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Clinical Director, Washington University School of Medicine

Adverse effects: Most of the adverse effects involve problems in fluid and electrolyte balance. Potassium depletion: Hypokalemia is the most frequent problem encountered with the thiazide diuretics, and it can predispose patients who are taking digitalis to ventricular arrhythmias (Figure 22. Often, K+ can be supplemented by diet alone, such as by increasing the intake of citrus fruits, bananas, and prunes. Activation of the renin-angiotensin-aldosterone system by the decrease in intravascular volume contributes significantly to urinary K+ losses. Under these circumstances, the K+ deficiency can be overcome by spironolactone, which interferes with aldosterone action, or by administering triamterene, which acts to retain K+. Limiting water intake and lowering the dose of diuretic can prevent this condition. Hyperuricemia: Thiazides increase serum uric acid by decreasing the amount of acid excreted by the organic acid secretory system. Being insoluble, the uric acid deposits in the joints, and a full-blown attack of gout may result in individuals who are predisposed to gouty attacks. Hypercalcemia: the thiazides inhibit the secretion of Ca2+, sometimes leading to elevated levels of Ca2+ in the blood. Hyperglycemia: Patients with diabetes mellitus who are taking thiazides for hypertension may become hyperglycemic and have difficulty in maintaining appropriate blood sugar levels. Hyperlipidemia: the thiazides can cause a 5- to 15-percent increase in serum cholesterol as well as increased serum low-density lipoproteins. Hypersensitivity: Bone marrow suppression, dermatitis, necrotizing vasculitis, and interstitial nephritis are very rare. Individuals who are hypersensitive to sulfa drugs may also be allergic to the thiazide diuretics. Thiazide-like analogs these compounds lack the thiazide structure, but like the thiazides, they have the unsubstituted sulfonamide group and share their mechanism of action. It has a very long duration of action and, therefore, is often used to treat hypertension. At low doses, it shows significant antihypertensive action with minimal diuretic effects. Indapamide is metabolized and excreted by the gastrointestinal tract and the kidneys. It is therefore less likely to accumulate in patients with renal failure and may be useful in their treatment. Compared to all other classes of diuretics, these drugs have the highest efficacy in mobilizing Na+ and Clfrom the body. Ethacrynic acid has a steeper dose-response curve than furosemide, but it shows greater side effects than those seen with the other loop diuretics and its use is therefore limited. Mechanism of action: Loop diuretics inhibit the cotransport of Na+/K+/2Cl- in the luminal membrane in the ascending limb of the loop of Henle. The loop diuretics are the most efficacious of the diuretic drugs, because the ascending limb accounts for the reabsorption of 25 to 30 percent of filtered NaCl and downstream sites are not able to compensate for this increased Na+ load. Actions: the loop diuretics act promptly, even among patients who have poor renal function or have not responded to thiazides or other P. Changes in the composition of the urine induced by loop diuretics are shown in Figure 22. In patients with normal serum Ca2+ concentrations, hypocalcemia does not result, because Ca2+ is reabsorbed in the distal convoluted tubule. The prostaglandins have a role in their diuretic action, and substances such as indomethacin that interfere in prostaglandin synthesis can reduce the diuretic action of these agents. Therapeutic uses: the loop diuretics are the drugs of choice for reducing the acute pulmonary edema of heart failure. Because of their rapid onset of action, particularly when given intravenously, the drugs are useful in emergency situations, such as acute pulmonary edema, which calls for a rapid, intense diuresis. Loop diuretics (along with hydration) are also useful in treating hypercalcemia, because they stimulate tubular Ca2+ excretion. Adverse effects: the adverse effects of the loop diuretics are summarized in Figure 22. Ototoxicity: Hearing can be affected adversely by the loop diuretics, particularly when used in conjunction with the aminoglycoside antibiotics.

Typically the sorbitol powder, flavour and lubricant are mixed and then fed to the tabletting machine. The mixing and tabletting must be carried out in air conditioned areas as sorbitol is hygroscopic. Sorbitol powder manufacturers usually make several grades of sorbitol powder of different particle size and all can be used to make tablets. There has to be a trade-off however between product texture and flowability of product to the tabletting dies. The large particle size grades flow easily and fill the dies but give a coarse mouth-feel whilst the finer grades flow less readily but give a smoother finished product. Whilst all commercially manufactured sorbitol is the gamma polymorph this alone does not guarantee a hard tablet, the physical state of the sorbitol powder is equally important. For example under the same tabletting conditions, an open structured sorbitol powder will give a harder tablet than a powder with a more dense structure. Mannitol is also used in tabletting but more so for pharmaceutical than food products. Fine powder grades are typically used in wet granulated formulations and larger particle sizes in directly compressible products where good product flow is essential to fill the tabletting dies. Mannitol is also used in directly compressed chewable tablets where its slower solubility is utilised to provide sweetness for the duration the product is in the mouth. Sugar was traditionally used as a cryoprotectant for the protein during the freezing step and whilst it functioned effectively in this role it made the product too sweet. During the freezing process the sorbitol protects the protein from denaturation which would otherwise reduce its gel forming ability and gel strength. The end result of this is reduction in its water holding capacity and a less succulent product. When sausages are grilled, sugar and glucose syrups normally used in the product caramelise and char, whereas sorbitol will not. Crystalline sorbitol however continues to be used in these products owing to its lower cost. A high purity sorbitol solution is used to coat the centres and sorbitol powder is added to provide crystallisation nuclei. Whilst the low cost of crystalline sorbitol would seem to make it attractive in this application, its hygroscopicity leads to unacceptable moisture increases during refining and its powerful cooling effect is not desirable in chocolate. All are essentially similar and have the same objective ­ to present the consumer with safe, high-quality food ingredients. Sorbitol powder has the E number 420 (i) sorbitol syrups E 420 (ii) and mannitol E 421. They all are authorised for food use at quantum satis for the range of food products listed in the Regulations. Despite being first-generation products they should not be discounted from new product development. Modification of the crystalline structure of sorbitol and its effects on tabletting characteristics, Pharmaceutical Technology, 1984, 8, 50­56. Besides being a healthy sweetener, tagatose can be used as a flavour enhancer and flavour creator in minor dosages in many applications like beverage systems and confectionery products. Tagatose is a keto hexose of the aldose galactose, like fructose is the keto hexose of glucose. Tagatose is determined to be 92% as sweet as sucrose, based on an equivalent sweetener taste test. The Maillard reaction has been followed in different model systems with the aim of classifying the kinetic mechanism of tagatose versus other Maillard-reactive sweeteners. As a result, it has been documented that tagatose creates totally different flavour systems than any other sweeteners ­ a reaction that can be used very beneficially by the food manufactures in creating specific toffee or malt flavours, for example in different confectionery products or malt characteristic foods like cereals. The reaction flavour potential is a very important parameter that can be used to create toffee or malt flavours ­ however in certain food systems like in bakery or traditional cooked cereals where the products undergo a very high temperature treatment at relative low-moisture contents, the Maillard reaction is very difficult to control and there is a risk that bitter flavour notes will develop. These properties all have implications that need to be considered when using tagatose in different food applications. Tagatose Sucrose the solubility of tagatose in comparison with other sweeteners appears in. Due to the fact that tagatose is a monosaccharide, the depression it has on freezing point and water activity is greater than sucrose ­ the effects are demonstrated in Figs 14.

Parrot beak nails can occur as a primary nail dermatosis or secondary to finger pulp atrophy. Up-slanting Nails (Upturned Nails, Ski Jump Nails) Downloaded by [Chulalongkorn University (Faculty of Engineering)] at the variation in nail contour (small: brachyonychy and concave) and in nail direction (returned small nails) may be observed in children or adolescent with lower-limb lymphedema. Lymphedema in adults is classically divided into two forms, primary and secondary, essentially after cancer treatment. Pediatric lymphedema may be a part of syndromic form, with or without gene implication (Turner, Noonan, Hennekam syndromes and Waldmann disease)22 (Table 4. Classically, lymphedema involves one limb or two limbs under the knee (foot, ankle, and calf). Lymphedema affects commonly the nail anatomy23 with small hyperplastic concave nails and increased insertion angle. In adolescents, primary lymphedema of the lower limbs is associated with the up-slanting toenails and soft upturned small nails in children. In Mosaic Turner syndrome, although an intermediate mean fingernail angle is noted, no clear correlation between mean fingernail angle and severity of other manifestations has been shown. Small dysplastic upturned toenails, deep creases, and swollen sausage-like toes may be observed. Nail Consistency Variations Changes in nail consistency may be due to impairment of one or more factors on which the health of the nail depends and includes elements like variations in the water content or the keratin constituent. Changes in the intercellular structures, cell membranes, and intracellular changes in the arrangement of keratin fibrils have been revealed by electron microscopy. After prolonged immersion in water, this percentage increases and the nail becomes soft; this makes toenail trimming much easier. Splitting, which results from this brittle quality, probably is partly due to repeated uptake and drying out of water. The different orientation of keratin fibrils within the layers appears to lend characteristics of both toughness and flexibility. Hardness of Nail Hard nails are a major characteristic of the pachyonychia congenita syndrome and the yellow nail syndrome. A study of hardness of fingernails in well-nourished and malnourished populations revealed that the hardest nails were those of Filipino infants and children suffering from protein­energy deficiency. In children up to 12 years of age, hardness did not appear to be influenced by the age, sex, and racial origins of individuals, or the environmental conditions to which nail specimens were exposed. Thickening of the toenails should not be over interpreted in children under the age of 10 years. In the early stages of walking, toenails thickening can represent a reactive change equivalent to the development of a hammertoe. The immature muscles of the foot can direct the toe so that the pulp is plantar-flexed, making the free edge of the nail tap against the ground. For this reason, it is important to examine young children as they move about the consulting room unhindered, so that the natural positions of the toes are apparent. In young children, koilonychias may occur due to contact with water and/or chemicals. For very soft nails, the term hapalonychia is used: such nails may be thinner than usual and bend easily and break or split at the free edge. Soft nail disease is an unusual, congenital nail dystrophy with anatomical and junctional defect of the nail matrix. When the thickening is regular and confined to the nail plate, it is due to the involvement of matrix and is sometimes called onychauxis, a sign reported in association with the eunuchoid state. Hyperplastic subungual tissues, especially of the hyponychium can alter the nail plate, and nail consistency may be hard as in pachyonychia congenita or soft as in psoriasis, pityriasis rubra pilaris, chronic eczema, and onychomycosis. Downloaded by [Chulalongkorn University (Faculty of Engineering)] at Brittle Nails We consider that usually the brittle nail syndrome encompasses six main types which are as follows29: 1. Onychorrhexis is made of shallow parallel furrows running in the superficial layer of the nail. It may result in an isolated split at the free edge, which sometimes extends proximally.

Abdominal structures enter the thorax A; may occur due to congenital defect of pleuroperitoneal membrane, or as a result of trauma. Commonly occurs on left side due to relative protection of right hemidiaphragm by liver. Most commonly a hiatal hernia, in which stomach herniates upward through the esophageal hiatus of the diaphragm. Goes through the internal (deep) inguinal ring, external (superficial) inguinal ring, and into the scrotum. Occurs in infants owing to failure of processus vaginalis to close (can form hydrocele). Diaphragmatic hernia A Indirect inguinal hernia B An indirect inguinal hernia follows the path of descent of the testes. Bulges directly through parietal peritoneum medial to the inferior epigastric vessels but lateral to the rectus abdominis. Protrudes below inguinal ligament through femoral canal below and lateral to pubic tubercle. Femoral hernia More likely to present with incarceration or strangulation than inguinal hernias. Octreotide is an analog used to treat acromegaly, carcinoid syndrome, and variceal bleeding. Motilin receptor agonists (eg, erythromycin) are used to stimulate intestinal peristalsis. Gastric acid Parietal cells (stomach) Pepsin Chief cells (stomach) Mucosal cells (stomach, duodenum, salivary glands, pancreas) and Brunner glands (duodenum) Protein digestion Pepsinogen (inactive) is converted to pepsin (active) in the presence of H+. Iron Fist, Bro Clinically relevant in patients with small bowel disease or after resection. Peyer patches A Unencapsulated lymphoid tissue A found in lamina propria and submucosa of ileum. B cells stimulated in germinal centers of Peyer patches differentiate into IgA-secreting plasma cells, which ultimately reside in lamina propria. IgA receives protective secretory component and is then transported across the epithelium to the gut to deal with intraluminal antigen. Unconjugated bilirubin is removed from blood by liver, conjugated with glucuronate, and excreted in bile. Composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or ruptured intraoperatively. Mucoepidermoid carcinoma-most common malignant tumor, has mucinous and squamous components. Warthin tumor (papillary cystadenoma lymphomatosum)-benign cystic tumor with germinal centers. Esophageal pathologies Boerhaave syndrome Transmural, usually distal esophageal rupture with pneumomediastinum (arrows in A) due to violent retching. Subcutaneous emphysema may be due to dissecting air (crepitus may be felt in the neck region or chest wall). Dilated submucosal veins (red arrows) B C in lower 1 /3 of esophagus (white arrow) 2° to portal hypertension. Partial-thickness mucosal lacerations at gastroesophageal junction due to severe vomiting. Often presents with hematemesis and may be misdiagnosed as ruptured esophageal varices. Chronic gastritis H pylori Autoimmune Affects antrum first and spreads to body of stomach. Mйnйtrier disease A Hyperplasia of gastric mucosa hypertrophied rugae (look like brain gyri A), excess mucus production with resultant protein loss and parietal cell atrophy with acid production. Often presents late, with weight loss, early satiety, and in some cases acanthosis nigricans or Leser-Trйlat sign. Intestinal-associated with H pylori, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, chronic gastritis. Diffuse-not associated with H pylori; signet ring cells (mucin-filled cells with peripheral nuclei) A; stomach wall grossly thickened and leathery (linitis plastica).