The graft for the nipple can be harvested from many sites including the groin and transferred to the reconstructed breast mound purchase accutane line. The area around the nipple is then tattooed to match the pigmentation of the opposite areola discount accutane 40 mg with visa. Skin and areola sparring mastectomy’s can also be performed for immediate reconstruction procedures order accutane once a day. Other complications  Wound hypertrophic scarring (15-28%)  Haematoma (5-15%)  Minor latissimus dorsi weakness  When the tissue graft is combined with implantation then it carries the same risks and complications associated with implantation cheap accutane 5 mg overnight delivery. Implications for Physiotherapy  Women are advised to avoid strenuous arm exercises for 6–8 weeks if the anterior axillary fold has been reconstructed (Berger et al 1998). The alterations in body image occur when there is a discrepancy between the way someone formerly perceived herself and how she now sees herself as a result of cancer and its treatment (Hoopwood 1993). Asking about body image concerns Clinicians should be alert to a woman’s body image concerns throughout treatment. They should explore whether the woman has significant concerns about the impact of treatments on her body or self by asking questions. Psychological Impact of Breast Cancer Treatment Study Outcome Outcome measures ‘Partial Mastectomy Questionnaires - Women who had undergone and Breast completed 4 years chemotherapy had more sexual Reconstruction: A post partial dysfunction, poorer body image, and Comparison of their mastectomy or more psychological distress. Effects on Psychosocial immediate -Factors predictive of greater Adjustment, Body reconstruction after psychosocial distress included Image, and Sexuality’ mastectomy. Survivors’ measures of health- -The psychosocial impact of type of related quality of primary surgery for breast cancer (Rowland et al 2000) life, body image, occurs largely in areas of body image and physical and and feelings of attractiveness, women sexual functioning receiving lumpectomy experienced more positive outcomes. Continuation of Exercise Most adults, especially women, prefer moderate intensity to vigorous intensity exercise, and are more likely to continue moderate exercise in the long-term (Pinto and Maruyama 1999). This shows the importance of patient preference when prescribing exercise, especially in the long-term. Aim for 1–2 sets (of 8–12 repetitions) of 8–10 different resistance large-muscle group exercises at moderate intensity, 2 or 3 non-consecutive days per week (Jones and Demark-Wahnefried 2006). Benefits:  Higher physical health  Decreased mortality risk from breast cancer (Kendall et al 2005; Holmes et al 2005) [However, 62. Motivation A Cochrane review of exercise in breast cancer patients recommended that because effective exercise interventions require behavioural change to improve adherence and sustainability, “strategies for behaviour change should underpin these interventions” (Markes et al 2009). Self-Determination Theory The more autonomous the level of motivation, the higher adherence to exercise will be (Wilson, cited in Milne et al 2008). Incorporating this into patient education in breast cancer  Beginning exercise interventions immediately after adjuvant treatment can lead to increased autonomy in motivation by 12 weeks (Milne et al 2008). Return to Work 57% of cancer survivors reduce hours of work after diagnosis by >4hrs/week. Individuals who reduced their job duties/hours, there was a higher prevalence of psychosocial issues such as fear, boredom, 110 anxiety, depression and feeling useless (Steiner et al 2008). However, in a Canadian study of breast cancer survivors, there was no significant reduction of work parameters. Only slightly more breast cancer survivors became unemployed in the 3 year follow-up compared to the controls (21% versus 15%) (Maunsell et al 2004). Geographical, cultural and socioeconomic factors may play a role in prevalence in return to work, however, we as physiotherapists should be aware of the potentially adverse psychosocial effects of unemployment, enquire as to whether return to work is important to the patient and incorporate return to work into goals and treatment plan. Factors that influence Return to Work Barriers Facilitators Emotional: guilt, unrealistic expectations Support from co-workers, employers, and/or occupational health dept. Breast Cancer Recurrence With improving treatments and advances in knowledge, a high survival rate exists and most women go on to live full lives without any complications. Survival Rates Relative Survival (%) 1 Year 5 Year 10 Year Sex 2005-2009 2005-2009 2007* Female 95. Normally as a result of failure of the initial treatment, especially with breast- conserving therapies. Emotions felt at time of a recurrent diagnosis:  Patients cope surprisingly well  Some do display depressive symptoms relating to loss of hope, anxieties and fear of death  Others show raises in stress levels and an urgent need to adapt for increased disability (Weisman and Worden 1985; Anderson et al 2005, cited in Kissane et al 2010) Patient advice on coping with recurrence:  Be informed: Find out how to be pro-active about treatments, decision making and preventative strategies in order to gain control over your condition. Physiotherapy and Palliative Care Physiotherapy is now regarded as part of the multidisciplinary palliative team. The study found that:  65% of palliative patients were referred for physiotherapy  The most common interventions were gait re-education, transfer training, and exercise. Psychosocial issues in palliative care Psychosocial care addresses the psychological experiences of loss and facing death for patients. It involves the spiritual beliefs, culture, and values of those concerned and the social factors that influence their experience (Jeffery, 2003). Psychosocial assessment Healthcare professionals need to assess individual strengths, coping styles and stress. Difficulties in communication are among the most frequently reported problems of cancer patients (Wright et al 2002). Patient satisfaction is higher when clinicians:  Smiled a lot  Used an expressive tone of voice  Increased eye contact and face  Leaned forward  Gestured (Griffith et al 2003) Listening It is important to actively listen to the patient. The important behavioural aspects of effective listening are: S-O-L-E-R  Sit squarely in relation to the patient  Maintain an Open position  Lean slightly towards the client  Maintain Eye contact with the patient  Relax around the patient (Egan 1990) Barriers to effective listening:  Temptation to tell them what to do, as opposed to letting them share their feelings  Not enough time to listen, share feelings, experiences  A feeling of vulnerability and fear of what the patient may ask (Donoghue and Siegel 2005) Responding to difficult emotions 1) Acute emotional distress Acute stress disorder is present in almost one third of patients after diagnosis (Kangas et al 2007). A distressed patient may be one who is demanding, unable to make decisions or angry (Bylund et al 2006; Knobf 2007). Patients exhibit a range of emotions post diagnosis including, mood changes such as:  Worry  Concerns with body image  Sadness  Sexuality  Anger  Employment  Fear of recurrence  Relationship issues 119 Responses of the clinician to emotional distress  Listen; ask open ended questions and show care, compassion and interest. Clinicians meeting anger may feel threatened, become defensive or, indeed, angry in response. These reactions are generally considered unhelpful as they are likely to result in an escalation of the patients anger (Cunningham, 2004). Develop a shared understanding of the experience, and develop shared goals from this point. After being told their diagnosis, approximately 20% of patients deny they have cancer; 26% partially suppress awareness of implementing death and 8% demonstrate complete denial (Greer, 1992). Strategies and communication skills for clinicians  Exclude misunderstanding or inadequate information  Determine whether denial requires management  Explore emotional background to fears  Provide information tailored to the needs of the patient and clarify goals of care  Be aware of cultural and religious issues  Monitor the shifting sand of denial as the disease progresses  Aim to increase a person’s self esteem, dignity, moral and life meaning (Greer 1992; Watson et al 1984; Erbil et al 1996; Schofield et al 2003) Useful Link for communication skills in cancer care: http://pro. Other Programmes to Support Cancer Patients Travel2Care scheme This scheme helps patients who are suffering from genuine financial hardship with travel costs due to travelling to a cancer centre. Care to drive programme Care to Drive is a volunteer-led transport initiative in which the Irish Cancer Society recruits and trains volunteers to drive patients to and from their chemotherapy appointments. Tax relief can also be claimed back on travelling costs for insured cancer patients. Dengue Fever 1 Introduction Dengue has a wide spectrum of clinical presentations, often with unpredictable clinical evolution and outcome. Reported case fatality rates are approximately 1%, but in India, Indonesia and Myanmar, focal outbreaks away from the urban areas have reported case- fatality rates of 3-5%. To observe for the following Danger signs and report immediately for hospital admission • Bleeding: - red spots or patches on the skin - bleeding from nose or gums - vomiting blood - black-coloured stools - heavy menstruation/vaginal bleeding • Frequent vomiting • Severe abdominal pain • Drowsiness, mental confusion or seizures • Pale, cold or clammy hands and feet • Difficulty in breathing Out -patient laboratory monitoring- as indicated • Haematocrit • White cell count • Platelet count 5. If not tolerated, start intravenous isotonic fluid therapy with or without dextrose at maintenance. If the haematocrit remains the same, continue with the same rate for another 2–4 hours and reassess. If the vital signs/haematocrit is worsening increase the fluid rate and refer immediately. Start with 5–7 ml/kg/hour for 1–2 hours, then reduce to 3–5 ml/kg/hr for 2–4 hours, and then reduce to 2–3 ml/kg/hr or less according to the clinical response. If the haematocrit remains the same or rises only minimally, continue with the same rate (2–3 ml/kg/hr) for another 2–4 hours. If the vital signs are worsening and haematocrit is rising rapidly, increase the rate to 5–10 ml/kg/hour for 1–2 hours. Reassess the clinical status, repeat the haematocrit and review fluid infusion rates accordingly. Reduce intravenous fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase. This is indicated by urine output and/or oral fluid intake that is/are adequate, or haematocrit decreasing below the baseline value in a stable patient. Parameters that should be monitored include hourly vital signs and peripheral perfusion. Internal bleeding is difficult to recognize in the presence of haemo-concentration. First correct the component of shock according to standard guidelines with early use of packed cell transfusion.

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K eep the clientcovered as m uch aspossible F igure4D orsalrecum bentposition 180 Basic ClinicalN ursing Skills 3 30mg accutane sale. Caution:U nconscious clients trusted 5 mg accutane, pregnantwom en order accutane on line amex,clients with abdom inalincisions buy on line accutane,and clients with breathing difficulties cannot lie in this position. The rightknee is flexed againstthe abdom en,the leftknee is flexed slightly,the leftarm is behind the body,and the rightarm is in a com fortableposition. Caution: The clientwith leg injuries or arthritis often cannotassum ethisposition F igure6Sim ’sposition 181 Basic ClinicalN ursing Skills 5. K nee-ch estPosition:-is used forrectal andvaginalexam inationsandastreatm enttobring the uterus into norm alposition. The clientis onthe knees with the chestresting on the bed and the elbow rested on the bed,orwith the arm s above the head,the client’s head is turned to the side. Itis sim ilarto dorsal recum bentposition,exceptthatthe client’s legs are wellseparatedandthekneesareacutelyflexed. F igure9 L ithotom yposition 183 Basic Clinical Nursing Skills Crutch Walking Crutches: - are walking aids made of wood or metal in the form of a shaft. Application of Nursing Process Assessment - Assess physical ability to use crutches and strength of the client’s arm back, and leg muscle. Implementation/Procedure - Teaching muscle- strengthening exercises - Measuring client for crutches 184 Basic Clinical Nursing Skills - Teaching crutch walking: Four-point gait, Three-point gait, two-point gait. Four-Point Gait Equipment - Properly fitted crutches - Regular, hard soled street shoes - Safety belt, if needed Procedure 1. Three-Point Gait The Equipment is Similar with Four Gait 186 Basic Clinical Nursing Skills Procedure 1. The gait can be performed when the client can bear little or no weight on one leg or when the client has only one leg. Put weight on the crutch handles and transfers unaffected extremity to the step where crutches are placed. Document the following points: - Time and distance of ambulation on crutches - Balance - Problems noted with technique - Remedial teaching - Client’s perception on the procedure Helping the client into Wheelchair or Chair Supplies and Equipment - Wheelchair - Slippers or shoes (non-skid soles) - Robe - Transfer self (optional) 191 Basic Clinical Nursing Skills Procedure 1. Obtain help from another person if the client is immobile, heavy, or connected to multiple pieces of equipment. Fluid & Electrolyte Balance Normal body function depends on a relatively constant volume of water and definite concentration of chemical compounds (electrolyte). Electrolyte – is a compound that dissociate in a solution to break up in to separate electrically charged particles (ions) – cation, anions Distribution of Body Water in Adult Body water is contained with in two major physiological reservoirs (compartments). Extra cellular fluid about 20% of body weight (20 liters) in which: a) 5 liter in intra vassal b) 15 liter interstissual – tissue space the space between blood and the cells. A part from this the extra cellular fluid contains other fluids, which are usually negligible, considering their concentration in the body. NaCl Na + Cl Intracellular fluid and extra cellular fluid are separated by cell membrane, which is semi permeable. The difference is maintained by the cells, which actively reject certain electrolytes, and retain others. The difference is maintained by cellular action referred as sodium pump, which reject sodium from the cells. Pincytosis 197 Basic Clinical Nursing Skills Substances are transported between cellular and extracellular fluids between biological membranes. Osmotic pressure of the blood protein (colloid osmotic pressure) – which is pulling or holding force opposing the flow of fluid across the vascular membrane When blood enter the arteriol and the capillaries hydrostatic pressure is greater than osmotic pressure and fluid filters out of the vessels. The movement of fluid out of the vessel is facilitated also by negative hydrostatic pressure – sucking fluid from plasma and the osmotic pressure in the interistissual space. The result of the force that promotes the movement of fluid through the capillary is the sum of positive out ward pressure from within the capillaries and the negative hydrostatic pressure and the osmotic pressure in the interstissual spaces. Effect of osmosis as applied to different extracellular solute concentration will give isotonic, hyper tonic and hypotonic solution. When all contributions to osmolality are summed the total serum osmolality ranges from 275 mosm/kg to 290 mOsm/kg. Solutions can be categorized according to how their osmolality compared with that of extracellular fluids. Hypotonic fluids are distributed in proportion of ⅓ to the extracellular compartment and ⅔ of intracellular compartment. When 199 Basic Clinical Nursing Skills hypertonic fluids are added to the vascular space, the extracellular osmolality becomes greater than that of intracellular fluid. Decreased fluid intake due to: (a) Inability to swallow (b) Lack of available fluid (c) Lack of thirst sensation 3. Deficiency of electrolyte (a) Deficiency of aldostrone – during addson’s disease (b) Relative decrease of electrolyte 200 Basic Clinical Nursing Skills Effects and Manifestations of fluid deficit The effect depends on severity: Usually, the first sign is thirst, dry skin, - Decreased blood pressure - Oliguria - Retention of wasts acidosis - Increased haemoglobin and hematocrit - Loss of strength and a pathy - Disturbance in cellular function in the brain B Coma B death Excess Fluid Causes of excess fluid in the body 1. Conversely, bases are chemical substances that combine with 201 Basic Clinical Nursing Skills hydroxyl ions in a chemical reaction. The acidity or alkalinity of a solution depends upon the concentration of hydrogen ions and hydroxyl ions. Kidney Regulation The kidneys play an important role in maintaining acid base balance + by execration of H and forming hydrogen carbonate. Metabolic Acidosis Cause: - Increased acid production - Uncontrolled diabetes mellitus - Increased alcohol intake 204 Basic Clinical Nursing Skills - Excessive administration of drugs e. The body can make some nutrients if adequate amount of necessary precursors (building blocks) are available. Essential nutrients are those that a person must obtain through food because the body can not make them in sufficient quantities to meet its needs. In addition to meeting physiologic requirements, diet also used to satisfy a variety of personal, social, and cultural needs. The 209 Basic Clinical Nursing Skills current philosophy is that no good foods or bad foods exist, and that all foods can be enjoyed in moderation. Dietary Guidelines The purpose of dietary guidelines is to provide a healthy public with practical and positive suggestions for choosing a diet that meets nutritional requirements, support activity, and reduces the risk of malnutrition and chronic disease. These guidelines are not intended as a diet prescription for specific individuals, but serve as a starting point from which people can plan healthy diets. A guideline for healthy diet Guide Line Rationale B Eat a variety of foods - No single food supplies all 40-plus essential nutrients in amounts needed variety also helps reduce the risk of nutrient toxicity and accidental contamination B Balance the food you - Excess weight increases the risk of eat with physical numerous chronic diseases. Such activity – maintain or as hypertension, heart disease, and improve your weight diabetes B Choose a diet with - Plant foods provide fiber, complex plenty of gain carbohydrates, vitamins, minerals, products, vegetables, and other substances important for and fruits good health B Choose a diet low in - High fat diets increase the risk of fat, saturated fat, and obesity, heart diseases, and certain cholesterol types of cancer B Choose a diet - Foods high in added sugar are moderate in sugars “empty calories”. Both sugar and starches promote tooth decay B Choose a diet that is - A high salt intake is associate with moderate in salt and higher blood pressure sodium 211 Basic Clinical Nursing Skills Therapeutic Nutrition Therapeutic nutrition is a modification of nutritional needs based on the disease condition or the excess or deficit of a nutrition status. Combination diets, which include alterations in minerals, vitamins, proteins, carbohydrates, fats as well as fluid and texture, are prescribed in therapeutic nutrition. Gastrostomy/Jejunostomy Feedings A gastrostomy feeding is the installation of liquid nourishment through a tube that enters a surgical opening (called a gastrostomy) through the abdominal wall in to the stomach. A jejunostomy feeding is the installation of liquid nourishment through a tube that enters a surgical opening (a jejunostomy) through the abdominal wall in to the jejunum. When there is an obstruction the esophagus, they may be come permanent, for example, after removal of the esophagus. Inserting a Nasogastric Tube Purposes - To administer tube feedings and medications to clients unable to eat by mouth or swallow a sufficient diet without aspirating food or fluid into the lungs 212 Basic Clinical Nursing Skills - To establish a means for suctioning stomach contents to prevent gastric distention, and vomiting. Ask the client to hyperextend the head, and using a flash light observe the intactness of the tissue of the nostrils. Examine the nares for any obstructions or deformities by asking the client to breath through one nostril while occluding of the other. Determine how far to insert - Use the tube to mark off the distance from the tip of the client’s nose to the tip of the ear lobe and from the tip of the ear lobe to the tip of the sternum. Once the tube reaches the oropharynix (throat) the client will feel the tube in the throat and may gag or retch. In the cooperation with the client, pass the tube 5 to 10 cm (2 to 4 in) with each swallow, until the indicated length is inserted. If the client continuous to gag and the tube does not advance with each swallow, with draw it slightly, and inspect the throat by looking through the mouth. Attach the tube to the suction source or feeding apparatus as ordered, or clamp the end of the tubing.

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Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to comple- ment receptors buy accutane 20 mg. Phosphate is essential for stimulation of V gamma 9V delta 2 T lymphocytes by mycobacterial low molecular weight ligand order accutane mastercard. Type 2 Cytokine gene activation and its relationship to extent of disease in patients with tuberculosis buy accutane cheap online. Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respi- ratory tract infection 30 mg accutane for sale. The ability of heat-killed Myco- bacterium vaccae to stimulate a cytotoxic T-cell response to an unrelated protein is as- sociated with a 65 kilodalton heat-shock protein. Effect of pre-immunization by killed Mycobacterium bovis and vaccae on immunoglobulin E response in ovalbumin- sensitized newborn mice. Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7. Inhibition of an established allergic response to ovalbumin in Balb/c mice by killed Mycobacterium vaccae. Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat. Selective receptor blockade during phagocytosis does not alter the survival and growth of Mycobacterium tuberculosis in human macrophages. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary in- flammation. Differential regulation of lipopolysacharide- induced interleukin 1 and tumor necrosis factor synthesis; effect of endogenous and ex- ogenous glucocorticoids and the role of the pituitary-adrenal axis. With the advent of effective antibiotic therapy in the ’50s, the prevalence of the disease, and research on it, declined pre- cipitously. Hippocrates thought it was inherited, while Aristotle and Galen believed it was contagious (Smith 2003). As the disease was more common in particular families and racial or ethnic groups, a heritable component to susceptibility was a plausible assumption, but one that has defied solid experimental proof, perhaps due to the difficulty in eliminating the confounding biases of environment and exposure. While there are several recent reviews of the subject (Bellamy 2005, Bellamy 2006, Fernando 2006, Hill 2006, Ottenhoff 2005, Remus 2003), it is hard to come to definitive conclusions on most of the genes, because the accumulated literature is often contradictory. This has led to the recent publication of meta-analyses attempting to examine the body of published work on particular genes to determine whether a convincing consensus emerges (Kettaneh 2006, Lewis 2005, Li 2006). In addition, it will review studies performed prior to the molecular era to illustrate the history of the field, which may help to clarify why finding genetic determinants has been elusive. The basic epidemiological designs employed in studies of genetic association, in approximate decreasing order of confidence that the results obtained are free of the complicating influences of environment and exposure are: • twin studies comparing disease concordance in monozygotic vs. While this tour is not exhaustive, it attempts to critically present most of the relevant published work. Stocks and Karn (Stocks 1928) devised a correlation coefficient based on sibling disease concurrence expected by chance. Although the attempt was interesting in its design, it could not assure comparability of environment and exposure, as a tuberculous relative could have had a con- founding effect, either as a source of exposure or as a marker for lower socioeco- nomic status. To address the obvious criticism that the spouses could have been exposed in childhood from the affected relative, Puffer stated that two thirds had no known household contact, although the contact may have been forgotten or missed. Overall, due to the near impossibility of controlling for household exposure, the family studies failed to convincingly demonstrate a genetic predisposition. Monozygotic twins are genetically identical, while dizygotic twins are only as genetically similar as other siblings. The concordance in monozygotic twins can also serve as a measure of penetrance − the proportion of gene carriers who express the trait (Cantor 1992). This study would appear to be solid evidence supporting hereditary influences, but it is weakened by several sources of potential bias specific to twin studies (Cantor 1992, Fine 1981) that are worth examining in detail because they again illustrate the difficulties in isolating genetic components from differences in exposure, and the importance of experimental design. Table 6-1: Twin studies Monozygotic Dizygotic Monozygotic Dizygotic Total Pairs Concordant pairs Reference N % N % N % N % Diehl 1936 80 39 125 61 52 65 31 25 Dehlinger 1938 12 26 34 74 7 58 2 6 Kallman 1943 78 25 230 75 52 66 53 23 Harvald 1956 37 26 106 74 14 38 20 19 Simonds 1963 55 27 150 73 18 32 21 14 The Prophit study set out to re-examine the conclusions of Kallman and Reisner’s study by trying to correct all its shortcomings (Simonds 1963). A conservative conclu- sion might be that some inheritable component exists, but it has a maximal pene- trance of only 65 %, and the most careful study ever performed found only 31. While the near fixation on this topic by authors such as Rich (Rich 1951) might be ascribed to the prevailing racism of the period, the as- sumption of greater susceptibility of Africans and African Americans continues to be cited in current literature, with investigators now using molecular findings to try to explain it (Liu 2006). While Rich gave equal credit to “the marked influence of environment… in different economic strata of individual communities within a given country” for Whites, he attributed the higher rates in Africans and African- Americans predominantly to the effects of genetic composition. James McCune Smith in de- bunking the notion that African Americans were genetically predisposed to rickets by showing that whites of the same low socioeconomic status were similarly pre- disposed (Krieger 1992). It’s interesting that these three commonly cited examples all involve foreign conscripts or internees on a colonizer’s military base, and rely on the dubious assumption that their physical and emotional environments were the same as those of the host soldiers. This theory, though still cited in current literature (Fernando 2006), is completely unproven and will likely remain so. Nonetheless, the abundance of literature describing increased susceptibility and a more progressive disease course in Africans and Native Americans suggests that some racial difference may, in fact, exist. Putting aside the theory for the origin of racial differences, are there any studies that have sufficiently controlled for environment and exposure, in order to credibly document a difference? The difficulty in proving a genetic component for human susceptibility 215 rates of 936 and 725 per 100,000 were much higher than rates seen in any other study, but there is no data on other risk factors. In the Alabama study, the overall racial difference was predominantly due to very high rates in young Black women. The best single study was among Navy recruits, because the environment and follow-up were usually equivalent, at least once they were in the Navy. In that study, African Americans had an annual rate only 17 % higher than whites (91/78), but the Asians (195) had a rate more than double that of African Americans. The difficulty in proving a genetic component for human susceptibility 217 residents with positive skin tests. Al- though the nursing home setting convincingly controls for sources of bias, includ- ing age and sex, there is no data on the residents’ weights, general health, or pat- terns of association and rooming. Even if African-Americans have a slightly increased rate of infection, the fact that there was no difference in the rate of progression to disease deflates the credibility of arguments that their immune system is less capable of controlling the infection. No racial differences were found, leading the authors to question the validity of the conclusions from the nursing home study (Hoge 1994). McKeown concluded that improved nutrition was responsible for the decline in mortality and the increase in population, while others later argued that more im- portant factors were the general improvements in living standards and such public health measures as improved housing, isolation of infectious individuals, clean drinking water, and improved sanitation (Szreter 2002). Nonetheless, it is generally accepted that this dramatic decrease was mainly the result of societal factors. There are over 100 different primary genetic immunodeficiencies that predispose to infections with a variety of viruses, bacteria, fungi and protozoa, but only a few have been associated with severe mycobacterial infections (Casanova 2002). A patient was recently described, who had been clinically diagnosed with hyper IgE syndrome and was unusually susceptible to various microorganisms including mycobacteria, as well as virus and fungi (Minegishi 2006). A mutation was found in the gene for tyrosine kinase 2 (Tyk2), a non-receptor tyrosine kinase of the Janus kinase family. This defect in neutrophil killing makes them susceptible to severe recurrent bacterial and fungal infections. Affected patients are predisposed to dis- seminated infections with atypical mycobacteria, septicemia from pyogenic bacte- ria, and viral infections. Overall, mycobacterial infections occur in perhaps a third of patients with severe combined immunodeficiency and anhydrotic ectodermal dysplasia with immunode- ficiency. Mendelian susceptibility to mycobacterial disease Perhaps the most convincing evidence for genes involved in human susceptibility to mycobacteria has come from studying those rare patients with genetic mutations that selectively increase their susceptibility to mycobacteria, salmonella and occa- sionally virus (Casanova 2002, Fernando 2006, Ottenhoff 2005). Most of the my- cobacterial infections in these unfortunate children and adolescents are not caused by M. The mutations responsible for this susceptibility have been identified in many af- flicted individuals, and found to be transmitted by classic Mendelian inheritance. Although the defects are heterogeneous, they often occur in children of consan- guineous parents, with several cases in the same family. The inheritance is most commonly autosomal recessive, but autosomal dominance has been reported in some families, and there is at least one example of X-linked recessive inheritance. The severity and prognosis correlate with the immune response to the infections: children who form lesions typical of lepromatous leprosy - poorly defined, with many mycobacteria but no epithelioid or giant cell - generally succumb to overwhelming infections that are often resistant to cure even with intensive antibiotic therapy. In contrast, patients who form granulomas similar to those of tuberculoid leprosy - paucibacillary, well defined, with giant and epithelioid cells - generally respond to therapy and survive (Ottenhoff 2005). The mycobacteria involved were both slow- and fast-growing species, and even included the generally innocuous M. Only one death has been reported, and there is wide variation in the clinical presentation between family kindreds and even among family members affected by the same mutation.

H. Lee. King College.