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Indirect evidence in responsive tissues such as the prostate protonix 40mg free shipping diet gastritis kronis, breast 40 mg protonix for sale chronic gastritis food allergy, endometri- support of this hypothesis includes the finding of andro- um and ovary purchase 40 mg protonix free shipping gastritis symptoms baby. Evidence exists for the importance of these gen receptors in the outer root sheath of sebaceous folli- autocrine and paracrine effects of androgens and growth cles, the clinical observation that antiandrogens may factors in the regulation of sebaceous glands. In addition reduce follicular casts and the finding of activity of andro- to androgen receptors, sebocytes also possess receptors for gen-metabolizing enzymes such as 3ß-HSD, 17ß-HSD growth factors such as epidermal growth factor (EGF) and and 5·-reductase in follicles. Furthermore, the activity of insulin-like growth factor I (IGF-I). Evidence exists 17ß-HSD and 5·-reductase is significantly greater in for the role of EGF, IGF-I and keratinocyte growth factor infrainfundibular keratinocytes compared to keratino- (KGF) in modulating sebaceous gland growth. For exam- cytes obtained from the interfollicular epidermis, suggest- ple, growth of sebocytes is enhanced by supplementation ing that follicular keratinocytes have a greater propensity of cell culture medium with EGF and insulin. Direct evidence in sup- of experimental animals with KGF stimulates growth of port of the effects of androgens on follicular keratiniza- hair and sebaceous glands [34, 35]. Mechanism of Androgen Action in Acne Several important enzymes involved in lipid metabo- Androgens are thought to stimulate the growth and dif- lism have been identified in sebaceous glands. These ferentiation (sebum production) of sebaceous glands. The include 3-hydroxy-3-methylglutaryl-coenzyme A (HMG- exact mechanism by which this is accomplished has not CoA) reductase which is the rate-limiting enzyme in the been defined. Androgens such as testosterone and DHT synthesis of cholesterol and acetyl CoA carboxylase which form complexes with nuclear androgen receptors. The is the key in the synthesis of fatty acids. Whether or androgen/receptor complex then interacts with DNA in not androgens act by stimulating these enzymes remains the nuclei of sebaceous cells to regulate genes involved in to be determined. The exact target genes In summary, there is strong clinical and experimental have not been identified, but likely candidates would evidence that androgens stimulate the proliferation of include genes for various growth factors or enzymes sebaceous glands and sebum secretion. Acne is associated involved in lipid production (lipogenic enzymes) (ta- with systemic circulating hyperandrogenism. Acne subjects with 60 Dermatology 2003;206:57–67 Thiboutot/Chen Fig. This 28- patient developed acne and hirsutism as a result of an androgen- year-old patient had recalcitrant acne and an elevated serum testos- producing tumor of the adrenal gland. As in the case of persensitive’ to androgens either due to an increased androgens, it is not known if circulating estrogens or local- number of androgen receptors or abnormal postbinding ly-produced estrogens are important in modulating se- response [37, 38]. Estrogens may act by several mechanisms, they may: (1) directly oppose the effects of androgens locally within the sebaceous gland; (2) inhibit the produc- Estrogens and Sebum Production tion of androgens by gonadal tissue via a negative feed- back loop on pituitary gonadotrophin release; (3) regulate Very little is known about the role of estrogens in genes that negatively influence sebaceous gland growth or modulating sebum production. It is important to note, however, that the temically in sufficient amounts will decrease sebum pro- expression of estrogen receptors in the sebaceous gland is duction. The dose of estrogen required to suppress sebum not well defined [41–43]. Furthermore, if high circulating production however is greater than the dose required to levels of estrogen antagonized androgen effects, it would suppress ovulation. Although some patients acne will become difficult to explain the exacerbation of acne that respond well to lower-dose agents containing 0. The major active estrogen is estra- Growth Hormone, Prolactin and Acne diol which is produced from testosterone by the action of the enzyme aromatase. Aromatase is active in the ovary, Growth hormone is secreted by the pituitary gland. Estradiol can acts on the liver and peripheral tissues to stimulate the be converted to the less potent estrogen, estrone by the production of insulin-like growth factors (IGFs) formerly action of the 17ß-HSD enzyme. There are two forms of IGF, Update and Future of Hormonal Therapy Dermatology 2003;206:57–67 61 in Acne termed IGF-1 and IGF-2. IGF-1 is the more prevalent continue oral contraceptives 4–6 weeks prior to the endo- growth factor. It has been hypothesized that growth hor- crine evaluation.

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An average woman acquires 98% of her total skeletal bone mass by about age 20 and can lose up to 20% of her bone mass in the first 5 years after menopause discount protonix 40mg amex gastritis operation. The best defense against developing osteoporosis in later life is to build strong bones during childhood and early adulthood by taking a balanced diet rich in calcium and vitamin D generic protonix 20mg overnight delivery gastritis diet ketosis, fol- lowing a healthy lifestyle with no smoking effective 40 mg protonix gastritis diet , and performing regular weight-bearing exercise. Significant risk of osteoporosis has been reported in people of all ethnic backgrounds, but it is more common among whites and Asians, and white women after age 65 are twice as likely as African- American women to get fractures. Specialized bone density tests can detect osteoporosis before a frac- ture occurs, and can also predict your chances of bone fracture in the future. Tests conducted at appropriate intervals can measure rate of bone loss and monitor treatment benefit. People over 50 years of age have an average 1 in 4 chance of dying in the year following a hip fracture, and among those who survive there is 1 in 4 chance that they will require long-term care afterward. A woman’s risk of hip fracture is equal to her combined risk of breast, uterine, and ovarian cancer. Osteoporosis is often thought of a disease of old people, or women past the age of menopause. Drug therapy for osteoporosis Bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) are very helpful, and are more widely used than treatment with calcitonin (Miacalcin). Calcium tablets may be needed if the calcium intake in your diet needs to be supple- mented. For women after the menopause the female hormone estrogen helps to prevent or slow down osteoporosis. Brand names include Premarin (with- out progesterone), Prempro (with progesterone), Estratab (esterified estrogen), and others. Raloxi- fene (Evista) is the first in a new class of drugs called selective estrogen receptor molecules (SERMs) that slow bone loss like estrogens do, but without some of estrogen’s untoward effects on the breast and uterus. Therefore, raloxifen can be an alernative choice for women at increased risk for cancer of the breast or uterus. However, like estro- gens, it is associated with increased risk of blood clots and stroke. Spinal fracture in AS Recent studies indicate that osteoporosis can also occur in many people with AS in early stages of thefacts 67 AS-09(65-70) 5/29/02 5:50 PM Page 68 Ankylosing spondylitis: the facts their disease. It can be a result of inflammation in the early stages of AS, as well as a result of immobil- ity in the later stages of the disease. In advanced AS the spine usually has a low bone mass, i. This structural deterioration, along with immobility due to bony fusion, makes the spine fragile and very susceptible to fracture. People with AS are five times more likely to get spinal fractures than the general population. These fractures may follow a relatively minor trauma, especially in people with long-standing AS that has resulted in a fused spine. They usually affect the lower neck (cervical spine). The two commonest causes are falls and motor vehicle accidents. The pain associated with spinal fractures may be overlooked, or wrongly attributed to exacerbation of the underlying AS. The best early clues to spinal fracture may be an acute or unexplained episode of back pain, even in the absence of a history of physi- cal injury, that is aggravated by movement and may sometimes be associated with localized spinal ten- derness. There may be neurological signs and symptoms as a result of the fracture. The displaced ends of the fractured cervical spine (neck) compressing the spinal cord may cause quadriplegia (weakness or paralysis of all four limbs), the most dreaded compli- cation of AS. Isolated or multiple vertebral com- pression fractures without displacement may also occur. If you have a fused spine it is wise to carry a suitable personalized information card. The card should state that your spine, including your neck, is fused as a result of AS, and that you are therefore 68 thefacts AS-09(65-70) 5/29/02 5:50 PM Page 69 Some later manifestations much more prone to spinal fracture due to any fall or motor vehicle accident, even after a relatively trivial injury. The card should include your name, address, and phone number, a photograph (includ- ing a picture showing the spinal deformity), your blood group type, a list of medicines you are taking, any allergy history, and contact details of your doctor. Inflammation of the discs in the back (spondy- lodiscitis) may sometimes occur without any physi- cal trauma or infection.

Risk factors for their development include wound tension protonix 40 mg on line gastritis diet 50, ear piercing cheap 20mg protonix with amex gastritis erosive diet, healing by second intention protonix 40 mg mastercard gastritis diet 2, young age, and deep laceration. Intralesional steroids admin- istered at doses of 10 to 40 mg/ml every month for up to 6 months have been shown to effectively flatten keloids, although several side effects may occur. Cryotherapy given as a 30-second application once a month for 3 months has been found to be a safe and effec- tive treatment. A 16-year-old female patient comes to your office complaining of acne, which she has had for 3 years. The lesions have been small in size, not painful, and not swollen, and they have not progressed over this period. She says the acne is bothering her, and she would like to be treated. On physical examination, the patient is found to have multiple comedones measuring 0. Which of the following is the most appropriate treatment for this patient? Educate the patient about diet and about trying to avoid chocolate and fatty meals B. Start oral contraceptives Key Concept/Objective: To know the appropriate treatment of comedonal acne Comedones consist of keratinized cells and sebum. Comedonal acne consists of a pre- dominance of open and closed comedones, without inflammatory findings such as ery- thematous papules, pustules, nodules, or cysts. The treatment for this form of acne should be directed toward improving the abnormal follicular keratinization process. The best option is topical retinoids, such as tretinoin or adapalene. Also, comedolytic agents such as salicylic acid may be used. Oral agents are not indicated in this mild and noninflam- matory form of the disease. There is no role for dietary change in the management of acne. Oral contraceptives can be beneficial for patients with acne; these agents are ideal in women who are seeking birth control methods and in women who are not candidates for or have not responded to other treatments. A 23-year-old man has a 5-year history of severe acne with scarring. He has been treated in the past with multiple courses of topical agents, including retinoids, benzoyl, topical antibiotics, and oral antibiotics for 1 year. His lesions have not improved sig- nificantly through these agents. On physical examination, the patient has multiple large cysts and abscesses that are confluent and form sinus tracts. Which of the following options are indicated in the management of this patient? Change the oral antibiotic being used, because the presence of a resist- ant organism is very likely B. Refer to a physician who is authorized to administer oral isotretinoin to consider starting this therapy C. Perform a fungal culture of the lesions to exclude Malassezia folliculitis E. Reassure the patient that acne is a disease of adolescents and that his symptoms should improve in the next few months Key Concept/Objective: To know the indications for oral isotretinoin Acne conglobata is a severe, scarring form of acne, with cysts, abscesses, and sinus tracts. This form of acne responds poorly to topical agents or oral antibiotics alone. Intralesional injections of corticosteroids and drainage of the abscesses are temporarily helpful, but these patients usually need oral isotretinoin for lasting improvement.

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