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The hormonal cascade known as the hypothalamic-pituitary-thyroid axis employs G-protein transducers that activate both adenylate cyclase and phospholipase C erectile dysfunction klonopin buy nizagara cheap online. However, the free, or "unbound," T3 and T4 are responsible for the biological effects of the thyroid hormones. The thyroid hormones enter the cell either by simple or carrier-mediated diffusion across the cell membrane. The net effect of increased thyroid hormones is an increase in basal metabolic rate. This is accomplished by increasing the expression of genes that code for enzymes in both the catabolic and anabolic pathways of fats, carbohydrates and proteins, as well as the expression of the Na-K pump. The careful regulation of thyroid hormone secretion is therefore important in the overall regulation of metabolism. The thionamides act by inhibiting the enzyme thyroid peroxidase, an enzyme on the apical membrane of the thyroid follicular cell that faces the lumen. Radioactive iodine treatments cause the progressive destruction of thyroid cells, thus reducing thyroid function over a period of several weeks to months. From which of the following essential amino acids are the thyroid hormones synthesized Which of the following tests would be most helpful to obtain an accurate diagnosis Electrocardiogram Free thyroxine level Serum cortisol levels Serum electrolytes Serum glucose level Answers [7. Thyroid hormones are synthesized from tyrosyl residues on thyroglobulin in the colloidal space of the thyroid follicular cells. Although tyrosine can be obtained from the diet, it can also be synthesized from the essential amino acid phenylalanine by the action of phenylalanine hydroxylase. Thyroid hormones are similar to steroid hormones in that they bind to receptors in the nucleus of the cell. This patient appears to have a hyperthyroid condition even though the thyroid does not appear to be enlarged. The free thyroxine level is a direct measure of the amount of free T4, the biologically active T4, in the serum. Hormones that bind to cell-surface receptors activate or form a complex with a transducer protein in the membrane that will cause the activation of some enzymatic activity in the cytoplasm of the cell, producing a second messenger. Nuclear receptors are intracellular proteins present in either the cytosol or the nucleus that bind hormones (steroids) which cross the cell membrane by simple diffusion. His medical history is significant for abdominal distention, failure to pass stool, and emesis as an infant. He has several relatives with chronic lung and "stomach" problems, and some have even died at a young age.

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Pharmacologic approaches that facilitate weight loss and bariatric surgery should be considered in selected patients (Chap erectile dysfunction low blood pressure purchase nizagara paypal. As for the general population, a diet that includes fruits, vegetables, fiber-containing foods, and low-fat milk is advised. Historically, nutrition education imposed restrictive, complicated regimens on the patient. Current practices have greatly changed, though many patients and health care providers still view the diabetic diet as monolithic and static. As for the general population, a healthy diet includes fruits, vegetables, and fiber-containing foods. Currently, evidence does not support supplementation of the diet with vitamins, antioxidants (vitamin C and E), or micronutrients (chromium) in patients with diabetes. The majority of these individuals 298 are obese, and weight loss is strongly encouraged and should remain an important goal. Skeletal muscle is a major site for metabolic fuel consumption in the resting state, and the increased muscle activity during vigorous, aerobic exercise greatly increases fuel requirements. If the insulin level is too low, the rise in catecholamines may increase the plasma glucose excessively, promote ketone body formation, and possibly lead to ketoacidosis. Untreated proliferative retinopathy is a relative contraindication to vigorous exercise, as this may lead to vitreous hemorrhage or retinal detachment. A large number of blood glucose monitors are available, and the certified diabetes educator is critical in helping the patient select the optimal device and learn to use it properly. By combining glucose measurements with diet history, medication changes, and exercise history, the physician and patient can improve the treatment program. Urine glucose testing does not provide an accurate assessment of glycemic control. Currently, the use of these devices in routine diabetes management is limited, and they do not replace the need for a traditional glucose meter. This rapidly evolving technology requires substantial expertise on the part of the diabetes management team and the patient. Although clinical experience with these devices is limited, they appear to provide useful short-term information about the patterns of glucose changes as well as an enhanced ability to detect hypoglycemic episodes. Blood measurement of -hydroxybutyrate is preferred over urine testing with nitroprusside-based assays that measure only acetoacetate and acetone. Assessment of Long-Term Glycemic Control Measurement of glycated hemoglobin is the standard method for assessing long-term glycemic control. There are numerous laboratory methods for measuring the various forms of glycated hemoglobin, and these have significant interassay variations.

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It is generally sexually transmitted erectile dysfunction melanoma generic 25 mg nizagara with amex, caused by organisms such as Chlamydia or Neisseria gonorrhoeae (gonorrhea). The diagnosis is made clinically based on the typical history and physical examination. Nearly all patients have cervical motion tenderness, that is, pain with motion and palpation of the cervix. Quinolone antibiotics have been popular in the past; however, increasing bacterial resistance, particularly in Southeast Asia and California, has rendered these agents less desirable. More recently, a family of fluoroquinolones has been produced that contain a fluorine substituent at position 6 and a carboxylic acid moiety in the 3 position of the basic ring structure. R1, R7, and X are substituted with different side chains for the purpose of increasing bioavailability of the compound. The A subunits, which carry out the strand-cutting function of the gyrase, are the site of action of the quinolones. Mutations in gyrA gene that encodes the A subunit of the polypeptide can confer resistance to these drugs. Quinolones inhibit eukaryotic topoisomerase at much higher concentrations (100 to 1000 g/mL). The general structure of chromatin has been found to be remarkably similar in the cells of all eukaryotes. There are five types of histones that are evolutionarily conserved: H1, H2A, H2B, H3, and H4. Eight histone molecules (two each of H2A, H2B, H3, and H4) form an ellipsoid approximately 11 nm long and 6. The question of how the highly ordered nucleosome is formed can be explained by the fact that nucleosome assembly is facilitated by molecular chaperones. The nickingclosing enzyme acts to provide the nucleosome with its preferred level of supercoiling. Six nucleosomes are packed per turn further into a spiral or solenoid to form a regular array of polynucleosomes of 30 nm length. This higher order packaging is one of the most fascinating but also most poorly understood aspects of chromatin. All chromosomes adopt a highly condensed conformation during mitosis and reflect a coarse heterogeneity of chromosome structure. Other complex chromosomal structures found in eukaryotes are in histone-depleted metaphase chromosomes.

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However erectile dysfunction in diabetes type 2 buy nizagara 100 mg mastercard, the most physiologic regimens entail more frequent insulin injections, greater reliance on short-acting insulin, and more frequent capillary plasma glucose measurements. Multiple-component insulin regimens refer to the combination of basal insulin and bolus insulin (preprandial short-acting insulin). Such regimens offer the patient with type 1 diabetes more flexibility in terms of lifestyle and the best chance for achieving near normoglycemia. The insulin aspart, glulisine, or lispro dose is based on individualized algorithms that integrate the preprandial glucose and the anticipated carbohydrate intake. To this insulin dose is added the supplemental or correcting insulin based on the preprandial blood glucose [one formula uses 1 unit of insulin for every 2. For each panel, the y axis shows the amount of insulin effect and the x axis shows the time of day. A multiple-component insulin regimen consisting of longacting insulin (^, one shot of glargine or two shots of detemir) to provide basal insulin coverage and three shots of glulisine, lispro, or insulin aspart to provide glycemic coverage for each meal. Such regimens usually prescribe two-thirds of the total daily insulin dose in the morning (with about two-thirds given as long-acting insulin and one-third as shortacting) and one-third before the evening meal (with approximately one-half given as long-acting insulin and one-half as short-acting). The drawback to such a regimen is that it enforces a rigid schedule on the patient, in terms of daily activity and the content and timing of meals. These sophisticated insulin infusion devices can accurately deliver small doses of insulin (microliters per hour) and have several advantages: (1) multiple basal infusion rates can be programmed to accommodate nocturnal versus daytime basal insulin requirement, (2) basal infusion rates can be altered during periods of exercise, (3) different waveforms of insulin infusion with meal-related bolus allow better matching of insulin depending on meal composition, and (4) programmed algorithms consider prior insulin administration and blood glucose values in calculating the insulin dose. These devices require a health professional with considerable experience with insulin infusion devices and very frequent patient interactions with the diabetes management team. Insulin infusion devices present unique challenges, such as infection at the infusion site, unexplained hyperglycemia because the infusion set becomes obstructed, or diabetic ketoacidosis if the pump becomes disconnected. Efforts to create a closed-loop system in which data from continuous glucose measurement regulates the insulin infusion rate continue. Other Agents That Improve Glucose Control 303 the role of amylin, a 37-amino-acid peptide cosecreted with insulin from pancreatic beta cells, in normal glucose homeostasis is uncertain. Addition of pramlintide produces a modest reduction in the A1C and seems to dampen meal-related glucose excursions. The short-acting insulin given before the meal should initially be reduced to avoid hypoglycemia and then titrated as the effects of the pramlintide become evident. Reduction in cardiovascular risk is of paramount importance as this is the leading cause of mortality in these individuals.

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In older patients erectile dysfunction age 32 purchase discount nizagara line, and in those with some degree of nodular disease or fibrosis, fewer than one-third demonstrate significant shrinkage of the goiter. Exceptions include documented evidence of tracheal compression or obstruction of the thoracic inlet, which are more likely to be associated with substernal multinodular goiters. Subtotal or near-total thyroidectomy for these or cosmetic reasons should be performed by an experienced surgeon to minimize complication rates, which occur in up to 10% of cases. It is rarely associated with transient acute swelling of the thyroid, which is usually inconsequential unless there is severe tracheal narrowing. If not treated with levothyroxine, patients should be followed after radioiodine treatment for the possible development of hypothyroidism. Diagnosis On examination, thyroid architecture is distorted, and multiple nodules of varying size can be appreciated. Because many nodules are deeply embedded in thyroid tissue or reside in posterior or substernal locations, it is not possible to palpate all nodules. Tracheal deviation is common, but compression must usually exceed 70% of the tracheal diameter before there is significant airway compromise. Pulmonary function testing can be used to assess the functional effects of compression and to detect tracheomalacia, which characteristically causes inspiratory stridor. Ultrasonography can be used to identify which nodules should be biopsied, including large, dominant nodules or those with sonographic characteristics suggestive of malignancy. T4 suppression is rarely effective for reducing goiter size and introduces the risk of thyrotoxicosis, particularly if there is underlying autonomy or if it develops during treatment. Contrast agents and other iodine-containing substances should be avoided because of the risk of inducing the Jod-Basedow effect, characterized by enhanced thyroid hormone production by autonomous nodules. Radioiodine is being used with increasing frequency because it often decreases goiter size and may selectively ablate regions of autonomy. Earlier concerns about radiation-induced thyroid swelling and tracheal compression have diminished as recent studies have shown this complication to be rare. As in nontoxic goiters, many nodules are polyclonal, while others are monoclonal and vary in their clonal origins. The T4 level may be normal or minimally increased; T3 is often elevated to a greater degree than T4. Thyroid scan shows heterogeneous uptake with multiple regions of increased and decreased uptake; 24-h uptake of radioiodine may not be increased.

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Neurophysin: A protein that is secreted with oxytocin and vasopressin from the posterior pituitary gland doctor for erectile dysfunction philippines cheap nizagara 25 mg without prescription. Renin: A protease that is synthesized by the juxtaglomerular cells of the kidney and secreted into the bloodstream in response to conditions of hypovolemia and hyponatremia. Vasopressin: Antidiuretic hormone; a nine-amino acid peptide that is synthesized by the hypothalamus and controls resorption of water by distal tubules of the kidney. It stimulates the insertion of water channels (aquaporins) into the apical membranes of kidney tubules. It functions to conserve body water by reducing the output of urine, and thus it is known as an antidiuretic. Vasopressin is synthesized in the supraoptic nucleus of the hypothalamus where it is bound to a neurophysin protein carrier, packaged in granules, and delivered by intracellular transport to nerve terminals in the posterior pituitary. Its secretion is increased by dehydration or stress and decreased after alcohol consumption. Water is resorbed across the renal epithelium into the blood leading to a decrease in plasma osmolarity and an increase in the osmolarity of urine. In the absence of vasopressin, the kidney cannot resorb water and it flows out as urine. This condition can arise from a deficiency in vasopressin secretion from the posterior pituitary as a result of hypothalamic tumors, injury (as in the case of this patient) or infection. The steroid hormone aldosterone, synthesized in the zona glomerulosa of the adrenal cortex, also plays an important role in maintaining blood osmolarity. It binds its receptors in the cytoplasm of epithelial cells of the distal colon and the renal nephron, followed by translocation of the hormone-receptor complex to the nucleus and activation of transcription of ion transport genes to increase Na+ reabsorption and K+ secretion. Renin is a proteolytic enzyme that is released from the kidney in response to sympathetic neuron stimulation, renal artery hypotension, or decreased Na+ delivery to renal distal tubules. These symptoms appeared shortly after the surgery and had never been observed previously. Osmolarity of the urine was below normal, even if liquid consumption was restricted. Damage to the thirst mechanism from surgical trauma, leading to excessive consumption of liquids B. Damage to the pituitary or hypothalamus from surgical trauma, leading to decreased secretion of vasopressin C. Vasopressin, and its analog desmopressin, acts by increasing insertion of aquaporin (water channels) into the renal distal tubule membrane, permitting increased resorption of water from the urinary filtrate. Aldosterone acts independent of vasopressin to increase water resorption by the kidney, by stimulating the insertion of ion transporters into the membrane of distal colon and kidney distal tubule.

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Together erectile dysfunction treatment in rawalpindi buy 50 mg nizagara with mastercard, these reversible conditions account for 25% of delayed puberty in girls. Congenital hypogonadotropic hypogonadism in girls or boys can be caused by mutations in several different genes or combinations of genes (Chap. Family studies suggest that genes identified in association with absent puberty may cause delayed puberty and that there may be a genetic susceptibility to environmental stresses such as diet and exercise. In a study of 5574 English and American women who ultimately conceived, pregnancy occurred in 50% within 3 months, 72% within 6 months, and 85% within 12 months. The infertility rate has remained relatively stable over the past 30 years, although the proportion of couples without children has risen, reflecting a trend to delay childbearing. This trend has important implications because of an age-related decrease in fecundability, which begins at age 35 and decreases markedly after age 40. These investigations include a semen analysis in the male, confirmation of ovulation in the female, and, in the majority of situations, documentation of tubal patency in the female. In some cases, after an extensive workup excluding all male and female factors, a specific cause cannot be identified and infertility may ultimately be classified as unexplained. Infertility can be attributed primarily to male factors in 25% and female factors in 58%, and is unexplained in about 17% of couples. Infertility is invariably associated with psychological stress related not only to the diagnostic and therapeutic procedures themselves but also to repeated cycles of hope and loss associated with each new procedure or cycle of treatment that does not result in the birth of a child. These feelings are often combined with a sense of isolation from friends and family. Counseling and stress-management techniques should be introduced early in the evaluation of infertility. Infertility and its treatment do not appear to be associated with longterm psychological sequelae. A description of the range of investigations that may be required and a brief description of infertility treatment options, including adoption, should be reviewed. Initial investigations are Infertility 14% of reproductive aged women 5 million couples in the U. These disorders, which include ovulatory dysfunction and abnormalities of the uterus or outflow tract, may present as amenorrhea or as irregular or short menstrual cycles.

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The possible sites include subepithelial erectile dysfunction generics nizagara 25 mg order without prescription, intramembranous, subendothelial, and mesangial. In membranoproliferative cases, the complexes are found in a subendothelial location. Acute Diffuse Glomerulonephritis Acute diffuse glomerulonephritis occurs mostly in children and typically follows (1 to 4 weeks) a group A b-hemolytic streptococcal infection. Crescentic Glomerulonephritis In crescentic glomerulonephritis, usually at least 50 percent of the glomeruli are involved. There are focal disruptions of the glomerular basement membrane with formation of crescents. A crescent is defined as at least three layers of cells between the visceral and parietal epithelium. In the pauci-immune type, Wegener granulomatosis and polyarteritis nodosa are the principal examples. Histology shows that the glomeruli are diffusely enlarged with marked intracapillary hypercellularity and lobular accentuation. Additional workup finds hypertension, periorbital edema, and impaired renal function with slightly increased amounts of protein in the urine. A renal biopsy most likely would reveal electron-dense deposits in which of the following sites Crescents within the glomeruli Fibrinoid necrosis of the efferent arterioles Fibromuscular hyperplasia of the afferent arterioles "Spike and dome" appearance of the glomerular basement membrane E. Which of the following types of autoantibodies is most likely to be present in this individual Acute diffuse proliferative glomerulonephritis most commonly presents in children after a group A -hemolytic streptococcal infection; this explains the other name of this disorder: acute poststreptococcal glomerulonephritis. Children develop signs of the nephritic syndrome with hematuria, mild periorbital edema, and increased blood pressure. This disorder is characterized by irregular larger subepithelial (between the basement membrane and epithelial cells) electron-dense deposits. Rapidly progressive glomerulonephritis is characterized histologically by the presence of crescents within glomeruli (crescentic glomerulonephritis). A crescent, which is defined as having at least three layers of cells between the visceral and parietal epithelium, is composed of visceral and parietal epithelial cells, inflammatory cells, and fibrin. Type I rapidly progressive glomerulonephritis is characterized by the finding of linear deposits of IgG and C3 within the glomerular basement membrane using immunofluorescence. Most patients are found to have Goodpasture disease, in which autoantibodies to the glomerular basement membrane are present. The clinical presentation of the various types of glomerulonephritis can be one of the following six: nephritic syndrome, nephrotic syndrome, acute renal failure, chronic renal failure, isolated proteinuria, and isolated hematuria. Renal biopsy is examined by light microscopy, electron microscopy, and immunofluorescence. She also has developed hypertension and has had several bacterial and vaginal yeast infections over the last 10 years. Her two pregnancies were uncomplicated, although she required cesarean deliveries for large babies of 9 lb and 9.

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European and Chinese populations show an order of magnitude higher incidence than persons of African descent erectile dysfunction prevention order nizagara canada. This population specific expression of disease causing alleles may explain the wide range of incidence reported for this disease entity (5 to 350 cases/million live births). Normal conversion of phenylalanine into the amino acid tyrosine catalyzed by phenylalanine hydroxylase. Tyrosine can be further metabolized to produce various neurotransmitters such as dopamine, epinephrine, and norepinephrine. This enzyme, like phenylalanine hydroxylase, requires molecular oxygen and tetrahydrobiopterin. As is the case for phenylalanine hydroxylase, the tyrosine hydroxylase reaction is sensitive to perturbations in dihydropteridine reductase or the biopterin synthesis pathway, anyone of which could lead to interruption of tyrosine hydroxylation, an increase in tyrosine levels, and an increase in transamination of tyrosine to form its cognate -keto acid, para-hydroxyphenylpyruvate, which also would appear in urine as a contributor to phenylketonuria. Ring closure of the alanine portion of dopaquinone forms a pyrrole ring and subsequent reactions give rise to the melanins, the primary dark pigment associated with skin color being eumelanin. Thus in a situation wherein phenylalanine hydroxylase activity is deficient, not only does the -keto cognate transamination product phenylpyruvate increase but so also does the level of phenylalanine. Thus, excess phenylalanine inhibits tyrosinase and melanin formation resulting in hypopigmentation of skin and hair in affected persons. Conversion of tyrosine to dopaquinone by the enzyme tyrosinase, a Cu+2-dependent enzyme in melanocytes. The symptoms are the same so you order a test on phenylalanine hydroxylase to confirm your diagnosis of phenylketonuria. To your surprise the phenylalanine hydroxylase activity is well within the normal range. Tyrosine: -ketoglutarate transaminase Tyrosinase Homogentisic acid oxidase Dihydropteridine reductase Dopamine hydroxylase [38. Excess formation of melanin Excess phenylalanine in the serum and tissues Hyposecretion of melatonin Excessive stimulation of tyrosinase Low levels of para-hydroxyphenylpyruvate Answers [38. The correct response is very low levels of phenylalanine hydroxylase, a key enzyme in the metabolic sequelae of phenylketonuria, that is, elevated phenylalanine, phenylpyruvate, and para-hydroxyphenylpyruvate in blood. Homogentisic acid is an intermediate in the breakdown of tyrosine to fumarate and acetoacetate. Vitamin B12 is required in the metabolism of branched-chain amino acids not phenylalanine. This enzyme reduces dihydrobiopterin to tetrahydrobiopterin the obligate electron donor for phenylalanine hydroxylase.

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Serum lipase levels also rise erectile dysfunction doctor atlanta purchase generic nizagara line, but they remain elevated after the -amylase levels have returned to normal and may take 7 to 10 days to normalize. Most cases (85 to 90 percent) of acute pancreatitis that are caused by gallstones will resolve on their own, and therefore conservative treatment modalities are appropriate. These include pain management with analgesics, administration of intravenous fluids to maintain the intravascular volume and electrolyte balance, as well as removal of oral alimentation to decrease the secretion of pancreatic juice. Nasogastric suction has also been used to decrease gastrin release from the stomach and to eliminate gastric emptying into the duodenum. However, controlled trials have not demonstrated the efficacy of nasogastric suction in the treatment of mild to moderate acute pancreatitis. Amylose, amylopectin, and maltose Glucose, galactose, and fructose Glucose, sucrose, and maltotriose Limit dextrins, maltose, and maltotriose Limit dextrins, lactose, and sucrose [19. A liver biopsy reveals glycogen with an abnormal, amylopectinlike structure with long outer chains. Amylopectin is plant starch that has some (16) branch points, but not as many as normal glycogen. Glycogen, which has an amylopectin-like structure, has fewer branch points than normal glycogen and would be less soluble within the cell. Since the patient did not have any problems while being breast-fed, then the most likely enzyme to be deficient is pancreatic lipase, since gastric lipase is most active on short chain triglycerides, such as those that are found in breast milk. Acute pancreatitis occurs from autodigestion of the acinar cells by inappropriate activation of the pancreatic enzymes (especially trypsinogen) within the cell, leading to cellular injury mediated by proinflammatory cytokines. The three major breakdown products of amylase are maltose, maltotriose, and -dextrins. Enzymes in the brush border of the intestines continue to digest the carbohydrates. On examination she is found to have elevated blood pressure, proteinuria, increased liver function tests, prolonged clotting studies, hyperbilirubinemia, hypofibrinogenemia, and hypoglycemia. A pelvic ultrasound identified a viable intrauterine pregnancy measuring approximately 35-week gestation. After admission, the mother underwent an emergent cesarean delivery, and she subsequently developed a worsening hypoglycemia and coagulopathy and went into hepatic coma with renal failure. After reviewing all the laboratory results and her clinical picture, the patient was diagnosed with acute fatty liver of pregnancy. Cause of hypoglycemia: Decreased liver glycogen after liver undergoes fatty infiltration and subsequent liver failure. Histology reveals swollen hepatocytes in which the cytoplasm is filled with microvesicular fat. Affected patients may become jaundiced or encephalopathic from liver failure, usually reflected by an elevated ammonia level. Management is delivery, with supportive measures such as magnesium sulfate to prevent seizures, replacement of blood or clotting factors, and management of the blood pressure.

Gonzales, 51 years: These benign tumors are found within the major lactiferous ducts, usually near the nipple.

Rozhov, 44 years: This results in defective nuclear maturation and the nuclear chromatin is more finely dispersed than normal and has an open stippled appearance.

Karlen, 59 years: These tumors generally pursue a benign course, with 9­30% associated with metastases.

Vigo, 22 years: The term lentiginous refers to the radial extension of the lesion cells along the epidermal-dermal junction.

Yokian, 35 years: Glioblastoma Multiforme Glioblastoma multiforme is the most common primary intracranial neoplasm in adults, occurring most often in individuals in late middle age and older.

Kliff, 61 years: Hypocalcemia is usually reversed with tissue repair and restoration of renal function as phosphorus and creatinine values return to normal.

Keldron, 26 years: The production of calcitonin is a useful clinical tool for the diagnosis and to follow the postoperative progression of the carcinoma.

Pedar, 62 years: This is in contrast to the glycerol backbone found in lipids such as phospholipids.