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During a the other hand 100mg extra super cialis with visa, a phobia may be so dis- panic attack buy extra super cialis 100 mg without prescription, individuals experience short- abling that individuals are unable to func- ness of breath, increased heart rate and tion effectively in their day-to-day activ- palpitations, sweating, and, at times, nau- ities if the phobia causes them to avoid sea or other physical discomfort. Panic particular objects or situations or causes attacks are not triggered by a certain event such anxiety that they are unable or un- and, at least initially, are unpredictable. In themselves, they may be Obsessive-Compulsive Disorder only mildly debilitating. Obsessive-compulsive disorder is a chron- Panic disorder is distinguished from gen- ic disorder that can cause significant dis- eralized anxiety in that individuals with ability if not treated, with symptoms panic disorders become preoccupied with following a waxing and waning course the physical symptoms associated with a (Maj, Sartorius, Okasha, & Zohar, 2002). Treatment Individuals with an obsessive-compulsive focuses on amelioration of symptoms disorder have recurrent obsessions (per- through medication and counseling. Agoraphobia For instance, they may have recur- Panic disorders are sometimes accompa- rent thoughts of the death of a loved one, nied by agoraphobia, the fear of being in or they may have an irresistible urge to a situation or place in which it might be perform repetitively some behavior that difficult or embarrassing to escape or in seems purposeless, such as turning a light which there may be no help available if on and off three times before retiring for the individual experiences a panic attack. Attempts by individuals to ig- Although not all individuals who have nore the compulsions only increase anx- panic attacks experience agoraphobia, iety, discomfort, and distress. Medi- venture outside their home alone, or they cation is often used in combination with may be reluctant to travel by car, bus, or cognitive-behavioral therapy, especially other common means of transportation. The term phobia refers to fear and anxi- Posttraumatic Stress Disorder ety related to specific situations, persons, or objects. Different types of phobias are cate- Posttraumatic stress disorder (PTSD) was gorized on the basis of the object of fear. PTSD is an anxiety dis- distress and impairment in social, occupa- order that develops after an individual has tional, and interpersonal functioning experienced or observed a traumatic or life- (American Psychiatric Association, 2000). The symptoms of the disorder may include persistent recol- Somatization disorder is a type of soma- lection of the event, sleep difficulties and toform disorder that is characterized by recurrent nightmares, difficulty in concen- recurrent, multiple physical complaints trating, and a feeling of hypervigilance or for which a medical cause cannot be increased arousal (Khouzam & Donnelly, found. Individuals may persistently reex- tressing that they impair social or occupa- perience the event in distressing images, tional function. Because physical symp- nightmares, or flashbacks; they may avoid toms are often similar to symptoms of a reminders of the event, including persons variety of medical conditions, individuals or places; or they may have hyperarousal may receive medical treatment for their symptoms, such as insomnia, irritability, symptoms even though no organic cause impaired concentration, or hypervigilance can be found. Individuals may demon- Individuals with somatization disorder strate little emotion or appear detached do not consciously produce the symptoms and lose interest in previously enjoyed ac- but truly experience them, even though tivities or in important close relationships. Although many individuals experience Conversion Disorder acute forms of PTSD at some time during their life, most recover. When PTSD per- Another type of somatoform disorder is sists, it can be debilitating and require psy- conversion disorder, in which individuals chological and pharmacologic interven- lose a physical function, often related to a tion (Ursano, 2002). Symp- nature of their condition and can facilitate toms do not typically follow a pattern that recovery. Cognitive therapy and anxiety would correspond to a specific disease or management therapies can also be help- injury. Hypochondriasis Somatoform Disorders Hypochondriasis, another type of som- atoform disorder, is characterized by pre- Somatoform disorders are conditions in occupation with physical illness. Indi- which individuals experience physical viduals with this condition may fear or symptoms for which no organic cause can believe they have a serious physical illness Common Psychiatric Disabilities 189 or perceive the symptoms of a coexisting new identity without being able to recall disease or condition in an exaggerated their previous identity. For example, they may perceive a sia is the inability to recall events that cough associated with a common cold as occurred within a certain period of time a sign of tuberculosis or lung cancer. Dissociative Pain Disorder identity disorder, formerly known as multi- ple personality disorder, is a condition in Pain disorder is a preoccupation with which at least two personalities exist with- pain that is severe enough to cause in the same individual and control the impairment in function at home, school, individual’s behavior. Personality Disorders Individuals with pain disorder do not con- sciously produce the symptoms of a pain Everyone has personality traits or char- and actually experience the pain report- acteristics. This disorder can be extremely inca- they can interfere with the ability to func- pacitating, often severely limiting social tion, especially during times of crisis. Personality disorders describe disorders characterized by inflexible or maladaptive Factitious Disorders behaviors that have usually lasted a long time and that impair interpersonal or Although not severely disabling, a vari- occupational functioning or cause subjec- ety of other types of mental disorders may tive distress (American Psychiatric Asso- interfere with effective functioning. They may assume the sick role (American Psychiatric rationalize their actions, blaming others Association, 2000). A factitious disorder for their situation or misfortune without differs from malingering (in which indi- examining their own responsibility for the viduals also produce symptoms intention- situation at hand. When a personality disorder exists in combination with other mental Dissociative Disorders disorders, the prognosis is more guarded, and treatment and management of the Conditions in which individuals expe- personality disorder are more difficult. At rience an alteration in memory, conscious- times, these individuals may not have a ness, or identity for no organic reason are full-blown personality disorder but rather called dissociative disorders. Dissociative maladaptive personality traits that may fugue is a condition in which individuals interfere with the treatment or diagnosis leave their environment and assume a of the concomitant disorder. The diagnosis of mental conditions is The most commonly used intelligence often an art as well as a science.

In this type of hemophilia discount extra super cialis 100 mg otc, a protein in clotting Leukemia Factor VIII is deficient buy extra super cialis 100 mg with amex. The next most com- mon type is hemophilia B, also called The leukemias are caused by the cancer- Christmas disease, in which clotting Factor ous production of lymph cells or white IX is defective. They are discussed in greater philia is von Willebrand’s disease, in which detail in Chapter 16. Hemophilia The severity of hemophilia varies along a continuum from a tendency toward slow, Hemophilia is an inherited, potentially prolonged, persistent bleeding to a ten- disabling condition associated with high dency toward severe hemorrhage, and it financial costs (Beeton, 2002). Several is categorized as mild, moderate, or severe inherited blood disorders make up the depending on the level of clotting factor condition known as hemophilia, a chron- present. Individuals with mild hemophilia ic bleeding disorder in which there is a will probably experience abnormal bleed- deficiency in or absence of one of the clot- ing only after major injuries or minor sur- ting factors (Bolton-Maggs & Pasi, 2003). Individ- Individuals with hemophilia have a bleed- uals with moderate hemophilia may have ing tendency. Although they do not ini- prolonged bleeding after major trauma or tially bleed faster, the normal clotting surgery. Individuals with severe disease may 238 CHAPTER 8 CONDITIONS OF THE BLOOD AND IMMUNE SYSTEM bleed spontaneously and have hemor- episodes when they do occur. Because of the higher concentra- ankles are affected most frequently, al- tions of clotting factors, plasma concen- though elbows may become involved lat- trates are given more frequently than is er. Clotting factors are usually result from damage to the joint structure replaced through intravenous infusion and from atrophy (wasting) of surround- (infusing substance directly into a vein). Bleeding into the muscle, if The amount, type, and duration of the severe, may exert pressure on nerves and infusion depend on the individual’s clot- cause a temporary sensory loss. If the hem- ting deficiency and the size and severity orrhage damages muscle tissue, fibrous tis- of the bleeding problem. Treatment may sue may form, causing varying degrees of be instituted prior to surgery to prevent functional loss. Early treatment of bleeding helps to pre- Treatment for Hemophilia vent complications. Consequently, learn- ing to administer clotting factor concen- Hemophilia is not curable and requires trates at home is beneficial. To do so, how- treatment for bleeding problems through- ever, individuals must be able to calculate out the individual’s life. With proper care the appropriate dose and mix and admin- and treatment, however, individuals with ister the concentrate intravenously. Home hemophilia can manage their chronic dis- therapy is appropriate for mild bleeding ease, and their life expectancy approach- but is not sufficient when major bleeding es normal (Teitel et al. Major bleeding requires medical To prevent damage from abnormal bleed- evaluation. There are therapies that involve intravenous infu- over 100 comprehensive hemophilia treat- sion, there is the chance of the transmis- ment centers throughout the country that sion of infection such as hepatitis and help individuals with hemophilia manage human immunodeficiency virus (HIV) their condition physically and psycholog- (Parish, 2002). These care centers emphasize early should always be sterile and never shared. Individuals who Because there is no cure for hemophil- receive blood products intravenously can ia, treatment is directed toward prevent- also develop an allergic reaction to the in- ing any injury that could precipitate fusion. Such reactions should be reported bleeding and toward controlling bleeding to a physician promptly. Conditions Affecting the Blood or Immune System 239 Individuals with bleeding into a joint being unable to control bleeding may may require joint immobilization for sev- result in passivity and inactivity. At oth- eral days in addition to replacement ther- er times, if individuals have had difficul- apy. Joint pain may be treated with anti- ty adjusting to the condition, are uncer- inflammatory medications and analgesics. Although replacement therapy and home Physical therapy or prescribed exercise car- treatment have done much to improve ried out at home may be necessary to main- the lives of individuals with hemophilia tain the range of motion of the affected and to decrease the disability resulting joints. If the joints undergo severe degen- from the condition, treatments are very eration, reconstructive orthopedic surgery, expensive. This expense may be an addi- such as joint replacement, may also be tional source of stress. Individuals Individuals with hemophilia may expe- with hemophilia should always wear a rience both acute and chronic pain if there Medic Alert identification bracelet or has been bleeding into the joints.

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The names of the first electronic messages often even carry the names of their paper counterpart: electronic discharge letter buy extra super cialis 100mg without a prescription, electronic prescription effective 100mg extra super cialis, etc. At first glance, little has changed compared to the previous paper based communication, except the speed of delivery. At this stage, the infrastructure (for example computers, lines) required for ICT has been installed, but its impact on the processes is still very limited. Subsequently, however, the ability to send data using electronic communication is used to support new forms of collaboration between healthcare professionals. At present, the emphasis has shifted from replacing paper documents to sharing data between colleagues. As clinicians increasingly share data, issues such as the standardisation of the content of medical records are becoming important areas of research. In addition, the fact that data can be transferred easily over distances enables clinicians to interpret data while the patient is located miles away (resulting in, for example, the so-called “telediagnosis”), or to communicate with patients over longer distances using, for example, the internet. In this chapter we will focus on the contribution of medical informatics to diagnostic decision support. We believe that the use of ICT in the domain of diagnostic decision support is still in an early stage. Although in a few specialties (for example radiology), ICT is used extensively for decision support, most clinicians have little or no experience with decision support systems. Many researchers argue that the fundamental enabling technology is the introduction of electronic medical records. Once electronic medical records are available, they argue, we will witness a rapid increase in the use of diagnostic decision support systems. The entries in the record enabled the clinician to recall previous episodes of illness and treatment. In recent years, however, medical records have been used increasingly for other purposes: they are used as a data source for purposes ranging from billing the patient to performing epidemiological studies, and from performing quality control to defending oneself against legal claims. One of the major barriers for using the data in such ways is the inaccessible and often unstructured nature of the paper record. The introduction of computer based medical records to a large degree, removes that barrier. Recent decades have seen a rapid increase in the role of computers in medical record keeping, and professional organisations have started to play an active role in the introduction of electronic records. For example, in 1978 the first Dutch general practitioners started using personal computers in their practices. In 1990, 35% of Dutch GPs were using one or more computer applications; although the majority of these are administrative, an increasing number of clinicians use computer stored medical records. Other countries, such as the United Kingdom, have also witnessed a rapid introduction of electronic records into primary care. In secondary care, although progress has been made, the introduction of electronic records is slower. The explicit purpose of automating medical records is to use the data in those records to support not only the care of individual patients, but also applications such as decision support, quality control, cost control, or epidemiology. The reliability of clinical data, for example, has long been questioned, and tensions between reimbursement schemes and coding schemes have been discussed. Some researchers argue that the process of automation may further reduce the reliability of data. Burnum,4 for example, states: “With the advent of the information era in medicine, we are pouring out a torrent of medical record misinformation”. Although we disagree with this pessimistic view, we acknowledge that medical data are recorded for a specific purpose and that this purpose has an influence on what data are recorded and how. In developing systems that record medical data, designers make decisions about how to model those data in order to perform a given task. For example, in designing the computer based medical record system Elias,3 the designers focused on issues such as ease of data entry and emulating existing paper records. The same designers 170 DIAGNOSTIC DECISION SUPPORT subsequently discovered significant limitations in the Elias records when they developed a decision support system that uses these records as a data source. First, data recorded on computer can be readily retrieved and reused for a variety of purposes.

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Whether this is due to the action of inhaled nicotine is uncertain proven extra super cialis 100 mg, but nicotine is known to stimulate presynaptic receptors on cholinergic nerve terminals which purchase extra super cialis 100 mg mastercard, unlike the muscarinic ones, result in increased ACh release. MODULATING GLUTAMATE FUNCTION If long-term potentiation (LTP) is important in memory function and as it can be blocked by glutamate NMDA antagonists (see above) then increasing NMDA activity is of putative value in AzD. In reality this presents a problem because overstimulation of the receptor could not only increase neuronal function up to convulsive level but even cause neurotoxicity. Briefly, NMDA applied to rat cortex causes retrograde degeneration of cholinergic neurons in nucleus basalis while NMDA antagonists prevent anoxic destruction of cultured hippocampal neurons and brain damage caused by cerebral vascular occlusion in rodents. The ischaemia the latter produces causes such an excessive neuronal discharge and release of glutamate that the intense activation of NMDA receptors produces a prolonged neuronal depolarisation, Ca2‡ entry and cell death. Possibly a weak partial NMDA agonist, or a drug acting at one of the NMDA receptor subsites (see Chapter 10) like that for glycine, may be of some value. GABA Although there is no neuropathological evidence to implicate GABA in AzD it is known that agonists at the benzodiazepine receptor site not only augment GABA function but also cause amnesia. So it is possible that an inverse agonist, or perhaps even an antagonist, for the benzodiazepine receptor could have the opposite effect and improve memory. In humans, one antagonist, the b carboline derivative ZK93426, showed some improvement in learning and memory tests. It also improves acquisition in animal-learning tests and counteracts the impairment caused by scopolamine, as does the b-carboline inverse agonist DMCM. The fear of inducing anxiety or even convulsions with inverse benzodiazepine agonists has prompted the evaluation of partial inverse agonists (see Abe, Takeyama and Yoshimura 1998). OTHER NTs There have been few attempts to manipulate the monoamines in AzD and those using selegiline, the MOAB inhibitor, have shown little effect although the 5-HT3 antagonist, ondansetron, may give a slight improvement. Despite the clear loss of somatostatin in AzD a synthetic analogue L-363586 had no beneficial effect on memory loss. ATTENUATION OF DEGENERATION Even if NT manipulation had provided an effective therapy in AzD it would still be important to stop the progression of degeneration and the disease process itself. The activity of b-amyloid might be reduced by: (a) stopping its production by reducing the phosphorylation and proteolysis of APP (b) increasing its breakdown (c) counteracting its toxic effects through plaque formation APP is normally cleaved within the Ab sequence by an unidentified protease, so- called a-secretase, so that most of the extracellular APP is released in a soluble form into the extracellular fluid (see Checler 1995). When b-amyloid is formed another protease (b) splits APP so that the complete Ab sequence persists at the extracellular end of the remaining membrane and intracellular APP chain. This is then cleaved by anaother protease (g-secretase) to release the b-amyloid (Fig. Potentiation of a- or blockage of b- and g-secretase could reduce the production of Ab which becomes insoluble and is precipitated (see Hardy 1997). The b-amyloid (Ab4) sequence is partly extracellular and partly in the membrane. NEUROTROPHIC FACTORS Whether or not the production of b-amyloid can be curtailed, it would be desirable to either replace the damaged neurons or encourage the remaining functional ones to ramify further and exhibit more influence. The former, which requires tissue or cell line grafts, is currently not feasible and barely investigated experimentally but there is much interest in the possible use of neurotrophic proteins (neurotrophins) that encourage neuronal growth and differentiation. A number of these have been isolated and identified but the first to be discovered (see Levi-Montalcini 1987), and the most studied, is nerve growth factor (NGF) which, despite its name, is not universally effective on all neurons. In the periphery it is mainly released in tissues containing sympathetic nerves that take it up and transport it retrogradely to the cell body where it acts. In the brain, however, it has more influence on cholinergic than noradrenergic or other neurons so that NGF protein and MRNA expression is highest in cholinergic innervated areas of the brain such as the hippo- campus and cortex while its binding sites (receptors) are mainly in subcortical regions with cholinergic neurons like the nucleus basalis. So it may be assumed that normally the cortically produced NGF is transported back to cholinergic subcortical neurons where it exerts its trophic action. Certainly NGF increases ChAT production when added to cultured cholinergic neurons and its intraventricular infusion in rats and primates prevents the loss of ChAT activity in and degeneration of, cholinergic neurons caused by transection of the septal hippocampal cholinergic pathway, or ibotenic acid injection into the nucleus basalis. Intraventricular NGF has also been shown to improve learning and memory in aged rats and those with lesions to cholinergic pathways. So if NGF is so important for the growth and function of the cholinergic neurons, that appear so vulnerable in AzD, can they be restored and AzD controlled by administering NGF? Before that question can be answered some practical problems have to be overcome, namely how to obtain and administer it. If immune reactions are to be avoided then recombinant human factor should be used and that cannot be produced in large quantities. In any case, it is a large protein that will have to be injected directly into the brain. Even if these problems can be overcome the spread and intensity of any NGF effect has to be restricted so that excessive neuritic growth and inappropriate increases in synaptic connections do not occur.

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