Jeffrey A Brinker, M.D.
- Professor of Medicine
- Joint Appointment in Radiology and Radiological Science
Although it is a histologically benign tumor purchase serophene with american express pregnancy 0-9 weeks, the prognosis may be unfavorable because of its expansile growth 100mg serophene sale womens health quizzes. Atypical teratoid/rhabdoid tumor is a highly malignant tumor that may occur in the newborn (Figure 20 generic 25mg serophene amex menstrual games. It may occur as a solitary tumor or concomitantly with rhabdoid tumor of the kidney or liver. It is characterized by aggressive growth, early metastases through the cerebrospinal? Tumor sizes of 8?10 cm have been reported, and hydramnios is present in 30% of cases. Hemangioma: Localized proliferation of vascular tissue which rarely presents as fetal neck masses Complex sonographic appearance with many small vascular channels and an almost solid appearance. Progress in molecular and inherited cancer syndromes has led to the further understanding of carcinogenesis. Isaacs H Jr: Tumors of Fetus and Infant: An Atlas, Springer-Verlag, New York, 2002. Microscopically a keratinous plug and an intra or subcorneal vesicle communicates with the underlying sweat duct, sometimes with a mild in? Milia are pearly yellow 1 to 3-mm papules on the face, chin, and forehead of 50% of newborns. Microscopically they are miniature epidermal inclusion cysts, which arise from the pilosebaceous apparatus of vellus hairs. Seborrheic Dermatitis the scalp is most often affected in the newborn and is often associated with in complete removal of the vernix caseosa. Section of skin of a newborn showing cyst containing kerati naceous and colloid material. Leiner disease (desquamative erythroderma) isamoresevereformofse borrheic dermatitis. This condition on the body is erythematous and covered by gray-white brawny or greasy scales. Intermittent fever, diarrhea, generalized lymphadenopathy, edema, and albuminuria may be present. They are char acterized by a separation within the epidermis or between the epidermis and dermis with clefts that may be subcorneal, intraepidermal, suprabasal, A B 21. It begins with skin tenderness, erythema, a scalded appearance, and cleavage of the epidermis and is associated with skin and enteric infec tions. Staphylococcal Scalded Skin Syndrome (Ritter Disease) Thisclinicallyresemblestoxicepidermalnecrolysis. Microscopically there are mild changes in the necrolysis) with desquamation of skin. It presents with variably pruritic vesi clesandbullaeusuallylocatedontheperineum,thighs,buttocks, and lower abdomen, and less commonly on the arms, face, and legs. Blisters tend to cluster around the periphery of older, re solving lesions, giving it a string of pearls? appearance. The vesicles are caused by separation of the basal layer from the basement membrane with neutrophils and eosinophils. Acrodermatitis Enteropathica this is an autosomal recessive vesiculobullous disease due to a zinc de? The lesions are weeping, crusted erythematous patches affecting the diaper region, perioral, acral, and intertriginous areas (Figure 21. It may present in the neonatal period with diarrhea, anooral dermatitis, and alopecia. Affected infants have a defect in zinc binding protein in the gastrointestinal tract with resultant zinc malabsorption. Breast milk is protective because it contains a zinc binding ligand that facilitates zinc absorption. Acquired forms of this disease occur in infants receiving hyperalimentation with a low or absent zinc content and in malabsorption states (cystic? Incontinentia Pigmenti Incontinentia pigmenti is an X-linked dominant trait and is lethal in males. Ichthyosis the most severe form of ichthyosis occurs as the harlequin fetus, which is inherited as an autosomal recessive characteristic and is present at birth (Figure 21. The hands may appear moist and weeping with no apparent skin covering, and the nails may be A B 21. This infant developed thick plate-like scales and ectro pion immediately after birth followed by respiratory failure and death. The collodion baby (lamellar ichthyosis) is encased in a thick cellophane-likemembranewithanincidenceof1/300,000births. The skin is rough and scaly, and the lesion is most prominent on the extensor surfaces, especially elbows and knees. X-linked ichthyosis is characterized by generalized large, dark scales with sparing of the palms and soles. In one-third, the lesions are present at birth; the incidence is 1/6,000 male births. Prenatal diagnosis by fetoscopic skin biopsy in all forms of ichthyosis is possible. Menkes kinky hair syndrome is X-linked due to a defect in intestinal copper absorption resulting in a low serum copper level and low ceruloplasmin. These lesions last 3 or 4 days and usually disappear with no sequelae, but in malnourished or compromised infants secondary infection may cause serious illness. Skinbiopsyrevealshyperkeratosis,acanthosis,andintracornealvesicleswith small collections of neutrophils, eosinophils, and keratinous debris.
Herbs and spices have been used for centuries by many cultures to purchase serophene australia womens health zone exit health improve the flavor and aroma of foods cheap serophene 50 mg with amex womens health of central ma. Essential oils show antimicrobial properties discount serophene uk pregnancy effacement, and are defined by Hargreaves as a group of odorous principles, soluble in alcohol and to a limited extent in water, consisting of a mixture of esters, aldehy des, ketones, and terpenes. Scientific studies have identified the active antimicrobial agents of many herbs and spices. These include eugenol in cloves, allicin in garlic, cinnamic aldehyde and eugenol in cinnamon, allyl isothiocyanate in mustard, eugenol and thymol in sage, and isothymol and thymol in oregano . Fats, oils, or fatty foods are deemed rancid if a significant deterioration of the sensory quality is perceived, particularly aroma or flavor, but appearance and texture may also be affected. Antioxidants are used to control oxidation in foods, and they also have health functionality by reducing risk of cardiovascular diseases and cancer, and slowing down the aging process. Although not pri marily used to reduce the moisture content of food, the heat associated with the generation of smoke also gives a drying effect. Smoking not only imparts desir able flavor and color to some foods, but some of the compounds formed during smoking also have a pre servative effect (bactericidal and antioxidant). Hydrogen ion concentration, measured as pH, is a controlling factor in regulating many chemical, bio chemical, and microbiological reactions. Microorganisms require water, nutrients, appropriate temperature, and pH levels for growth. Many weak lipophilic organic acids act synergistically at low pH to inhibit microbial growth. The efficacy of acids depends to a large extent on their ability to equilibrate, in their undissociated forms, across the microbial cell membrane and in doing so, interferes with the pH gradient that is normally maintained between the inside (cytoplasm) of the cell and the food matrix surrounding it. In addition to weak lipophilic acids, other preservatives widely used in foods include esters of benzoic acid, which are effective at higher pH values than organic acids. Inorganic acids, such as sulfate and nitrite, are most effective at reduced pH values, like organic acids. While these preservatives are employed at ppm levels of hundreds to thousands, the acids used principally as acidulants are often employed at percentage levels. These acids may exert their influ ence by the denaturing effect of low pH on enzymes present on the cell surface and by lowering of the cytoplasmic pH due to increased proton permeability when the pH gradient is very large. The primary effect of such acids is to lower cytoplasmic pH and undissociated acids may have specific effects on metabolism that amplify the effects of the weak acid. The pH affects not only the growth of microorganism but also other components and processes, such as enzyme stability, gel formation, and stability of proteins and vitamins . Antimicrobial enzymes also have current applications and further future potential in the food industry. They play a significant role in the defense mechanisms of living organisms against infection by bacteria and fungi. Many lytic enzymes now used in the food industry to degrade unwanted polysaccharides have potential for use as novel and natural food preservatives. One such enzyme, lysozyme from hen egg whites, has been known for many years and is used against clostridial spoilage in hard cooked cheese in France . When enzymes are used, it is very important to maintain its activity for its effect in preservation. Hydrolytic antimicrobial enzymes function by degrading key structural components of the cell walls of bacteria and fungi, whereas antimicrobial oxi doreductases exert their effects by the in situ generation of reactive molecules. Nonmedical antibiotics, such as natamycin and nisin, produced either by microbes or synthetically, inhibit microbes at very low concentration. Organisms present in food can become resistant to antibiotics and colonize the gut of animals and man. Also, antibiotics are used in growth enhancement and disease control in healthy animals. However, the increasing incidence of antibiotic resistance is of great concern and is becoming a complicated issue. Antimicrobial agents or preservatives are diverse in nature, but legal, toxicological, marketing, and consumer considerations have created a trend such that both the number and amount of preservatives in use are diminishing rather than increasing . Such modifications can also improve the sensory, nutritional, and functional properties of foods. Changes experienced by foods during processing include glass formation, crystallization, caking, cracking, stickiness, oxidation, gelatinization, pore formation, and collapse. Through precise knowledge and understanding of such modifications, one can develop safe, high-quality foods for consumption . Scott in 1953 clearly identified that the activity of water as a medium is clearly correlated with the deterioration of food stability due to the growth of microor ganisms and for stability this is more important than the total amount of water. This concept helps us to develop generalized rules or limits for stability of foods using water activity. Since then the scien tific community has explored the great significance of water activity in determining the physical charac teristics, processes, shelf life, and sensory properties of foods. The minimum water activity is the limit below which a microorganism or group of microorganisms can no longer reproduce. The critical limits of water activity may also be shifted to higher or lower levels by other factors, such as pH, salt, antimicrobial agents, heat treatment, and temperature to some extent. Removing water, adding solutes, or change of solute?water interactions can reduce the water activity of a food.
The rate of reaction of malonaldehyde with -amino groups of myosin was greater at 20?C than at 0?C and almost equal to buy discount serophene online menopause 40 that of 20?C  order cheap serophene line menstrual ultrasound. Oxidant levels should be increased in frozen dough formulations order serophene 25 mg visa breast cancer knitting patterns, as oxidants increase dough strength. Generally, short ening protects dough structure from damage owing to ice crystallization . Pineapple for processing should be of optimum ripeness, with yellow color and good aroma and flavor, and free from blemishes, such as black heart, water blister, yeasty rot, or brown spot. For frozen pineapple slices, semitranslucent, highly colored slices are generally consid ered the most attractive and have the best flavor. Pineapple color is important because it is often the basis for judging product acceptability. The golden color of pineapple fruit is mainly due to carotenoids, which become more predominant with ripening as chlorophyll content decreases. Heat processing, freezing, and thawing lead to cell disintegration, pigment degradation, and isomerization of carotenoids [26,87,180]. No differences were found in sensory analysis (color and appear ance) between the cultivars, frozen at different rates, compared with fresh product, or after 1 year frozen storage. Color and flavor are important sensory attributes, and vitamin content is a functional attribute of frozen foods. The green color of vegetables is lost by chlorophyll degradation during freezing and frozen storage resulting from the conversion of chlorophyll to pheophytins or the destruction of both chlorophyll and pheophytins, giving a dull khaki color. During storage, chlorophyll is converted to pheophytin with a loss of green color and vitamin C; these can be used as objective indicators of quality [135,142,187]. Chlorophyll was bleached during fat peroxidation and oxidation of glycolic acid and by -hydroxy acid dehydrogenase and chlorophyllase, which hydrolyze the phytal ester group of chlorophylls and pheophytins . Storage temperature and time, acidity, and blanching time affect the loss of chloro phyll in frozen vegetables. Various inorganic salts, such as sodium chloride, potassium sulfate, sodium sulfate, and sodium or ammonium bicarbonate, have been used to reduce chlorophyll loss . Carotene retention curves were sigmoidal with three regions: initi ation, acceleration, and retardation. Martins and Silva  reported a high sensibility of chlorophylls (a and b color values) at 18?C, and results showed that color a and b values retained only 10. Food Preservation by Freezing 645 In poultry, a light surface color for carcasses is considered important and is best achieved with rapid surface freezing, which generates a smooth chalky white surface. This is achieved by supercooling the product and forcing nucleation of a high number of small ice crystals. These crystals stay small because there is little water migration to already formed crystals during such a fast process. Numerous small ice crystals cause the surface to reflect light and appear white in color . An alternative approach is to crust freeze the outer part of the carcass rapidly using liquid brine immersion, spray systems, or cryo genics such as liquid nitrogen or carbon dioxide, and then to move the partially frozen bird to air blast or cold storage for the remainder of the process. A freezing front migration rate of 2?5 cm/h is recom mended to achieve fast freezing effects and 0. Darkening of bones is a condition that occurs in immature chickens and has become more prevalent as broilers are marketed at younger ages. Darkening may arise during chilled storage or during the freez ing and defrosting process. It occurs because some of the heme pigment normally contained in the inte rior of the bones of particularly young chickens leaches out through spongy areas and discolors the adjacent muscle tissues [5,176]. Leaching only occurs in carcasses from relatively young birds because the bones are not completely calcified and are more porous than in mature birds . The development of dark bones was greatly reduced by a combination of freezing and storage at 35?C and immediate cooking after rapid thawing . Apart from this combination, the freezing rate, time between slaughter and freezing, temperature and length of storage, and temperature fluctuations during storage have no marked influence in preventing this discoloration . While taste qualities do not change, the appearance constitutes a negative factor in consumer acceptance . In crustacean seafood, a dark discoloration defined as blackspot or melanosis is developed after the trauma of the capture, string, and thawing process; it is unattractive to consumers and reduces the mar ket value. This oxidative enzyme reaction, followed by autoxidation and polymerization, may be pre vented by applying sulfiting agents in combination with freezing . Further, quick freezing appeared as a good method in addition to the sulfiting agent to prevent the melanosis phenomenon, and following storage for 3 months did not affect the appearance of blackspots. For example, freezing of strawberries is usually associated with a reduction in aroma and the development of off-flavor. The decrease in aroma is due to a rapid decomposition and diffusion of esters [43,49], whereas the concentrations of franeol and meso furane linked to strawberry flavor are not affected by freezing . The off-flavor of frozen strawberries differs from that of frozen vegetables [99,137,192]. The identity of H2S was verified both chemically and using gas chromatography?mass spectroscopy analyses. The olfactory properties by sensory analysis indicated the presence of sulfurous compounds. Usually, H2S is derived from the sulfur-containing amino acids cysteine or methionine during processing. The duration of the production of H2S was longer in strawberries at 40?C and 80?C than at 20?C.
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These substances exert their toxic Thermal and electrical burns 100 mg serophene overnight delivery womens health 7 flat belly, fall in body temperature below effects depending upon their mode of absorption buy discount serophene 25mg line pregnancy cramps, 35?C (hypothermia) and elevation of body temperature above distribution serophene 100mg fast delivery breast cancer surgery, metabolism and excretion. Environmental chemicals may have slow systemic injury and death as occurs on immersion in cold damaging effect or there may be sudden accidental exposure water for varying time. Hyperthermia likewise, may be localised as in cutaneous Some of the common examples of environmental burns, and systemic as occurs in fevers. The most serious complications of burns pesticides, fungicides, herbicides and organic fertilisers are haemoconcentration, infections and contractures on which may pose a potential acute poisoning as well as long healing. The problem is particularly alarming in developing countries like India, China and Mexico where Electrical burns may cause damage firstly, by electrical farmers and their families are unknowingly exposed to these dysfunction of the conduction system of the heart and death hazardous chemicals during aerial spraying of crops. During radiotherapy, some normal cells coming vapours are used in industry quite commonly and their in the field of radiation are also damaged. In general, exposure may cause acute toxicity or chronic hazard, often radiation-induced tissue injury predominantly affects by inhalation than by ingestion. Such substances include endothelial cells of small arteries and arterioles, causing methanol, chloroform, petrol, kerosene, benzene, ethylene necrosis and ischaemia. Pollution by occupational exposure to toxic organs: metals such as mercury, arsenic, cadmium, iron, nickel and 1. Gastrointestinal tract: strictures of small bowel and contaminant in several preservatives, herbicides and oesophagus. Haematopoietic tissue: pancytopenia due to bone marrow combustion of plastic, silk and is also present in cassava and depression. These substances causing injury as sunburns, chronic conditions such as solar keratosis pneumoconioses are discussed in chapter 17 while those and early onset of cataracts in the eyes. In the Western world, nutritional Their deficiencies result in a variety of lesions and deficiency imbalance is more often a problem accounting for increased syndromes. Water intake is essential to cover the losses in health problem, particularly in children. In order to retain stable weight cellulose, hemicellulose and pectin, though considered non and undertake day-to-day activities, the energy intake must essential, are important due to their beneficial effects in match the energy output. The average requirement of energy lowering the risk of colonic cancer, diabetes and coronary for an individual is estimated by the formula: 900+10w for artery disease. Since the requirement Pathogenesis of Deficiency Diseases of energy varies according to the level of physical activities the nutritional deficiency disease develops when the performed by the person, the figure arrived at by the above essential nutrients are not provided to the cells adequately. Dietary proteins provide the body with amino decreased amount of essential nutrients in diet. Secondary or Nine essential amino acids (histidine, isoleucine, leucine, lysine, conditioned deficiency is malnutrition occurring as a result methionine/cystine, phenylalanine/tyrosine, theonine, of the various factors. These are as under: tryptophan and valine) must be supplied by dietary intake i) Interference with ingestion. The such as malabsorption syndrome, chronic alcoholism, recommended average requirement of proteins for an adult neuropsychiatric illness, anorexia, food allergy, pregnancy. Fats and fatty acids (in particular linolenic, linoleic and arachidonic acid) should comprise about 35% of diet. A healthy individual requires Dietary imbalance and overnutrition may lead to diseases 4 fat-soluble vitamins (A, D, E and K) and 11 water-soluble like obesity. Obesity is defined as an excess of adipose tissue that vitamins (C, B1/thiamine, B2/riboflavin, B3/niacin/nicotinic imparts health risk; a body weight of 20% excess over ideal weight 244 for age, sex and height is considered a health risk. Insufficient pushing of oneself out of the chair leading to inactivity and sedentary life style. The lipid storing cells, adipocytes comprise the adipose tissue, and are present in vascular and stromal compartment in the body. Besides the generally accepted role of adipocytes for fat storage, these cells also release endocrine-regulating molecules. Adipose mass is increased due to enlargement of adipose cells due to excess of intracellular lipid deposition as well as 2. Obesity often important environmental factor of excess consumption of exacerbates the diabetic state and in many cases weight nutrients can lead to obesity. A strong association between hyperten observations that obesity is familial and is seen in identical sion and obesity is observed which is perhaps due to twins. Weight reduction leads to and its protein product leptin, and db gene and its protein significant reduction in systolic blood pressure. Total blood and pathological changes described below and illustrated in cholesterol levels are also elevated in obesity. As a result of atherosclerosis and increased adipose stores in the subcutaneous tissues, hypertension, there is increased risk of myocardial infarction skeletal muscles, internal organs such as the kidneys, and stroke in obese individuals. Many obese individuals exhibit hyper this is characterised by hypersomnolence, both at night and glycaemia or frank diabetes despite hyperinsulinaemia. This during day in obese individuals along with carbon dioxide is due to a state of insulin-resistance consequent to tissue retention, hypoxia, polycythaemia and eventually right-sided insensitivity. The term pickwickian 245 syndrome was first used by Sir William Osler for the sleep apnoea syndrome). These individuals are more prone to develop degenerative joint disease due to wear and tear following trauma to joints as a result of large body weight. Diet rich in fats, particularly derived from animal fats and meats, is associated with higher incidence of cancers of colon, breast, endometrium and prostate. Its causes may be the following: i) deliberate fasting?religious or political; ii) famine conditions in a country or community; or iii) secondary undernutrition such as due to chronic wasting Figure 9. After about one week of starvation, protein A starved individual has lax, dry skin, wasted muscles breakdown is decreased while triglycerides of adipose tissue and atrophy of internal organs. The following metabolic changes by most organs including brain in place of glucose. Starvation take place in starvation: can then continue till all the body fat stores are exhausted 1.
Recurrences can be brought on by stress order serophene 50 mg otc menstruation exercise, fatigue generic serophene 50 mg unusual women's health issues, depression buy serophene 25 mg with amex women's health clinic on wright street, immunosuppression and concurrent illness. Type 1 is associated with lesions on the face and fingers, and sometimes genital lesions. Type 2 is associated almost entirely with genital infections, and affects the genitalia, vagina, and cervix and may predispose to cervical dysplasia. Transmission: spread through skin-to-skin contact, usually when skin is broken or lesions present, but asymptomatic viral shedding a possible route of transmission. Neonatal transmission is rare (1 in 10,000 live births), but carries risk of ophthalmic infection? Symptomatic treatment: salt bathing, local anaesthetic creams, oral analgesia, oral fluids. Counselling and follow-up important written information for patients and partners, Herpes Helpline (0508 11 12 13)? Symptoms: Dermatomal pain, then fever malaise for several days, then macule-papules + vesicles, especially in thoracic or ophthalmic division of trigeminal dermatomes. If shingles around eye (especially end of nose), then are likely to have a dendritic ulcer on cornea. Stain with Fluorescein and shine on blue light, corneal abrasions will shine green. Maybe: fever, myalgia, acute pharyngitis, hepatosplenomegaly, atypical mononucleosis? Clinical: Often acquired in childhood, present in older age with solitary cysts (liver, lung, brain)? Diagnosis: Serology: haemaglutination test + complement fixation test Cryptosporidium? Oral vaccine: attenuated live strain, doses at 0, 3 and 5 days gives protection for one year. Rabies: Only for people intending to work longer term in rural/agricultural areas of Asia rd Pyrexia of unknown origin if returning from 3 world? Typhoid: usually constipated, used to die of peritonitis, bradycardia, high spiking fever, takes days for temperature to go down? Eosinophilic Meningitis Antibiotic Treatment Summary G +ive Cocci Strep pneumonia Oral: Amoxycillin. Resistant (eg kids): Ceftriaxone Resistant and Meningitis: Cefotaxime + Vancomycin (act synergistically) Resistant and Endocarditis: Vancomycin Strep faecalis Trimethoprim Strep agalactiae Penicillin. Elderly/immunocompromised: ciprofloxacin (quinolone not in kids) Clostridium difficile Metronidazole Enterococcus faecalis Amoxycillin G ive Bacilli E Coli Trimethoprim. Consider gentamycin or cotrimoxazole Campylobacter Jejuni Erythromycin Infectious Diseases 511 H Influenzae Cefaclor, Augmentin, Tetracycline 5% resistant to penicillin, not sensitive to erythromycin Legionella Erythromycin. Maybe Tobramycin or piperacillin Meningitis: Ceftazidine Gardnerella Vaginalis Metronidazole. Metronidazole is otherwise inactive against aerobes Bordetella Pertussis Erythromycin Branhamella Catarrhalis Augmentin, cefaclor, tetracycline, cefuroxime 70% penicillinase Anaerobes Bacteroides Fragilis Metronidazole. Not penicillin or cephalosporins Helicobacter Pylori Clarithromycin + metronidazole + omeprazole (7 days) Cocci Neisseria Meningitidis Penicillin. Prophylaxis: Rifampicin, ceftriaxone if pregnant Neisseria Gonorrhoea Stat: Amoxycillin + Probenecid Ciprofloxacin or tetracycline if penicillin allergy or resistant. Cellular wall similar to G-ive but not actually a G-ive bacteria Others nd Mycoplasma Erythromycin. Maybe Paromomycin (oral, non-absorbed aminoglycoside) Giardiasis Tinidazole stat or metronidazole 7 days Trichomonas Doxycycline, Metronidazole Pneumocystis Carinii Cotrimoxazole Pneumonia Malaria Prophylaxis Mefloquine weekly: good for chloroquine resistant falciparum. Not epilepsy, pregnant, babies Doxycycline daily: Esp Mefloquine resistant falciparum. Not kids or pregnant Chloroquine + Proguanil: if pregnant Chloroquine weekly: if no chloroquine resistant falciparum Plasmodium Falciparum Quinine sulphate + doxycycline Plasmodium Vivax Chloroquine 3 days then primaquine 2 weeks Amoebiasis Metronidazole + diloxanide furoate Worms Filariasis Ivermectin Intestinal worms Hookworm, roundworm, pinworm: Medendazole Strongyloides Stercoralis: Thiabendazole Tapeworms: Niclosamide th th 512 4 and 5 Year Notes Antibacterials Penicillins Use for Notes Penicillin G (iv/im) Streptococci Not Enterococcus faecalis, resistance in kids to (Oral form: Pen V) strep pneumoniae Staphylococci But 80% produce penicillinase N Gonorrhoeae Some produce penicillinase N Meningitidis T Pallidum Leptospira Syphilis Anaerobes Peptostreptococci, Clostridia, Fusobacteria, Bacteroides (not B fragilis), Actinomyces Amoxycillin As above plus: Enterococcus faecalis Listeria monocytogenes Haemophilus influenzae 6 % produce penicillinase Some E coli 48% resistant Most Proteus mirabilis 20% produce penicillinase Augmentin Clavulanic acid inhibits penicillinase. Principle use is infectious exacerbations of chronic bronchitis Haemophilus influenzae Increasing E coli resistance Branhamella Catarrhalis Flucloxacillin Staph Aureus Penicillinase producers. Immunisation is delivered to individuals and provides individual protection and benefit? Some level of immunisation protects unimmunised people who would otherwise have caught it? Efficacy: Does intervention provide a specific outcome (eg an IgG response) under ideal lab circumstances? Check vaccines due for each patient: either age groups (neonates, children, adolescents, adults, elderly) or specific exposure situations (occupational, travel, post-exposure)? Discuss and obtain informed consent: Written consent only required for children if care giver not present? Local or systemic reactions (fever, rash, joint pains): symptoms of immune activation. Only 1% of infected get severe clinical disease: severe muscle pain, neck and back stiffness? Need to vaccinate guys as well otherwise they will maintain a population reservoir which women with vaccine failure will catch? First order kinetics: rate of transport or elimination proportional to drug concentration in the compartment? So if dose rate is greater than clearance rate, then a small increase in dose rate leads to a dramatic increase in plasma concentration (ie accumulation) Michaelis-Menten kinetics?