Martin K. Rutter MD, FRCP

• Senior Lecturer and Honorary Consultant Physician
• Manchester Diabetes Centre
• Manchester, UK

A survey by the Netherlands consumer organisation indicated low to moderate phosphorus levels in the commonly sold supplements arrhythmia natural treatment buy 8 mg perindopril, i hypertension yoga poses discount 8 mg perindopril free shipping. Nutritional requirements and recommendations the phosphorus requirement has often been linked to the calcium requirement blood pressure keeps spiking buy perindopril 8 mg low cost, allowing a Ca: P weight ratio of about 1 arrhythmia zoloft effective 4mg perindopril. For the younger age groups blood pressure medication making blood pressure too low purchase perindopril, a factorial approach was used heart attack calculator purchase perindopril 4 mg without prescription, taking into account phosphorus accretion in bone and (lean) tissues. As the body can maintain a phosphate (and calcium) balance over a wide range of intakes and Ca:P ratios, this ratio is nowadays considered of limited value for evaluation of dietary adequacy. Only in infants and children under conditions of rapid growth such a ratio has some relevance to enable optimal growth. Function, uptake and distribution Net absorption from a mixed diet has been reported to vary between 55-70% in adults (Lemann 1996; Nordin, 1986) and between 65-90% in infants and children (Ziegler and Fomon, 1983). There is no evidence that, contrary to calcium, absorption efficiency varies with dietary intake. Phosphate absorption is greatest in jejunum and takes place by a saturable, active transport mechanism, facilitated by 1,25-dihydroxyvitamin D, as well as by passive diffusion (Chen et al, 1974). Some forms of dietary phosphorus are less bioavailable, especially phosphorus present in phytic acid in the outer coatings of cereal grains. The actual bioavailability depends on the way these grain products are processed and the amount of residual phytate. Some dietary components, as well as colonic bacteria, contain phytase activity rendering phytate phosphorus more available. The phosphorus content of the adult human body is about 700 g (as elemental phosphorus). About 85% of total phosphorus is present in the skeleton, the remainder in the soft tissues and in the extracellular fluids (circa 1%) (Lloyd and Johnson, 1988). Total phosphorus concentration in whole blood is approximately 13 mmol/L (40 mg/dL). Approximately 70% is present as organic phosphates, such as in the phospholipids of red blood cells and in the plasma lipoproteins. These anion forms are interconvertible and effective buffers of blood pH and involved in regulation of the whole body acid-base balance. Serum Pi is less tightly controlled than serum calcium and varies throughout the day following a circadian rhythm with peaks in the early morning and the afternoon (Portale et al, 1989; Calvo et al, 1991). Hyperphosphatemia, associated with clear clinical symptoms, has only been reported in patients with end-stage renal disease, i. Phosphate is filtered at the glomerulus and 80-90% is reabsorbed in the proximal renal tubules. Pi transport in the proximal tubule is driven by a Na+-dependent Pi transporter protein, residing in the brush-border membrane. Dietary phosphorus intake also has a direct effect on the renal Pi excretion rate. Deficiency the development of a dietary-induced phosphorus deficiency is very unlikely due to the ubiquitous presence in foods. Hypophosphatemia can occur in patients and infants receiving poorly managed parenteral nutrition, and in patients suffering from liver disease, sepsis, antacid therapy with aluminium containing drugs, and in diabetic ketoacidosis. Symptoms include anorexia, anaemia, muscle weakness, bone pain, rickets, and ataxia (Lotz et al, 1968). Inadequate intake of calcium and phosphorus has been associated with pathogenesis of bone disease in newborn infants (Bishop, 1989). Secondary hyperparathyroidism leads to increased bone resorption which might adversely affect bone mineral density and skeletal integrity, and result in ectopic calcification. Such phosphorus induced effects have been observed in animal studies, but not in humans, except in patients with end-stage renal disease. In some supplementation studies using high phosphorus dosages, osmotic diarrhoea and mild gastrointestinal symptoms have been reported. Acute toxicity Histological and histochemical changes have been described in the kidneys of rats fed for 24 to 72 hours a diet containing 10% disodium acid phosphate (providing approximately 5 g/kg body weight/ day equivalent to about 1200 mg elemental phosphorus/kg body weight/day elemental phosphorus) (Craig, 1957). Ritskes-Hoitinga et al (1989) found marked kidney calcification and a rise in albumin concentration in urine in female rats fed for 28 days a diet containing 0. It was concluded that dietary phosphorus-induced nephrocalcinosis is associated with impaired kidney function in rats. Sub-chronic toxicity Pathological effects in the parathyroid, kidneys and bones have been observed in mature male rats fed a diet containing an excessively high level of sodium orthophosphate (8% in the diet which is approximately 4 g/kg body weight/day, providing about 1 g/kg body weight/day elemental phosphorus or 38 mmol phosphorus/kg body weight/day) for 7 months or until the animals succumbed (Saxton and Ellis, 1941). Microscopic examinations of the tissues at the time of death revealed hypertrophy and hyperplasia of parathyroid cells. The long bones of the animals appeared thickened and more fragile than those of control animals. In a study with three groups of 12 rats an adequate absorption and utilisation of calcium, phosphorus and iron was found after feeding a control (P: 210 mg/kg body weight/day; Ca: 280 mg/kg body weight/day), a normal orthophosphate (P: 215 mg/kg body weight/day; Ca: 235 mg/kg body weight/day), and a high orthophosphate diet (P: 650 mg/kg body weight/day; Ca: 250 mg/kg body weight/day). The experiment was conducted in three stages, with experimental observations made when animals had consumed the test diets for 50, 60 and 150 days (Dymsza et al, 1959). No adverse physiological effects were observed clinically, at autopsy, or on histological examination. The authors concluded that at both high and normal levels of dietary phosphorus the calcium, phosphorus and iron absorption and utilisation were adequate. Haut et al (1980) investigated phosphate-induced renal injury in uninephrectomised, partially nephrectomised and intact rats. None of the animals on a normal phosphorus intake (250 mg/kg body weight/day) showed any abnormalities. Four of 6 intact animals on the 1 % phosphorus diet (500 mg/kg body weight/day) had normal kidney calcium concentrations (one animal showed histological alterations in the kidneys). In contrast, all but one of the partial and uninephrectomised animals on a 1 % phosphorus diet (500 mg/kg body weight/day) had increased kidney calcium concentrations; 5 of the six animals in the group exhibited histological changes in the kidney. It was concluded that as renal functional mass is reduced, the nephrotoxicity of phosphorus is greatly enhanced. Diets low in calcium alone (40 mg/100 g) or low in both calcium and phosphorus (90 mg/100 g) led to the development of radiologic rickets and histologic features of osteomalacia at both 8 and 16 months. The diet which was low in calcium but which had a normal phosphorus content (310 mg/100 g) was associated with histologic features of hyperparathyroidism at 16 months; such features did not develop in animals fed the low calcium, low phosphorus diet. Biochemically the low calcium, normal phosphorus diet was associated with a transient fall in serum calcium around 8 months and a more persistent elevation in serum phosphorus and alkaline phosphatase values during the latter half of the study. These biochemical changes were not seen in the baboons on the low calcium, low phosphorus diet. Reproductive toxicity Long-term effects of dietary phosphoric acid in three generations of rats have been investigated (Bonting and Jansen, 1956). No harmful effects on growth or reproduction were observed, and also no significant differences were noted in haematological parameters in comparison with control animals. The quality of these older studies would be considered limited by current standards. Acute effects Osmotic diarrhoea and other mild gastrointestinal effects, including dyspepsia, nausea and vomiting have been observed as side effects in some individuals participating in supplementation studies using higher supplemental dosages (between 750-2250 mg/day; total oral intakes up to 3008 mg phosphorus/day) (Bernstein and Newton, 1966; Bell et al, 1977; Broadus et al, 1983; Grimm et al, 2001, Brixen et al, 1992; Whybro et al, 1998). Adjustment in calcium-regulating hormones and effect on calcium balance and skeletal mass High phosphorus intake results in the post-absorptive state in an increase in the serum Pi fraction and a subsequent temporary decrease in the serum ionized calcium level. Most of the studies, summarized in Table 2, are of relatively small size (number of subjects included) and of short duration (single dose up to treatment of maximum 6 weeks), except some studies in patient groups, such as hypercalciuria patients (maximum 5 years) (Bernstein and Newton, 1966), multiple myeloma patients and osteoporotic women (maximum 15 months) (Goldsmith et al, 1968 and 1976), and hyperparathyroidism patients (12 months) (Broadus et al, 1983). No evidence of bone remodelling n=79 P-containing tablets given on > Nausea, vomiting and diarrhoea in 2/19 top of regular diet patients at 750 mg dose, 3/19 at 1500 mg dose; (not specied) 7/20 at 2250 mg dose Study 1: 1000 mg/day for 1 week; standard diet: 800 mg/ Urine P ^; urine Ca v; no changes in s-Pi, Healthy men day of Ca and P each. In nearly all studies phosphorus supplementation resulted in an increased phosphate excretion and decreased calcium excretion. This effect was already reported in the study by van den Berg et al (1980) and Broadus et al (1983), but not found in the studies from Calvo et al (1990) and Brixen et al (1992). Variable effects after phosphorus supplementation have been reported for markers of bone resorption. In the study by Goldsmith et al (1976) a decrease in bone-forming surface and bone-resorbing surfaces was found in a group of postmenopausal women with osteoporosis, given a daily dose of 1 gram phosphorus (as inorganic phosphate) on top of their normal diet. In an earlier study from the same authors (Goldsmith et al, 1968) in multiple myeloma patients on radiation or drug therapy (cyclophosphamide or melphalan), and suffering from bone pain and urinary calcium losses, oral and/ or intravenous treatment with phosphate supplements (1000-2000 mg/day phosphorus) reduced the hypercalciuria, even in absence of hypercalcemia. In one patient even recalcification of the cervical spine was noted after 9 months on the 2 g per day oral phosphorus dose. However, in a follow-up study by the same authors (Calvo and Heath, 1990) using similar dose levels, but for a longer period (28 days), urinary hydroxyproline excretion did not significantly change. Plasma osteocalcin, a sensitive and specific marker of osteoblastic activity, an indicator for bone formation, remained unchanged. In a controlled metabolic balance study in premenopausal women (n=8) doubling of the basal phosphorus intake from 1166 mg/day up to 2310 mg/day, by giving an additional mixture of sodium and potassium phosphate supplement for at least 4 months, while maintaining the calcium and protein intake constant, no evidence for bone remodelling was found as measured by radiocalcium kinetics and histomorphometry (Heaney and Recker, 1987). However, no clinical studies have linked high phosphorus intake, with or without adequate calcium intake, to lower bone mass, or higher rates of bone loss in humans. Neonates and young infants have a lower renal excretion capacity and, as a consequence, higher serum Pi values than older infants and adults at comparable (relative) intakes. This favours skeletal mineralization, but too high levels might adversely effect bone accretion, and in severe cases lead to rickets, and hypocalcaemic tetany. Consumption of soft drinks with added phosphoric acid has also been associated with hypocalcaemia in children (Mazarlegos-Ramos et al, 1995). This might be related however to low calcium intakes, rather than soft drink consumption as such, but no data on calcium intake were provided. Women Comparative studies in 20-40 year old women with carbonated beverages (567 mL) containing phosphoric acid or citric acid as the acidulant, did not indicate an effect on urinary calcium excretion (Heaney and Rafferty, 2001). Ectopic calcification Ectopic calcification as a result of high dietary phosphorus intake, as has been observed in mice and rats with normal kidney functions before exposure, has not been reported in humans with an adequate renal function. This might occur however in patients with end-stage renal disease associated with a variety of syndromes and (malignant) conditions. However, in these conditions, the hyperphosphatemia is not a direct, but a secondary effect. Interaction with mineral and trace element absorption Bour et al (1984) reported that high intakes of polyphosphates could interfere with absorption of iron, copper and zinc. However, this was not confirmed in a study by Snedeker et al (1982) who found no significant effect on iron, copper and zinc balance in 9 adult males after feeding a high phosphorus diet (2383 mg daily), in combination with a moderate (780 mg) or high (2442 mg) calcium diet for 39 days. Studies from Spencer et al (1965) and Heaney (2000) have shown that over a wide range of Ca:P ratios in the regular diet, i. Osmotic diarrhoea and other mild gastrointestinal effects Mild gastrointestinal complaints were reported in some individuals in some, but not all supplementation studies, at supplemental phosphorus intakes 750 mg/day (see Table 2). The Panel did not consider this effect as a suitable critical endpoint for setting an upper level. This effect depends on the actual increase in serum Pi, and the subsequent (small) decrease in the serum ionized calcium level. After the renal excretion capacity has fully developed and remains intact, the excess absorbed phosphate is excreted and serum Pi levels are kept within the normal range, i. The skeletal effects of carbonated beverage consumption, if any, as reported in a relatively small study in children (Mazarlegos-Ramos et al, 1995) might be due to milk displacement, i. A comparative study in adult women showed no effect of phosphoric acid compared to citric acid as the acidulant in carbonated beverages on urinary calcium excretion (Heaney and Rafferty, 2001). It cannot be excluded therefore that the observed effects in some of the animal studies were associated with the relatively low calcium intakes, rather than the high phosphorus intake as such. Decreased absorption and increased renal excretion therefore protect the human body against the development of chronic hyperphosphatemia under conditions of high phosphorus intake. The role of the phosphatonins in these processes remains to be established (Blumsohn, 2004). In some individuals, however, mild gastrointestinal symptoms, such as osmotic diarrhoea, nausea and vomiting, have been reported if exposed to supplemental intakes >750 mg phosphorus per day. Estimates of current intakes of phosphorus in European countries indicate total mean dietary and supplemental intakes around 1000-1500 mg phosphorus per day, with high (97. There is no evidence of adverse effects associated with the current intakes of phosphorus. Observational data suggest that high phosphorus intakes might aggravate the effects of a state of secondary hyperparathyroidism in individuals with inadequate calcium intakes, or an inadequate vitamin D status. The Panel considers that these data are not sufficient to establish the occurrence of such effects. The effect of oral sodium phosphate on the formation of renal calculi and on idiopathic hypercalcuria. Effect of level and form of phosphorus and level of calcium intake on zinc, iron and copper bioavailability in man. Effect of a short course of oral phosphate treatment on serum parathyroid hormone (I-84) and biochemical markers of bone turnover: a dose-response study. A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. Relationships between bone mineral density, serum vitamin D metabolites and calcium:phosphorus intake in healthy perimenopausal women.

Epigaea repens (Trailing Arbutus). Perindopril.

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Insoluble coloured fibrin by the action of pancreatic proteases disintegrates into low-molecule heart attack or anxiety buy discount perindopril 4 mg line, soluble products which transit along with the dye into the solution hypertension 2013 buy perindopril visa. Fatty acids released by pancreatic lipase alter the basic pH into an acid pH they acidify milk changing the litmus colour from blue to red hypertension unspecified purchase perindopril 2 mg on-line. Pancreatic amylase can be detected by means of starch blood pressure chart heart.org buy perindopril 4mg amex, which under the action of this enzyme can be degraded to reducing sugars hypertension questionnaire 2 mg perindopril with amex. In the sample containing starch and pancreatic juice hypertension of the heart buy perindopril online now, the hydrolysis of starch will occur, and its consequence is the loss of a reaction with iodine and the appearance of reducing properties, which are demonstrated by the starch degradation products. Bile, produced by the liver, plays an important role in the digestion of acylglycerols and the absorption of lipolysis products into the bloodstream. This increases the contact surface of fat with pancreatic lipase (enzyme with substrate), which eases the process of lipolysis. The released fatty acids bind with the bile acids, and in this form are absorbed from the gastrointestinal tract. Proper digestion and absorption of fat determines the absorption of fat-soluble vitamins: A, D, E and K. The border of structural constituents 53 is visible between the water and the oil, and in a test tube containing bile acids a stable suspension (emulsion) forms. Intestinal juice, produced by the glands of the small intestine, contains a number of hydrolytic enzymes finishing the digestive process of food to absorbable products. The main end-products of intestinal digestion are free amino acids, simple sugars and fatty acids, which are absorbed into the blood. The products of their degradation are involved in the re-synthesis of these lipids in the wall of the small intestine, and in this form they are absorbed into the lymph. The large intestine is only the place where bacterial fermentations, water absorption and the excretion of certain salts take place. Detection of bile acids In 1 ml of diluted bile solution, dissolve a few crystals of sucrose. Then to one of the test tubes, add 2 ml of gastric juice, and 2 ml of water to the second. Detection of lactic acid in pathological gastric content Add two drops of FeCl3 solution to 2 ml of 1% phenol. Calculate the free, related and total acidity by multiplying by 10 the volumes of 0. Examine whether the tested liquid contains pepsin, amylase, lipase, pancreatic proteases. The Enzyme-Substrate Complex is formed as a result of an "effective collision" of the enzyme molecule with the substrate molecule. It is such a collision after which the two molecules receive sufficient energy to enter into a chemical reaction. At a constant concentration of the enzyme, the number of such collisions increases with the increase of substrate concentration. With substrate deficiency in the reacting system, not all enzyme molecules are involved in the reaction. The increased substrate concentration causes that more enzyme molecules will be in contact with the substrate. For this reason, the velocity of the enzymatic reaction increases with the increase of the substrate concentration. After reaching a certain concentration value, all enzyme molecules come into contact with the substrate. Further increase in substrate concentration does not increase the velocity of enzymatic reaction. Some enzymatic reactions reach maximum velocity even at low concentrations of substrate. In some cases, maximum velocity is achievable with high concentrations of substrate. This is such a concentration of substrate (expressed in moles per 57 litre) that the enzymatic reaction velocity equals half of the maximum velocity. In order to determine the maximum velocity and the Michaelis constant, we incubate an enzyme of a fixed concentration with a substrate of a variable (increasing) concentration for the same amount of time. After stopping the incubation, we mark the reaction product in every test tube (a measure of the quantity of used substrate) and graph the dependence of the reaction velocity (on the Y-axis) on substrate concentration (on the X-axis). Saccharase (sucrase, invertase) is an enzyme that breaks down sucrose into glucose and fructose. During the reaction, one molecule of a non reducing substrate (sucrose) splits into two molecules of reducing products (glucose and fructose). The progress of the reaction can be assessed by measuring the growth rate of the reducing sugars in the incubation liquid. The reaction products, glucose and fructose, can be determined using the Folin-Wu method. In the next stage, the copper (I) ions transfer electrons to the phosphomolybdic anion and form a coloured 58 complex known as molybdenum blue. The course of the reaction Prepare substrate solutions of different concentrations. Fill the contents of the test tubes 1-4 with distilled water up to 10 ml and mix thoroughly. To test tubes from 1 through 4 measure 1 ml of previously prepared sucrose solutions of the following concentrations: test tube no. To test tube 6 (control test) add 1 ml of yeast extract and heat for 5 minutes in a boiling water bath to inactivate the enzyme, then cool and add 1 ml of 0. After that time, immediately insert the test tubes into a boiling water bath for 5 minutes to stop the reaction by thermal inactivation of the enzyme. Quantitatively transfer the content of each test tube (from 1 to 6) to 100 ml volumetric flasks (with a stopper) (rinsing each test tube with distilled water 3 times). Next, fill the contents of the flasks with distilled water up to 100 ml and mix thoroughly. Determination of reducing sugars in the post-incubation liquid Make all determinations twice. Place all the test tubes in a boiling water bath for exactly 8 minutes, then immediately immerse them in cold water. After cooling, add 1 ml of phosphomolybdic acid to each test tube, mix, fill with distilled water to 5 ml and mix again. Determine the absorbance of light with a wavelength of 650 nm (test tubes 1-10) compared to the control (test tubes 11-12). Then, add 2 ml phosphomolybdic acid, fill up to 10 ml with distilled water and mix thoroughly. Determine the absorbance of the tested samples (2-5) at 650 nm compared to the control sample (test tube no. On the Y-axis indicate the absorbance and on the X-axis the quantity of glucose in micromoles. Results presentation the determined amount of reducing sugars in micromoles multiplied by a factor of 5 gives the reaction speed in the individual samples expressed in micromoles of sucrose decomposed within 1 minute. The factor was calculated taking into account the following data: the initial volume of the substrate (1 ml) was diluted to 100 ml. Therefore, the measurement result should be multiplied by 100, divided by 2 and by 10. Calculate the concentration of sucrose (substrate) in the reacting system remembering that the sucrose solutions were diluted twice with the yeast extract. On the Y-axis indicate the reaction velocity and on the X-axis the concentration of the substrate. Derivative units are milikatals (mkat = 1 x 10-3 kat), microkatals (kat = 110-6 kat), nanokatals (nkat = 110-9 kat) and picokatals (pkat = 110-12 kat). Saccharase (sucrase, invertase) is one of the disaccharidases associated with the surface of the ruffled border of the mucous membrane of the small intestine, which breaks down sucrose contained in foods into glucose and fructose. Its preparation involves mechanical homogenization of yeast cells, lipid extraction with ether, saccharase extraction with distilled water and separation of the insoluble components of the homogenate by filtration on a Buchner funnel. After the incubation, determine the quantity of the obtained products (reducing sugars) and calculate how many moles of sucrose had broken down during 1 second (activity in katals). The reaction products, namely glucose and fructose, are determined using the Folin-Wu method. In the next stage, the 63 copper (I) ions transfer electrons to the phosphomolybdic anion and form a coloured complex known as molybdenum blue. From the quantities of the formed products (hexoses) calculate the amount of broken down substrate (sucrose), keeping in mind that from one mole of sucrose, 2 moles of hexoses (reducing sugars) form. For this purpose, a diagram should be drawn on graph paper showing the dependence of the quantities of broken down sucrose on the time of the reaction. On the Y-axis note the number of micromoles of decomposed substrate and on the X-axis the reaction time in minutes. It represents the directly proportional relationship between the amount of broken down substrate and the reaction time. The calculation of enzyme activity involves the calculation of the number of moles of substrate, which had been broken down in one second by the saccharase contained in 1 ml of undiluted yeast extract. This is equivalent to the calculation of enzyme activity in katals or its derivatives. Preparation of saccharase Students are given a ready extract of saccharase, which should be diluted. Dilution of extract Transfer 1 ml of saccharase extract to a 50 ml volumetric flask, fill with distilled water to the line and mix thoroughly. Measurement of enzyme activity Prepare 10 test tubes and label them with the serial numbers from 1 to 10. Place all test tubes (in rack) in a boiling water bath for exactly 8 minutes, then immediately immerse them in cold water. After cooling, add 1 ml of phosphomolybdic acid solution to each test tube, mix and fill up to 5 ml with distilled water. Measure the absorbance of samples 3-10 at 650 nm compared to the control samples (test tubes 1 and 2). Results presentation From the amount of micromoles of reducing sugars in the various tests, calculate the number of micromoles of sucrose decomposed by 1 ml of undiluted yeast extract. Based on the results contained in the Table, plot the relationship between the amount of decomposed sucrose (Y-axis) and the incubation time (X-axis). Calculate enzyme activity in international enzymatic units and microkatals per ml of undiluted extract. Competitive inhibition A competitive inhibitor displays structural similarity to the substrate and competes with it for the enzyme active site. The enzyme "cannot" distinguish the substrate from the inhibitor and "accidentally" (instead of the substrate) binds the competitive inhibitor in its active site. In the presence of the enzyme, substrate and inhibitor, two reactions can take place: A. Enzyme + Inhibitor Enzyme-Inhibitor the number of enzyme molecules (at a constant concentration) involved in the reaction depends on the relative concentrations of the substrate and the inhibitor. The higher the concentration of the substrate in relation to the inhibitor, the fewer molecules will bind to the enzyme inhibitor. A constant concentration of the enzyme and the inhibitor and increasing concentrations of the substrate cause a disconnection of a growing number of inhibitor molecules from the enzyme, and the inhibitor is replaced by the substrate. The Enzyme-Inhibitor complex is converted into the Enzyme Substrate complex and the inhibitor is displaced from the enzyme active site. Inhibition of the reaction caused by a competitive inhibitor may therefore be reversed by increasing substrate concentration. With appropriately high concentrations of substrate, the maximum reaction velocity (Vmax) reaches the value observed in a system not containing an inhibitor, despite the presence of the inhibitor. In other words, to achieve 67 Vmax in the presence of a competitive inhibitor, higher substrate concentrations are needed than in a system free of this inhibitor. Non-competitive inhibition A non-competitive inhibitor shows no similarity to the substrate. It binds to the enzyme outside the active site (at a different place than the substrate). The active site of the enzyme binds the substrate, but "cannot" turn it into a product. Even a substantial increase in substrate concentration is no longer able to reverse inhibition. Enzyme-Substrate + Inhibitor Enzyme-Substrate-Inhibitor Both the complex: Enzyme-Inhibitor and Enzyme-Substrate-Inhibitor are inactive and "cannot" transform the substrate into a product. Succinate dehydrogenase oxidizes succinate to fumarate by disconnecting 2 hydrogen atoms. Starting with the latter, further transport of electrons occurs independently of the transport of protons. The electrons pass through cytochrome b, cytochrome c1, cytochrome c and cytochrome a+a3 to oxygen.

Assess the patient for other etiologies of altered mental status including hypoxia (pulse oximetry 94%) hypertension zone tool order perindopril from india, hypoglycemia blood pressure goals jnc 8 discount perindopril online master card, hypotension blood pressure medication raise blood sugar buy perindopril 4mg low cost, and traumatic head injury 4 pre hypertension emedicine discount perindopril 2mg overnight delivery. Legally prescribed opioids are also manufactured as an adhesive patch for transdermal absorption blood pressure stroke range generic perindopril 2mg overnight delivery, and if found heart attack man perindopril 4 mg with mastercard, should be removed from the skin Treatments and Interventions 1. Critical resuscitation (opening and/or maintaining the airway, provision of oxygen, ensuring adequate circulation) should be performed prior to naloxone administration 2. If the patient has respiratory depression from a confirmed or suspected opioid overdose, consider naloxone administration a. The administration of the initial dose or subsequent doses can be incrementally titrated until respiratory depression is reversed 3. The cartons of naloxone auto-injectors prescribed to laypersons contain two naloxone auto-injectors and one trainer. High-potency opioids [see Key Considerations] may require higher and/or more frequently administered doses of naloxone to reverse respiratory depression and/or to maintain adequate respirations 5. Regardless of the doses of naloxone administered, airway management with provision of adequate oxygenation and ventilation is the primary goal in patients with confirmed or suspected opioid overdose Patient Safety Considerations 1. The clinical opioid reversal effect of naloxone is limited and may end within an hour whereas opioids often have a duration of 4 hours or longer b. Monitor the patient for recurrent respiratory depression and decreased mental status 277 3. Patients with altered mental status secondary to an opioid overdose may become agitated or violent following naloxone administration due to opioid withdrawal therefore the goal is to use the lowest dose as possible to avoid precipitating withdrawal b. Be prepared for this potential scenario and take the appropriate measures in advance to ensure and maintain scene safety 4. Overuse and abuse of prescribed and illegal opioids has led to an increase in accidental and intentional opioid overdoses 4. Opioids have a high potential for abuse, but have an accepted medical use in patient treatment and can be prescribed by a physician c. Frequent legally prescribed opioids include codeine, fentanyl, hydrocodone, morphine, hydromorphone, methadone, morphine, oxycodone, and oxymorphone d. Some opioids are manufactured as a combination of analgesics with acetaminophen, acetylsalicylic acid (aspirin), or other substances b. In the scenario of an overdose, there is a potential for multiple drug toxicities c. Fentanyl is 50-100 times more potent than morphine it is legally manufactured in an injectable and oral liquid, tablet, and transdermal (worn as a patch) forms however much of the fentanyl adulterating the heroin supply are illegal fentanyl analogs such as acetyl fentanyl b. In the concentration in which it is legally manufactured (3 mg/mL), an intramuscular dose of 2 mL of carfentanil will sedate an elephant 278 c. The risk of respiratory arrest with subsequent cardiac arrest from an opioid overdose as well as hypoxia (pulse oximetry 94%), hypercarbia, and aspiration may be increased when other substances such as alcohol, benzodiazepines, or other medications have also been taken by the patient b. Pediatric Considerations: the signs and symptoms of an opioid overdose may also be seen in newborns who have been delivered from a mother with recent or chronic opioid use. American College of Medical Toxicology and the American Academy of Clinical Toxicology, Preventing Occupational Fentanyl and Fentanyl Analog Exposure to Emergency Responders. Revision Date: September 8, 2017 280 Airway Respiratory Irritants Aliases Respiratory irritant, airway injury, respiratory injury, chemical respiratory injury, toxic inhalation Patient Care Goals Rapid recognition of the signs and symptoms of confirmed or suspected airway respiratory irritants. Inhalation of a variety of gases, mists, fumes, aerosols, or dusts may cause irritation or injury to the airways, pharynx, lung, asphyxiation, or other systemic effects 2. Inhaled airway/respiratory irritant agents will interact with the mucus membranes, upper and lower airways based on solubility, concentration, particle size, and duration of exposure 3. The less soluble and smaller the particle size of the agent the deeper it will travel into the airway and respiratory systems the inhaled toxic agent will go before reacting with adjoining tissues thus causing a greater delay in symptom onset Signs and Symptoms 1. As the type, severity and rapidity of signs and symptom onset depends on agent, water solubility, concentration, particle size, and duration of exposure, the below signs and symptoms are often overlapping and escalating in severity 2. Some agents do not have clear warning properties and will often have delayed onset of any sign or symptom: a. High water solubility/highly irritating (oral/nasal and pharynx, particle size greater than 10 micrometers) a. Intermediate water solubility (bronchus and bronchiole, particle size 5 to 10 micrometers) a. Low water solubility/less irritating (alveolar, particle size less than 5 micrometers) a. These agents or substances are a diverse class of substances that include volatile solvents, aerosols, and gases b. These chemicals are intentionally inhaled to produce a state that resembles alcohol intoxication with initial excitation, drowsiness, lightheadedness, and agitation c. The abusers of these inhaled agents are often called huffers, sniffers, baggers, or snorters these individuals often present after inhaling an aerosol or gas with a loss of consciousness and the presence of the aerosol can or residue/paint around or in the mouth, nose, and oral pharynx d. Inhalants of abuse (volatile solvents, cosmetics/paints, propellants/asphyxiants/nitrous oxide) g. High concentrations and or protracted exposure may develop non-cardiac pulmonary edema q. Often have none of the above symptoms for first half hour to several hours then are much milder until more severe lower respiratory tract symptoms develop i. Distinctive rotten egg smell which rapidly causes olfactory fatigue/loss of sense of smell b. Heavier than air displacing oxygen from low lying areas and closed spaces causing direct asphyxia b. Make sure the scene is safe as many gases are heavier than air and will build up in low lying areas. Pertinent cardiovascular history or other prescribed medications for underlying disease 13. Administer (humidified if available) oxygen and if hypoventilation, toxic inhalation or desaturation noted, support breathing a. Maintain the airway and assess for airway burns, stridor, or airway edema and if indicated, perform intubation early (recommendation to avoid supraglottic airways cricothryoidotomy may be required in rarer severe cases b. This medication should be repeated at this dose with unlimited frequency for ongoing distress 4. Treat topical chemical burns [see appropriate Toxins and Environmental section guideline(s)] 10. In severe respiratory irritation, in particular hydrogen sulfide, with altered mental status and no improvement with removal from the toxic environment, administer oxygen (humidified if available) as appropriate with a target of achieving 94-98% saturation consider consultation for transfer to a hyperbaric oxygen therapy Medication Administration 1. Generally, speaking to patients with exposure to highly soluble airway/respiratory irritants you will find that they have self-extricated due to the warning properties such as the smell, rapidity of onset of irritation, and other symptoms 2. Airway respiratory irritants can exacerbate underlying reactive airway diseases. As patients may be off gassing (particularly hydrogen sulfide and hydrogen cyanide) in the back of the transport vehicle, it is recommended to have adequate ventilation of the patient compartment 3. Removal from the toxic environment, oxygen (humidified if available), general supportive therapy, bronchodilators, respiratory support, and time are core elements of care as there are no specific antidotes for any of these inhaled agents with the exception of heavy metals that may be chelated by physicians after agent identification 4. Hydrogen sulfide causes the cells responsible for the sense of smell to be stunned into inaction and therefore with a very short exposure will shut down and the exposed victim will not perceive the smell yet the victim continues to absorb the gas as it is still present 5. Household bathroom, kitchen, and oven cleaners when mixed can generate a varied of these airway respiratory irritants (ammonia, chloramine, and chlorine gas releases are particularly common). A very common exposure is to chloramine, a gas liberated when bleach (hypochlorite) and ammonia are combined. Chloramine then hydrolyzes in the distal airways and alveoli to ammonia and hypochlorous acid 7. Some inhalants can cause the heart to beat rapidly and erratically and cause cardiac arrest b. This syndrome most often is associated with abuse of butane, propane and effects of the chemicals in the aerosols Pertinent Assessment Findings 1. Patient may describe a specific odor (chlorine swimming pool smell, ammonia smell, fresh mowed hay smell [phosgene]) which may be helpful but should not be relied upon as the human nose is a poor discriminator of scent 2. Baydala L, Canadian Paediatric Society, First Nations, Inuit and Metis Health Committee. Effects of infusion of human methemoglobin solution following hydrogen sulfide poisoning. Exaggerated responses to chlorine inhalation among persons with nonspecific airway hyperreactivity. Occupationally related hydrogen sulfide deaths in the United States from 1984 to 1994. Acute accidental exposure to chlorine gas in the Southeast of Turkey: a study of 106 cases. High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide poisoning induced cardiac depression in sheep. Exposure to identifiable agents that are not intended to cause significant injury or fatality Exclusion Criteria 1. Exposure to chlorine, phosgene, ammonia or other agents that are intended to cause significant injury or fatality 2. Move affected individuals from contaminated environment into fresh air if possible 2. Irrigation with water or saline may facilitate resolution of symptoms and is recommended for decontamination of dermal and ocular exposure 5. Exposed individuals who are persistently symptomatic warrant further evaluation and treatment per local standards Patient Safety Considerations 1. Toxicity is related to duration of exposure and concentration of agent used (exposure in non-ventilated space) 2. Traumatic injury may result when exposed individuals are in proximity to the device used to disperse the riot control agent. Toxicity is related to time of exposure and concentration of agent used (exposure in non ventilated space). Symptoms begin within seconds of exposure, are self-limited and are best treated by removing patient from ongoing exposure. A randomized controlled trial comparing treatment regimens for acute pain for topical oleoresin capsaicin (pepper spray) exposure in adult volunteers. Revision Date September 8, 2017 292 Hyperthermia/Heat Exposure Aliases Hyperthermia, heat cramps, heat exhaustion, heat syncope, heat edema, heat stroke Definitions 1. As it progresses tachycardia, hypotension, elevated temperature, and very painful cramps occur. Heat Stroke: occurs when the cooling mechanism of the body (sweating) ceases due to temperature overload and/or electrolyte imbalances. When no thermometer is available, it is distinguished from heat exhaustion by altered level of consciousness 4. Heat Syncope: is a transient loss of consciousness with spontaneous return to normal mentation attributable to heat exposure 5. Heat Edema: is dependent extremity swelling caused by interstitial fluid pooling Patient Care Goals 1. Mitigate high risk for agitation and uncooperative behavior Patient Presentation Inclusion Criteria 1. Excited delirium [see Agitated or Violent Patient/Behavioral Emergency guideline] Exclusion Criteria 1. Confined space Pediatric Considerations: Children left in cars who show signs of altered mental status and elevated body temperature should be presumed to have hyperthermia 3. Place on cardiac monitor and record ongoing vital signs and level of consciousness 7. Continually misting the exposed skin with tepid water while fanning the victim (most effective) c. Monitor for arrhythmia and cardiovascular collapse (see Cardiovascular section guidelines) 11. All patients suffering from life threatening heat illness (including heat stroke) should be transported to the hospital Patient Safety Considerations Consider use of physical securing devices (see Agitated or Violent Patient/Behavioral Emergency guideline) to protect vascular access sites. Patients at risk for heat emergencies include neonates, infants, geriatric patients, and patients with mental illness 2.

Diseases

• Sparse hair ptosis mental retardation
• Alternating hemiplegia of childhood
• Dentin dysplasia, radicular
• Granulomas, congenital cerebral
• Stratton Parker syndrome
• Central serous chorioretinopathy
• Vaginismus

The table below presents specific label elements for substances and mixtures which are classified as posing an aspiration toxicity hazard arteria labyrinth cheap perindopril 8mg visa, Categories 1 and 2 blood pressure spikes buy 8 mg perindopril fast delivery, based on the criteria set forth in this chapter arteriosclerosis buy discount perindopril on line. It is strongly recommended that the person responsible for classification study the criteria Does the mixture contain 10% of an ingredient or ingredients classified in before and during use of the decision logic arteriovenous fistula purchase perindopril online from canada. Classification not Warning No possible No Yes Yes Mixture: Does the mixture as a whole show aspiration Not classified See decision logic 3 blood pressure medication regimen discount perindopril 4 mg mastercard. Yes Category 1 (a) Is there practical experience in humans from reliable and good quality evidence blood pressure chart pictures best buy for perindopril, for example, certain hydrocarbons, turpentine and pine oil, or Danger Yes (b) Is the substance a hydrocarbon with a kinematic viscosity 2 20. Availability of a substance means the extent to which this substance becomes a soluble or disaggregate species. Bioavailability (or biological availability) means the extent to which a substance is taken up by an organism, and distributed to an area within the organism. It is dependent upon physico-chemical properties of the substance, anatomy and physiology of the organism, pharmacokinetics, and route of exposure. Bioaccumulation means net result of uptake, transformation and elimination of a substance in an organism due to all routes of exposure. Bioconcentration means net result of uptake, transformation and elimination of a substance in an organism due to waterborne exposure. Chronic aquatic toxicity means the intrinsic property of a substance to cause adverse effects to aquatic organisms during aquatic exposures which are determined in relation to the life-cycle of the organism. Complex mixtures or multi-component substances or complex substances means mixtures comprising a complex mix of individual substances with different solubilities and physico-chemical properties. In most cases, they can be characterized as a homologous series of substances with a certain range of carbon chain length/number of degree of substitution. Degradation means the decomposition of organic molecules to smaller molecules and eventually to carbon dioxide, water and salts. Long-term (chronic) hazard, for classification purposes, means the hazard of a chemical caused by its chronic toxicity following long-term exposure in the aquatic environment. Short-term (acute) hazard, for classification purposes, means the hazard of a chemical caused by its acute toxicity to an organism during short-term aquatic exposure to that chemical. The criteria for classification of a substance into Chronic 1 to 3 follow a tiered for all aquatic organisms and data on other species such as Lemna may also be considered if the test methodology is approach where the first step is to see if available information on chronic toxicity merits long-term hazard classification. Other validated demonstrated, classification can occur if the substance is both not rapidly degraded and has a potential to and internationally accepted tests could also be used. A pass level in these tests can be considered as indicative of rapid degradation in most environments. Special guidance on data interpretation is provided in the Guidance Document (Annex 9). Considering the complexity of this endpoint and the breadth of the application of the system, the Guidance Documents are considered an important element in the operation of the 72 or 96hr ErC50 (for algae or other aquatic plants) >10 but 100 mg/l (Note 3) harmonized scheme. The harmonized scheme is considered suitable for use for packaged goods in both supply and use and multimodal transport schemes, and elements of it may 220 221 220 Copyright@United Nations, 2017. In absence of adequate chronic toxicity data, the subsequent step is to combine two types of information, i. It is considered that for such poorly soluble substances, the toxicity may not have been adequately assessed in the short-term test due to the low exposure levels and potentially slow uptake into the organism. Some regulatory systems may extend this range beyond an L(E)C50 of 100 mg/l through the introduction of another category. The harmonized scheme is considered suitable for use for packaged goods in both supply and use and multimodal transport schemes, and elements of it may 220 221 221 Copyright@United Nations, 2017. Where it can be shown that this is not the case, professional x judgment should be used in deciding if classification should be applied. Data on other organisms may also be considered, (b) Long-term (chronic) aquatic hazard (see also figure 4. When no useful data on degradability are available, either experimentally determined or (ii) Rapidly degradable substances for which there are adequate chronic toxicity data available estimated data, the substance should be regarded as not rapidly degradable. Distinction can be made between the short-term (acute) hazard and the long and which are not rapidly degradable and have a log Kow 4, indicating a potential to bioaccumulate, will be term (chronic) hazard and therefore separate hazard categories are defined for both properties representing a gradation classified in this category unless other scientific evidence exists showing classification to be unnecessary. All rights reserved circumstances, however, when a weight of evidence approach may be used. Many substance may give rise to short-term dangers arising from accidents or major spillages. Details regarding the interpretation of these data are further elaborated in the guidance document of Annex frameworks. The category Acute 1 may be further sub-divided to include an additional category for acute toxicity 9. Thus where such rapid considered that the acute toxicity itself does not describe the principal hazard, which arises from low concentrations degradation can be shown, the substance should be considered as rapidly degradable. The intrinsic properties of a lack of rapid considered and may be of particular importance where the substances are inhibitory to microbial activity at the degradability and/or a potential to bioconcentrate in combination with acute toxicity may be used to assign a substance concentration levels used in standard testing. They go beyond that of protecting aquatic ecosystems, although that clearly is included. These levels of biodegradation must be achieved within 10 days of the start of degradation 4. In this case, and where there is sufficient justification, the 10-day window levels and taxa, and the test methods are highly standardized. Data on other organisms may also be considered, condition may be waived and the pass level applied at 28 days as explained in Annex 9 however, provided they represent equivalent species and test endpoints. Rather the substance may be transformed by normal environmental processes to either over longer time scales even when actual water concentrations are low. The potential to bioaccumulate is determined by increase or decrease the bioavailability of the toxic species. Equally the use of bioaccumulation data should be treated the partitioning between n-octanol and water. Some relationships environment depending on the intrinsic toxicity of the bioavailable inorganic species and the rate and amount of this can be observed between chronic toxicity and bioaccumulation potential, as toxicity is related to the body burden. The absence of rapid degradation in the environment can mean that a substance in the water has the potential to exert toxicity over a While experimentally derived test data are preferred, where no experimental data are available, wide temporal and spatial scale. However, a chemicals for which their mode of action and applicability are well characterized. Reliable calculated toxicity and log 224 225 224 Copyright@United Nations, 2017. Acute toxicity data are the most readily fail in the screening test does not necessarily mean that the substance will not degrade rapidly in the environment. Hazards categories up to degradation data are available in the form of degradation half-lives and these can also be used in defining rapid L(E)C50 values of 100 mg/l are thus defined although categories up to 1000 mg/l may be used in certain regulatory degradation. It is anticipated that biodegradation would not normally qualify in the assessment of rapid degradability unless it can be demonstrated that their use would be restricted to regulatory systems concerning bulk transport. At toxicity levels above this, it is tests does not mean that the substance will not be degraded rapidly in the real environment. Thus, a number of hazard categories are defined which are based on levels of the hydrolysis products do not fulfil the criteria for classification as hazardous to the aquatic environment. Chronic toxicity data are not available for many substances, however, and in those cases it is definition of rapid degradability is shown below. Other evidence of rapid degradation in the environment may also be necessary to use the available data on acute toxicity to estimate this property. The range of available data and guidance on its interpretation are provided to a long-term (chronic) hazard category. Some degraded (biotically and/or abiotically) in the aquatic environment to a level >70% within a substances are difficult to test under standard procedures and thus special guidance will be developed on data 28-day period. The relationship between the partition coefficient of an organic substance with care. Reliable calculated toxicity and log 224 225 225 Copyright@United Nations, 2017. In order to make use of all available data for purposes of classifying the aquatic environmental hazards of the mixture, the following assumption has been made and is applied Table 4. Generally this would mean measured test data, but in order to avoid the derived L(E)C50 or unnecessary testing it can, on a case-by-case basis, also be estimated data. There are no degradability and bioaccumulation data for mixtures the aquatic hazard classification of a tested production batch of a mixture can be assumed to be as a whole. This ensures that the for more than one ingredient in the mixture, the combined toxicity of those ingredients may be calculated using the classification process uses the available data to the greatest extent possible in characterizing the hazards of the mixture following additivity formulas (a) or (b), depending on the nature of the toxicity data: without the necessity for additional testing in animals. The classification should equivalent or lower aquatic hazard classification than the least toxic original ingredient and which is not expected to normally be based on the data for fish, crustacea and algae/plants (see 4. Degradability and bioaccumulation tests for mixtures are not used as they are usually difficult to interpret, substantially equivalent to that of another untested production batch of the same commercial product when produced by and such tests may be meaningful only for single substances. When adequate toxicity data are available mixture, this data will be used in accordance with the following agreed bridging principles. Ingredients with a where: classification in a high toxicity band may therefore contribute to the classification of a mixture in a lower band. The calculation of these classification categories therefore needs to consider the contribution of all ingredients classified Ci = concentration of ingredient i (weight percentage); Acute 1/Chronic 1 to Acute 3/Chronic 3 together. Active ingredients in pesticides often possess such high aquatic toxicity but also some other substances like the calculated toxicity may be used to assign that portion of the mixture a short-term (acute) organometallic compounds. Therefore, multiplying factors should be applied to account for highly toxic ingredients, as described in 4. As a consequence the classification procedure is where: already completed if the result of the classification is Chronic 1. A more severe classification than Chronic 1 is not possible, therefore it is not necessary to undergo the further classification procedure. However, when toxicity data for each ingredient are not available in the same taxonomic group, the toxicity of the concentrations of classified ingredients value of each ingredient should be selected in the same manner that toxicity values are selected for the classification of substances, i. Ci = concentration of ingredient i (weight percentage) covering the rapidly degradable ingredients; 4. If the i covering the rapidly degradable ingredients, in mg/l; result of the calculation is a classification of the mixture as Acute 1, the classification process is completed. If the result of the calculation is classification of the mixture as Acute 2, the classification process is completed. A mixture is classified as Acute 3 if 100 times the sum of the concentrations (in %) of all the calculated equivalent toxicity may be used to assign that portion of the mixture a long ingredients classified as Acute 1 multiplied by their corresponding M factor plus 10 times the sum of the concentrations term (chronic) hazard category, in accordance with the criteria for rapidly degradable (in %) of all ingredients classified as Acute 2 plus the sum of the concentrations (in %) of all ingredients classified as substances (Table 4. The calculated acute and chronic Sum of the concentrations (in %) of ingredients classified as: Mixture is classified as: toxicity may then be used to classify this part of the mixture as Acute 1, 2 or 3 and/or Chronic 1, 2 or 3 using the same a Acute 1 M 25% Acute 1 criteria described for substances. If the sum of the concentrations (in %) of Acute toxicity M factor Chronic toxicity M factor these ingredients multiplied by their corresponding M factor is 25% the mixture is classified as Chronic 1. If the result of the calculation is classification of the mixture as Chronic 2, the classification process is completed. The competent authority can concentrations of classified ingredients is summarized in Table 4. The multiplying factors to be applied to these ingredients are defined using the toxicity value, as summarized in Table 4. Therefore, in order to classify a mixture containing Acute/Chronic 1 ingredients, the classifier needs to be informed of the value of the M factor in order to apply the summation method. A mixture is classified as Chronic 2 if 10 times the sum of the concentrations (in %) of all ingredients 0. A mixture is classified as Chronic 3 if 100 times the sum of the concentrations (in (continue in factor 10 intervals) (continue in factor 10 intervals) %) of all ingredients classified as Chronic 1 multiplied by their corresponding M factor plus 10 times the sum of the a Non-rapidly degradable concentrations (in %) of all ingredients classified as Chronic 2 plus the sum of the concentrations (in %) of all b Rapidly degratdable ingredients classified as Chronic 3 is 25%. A mixture is classified as Chronic 4 if the sum of the concentrations (in %) of In the event that no useable information on acute and/or chronic aquatic toxicity is available for one or ingredients classified as Chronic 1, 2, 3 and 4 is 25%. Annex 3 (M 10 Chronic 1) + Chronic 2 25% Chronic 2 contains examples of precautionary statements and pictograms which can be used where allowed by the competent authority. When a mixture contains ingredients Hazard statement Very toxic to aquatic life Toxic to aquatic life Harmful to aquatic life classified as Acute or Chronic 1, the tiered approach described in 4. Alternatively, the additivity formula (see Symbol Environment Environment No symbol No symbol 4. No Not classified for Acute 1 Classification can be based on either measured data and/or calculated data (see 4. No Not classified for Acute 2 Labelling requirements differ from one regulatory system to another, and certain classification categories may only be used in one or a few regulations. Alternatively, in the case of a mixture with highly toxic ingredients, if toxicity values are available for these highly toxic ingredients and all other ingredients do not significantly contribute to the hazard of the mixture, then the additivity formula may be applied (see 4. Yes Acute 1 Sum of the concentrations (in %) of ingredients classified as: 4 Yes Acute 1 M 25% Warning No Sum of the concentrations (in %) of ingredients classified as: 2 4 Acute 2 (Acute 1 M 10) + Acute 2 25% Yes No Sum of the concentrations (in %) of ingredients classified as: 2 Acute 3 4 Yes (Acute 1 M 100) + (Acute 2 10) + Acute 3 25%

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References

• Shetty V, Freymiller E. Teeth in the line of fracture: a review. J Oral Maxillofac Surg 1989;47:1303.
• Hiatt JR, Busuttil RW, Wilson SE. Impact of routine arteriography on management of penetrating neck injuries. J Vasc Surg. 1984;1(6):860-866.
• Guillou L, Gloor E, Anani PA, Kaelin R. Bronchial granular-cell tumor. Report of a case with preoperative cytologic diagnosis on bronchial brushings and immunohistochemical studies. Acta Cytol 1991;35(4):375-80.
• American Joint Committee on Cancer Ophthalmic Oncology Task Force. International validation of the American Joint Committee on Cancer's 7th edition classification of uveal melanoma. JAMA Ophthalmol 2015;133(4):376- 383.
• Mishra J, Ma Q, Prada A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14:2534-2543.