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By: Soheir Saeed Adam, MBBCh

  • Assistant Professor of Medicine

https://medicine.duke.edu/faculty/soheir-saeed-adam-mbbch

Because proteins order norvasc 2.5 mg with mastercard blood pressure 200 over 100, on occasion purchase norvasc 10mg blood pressure numbers what do they mean, may be deleterious to embryos norvasc 5mg for sale arrhythmia qt prolongation, protein free media have 22 been successfully used in limited studies purchase norvasc 5 mg free shipping hypertension 14070. Pregnancy rates were 24 increased and blastomere fragmentation reduced when human embryos were cultured on outgrowths of bovine tissue. The explanation for the beneficial effect could be the secretion of an “embryotrophic” factor by the somatic cells or their removal of detrimental components from the media. Bavister suggested that greater attention 25, 26 to culture media quality can yield the same gains as those seen with co-culture, and this has been confirmed by recent experience. In addition, co-culture with 27 granulosa cells has not helped couples with previous fertilization failures. Fertilization the day after insemination, cumulus cells that remain attached to the zona pellucida are removed, and the egg is examined for evidence of fertilization (the presence of 2 pronuclei). Approximately 6% of oocytes contain 3 or more pronuclei, indicating penetration by more than one sperm. It is important to identify and discard these abnormal embryos at this early stage because they have the potential to cleave and appear normal at later preimplantation stages. If the diagnosis is missed at the pronuclear stage, the embryos will be transferred and the result will be a failure to implant or a spontaneous miscarriage. A failure to fertilize is sometimes viewed by clinicians as a “human egg test” for that specific couple. However, fertilization failure in one cycle, despite normal sperm and eggs, is not an absolute indication of an insurmountable problem. About two-thirds of embryos survive the freezing and the subsequent thawing process. The transfer of cryopreserved embryos adds significantly (15% delivery per transfer) to the success rate with a single retrieval and lowers the cost. Older age of the woman is associated with a decrease in pregnancy rates, not only because of a decrease in the number of 30 oocytes and a reduction in oocyte and embryo quality, but also because fewer embryos are available for cryopreservation. Embryo Transfer Embryos have been transferred successfully at any stage from the pronuclear to the blastocyst, although most commonly, they are transferred when development is between the 8- and 10-cell stage, approximately 72–80 hours after retrieval. High order multiples can create unfortunate outcomes for the pregnancy, the children, and for subsequent family life. It is not unusual for patients to welcome the prospects for a multiple birth, and they must be informed of the associated risks. The guidelines of the American Society for Reproductive Medicine are more liberal, and they are influenced by the age of the woman. The recommendation is for no more than 3 embryos to be transferred in women younger than age 35, no more than 4 at age 35–40, and no more than 5 in women older than age 40. Our preference is to transfer 2 good quality 8–10 cell embryos in women under the age of 35, whereas women between age 35–39 may have 2–3 good quality embryos transferred. It may be reasonable to place higher numbers in women age 40 and older, but this is influenced by the experience of the individual 31 program. At least one study did not experience a decrease in multiple birth risk in older women. While we cite “good quality” of the embryos as a qualification, it must be recognized that this assessment is highly subjective. The ability to use fetal reduction to limit the number of continuing fetuses lessens somewhat the concerns over the major hazards of multiple pregnancies. In experienced hands, the risk of losing the 32 entire pregnancy from selective fetal reduction is less than 10%. However, moral concerns and the psychological impact of fetal reduction are important considerations. Success with culture to the blastocyst stage has raised the hope that high pregnancy rates can be achieved with the transfer of only one blastocyst (reaching this 26 stage in culture is predictive of excellent potential). Ancillary medications given around the time of transfer, such as prostaglandin inhibitors, tranquilizers, or antibiotics are of no proven value. Several options are available, including progesterone vaginal suppositories, 50–100 mg daily, progesterone in oil, 50–100 mg im daily, one application of vaginal progesterone daily, or oral micronized progesterone, 200 mg tid. The value of luteal phase supplementation can be questioned, but there is no doubt that it provides some psychologic benefit for both patient and physician. If weekly determinations demonstrate appropriate elevations, ultrasonography 5 weeks after the transfer should reveal a fetal heart beat. The presence of a rapid heartbeat is an excellent prognostic sign, and if the woman is under age 30, the chance for a spontaneous miscarriage is near zero; between age 31–35, the risk of spontaneous 33 miscarriage is 4%.

Because the pannus grows in from the margins order norvasc 2.5 mg online blood pressure chart and pulse, the earliest radiographic erosions are seen at the margins discount 10 mg norvasc overnight delivery blood pressure 10070, and the contract surfaces are spared until relatively late cheap norvasc 10mg with visa blood pressure xls. Steroid therapy causes expansion of metacarpals and phalanges secondary to changes in the marrow fat (steroid lipomatosis) order norvasc 10 mg with amex heart attack complications. Destructive changes in these joints necessitate rheumatologic and frequently orthopedic care. Finding these crystals in joint fluid is the diagnostic sine qua non of this metabolic imbalance. Typically, the first metatarsophalangeal joint is the classic site, but certainly the process can present in any joint, including the spine. The acute onset and signs of acute inflammation should suggest the diagnosis, which is best confirmed by arthrocentesis. The finding of needle-like, negatively birefringent crystals under polarized light confirms the diagno- sis. However, in the presence of late destructive changes, surgical intervention can be considered. Pseudogout is one of the many causes of chondrocalcinosis and should not be considered synonymous with it. Basic Science of Bone and Cartilage Metabolism 29 birefringent crystals, rhomboid in shape, attests to the diagnosis. The calcium pyrophosphate crystals are radiopaque and, as such, can be viewed on standard radiographs as calcification of cartilage, including the menisci and articular surfaces. The condition rarely mandates surgical interven- tion, and treatment frequently revolves around nonsteroidal antiinflamma- tory drugs or intraarticular steroid injections. As a result, homogentisic acid accumulates and targets articular cartilage for its deposition. The articular cartilage is stiff- ened by the presence of this by-product and loses its resiliency. The net result is fissuring and fibrillation of the articular surface; these changes radiographically and pathologically mimic osteoarthritis. The unique feature of this condition is the fact that this material pigments and stains the cartilage black. Notice the diminution of the intervertebral disks, black discol- oration of the cartilage components, virtual disappearance of all joint spaces, and bony bridging. Delahay Vascular Disease this diagnostic category is a somewhat diverse grouping of clinical entities that are best considered under this heading lest they be overlooked. Circulatory Disease: Avascular Necrosis Afflictions of the vascular tree, especially the arterial side, tend to produce similar lesions in bone, despite the etiology. Bone deprived of a portion of its blood supply becomes necrotic, as do all other tissues. Depending on the extent of the vascular involvement, the infarcts can range from small areas of bony necrosis in the metaphysis. In truth, the dead tissue is incapable of changing its density because no viable cells exist. Bone from central area of infarction, exhibiting infarcted fatty tissue, obliterated vessels, and infarcted bone. The sclerotic area represents infarction of the marrow cavity with formation of calcium soaps and new bone from the reparative margins. The necrotic bone then appears to be more dense on the radiograph—so-called relative radiodensity. There is also some compaction of dead trabeculae; as well as marrow necrosis with subsequent saponification and calcification of the dead fat, to additionally explain the sclerotic changes seen on radiographs. Clinical radiograph (A), specimen radiograph (B), and correspond- ing macrospecimen (C) of femoral head from a 26-year-old patient on long-term steroid therapy for idiopathic thrombocytopenic purpura with progressive pain and disability of both hips. Note the crescent sign, a cleft beneath the articular cartilage resulting from compression fractures of dead trabeculae.

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Severe hypertension in pregnancy: hydralazine or labetalol: a randomized clinical trial quality norvasc 5mg heart attack x factor. For acute ischemic stroke buy 2.5 mg norvasc otc 2014, the guidelines do not sodium nitroprusside for hypertensive emergencies present- recommend a single specifc agent or class of agents but state ing with neurologic injury order norvasc 5mg without prescription blood pressure chart pdf. Furthermore cheap norvasc 5mg mastercard hypertension 65 years and older, clevidipine may have that an individualized approach is most appropriate, with con- a better blood pressure variability profle than nitroglycerin or sideration of agents such as labetalol, nicardipine, hydralazine, sodium nitroprusside, lead to a lesser volume administered and enalaprilat (Jauch 2013). Given the beneft of nicardipine than nicardipine, and allow potentially faster attainment of and clevidipine compared with the other agents with respect to blood pressure goals than the other agents. Regarding despite these advantages, major clinical outcomes have not acute hemorrhagic stroke . Finally, in pregnancy-associated severe hyper- on which agents to use for the early aggressive reduction in tension, labetalol may be associated with fewer maternal patients who would qualify for such aggressive reductions adverse effects than hydralazine, but the agents’ impact on (see earlier text in Treatment Goals: Acute Hemorrhagic Stroke fetal or maternal clinical outcomes may not differ. Understanding the safety profles of each medica- Comparisons between these agents have failed to show supe- tion and data published in comparative studies (see Table 1-6) riority; thus, the guidelines recommend selecting an agent is important. Table 1-7 lists the individual agents, potential on the basis of adverse effects, contraindications, and cli- indications, and key considerations for use. For patients Current available guidelines and consensus opinions sup- with cocaine-induced hypertension, benzodiazepines are port the data synthesized in Table 1-7. International guidelines an effective frst-line therapy, but additional blood pressure for the medical management of acute aortic dissection rec- control may be warranted (Richards 2006). When additional ommend β-blockers to reduce the force of ventricular ejection blood pressure control is needed, α-blocking agents . Updates in Therapeutics: Critical Care Pharmacy Preparatory Review Course, 2017 ed. Hypertensive Emergencies in the • the frst step in assessing a patient for hypertensive crisis Emergency Department. Emerg Med Clin North Am is determining the presence or absence of target-organ 2015;33:539-51. Hypertensive crises: hypertensive patient-specifc chief concerns, physical examination fnd- emergencies and urgencies. Retrospective analysis from Safe Implementation of pregnancy-associated acute hypertension, and aortic dissection) to the general principles of treatment, which Thrombolysis in Stroke-International Stroke Thrombolysis will allow for target goal development. Report of the American • Patients with exceptions have unique treatment goals College of Obstetricians and Gynecologists’ task leading to unique medication selection. Obstet Gynecol • the goal of medication selection is to provide “smooth” 2013;122:1122-31. Lower treatment be limited because of a lack of control of concurrent tachycar- blood pressure is associated with greatest reduction in dia. If concurrent tachycardia is present, added combination hematoma growth after acute intracerebral hemorrhage. In addition, for patients with hypertensive sure-lowering and greater attenuation of hematoma emergency caused by pheochromocytoma, phentolamine is growth in acute intracerebral hemorrhage. Impact of perioperative considerations for renal replacement therapy, as needed, for blood pressure variability on health resource utilization volume removal (Rhoney 2009). Emergency reduction, hypertension in damage to differentiate hypertensive emergency from hyper- pregnancy, and hypertension in the elderly. Effects of antihypertensive treat- treatment principles of hypertensive emergency (compelling ment on cerebral perfusion. Hemodynamic selected on the basis of treatment goals, presenting target-or- effects of intravenous metoprolol. Patient Saf Surg Mothers’ Lives: reviewing maternal deaths to make moth- 2008;2:13. Liver disease selectively Report of the Joint National Committee on Prevention, modulates cytochrome P450–mediated metabolism. Clin Detection, Evaluation, and Treatment of High Blood Pharmacol Ther 2006;80:235-45. Neural and humoral mech- nicardipine, diltiazem and verapamil on coronary blood anisms involved in blood pressure variability. Therapeutic interchange of clevidipine for sodium nitroprusside in cardiac surgery.

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Only the peripheral one-third of the meniscus receives a blood supply generic norvasc 10 mg with visa hypertension disorder, and therefore the potential for healing after injury is limited purchase norvasc 10mg on line prehypertension 2016. Location and type of meniscal tearing in a symptomatic knee determine one’s ability for potential healing generic norvasc 10mg with visa blood pressure 0f 165. Meniscal injuries are best categorized by the location of the tear as well as the morphology of the tear order norvasc 10mg otc blood pressure keeps going down. The location can be best described in reference to the blood supply of the meniscus. Red–red tears involve the peripheral one-third of the meniscus and have excellent healing potential. Red–white tears involve a zone of the meniscus with good blood supply on the peripheral aspect of the tear and poor blood supply on the more-central portion and have intermediate healing potential. White–white tears involve those tears in the avascular zone completely with poor healing potential. A Vertical Longitudinal B Oblique C Degenerative D Transverse (Radial) E Horizontal Figure 6-4. Klimkiewicz Evaluation of Common Sports Medicine Injuries the principles involved in the initial evaluation of the injured athlete focus on history and physical examination in combination with auxiliary tests and are similar in comparison to other orthopedic injuries. This subspe- cialty differs from that of a general orthopedic setting in two distinct manners. One large difference in the management of the athlete is the ability to provide prompt “on-the-field” attention as a result of game time coverage by the sports medicine physician; this allows one to often visual- ize the injury directly and distinguish as to whether the mechanism was a direct result of blunt trauma as compared to a more-indirect mechanism (i. Additionally, it provides one with a golden window of time to evaluate the injury before the effects of swelling and subsequent pain and spasm complicate the physical exam. It often allows one the opportunity to make the diagnosis without the need for auxiliary tests that are often required when evaluating these injuries on a more-subacute basis. Furthermore, the sports medicine physician is often asked the safety of returning to play in light of a specific injury. Knowledge of the common injuries as well as the sporting activities themselves is important in making these decisions. The following sections focus on the history as well as physi- cal examination in the sports medicine setting. History the history in many sporting injuries is straightforward and related to acute trauma. Examples include twisting the ankle when coming down for a rebound, feeling the shoulder “pop out” when being tackled, or hearing a “pop” within one’s knee on cutting cross-field. Important in this history is the mechanism of injury, as this often relates very closely with the struc- ture injured. When this is more ambiguous on questioning the athlete, input from other players, trainers, and coaches as well as game-time film can be invaluable in determining the mechanism of injury. Other injuries within this field are a result of microtrauma, or overuse, and have no spe- cific mechanism of injury. For these insidious conditions, its important to obtain the specifics of recent activity including change in recent activity, change in shoe wear or other equipment, the surface involved (track to road, flat surface to hills, etc. Other pertinent details include whether this problem has occurred before, and if so, how it happened, what type of treatment was rendered, and what was the outcome. Previous problems may alert the clinician to a different treatment problem to prevent recurrence of the injury. Examples include the management of “first-time” as opposed to recurrent shoulder dislocations. Sports Medicine 267 Symptoms that occur with activity and improve with rest are typical of overuse injuries. Nocturnal awakening usually indicates more serious injury or an underlying systemic disorder. Such a distinction is important in distinguishing shin splints from a stress fracture in a long-distance runner. In the athlete with intermittent knee symptoms, pain in the anterior aspect of the knee that is worse with stair climbing or with prolonged sitting suggests problems related to the patellofemoral joint. Symptoms that occur predict- ably with cutting and pivoting activities, accompanied by swelling and instability, suggest an internal derangement of the knee such as a meniscus injury or tear of the anterior cruciate ligament.

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The Physiologic Feedback Loop Energy expenditure is composed of the basal metabolic rate purchase norvasc 2.5mg with amex blood pressure jnc, diet and temperature-induced heat production discount norvasc 5mg with mastercard heart attack queen, and the energy necessary for physical activity safe norvasc 5 mg prehypertension fatigue. Leptin 35 induces weight loss in mice due to decreased appetite and food consumption and an increase in heat production and activity 5mg norvasc amex arteria digitalis palmaris communis. In humans, there is no surge of leptin after meals, and the acute administration of insulin does not stimulate an increase in leptin levels. However, an increase in ob gene expression occurs in humans with chronic insulin stimulation, 37 a situation that would be similar to overeating. In addition, at least one study has found an acute increase in leptin levels following the induction of hyperinsulinemia 38 (but only in women, not in men). It is likely that insulin is at least one regulator of the ob gene and its secretion of leptin. This protein binds to a melanocortin receptor in melanocytes in the skin, thus preventing melanocyte-stimulating hormone action. Agouti rats have high levels of this protein and have yellow instead of black fur. Melanocortins 39, 40 have been demonstrated in the hypothalamus, produced in the arcuate nucleus. The arcuate nucleus lies outside the blood-brain barrier (there is no blood-brain barrier in the medial basal hypothalamus) and can be reached by leptin in the circulation. Fasting decreases leptin more than 42 expected by the decrease in fat content, indicating the presence of other control mechanisms. Feeding increases leptin levels, but slowly, correlating with insulin 37, 47 36 levels. The hyperphagia of diabetes mellitus reflects a deficiency in this insulin action. These relationships are further confused by evidence that glucocorticoids 50 stimulate leptin synthesis and secretion in humans. Leptin in Obese People Most studies have indicated that nearly all obese individuals have elevated leptin levels, probably due to an increase in Lep gene expression and partly due to greater 51, 52 and 53 production because of larger fat cells. The greater weight of these individuals represents the leptin level at which stability is achieved, when leptin resistance 38 is overcome. In lean individuals, leptin levels are similar in men and women, but in women, as weight increases, leptin increases 3 times more rapidly than in men. Obese postmenopausal black women have 20% lower leptin levels than white 56 women. These lower leptin levels correlate with a lower resting metabolic rate in the black women. The lower levels may indicate a greater sensitivity to the leptin mechanism in black women. In obese individuals, fat cells produce leptin normally and a prevalent genetic failure has not been identified. This may be due to a transport problem of leptin into the brain, as indicated by the finding that leptin level differences between obese and lean 58, 59 individuals are greater in blood than in cerebrospinal fluid. At least in the mouse, this resistance is present only in the periphery in that leptin administered in the 60 brain still works. Diet-induced obesity in mice responds to leptin treatment, and it is expected that the majority of overweight humans would also. However, in genetically normal animals, leptin treatment does not 62 always reduce weight by reducing food intake. Another important subject for research is the regulation of leptin binding to proteins in the circulation. When life was tougher, leptin served the purpose of meeting the threat of starvation. During periods of food availability, individuals with leptin defects could consume large amounts and store excess fat. Today, with no shortage of food, these individuals who survived during food shortages in the past now become obese, and succumb to the complications of obesity. But the most vexing problem is that 90% to 95% of people who 64 lose weight subsequently regain it.

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References:

  • https://pharmacy.rutgers.edu/wp-content/uploads/Pceutics-grad-program-Course-Layout-08-03-2012.pdf
  • http://docshare02.docshare.tips/files/5391/53915598.pdf
  • https://www.abpi.org.uk/media/1627/guidelines_phase1_clinical_trials.pdf
  • http://people.dbmi.columbia.edu/~chw7007/papers/chapter%2010.pdf