated a group of novel alkaloids in Maytenus species that may be responsible for its effectiveness in treating arthritis and rheumatism. Achyrocline satureoides (Macela) 793,855-863 There is an extensive bibliography on the action of Achyrocline satureoides. Achyrocline satureoides has been of recent clinical interest and its uses in natural medicine have been validated by science since the mid-1980s. In animal studies with mice and rats, macela demonstrated analgesic, anti-inflammatory, and smooth muscle-relaxant properties internally (gastrointestinal muscles) and externally without toxicity. This may well explain why Achyrocline satureoides has long been used effectively for many types of gastrointestinal difficulties as well as asthma. In vitro studies have demonstrated that macela is molluscicidal, and mutagenic against Salmonella and E. Other research on macela has concentrated on its anti-tumorous, antiviral, and immuno-stimulant properties. It was shown to pass the initial anti-crustacean screening test used to predict antitumor activity in 1993. In the mid-1980s German researchers extracted the whole dried plant and demonstrated that in humans and mice it showed strong immuno-stimulant activity by increasing phagocytosis. They isolated a plysaccharide fraction in the Achyrocline satureoides extract that seemed to be resonsible for this effect. In the mid-1990s Japanese researchers showed that an extract of Achyrocline satureoides flowers inhibited the growth of cancer cells by 67% in vitro. Morinda citrifolia It is a shrub of equatorial Africa, South-East Asia, Polynesia and the Caribbean, it is known by a number of names (Bumbo africano, Gelso indiano, Gran Morinda, Lada, Mengkudo, Nhau, Nonu, 577 Noni, Nono). An immune-modulating substance has been found in its fruit, alongside other particularly interesting molecules for other anti-neo-plastic activities, still being studied. Physalis angulata (Mullaca) 793,864-872 There is an extensive bibliography on the action of Physalis angulata. Pytochemical studies on Physalis angulata reveal that it contains flavonoids, alkaloids, and many different types of plant steroids, some of which have never been seen before in science. The new steroids found in Physalis angulata have received the most attention, and many of the documented properties and actions are attributed to these steroids. In several in vivo animal tests and in vitro lab tests, an extract of the entire plant of Physalis angulata and / or its steroidal fractions demonstrated immune stimulant properties by strongly enhancing blastogenesis, antibody responses, and increased T and B lymphocyte production. Various water, alcohol, and ethanol extract of Physalis angulata and its plant steroids have shown strong in vitro and in in vivo cytotoxic activity against numerous types of cancer cells, including leukaemia, lung, colon, cervix, and melanomas. It is characterized by a certain immune stimulating action, particularly on T lymphocytes. Its value depends on the fact that it is cultivated without the use of fertilizers or chemical substances.

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