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Although polioviruses pregnancy signs discount fosamax 70 mg line, like rhinoviruses menstrual calculator cheap 70 mg fosamax amex, belong to the picornavirus family, there are only three poliovirus serotypes. Poliovirus vaccines embody every of the three serotypes to present protection against poliomyelitis. Interferons In addition to adaptive humoral and cellular protection mechanisms, viral infections elicit an inducible defense mechanism, the interferons. These are proteins synthesized by host cells in response to viruses and different proinflammatory agents. Interferons inhibit virus replication not directly by inducing the expression of cellular proteins that inhibit the protein synthesis machinery. The discovery and practical applications of interferons are discussed in Chapter 44. There are three major sorts of interferons: interferon is produced by leukocytes, interferon- is produced by fibroblasts and epithelial cells, and interferon- is normally produced by T cells activated by particular antigens. Newly produced interferon is released into the extracellular fluid and binds to particular interferon receptors on adjoining cells. Consequently, Antibody Response Most viruses are sufficiently antigenic to stimulate a selected immune response. Viruses contain many foreign proteins, each of which can comprise multiple antigenic websites. Chapter 31: Biology of Viruses 335 interferon tends to act locally rather than systemically. Binding of interferon to its receptor leads to a series of intracellular signaling events. These events in turn result in the expression of a lot of mobile genes that act in concert to create an "antiviral state. In other cases, the most effective that could be accomplished clinically is to determine the group of viruses that are the doubtless pathogens. More definitive diagnosis is often necessary because many of the out there antiviral agents have actions that are restricted to sure types of viruses. To make a definitive prognosis, the clinician should isolate the virus in tissue tradition, identify the virus or detect virus-specific antigens or viral nucleic acids in tissues or body fluids, or reveal specific serologic responses (Table 31-3). Isolation of virus from scientific specimens normally includes inoculation of cultured cells. The identity of the virus may be confirmed by staining contaminated cells with antibodies to Virus-Induced Immunopathology Immunological injury results from cell lysis elicited by one or more of the antiviral host defense mechanisms. Such injury was seen in youngsters immunized with an inactivated measles virus vaccine who experienced severe illness when later infected with measles virus.

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The restriction of light- and heavy-chain expression to a single member of the chromosome pair encoding them menstruation vaginal itching buy fosamax cheap online, either maternal or paternal breast cancer sayings purchase fosamax 70 mg with visa, is termed allelic exclusion. Heavy and lightweight chains may be expressed from each paternal chromosomes, from each maternal chromosomes, or from one each. Diversity of several orders of magnitude are also added by an enzyme, terminal deoxyribonucleotidyl transferase (TdT), that removes or provides nucleotides between the V, D, and J genes in a process generally known as junctional diversity. The internet effect is that junctional variety significantly will increase V region diversity in order that no less than 1010 specificities may be generated. While present process rapid proliferation following activation, B cells also can accumulate small mutations in the V, D, and J genes of their light- and heavy-chain genes. Initially, B cells synthesize and display monomeric IgM (and IgD) on their cell surfaces. B cells, nonetheless, have the ability to change the immunoglobulin isotype they 96 Part 1: Principles produce to IgG, IgE, or IgA, a process often identified as the isotype swap, and by doing so influence the last word nature of the humoral immune response. Immunoglobulins may be likened to the "ballistic missiles" of the adaptive immune system: their V areas form a specific "warhead," and their constant areas represent the "rocket" portion of the molecule. Although a single B cell can manufacture a single type of warhead, it can be placed on totally different rockets. The intracellular equipment of the stimulated B cell is such that immunoglobulins of only a single isotype can be produced at a given time. The isotype finally determines whether an antibody activates complement, is secreted right into a lumen or onto a mucous membrane, or is immobilized by certain tissues of the physique. Isotype switching permits the adaptive immune system to direct antibodies with identical specificity toward a big selection of immune responses. The nature of the constant region (particularly the Fc region) of the immunoglobulin determines what kind of interplay will happen with different cells and molecules of the immune system. IgG is the only isotype that can cross the placenta and enter the fetal circulation. Maternally derived IgG offers the first immunologic safety for newborns until their own immune techniques turn out to be enough at about 6 months of age. IgA can dimerize, and specialised secretory epithelial cells can internalize dimeric IgA, transport it throughout the cell, and release it to the outside in saliva, tears, breast milk, and mucus secretions. Secreted IgA (sIgA) is extremely necessary in immunologic features involving the alimentary and respiratory tracts and may present some immunologic protection to nursing infants. Junctional diversity, a process mediated by TdT, contributes tremendously to the variety of attainable specificities, similar to that seen for immunoglobulins.

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There are three antigenic sorts zyrtec menstrual cycle order on line fosamax, or serotypes womens health 5 minute abs generic fosamax 70mg online, of polioviruses; most epidemics have been caused by sort 1. Other enteroviruses embody coxsackieviruses, first isolated throughout a polio outbreak in Coxsackie, New York, and echoviruses (for "enteric cytopathic human orphan viruses"). More lately found enteroviruses are simply assigned a number, as in enterovirus 70. Rhinoviruses, that are respiratory pathogens, are now categorized throughout the enterovirus genus based on sequence homology. Information in regards to the biology and replication of this virus, and comparisons of the nucleotide and amino acid sequence of the viral genome with that of other picornaviruses, led to reclassification of hepatitis A virus into a separate genus, hepatovirus. Nine of the eleven instances have been boys 12 to 17 years of age, and all 9 have been members both of the soccer or soccer group. The scientific histories of those patients have been similar: They reported "flulike" signs, fever as a lot as 39�C, sore throat, and muscle pains. Two to three days later, they complained of a stiff neck, elevated muscle ache, and fever up to 41�C. Those symptoms have been followed by flaccid paralysis of the legs that various in depth from comparatively minor to completely incapacitating. During the primary three weeks of October, 17 different college students were seen on the college infirmary with nonspecific complaints that advised an acute viral syndrome. Poliomyelitis was recognized by serological research that demonstrated a rising titer of antibodies to sort 1 poliovirus however not varieties 2 and three. The prognosis was confirmed by the isolation of kind 1 virus from the feces and throat washings of patients with paralytic disease. An immunization survey of the public schools revealed that greater than 95% of their college students had been vaccinated. Poliomyelitis has been eradicated from the United States and nearly eliminated from most international locations. Paradoxically, its dreaded consequences, paralysis and death, are extra frequent in unvaccinated people dwelling in countries with a high normal of sanitation. Poliomyelitis remains a wonderful model for understanding the epidemiology and pathogenesis of viral infections due to its well-understood and relatively simple replication cycle and the relative ease with which it might be studied within the laboratory. Several related viruses (other enteroviruses) continue to cause essential illnesses in the United States. Chapter 32: Picornaviruses and Coronaviruses 339 a single particular person who sheds excessive amounts of virus from the gastrointestinal tract can be the supply of infection.

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In latest years menstruation 3 times a month cheap fosamax 70mg, -lactam resistance has emerged among pneumococcal isolates within the United States menopause vaginal dryness purchase discount fosamax on line. Up to 50% of isolates are partially or utterly resistant in lots of components of the country. This growth makes it crucial to use combination therapy with vancomycin (a glycopeptide antibiotic with a mechanism of action that differs from that of -lactam drugs) for empiric therapy of bacterial meningitis, till resistance to cephalosporins has been definitively excluded by culture and susceptibility testing. An essential facet of the treatment of meningitis is the control of increased intracranial stress. Cerebral edema can further decrease the already diminished cerebral blood circulate and depress oxidative glucose metabolism. Supportive measures must be certain that the patient is adequately oxygenated and that the blood glucose is in the normal range. Dexamethasone, a glucocorticoid with potent anti-inflammatory activities, decreases the incidence of deafness as a consequence of H. In adults, the role of steriods in enhancing outcomes in acute bacterial meningitis stays uncertain. In addition, aseptic meningitis may finish up from noninfectious etiologies, such as cancer or autoimmune illness. His enchancment without antibacterial remedy further supported a viral etiology. Four weeks following her arrival, her oldest youngster returned from youngster care with chicken pox. With decision of her symptoms, ventricular drainage was discontinued and he or she was discharged to receive 10 additional months of remedy with isoniazid and rifampin. The organisms then spread all through the subarachnoid space and characteristically turn into most prevalent in the basilar cisterns. As cell-mediated immunity returns, it elicits an intense delayed-type hypersensitivity response to the organisms. During main pulmonary Chapter 61: Infections of the Central Nervous System 623 sensitivity for the analysis of tuberculous meningitis, being positive in only 5 to 25% of instances. Mycobacterial tradition may require as a lot as 6 weeks for progress and identification of the organism. An intradermal pores and skin test utilizing purified protein derivative could or may not be constructive in fulminant tuberculosis, nevertheless it must be constructive when repeated after weeks to months of effective antituberculous therapy. The hallmark of encephalitis is the acute onset of a febrile illness accompanied by headache and altered psychological standing.

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The disease is frequent in many developing nations pregnancy week 6 order genuine fosamax on line, the place canine rabies perpetuates breast cancer 2 day walk purchase fosamax from india, and millions of individuals are vaccinated after being bitten by potentially rabid animals, mainly canines. This chapter discusses the distribution of rabies in varied parts of the world and the animals involved, replication and unfold of the virus in these animals, diagnosis of the illness, and prevention of persons exposed to the virus (including the essential question of whether or not or to not use postexposure prophylaxis). He saved the bat unrestrained in his home for 2 days and launched it outdoors after the bat appeared nicely. Five weeks later, he went to the local emergency department complaining of numbness and pruritus of the left ear and face, headache, chest pain, and difficulty swallowing water. Based on his history of bat chew, he was handled with rabies vaccine and rabies immune globulin. He obtained experimental treatment for rabies including coma induction and administration of amantadine. Based on genetic sequencing, the rabies virus variant was identified as identical to these viruses found in silver-haired bats. The agent that causes rabies belongs to the Rhabdoviridae family, genus Lyssavirus. The greatest known member of that genus is rabies virus, but rabies-related viruses from the Old World can even trigger the illness. Rabies and rabies-related viruses are rod or bullet shaped and comprise an envelope. These viruses are fairly large in contrast with most different viruses (~180 nm in size and 75 nm in width;. The rabies virus genome consists of solely five genes that each encodes a single protein. An official informed them that no circumstances of rabies in canine had been reported in Washington for decades. The county animal management department was dispatched to seek for the canine, discovered a possible suspect, and positioned the animal in quarantine, the place it remained wholesome for the subsequent 10 days earlier than being claimed by its owner. If this incident occurred outside the United States, would the protocol have been the same Chapter 35: Rabies 369 Resistance to rabies infection has long been correlated with the presence of neutralizing antiviral antibodies, and that relationship has been nicely established in a selection of experimental animal studies. Some of the viruses on this group could elicit the formation of antibodies that cross-react in opposition to different members of the group. Those instances are either imported or related to exposures to wild or unidentified animals. Consequently, people from regions of endemic rabies are vaccinated after exposure to canine and cats that are recognized to be rabid or have escaped examination and observation. In contrast, most rabies circumstances in the United States are present in wild, not home, animals. In almost all of Africa and Asia, rabies continues to be a illness of canine that accounts for greater than 90% of human rabies deaths. Where canine rabies exists, human rabies remains common, and tens of millions of individuals are vaccinated annually for exposures to rabid animals, mostly canines.

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Depending on the virus replication strategy menopause 45 cheap fosamax 35 mg online, the virus may must women's health clinic yeovil quality 35 mg fosamax encode some enzymes or incorporate a vital replication enzyme in the virion. Viral pathogenesis is determined by an ordered series of interactions between a virus and its host: entry, uncoating, and primary replication; many viruses then unfold to other target tissues inside the physique. Many elements of innate and adaptive immunity act to defend in opposition to viral infections. Cell-meditated immunity is liable for termination of acute viral infections, and humoral immunity is responsible for protection against reinfection. New viruses doubtless will proceed to emerge, posing distinctive challenges for the development of antiviral medication and vaccines. The ease of international journey and the specter of bioterrorism have brought on considerations that comparatively exotic pathogens (Ebola virus, Lassa fever virus, and West Nile virus) or viruses from the past (smallpox virus) could appear unexpectedly. The common rules mentioned on this chapter might present a framework for understanding the biology of these rising pathogens, but each new virus is more probably to have its personal specific life cycle, evolutionary diversifications, and interactions with the immune system. Enteroviruses embody polioviruses, coxsackieviruses, echoviruses, rhinoviruses, and others. Enteroviruses (except rhinoviruses) Encounter: Wild-type polioviruses have been eradicated from the Western Hemisphere because of immunization programs, however they persist in some components of Asia and Africa. Replication: these viruses replicate in the intestine and can be shed within the stool weeks to months after an infection. Damage: Polioviruses could cause asymptomatic infection, aseptic meningitis, or flaccid paralysis. Other enteroviruses might trigger aseptic meningitis, myocarditis (heart), pleuritis (lung), herpangina (pharynx), febrile rashes, or different manifestations. Diagnosis: Suspected polio warrants viral detection with nucleic acid amplification and culture. Clinical features of most enterovirus infections are Spread and Replication: Rhinoviruses infect the upper respiratory tract and trigger mild infections (common cold) but in addition can produce extreme lower respiratory tract illness. Damage: Probably trigger injury by mechanisms apart from virus-induced cytopathology. Prevention: Rhinoviruses comprise greater than a hundred serotypes, making improvement of an effective vaccine tough. Prevention: Poliovirus an infection could be prevented with either an inactivated vaccine (Salk) or an infectious, attenuated vaccine (Sabin). Rhinoviruses Encounter: Transmitted person-to-person through contamination or aerosols. The genus Enterovirus consists of 10 species, of which 7 contain human pathogens: human enterovirus A�D and human rhinovirus A�C. In nations with temperate climates, outbreaks of enterovirus disease usually occur in the summertime or early fall; within the tropics, the illnesses caused by these viruses are endemic and occur throughout the year. The main portal of entry is the mouth, and transmission is primarily from personto-person by way of the fecal�oral route, through contaminated surfaces or ingesting water. Virus particles then traverse the basement membrane, invade the subepithelial tissues, and enter the bloodstream to set up a viremia.

Syndromes

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• Severe change in acid levels in the blood
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Treatment with intravenous doxycycline was begun for the suspected diagnosis of Rocky Mountain noticed fever women's health clinic rock springs wy fosamax 70mg low cost. She was despatched house after four days in the hospital with instructions to take oral doxycycline for 3 extra days women's health big book of exercises barnes and noble buy fosamax 35 mg overnight delivery. Her mom had removed a number of ticks from her body almost every day through the month of May before she became sick. A serum sample was collected and sent, along with one collected during the acute phase of her hospitalization, to the state public well being laboratory. A dramatic rise in titer of antibody to Rickettsia rickettsii was detected in the convalescent pattern. Why was the serological check for Rocky Mountain spotted fever adverse within the hospital Assuming that rickettsiae had been circulating in the blood, why had been the blood cultures unfavorable The most common rickettsiosis in the United States is Rocky Mountain noticed fever. It impacts roughly 2,000 people annually, mostly within the japanese and southern states quite than in the Rocky Mountains the place it was first described. This disease may be extremely serious and, if untreated, has a mortality rate of about 20%. Because the disease responds nicely to sure antibiotics, particularly in the early levels, a speedy analysis is crucial. Injury in the lungs, central nervous system, and other systemic microcirculation might cause neurological signs, seizures, coma, acute respiratory failure, shock, and acute renal failure. Q fever differs considerably from the typhus and spotted fever infections in that it has an acute kind, manifested mainly as pneumonia, and a persistent kind, by which the center valves are often affected. The causative agent, Coxiella burnetii, grows within the macrophages within the lung, liver, bone marrow, and spleen, where it stimulates granuloma formation. A methodology to cultivate Coxiella in cell-free medium has been devised, eradicating its obligate intracellular standing. In one other type of rickettsiosis, referred to as ehrlichiosis, the organisms develop in white blood cells. Ehrlichioses are tick-transmitted infections of monocytes and macrophages or neutrophils with systemic manifestations brought on by the host response. Spotted fever and typhus rickettsiae have lipopolysaccharides that are antigenically distinct for every group. Rickettsiae are highly adapted to the intracellular niche, where they propagate by binary fission with a technology time of 8 to 10 hours. They have reduced their genome size by elimination of genes which served capabilities that the host cell offers. These small bacteria can grow extra efficiently as a end result of their genomes are smaller and so they require fewer constructing blocks and less energy. The ticks concerned in Rocky Mountain spotted fever (Dermacentor species) are totally different from the Ixodes concerned in Lyme illness (see Chapter 25). When some wild animals are bitten by Dermacentor ticks, they turn out to be transiently contaminated and a transient reservoir of the rickettsiae.

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The isolation of typhoid bacilli from numerous sources in the middle of untreated typhoid fever menstrual toxic shock syndrome buy fosamax with amex. The late rise in positive stool cultures is brought on by secondary invasion of the intestine by organisms from the gallbladder women's health clinic vancouver wa order fosamax 70mg online. Chapter 17: Invasive and Tissue-Damaging Enteric Bacterial Pathogens: Bloody Diarrhea and Dysentery 217 layer in such a means as not to disrupt the tight junctions between the enterocytes. Once ingested this fashion, the Salmonella could be disseminated by the bloodstream to deeper tissue. Binding of the organisms results in activation of phospholipase A2; release of arachidonic acid; production of prostaglandins, leukotrienes, and hepoxilins; and a sharp enhance in intracellular calcium concentration. As yet, the mechanism by which fluid secretion is induced by Salmonella stays uncertain. This capacity to invade and cause irritation is critical however not adequate to cause diarrhea in experimental animals. Disease is dependent on transepithelial indicators, probably cytokines, elicited by the organism to recruit neutrophils. The microbial contribution to macrophage survival has been extensively studied in S. The results of PhoP�PhoQ-regulated modification is microbial resistance to innate killing mechanisms of the host immune system, significantly killing by cationic peptides. This sort of floor transforming is seen in both Gramnegative and Gram-positive pathogens. This area encodes genes which may be turned on when salmonellae enter eukaryotic cells. Other plasmid genes encode resistance to complement by blocking meeting of the terminal attack complicated on the cell floor, thus enabling the organisms to resist that host protection mechanism. Susceptibility to all three microbes is a results of a mutation at amino acid 169 of this gene, which eliminates its exercise and allows intraphagosomal survival. A human homologue of this gene has been recognized and is part of a family of at least three genes that management a pure macrophage-specific membrane transport protein. Invasion of the gallbladder by typhoid bacilli may be momentary or might end result within the long-term colonization that characterizes the typhoid provider state, particularly within the presence of gallstones. Typhoid bacilli survive well in gallstones and could be recovered from the middle of a stone; viable organisms should be obtained after dipping stones in antibiotics. Gallstones are a supply of prolonged asymptomatic carriage and excretion of the organism in stool. The supply of secondary intestine invasion could additionally be micro organism from the bloodstream during the extended secondary bacteremia or micro organism shed in the bile that penetrate M cells. Such secondary reinvasion leads to severe bleeding and/or perforation attributable to the marked inflammatory response induced within the Peyer patches.

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Antibodies play a role within the elimination of fungi from the physique by participating in the extracellular killing of some filamentous fungi and Chapter 46: Introduction to the Fungi and Mycoses 471 endemic mycoses however rarely useful in the diagnosis of opportunistic fungal infections women's health clinic bowling green ky fosamax 35mg with amex. The detection of fungal antigens in physique fluids weaknesses of women's health issues purchase cheap fosamax on-line, urine, and serum has proved both sensitive and particular for the prognosis of some opportunist fungi as properly as a quantity of endemic mycoses. They are eukaryotes, which means that they share some metabolic pathways and structural parts with mammalian cells. A variety of diagnostic tests can be found to decide if a fungal infection is current. For those who do require systemic antifungal agents, toxicity is a problem because fungi share with mammalian cells many pathways and constructions which may be targeted by antifungal agents. Compared with antibacterial brokers, the variety of efficient antifungal agents is kind of small. The diseases that occur within the United States embody histoplasmosis, blastomycosis, and coccidioidomycosis. Paracoccidioidomycosis occurs in South America and penicilliosis occurs in Southeast Asia; both of those ailments might be discussed briefly. All the fungi that trigger endemic mycoses are dimorphic, existing in the environment as molds and in hosts as both yeasts or spherules. Approximately 2 weeks after serving to his uncle clean out some hen coops, he developed fever, cough, chest tightness, and malaise. An oral macrolide for per week had provided no benefit, and his cough was worsening. The bodily examination was normal; the chest radiograph showed hilar lymphadenopathy and a patchy lower lobe infiltrate. Although the differential prognosis was broad, she thought that acute pulmonary histoplasmosis was the more than likely risk and ordered acute and convalescent antibody titers to help set up the prognosis. The following day, she was consulted on a 58-year-old girl who was in the intensive care unit and had obtained a kidney transplant 18 months before. A bronchoscopic lung biopsy confirmed tiny oval, budding, intracellular yeasts in alveolar macrophages, and a test for Histoplasma antigen was constructive. Kidney transplant recipient with diffuse pulmonary infiltrates that have been caused by Histoplasma capsulatum. Patchy pneumonitis and hilar lymphadenopathy typical of acute pulmonary histoplasmosis in an immunocompetent host. Chronic cavitary pulmonary histoplasmosis with bilateral cavitary upper-lobe infiltrates and lowerlobe scarring. She had initially seen the man 6 months earlier when he came into the hospital with increasing fatigue, dyspnea, fevers, night time sweats, anorexia, 20-pound weight reduction, and cough productive of yellow sputum blended with blood.

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The toxin is first secreted into the periplasmic space-through the usual secretory pathway additionally used by many different (non�toxin-related) molecules-where it assembles into its final quaternary construction breast cancer 3 day walk michigan order fosamax 35mg fast delivery. In a second step womens health resource center lebanon nh buy fosamax 70 mg free shipping, the toxin is transferred throughout the outer membrane, apparently without unfolding. Translocation across the outer membrane may require a devoted protein pore via which the toxin, but not other proteins, can pass. Once extracellular, the secreted toxins achieve access to the host cell by first binding to host floor molecules. Rather, the secreted protein is delivered instantly from the microbe into the host cell by a process that has been likened to injection with a syringe. The complicated of proteins required for this mechanism is collectively called the injectisome. For Shigella the system is used to switch proteins that trigger the host cell to take up the microbe. Host cell invasion by shigellae is the primary step in its eventual intracellular survival and cell-to-cell unfold. Some of the conserved proteins seem to kind a pore within the host cell membrane, by way of which other proteins can pass into the cytosol of the host. Once the flagellum is completed being assembled, secretion of the opposite proteins then ceases. Oral fluids normally suffice to correct the mild-to-moderate degree of dehydration and electrolyte abnormality. In extra severe instances that contain bloody diarrhea or dysentery and high fever, the use of efficient antibiotics reduces the duration of sickness and the period of infectivity to others. Reducing the infective interval is particularly important because the small inoculum needed for an infection with Shigella frequently leads to transmission to different household members. To make educated empiric selections on which drug to use, clinicians should pay attention to the drug susceptibility sample of pathogens encountered in their communities and establishments. No vaccine for shigellosis has been licensed, but many research are underneath method utilizing a variety of strategies. In some approaches, virulence antigens, the Ipas, are being altered and packaged in numerous ways; different methods depend on delivering the O antigen of Shigella within the vaccine preparation. A main objective is to produce live, attenuated vaccines that might be administered by mouth and will immunize the gut itself. Ultimately, nevertheless, these vaccines should be tested in people because no animal mannequin actually mimics human shigellosis. Less typically within the United States, bloody watery diarrhea is attributable to different pathogens, including Shigella, Salmonella, Campylobacter jejuni, or, extra uncommonly, Yersinia enterocolitica. Later that morning, he had a watery diarrhea every 15 to 30 minutes, initially with small quantities of seen blood. Later that day, brilliant purple stools consisting of what seemed to be pure blood appeared.