By R. Domenik. Trinity College, Hartford Connecticut.

New England Journal of Medicine This patient has a significant haemolytic anaemia generic 600mg neurontin, which is 1996; 335: 800–6 purchase 800 mg neurontin otc. The lack of this enzyme often only becomes clinically manifest when the red cell is stressed purchase neurontin 300 mg line, as in the presence of an oxidant such as chloroquine (other common drugs that precipitate haemolysis include primaquine, dap- sone, sulphonamides, the 4-quinolones, nalidixic acid and ciprofloxacin, nitrofurantoin, aspirin and quinidine). The patient should be asked whether anyone in his family has ever experienced a similar condition, as it is inherited as an X-linked defect. Patients whose ethnic origins are from Africa, Asia, southern Europe (Mediterranean) and Oceania are more commonly affected. Stopping the chloroquine and treating with folate and iron should improve the anaemia and symptoms. Telomeres are pro- In addition to surgery, radiotherapy and chemotherapy, atten- duced and maintained by telomerase in germ cells and tion to psychiatric and social factors is also essential. Telomerase loses its function in the course of staging is important and where disease remains localized cure, normal cell development and differentiation. In some cases, cells, a component of the telomere is lost with each cell division, chemotherapy is given following surgery in the knowledge that and such telomeric shortening functions as an intrinsic cellular widespread microscopic dissemination almost certainly has clock. Approximately 95% of cancer cells re-express telomerase, occurred (this is termed ‘adjuvant chemotherapy’). The newest, so- called ‘molecularly targeted’, anti-cancer agents target ligands or Clones of neoplastic cells expand, invade adjacent tissue and receptors or pivotal molecules in signal transduction pathways metastasize via the bloodstream or lymphatics. In approximately 50% of human cancers, genetic mutations • Invasion and metastasis contribute to the neoplastic transformation. Some cancer cells • Evasion of apoptosis overexpress oncogenes (first identified in viruses that caused • Sustained angiogenesis sarcomas in poultry). Alternatively, neoplastic cells may overexpress growth factor receptors, or underexpress proteins (e. The overall effect of such The number of cytotoxic drugs available has expanded rapidly genetic and environmental factors is to shift the normal balance and their cellular and biochemical effects are now better defined, to dysregulated cell proliferation. Because of this, their dose–cytotoxicity rela- tionships follow first-order kinetics (cells are killed exponen- tially with increasing dose). Cytotoxic drugs are given at very high doses over a short period, thus rendering the bone marrow aplastic, but at the same time achieving a very high tumour cell Dose kill. Their dose–cytotoxicity curve is initially exponential, but at higher doses the response approaches a maximum (see Figure 48. Until the kinetic behav- iour of human tumours can be adequately characterized in individual patients the value of this classification is limited. The major mechanisms of human tumour drug resistance are Cytotoxic cancer chemotherapy is primarily used to induce summarized in Table 48. The ability to predict the sensitivity and maintain a remission or tumour response according to the of bacterial pathogens to antimicrobial substances in vitro pro- following general principles. It often entails complex regi- duced a profound change in the efficacy of treatment of infec- mens of two to four drugs, including pulsed doses of a cyto- tious diseases. The development of analogous predictive tests toxic agent with daily treatment with agents with different has long been a priority in cancer research. Knowing the details of such regimens is not be desirable because, in contrast to antimicrobial drugs, anti- expected of undergraduate students and graduate trainees in cancer agents are administered in doses that produce toxic oncology will refer to advanced texts for this information. Unfortunately, currently, clinically useful predictive drug sensitivity assays against tumours do • Drugs are used in combination to increase efficacy, to inhibit not exist. Chemotherapeutic drugs vary in adverse effects and there is • Treatment may be prolonged (for six months or longer) considerable inter-patient variation in susceptibility. The most and subsequent cycles of consolidation or for relapsed frequent adverse effects of cytotoxic chemotherapy are sum- disease may be needed. The • Cancer chemotherapy slows progression through the mechanisms of chemotherapy-induced vomiting include cell cycle. Reduced intracellular drug Doxorubicin Lomustine, carmustine Bleomycin concentration Cyclophosphamide Mitomycin C Cytarabine (i) increased drug efflux Anthracyclines (e. Increased detoxification 6-Mercaptopurine, alkylating lored to the emetogenic potential of the chemotherapy to be administered. It may also be necessary to give the patient a of drug agents supply of as-needed medication for the days after chemother- 4. No prophylactic anti-emetic treatment is 100% effective, target enzyme especially for cisplatin-induced vomiting. Decreased number of Hormones, lar catheters for intravenous cytotoxic drug administration is receptors for drug glucocorticosteroids mandatory. Agent-specific organ toxicity products (red cells and platelet concentrates) and early antibi- 3. The peripheral neuropathy with availability and use of recombinant haematopoietic growth vinca alkaloids, taxanes) factors (erythropoietin (Epo), granulocyte colony-stimulating 4. Infertility/teratogenicity caused by various chemotherapeutic regimens is a clear-cut 6. Second malignancy advance in supportive care for patients undergoing cancer chemotherapy. It is often enhance the ability to minimize cytotoxic induced bone mar- routine to use two- or three-drug combinations as prophyl- row suppression. However, many resume normal menstru- ation when treatment is stopped and pregnancy is then pos- 1000 sible, especially in younger women who are treated with lower 500 Secondary fall total doses of cytotoxic drugs. Sperm storage before chemotherapy can be considered for 100 03 9 15 21 03 9 15 21 27 33 39 45 51 57 males who wish to have children in the future.

The elderly are subject to a variety of complaints generic neurontin 400mg mastercard, many of which are Absorption of carbohydrates and of several nutrients order neurontin 800mg overnight delivery, includ- chronic and incapacitating neurontin 800 mg, and so they receive a great deal of ing iron, calcium and thiamine, is reduced in elderly people. There is a growing evidence base for the use of Lipid-soluble drugs are absorbed by simple diffusion down drugs in elderly patients, with important implications for pre- the concentration gradient (Chapter 3), and this is not scribing of many important classes of drugs, including statins, impaired by age. However, age per se does not affect drug angiotensin receptor blockers, vitamin D and bisphosphonates absorption to a large extent (Figure 11. Adverse drug reactions and drug interactions become more common with Drug increasing age. In one survey in general ↓Intestinal blood flow practice, 87% of patients over 75 years of age were on regular drug therapy, with 34% taking three to four Absorption↔ different drugs daily. The most commonly prescribed drugs were diuretics (34% of patients), analgesics (27%), ↓Weight tranquillizers and antidepressants (24%), hypnotics (22%) ↓Lean body mass and digoxin (20%). All of these are associated with a high ↑Fat ↓Hepatic blood flow incidence of important adverse effects. Drug elimination becomes less efficient with increasing ↓Concentration of age, leading to drug accumulation during chronic dosing. Homeostatic mechanisms become less effective with water-soluble drugs advancing age, so individuals are less able to compensate for adverse effects, such as unsteadiness or postural Metabolism↓ hypotension. The central nervous system becomes more sensitive to the actions of sedative drugs. Increasing age produces changes in the immune response ↓Renal blood flow Excretion↓ that can cause an increased liability to allergic reactions. Impaired cognition combined with relatively complex dose regimens may lead to inadvertent overdose. Although diazepam and lidocaine, whereas the distribution of polar glomerular filtration rate declines with age, this is not necessar- drugs such as digoxin is reduced compared to younger adults. The reduced clearance of benzodiazepines and to estimate this if necessary using a nomogram (see has important clinical consequences, as does the long half-life of Chapter 7) that incorporates height and weight, as well as age, several active metabolites (Chapter 18). Consequently, confusion or memory the elderly secondary to reduced renal excretion and/or impairment may be falsely attributed to ageing rather than to hepatic clearance are listed in Table 11. The principal age-related changes in pharmacokinetics are summarized in Figure 11. Key points 120 Key points 100 Pharmacokinetic changes in the elderly include: 80 • Absorption of iron, calcium and thiamine is reduced. It is Atenolol common clinical experience that benzodiazepines given to the Cimetidine elderly at hypnotic doses used for the young can produce pro- Diazepam longed daytime confusion even after single doses. The inci- Digoxin dence of confusion associated with cimetidine is increased in Non-steroidal anti-inflammatory drugs the elderly. Other drugs may expose physiological defects that Oral hypoglycaemic agents are a normal concomitant of ageing. Key points The prescription of hypnotics (see Chapter 18) should be Pharmacodynamic changes in the elderly include: minimized and restricted to short-term use. Although depression is common in old age and may indeed phenothiazines, beta-blockers, tricyclic antidepressants, need drug treatment, this is not without risk. Tricyclic antide- pressants can produce worthwhile remissions of depression but should be started at very low dosage. They are generally well This is commonly due to a failure of memory or to not under- tolerated by the elderly, although hyponatraemia has been standing how the drug should be taken. It is therefore essential that the drug regimen is kept as simple as possible The anticholinergic group of anti-parkinsonian drugs (e. There is scope for improved methods trihexyphenidyl, orphenadrine) commonly cause side effects of packaging to reduce over- or under-dosage. Glaucoma regimens are confusing and increase the risk of adverse inter- may be precipitated or aggravated and confusion may occur actions (see Chapter 13). Cerebral function in old people is easily disturbed, resulting in disorientation and confusion. It is shorter time, their sleep is more likely to be broken and they are important to start with a low dose and monitor carefully. Before hypnotics are commenced, other possible factors likely to suffer severe consequences, such as falls/fractures should be considered and treated if possible. Hypokalaemia due to decreased potassium intake (potassium-rich foods are often expensive), faulty homeo- Diabetes is common in the elderly and many patients are static mechanisms resulting in increased renal loss and the con- treated with oral hypoglycaemic drugs (see Chapter 37). It is comitant use of diuretics is more common in the elderly, and is best for elderly patients to be managed with diet if at all possi- a contributory factor in some patients. In obese elderly diabetics who remain symptomatic on prescribed when there is no indication for it (e. In one drugs because of the risk of hypoglycaemia: chlorpropamide series of geriatric patients on digoxin, the drug was withdrawn (half-life 36 hours) can cause prolonged hypoglycaemia and is in 78% of cases without detrimental effects. Brisk diuresis in patients with mental impairment or reduced The decline in renal function must be borne in mind when an mobility can result in incontinence. For many patients, a thia- antibiotic that is renally excreted is prescribed, especially if it is zide diuretic, such as bendroflumethiazide, is adequate. Appendix 3 diuretics, such as furosemide, should be used in acute heart of the British National Formulary is an invaluable practical guide. Broad-spectrum drugs including uncommon with low doses of diuretics, but plasma potassium cephalosporins and other beta-lactams, and fluoroquinones are should be checked after starting treatment. If clinically important common precursors of Clostridium difficile infection which has a hypokalaemia develops, a thiazide plus potassium-retaining high mortality rate in the elderly.

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Also buy neurontin 800 mg on-line, the study and practice of solving interpersonal and inter- Most conflict resolution programs employ some form group conflict purchase neurontin 300mg amex. In the negotiation process cheap 300 mg neurontin fast delivery, parties with “Conflict” from the Latin root “to strike together” opposing interests hold conversations to settle a dispute. Conflict to win as many concessions to his or her own self-interest may take place within one person, between two or more as possible (win-lose), or integrative, where parties at- people who know each other, or between large groups of tempt to discover solutions that embody mutual self-inter- people who do not know each other. Research on games theory and the decision- al confrontation between persons, or merely symbolic making process suggest that the face-to-face conversation confrontation through words and deeds. The conflict involved in direct negotiation may actually influence peo- may be expressed through verbal denigration, accusa- ple to act in the interest of the group (including the oppos- tions, threats, or through physical violence to persons or ing party), or some other interest beyond immediate self- property. The The success of a given instance of conflict resolu- issues of the conflict may be varied, ranging from the tion depends on the attitudes and skills of the disputants simple to the complex. If one person decides to begin the project without the input of the other person, this per- son’s attitude has already jeopardized the conflict resolu- tion process. It is the mediator’s role to clearly lay out the issues of the conflict and to help the disputants arrive at the appropriate response to the conflict. There are sev- eral responses to a conflict: withdrawing from a conflict; demanding or requesting the opposing party to concede; providing reasons the opposing party should concede (appealing to norms); proposing alternatives to the op- posing party; and proposing “if” statements, suggesting willingness to negotiate. Perspective taking, or articulat- ing and validating the feelings and thoughts of the other party (“I see that you want…. Integration of interests (“We both want…”) reflects the highest level, leading to a consensual settlement of negotiations. According to the principles of conflict resolution, the only true solution to a conflict is one that attempts to satisfy the inherent needs of all the parties involved. Conflict Resolution in the Schools: A conformity and compliance work to make them adhere to Manual for Educators. It made use of an optical illusion called the autokinetic National Institute for Dispute Resolution. In Sherif’s experiment, several subjects were placed together in a room with a stationary light. As the indi- Adaptation of one’s behavior or beliefs to match viduals listened to the descriptions of others, their an- those of the other members of a group. The power of social Conformity describes the adaptation of behavior norms was demonstrated even more strikingly when the that occurs in response to unspoken group pressure. It subjects continued to adhere to the norm later when they differs from compliance, which is adaptation of behavior were retested individually. Individuals conform to or strates one of the important conditions that produces comply with group behavior in an attempt to “fit in” or conformity: ambiguity. In most cases, swer to the question asked of the subjects, so they were conforming to social norms is so natural that people more vulnerable to reliance on a norm. However, each subject was Sigmund Freud viewed the conscience as one of tested in a room full of “planted” peers who deliberately two components of the superego, the other being the gave the wrong answer in some cases. In this scheme, the conscience prevents people fourths of the subjects tested knowingly gave an incorrect from doing things that are morally wrong, and the ego- answer at least once in order to conform to the group. This theory suggests that the conscience is Asch’s experiment revealed other factors—notably developed by parents, who convey their beliefs to their unanimity and size of the majority—that influence con- children. They in turn internalize these moral codes by a formity even when ambiguity isn’t an issue. Even one dissenter decreases the Other psychologists have proposed different theo- incidence of conformity markedly. People who follow the lead of an initial dissenter Further Reading may even disagree with that person and be dissenting Weissbud, Bernice. Although the ambiguity and unanimity of the situation are powerful contributors Consciousness to the incidence of conformity, they are not the sole de- Awareness of external stimuli and of one’s own terminants. Individuals who have a low status within a group or are unfamiliar Wilhelm Wundt’s investigations of consciousness, with a particular situation are the ones most likely to begun in 1879, were central to the development of psy- conform. Wundt’s approach, called members of a study or activity group, or new residents to structuralism, sought to determine the structure of con- a community are more likely to be affected by the pres- sciousness by recording the verbal descriptions provided sure to conform. Personality traits, such as concern by laboratory subjects to various stimuli, a method that with being liked or the desire to be right, also play a role. Certain cultures proach to the study of consciousness was the functional- are more likely than others to value group harmony over ism of William James,who focused on how conscious- individual expression. Behavior- ganization managers, and even parents can establish an ism,pioneered by John B. Watson in the early 1900s, atmosphere or “culture” that either fosters conformity or shifted interest from conscious processes to observable allows for dissension and individuality. Teaching Your Child to was at the heart of Sigmund Freud’s model of human Handle Peer Pressure. He also formulated the concept of the preconscious,which functions as an Conscience intermediate or transitional level of mind between the The moral dimension of human consciousness, the unconscious and the conscious. A preconscious thought means by which humans modify instinctual drives can quickly become conscious by receiving attention, to conform to laws and moral codes. In contrast, the re- In meditation, an altered state of consciousness is pressed material contained in the unconscious can only achieved by performing certain rituals and exercises. The collective unconscious con- widely used in the United States for purposes of relax- tains images and symbols, called archetypes, that Jung ation. It has been found that during this type of medita- found are shared by people of diverse cultures and tend tion, people consume less oxygen, eliminate less carbon to emerge in dreams,myths, and other forms. In Jung’s dioxide, and breathe more slowly than when they are in view, a thorough analysis of both the personal and col- an ordinary resting state. Although sleep suspends the voluntary exercise of stances as alcohol, tobacco, and coffee. The major cate- both bodily functions and consciousness, it is a much gories of psychoactive drugs include depressants, which more active state than was once thought.

Some early psychological research showed that best neurontin 300 mg, when compared with monolingual children neurontin 800mg on-line, bilingual children performed more slowly when processing language generic neurontin 300mg with mastercard, and their verbal scores were lower. But these tests were frequently given in English, even when this was not the child‘s first language, and the children tested were often of lower socioeconomic status than the [22] monolingual children (Andrews, 1982). More current research that has controlled for these factors has found that, although bilingual children may in some cases learn language somewhat slower than do monolingual children [23] (Oller & Pearson, 2002), bilingual and monolingual children do not significantly differ in the final depth of language learning, nor do they generally confuse the two languages (Nicoladis & [24] Genesee, 1997). In fact, participants who speak two languages have been found to have better cognitive functioning, cognitive flexibility, and analytic skills in comparison to monolinguals [25] (Bialystok, 2009). Furthermore, the increased density is stronger in those individuals who are most proficient in their second language and who learned the second language earlier. Thus, rather than slowing language development, learning a second language seems to increase cognitive abilities. Structural plasticity in the bilingual brain: Proficiency in a second language and age at acquisition affect grey-matter density. Some species communicate using scents; others use visual displays, such as baring the teeth, puffing up the fur, or flapping the wings; and still others use vocal sounds. Male songbirds, such as canaries and finches, sing songs to attract mates and to protect territory, and chimpanzees use a combination of facial expressions, sounds, and actions, such as slapping the ground, to convey aggression (de [27] Waal, 1989). Honeybees use a “waggle dance‖ to direct other bees to the location of food [28] sources (von Frisch, 1956). The language of vervet monkeys is relatively advanced in the sense that they use specific sounds to communicate specific meanings. Vervets make different calls to signify that they have seen either a leopard, a snake, or a hawk (Seyfarth & Cheney, [29] 1997). Despite their wide abilities to communicate, efforts to teach animals to use language have had only limited success. One of the early efforts was made by Catherine and Keith Hayes, who raised a chimpanzee named Viki in their home along with their own children. Researchers speculated that Viki‘s difficulties might have been in part because the she could not create the words in her vocal cords, and so subsequent attempts were made to teach primates to speak using sign language or by using boards on which they can point to symbols. Washoe, who lived to be 42 years old, could label up to 250 different objects and make simple requests and comments, such as “please tickle‖ and “me sorry‖ (Fouts, [31] 1997). Washoe‘s adopted daughter Loulis, who was never exposed to human signers, learned more than 70 signs simply by watching her mother sign. He learned faster when he was younger than when he got older, he learns by observation, and he can use symbols to comment on social interactions, rather than simply for food treats. Kanzi can also create elementary syntax and understand relatively complex commands. Video Clip: Language Recognition in Bonobos The bonobo Kanzi is the most proficient known nonhuman language speaker. Kanzi usually requires many trials to learn a new sign, whereas human babies can speak words after only one exposure. Kanzi‘s language is focused primarily on food and pleasure and only rarely on social relationships. Although he can combine words, he generates few new phrases and cannot master syntactic rules beyond the level [33] of about a 2-year-old human child (Greenfield & Savage-Rumbaugh, 1991). With some exceptions, the information that can be communicated in nonhuman species is limited primarily to displays of liking or disliking, and related to basic motivations of aggression and mating. Humans also use this more primitive type of communication, in the form of nonverbal behaviorssuch as eye contact, touch, hand signs, and interpersonal distance, to communicate their like or dislike for others, but they (unlike animals) also supplant this more primitive communication with language. Although other animal brains share similarities to ours, only the human brain is complex enough to create language. What is perhaps most remarkable is that although language never appears in nonhumans, language is universal in humans. Language and Perception To this point in the chapter we have considered intelligence and language as if they are separate concepts. The idea that language and its structures influence and limit human thought is called linguistic relativity. The most frequently cited example of this possibility was proposed by Benjamin Whorf (1897– 1941), an American linguist who was particularly interested in Native American languages. Whorf argued that the Inuit people of Canada (sometimes known as Eskimos) had many words for snow, whereas English speakers have only one, and that this difference influenced how the different cultures perceived snow. Whorf argued that the Inuit perceived and categorized snow in finer details than English speakers possibly could, because the English language constrained perception. Although the idea of linguistic relativism seemed reasonable, research has suggested that language has less influence on thinking than might be expected. For one, in terms of perceptions of snow, although it is true that the Inuit do make more distinctions among types of snow than do English speakers, the latter also make some distinctions (think “powder,‖ “slush,‖ “whiteout,‖ and so forth). And it is also possible that thinking about snow may influence language, rather than the other way around. In a more direct test of the possibility that language influences thinking, Eleanor Rosch [34] (1973) compared people from the Dani culture of New Guinea, who have only two terms for color (“dark‖ and “bright‖), with English speakers who use many more terms. Rosch hypothesized that if language constrains perception and categorization, then the Dani should have a harder time distinguishing colors than would English speakers. But her research found that when the Dani were asked to categorize colors using new categories, they did so in almost Attributed to Charles Stangor Saylor. Similar results were found by Frank, Everett, [35] Fedorenko, and Gibson (2008), who showed that the Amazonian tribe known as the Pirahã, who have no linguistic method for expressing exact quantities (not even the number “one‖), were nevertheless able to perform matches with large numbers without problem. Although these data led researchers to conclude that the language we use to describe color and number does not influence our underlying understanding of the underlying sensation, another more recent study has questioned this assumption. Roberson, Davies, and Davidoff [36] (2000) conducted another study with Dani participants and found that, at least for some colors, the names that they used to describe colors did influence their perceptions of the colors.

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