By R. Bernado. University of Mary Hardin-Baylor.

Otherwise 100 mg clomiphene, she is in good health cheap 100 mg clomiphene with visa, and she exercises regularly discount 25mg clomiphene overnight delivery. Her main concern today is her risk of 14 BOARD REVIEW breast cancer generic 100mg clomiphene visa. She has a close friend who was recently diagnosed with breast cancer, and she is now very worried that she might one day get it. Which of the following statements regarding the risk factors for breast cancer is true? Because of germline mutations of either BRCA1 or BRCA2, the breast- ovarian cancer syndrome is inherited in an autosomal recessive fashion B. Reproductive risk factors include late menarche, early menopause, and increasing parity C. The diagnosis of breast cancer in first-degree relatives younger than 50 years is associated with a threefold to fourfold increased risk D. Women between the ages of 40 and 50 years are at greatest risk; 75% of all breast cancers are diagnosed in that age group Key Concept/Objective: To understand the risk factors for breast cancer In first-degree relatives younger than 50 years, the diagnosis of breast cancer is associated with a threefold to fourfold increased risk. Several familial breast cancer syndromes and their associated molecular abnormalities have been identified. These include the breast- ovarian cancer syndrome, which is attributed to germline mutations in either of two breast cancer susceptibility genes, BRCA1 and BRCA2. These mutations are inherited in an autosomal dominant fashion and can therefore be transmitted through both the maternal and the paternal lines. Reproductive risk factors include early menarche, late menopause, late first pregnancy, and nulliparity. All are felt to lead to a condition of prolonged estro- gen exposure to the breast. On clinical examination, a 54-year-old woman is noted to have a nontender mass in the upper outer quadrant of her left breast. There are no overlying skin changes, and there is no palpable adenopathy in the axilla. You immediately set up an appointment for mammography, but your patient is obviously disturbed. She has several questions regarding the therapy for breast cancer. Which of the following statements regarding breast cancer therapy is true? For women with stage I or II breast cancer, the survival rate with breast conservation therapy involving lumpectomy and radiotherapy is identical to the survival rate with modified radical mastectomy B. Sentinel lymph node mapping is difficult to perform and offers no benefit to axillary lymph node dissection C. The benefit of tamoxifen is limited to 5 years, and therefore, the rec- ommendation is to discontinue therapy after 5 years D. Aromatase inhibitors offer a viable alternative to tamoxifen therapy for premenopausal women Key Concept/Objective: To understand the basic principles of breast cancer therapy Breast conservation therapy that involves lumpectomy with radiotherapy and modified radical mastectomy that involves removal of the breast and axillary nodes provide identi- cal survival rates for women with stage I or II breast cancer. Sentinel lymph node mapping involves injection of a radioactive tracer, vital blue dye, or both into the area around the primary breast tumor. The injected substance tracks rapidly to the dominant axillary lymph node—the so-called sentinel lymph node. This node can be located by use of a small axillary incision and visual inspection or by use of a handheld counter. If the sentinel node is tumor free, the remaining lymph nodes are likely to be tumor free as well, and further axillary surgery can be avoided. The benefit of tamoxifen increases with the duration of treatment; the proportional reductions in 10-year recurrence and mortality were 47% and 26%, respectively, with 5-year regimens of tamoxifen therapy. The aromatase inhibitors specifically inhibit this conversion, leading to further estrogen deprivation in older women.

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Acne lesions beginning before puberty increases the risk of severe acne and often isotretinoin is necessary to obtain control of the acne lesions clomiphene 50 mg discount. At the beginning buy clomiphene 50mg with mastercard, reten- Facial Acne in Adults tional lesions are predominant best clomiphene 100mg. There are few studies about the prevalence and speci- Other Factors Known to Influence Acne ficities of facial acne in the adult population buy clomiphene 100 mg mastercard. Several stud- Cigarette Smoking ies have been reported recently: A recent study indicates that acne is more frequent in In England, 749 employees of a hospital, a universi- smokers. This work has been performed among 891 ty and a large manufacturing firm in Leeds, older than 25 citizens in Hamburg (age 1–87 years; median: 42). Facial acne was recorded in 231 maximum frequency of acne lesions was noted between women and 130 men giving an overall prevalence of 54% 14 and 29 years. It was mainly ‘physiological smokers and among them 40. The majority believed that there was no effec- of acne is obtained by the association of three factors: tive therapy for acne. In Australia, 1,457 subjects from central Victoria aged 620 years were examined. There An evaluation of the difference in acne according to was a clear decrease with age from 42% in the age group skin color has been performed at the Skin Color Center in 20–29 years to 1. This study has been performed among 313 classified as mild in 81. Less than 20% were using a treatment on the between the acne group and the non-acne group for poor advice of a medical practitioner. The features of acne in adult women: quality of life assessed by a self-administered French – A postal survey was sent to 173 adult pre-menopausal translation of the DLQI was moderately impaired and women treated for acne between 1988 and 1996 in the more in the ‘clinical acne’ group. Acne was reported to be persistent in 80% of the women This study confirms that acne in the adult female is and 58% of them had an ongoing need for treatment. A high percentage this selected population, acne in adult women was partic- starts during adulthood without any acne during adoles- ularly persistent and desperately recurring. In all studies, few adult females – Another survey investigated the effect of the menstrual had sought out medical treatment. The reasons varied: cycle on acne in 400 women aged 12–52 years: 44% they were not bothered by their acne; they thought that had premenstrual flare. Women older than 33 years had a their acne would clear spontaneously, or they believed 53% rate of premenstrual flare. The above-mentioned that there was no effective therapy. In our study, among study noted a premenstrual flare in 83% of the adult women in the acne group who received some form of women with acne. We have conducted an epidemiological study of acne Topical treatment is often irritating. Our study shows that in adult females in France. A self-administered ques- women with acne had sensitive skin. The management of tionnaire was sent to 4,000 adult women aged 25–40 years acne in the adult female is difficult. Oral therapies are not representative of the French population. Three dermato- very effective and the acne is desperately recurring. A definition of acne cal therapy is not well tolerated. A total of 3,394 women completed the questionnaire of which 3,305 were useable. In 17% of the cases, it was ‘clinical acne’ – with 6. A pre- menstrual flare was recorded in 78% of women with ‘clin- ical acne’.

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Most patients with peripheral vascular atherosclerosis also have coronary atheroscle- rosis purchase 25mg clomiphene mastercard; mortality in patients with peripheral vascular disease is usually caused by myocar- dial infarction or stroke clomiphene 25 mg overnight delivery. This patient’s risk of myocardial infarction far outweighs her risk of developing limb ischemia or of requiring limb amputation generic 25mg clomiphene free shipping. Although the risk of lung cancer is 10-fold higher in cigarette smokers than in nonsmokers buy cheap clomiphene 25mg on-line, this patient is less still likely to develop lung cancer than myocardial infarction: annual deaths from myocardial infarction attributable to smoking are estimated at 170,000, whereas deaths from lung can- cer that are attributable to smoking number 100,000. Moreover, this patient’s coronary risk factors would place her more at risk than would be indicated by these statistics. Because this patient does not use hypoglycemic agents, she is unlikely to experience hypoglycemia. Although 2% to 4% of patients with intermittent claudication develop critical limb ischemia annually, death and morbidity from myocardial infarction are much more like- ly. A 45-year-old woman is receiving enoxaparin and warfarin for deep vein thrombosis (DVT) of the right thigh, which developed after she underwent an abdominal hysterectomy 3 weeks ago. On day 5 of treat- ment, she reports abrupt onset of pain in her left leg. On examination, her blood pressure is 150/90 mm Hg; she has a regular heart rate of 95 beats/min without murmur; and she has lower extremity petechiae. Her left foot is pale, pulseless, and cold, and there is an absence of sensation. Results of laboratory testing are as follows: prothrombin time, 45; INR for prothrombin time, 2. Which of the following changes in this patient’s medication regimen should be made next? Discontinue warfarin therapy Key Concept/Objective: To be able to recognize heparin-induced thrombocytopenia and associat- ed acute arterial thrombosis and to understand that heparin must be discontinued immediately in patients with this condition This patient is experiencing an acute arterial occlusion. Given her heparin use and her low platelet count, heparin-induced thrombocytopenia is the likely diagnosis. Discontinuance of heparin therapy as soon as possible is key in reversing this antibody-mediated process. Increasing the heparin dose or even continued exposure to low doses of heparin (as through heparin I. Although therapy with catheter-directed tissue plasminogen activator (t-PA) is used for acute arterial occlusion in many cases, this patient’s recent abdominal surgery is an absolute contraindication to t-PA therapy. This patient’s low platelet count and her use of oral warfarin are relative contraindications to the use of thrombolytic ther- apy. She needs continued anticoagulation for her DVT and new arterial thrombus; there- fore, warfarin should be continued at its currently therapeutic dosage. A 44-year-old man presents to your office complaining of right leg pain and swelling of 3 days’ duration. The patient was well until he had a wreck while riding his dirt bike 1 week ago. The patient states that 46 BOARD REVIEW he injured his right leg in this accident. Initially, his leg was moderately sore on weight bearing, but swelling and persistent pain have now developed. On physical examination, you note an extensive bruise on the patient’s right calf and 2+ edema from the foot to the midthigh. You suspect trauma-asso- ciated deep vein thrombosis (DVT). Which of the following statements regarding DVT is true? Thrombi confined to the calf are large and typically result in pul- monary venous thromboembolism (VTE) ❏ B.

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It is also well known that leaflet passive distension may activate lymph flow within collectors purchase clomiphene 50 mg online. Besides cheap 25mg clomiphene with mastercard, there are indications that an externally induced (through manual lymphatic 1 drainage and Endermologie techniques) or internally induced (through pressure increases) passive distension of lymphatic vessels increases the speed of the lymphatic flow buy clomiphene 25mg cheap. Such activity releases and drains a great amount of water from tissues and buy generic clomiphene 100mg line, mainly, a substantial amount of proteins. Intense body exercise increases the amount of tissue water and proteins transported from the lymphatic system, as long as they are free and functional, particularly at the ingu- inal and paraaortic nodes. Clinical observations and recent research have shown that—in the case of pathologies characterized by lymphedema—there is something else besides lymphatic vessel damage. An hypothesis is developing in which the autonomic nervous system and fibroblast contrac- tility play a relevant role in the formation of lymphedema in addition to adipocyte activity. VARIATIONS IN LYMPH The amount of lymph may increase and stagnate as a consequence of an increase in mean capillary pressure, due either to variations in permeability or osmotic gradients or to peri- pheral venous pathologies. Cases were reported where tissue hypoxia initially increased the lymphatic flow and was later followed by stagnation and a concomitant increase in interstitial pressure. In fact, it is well known that individuals with intestinal absorption disorders, espe- cially those involving flora alterations of the putrefying–fermentative type, show liquid retention and a decrease in peripheral lymphatic flow. Although this may be partially attributed to a cleansing deficit in kidney and liver efferent vessels, it is more likely due to compositional alterations of the interstitial liquid involving lipoprotein excess on the thematic side derived from a toxic-induced peripheral metabolic blocking of the ‘‘interstitial tissue–lymphatic tissue–adipocyte’’ cycle. Tissue acidification and, in some cases, even a bacterial component belonging to the Streptococci family have been detected. It seems, then, that there are important relationships between the time during which lymph is formed and the metabolic life of adipocytes: when water from the interstitial matrix is available, it may be either included in the lymph or used for metabolic processes. The existence of a ‘‘lymph adipose system’’ might be hypothesized to explain the main peripheral metabolic processes in tissues. Such a system would be represented mainly by the subcutaneous tissue, the mesenterium, and perivascular tissues. THE FIBROBLAST AND THE INTERSTITIAL MATRIX The connective tissue includes the dermis and the subcutaneous tissue, which are made up of three main elements: fibroblast cells; collagen and elastin macromolecules; and the extracellular matrix. The fibroblast is the genuine connective tissue synthesizing proteoglycans, tropocolla- gen, and tropoelastin. Fibroblasts issue fila- ments connected with different cells—adipose cells among others—that make the cell 1 sensitive to traction (hence the therapeutic response to Endermologie techniques). Droplets of water or lymph slide along the surface of these filaments. Collagen and elastin are the major products of fibroblasts and play the essential plastic role within the matrix. The extracellular matrix is mainly composed of proteoglycans (besides glycoproteins), which collaborate in the regulation of osmotic pressure and fluid movement. If there is an excess of hyaluronidase, the tissue is in a sol phase and liquids are able to flow, whereas in the gel phase, liquids are bound. Proteoglycan macromolecules are rich in anions that capture other positively charged ions such as sodium and calcium, thus regulating cell and matrix polarity (34–36). THE ADIPOCYTE Adipose tissue is characterized by the presence of a high number of adipose cells forming a tissue with scarce ground reticular substance. Adipocytes are closely associated with local and systemic metabolism and are a two- fold source of energy with respect to glycides and proteins. According to the area, activity, and embryological origin, primary fat (brown colored and preferentially located in cavi- ties) may be distinguished from the secondary type (whitish fat located at subcutaneous level, within the muscle interstitium and in the omentum, mesenterium, and peritoneum). While cells of the primary fat tissue are steatoblastic from the embryological point of view, white fat tissue cells instead derive from normal mesenchimal (mesenchymal) cells. In fact, every fibroblastic cell may be transformed into an adipose cell under specific conditions or body requirements. Under electron microscopy, secondary adipose cells show a complex of Golgi’s corpuscles, mitochondria, and ribosomal spread within a cytoplasm, which becomes thinner near the central fat drop. The adipose drop has no membrane of its own and proffers filaments that extend to the cell surface. The plasmatic membrane—which has pinocytotic invaginations—is surrounded by a glycoprotein membrane varying according to metabolism. On the surface of the adipose cell, nude nervous axons may be seen.

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