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By F. Mortis. Saint John Fisher College. 2018.

The results showed that those in the preparation stage smoked less trusted 100 mg trandate, were less addicted discount trandate 100 mg mastercard, had higher self-efficacy generic trandate 100 mg line, rated the pros of smoking as less and the costs of smoking as more buy generic trandate 100mg online, had made more prior quitting attempts than the other two groups purchase trandate 100mg mastercard. The results were then analysed to examine the relationship between stage of change and smoking cessation. At both one and six months, the subjects in the preparation stage had made more quit attempts and were more likely to not be smoking. Conclusion The results provide support for the stages of change model of smoking cessation and suggest that it is a useful tool for predicting successful outcome of any smoking cessation intervention. Clinical interventions: promoting individual change Clinical interventions often take the form of group or individual treatment programmes based in hospitals or universities requiring regular attendance over a 6- or 12-week period. These interventions use a combination of approaches that reflect the different disease and social learning theory models of addiction and are provided for those individuals who seek help. Disease perspectives on cessation Within the most recent disease models of addiction, nicotine and alcohol are seen as addictive and the individual who is addicted is seen as having acquired tolerance and dependency to the substance. For example, nicotine fading procedures encourage smokers to gradually switch to brands of low nicotine cigarettes and gradually to smoke fewer cigarettes. It is believed that when the smoker is ready to completely quit, their addiction to nicotine will be small enough to minimize any withdrawal symptoms. Although there is no evidence to support the effectiveness of nicotine fading on its own, it has been shown to be useful alongside other methods such as relapse prevention (for example, Brown et al. Nicotine replacement procedures also emphasize an individual’s addiction and depend- ency on nicotine. For example, nicotine chewing gum is available over the counter and is used as a way of reducing the withdrawal symptoms experienced following sudden cessation. The chewing gum has been shown to be a useful addition to other behavioural methods, particularly in preventing short-term relapse (Killen et al. More recently, nicotine patches have become available, which only need to be applied once a day in order to provide a steady supply of nicotine into the bloodstream. They do not need to be tasted, although it could be argued that chewing gum satisfies the oral component of smoking. However, whether nicotine replacement procedures are actually compensating for a physiological addiction or whether they are offering a placebo effect via expecting not to need cigarettes is unclear. Treating excessive drinking from a disease perspective involves aiming for total abstinence as there is no suitable substitute for alcohol. Social learning perspectives on cessation Social learning theory emphasizes learning an addictive behaviour through processes such as operant conditioning (rewards and punishments), classical conditioning (associations with internal/external cues), observational learning and cognitions. Therefore, cessation procedures emphasize these processes in attempts to help smokers and excessive drinkers stop their behaviour. These cessation procedures include: aversion therapies, contingency contracting, cue exposure, self-management techniques and multi-perspective cessation clinics: 1 Aversion therapies aim to punish smoking and drinking rather than rewarding it. Early methodologies used crude techniques such as electric shocks whereby each time the individual smoked a puff of a cigarette or drank some alcohol they would receive a mild electric shock. However, this approach was found to be ineffective for both smoking and drinking (e. Wilson 1978), the main reason being that it is difficult to transfer behaviours that have been learnt in the laboratory to the real world. In an attempt to transfer this approach to the real world alcoholics are sometimes given a drug called Antabuse, which induces vomiting whenever alcohol is consumed. This has been shown to be more effective than electric shocks (Lang and Marlatt 1982), but requires the individual to take the drug and also ignores the multitude of reasons behind their drink problem. Imaginal aversion techniques have been used for smokers and encourage the smoker to imagine the negative consequence of smoking, such as being sick (rather than actually experiencing them). However, imaginal techniques seem to add nothing to other behavioural treatments (Lichtenstein and Brown 1983). Smokers are required to sit in a closed room and take a puff every 6 seconds until it becomes so unpleasant they cannot smoke any more. Although there is some evidence to support rapid smoking as a smoking cessation technique, it has obvious side effects, including increased blood carbon monoxide levels and heart rates. Other aversion therapies include focused smoking, which involves smokers concentrating on all the negative experi- ences of smoking and smoke-holding, which involves smokers holding smoke in their mouths for a period of time and again thinking about the unpleasant sensations.

Other studies have focused on emotional (non) expression and an emotionally inexpressive coping style known as ‘type C’ and have described a link with illness (e buy cheap trandate 100 mg online. Whilst other researchers have highlighted the importance a repressive coping style (e proven trandate 100mg. This research consistently indicates that non-expression of emo- tions trandate 100 mg on-line, particularly negative emotions in stressful situations can be harmful for health cheap 100mg trandate otc. There is also evidence that encouraging emotional expression through writing or dis- closure groups may be beneficial buy trandate 100 mg lowest price. This has involved randomly allocating participants to either the experimental or control group with both groups being asked to write for three to five consecutive days for 15 to 30 minutes each day. The experimental group are asked to ‘write about your very deepest thoughts and feelings about an extremely emotional issue that has affected you and your life. The control group is asked to write about more superficial topics such as how they spend their time. This intervention has been used with a range of people including adults, children, students, patients and maximum security prisoners and survivors of the holocaust who disclose a range of traumatic experi- ences including relationship break-ups, deaths and abuse. Greenberg and Stone 1992; Pen- nebaker and Beall 1986), re-employment following job loss (e. For example, it has resulted in changes in T helper cell responses (Pennebaker et al. However, as with all associations research indicates that the impact of emotional expression might vary according to aspects of the task and aspects of the individual. Aspects of the task Writing versus talking: Some research has compared the effectiveness of writing versus talking either into a tape recorder or to a therapist (e. The results showed that both writing and talking about emotional topics were more effective than writing about superficial topics. Type of topic: Some research has shown that changes in outcome only occur after writing about particularly traumatic experiences (e. Others have found that it is the relevance of the topic to the outcome variable which is important. For example, Pennebaker and Beall (1986) found that writing about the experience of coming to college had a greater impact upon college grades than writing about ‘irrelevant’ traumatic experiences. Amount of writing: Research using the writing paradigm has varied the stipulated time of writing both in terms of the length of sessions (from 15 to 30 minutes) and the spread of sessions (over a few days to over a month). Smyth (1996) carried out a meta analysis and concluded that writing over a longer period might be the most effective approach. Aspects of the individual Demographics: Pennebaker (1997) concludes that the effectiveness of emotional expression does not seem to vary according to age, level of education, language or culture. Personality and mood: Pennebaker (1997) also concludes that anxiety, inhibition or constraint do not influence the effectiveness of writing. Use of language: To explain the effectiveness of writing Pennebaker and colleagues (2001) developed a computer programme to analyse the content of what people were writing during the task. They coded the transcripts in terms of the types of words used: negative emotion words (sad, angry), positive emotion words (happy, laugh), causal words (because, reason) and insight words (understand, realize). The results from this analysis showed that greater improvement in health was associated with a high number of positive emotion words and a moderate number of negative emotion words. More interestingly, they also found that those who showed a shift towards more causal and insight words also showed greater improvement (Pennebaker et al. They con- cluded from this that this shift in language use reflected a shift from poorly organized descriptions towards a coherent story and that a coherent story was associated with better health status. Stress Stress can cause illness through physiological changes such as raised heart rate, blood pressure, heart beat irregularities and an increase in fatty deposits (see above). Research on rats showed that stressors such as tail pinching, a loud noise and electric shocks could produce immunosuppression (Moynihan and Ader 1996). One area of research which has received much attention relates to the impact of caregiver stress. Using a punch biopsy which involves removing a small area of skin and tissue they explored the relationship between caregiver stress and the wound healing process. The results showed that wound healing was slower in the caregivers than the control group. The wound healing para- digm has also been used to show links between stress and slower healing in students during an exam period (Marucha et al.

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Finally cheap 100 mg trandate otc, it may also be possible that Tcells can become temporarily “anergized” by partial or incom- plete antigen stimulation purchase trandate 100mg on-line. As a general rule cheap trandate 100 mg on line, self-reactive (autoimmune) B cells are not generally deleted by negative selection and can therefore be present in the periphery best 100mg trandate. Exceptions to this rule include B cells specific for membrane-bound self-determinants buy discount trandate 100mg on-line, some of which are deleted or aner- gized. B cells react promptly to antigens, even self-antigens, which are ar- ranged repetitively. However, they only react to soluble monomeric antigens if they additionally receive T cell help. Thus, B-cell non-reactivity largely results from a lack of patterned antigen presentation structures or as a result of T-cell tolerance. Tolerance is acquired, and can be measured as the selective absence of immunological reactivity against specified antigens. T-Cell Tolerance A distinction can be made between central tolerance, which develops in the thymus and is based on the negative selection (deletion) of Tcells recognizing self antigens present in the thymus, and peripheral tolerance. Peripheral tolerance results in the same outcome as central tolerance, however, this Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license Immunological Tolerance 91 formoftoleranceinvolvesantigenrecognitionbyantigen-reactiveperipheralT cells, followed by a process of clonal cell proliferation, end differentiation and death. The following mechanisms have been postulated, and in some cases confirmed, to account for a lack of peripheral T-cell responsiveness (Table 2. Most self-antigens, not present in the serum or in lymphohema- topoietic cells, belong to this category and are ignored despite the fact that they are potentially immunogenic. Certain viruses, and their antigens, actu- ally take advantage of this system of ignorance. For instance, the immune system ignores the rabies virus when it is restricted to axons, and papilloma viruses as long as the antigens are restricted to keratinocytes (warts). The main reason why many self antigens, and some foreign antigens, are ignored by T cells is that immune responses can only be induced within the spleen or in lymph nodes, and non-activated (or naive) T cells do not migrate into the periphery. It has also been postulated that those naive T and B cells which do encounter antigens in the periphery will become anergized, or inactivated, due to a lack of the so-called costimulatory or secondary signals at these sites. Experiments seeking to understand the “indifference” of T cells are summarized in the box on p. In all probability, a great many self-antigens (as well as periph- eral tumors) are ignored by the immune system in this way. During such a scenario the responding T cells differentiate into short- lived effector cells which only survive for two to four days. This induction phase may actually correspond to the postulated phenomenon of anergy (see Table 2. Should this be the case, anergy—defined as the inability of T cells to react to antigen stimulation in vitro—may in fact be explained by the responding cells having already entered a pathway of cell death (apoptosis) (see Fig. Once all the terminally differentiated effector T cells have died, immune reactivity against the stimulating antigen ends. Tolerance is hereafter maintained, as should the responsible antigen have entered into the thymus those newly maturing thymocytes will be subjected to the process of negative selection (e. Moreover, those newly matured T cells which may have escaped negative selection and emigrated into the per- Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license 92 2 Basic Principles of Immunology iphery will continuously be induced to undergo activation and exhaustion within the secondary lymphoid organs. Successful estab- lishment of lymphocyte chimerism following liver transplants appears to based on the same principle. Following sensitization of the skin flap with a contact antigen the animal reacted to a second antigenicexposureof the remaining(intact) skinwith accelerated kinetics. When the lymph vessel leading from the prepared skin flap to the lymph node was interrupted, or the draining lymph node was destroyed prior to the initial sensitiza- tion, the typical secondary response was not observed—leading to the conclusion that no T cell response was induced. Following an initial sensitization at any other location on the skin the secondary response was observed, even on the skin flap regardless of interruption of the lymph vessel or destruction of the draining lymph node. This result indicated that the antigen-experienced effector lympho- cytes reached the site of antigen via the bloodstream. This artificially in- tegrated “self antigen” was ignored by the host’s immune system, as indicated by the absence of b cell destruction or autoimmunity (diabetes). This model demonstrated that many self-antigens are ignored by the immune sys- tem simply because they are only present outside of the lymphatic system. How- ever, should such antigens enter the immune system in a suitable form (in this case by viral infection) the host will produce an autoimmune T-cell response.

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Use the terms that follow to identify the bones and structures of the appendicular skeleton shown in Figure 5-10 cheap trandate 100mg without a prescription. The structure of the humerus that articulates with the head of the radius is the a discount trandate 100mg visa. Hands Arthrology: Articulating the Joints Arthrology cheap trandate 100mg with mastercard, which stems from the ancient Greek word arthros (meaning “jointed”) order trandate 100mg otc, is the study of those structures that hold bones together quality 100mg trandate, allowing them to move to vary- ing degrees — or fixing them in place — depending on the design and function of the joint. The term articulation, or joint, applies to any union of bones, whether it moves freely or not at all. Chapter 5: A Scaffold to Build On: The Skeleton 83 Inside some joints, such as knees and elbows, are fluid-filled sacs called bursae that help reduce friction between tendons and bones; inflammation in these sacs is called bursitis. Some joints are stabilized by connective tissue called ligaments that range from bundles of collagenous fibers that restrict movement and hold a joint in place to elastic fibers that can repeatedly stretch and return to their original shapes. The three types of joints are as follows: Fibrous: Fibrous tissue rigidly joins the bones in a form of articulation called synarthrosis, which is characterized by no movement at all. Cartilaginous: This type of joint is found in two forms: • Synchondrosis articulation involves rigid cartilage that allows no move- ment, such as the joint between the ribs, costal cartilage, and sternum. Synovial: Also known as diarthrosis, or freely moving, joints, this type of articula- tion involves a synovial cavity, which contains articular fluid secreted from the synovial membrane to lubricate the opposing surfaces of bone. The synovial membrane is covered by a fibrous joint capsule layer that’s continuous with the periosteum of the bone. Ligaments surrounding the joint strengthen the capsule and hold the bones in place, preventing dislocation. In some synovial joints, such as the knee, fibrous connective tissue called meniscus develops in the cavity, dividing it into two parts. There are six classifications of moveable, or synovial, joints: Gliding: Curved or flat surfaces slide against one another, such as between the carpal bones in the wrist or between the tarsal bones in the ankle. Hinge: A convex surface joints with a concave surface, allowing right-angle motions in one plane, such as elbows, knees, and joints between the finger bones. Pivot (or rotary): One bone pivots or rotates around a stationary bone, such as the atlas rotating around the odontoid process at the top of the vertebral column. Condyloid: The oval head of one bone fits into a shallow depression in another, allowing the joint to move in two directions, such as the carpal-metacarpal joint at the wrist, or the tarsal-metatarsal joint at the ankle. Saddle: Each of the adjoining bones is shaped like a saddle (the technical term is reciprocally concavo-convex), allowing various movements, such as the car- pometacarpal joint of the thumb. Ball-and-socket: The round head of one bone fits into a cup-like cavity in the other bone, allowing movement in many directions so long as the bones are nei- ther pulled apart nor forced together, such as the shoulder joint between the humerus and scapula and the hip joints between the femur and the os coxa. Use the terms that follow to identify the structures that form a synovial joint shown in Figure 5-11. The structure in the knee that divides the synovial joint into two separate compartments is the a. Movement toward the midline of the body Chapter 5: A Scaffold to Build On: The Skeleton 87 Answers to Questions on the Skeleton The following are answers to the practice questions presented in this chapter. The term hemopoiesis also would be correct here, but it’s not one of the answer options. Back to Greek again: peri means “around” and osteon means “bone,” so the periosteum is “around the bone. Described by anatomist William Sharpey in 1846, these are also called perforating fibers. This is where you’ll find yellow marrow, although in infants red marrow also is present. These separate floating plates are why you can see a bald baby’s pulse throbbing on the top of its head. Ironically, anatomist Alfred Wilhelm Volkmann was most noted for his observations of the physiology of the nervous system, not bones. The epiphyseal and diaphyseal areas remain separated by a layer of uncalcified cartilage called the 20. Later it helps absorb bone tissue from the center of the long bone’s shaft, forming the 22. After ossification, the spaces that were formed by the osteoclasts join together to form 23. Haversian canal systems, which contain the blood vessels, lymphatic vessels, and nerves. Unlike bones in the rest of the body, those of the skull and mandible (lower jaw) are first laid down as 24.

It also introduces the stereochemical and water solubility factors that should be taken into account when selecting a structure for a lead compound cheap trandate 100mg on-line. These objectives will normally require a detailed assessment of the pathology of the disease and in some cases basic biochemical research will be necessary before initiating a drug design investigation (Figure 3 trandate 100 mg without a prescription. The information obtained is used by the team to decide what intervention would be most likely to bring about the desired result trandate 100mg without a prescription. Once the point of intervention has been selected discount trandate 100 mg free shipping, the team has to propose a structure for a lead compound that could possibly bring about the required change purchase trandate 100mg with amex. This frequently requires an extensive literature and database search to identify compounds found in the organism (endogenous compounds) and compounds that are not found in the organism (exogenous compounds) that have some biological effect at the intervention site. Molecular modelling techniques (see Chapter 5) are sometimes used to help the team reach a decision. In many cases, a number of structures are found to be suitable, but the expense of producing drugs dictates that the team has to choose only one or two of these compounds to either act as the lead or to be the inspiration for the lead compound. Assessment of the biochemical and biological processes of the disease and/or its cause. This uses a simultaneous multiple synthesis technique to produce large numbers of potential leads. These potential leads are subjected to rapid high throughput biological screening to identify the most active lead compounds. Once the structure of the proposed lead has been agreed, it becomes the responsibility of the medicinal chemist to devise a synthetic route and prepare a sample of this compound for testing. Once synthesized, the compound undergoes initial pharmacological and toxicological testing. The results of these tests enable the team to decide whether it is profitable to continue development by preparing analogues (Figure 3. The usual scenario is to prepare a series of analogues, measure their activity and correlate the results to determine the structure with optimum activity. The selection of a lead compound and the development of a synthetic path- way for its preparation (see Chapters 10 and 11) is not the only consideration at the start of an investigation. Researchers must also devise suitable in vivo and in vitro tests to assess the activity and toxicity of the compounds produced. There is no point in carrying out an expensive synthetic procedure if at the end of the day it is impossible to test the product. Consequently, the overall shape of the structure of a molecule is an important consideration when designing an analogue. Some structural features impose a considerable degree of rigidity on a structure, whilst others make the structure more flexible. Other structures give rise to stereoisomers, which can exhibit different potencies, types of activity and unwanted side effects (see Table 2. This means that it is necessary to pharma- cologically evaluate individual stereoisomers and racemates. Consequently, one must take into account all these stereochemical features when proposing struc- tures for potential leads and analogues. However, the extent to which one can exploit these structural features will depend on our knowledge of the structure and biochemistry of the target biological system. The former includes esters and amides as well as aliphatic conjugated systems, aromatic and heteroaromatic ring systems. The binding of these rigid structures to a target site can give infor- mation about the shape of that site as well as the nature of the interaction between the site and the ligand. Furthermore, the fact that the structure is rigid means it may be replaced by alternative rigid structures of a similar size and shape to form analogues, which may have different binding characteris- tics and possibly as a result a different activity or potency (see sections 2. Archer also concluded that a ligand appeared to assume different conformations when it bound to the different sub-types of a receptor. The main methods of introducing conformational restrictions are by using either bulky substituents, unsaturated structures or ring systems. In all cases, the structures used must be chosen with care, because there will always be the possibility that steric hindrance will prevent the binding of the analogue to the target. However, if sufficient information is available, molecular modelling (see section 5. Since these stereoisomers have different shapes, biologically active stereoisomers will often exhibit differences in their potencies and/or activities (Table 2. These pharmacological variations are particularly likely when a chiral centre is located in a critical position in the structure of the molecule.

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