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• Clinical Associate Professor
• Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky

http://pharmacy.uky.edu/faculty/hsdivi1/Holly-Divine

This is in contrast to the severe hepatocellular necrosis that was observed in animals exposed to a control diet for 15 weeks followed by a 3-week exposure to 640 mg Cu/kg/day (Haywood and Loughran 1985) blood sugar journals order 60caps diabecon free shipping. At higher doses diabetes prevention program diet cheap 60caps diabecon fast delivery, the onset of the necrosis and regeneration occurred earlier as compared to lower doses blood glucose 310 buy discount diabecon 60 caps on line. Additionally diabetic vegetarian recipes buy diabecon with mastercard, there appears to be an upper limit of copper intake diabete 92 discount generic diabecon canada, which would induce copper tolerance; doses that exceed this level would result in permanent damage to the liver blood sugar keeps going up trusted 60caps diabecon. Dietary exposure of rats to 550 mg Cu/kg/day as copper sulfate for 15 weeks resulted in chronic hepatitis with no evidence of regeneration of parenchymal tissue (Haywood and Loughran 1985). It appears that rats and pigs are equally sensitive to high levels of copper in the diet or drinking water. In contrast, mice do not appear to be as sensitive to the hepatic toxicity of copper as rats. Congestion of the glomeruli and denudation of tubular cells were observed in four individuals consuming a single lethal dose of copper sulfate (Chuttani et al. Acute renal failure was reported in 5 of 125 individuals intentionally ingesting large doses of copper sulfate (Ahasan et al. Hematuria, glycosuria, cylindruria, and proteinuria, indicative of renal tubular damage, were observed in a child who drank a solution containing approximately 3 g of copper sulfate (Walsh et al. A number of animal studies confirm that the kidney is a target of copper toxicity. Renal toxicity as a result of copper loading follows a specific time course (Haywood 1980, 1985; Haywood et al. However, eosinophilic droplets were observed in the epithelial cell cytoplasm of the proximal convoluted tubules in rats exposed to 450 mg Cu/kg/day for 2 weeks (Haywood et al. The number of eosinophilic droplets increased with increasing duration (Haywood 1980, 1985). After 9 weeks, extensive desquamation of the epithelial cells of the proximal convoluted tubules was evident in rats exposed to 180 mg Cu/kg/day (Haywood 1980). An increase in protein droplets in epithelial cell cytoplasm and the lumen of the proximal convoluted tubules was observed in rats exposed to 10 or 92 mg Cu/kg/day as copper sulfate in drinking water or diet, respectively, for 2 weeks or to 33 mg Cu/kg/day as copper sulfate in the diet for 13 weeks. No studies were located regarding body weight effects in humans following oral exposure to copper. More severe decreases in body weight gain and weight loss have also been reported (Haywood 1985; Haywood and Loughran 1985); the weight loss was reported at lethal concentrations. Only one study examined the effect of copper on body weight gain following chronic-duration exposure (lifetime exposure beginning at 58 days of age); this study found no biologically significant effect in mice exposed to 42 mg Cu/kg/day as copper gluconate in drinking water (Massie and Aiello 1984). Impaired performance on the remaining immune function tests were observed at 26 mg Cu/kg/day as copper chloride (Pocino et al. No effects on spontaneous motor activity (assessed using an actophometer), learning ability (assessed using a pole climbing chamber), or relearning capacity and memory (assessed using a Y-maze) were observed in rats fed a diet containing 23 mg Cu/kg/day as copper sulfate (Murthy et al. However, a 25% decrease in a dopamine metabolite, 3, 4-di hydroxyphenylacetic acid, was found in the corpus striatum. Reproductive performance, as assessed by the length of gestation, number of kits whelped, and average kit weight, was not adversely affected in minks fed a diet containing 12 mg Cu/kg/day as copper sulfate (Aulerich et al. There are limited data on the developmental toxicity of copper in experimental animals. Exposure of mouse dams to a higher dose, 208 mg Cu/kg/day as copper sulfate in the diet, resulted in decreased mean litter size and decreased fetal body weights; the statistical significance of these effects is not known (Lecyk 1980). No statistically significant alterations in newborn mortality or body weight were observed in the offspring of mink exposed to 13 mg Cu/kg/day as copper sulfate in the diet (Aulerich et al. There was a trend toward increased kit mortality between birth and 4 weeks of age in the offspring of mink exposed to 6 or 13 mg Cu/kg/day. The incidences were 12, 9, 19, 38, and 32% in the 1, 6, 3, 6, and 13 mg Cu/kg/day groups, respectively; the statistical significance of this effect was not reported. Several oral studies have examined the carcinogenicity of copper compounds in animals. An increased occurrence of hepatocellular carcinomas has been reported in Long-Evans Cinnamon rats (Sawaki et al. Hemolytic anemia was observed in a severely burned and debilitated child in whom copper sulfate crystals were being applied to granulation tissue. Because the skin was severely damaged, this study cannot be used to predict the dermal toxicity of copper following exposure to intact skin. No studies were located regarding hematological effects in animals following dermal exposure to copper. Eye irritation has been reported by factory workers exposed to copper dust (Askergren and Mellgren 1975). No studies were located regarding ocular effects in animals following exposure to copper. Saltzer and Wilson (1968) reported a case of a woman who had recurrent pruritus on her ring finger and wrist caused by copper metal in her ring and wristwatch. Allergic contact dermatitis has been observed in individuals following a patch test using a copper penny and/or a copper sulfate solution (Barranco 1972; Saltzer and Wilson 1968). No studies were located regarding the following health effects in humans and/or animals after dermal exposure to copper: 3. A dramatic decrease in pulse pressure and heart rate was observed in New Zealand white rabbits infused with 2. An in vitro study (Holland and White 1988) demonstrated that cupric ions and cuprous ions decrease human spermatozoa motility. Several studies have examined the carcinogenicity of copper compounds following parenteral administration. No significant alterations in tumor incidence were observed in male Wistar rats receiving subcutaneous injections of 2 mg Cu/kg/day as copper acetate (Yamane et al. Several studies have assessed the genotoxicity of copper sulfate following oral or parenteral exposure; the results of these in vivo genotoxicity studies are summarized in Table 3-3. Significant increases in the occurrence of micronuclei and chromosomal aberrations have been observed in chick bone marrow cells and erythrocytes (Bhunya and Jena 1996) and mouse bone marrow cells (Agarwal et al. Increases in the occurrence of recessive lethals (Law 1938) and sperm abnormalities (Bhunya and Pati 1987) have also been observed in Drosophila and mice, respectively. Several studies copper sulfate and copper chloride genotoxicity did not find significant increases in the occurrence of reverse mutations in Salmonella typhimurium (Marzin and Phi 1985; Tso and Fung 1981; Wong 1988) or Saccharomyces cerevisiae (Singh 1983). The increase in sister chromatid exchange in Chinese hamster cells (Sideris et al. Copper oxide was observed in alveolar capillaries 3 hours after albino rats were exposed to a welding dust aerosol generated from pure copper wires (no additional exposure information was provided) (Batsura 1969). The site of maximal copper absorption is not known for humans, but it is 64 assumed to be the stomach and duodenum because of the rapid appearance of Cu in the plasma after oral administration (Bearn and Kunkel 1955). Copper is absorbed from the gastrointestinal tract as ionic copper or bound to amino acids. Absorption of the latter apparently involves at least two kinetically distinguishable processes. The first mechanism transports copper from the mucosal side of the intestine to the serosal side. Only a small fraction of the ingested copper is transported via this mechanism (Crampton et al. The second mechanism of copper absorption involves the delivery of copper to the absorptive surface, mucosal uptake and binding to metallothionein or another intestinal binding protein (Evans and LeBlanc 1976). The copper bound to metallothionein can be slowly released to the blood (Marceau et al. These factors include: the amount of copper in the diet (Farrer and Mistilis 1967; Strickland et al. The absorption of copper appears to be inversely related to the amount of copper in the gastrointestinal tract (Strickland et al. In humans, the amount of stored copper does not appear to influence copper absorption (Strickland et al. In rats, the absorption of copper appears to be inversely related to the amount of cadmium in the diet (Davies and Campbell 1977). The amount of copper retained in the intestinal mucosal cells was also inversely related to cadmium dietary concentration. In addition, increased levels of zinc in the diet result in decreased in copper absorption in humans and rats (Hall et al. A decrease in copper absorption has been observed in infants with high intakes of iron (Haschke et al. Apparently conflicting results have been reported on the effect of ascorbic acid on copper absorption in humans. Based on a decrease in serum ceruloplasmin levels, Finley and Cerklewski (1983) concluded that a diet high in ascorbic acid resulted in a decrease in copper status. A decrease in serum ceruloplasmin activity was also found; however, the amount of ceruloplasmin protein was not affected. Studies in humans and animals provide suggestive evidence of age-related changes in copper absorption. The levels of copper retained in the intestine were greater in the suckling rats than in the weanling or adolescent rats. However, the increased retention was not related to increased metallothionen levels; the levels of metallothionen (after zinc induction) were higher in the adolescent rats compared to the younger rats. The relatively small range of doses used in this study does not allow for a determination of whether copper absorption is saturable in infants. Human studies did not find that increased levels of fiber (cellulose or phytate) (Turnland et al. However, a study in rats found an increase in fecal excretion of copper (and a decrease in apparent absorption) in rats fed a high fiber (potato fiber or sugar beet pulp) diet (Gralak et al. However, the absorption rate of copper into the circulatory system was decreased when administered in the infant formula or fulvic acid solutions. Following a copper azide explosion that yielded metallic copper and nitrogen fumes, a small increase in serum copper levels was found in the affected worker (Bentur et al. Similarly, animal studies demonstrate that copper can pass through dermal barriers when applied with an appropriate vehicle. Less than 6% of copper deposited on ex vivo human skin samples was absorbed (Pirot et al. There is some evidence that albumin plays a passive role in copper transport, carrying a large portion of the exchangeable copper in the circulation and releasing this to other carriers for actual cell-specific uptake. There is also evidence that transcuprein is another plasma protein carrier (Weiss and Linder 1985). In most organs and tissues, copper turnover is biphasic (Levenson and Janghorbani 1994). Several specific binding proteins for copper have been identified that are important in the uptake, storage, and release of copper from tissues. In the liver and other tissues, copper is stored bound to metallothionein and amino acids and in association with copper-dependent enzymes. Several studies have shown that copper exposure induces metallothionein synthesis (Mercer et al. Increased levels of metallo thionein may be associated with resistance to copper toxicity in pigs (Mehra and Bremner 1984). Copper exposure has also been shown to induce ceruloplasmin biosynthesis (Evans et al. After the oral administration of radioactive copper as copper acetate in healthy humans, 72% was excreted in the feces (Bush et al. The remainder of the fecal copper is derived from unabsorbed copper and copper from desquamated mucosal cells. Copper in bile is associated with low molecular weight copper binding components as well as macromolecular binding species (Gollan and Dellar 1973). The numerical estimates of these model parameters are incorporated within a set of differential and algebraic equations that describe the pharmacokinetic processes. If the uptake and disposition of the chemical substance(s) are adequately described, however, this simplification is desirable because data are often unavailable for many biological processes.

These oils are (largely) kept and processed in closed systems during the refining process and aerosol formation is unlikely to occur diabetes signs of purchase diabecon 60caps with amex. Animal data are in line with the observations on carcinogenicity of mildly refined mineral oils blood sugar machine purchase diabecon 60 caps visa. No human data on the reproduction toxicity diabetes medications depression buy diabecon with paypal, immunological effects managing diabetes 2 buy diabecon cheap online, or neurological effects of highly refined mineral oil mists are available test zu diabetes cheap 60 caps diabecon free shipping. Significant oil deposition and lipid microgranuloma formation occurred in dogs after 12 months of inhalation exposure to 100 mg/m3 managing diabetes journals buy diabecon. Long-term inhalation studies in animals show that oil-filled macrophages accumulate in the lungs and that microgranulomas occur at exposure levels of 100 mg/m3. Few oil-filled macrophages with no other tissue response were found in the lungs in several animal species, including dogs and rodent species, at chronic (12-24 months) exposure levels of 5 mg/m3. According to the Committee, the occurrence of oil-filled macrophages is a normal physiological reaction and not an adverse health effect. A factor correcting for exposure duration is not deemed necessary as the exposure time in the studies of Wagner et al. An interspecies factor is not needed as the occurrence of microgranulomas in the lungs is a local effect. In addition, skin exposure to highly refined base oils does not induce skin tumours. In addition, these oils appeared to have no mutagenicity in the Modified Ames test. Chemically, the hydrocarbons in synthetic oils are similar to the hydrocarbons in mineral oils: the synthetic oils are mostly short-chain highly branched alkanes, whereas the mineral oils consist of cyclic and non-cyclic longer-chain paraffins. The physical properties of synthetic and mineral oils, however, differ because of the differences in chain lengths of the hydrocarbons. In other words, mixed exposure to different types of fluids, including the fluids that contained both mineral oil and water, has likely occurred. Overall, it is evident that in many studies mixed exposure has occurred and that this may have resulted in adverse health effects of non-mineral oil components superimposed on those associated with straight mineral oil exposure. This introduces uncertainty in straight mineral oil as the causative agent of the observed adverse health effects. The Committee notes that aerosol samples have been collected with different devices and that exposures have been measured in different ways, sometimes as the thoracic mass fraction36, 50, 72, sometimes as the inhalable mass fraction35, 74, and other times as the total mass fraction. Measurements of aerosol concentrations have included gravimetry with or without extraction by a suitable solvent system, and light scatter. It is likely that the difference in methods used to monitor aerosol mass concentrations has introduced bias in the reported mass concentrations. The chemicals added to enhance performance and inhibit growth of microorganisms have regularly changed across calendar time and job title. From the available studies, however, it does not become clear to what extent non-mineral oil components have contributed to the adverse health effects observed. A few studies74, 111 have determined the amount of micro-organisms and endotoxin present, but in most studies microbial contamination was unknown. This was reported in 199238 and confirmed in an extended follow-up to 199434, and in several case-control studies from this same cohort. No other cohort studies with quantitative exposure-response data on cancer have been published since. While the available data do not warrant a classification as known or presumed to be carcinogenic to man, they indicate that there is cause for concern. These studies show that adverse effects on the respiratory system are of major concern. This small effect size also justifies a small factor to extrapolate this lowest-observed-adverse-effect-level into a no-adverse-effect level. For this, the Committee applies a factor of 2 and calculates a no-adverse effect-level of 0. The Committee assumes that in the epidemiological studies sensitive workers were likely included. In conclusion, to protect against non-carcinogenic adverse health effects the Committee recommends a health-based occupational exposure limit of 0. Insufficient data are available on the systemic toxicity of highly refined mineral base oils, but the available studies indicate that the systemic toxicity is small. In addition to existing exposure limits for specific substances, the Dutch Expert Committee on Occupational Safety recommends a health-based occupational exposure limit of 0. Prostate cancer incidence in relation to time windows of exposure to metalworking fluids in the auto industry. Respiratory symptoms, ventilatory impairment, and bronchial reactivity in oil mist-exposed automobile workers. Effects of blasting fumes on exposure and short-term lung function changes in tunnel construction workers. Registry-based case-control studies of liver cancer and cancers of the biliary tract nested in a cohort of autoworkers exposed to metalworking fluids. The influence of occupational exposure to pesticides, polycyclic aromatic hydrocarbons, diesel exhaust, metal dust, metal fumes, and mineral oil on prostate cancer: a prospective cohort study. An attempt to define a just detectable effect for airborne chemicals on the respiratory tract in mice. An outbreak of hypersensitivity pneumonitis at a metalworking plant: a longitudinal assessment of intervention effectiveness. Assessment of the morphology and significance of the lymph nodal and hepatic lesions produced in rats by the feeding of certain mineral oils and waxes. Proceedings of a pathology workshop held at the Fraunhofer Institute of Toxicology and Aerosol Research Hannover, Germany, May 7-9, 2001. Metalworking fluid mist occupational exposure limits: a discussion of alternative methods. Further analysis of cancer mortality patterns among workers exposed to cutting oil mists. N-nitrosodiethanolamine urinary excretion in workers exposed to aqueous metalworking fluids. Determination of N-nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids. A review of exposure conditions and possible health effects associated with aerosol and vapour from low-aromatic oil-based drilling fluids. Exposure-response models based on extended follow-up of a cohort mortality study in the automobile industry. A strategy to reduce healthy worker effect in a cross-sectional study of asthma and metalworking fluids. Respiratory health of automobile workers and exposures to metal-working fluid aerosols: lung spirometry. Mortality studies of machining fluid exposure in the automobile industry I: A standardized mortality ratio analysis. A study of mortality, symptoms, and respiratory function in humans occupationally exposed to oil mist. Recommendation from the Scientific Committee on Occupational Exposure Limits for aerosols of severely refined mineral oils. Metal working fluid-associated hypersensitivity pneumonitis: an outbreak investigation and case-control study. Quantitative exposure to metalworking fluids and bladder cancer incidence in a cohort of autoworkers. Contact sensitizations in metalworkers with occupational dermatitis exposed to water-based metalworking fluids: results of the research project "FaSt". Factors contributing to the acute and subchronic adverse respiratory effects of machining fluid aerosols in guinea pigs. Mycobacterium immunogenum causes hypersensitivity pneumonitis-like pathology in mice. Respiratory health of automobile workers exposed to metal-working fluid aerosols: Respiratory symptoms. Hypersensitivity pneumonitis due to metal working fluids: Sporadic or under reported Estimation of historical exposures to machining fluids in the automotive industry. The presence of urinary cellular sediment and albuminuria in newspaper pressworkers exposed to solvents. Health-based calculated occupational cancer risk values of benzo[a]pyrene and unsubstituted non-heterocyclic polycyclic aromatic hydrocarbons from coal-derived sources. Mineral oils: untreated and mildly-treated oils (Group1); highly refined oils (Group 3). Respiratory symptoms and conditions related to occupational exposures in machine shops. Acute pulmonary responses among automobile workers exposed to aerosols of machining fluids. Respiratory symptoms and exposure-response relations in workers exposed to metalworking fluid aerosols. Rectal cancer and exposure to metalworking fluids in the automobile manufacturing industry. Airway responsiveness, respiratory symptoms, and exposures to soluble oil mist in mechanical workers. Mutagenic/carcinogenic hazards in a cold rolling steel plant exposed to mineral oils: environmental monitoring phase. Aerosol mapping of a facility with multiple cases of hypersensitivity pneumonitis: demonstration of mist reduction and a possible dose/response relationship. Respiratory symptoms and ventilatory lung function in machine shop workers exposed to coolant-lubricants. Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant. Acute respiratory effects on workers exposed to metalworking fluid aerosols in an automotive transmission plant. Mortality and incidence of cancer among oil exposed workers in a Norwegian cable manufacturing company. Work-related asthma and respiratory symptoms among workers exposed to metal-working fluids. Correlation of mutagenic and dermal carcinogenic activities of mineral oils with polycyclic aromatic compound content. Evaluation of the acute respiratory effects of aerosolized machining fluids in mice. Lack of carcinogenicity of medium viscosity liquid paraffin given in the diet to F344 rats. Distribution, effect, and fate of oil aerosol particles retained in the lungs of mice. Mortality among bearing plant workers exposed to metalworking fluids and abrasives. Lung function and radiographic signs of pulmonary fibrosis in oil exposed workers in a cable manufacturing company: a follow up study. Pulmonary fibrosis in cable plant workers exposed to mist and vapor of petroleum distillates. Subacute inhalation toxicity of mineral oils, C15-C20 alkylbenzenes, and polybutene in male rats. Respiratory symptoms and lung function abnormalities among machine operators in automobile production. Cytogenetic analysis of peripheral blood lymphocytes in glass workers occupationally exposed to mineral oils. Controlling health risks from workplace exposure to metalworking fluids in the United Kingdom engineering industry. Pulmonary pathology from inhalation of a complex mineral oil mist in dogs, rats, mice and gerbils. A nested case-control studt of stomach cancer mortality among automobile machinists exposed to metalworking fluids. Occupational dermatitis and allergic respiratory diseases in Finnish metalworking machinists. Occupational exposure to metalworking fluids and risk of breast cancer among female autoworkers. Metalworking fluid with mycobacteria and endotoxin induces hypersensitivity pneumonitis in mice. Results of chronic dietary toxicity studies of high viscosity (P70H and P100H) white mineral oils in Fischer 344 rats. Relationships between inhalable, thoracic, and respirable aerosols of metalworking fluids. Investigation into the impact of introducing workplace aerosol standards based on the inhalable fraction. Summary of the findings from the exposure assessments for metalworking fluid mortality and morbidity studies. Risk of upper aerodigestive tract cancers in a case-cohort study of autoworkers exposed to metalworking fluids.

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Blood vessels, nerves, and lymphat hypoglycemia (low blood sugar), which is the pre ics branch through the mesentery to supply the dominant finding in a number of metabolic dis intestine. Other mesenteries exist to support the sig eases, and jaundice (yellowing) or other evidence moid colon, appendix, transverse colon, and por of liver disease. Also known as inborn error of mesoderm the middle of the three primary germ metabolism. The metabolic rate, basal See basal metabolic mesoderm differentiates (specializes) to give rise to rate. See also differentiation; ectoderm; processes that occur within a living organism. Metabolism consists of anabolism (the buildup of substances) and catabolism (the breakdown of sub mesodermal Pertaining to the mesoderm or to stances). Cells that have metastasized are like those in the Methotrexate is an effective but potentially danger original (primary) tumor. People taking methotrexate must cer begins in the stomach and spreads to the lung, have their lung, liver, and kidney function moni the cancer cells in the lung are metastatic stomach tored regularly, and they need blood testing to be cancer cells. Methotrexate should be taken on an metatarsal One of the five cylindrical bones that empty stomach. Metrorrhagia can mon medical use for methadone is as a legal substi cause significant anemia. It may also be a sign of tute for heroin in treatment programs for drug underlying disease, such as hormone disorder, uter addiction. For exam munity outside of hospitals and other health facili ple, diabetes predisposes to the development of ties. Normal standards are sign because it is almost always associated with available for penis length. Many reflect failure of normal hormonal stimulation or factors can impair the growth of the brain, includ failure of normal development (a birth defect). For example, microcytic ane consists of two microscopes in series, the first serv mia is characterized by small red blood cells. The ing as the ocular lens (close to the eye), and the opposite of microcytic is macrocytic. Microorchidism is a diagnostic feature, for example, microscopic Too small to be seen without the aid of Prader-Willi syndrome and certain other multiple of a microscope, as opposed to macroscopic. Microorchidism may also example, a microscopic tumor is too small to be result from shrinkage (atrophy) of the testis due to seen without a microscpe. The opposite of microscopic anatomy See anatomy, micro microorchidism is macroorchidism. The ruler is pressed firmly into the soft tissue over the pubic bone (the symphysis pubis) because in obese boys and men, a seemingly small penis may. See also syncope; vaso migraines account for no more than 20 percent of vagal reaction. This is the most frequent type of migraine, account middle ear infection See ear infection. Many midwives also provide pre migraine, ocular A migraine involving the eyes natal care for pregnant women, birth education for that results in distortion of visual images, accompa women and their partners, and care for mothers nied or followed by headache. Others migraine, ophthalmoplegic A rare condition work with physicians as part of a team. Visual auras may include flashing lights, geometric patterns, or distorted midwife, certified professional A midwife vision. Some people may have aural auras that who has completed a degree in midwifery at a cre involve hearing sounds (usually buzzing) that are dentialed educational institution. The auras experienced by migraine sufferers midwife assistant A person who assists a mid are similar to those associated with epilepsy. Other arteries in on one or both sides of the head that may be accom the brain and scalp then open, and throbbing pain panied by nausea, vomiting, increased sensitivity of is perceived in the head. The tendency to migraine the eyes to light (photophobia), increased sensitiv is inherited and appears to involve serotonin. This ity to sound (phonophobia), dizziness, blurred brain chemical (neurotransmitter) is involved in vision, cognitive disturbances, and other symptoms. Not all severe headaches are migraine, abdominal An attack of abdominal migraines and not all migraines are severe. Factors pain that may be preceded by a migraine aura and known to make migraines worse in some patients accompanied by nausea, vomiting, and cognitive include stress, food sensitivities, menstruation, and disturbance. Miliary is about a 5 percent chance that one member of the aneurysms tend to affect minute arteries in the brain couple is carrying a chromosome translocation that or in the retina of the eye. Each consists of two sets of membranes: a smooth, continuous outer minimally invasive surgery A type of surgery coat and an inner membrane arranged in tubules or that is done through small incisions through which in folds that form plate-like double membranes instruments and imaging devices are passed; some (cristae). They not only convert sive surgery is performed in many different surgical nutrients into energy but also perform many other specialties. The mitochondrial chromosome is ally leave the hospital and resume normal activity much smaller than other chromosomes. It is round, sooner after minimally invasive surgery than with whereas the chromosomes in the nucleus are conventional open surgery. There are many copies of the mitochondrial chromosome in every cell, whereas mini-stroke See transient ischemic attack. All mitochondrial chromosomes are minor In general, something that is less than inherited from the mother. The mouth and palate contain numer chondrial chromosome that is responsible for a dis ous minor salivary glands. When severe, however, treatment with med is very small compared to the chromosomes in the ications and sometimes surgery is necessary. It is specialized in the information it carries, mitral prolapse See mitral valve prolapse. These mutations often impair the function of oxidative-phosphorylation mitral valve A valve in the heart that is situated enzymes in the respiratory chain. The manifest in tissues with a high energy expenditure, mitral valve permits blood to flow from the left such as those of the brain and muscle. Most people with mitral mitochondrial inheritance See inheritance, valve prolapse have no symptoms, however, those mitochondrial. More than 25 types of enzyme abnormalities mittelschmerz Pain due to ovulation that usually have been defined that fall into this category. They occurs at the midpoint between the menstrual peri result in a disease of cell metabolism and are ods. Patients mitosis the ordinary division of a body cell (a with mixed connective tissue disease typically have somatic cell) to form two daughter cells, each with features of each of these three component diseases. The treatment for mixed connective for the two members of a chromosome pair to sep tissue disease depends on which features are caus arate (to disjoin) normally so that both chromo ing symptoms. Treatment is often directed at sup somes go to one daughter cell while none go to the pressing the inflammation in the tissues by using other daughter cell. These medications include nonsteroidal mitral insufficiency A malfunction of the mitral anti-inflammatory drugs, cortisone drugs/steroids valve that permits the backflow of blood (regurgita (such as prednisone), and cytotoxic drugs (such as tion) from the left ventricle into the left atrium. Mixed mania is more common in bipolar children and women than in molecule the smallest unit of a substance that men. A person experiencing mixed mania may feel can exist alone and retain the character of that agitated, angry, irritable, and depressed all at once. In addition, this method is used to remove monochromatism 1 Total inability to perceive large tumors, tumors in hard-to-treat places, and color due to the lack of or damage to the cones of cancers that have recurred. Mohs surgery is micro the eye that perceive color, or the inability of the scopically controlled. The area of skin is removed nerves to translate information received from the under local anesthetic and is then carefully oriented cones. A person with true monochromatism per and serially examined under a microscope to ceives only black, white, and shades of gray. If the Complete monochromatism is usually an inherited tumor has not all been removed, the procedure is condition. Monoclonal antibodies can be made in large quantities in the mold One of a large group of fungi that can pro laboratory and are a cornerstone of immunology. Household mold Monoclonal antibodies are increasingly coming into is a common trigger for allergies. Monostotic fibrous dysplasia appears to be a different disorder from polyostotic fibrous dys mononeuritis Inflammation of a single nerve. The many causes of mononeuritis include diabetes mellitus, carpal tunnel syndrome, rheumatoid monozygous twins Identical twins. The treatment for called monozygous because they originate from a mononeuritis depends on the underlying cause. Mononeuritis multiplex causes a loss of func tion in the muscle tissue that is innervated by the morgue A place where dead bodies are kept affected nerves. Suggested treatment such as rheumatoid arthritis, systemic lupus erythe includes eating crackers or other high-carbohy matosus, vasculitis, Churg-Strauss syndrome, cryo drate foods first thing in the morning (even before globulinemia, and Sjogren syndrome. The treatment getting out of bed); eating small, frequent meals; for mononeuritis multiplex depends on the underly drinking extra fluids between meals; and avoiding ing cause. Mononucleosis can cause morphea Skin changes that are localized to one or more patchy areas of skin that become hardened, liver inflammation (hepatitis) and spleen enlarge dry, smooth, and slightly pigmented. Morphea is ment; a person with mononucleosis should avoid vigorous contact sports to prevent spleen rupture. Also known as mono and the kissing dis occurring member of a large chemical class of com ease. The name, which derives monosomy Missing one chromosome from a from Morpheus (the mythologic god of dreams) was coined in 1805 by German apothecary Adolf pair. For example, if a female has one X chromo Serturner to designate the main alkaloid in opium. Symptoms of Morquio syndrome A form of mucopolysaccha monostotic fibrous dysplasia may include pain and ridosis that is characterized by an inability to break fracture of the bone. Most cases are diagnosed in down keratan sulfate, which leads to abnormal adolescence or young adulthood and remain. The tube senses when the muscles of the ties of the skeleton, muscles, skin, teeth, and mus stomach and small intestine contract and squeeze cular organs. The contractions are recorded for leukocytes and cultured skin fibroblasts or by analysis by a computer. There is currently no treatment for Morquio syn drome, but physical therapy, medication, and some motion, range of See range of motion. Morquio syndrome is motion sickness A disorder of the sense of bal inherited in an autosomal recessive manner. Other common signs of motion sickness are mortality rate, fetal See fetal mortality rate. Symptoms usually stop when mortality rate, infant See infant mortality the motion that causes it ceases. For example, a motor neuron is a nerve cell mortality rate, neonatal See neonatal mortal that conveys an impulse to a muscle for contraction, ity rate. All females eases of the nervous system that are characterized are mosaics because of X-chromosome inactivation by steadily progressive deterioration of the motor (lyonization). Mosaic patterns can affect the way neurons in the brain, brainstem, and spinal cord. Motor neurons are the nerve about 5 percent of people with Down syndrome cells along which the brain sends instructions, in have a mosaic variant in which only some cells have the form of electrical impulses, to the muscles. Compared to others with degeneration of motor neurons leads to weakness Down syndrome, these individuals have fewer clini and wasting of muscles. Then shoulders and other muscles and are less likely to have heart and other problems may be affected. In the vast majority of cases, the intellect remains Such a cell might be referred to as the mother cell. An antro-duodenal motility study is performed to diagnose problems in mountain sickness See altitude sickness. To conduct the study, a tube is mouth, trench See acute membranous passed through the nose, throat, esophagus, and gingivitis. One form is characterized by cherry red spots in the eyes, gradual loss of vision, progressive mucosa A moist tissue membrane that lines some debilitating myoclonus (muscle spasms), and nor body cavities and organs. For example, the oral mucosa is the zation, and various psychological theories, but there mucous membrane that lines the mouth and throat. Mucositis is a common side effect of multiple enchondromatosis A condition char chemotherapy and of radiotherapy that involves any acterized by benign masses of cartilage, called part of the digestive tract. The enchon idly dividing mucosal cells that line the mouth, dromas tend to be in the bones of the hands and feet throat, stomach, and intestines, which normally and the long bones of the arms and legs. If a therapy destroys these cause pain, deform and shorten a limb, and predis cells, they may not be replaced right away, in which pose a person to fractures.

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Syndromes

• Feeling of being drunk (euphoria)
• Appropriate diet for age
• Heart attack
• Bone marrow begins to make blood cells.
• Tumors of pregnancy, including gestational trophoblastic disease
• Heart attack or stroke
• Rinse with water, cover with a clean dressing, and place a cold compress on the dressing to reduce pain and swelling.
• Vision changes

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These guidelines are intended to be comprehensive, but not exhaustive and seek to summarize information on treatment of patients presenting with priority diseases. Please indicate data/evidence on proven benefits of the indicated drug/recommended product (on the basis of efficacy, safety, suitability and/or costeffectiveness) in relation to the listed drug which is sought to be replaced. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permis sion of the publisher. McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. As you look into the eyes of a parent and child, you recognize that the responsibility is beyond measure and the balance between providing comprehensive preventative health care and recognizing the need for more in-depth system-specific investigation or treatment can turn on a dime. It requires practitioners to have a solid knowledge base, be thorough in their assessments, be insightful regarding preventative care approaches, and, most importantly, be able to recognize when an urgent treatment plan is needed. This book should serve as an assessment tool for students, residents, and practitioners who wish to evalu ate their pediatric knowledge base and clinical deductive skills. Comprehensive dedication to issues related to growth and development, feeding and nutrition, fluids, electrolytes, and metabolic disorders are included. The answers and discussion which follow each question include reference to key pediatric textbooks and American Academy of Pediatrics guidelines. It has been my pleasure to work with Catherine Johnson, Cindy Yoo, and Kirsten Funk from McGraw-Hill. To Lindsay and Nick, seeing you challenge yourself throughout life, be it at work or play, has inspired me to broaden my own horizons. In this book, you will find eleven chapters that will prepare you to answer questions on topics that pertain to common diseases in the infant and child. The content covers basic concepts for the beginning medical student as well as more advanced concepts for the senior student or resident training in pediatrics. The options include the correct answer and four distractors that represent plausible but incorrect options. The correct answer is evidence based and the critique provides appropriate references if you want to read more about a topic. Utilize the cover test; that is, do not look at the answers initially and read through the entire question. If you can narrow down to two answers, you will have a better chance of choosing the correct option. You have just confirmed the diagnosis of cystic between 10 and 15 years of age fibrosis in a 3-year-old child. A 12-year-old boy just returned from Boy Scout year-old boy with new onset of epilepsy. You suspect Lyme disease, most likely (A) lymphoma syndrome contracted by which of the following Compared to the previously available whole (A) Group A hemolytic streptococcus cell vaccine, which of the following best (B) Adenovirus describes these products Which of the following is the most likely risk factor for meconium aspiration syndrome 11. A newborn infant with stigmata of Down syn (D) strabismus drome has a heart murmur. A 2-year-old child is admitted because of weak and cries with palpation of his abdomen. Examination of the chest reveals generalized tell his mother that he has urinary tract infection wheezing. There is no history replacement with normal saline, administration of of vomiting or diarrhea. A 10-year-old boy has been having episodes of (A) adenocarcinoma repetitive and semipurposeful movements of the (B) squamous cell carcinoma face and shoulders. The Physical and neurologic examinations are entirely skin lesion began as a red macule on the thigh, normal. Birth and perinatal history paroxysms of severe colicky abdominal pain are unremarkable. An remainder of the examination including a com exploratory laparotomy reveals an edematous plete neurologic examination is within normal intestine without specific lesions. On the second postoperative day, tender swelling of both ankles and knees is (B) a porencephalic cyst noted. Which of the following additional find (C) gyriform calcifications ings would most likely be present in this child Physical exam ination reveals that the liver is enlarged to 5 cm (C) biliary atresia below the right rib cage, and the spleen is enlarged (D) breastfeeding jaundice 6 cm below the left rib cage. Attempts to (G) cholelithiasis visualize the retina are unsuccessful because (H) Crigler-Najjar syndrome of clouding of the corneas. For each numbered item select the one lettered option with which it is most closely 28. He has been asymptomatic and (C) condyloma acuminatum physical examination is otherwise normal. Small (pinhead to 1 cm), pearly papules with Abdominal ultrasound examination reveals a translucent tops and waxy, whitish material normal-size liver; gallbladder is not visualized. An otherwise well 4-week-old infant has remained jaundiced since day 3 of life despite 26. Soft, flesh-colored papular or pedunculated two exchange transfusions and continuous pho lesions around the genitalia and rectum totherapy. Optic atrophy is not lethal genetic disease in the Caucasian popula a recognized complication of phenytoin ther tion. If the examinee knew that been able to come up with that answer before a lymphoma-like syndrome has been reported looking at the list of choices. Borrelia burgdorferi, the spirochete carefully considering all subsequent choices, he that causes Lyme disease, is transmitted to or she might have selected (A). This is another straightforward, completely fac other four choices all are incorrect. As a change disease is the most common cause of matter of fact, two answers are not only incor nephrotic syndrome in childhood, and accounts rect, they are exact opposites of what actually for more than all other causes combined. The happens with cocaine, so it should be easy to be peak incidence is between 2 and 5 years of age. Serum lipids and cholesterol are elevated, postmaturity) and low birth weight (not macro as they are with other causes of nephrotic syn somia). Finally, the disease characteristically disproportionate decrease in head size is noted 7 8 1: Warm-Up Questions and Exam-Taking Skills in infants exposed prenatally to cocaine. Although it is ease in the general population is less than 1% but appropriate to think of diphtheria in patients about 40% of children with Down syndrome with acute exudative tonsillitis, there is noth have heart defects. The most common lesions in ing specific in this case to suggest that diag children with Down syndrome include atri nosis. It is esti tions can occur in infants with galactosemia or mated that 95% of Hib-immunized children will prune belly syndrome, there is no information develop protective antibody after a primary given to suggest that either diagnosis is present series starting when the child is 2 months of age. Vesicoureteral reflux is present in the correct answer to this question, there 25% of infants with urinary tract infection and fore, is (B). In causes encompass a diverse spectrum extend terms of immunogenecity, efficacy, and number of ing from poverty and lack of food, through poor doses, they do not differ but they are more expen parenting skills and misguided feeding to frank sive than whole cell products. If gastrointestinal problems had been Pediatrics has recommended that infants be a choice, the question would have been more placed to sleep on their backs. Because honey can contain ria include visceral lava migrans (Toxocara canis spores of Clostridium botulinum, this product infection) and retrolental fibroplasia. To answer the question correctly vated serum potassium level usually responds you must analyze the clinical findings and rapidly to administration of saline and steroids, recall the disease rather than selecting (recog and specific therapy with exchange resins or glu nizing) it from a list. These children often priorities, and tailor therapy to the specific ingest the toxic substance unobserved, and the pathophysiology involved. The stem of the question gives no muscarinic effects of these agents and is a use information except the age and sex of the patient ful part of treatment. The adrenal cortical hormones and secondary hyper lesions usually are on the extensor surfaces of trophy of the adrenal gland. Accumulation of the extremities and are more common on the androgen-like precursors of cortisol during fetal legs. While carcinoma of the lung is a believe this child most likely has: juvenile idio leading cause of intrathoracic mass in adults, it pathic arthritis, inflammatory bowel disease, is very rare in adolescents, even those who cystic fibrosis, Henoch-Schonlein purpura have a significant smoking history. The major features of this disease mosis, and sarcoid need to be considered but are colicky abdominal pain, nephritis, arthritis, were not listed as choices. Here again, you are required to make a diagno as a possible answer does not specify location sis but are not given a list of diseases from which or distribution, but is still the best answer. The appear to be fever, a localized rash, and only atypical feature in this case is that the child meningeal inflammation (headache and stiff was taken to the operating room. The malaise, fatigue, lethargy, generalized inal pain is the first complaint, diagnosis is vir lymphadenopathy, and arthralgia are less spe tually impossible until other features appear. The child most likely has Tourette syn Knowledge of the common infections carried by drome, a disorder characterized by blinking, ticks as well as the epidemiology of such infec twitching, grimacing, and jerking movements tions is essential to correctly answering the that often have a repetitive and semipurpose question. Referral to a child psychiatrist Dermatan and heparan sulfate Hurler syndrome may be a useful adjunct but has not been Galactose Galactosemia Mannose Mannosidosis shown to have consistent positive effects. This question deals with a rare but dramatic described has Hurler syndrome, a form of pediatric syndrome. The association of a unilateral facial heman Corneal clouding results from the deposition gioma, particularly in the distribution of the of mucopolysaccharide in that organ. The trigeminal nerve, and focal seizures suggests accumulation of mucopolysaccharide within Sturge-Weber disease, also referred to as Sturge the brain leads to mental retardation. Incidentally, national exami drome and did not know that it is characterized nations often use eponyms for diseases and by dermatan and heparan sulfate in the urine, syndromes even when other specific names you would not be able to answer the question. Larger lesions do occur bilirubin level of less than 13 mg/dL on day of but are infrequent. Lesions may occur anywhere but are the other conditions listed, such as breast milk most common on the arms and trunk. Physiologic papular, or pedunculated lesions occurring jaundice is clearly the most likely cause and around the genitalia and/or rectum. When the list of unconjugated hyperbilirubinemia for 4 weeks options is long (more than six), it becomes inef but is otherwise well. The normal serum levels ficient and time consuming to evaluate each of conjugated bilirubin and hepatic enzymes possible lettered choice for each numbered item. The Coombs test was negative, and decide what the best answer would be and look the hyperbilirubinemia is too severe and pro for it in the list of possible choices. A 6-year-old girl presents with unilateral non congenital malformations of the head and face in painful, nonsuppurative conjunctivitis and your clinic. Chest roentgenogram reveals minimal would help you to identify a cause for these cardiomegaly and a diffuse reticular pattern of symptoms You suspect the diagnosis of a brain tumor in a 2-year-old girl with a recent history of ataxia, 11. Laboratory evaluation reveals hemoglobin of 9 g/dL with white blood cell count of 11, 500 8. The (D) abdominal ultrasound infant was born at term after an uncomplicated (E) barium enema study pregnancy. A normal 6-month-old infant has a continuous Which dietary history finding best explains cardiac murmur and bounding peripheral this What other problem is this patient most likely Examination shows bilateral papillary edema.