Vitamin D: a pleiotropic hormone.
Kidney Int. 2010 Feb 24;
Authors: Verstuyf A, Carmeliet G, Bouillon R, Mathieu C
The secosteroid hormone 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is the natural ligand for the vitamin D receptor, a member of the nuclear receptor superfamily. Upon binding of the ligand, the vitamin D receptor heterodimerizes with the retinoid X receptor and binds to vitamin D response elements in the promoter region of target genes to induce/repress their expression. The target genes that have been identified so far are heterogeneous in nature and reflect the great spectrum of biological activities of 1,25(OH)(2)D(3). Within the last two decades, the receptor has been shown to be present not only in classical target tissues such as bone, kidney, and intestine, but also in many other nonclassical tissues, for example, in the immune system (T and B cells, macrophages, and monocytes), in the reproductive system (uterus, testis, ovary, prostate, placenta, and mammary glands), in the endocrine system (pancreas, pituitary, thyroid, and adrenal cortex), in muscles (skeletal, smooth, and heart muscles), and in brain, skin, and liver. Besides the almost universal presence of vitamin D receptors, different cell types (for example, keratinocytes, monocytes, bone, placenta) are capable of metabolizing 25-hydroxyvitamin D(3) to 1,25(OH)(2)D(3) by the enzyme 25(OH)D(3)-1alpha-hydroxylase, encoded by CYP27B1. The combined presence of CYP27B1 and the specific receptor in several tissues introduced the idea of a paracrine/autocrine role for 1,25(OH)(2)D(3). Moreover, it has been demonstrated that 1,25(OH)(2)D(3) can induce differentiation and inhibit proliferation of normal and malignant cells. Moreover, vitamin D deficiency is associated with an increased risk for nearly all major human diseases such as cancer, autoimmune diseases, cardiovascular, and metabolic diseases. In addition to the treatment of bone disorders with 1,25(OH)(2)D(3), these newly discovered functions open perspectives for the use of 1,25(OH)(2)D(3) as an immune modulator (for example, for the treatment of autoimmune diseases or prevention of graft rejection), inhibitor of cell proliferation, and inducer of cell differentiation (cancer).Kidney International advance online publication, 24 February 2010; doi:10.1038/ki.2010.17.
PMID: 20182414 [PubMed - as supplied by publisher]
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Vitamin D: a pleiotropic hormone.
Noninfectious penile lesions.
Am Fam Physician. 2010 Jan 15;81(2):167-74
Authors: Teichman JM, Sea J, Thompson IM, Elston DM
Family physicians commonly diagnose and manage penile cutaneous lesions. Noninfectious lesions may be classified as inflammatory and papulosquamous (e.g., psoriasis, lichen sclerosus, angiokeratomas, lichen nitidus, lichen planus), or as neoplastic (e.g., carcinoma in situ, invasive squamous cell carcinoma). The clinical presentation and appearance of the lesions guide the diagnosis. Psoriasis presents as red or salmon-colored plaques with overlying scales, often with systemic lesions. Lichen sclerosus presents as a phimotic, hypopigmented prepuce or glans penis with a cellophane-like texture. Angiokeratomas are typically asymptomatic, well-circumscribed, red or blue papules, whereas lichen nitidus usually produces asymptomatic pinhead-sized, hypopigmented papules. The lesions of lichen planus are pruritic, violaceous, polygonal papules that are typically systemic. Carcinoma in situ should be suspected if the patient has velvety red or keratotic plaques of the glans penis or prepuce, whereas invasive squamous cell carcinoma presents as a painless lump, ulcer, or fungating irregular mass. Some benign lesions, such as psoriasis and lichen planus, can mimic carcinoma in situ or squamous cell carcinoma. Biopsy is indicated if the diagnosis is in doubt or neoplasm cannot be excluded. The management of benign penile lesions usually involves observation or topical corticosteroids; however, neoplastic lesions generally require surgery.
PMID: 20082512 [PubMed - indexed for MEDLINE]
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Fever of unknown origin: a diagnostic approach to this vexing problem.
Clin Pediatr (Phila). 2010 Apr;49(3):207-13
Authors: Tolan RW
Fever is a common complaint leading families to seek medical attention. Its routine management is the bread and butter of pediatric practice. When fever is seen as prolonged beyond the expected time course (eg, 10 days for a presumed viral respiratory tract infection or 3 weeks for mononucleosis), concern for fever of unknown origin (FUO) may ensue. This diagnosis is among the most challenging for health care providers to approach and often involves referral to subspecialists. Generally, the pace of the evaluation should be guided by the severity of the disease, rather than the anxiety of the family or of the health care providers. It is useful to recognize that uncommon manifestations of common diseases are more likely than are rare diseases. Furthermore, clues to the diagnosis are frequently present in the history and physical examination but are not elicited or unappreciated (perhaps due to time constraints). Therefore, thoroughness and repetition are vitally important. Although the differential diagnosis of FUO is vast, a thoughtful, focused approach based on information gleaned from a thorough history and physical examination (together with any laboratory or other study results) is preferable to a “shotgun” or “running the list” one. Finally, FUO in special populations, including children in the hospital, those with HIV infection or other immunocompromise, and those in the developing world, require special consideration. Most children do well, compared to adults with FUO, but true FUO is not always a benign condition, necessitating the best care a health care provider can offer.
PMID: 20164070 [PubMed - in process]
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