By R. Gnar. Marymount Manhattan College. 2018.

For pathogens which exhibit moderate rates of proliferation and spread purchase benadryl 25mg, the T-cell response may cause extensive immunopathological damage purchase benadryl 25 mg online, and thus reduce the proportion of surviving hosts, some of which will controll virus, some not. A weakened immune defense system may not progress beyond an unfavorable virus-host balance, even when confronted with a static or slowly replicating patho- gen which represents an initially favorable balance. Although de- tails of the process are still sketchy, IgE-dependent basophil and eosinophil defense mechanisms have been described for model schistosomal infections. Usage subject to terms and conditions of license 102 2 Basic Principles of Immunology & Avoidance strategies. Infectious agents have developed a variety of stra- tegies by which they can sometimes succeed in circumventing or escaping immune responses, often by inhibiting cytokine action. Short-lived IgM responses can control bacteria in the blood effectively, but are usually insufficient in the controlof toxins. In such cases, immunoglobulinsof the IgGclass are more efficient, as a result of their longer half-life and greater facility for diffusing into tissues. Avoidance Mechanisms of Pathogens (with examples) Influence on the complement system. Some pathogens prevent complement fac- tors from binding to their surfaces: & Prevention of C4b binding; herpes virus, smallpox virus. Viruses can avoid confrontation with the immune defenses by restricting their location to peripheral cells and or- gans located outside of lymphoid tissues: & Papilloma viruses; infect keratinocytes. Infection agents can avoid immune defenses by mutating or reducing their expression of T- or B-cell epitopes. Usage subject to terms and conditions of license Immune Defenses against Infection and Tumor Immunity 103 Continued: Avoidance Mechanisms of Pathogens (with examples) Influence on lymphocytes and immunosuppression. Immune Protection and Immunopathology Whether the consequences of an immune response are protective or harmful depends on the balance between infectious spread and the strength of the ensuing immune response. As for most biological systems, the immune de- fense system is optimized to succeed in 50–90% of cases, not for 100% of cases. For example, immune destruction of virus-infested host cells during the eclipse phase of a virus infection represents a potent means of preventing virus replication (Fig. If a noncytopathic virus is not brought under im- mediate control, the primary illness is not severe—however, the delayed cy- totoxic response may then lead to the destruction of very large numbers of infected host cells and thus exacerbate disease (Tables 2. Since an infection with noncytopathic viruses is not in itself life-threatening to the Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license 104 2 Basic Principles of Immunology Table 2. Auto- “Healthy” or unknown infections, immunity occult carrier viruses, bacteria, (although infec- and endogenous tious agent is retroviruses unknown) Clinical None Chronic Variable disease symptoms disease symptoms, some- times delayed or asymptomatic Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license Immune Defenses against Infection and Tumor Immunity 105 Table 2. A similar situation is also observed for the cellular immune response against facultative intracellular tuberculosis and leprosy bacilli which themselves have relatively low levels of pathogenicity (Table 2. A healthy immune system will normally bring such infectious agents under control efficiently, and the immunological cell and tissue damage (which oc- curs in parallel with the elimination of the pathogen) will be minimal, en- suring that there is little by wayof pathological or clinical consequence. How- ever, should the immune system allow these agents to spread further, the result will be a chronic immunopathological response and resultant tissue destruction—as seen during hepatitis B as chronic or acute aggressive hepatitis and in leprosy as the tuberculoid form. Should a rapidly spreading infection result in exhaustion of the T cell response, or should an insufficient level of immunity be generated, the infected host will become a carrier. This carrier state, which only occurs during infections characterized by an absent or low- level of cytopathology, is convincingly demonstrated in hepatitis B carriers and sufferers of lepromatous leprosy. Because the im- muneresponse also acts toinhibit virus proliferation, the process of cellulardestruc- tion is generally a gradual process. Paradoxically, the process of immunological cell destruction would helpthevirus survivefor longer periodsin the host and hence facilitate its transmission. From the point of view of the virus this would be an as- tounding, and highly advantageous, strategy—butone with tragic consequences for the host following, in most cases, a lengthy illness. Influence of Prophylactic Immunization on the Immune Defenses Vaccines provide protection from diseases, but in most cases cannot entirely prevent re-infection. Vaccination normally results in a limited infection by an attenuated pathogen, orinduces immunity through the useofkilled patho- gens or toxoids. The former type of vaccine produces a very mild infection or illness capable of inducing an immune response and which subsequently protects the host against re-infection. The successful eradication of smallpox in the seventies so far represents the greatest success story in the history of vaccination. The fact is that vaccinations never offer absolute security, but instead improve the chances of survival by a factor of 100 to 10 000.

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Eosin stain Neutral stains are stains in which the acidic and basic components of stain are colored purchase benadryl 25mg mastercard. Simple staining method It is type of staining method in which only a single dye is used buy benadryl 25 mg mastercard. Usually used to demonstrate bacterial morphology and arrengement Two kinds of simple stains 1. Apply a few drops of positive simple stain like 1% methylene blue, 1% carbolfuchsin or 1% gentian violet for 1 minute. Negative staining: The dye stains the background and the bacteria remain unstained. Differential staining method Multiple stains are used in differential staining method to distinguish different cell structures and/or cell types. Most bacteria are differentiated by their gram reaction due to differences in their cell wall structure. Gram-positive bacteria are bacteria that stain purple with crystal violet after decolorizing with acetone-alcohol. Gram-negative bacteria are bacteria that stain pink with the counter stain (safranin) after losing the primary stain (crystal violet) when treated with acetone-alcohol. Cover the fixed smear with crystal violet for 1 minute and wash with distilled water. Ziehl-Neelson staining method Developed by Paul Ehrlichin1882, and modified by Ziehl and Neelson Ziehl-Neelson stain (Acid-fast stain) is used for staining Mycobacteria which are hardly stained by gram staining method. Once the Mycobacteria is stained with primary stain it can not be decolorized with acid, so named as acid-fast bacteria. Prepare the smear from the primary specimen and fix it by passing through the flame and label clearly 2. Place fixed slide on a staining rack and cover each slide with concentrated carbol fuchsin solution. Heat the slide from underneath with sprit lamp until vapor rises (do not boil it) and wait for 3-5 minutes. Cover the smear with 3% acid-alcohol solution until all color is removed (two minutes). Cover the smear with 5% malachite green solution and heat over steaming water bath for 2-3 minutes. Cover the smear with 1% aqueous crystal violet for 1 minute over steaming water bath. Water Peptone: Hydrolyzed product of animal and plant proteins: Free amino acids, peptides and proteoses(large sized peptides). It provides nitrogen; as well carbohydrates, nucleic acid fractions, minerals and vitamins. Other elements Carbohydrates: Simple and complex sugars are a source of carbon and energy. Water Deionized or distilled water must be used in the preparation of culture media. Basic /Simple / All purpose media It is a media that supports the growth of micro-organisms that do not require special nutrients. To subcuture pathogenic bacteria from selective/differential medium prior to performing biochemical or serological tests. Enriched media Media that are enriched with whole blood, lyzed blood, serum, special extracts or vitamins to support the growth of pathogenic bacteria. Enrichment media Fluid media that increases the numbers of a pathogen by containing enrichments and/or substances that discourage the multiplication of unwanted bacteria. Antibiotics) that prevent or slow down the growth of bacteria other than pathogens for which the media are intended. Differential media Media to which indicator substances are added to differentiate bacteria. Transport media Media containing ingredients to prevent the overgrowth of commensals and ensure the survival of pathogenic bacteria when specimens can not be cultured soon after collection. Amies transport media Stuart media Kelly-Blair media Choice of culture media The selection culture media will depend on: 1. The major pathogens to be isolated, their growth requirements and the features by which they are recognized. Whether the specimens being cultured are from sterile sites or from sites having normal microbial flora. The training and experience of laboratory staff in preparing, using and controlling culture media. Fluid culture media Bacterial growth in fluid media is shown by a turbidity in the medium. The major processes during preparation of culture media • Weighing and dissolving of culture media ingredients • Sterilization and sterility testing • Addition of heat-sensitive ingredients • Dispensing of culture media • pH testing of culture media • Quality assurance of culture media • Storage of culture media 1. Weighing and dissolving of culture media ingredients Apply the following while weighing and dissolving of culture media ingredients • Use ingredients suitable for microbiological use.

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Thienamycin itself is very labile and decomposes in water solution buy 25 mg benadryl visa, so is there- fore impractical for clinical use buy benadryl 25 mg mastercard. Meropenem is a fur- ther developed semisynthetic derivative of thienamycin, which resists the renal dihydropeptidase and can therefore be admin- istered without the peptidase inhibitor cilastin. Still another thienamycin derivative is ertapenem, which is structurally simi- lar to meropenem. Betalactams have never been of much use in the treatment of tuberculosis, and one reason for the lack of efficiency of betalactams in this context was found inthegenom esequenceofM. The defined daily dose of one of the new thien- amycin derivatives is more than 300 times more expensive than the corresponding dose of penicillin V. As mentioned earlier, these enzymes have the ability to hydrolyze the betalactam bond of betalactams to destroy their antibacterial activity completely. The cleavage product of this enzymic reaction with penicillin is penicilloic acid, which lacks antibacterial activity. They dif- fer from each other by having different substrate profiles toward penicillins, cephalosporins and monobactams, and carbapenems. They can be classified after their substrate profile, which can include clavulanic acid. Some of the betalactamases do not attack clavulanic acid, since it is not included in their substrate profile; clavulanic acid is simply not recognized by the active center of these enzymes. The oxacillinases also include the isoxazolyl derivatives cloxacillin, dicloxacillin, and flucloxacillin among their substrates, mediating resistance to these penicillin deriva- tives, originally marketed as penicillinase-stable penicillins. In later years two groups of betalactamases also hydrolyzing thien- amycins (imipenem, meropenem, ertapenem) have been identi- fied in pathogenic bacteria (carbapenemases). This illustrates the statement that for any clinically used betalactam, a betalactamase has also been found. The first horizontal transfer of betalac- tamase activity discovered between bacteria was described in 1963 by Naomi Datta in London and Polyxeni Kontomichalou in Athens. This means that ampicillin is a good substrate for this betalactamase, which could not at all degrade the cephalosporins cefotaxim, ceftazidim, or cefuroxime and also not the monobac- tam aztreonam or the carbapenem imipenem. This has changed the substrate profile of the enzyme to include in its substrate spectrum the cephalosporins cefotaxim and ceftazidim and the monobactam aztreonam. These amino acid changes dra- matically affect the resistance pattern of the host bacterium, which now retains only its susceptibility to imipenem. Those simple mutational changes have widened the substrate spec- trum of the betalactamase and in consequence also widened the pattern of resistance that it can mediate. The work of medicinal chemists to find new betalactams and to modify existing ones has aimed primarily at fighting resistance by finding derivatives outside the substrate spectra of clinically known betalactamases. This is a pathogen resistant to practically all betalac- tams, and thus very difficult to treat. It is carried by about 30% of the healthy human population on the skin and in the nostrils. The spread of strains resistant to methicillin and other antibiotics is thus a challenging public health prob- lem. The methicillin-resistant staphylococci also often show resistance to practically all other antibacterial agents. These pathogens seem to be insensitive to all clini- cally available antibacterial agents. The clin- ically most important of these involve Streptococcus pneumoniae pneumococci, causing bacterial pneumonia, otitis, septicemia, and many other diseases. Unfortunately, they show a rapid increase in resistance cor- related to a large international distribution of betalactams. Calculations have shown that within a short time almost half of all pneumococcal isolates at the Centers for Disease Control in Atlanta, Georgia will be penicillin resistant. Also in Scandinavia, penicillin-resistant pneumococci causing clinical problems have occurred at a frequency of 5 to 10%. The recombinants selected have been observed to occur in clones, which have spread epidemically all over the world. They have been identified as, for example, the ‘‘Spanish-American’’ clone and the ‘‘French’’ clone. The epi- demic spread of resistance clones could be partially controlled by strict hygiene and patient isolation. Where tested, measures of contagion protection have been shown to be quite effective. Close to half of all antibiotic prescriptions in Sweden are for penicillins, which means that almost all citizens have taken penicillin once or sev- eral times, mostly in the form of tablets. This intensive—too intensive—use of penicillins and of other betalactams in Sweden and in the world has for decades effected a selection pressure that has caused the now very widespread betalactam resistance among pathogenic bacteria. In an interview in the New York Times in 1945, he very farsightedly warned that overuse of penicillin could lead to the development of resistant bacteria.

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Travis indicates that it is essential that consumers have some control over their treatment (“they need to be a part of it…need to have some say”) considering that they will be consuming the medication (“It’s themselves that are going through it”) 25 mg benadryl free shipping. Whilst he does not directly link these elements of the therapeutic alliance to his adherence purchase benadryl 25mg visa, he could be seen to be referring partly to the consequences of non-adherence 214 when highlighting the negative outcomes associated with a poor treatment alliance (“otherwise, you’re not gonna get anywhere”). In the following extract, Amy also indicates that some of the components identified by Travis represent important aspects of the therapeutic alliance, associated with adherence outcomes. Amy provides more in depth detail about what an “authoritative” therapeutic alliance might look like as well, based on personal experiences: Amy, 10/02/2009 A: I think negotiation uh, where the client or patient feels like they’ve not only had a say but, not taking control but has an equal say of at least their opinion is being equally considered. Yeah, uh it’s not, (inaudible) or parent-like, it should be negotiated like you’re a colleague or a friend that you met at work or something but not an unprofessional friend... That kind of, familiarity and once you’ve developed a good working rapport with your psychiatrist, I think it’s important for your psychiatrist to build a good rapport or your occupational therapist or any treating health professional, develop a good rapport with their, uh, patient. The only thing you have to be wary of is developing too good of a rapport that um the patient can sometimes get transference from if you have (inaudible). Basically having a collaborative relationship where you can discuss things, it’s an open forum, as opposed to being I guess quite punitive and taking a more um- A: Yeah see a lot of doctors act just like parents, parent, naughty child attitude or starts um, regarding compliance with their patients, I think they’d be far more successful if, I mean I’ve-, sometimes you do need a firm 215 hand but not a heavy hand, like it is often practised today if patients aren’t compliant, I can only speak for myself in that uh, I’m more likely to be compliant if the-, I mean sometimes you do need to get tough on me, I admit, and uh, my brother and sister, in particular my brother being the disciplinarian has driven me to tears at points because I’ve been ridiculous and I’ve needed a big kick up the bum and he does that for me but he’s equally loving and caring as well. Rather than being authoritative I think the patient needs to feel like they’ve had an equal say and that’s being equally valued uh, as strongly as they feel about their opinion and like, it’s been at least considered by the psychiatrist or treating medical health professional. Most of all you need to feel heard and that your opinion is being considered and maybe even counted in moderation with their medical health care. Amy highlights several important components of a therapeutic alliance which she implies are associated with her adherence (“I’m more likely to be compliant if…)”. Specifically, Amy emphasizes the importance of “collaboration” with her prescriber, comprising “negotiation” whereby she feels that she has some “control” or an “equal say” and that her “opinion is being equally considered”. She additionally highlights the importance of consumers establishing a “good rapport” with their prescriber, whilst acknowledging the necessity of prescribers to be professional in their interactions with consumers. Amy contrasts a collaborative therapeutic alliance with one where there is a power imbalance, which she likens to a 216 “parent, naughty kid” dynamic to illustrate. Amy constructs the prevalence of “authoritative”, “punitive” prescribers as common (“a lot of doctors act just like parents”) and particularly evident when consumers are non- adherent (“a heavy hand, like it is often practiced today if patients aren’t compliant”). Amy could be seen to suggest that the power imbalance results from the consumer being non-adherent in the latter quote, whereas the alternative perspective is that consumers become non-adherent in response to an authoritative prescriber. She supports the need for prescribers to occasionally be “firm” with her to encourage adherence but indicates that such an approach is most effective when counterbalanced with “caring”. Below, Anna also highlights the importance of the consumer being “listened to” and contrasts this with her experience during a hospitalisation of being administered an exceptionally high dosage of medication which impeded her ability to contribute to treatment decisions (“And not have them so bombed so that they can make um decisions”): Anna, 18/02/2009 A: Hmm, I think too that the, the person needs to be listened to. That- 217 L: It’s like giving the client some control over their own treatment, or giving them- A: Could yeah, like give them like a small, a small dosage and maybe nice medications just to get them-, build them up slowly to a level rather than bombarding them with medication and you’re just left to it. Anna represents her experience of being over-medicated as compromising the capacity for collaboration in the therapeutic alliance. She reports an inability to recall consenting to another treatment, electroconvulsive therapy (“I can’t remember anything”), which she received in addition to medication in hospital, due to the effects of the medication. Anna reflects regret in relation to receiving the treatment, stating, “normally I would never have consented to that”. She suggests that rather than “bombarding” consumers with medication, initial treatment should involve a gradual increase in medication in order to ascertain optimum dosage. The extract raises concerns around the ethics of seeking the consent from inpatients who have been administered high dosages of medication, which in Anna’s case, reportedly compromised her decision-making and, thereby, undermined the capacity for a truly collaborative therapeutic alliance. Similarly, in the next extract, Amy talks about her limited control over her treatment as her psychiatrist experimented with different medications and dosages: Amy, 10/2/09 A: Not as a guinea pig, because too often people feel like guinea pigs with the medication, the psychiatrist’s, is all keen to, “oh I’ll give you new ones, oh 218 there’s this new one”. Amy likens her experiences of being encouraged to trial “new” medications and dosages (“They pump ‘em up”) to that of a “guinea pig”. By comparing consumers to guinea pigs, Amy works up a construction of consumers as psychiatrists’ subjects and thereby emphasises the significant power imbalance between prescribers and consumers. Amy suggests that her experiences of prescriber-directed experimentation are common amongst consumers “too often people feel like guinea pigs”. She could be seen to express frustration through the sarcastic remark “oh great, thanks” in relation to this practice. Whilst no direct linkages were made with adherence within the extract, it could be logically assumed that perceptions of oneself as being experimented on by psychiatrists may lead to non-adherence amongst some consumers. Indeed, Amy’s experience of experimentation with multiple medications was common amongst interviewees. Whilst Amy constructed experimentation as imposed by the psychiatrist, however, others indicated that they trialled various medications in collaboration with prescribers, as part of the process of finding a suitable medication and dosage. In the following extract, George talks about how his distrust of “doctors” due to his perception of them as having power over not only his treatment but his finances: George, 14/8/08 G: Coz like, I um, sorta lied, I said I wasn’t taking more marijuana, you know, thought I’d just gave it up because I was feeling sick and every time 219 she’d ask, I’d just tell her, no, no I don’t take it. Coz if you tell ‘em that you’re taking it they’ll just take your money off you, you know? George states that he is dishonest with his prescriber (“I um, sorta lied”) and strategically hides information relevant to his treatment due to fear of the consequences of not following his doctor’s orders, namely: “they’ll just take your money off you”.

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