Matthew Kiernan DSc, FRACP

• Professor of Medicine ?Neurology, University of New South Wales
• Consultant Neurologist, Prince of Wales Hospital, Sydney, NSW

However pulse pressure variation cheap inderal 40mg visa, the whole inhibition of bone resorption by a bisphosphonate heart attack jack look in my eyes purchase 80 mg inderal otc, at a dose which totally normalizes fasting urinary calcium excretion blood pressure readings chart buy cheap inderal on line, taken as a mirrored image of internet bone resorption arteria mesenterica inferior discount inderal online american express, is related to an roughly 30% decrease, but not a correction of plasma calcium (Rizzoli et al. Thus, the residual hypercalcemia may be attributed to a renal tubular reabsorption effect, which accounts for more than two-thirds of the elevated plasma calcium on this experimental model. Evaluation of bone resorption and renal tubular reabsorption of calcium and phosphate in malignant and nonmalignant hypercalcemia. Granulomatous Disorders Ectopic production of calcitriol is a explanation for hypercalcemia occurring in some malignancies of the hematopoietic system as nicely as in varied ganulomatous illnesses (Kallas et al. In active sarcoidosis, as a lot as 10% of the patients could become hypercalcemic, and even more hypercalciuric. Granuloma macrophages develop an increased activity of 1-alpha-hydroxylase enzyme resulting in larger production and circulating levels of calcitriol, hence to a markedly elevated intestinal absorption of calcium. Immobilization Very quickly after immobilization, there are an increase in bone resorption and an inhibition of bone formation, leading to calcium launch into the extracellular fluid (Stewart et al. Drug-Induced Vitamin D extra as a end result of iatrogenic administration of pharmacological doses of vitamin D is a uncommon reason for hypercalcemia. Large doses used to be given in the therapy of hypoparathyroidism before the availability of active vitamin D metabolites. Vitamin D extra is associated with increased calcium intestinal absorption and bone resorption (Rizzoli et al. Because of the prolonged half-life of the metabolite 25-hydroxyvitamin D, hypercalcemic�hypercalciuric syndrome can persist for several weeks to months, with an necessary morbidity and even permanent gentle tissues damages. Vitamin A intoxication-mediated hypercalcemia is very uncommon and may result from vitamin A supplementation or retinoic acid remedy for numerous problems (Valentic et al. Milk-alkali syndrome encompasses hypercalcemia, metabolic acidosis and renal failure (Orwoll, 1982). It was described in patients with peptic ulcer handled with massive quantities of milk and antacids, corresponding to calcium carbonate. Whilst hypercalcemia is usually corrected with hydration and reduction of calcium intakes, renal function alterations could persist. Mild hypercalcemia has been reported in as many as 5% of lithium-treated patients. Hypercalcemia: Other Causes than Primary Hyperparathyroidism Benign Familial Hypocalciuric Hypercalcemia 165 Various mutations in the calcium sensing receptor have been reported, which account for hyper- or hyposecretion of parathyroid hormone in relation with variations of extracellular calcium focus (Hu and Spiegel, 2003). In familial hypocalciuric benign hypercalcemia, circulating ranges of parathyroid hormone are insufficiently suppressed for the diploma of calcemia, and the renal tubular reabsorption of calcium is elevated through a parathyroid hormone-independent mechanism (Marx et al. This dysfunction appears to be due to mutations related to hypofunction of the cell membrane calcium sensing mechanism (Hannan et al. Interestingly, the same biochemical pattern could be encountered in patients handled with lithium salts (Bendz et al. Calcium sensing receptor exercise may be modulated by calcimimetics, which enhance its sensitivity to extracellular calcium (Marx, 2017). Management of Hypercalcemic Disorders Severe symptomatic hypercalcemia requires speedy intervention since the condition could also be life-threatening. Fluid remedy includes the administration of 2�3 L of isotonic saline over the first 24�48 h, with repeated measurements of plasma electrolytes, particularly potassium, because of the chance of extreme hypokalemia. Plasma calcium decreases not solely by restoring intravascular quantity and correcting thereby the hemoconcentration but additionally by altering proximal tubule calcium hyperreabsorption, which is the consequence of dehydration and quantity contraction (Hosking et al. But their effect is somewhat weak, because the calcium reabsorbed within the ascending limb represents a small fraction of the filtered load. By inflicting acute quantity loss, diuretics may further aggravate the volume contraction dependent hypercalcemia. In the management of hypercalcemia states, the combination of huge saline infusion with high doses of furosemide is of doubtful efficacy to markedly decrease renal tubular reabsorption and may be related to lifethreatening imbalances in electrolytes focus and fluid volumes. Attention must be paid to stop immobilization to avoid further disuse-induced stimulation of bone resorption and impaired bone formation. The subsequent step of remedy requires the correction of the disturbed calcium flux(es): the decrease in internet bone resorption and/or in renal tubular calcium reabsorption. The use of the former should be restricted to very severe hypercalcemia with neurological signs, requiring a fast decrease in calcemia. The most efficacious and used brokers within the administration of nonhyperparathyroid hypercalcemia are certainly the bone resorption inhibitors bisphosphonates (Rizzoli and Bonjour, 1992; Berenson, 2002; Body et al. Pamidronate is given on the dose of ninety mg intravenously in 250�500 mL of saline or 5% dextrose over 2 h. Zoledronate is given at a dose of four mg intravenously in 250 mL saline or 5% dextrose over 30 min. Ibandronate is given on the dose of four mg in 100 mL saline or 5% dextrose over 30 min. In response to intravenous bisphosphonates, calcemia begins to drop by 48 h and attain a nadir by 4 to 5 days. Conclusions the physiology of calcium homeostasis is regulated by coordinated bidirectional calcium fluxes, occurring on the ranges of gut, bone and kidney. These fluxes are influenced by calciotropic peptides or steroid hormones, and by a big selection of domestically produced components. In the management of extracellular calcium concentration, the kidney tubule reabsorptive capability performs a central function. Management of hypercalcemic disorders aside from major hyperparathyroidism, includes the treatment of the hypercalcemia causing disease and normalization of the irregular calcium fluxes. Calcium absorption in rat massive gut in vivo: Availability of dietary calcium. Influence of the disaccharide lactitol on intestinal absorption and physique retention of calcium in rats. Hyperparathyroidism and long-term lithium therapy-A cross-sectional research and the effect of lithium withdrawal. Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. Nature of calcemic impact of 1,25-dihydroxyvitamin D3 in experimental hypoparathyroidism. Naturally occurring mutations of the extracellular Ca2 � -sensing receptor: Implications for its construction and function. Rare causes of calcitriol-mediated hypercalcemia: A case report and literature review. Reversible hypercalcemia and hyperparathyroidism related to lithium remedy: Case report and evaluate of literature. For whom the bell tolls: Distress signals from long-lived osteocytes and the pathogenesis of metabolic bone illnesses. Calcimimetic use in familial hypocalciuric hypercalcemia-A perspective in endocrinology. Familial hypocalciuric hypercalcemia: the relation to major parathyroid hyperplasia. A human myeloma immunoglobulin G binding four moles of calcium related to asymptomatic hypercalcemia. Relation between serum and urinary calcium with specific reference to parathyroid exercise. Effect of thyroparathyroidectomy of calcium metabolism in rats: Role of 1,25-dihydroxyvitamin D3. Effect of hydrochlorothiazide on 1,25-dihydroxyvitamin D3-induced modifications in calcium metabolism in experimental hypoparathyroidism in rats. Role of bone and kidney in parathyroid hormone-related peptide-induced hypercalcemia in rats. Hypercalcemia and hyperosteolysis in vitamin D intoxication: Effects of clodronate remedy. Serum parathyroid hormone-related protein ranges and response to bisphosphonate remedy in hypercalcemia of malignancy. Biochemical evaluation of patients with cancer-associated hypercalcemia: Evidence for humoral and nonhumoral groups. Introduction the existence of a parathyroid hormone associated (or like) protein was first postulated by Albright (1941), while discussing a patient with renal carcinoma, a solitary metastasis and severe hypercalcemia.

Estrogen is thought to have an result on osteoclastogenesis and osteoclast operate by way of its results on native cytokines and progress components (produced by either bone cells or adjacent marrow cells estrogen) arteria gastroduodenalis order inderal 80mg online. In vivo animal studies recommend that blood pressure tool purchase inderal with a visa, because of arrhythmia omega 3 cheap inderal its androgenic structure blood pressure bottom number over 100 cheap inderal 10mg overnight delivery, exemestane could also be extra bone-sparing than letrozole (L�nning et al. The extra sudden and extreme estrogen deprivation, the larger the magnitude of bone loss. Some clinical studies investigated the impression of osteoporosis in scientific fractures. More fractures were noticed in sufferers on anastrozole in contrast with sufferers on tamoxifen. Discussion about the trade -off between high quality of life (Qol) and treatment length, contemplating threat of fracture, osteoporosis management, and cancer-associated threat, is a matter of concern and debate in day by day clinical apply. Non-steroidal anti-androgens monotherapy, although not normal, supplies some degree of bone safety. To consider the effects of anti-androgens on bone well being, Smith and colleagues randomized fifty two prostate cancer sufferers with out bone metastases to obtain Leuprolide or Bicalutamide, a nonsteroidal antiandrogen that competitively binds to androgen receptors. Results showed that bone loss is extra relevant with Leuprolide and instructed a possible protecting impact of Bicalutamide in bone fracture onset (Smith et al. Patients underneath castration for a chronic period of time can have lengthy survival, and the influence of remedy becomes significantly necessary at this stage. Rates of annual bone loss reported in prospective research range from 2% to 8% on the lumbar spine and from 1. Testosterone reduction to castrate levels is associated with a decline in serum estrogens (which outcome from testosterone conversion by peripheral aromatization). Fracture occasions significantly correlate with shorter survival in males with prostate cancer (Brufsky, 2008). By inducing ovarian failure, chemotherapy reduces endogenous estrogens and results in an elevated bone turnover, bone loss, and fracture risk. Small observational trials have confirmed that, regardless of ovarian operate, postmenopausal girls additionally experience chemotherapy-associated bone loss (Robinson et al. Chemotherapy-associated bone loss has been reported in breast most cancers inside 1 yr of initiation of adjuvant chemotherapy (Brufsky, 2008). In postmenopausal ladies, information means that patients receiving adjuvant chemotherapy can lose 1%�10% bone mass within 1 12 months of chemotherapy (Van Poznak, 2017). Risk components for chemotherapy-induced ovarian failure embody age-older premenopausal women are at larger risk�, chemotherapy type-risk associated with alkylating medication, similar to cyclophosphamide, is larger than with taxanes�, genetic elements, and higher doses and longer extent of chemotherapy (Shapiro, 2017; Doo and Shapiro, 2013). Kidney impairment impacts bone health as a outcome of electrolyte disorders, which include acute and persistent hypomagnesaemia. Doxorubicin might additional impair bone health through dose-dependent ovarian failure. Furthermore, in patients with brain major and secondary tumors, glucocorticoids are used to manage neurological signs related to peritumoral edema. Furthermore, maintaining these levels is thought to reduce the risk for hip fractures in aged girls (Brufsky, 2008; Ibrahim et al. However, conventional therapies for osteoporosis administration have been successfully used to date. Dosing and administration route is often totally different for preventive and therapy functions. Calcium and vitamin D serum levels should be corrected, and supplementation should be used even with normal serum levels, as bisphosphonates can cause hypocalcemia. Types of Bisphosphonates (Table 2) � Oral (Clodronate, Alendronate, Risedronate, Ibandronate): Patients should be instructed to take these drugs in an empty stomach, with loads of water and within the upright position. Afterwards, they want to keep upright for an hour time as a result of the restricted oral bioavailability of those medications (0. Oral bisphosphonates can be related to (sometimes severe) esophagitis, constipation, or abdomen discomfort. Alendronate improves bone mass density and reduces the risk of fractures in men with osteoporosis, although conflicting results have been reported for the oral bisphosphonates Alendronate and Risedronate (Ringe et al. Clodronate showed efficacy in bone loss prevention in premenopausal breast most cancers patients with chemotherapy-induced ovarian failure (Saarto et al. Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast most cancers: practical steering for prevention and remedy. Acid (4 mg every 6 months) can forestall adjuvant endocrine therapy-associated bone loss in premenopausal patients. Results showed that endocrine remedy with out Zoledronic acid led to significant (P � zero. Regarding safety concerns, each bisphosphonates and denosumab are well tolerated, although Zoledronic acid is associated with extra acute part reactions and renal dysfunction, and less hypocalcemia episodes. Prevalence of secondary causes of bone loss amongst breast cancer sufferers with osteopenia and osteoporosis. Bisphosphonate risedronate prevents bone loss in ladies with synthetic menopause due to chemotherapy of breast most cancers: A doubleblind, placebo controlled study. Randomized trial of Denosumab in sufferers receiving adjuvant aromatase inhibitors for nonmetastatic breast most cancers. Zoledronic acid prevents most cancers treatment-induced bone loss in premenopausal girls receiving adjuvant endocrine remedy for hormone-responsive breast cancer: A report from the Austrian breast and colorectal cancer examine group. Practical guidance for the management of aromatase inhibitor-associated bone loss. Aromatase inhibitor-associated bone loss in breast cancer sufferers is distinct from postmenopausal osteoporosis. Treatment-induced bone loss and fractures in most cancers sufferers undergoing hormone ablation remedy: Eficacy and security of Denosumab. Effects of exemestane administered for two years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast most cancers. Alendronate therapy of established main osteoporosis in men: 3-year outcomes of a prospective, comparative, two-arm study. A pilot examine of bone density loss in menopausal ladies treated with chemotherapy for most cancers. Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or regionally superior prostate cancer. Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: Effects on bone mineral density and body composition. Estrogen prevents bone loss via estrogen receptor a and induction of Fas ligand in osteoclasts. Van Poznak C (2017) Overview of the use of osteoclast inhibitors in breast most cancers. Short term intermittent intravenous clodronate within the prevention of bone loss related to chemotherapy induced ovarian failure. Efficacy of intravenous zoledronic acid in the prevention and therapy of osteoporosis: A meta-analysis. Pamidronate within the prevention of chemotherapy induced bone loss in premenopausal girls with breast cancer: A randomized managed trial. Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: Practical steering for prevention and therapy. Metastatic most cancers cells residing within the bone marrow alter the functions of boneresorbing (osteoclasts) and bone-forming (osteoblasts) cells (Weilbaecher et al. By disrupting the physiological stability between bone resorption and bone formation, metastatic cells promote skeletal destruction (Weilbaecher et al. Weakened bones due to skeletal metastases can then lead to occurrence of skeletal-related occasions, corresponding to fractures and compression of the spinal twine, bone ache and incapacity, contributing substantially to morbidity and mortality in sufferers with advanced most cancers (Weilbaecher et al. Bone metastasis is a stepwise sequence of occasions that include tumor cell colonization of the bone marrow, development of a most cancers niche, tumor cell interactions with bone cells (osteoclasts, osteoblasts) and release of signals from the resorbed bone matrix that promote skeletal tumor development. Bone Colonization by Tumor Cells Pre-metastatic Niche Experimental research counsel that, even before turning into clinically detectable, primary tumors launch soluble elements into the bloodstream that induce the formation of a tumor growth-favoring microenvironment (called "pre-metastatic niche") in distant organs in order to appeal to tumor cells to these websites (Peinado et al. Exosomes are additionally present in body fluids (blood, urine, saliva, and breast milk) (Vlassov et al. In most cancers, tumor-derived exosomes categorical distinct cell floor receptors (integrins) that are addressing them to particular organs (Hoshino et al. Specifically, tumor-derived exosomal integrins a6b4 and a6b1 are related to lung metastasis, whereas exosomal integrin avb5 is linked to liver metastasis in animals (Hoshino et al. These tumor-derived exosomes are up-taken by organ-specific cells (S100A4positive fibroblasts and Kupffer cells in lungs and liver, respectively), which then produce promigratory and proinflammatory 304 Encyclopedia of Endocrine Diseases, Second Edition, Volume four doi:10.

Experiments in cultured cells have demonstrated that Pax8 can activate transcription of thyroid-specific genes at their chromosomal locus arteria buccalis cheap inderal online american express. It has been demonstrated that in the absence of Pax8 arrhythmia powerpoint presentation cheap 40mg inderal visa, the expression of both Foxe1 and Hhex is strongly reduced within the precursors of follicular cells lower blood pressure quickly for test purchase inderal canada. Pax8 could then have a specific higher position within the regulatory pathway controlling the event of the thyroid hypertension abbreviation buy cheapest inderal. Foxe1 knockout mice show a perinatal lethal phenotype characterised by a severe cleft palate and athyreosis or ectopia of the thyroid. Furthermore, Foxe1 additionally might be implicated within the management of the survival of thyroid cells, as proven by the absence of thyroid in lots of Foxe1 knockout mice. During embryonic life, Hhex is current in the growing thyroid and in a quantity of organs derived from the foregut endoderm. Hhex may then be required to maintain the expression of these transcription factors in the thyroid. Tshr is detected within the creating thyroid after the completion of the migration of the primordium, throughout the same stage at which Tg seems and earlier than the primary evidence of follicular organization within the gland. Inactivating mutations on this receptor cause extreme hypothyroidism throughout postnatal life. These research indicated that Fgf2 and Bmp4 are key players of an evolutionarily conserved mechanism for thyroid specification (Nilsson and Fagman, 2017). This time period signifies an ectopic or hypoplastic thyroid (or both) in addition to the absence of the gland (athyreosis). These results affirm that the merchandise of these genes are required for an accurate thyroid morphogenesis (Table 2). On the contrary, mice carrying solely a practical allele of Titf1 present a really gentle, possible strain-dependent phenotype. The phenotype of the sufferers ranges from mild hypothyroidism to extreme hypoplasia of the thyroid. All sufferers present athyreosis, whereas in mice the absence of Foxe1 causes either athyreosis or defects in thyroid migration. The disease is inherited as an autosomal recessive trait, and the phenotype ranges from asymptomatic hyperthyrotropinemia to congenital hypothyroidism with severe hypoplasia of the thyroid. The different penetrance of the phenotype is most likely going because of the residual mutant receptor exercise (Grasberger and Refetoff, 2017). Most cases have a thyroid gland in situ; athyreosis is described solely in one case (Dimitri et al. The disruption of the Notch sign results in thyroid dysgenesis in zebrafish, suggesting a vital function of Notch pathway in thyroid improvement (Porazzi et al. Functional studies in zebrafish revealed that thyroid migration is disturbed in ntn1a morphant because of lack of correct steering exerted by dysplastic pharyngeal vessels. Recent studies have identified fibroblast progress components (Fgfs) and bone morphogenetic proteins (Bmps) as key players of an evolutionarily conserved mechanism for thyroid specification. However, extra factors required for thyroid anlage specification are still to be recognized. Mutations in genes involved through the initial steps of thyroid morphogenesis could presumably be liable for thyroid agenesis. Functional zebrafish studies primarily based on human genotyping point to netrin-1 as a link between aberrant cardiovascular improvement and thyroid dysgenesis. Pax8, a murine paired field gene expressed in the developing excretory system and thyroid gland. Hex: A homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors. A distinctive mixture of transcription components controls differentiation of thyroid cells. The T/ebp null mouse: Thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. The homeobox gene Hex is required in definitive endodermal tissues for regular forebrain, liver, and thyroid formation. Role of the thyroid-stimulating hormone receptor signaling in growth and differentiation of the thyroid gland. Proceedings of the National Academy of Sciences of the United States of America ninety nine, 5462�5467. Development of the thyroid gland: Lessons from congenitally hypothyroid mice and men. Glossary Chaperones Proteins that assist the noncovalent folding or unfolding and the meeting or disassembly of other macromolecular constructions. Circadian rhythm Physiological exercise that happens roughly every 24 h, or the rhythm of such activity. Deiodinase Enzymes containing selenium, within the form of the amino acid selenocysteine, and important within the activation and deactivation of thyroid hormones. Glycoprotein hormones Family of glycosylated, cysteinerich proteins consisting of an alpha and beta subunit. G-proteins Family of proteins involved in transmitting indicators from a big selection of totally different stimuli outside a cell into the within of the cell. Hypothalamus Region of the diencephalon on the base of the mind by which specialized nerve cells originate and produce neuropeptides that regulate the secretion of hormones from the pituitary gland. N-glycosylation the addition of sugar chains at the amide nitrogen on the aspect chain of asparagine. O-glycosylation the addition of sugar chains on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, serine, or threonine. Pituitary Small gland, the hypophysis cerebri, connected to the base of the brain by a stalk and positioned in a depression within the sphenoid bone (the sella turcica). Thyroxine (T4) 3,5,30,50-Tetraiodothyronine, the major hormonal product of the thyroid gland, formed by the coupling of two diiodotyrosine residues within the thyroglobulin molecule. The first findings of a attainable relationship between the pituitary and the thyroid was described greater than one hundred fifty years ago from Niepce but only in the center of the last century it was attainable to isolate the first thyrotropin-releasing factor from porcine hypothalamus (Schally et al. Indeed, thyroid hormones 398 Encyclopedia of Endocrine Diseases, Second Edition, Volume 4 doi:10. It is mainly expressed within the anterior pituitary, in neuroendocrine brain areas, within the autonomic nervous system, and in the brainstem. These latter stabilize the construction of each subunit that can be displayed in a "Y" shape, formed by three loops: loop 1 and three are parallel to one finish of the subunit, and loop 2 extends on the other end. The heterodimer is than fashioned by the 2 subunits which might be hinged head to tail and considerably back to back forming a protein barely curved with loops alpha 1, alpha three, and beta 2 at one end and loops beta 1, beta 3, and alpha 2 on the different finish. The beta subunit of glycoprotein hormones in then characterized by an extended C-terminal end after loop 3, that may make the so called "determinant loop. The glycoprotein hormones are characterized by varied N-glycosylation sites and certainly the carbohydrate residues represent round 20% and 10% respectively of the alpha and beta subunit molecular weights. A supplementary O-glycosylation website can be positioned on the free alpha subunit (Shupnik et al. The signal peptide permits the translocation of each alpha and beta precursors throughout the membrane of the rough endoplasmic reticulum the place the cleavage of the signal peptide and the glycosylation of some asparagine residues happen. These precursors, which are rich in mannose, are preassembled in the rough endoplasmic reticulum in conjunction with a dolichol phosphate provider and then moved to the glycosylation websites. The glycosylation course of plays a key function in permitting the proper folding of the two subunits in forming the heterodimer. Glycoprotein are maintained within the rough endoplasmic reticulum until the top of the method by chaperone molecules, and then, heterodimers move to the following compartment for the posttranslational modifications leading to the formation of advanced oligosaccharide chains. O-glycosylation of alpha subunit extra takes place in the proximal Golgi compartment, whereas sialylation and sulfation processes of the oligosaccharide complex within the Golgi distal compartment. On the opposite, thyroid hormones act both on the hypothalamus and pituitary with a unfavorable feedback mechanism. On the opposite, the infusion of excessive doses of dopamine for a chronic interval might cause central hypothyroidism. A novel mechanism for isolated central hypothyroidism: Inactivating mutations in the thyrotropin-releasing hormone receptor gene. Thyrotropin-releasing hormone and its receptors, a hypothesis for binding and receptor activation. Novel insights into the molecular mechanisms of human thyrotropin motion: Structural, physiological, and therapeutic implications for the glycoprotein hormone household.

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References

• Krendel DA, Gilchrist JM, Johnson AO, Bossen EH. Isolated deficiency of vitamin E with progressive neurologic deterioration. Neurology. 1987;37:538-540.
• Thabut G, Dauriat G, Stern JB, et al. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. Chest 2005; 127: 1531-1536.
• Lie JT: Cholesterol atheromatous embolism. The great masquerader revisited, Pathol Annu 27(Pt 2):17-50, 1992.
• Zhao B, Schwartz LH, Jiang L, et al. Shape-constraint region-growing for delineation of hepatic metastases on contrast-enhanced CT scans. Invest Radiol. 2006;41(10):753-762.
• Graham DY, Go MNF, Lew GM, et al: Helicobacter pylori infection and exaggerated gastrin release. Effects of inflammation and progastrin processing. Scand J Gastroenterol 28:690, 1993.
• Brereton RJ, Philp N, Buyukpamukcu N: Rupture of the urinary bladder in children. The importance of the double lesion, Br J Urol 52(1):15n20, 1980.
• Palusinski R, Barud W. Proscar and Propecia - a therapeutic perspective. Clin Endocrinol Metab 2004;89:6358-9.
• Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010;363(14):1324-1334.