Beth Israel Deaconess Medical Center, Division of Podiatric Surgery
Boston, Massachusetts
Alloderm acellular dermal graft: applications in aesthetic soft tissue augmentation depression symptoms video buy 50mg amitriptyline overnight delivery. A systematic review of topical negative pressure therapy for acute and chronic wounds depression test accurate buy discount amitriptyline 50 mg on line. It relies on new blood vessels from the recipient site bed to be generated (angiogenesis) depression legal definition amitriptyline 50mg on line. Full thickness - the full thickness skin graft leaves behind no epidermal elements in the donor site from which resurfacing can take place frontal depression definition generic 50mg amitriptyline amex. It is usually harvested with a scalpel between the dermis and the subcutaneous fat depression symptoms holden caulfield amitriptyline 25 mg discount. Split thickness - the split thickness skin graft leaves behind adnexal remnants such as hair follicles and sweat glands anxiety jaw muscle tension discount 25 mg amitriptyline with mastercard, foci from which epidermal cells can repopulate and resurface the donor site. The donor site is usually covered with an occlusive dressing and left to heal secondarily. Full thickness - Full thickness skin grafts are usually used to resurface smaller defects because they are more limited in size. They provide better color consistency, texture, and undergo less secondary contraction. Split thickness - Split thickness grafts are usually used to resurface larger defects. Plasmatic imbibition (First 24-48 hours) - Initially, the skin graft passively absorbs nutrients from the wound bed by diffusion. Inosculation - By day 3, the cut ends of the vessels on the underside of the dermis line up with and begin to form connections to those of the wound bed. Angiogenesis - By day 5, new blood vessels grow into the graft and the graft becomes vascularized. Poor wound bed - Because skin grafts rely on the underlying vascularity of the bed, wounds that are poorly vascularized with bare tendon or bone, or because of radiation or ischemia, will not support a skin graft. Shear - Shear forces separate the graft from the bed and prevent the contact necessary for revascularization and subsequent "take", which refers to the process of attachment and revascularization of a skin graft in the donor site c. Hematoma/seroma - Hematomas and seromas prevent contact of the graft to the bed and inhibit revascularization. Infection - Bacteria have proteolytic enzymes that lyse protein bonds needed for revascularization. Bacterial levels greater than 105 cells/gram of tissue in the wound will cause graft failure. Skin substitutes - these are used for temporary wound coverage, or as a bridge to another form of reconstruction, typically a skin graft. Tendon - Common donor sites are the palmaris longus, plantaris, extensor digitorum longus D. Bone - Common donor sites are the calvarium, iliac crest, tibial tuberosity, rib F. Flaps can be used when the wound bed is unable to support a skin graft (such as over exposed hardware), or when a more complex, larger, or more aesthetic reconstruction is needed. Flap harvest always leaves a donor site that will need to be closed either primarily, with a graft, or with another flap. Composite flap flap components are directly attached to each other and harvested on single pedicle. Chimeric flap flap components are harvested on their own vessel and freely mobile, with a single feeding vessel. Multi-segment fibula flap with fibula bone osteotomies, harvest of soleus muscle cuff based on muscle perforators, and independent skin paddle based on cutaneous perforators. By location - Flaps can be described by the proximity to the primary defect that needs to be reconstructed. Movement into the defect can be described as advancement, rotation, or transposition. Raised from tissue in the vicinity but not directly adjacent to the primary defect. Usually requires re-anastomosis of the blood vessels to recipient blood vessels in the primary defect (see "free flaps" below). There are a few examples of distant pedicled flaps, such as using a groin flap for hand reconstruction. Because of the random nature of the vascular pattern, these flaps are limited in dimensions, specifically in a length:base width ratio of 3:1. If designed longer than this ratio, a random blood supply often cannot support the flap (Figures 3, 4). Designed with a specific named vascular system that enters the base and runs along its axis. Detached at the vascular pedicle and transferred from the donor site to a recipient site. At the recipient site, the flap artery and vein are anastomosed to recipient vessels. This allows more flexibility as tissues can be transferred nearly anywhere but requires microsurgical skill and increased operative time. Typically harvested without the deep tissues in order to minimize donor site morbidity and to yield only the necessary amount of tissue for transfer. Perforators are described by their path from the main vessel to the skin (Figure 6). Mathes and Nahai classified fascial and fasciocutaneous flaps based on their vascular anatomy. Type B (center) are those flaps with a pedicle that has a septocutaneous perforator. Tissue type to be replaced: Muscle can eliminate more dead space, skin is better for resurfacing 4. Success depends not only on its survival but also its ability to achieve the goals of reconstruction. Flap failure results ultimately from vascular compromise or the inability to achieve the goals of reconstruction. Treatment for symptomatic lesions includes cryotherapy, snip excision, or shave excision B. Result from a proliferation of epidermal cells within the dermis, and arise from the infundibular portion of the hair follicle 2. Present as skin-colored to yellow, firm, movable nodules, often with a visible central punctum. Well circumscribed by a cyst wall made of stratified squamous epithelium, and communicate with the surface through a small opening, which may contain a keratinous plug or blackhead 4. Definitive treatment is surgical excision of the entire cyst (including cyst wall) C. Originate from the outer root sheath of the hair shaft, and are lined by stratified squamous epithelium, which undergoes keratinization 2. Present as firm, slow-growing subcutaneous nodules (clinically similar to epidermoid cysts, but they lack the central punctum) 3. Definitive treatment is surgical excision of the entire cyst (including cyst wall) D. Classically present as slow-growing, "rock- hard" subcutaneous masses, with a blue hue or ulcerative appearance 3. Bimodal distribution (first and sixth decades), although more common in children 4. Congenital cysts located along lines of fusion in the head and neck region, most commonly along the superior lateral orbital ridge, but also occurring at the scalp and the midline of the nose 2. Skin-colored, nontender, noncompressible, slow growing, and can arise in the dermis or subcutaneous tissue, or be fixed to underlying periosteum 3. Present clinically as hyperpigmented, waxy, verrucous papules with a characteristic "stuck-on" appearance 2. Appear in the fifth to seventh decades of life, usually on the head, neck, or trunk 3. Arise from the basal layer of the epidermis, are composed of well-differentiated basal cells 4. Removal is for cosmetic purposes only cryotherapy, shave biopsy, dermabrasion B. Hard, cone-shaped cutaneous projections typically caused by excessive epidermal growth and retention of keratin 2. Neoplasms of follicular origin that presents as multiple, yellowish-pink, translucent papules distributed symmetrically on the cheeks, eyelids, and nasolabial area 2. Presents as a solitary lesion (firm papule less than 2 cm in size) usually on the sole of the foot or the palm of the hand in persons older than 40 years. Closely set skin colored, brown, or gray-brown verrucous papules that may coalesce to form well-demarcated plaques, usually in a linear configuration along skin tension lines 2. For more extensive lesions not amenable to excision, treatments may include laser cryotherapy and electrodesiccation dermabrasion F. Adult-onset nodules, usually on the face or scalp, with smooth, flesh-colored, possibly telangectatic surfaces 2. Appears in early childhood, usually following minor trauma, as a rapidly growing, small (<1cm) red lesion 2. Present as asymptomatic yellow-orange papules and plaques, commonly on the medial eyelids 40 K. Correction of underlying hyperlipidemia is largely ineffective in treating xanthelasma Syringoma 1. Presents as asymptomatic, skin-colored to yellow papules and plaques commonly found on the eyelids and upper cheeks 2. Treatment is for cosmetic concerns, and includes laser therapy, cryotherapy, electrodessication, and excision Nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris or oculodermal melanocytosis) 1. Dermal melanocytic hamartoma that demonstrates bluish hyperpigmentation along the ophthalmic and maxillary divisions of the trigeminal nerve 2. Caused by the failure of complete embryonic migration of melanocytes from the neural crest to the epidermis, resulting in dermal nesting with the resultant dermal melanin causing the Tyndall effect 3. Has a bimodal age incidence, with a peak at 1 year of age and a second around puberty 5. Malignant degeneration to melanoma occurs in approximately 4% of reported cases 8. Treat with laser therapy either Q-switched laser with ruby (694 nm), alexandrite (755 nm), or neodymium: yttrium-aluminum-garnet (1064 nm) Nevus of Ito 1. Large blue-grey lesion that characteristically arises over the shoulder region and areas innervated by the posterior supraclavicular and lateral cutaneous brachial nerves 2. Clinically presents as a well-circumscribed pink papule that rapidly increases in size 4. Pigmented variant (spindled cell nevus of Reed) is dark brown to black in color with pseudopods at the periphery, giving it a "starburst" appearance 5. Present as a solitary, firm, hyperpigmented macule or thin papule on the lower extremity 2. Surgical excision only for symptomatic lesions (can be painful or pruritic) Lipoma 41 1. Present as soft, rubbery, nontender, slow-growing subcutaneous nodules that are freely movable on palpation 2. Presents as a hairless, solitary, linear, well-demarcated patch or thin plaque that is pink, yellow, orange, or tan in color, usually on the scalp 2. During adolescence, hormonal changes cause the lesion to thicken and become more verrucous and nodular in appearance 3. Treatments include topical imiquimod (Aldara), photodynamic therapy with 5aminolevulinic acid (Levulan), cryotherapy, 5-fluorouracil, retinoids, and diclofenac gel B. Associated with chronic sun exposure and are more commonly seen with lighter skin, increasing age, and tanning bed use 3. May metastasize (most often with lesions on the ear or lip, lesions > 2 cm in size, and in the immunosuppressed population) 6. Presents as a pink, pearly papule with overlying telangiectasia and rolled borders. Arises on sun-damaged skin of the head, neck, and upper extremities, with an increasing incidence with age, fair skin, chronic sun exposure, and a history of tanning bed use 42 3. High risk poorly defined borders, recurrent lesion, immunosuppressed patient, site of previous radiation, peri-neural involvement, aggressive histology (morpheaform, sclerosing, mixed infiltrative, basosquamous, or micronodular), >2cm in the trunk/extremities, or >1cm in the head and neck 4. Vismodegib and Sonidegib (a selective inhibitor of hedgehog pathway activation) are approved for the treatment of metastatic basal cell carcinoma and locally advanced basal cell carcinoma that has recurred after surgery, or in patients who are not surgical or radiation therapy candidates Figure 3. Risk factors include fair hair/skin, history of sunburns/sun exposure, and family/personal history of melanoma 3. Often arise from pre-existing lentigo maligna lesions, which can be present for many years, growing in a slow, radial fashion, before the vertical growth phase develops c. Commonly present as large, tan lesions with convoluted patterns and multiple amelanotic patches 7. Rarest form of melanoma in Caucasians but 30-60 % of melanoma in darkskinned individuals b. Often confused with common nevi, blue nevi, Spitz nevi, pyogenic granulomas, or hemangiomas 10. Medical treatment for melanoma is currently used for advanced melanoma only (usually Stage 3 or 4) and consists of immunomodulation and targeted molecular therapy toward mutations found in melanocytic lesions a. Interleukin-2 (immunomodulator that activates the host immune system to attack malignant cells, severe side effect profile) c. A 75-year-old man with a left cheek lesion presenting with asymmetry, borders irregularity, color variation, and diameter of 2. Presents as a firm, painless nodule (up to 2 cm in diameter) or a mass (>2 cm in diameter), usually in the head and neck region, classically red in color, but may be flesh-colored or blue, and often enlarges rapidly 2.
Washing baths are particularly prone to contamination by animal feces because even a small eck of feces in a washing tank that cleans multiple carcasses can contaminate all of them bipolar depression with psychosis order amitriptyline 25 mg free shipping. Animal feces also can contaminate fruit and vegetable crops depression hashtags buy generic amitriptyline 50 mg on line, either in the eld or through cross-contamination at various points along their path from initial production to the dinner plate mood disorder psychotic discount amitriptyline 50 mg amex. Clostridium botulinum anxiety burning sensation cheap 25mg amitriptyline visa, for example depression symptoms handout order amitriptyline 50 mg without prescription, is widespread in soil depression symptoms speech cheap 25 mg amitriptyline free shipping, whereas many Vibrio species thrive in seawater. Staphylococcus aureus and related species normally live quietly on human skin, in the nose, and elsewhere in the environment, but they can do considerable damage if they are allowed to grow on food and produce toxins that cause food poisoning. Group A streptococcus, the bacterial strains that are to blame for strep throat, are common malefactors spread this way. Most restaurants use "sneeze guards" at salad bars to cut down on oral transmission of strep infections by blocking the ne mists of spi le that people eject during sneezes or coughs. Finally, esh contamination, although not as common, is the primary source of infection by some parasitic worms and by a form of salmonella that infects hen ovaries and subsequently contaminates their eggs. Even if you know the foodborne pathogen that is causing an infection, however, tracing that infection back to its original source of contamination can be tedious and ultimately futile. Food and Drug Administration, the microbe can be transmi ed through meat, oysters, sh, and raw milk, among other foods. But the species is common in soil and water samples, as well as in animals such as beavers, pigs, and squirrels. Poor sanitation and sterilization by food handlers could contribute to contamination. So for that one foodborne pathogen, an illness could arise from environmental, human fecal, or animal fecal contamination. Likewise, campylobacter infections are normally associated with fecal contamination. Many other foodborne pathogens can also exploit multiple avenues to reach the kitchen one reason why they can be so di cult to avoid ingesting. Even so, a review of the records of foodborne outbreaks in which the source has been identi ed suggests that an overwhelming majority are linked to fecal contamination. And that means that most food contamination occurs through an external source it is basically dirt (or worse) on the outside that never reaches the interior of the food. Nevertheless, the fact that most microbial contamination arrives from a source beyond the food itself has multiple implications for food safety and kitchen practices, which are the subject of the next chapter. Like many people with culinary training, we had assumed that the problem was intrinsic to the food supply. Before a pig becomes pork, for example, the worm Trichinella spiralis that causes the disease trichinellosis (also called trichinosis) can infect the animal. We had naively assumed that all food pathogens are somehow just present in the food or its environment. For these and other reasons that cooks in well-developed countries need no longer worry about trichinellosis from pork, see Misconceptions About Pork, page 179. While millions of cooks in restaurants and homes overcook their pork with almost religious zeal, few have ever heard of the noroviruses that, through food, sicken nine million Americans every year. Overemphasis on the wrong pathogen also occurs with botulism a foodborne disease that strikes fear into the hearts of cooks everywhere. Any death is tragic, of course, but one needs to place the numbers in perspective; more than 20 times as many people die every year in the U. Meanwhile, Toxoplasma gondii, a protist primarily found in the feces of pet cats, sickens 112,500 people a year, killing 375 of them and thus claiming nearly 100 times as many victims as botulism does. Indeed, toxoplasma is the primary reason that protists command such a fat slice of the pie chart on page 113 T. Toxoplasma may cause schizophrenia and other psychological damage as well (see page 126). Salmonella bacteria do not live in chicken meat (muscle tissue), the source most commonly ngered as the culprit. Instead, the bacteria normally live in the intestinal tracts and feces of chickens and can contaminate the meat during slaughter and processing (except S. Investigations of the sources of other recent contagions have implicated hot peppers and tomatoes. Because bacterial foodborne illness generally results from exposure to feces, it follows that agents such as E. Meat, particularly ground beef, also has been implicated, but the common assumption that E. Why do trichinella and botulism evoke such paranoia while toxoplasma and noroviruses are virtually ignored? Why do so many people disregard the most common and easily thwarted sources of contamination from foodborne bacteria? Strawberries, spinach, and peanut butter are just as likely to harbor foodborne pathogens as meat, fish, and poultry are. Most recent outbreaks of foodborne illness have, in fact, been linked to fruits, vegetables, and nuts. Several different approaches are used, which can make things confusing to the uninitiated. Medical authorities sometimes modify this straightforward method to yield less obvious derivatives. When the pathogen is unknown or ill-defined, medical researchers may name a disease or condition after its symptoms. The term gastroenteritis, for example, describes an acute infection of the gastrointestinal system without specifying the responsible pathogen. Finally, doctors refer to some diseases or disease conditions by ad hoc names, bowing to popular usage or medical tradition. Most of us learned of the danger from our mothers as well as from some public health authorities and nearly all cookbook authors, who have insisted for years that pork should always be cooked well-done. Yet in reality the Trichinella roundworm has li le impact on either the number or severity of foodborne disease cases in the United States. Most of the few dozen other cases resulted from eating the meat of wild game bears in particular, but also boars and mountain lions or pork obtained directly from farms or home-raised pigs, to which industry standards and regulations do not apply (see Misconceptions About Pork, page 179). Although concern about foodborne worms can be overblown, no one wants to harbor parasites that can stick around for years or even decades. So all cooks should know some basic facts about the parasitic roundworms, ukes, and tapeworms that sometimes make their way into the food supply. Beyond Trichinella and other roundworms or nematodes, foodborne worms of note include ukes (trematodes) and tapeworms (cestodes). In general, these parasites produce disease through two main mechanisms: the worms either penetrate body tissue during invasive infections, or they live in the gut as noninvasive infections. Each larva burrows into a muscle cell, converting it into a so-called nurse cell by secreting proteins that promote the formation of blood vessels. Larvae can live in protective calcified cysts for years until the host dies and is eaten, which starts the cycle anew in another host. Trichinella worms can survive refrigeration, but sufficient freezing will kill the worms in pork. For other meats, and as an alternative for pork, safe cooking practices will render any worms in the food harmless. Life stages 2 Pigs, wild boar, bear, and other Contamination 3a Fresh meat is refrigerated, but parasites survive. Unsafe storage 4a Meat is insufficiently cooked Unsafe cooking animals get infected with parasites. Wild game Pork Roundworms, such as this female Trichinella, are among the few foodborne pathogens that naturally exist inside intact meat or fish. Contamination risk Low High Contamination risk Low High Wild game When ingested by another animal, larvae leave cysts and travel to the small intestine, where they mature. Contamination risk Low High Wild game Pork Wild game Pork Wild game Pork Roundworms Flesh-burrowing roundworms are among the few pathogens that normally live inside human food, typically buried deep inside the muscle tissue of domestic pigs as well as wild boars, bears, and other carnivorous animals. One Trichinella subspecies that lives in polar bears and walruses has been linked to outbreaks among Inuit communities near the Arctic Circle. With few exceptions, Trichinella infections do not cause death, although they can cause serious cardiac or neurological complications if they enter the heart or brain. In the wild, dead animals are invariably eaten by scavengers, which gives trichinae a chance to propagate. One way to prevent trichina worms from infecting livestock is to cook farm slops or feed that contains meat scraps before giving it to pigs. In the kitchen, however, killing trichinae does not require the excessive heat that most people imagine. Such overstatement may have arisen from good intentions, but at some point misleading recommendations become irresponsible. Bears, for example, hibernate in the winter, so their muscle cells contain special proteins that prevent the formation of ice crystals, and some health authorities fear that those proteins may also protect encysted Trichinella larvae from low temperatures. As a result, freezing may not be a reliable means of killing the worms in bear meat. Tapeworms, also called cestodes, have sucker-like parts on their heads that they use to anchor themselves to the intestinal walls of their hosts. A separate family of parasitic worms, known as nematodes or anisakids, includes species such as Anisakis simplex and Pseudoterranova decipiens (which is also listed under the genus Terranova or Phocanema). Fish or squid then eat the infected copepods, other marine mammals next eat the sh or squid, and the cycle continues. Such an infection can, in the meantime, generate quite a stomachache, with symptoms so severe that physicians sometimes misdiagnose the condition as appendicitis. A strong allergic reaction to the worms, although less common, could culminate in anaphylactic shock. Raw sh poses the biggest risk of infection because cooking sh to an internal temperature of 60 °C / 140 °F or more for at least one minute kills the worms. Several food safety guides assert that 15 seconds at an interior temperature of 63 °C / 145 °F will also do the trick. Not surprisingly, sushi-loving Japan is the epicenter of foodborne anisakid infections, also known as anisakiasis. Tokyo alone tallies about 1,000 cases annually, most of which are from home-prepared sushi and sashimi. Anisakid infection occurs more frequently in certain sh species that shermen catch near the shore, such as salmon, mackerel, squid, herring, anchovies, and rock sh, than it does in other species. Coastal sh are more likely to eat infected copepods that regenerate in seals and other marine mammals. Farmed salmon do not eat copepods and are therefore generally anisakidfree, as are wild tuna and other deep-ocean species. Despite this alarming statistic, human anisakiasis cases are still relatively rare because most ingested larvae die or pass harmlessly through the intestinal tract. And although some chefs can indeed nd a few worms through candling or handling, studies suggest that others may be easily missed, especially in salmon or mackerel. No ma er how experienced the sushi master, then, neither method is fully reliable. Freezing kills anisakids, and in this way the food industry ensures that worms pose no health risk in sh that is served raw. If done improperly, however, freezing can negatively a ect the taste and texture of the sh. Other notable nematodes include the giant intestinal roundworm, Ascaris lumbricoides, which can grow to 41 cm / 16 in. Investigators have linked ascariasis to cabbage and other raw produce that was grown in contaminated soil and to improper food handling in tropical regions and rural parts of the southeastern United States. Humans who eat raw or undercooked watercress or food that has been washed with contaminated water can accidentally ingest these cysts and contract a potentially serious invasive infection known as fascioliasis. Immature worms rst migrate through the liver, causing fever, in ammation, and abdominal pain as they go. Eventually they make their way to the bile ducts, where a progressive buildup of the parasites can in time block the ducts. Other species of liver uke are endemic to Asia and Eastern Europe, 2 Tapeworms can persist in raw, smoked, and dried foods but are killed by freezing (for 48 hours at -18 °C / -0. A live anisakid emerges from a piece of halibut we bought at a reputable, high-end organic grocery store near Seattle. But concern about species such as Fasciola hepatica has grown among public health authorities throughout western Europe especially France, Spain, and Portugal as well as in the Americas. Researchers have tied many infections, mostly in Asia, to eating raw, pickled, or poorly cooked freshwater crabs and craw sh (especially Chinese "drunken crabs") that are contaminated with lung ukes, another major uke group comprising eight known species. Investigators have also linked more than 65 uke species, primarily from Asia, to human intestinal tract infections. One noteworthy geographical exception is Nanophyetus salmincola, an intestinal worm that is sometimes called the "salmon-poisoning uke," which has been transmi ed to people in parts of the U. Health o cials have implicated the practice of eating raw, underprocessed, or smoked salmon and steelhead trout in many cases of human infection. Although exposure is o en fatal to dogs because of a secondary infection carried by the uke, the human disease generally leads to li le more than abdominal discomfort, diarrhea, and nausea. Like ukes, tapeworms are relatively uncommon in the United States and other developed countries, but they can persist for months or years inside travelers, immigrants, and others who have dined on raw or undercooked pork, beef, or freshwater sh that harbor the organisms. Unlike most other pathogens, both live out most of their lives inside human hosts, where they reproduce and produce their eggs. Unfortunately, tapeworms can survive for as many as 30 years within human intestines, where they can grow to astounding lengths up to 9. Once tapeworm eggs are shed through human feces, the hardy capsules remain viable for months while exposed, waiting until they are eaten by an intermediate host. A third tapeworm species, Diphyllobothrium latum, exploits small freshwater crustaceans as intermediates, which are in turn gobbled up by larger sh. Inside their animal hosts, tapeworm eggs hatch into tiny larvae that burrow into the intestinal wall and hitch a ride through the bloodstream to muscles and other tissues.
Halothane bipolar depression treatments order amitriptyline 25mg without prescription, however anxiety attack discount amitriptyline 50 mg with mastercard, has a significant negative chronotropic and inotropic effect depression pics purchase amitriptyline 50mg with amex, associated with a slight systemic vasodilation [24] depression symptoms quizzes cheap amitriptyline 25mg with visa. Propofol may cause hypotension through vasodilatation and moderate depression of myocardial contractility by inhibiting type L-calcium channels in the myocardium [29] economic depression definition pdf cheap amitriptyline 50mg line. However anxiety vs depression symptoms 50mg amitriptyline otc, there are no specific data on the hypotensive effects of these drugs [30]. Risk factors for the development of intraoperative hypotension are: advanced age, history of hypertension and use of volatile anesthetics rather than intravenous ones [31]. In literature Opioid Analgesics Regarding treatment with opioid analgesics, blood pressure is generally unchanged, except in cases in which the cardiovascular system is under stress. In this instance, hypotension is mediated by peripheral arterial and venous dilatation due to various factors, such as histamine release and depression of vasomotor center. For example, morphine may cause orthostatic hypotension through peripheral vasodilatation, decreased peripheral resistance and reduced vasomotor reflexes [24]. Particular attention should therefore be placed towards patients with hypovolemia, who are more sensitive to lowering of blood pressure. Antihypertensive and Cardiovascular Drugs Cardiovascular drugs are often related to orthostatic hypotension. Besides the type and mechanism of action of each drug, the total number of vasoactive drugs is crucial. In a study by Poon and Braun [46] in elderly subjects, prevalence of orthostatic hypotension was 35% in naive individuals and 65% in those taking at least three vasoactive drugs (p = 0. In this study, predictors of orthostatic hypotension are poorly controlled hypertension (prevalence 38% vs. Another study [48] shows that in elderly hypertensive patients undergoing pharmacological wash-out, prevalence of orthostatic hypotension is reduced from 23% to 0% during 12 months (p < 0. These data suggest that optimal treatment of hypertension may improve blood pressure regulation and may reduce orthostatic intolerance, which is often seen in patients on politherapy with vasoactive drugs and diuretics. Orthostatic hypotension was decreased in hypertensive subjects after treatment (prevalence of orthostatic hypotension pre-treatment: 20% in hypertensive subjects, 4% in normotensive, p = 0. These data suggest that optimal longterm antihypertensive treatment may result in reducing the burden of orthostatic hypotension. Among antihypertensive therapy, each drug class is related to a different prevalence of orthostatic hypotension, sometimes correlated to the specific mechanisms of action. Table 1 resumes cardiovascular drugs potentially implicated in hypotensive events and orthostatic hypotension. This may be due to the absence of a significant number of people treated with these drugs in the analyzed population. Although in combination with other vasoactive drugs nitrates may be significantly associated with orthostatic hypotension or syncopal events related to excessive blood pressure fall in orthostatism (p < 0. Calcium Channel Blockers Calcium channel blockers act on L-type calcium channels, reducing the entrance of calcium into smooth muscle cells of blood vessel walls: in this way, they determine vasodilatation, mainly on arteries. There are no studies that correlate dihydropyridine calcium channel blockers (in particular amlodipine [55] and nicardipine [56,57]) to orthostatic hypotension. This is likely due to their major effect towards vascular smooth muscle cells: during treatment with this class, compensatory increase in heart rate as a result of adrenergic stimulation on sinoatrial node is still possible. On the other hand, the prevalent effect of nondihydropyridine calcium channel blockers is dromotropic negative and inotropic negative. These drugs may determine, in fact, orthostatic hypotension is because of the lack of compensatory chronotropic response on standing [54]. In main population studies which analyzed the overall class of calcium channel blockers (without distinctions between dihydropyridines and non-dihydropyridines), orthostatic hypotension shows a 2-to-5-times increase in prevalence during treatment with these drugs, especially in elderly population [8,53,58], while there is no association between the use of calcium channel blockers and orthostatic hypotension in diabetes [52,59]. Considering the individual active principles, some studies show a correlation between the use of captopril and the onset of severe hypotensive events [61-63], first-dose orthostatic hypotension (estimated prevalence: 0,7-13,7% in Nitrates Nitrates may determine orthostatic hypotension through the induction of vasodilatation, predominantly on the venous district, due to the release of nitric oxide. The short half-life and rapid action of this drug are likely to be strongly linked to these events. On the other hand, ramipril and perindopril appear to be associated with a lower prevalence of orthostatic hypotension and hypotensive events [9,61,62,67,68]. Diuretics In large population studies, diuretic therapy does not appear to be related to orthostatic hypotension [9,11,51,52,73,74]. The wide majority of the studies in literature distinguish thiazide diuretics from non-thiazide diuretics. The hypotensive mechanism is mediated by the blockage of aldosterone on the final part of the distal tubule and collecting ducts, thereby reducing the reabsorption of sodium and free water. They act through inhibition of the symport Na+-K+-2Cl- in the thick ascending limb of loop of Henle, leading to inhibition of reabsorption of sodium and water. The acute effect of these drugs determines an increase in the capacitance of venous district and a reduced filling pressure of the left ventricle, resulting in decreased cardiac output. Thiazide diuretics determine the inhibition of the Na+-Cl- symport in the distal convoluted tubule: through this mechanism, they reduce sodium and water reabsorption determining plasma volume depletion, thus possibly inducing orthostatic hypotension. Poon and braun [46] noticed that in an elderly population 65% of patients with orthostatic hypotension was undergoing treatment with hydrochlorothiazide. Moreover, an increased prevalence of orthostatic hypotension has been detected in patients with heart failure treated with thiazide diuretics, if compared with patients treated with non thiazide diuretics [76]. Some studies [46,47] point out the increased risk of developing orthostatic hypotension with these drugs: it can be twice as high during intake of 1-antagonists. Prazosin is the fast-acting 1-antagonist with the greatest affinity for 1 receptor. It is, therefore, more closely related to orthostatic hypotension and syncopal events than other active ingredients, including terazosin and doxazosin. The latter are less powerful than prazosin but highly specific for 1 receptors and are thus associated with orthostatic hypotension (7-9%, mostly resulting in elderly) [81-83], while alfuzosin and tamsulosin are less associated with this adverse drug reaction (1,33. Central 2-agonists act on the 2 presynaptic receptors in the brainstem: they determine inhibition of sympathetic tone and reduction of vasopressor efferent impulses from the centers of the brainstem, determining orthostatic hypotension mediated by vasodilatation [87]. There are no studies in literature which evaluate the prevalence of orthostatic hypotension in hypertensive subjects treated with this class of drugs. However, in patients suffering from autonomic failure, the peripheral 2-agonist effect predominates, determining vasoconstriction: in these subjects, 2-agonists, such as clonidine, may increase blood pressure [88]. In particular, the concomitant administration of nitrates is contraindicated [90]. Moreover, an increased prevalence of orthostatic hypotension during treatment with sildenafil or tadalafil in combination with alphaantagonists (for example doxazosin) has been highlighted [91]. They can be divided into three main categories, according to their prevalent action on different types of -adrenergic receptors: non selective -blockers, selective 1-blockers, - nonselective -blockers. In older individuals with an initial, age-related, autonomic and baroreceptorial dysfunction, the use of these drugs may affect the compensatory response to orthostatism (increase of heart rate and peripheral vasoconstriction) [79], as noticed by Kamaruzzaman et al. There are no studies comparing the prevalence of orthostatic hypotension in patients treated with different types of -blockers. Conclusion Orthostatic hypotension is associated with higher morbidity and mortality. Antihypertensive drugs may determine orthostatic hypotension through multiple mechanisms. Although most of these drugs can theoretically lead to orthostatic hypotension according to the mechanism of action and the data sheet of the drug, in clinical practice this phenomenon does not occur constantly. This discrepancy is probably due to the establishment of compensatory mechanisms in response to the drop of blood pressure in orthostatism, to the pharmacokinetic and pharmacodynamic inter-individual variability, and to the influence of external factors or comorbidities which act on autonomic nervous system and renal function. In the treatment of hypertension of patients at risk of orthostatic hypotension, such as the -Blockers 1-antagonists inhibit the vasoconstrictor effect mediated by catecholamines through selective blockade of 1-adrenergic receptors, in the absence of changes in cardiac output, plasma renin levels, and baroreflex function. At high doses they determine further vasodilators effects, mainly on arteries, through the inhibition of the phosphodiesterase enzyme in smooth muscle cells of arterial walls. There are no experimental data regarding the prevalence of orthostatic hypotension in elderly patients treated with centrally-acting antihypertensive drugs, so the role of these drugs in the development of orthostatic hypotension is controversial. In the treatment of benign prostatic hypertrophy in subjects who also suffer from hypertension, a lower prevalence of hypotensive events during protracted treatment with alfuzosin and tamsulosin if compared to other -antagonists has been highlighted. Furthermore, the optimization of a pharmacological treatment of hypertension seems to be related to a reduced prevalence of orthostatic hypotension. Equally, it is useful to report preoperative autonomic failure or its associated comorbidities such as diabetes mellitus [92], in order to utilize anesthetics that cause less hemodynamic instability and a lower intra-operative blood pressure drop. Moreover, special caution is advised during the administration of psychoactive drugs in elderly people because they are more susceptible to their adverse effects, both cardiovascular and neuro-psychiatric. Simultaneous presence of two or more drugs in combination therapy often leads to a synergistic or additive effect, which contributes to a more significant reduction of blood pressure levels when compared to the action of a single drug. Considering the correlation between the number of vasoactive drugs and the blood pressure drop in orthostatism, after the detection of drug-induced orthostatic hypotension, a reduction in the number and type of hypotensive drugs is auspicable, in order to reduce morbidity, mortality and symptoms related to orthostatic hypotension, as well as a selection of therapies associated to a lower risk of orthostatic hypotension. Enlund M, Mentell O, Krekmanov L (2001) Unintentional hypotension from lidocaine infiltration during orthognathic surgery and general anaesthesia. Pacher P, Kecskemeti V (2004) Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns. Ungvari Z, Pacher P, Kecskemeti V, Koller A (1999) Fluoxetine dilates isolated small cerebral arteries of rats and attenuates constrictions to serotonin, norepinephrine, and a voltage-dependent Ca(2+) channel opener. Cherin P, Colvez A, Deville de Periere G, Sereni D (1997) Risk of syncope in the elderly and consumption of drugs: a case-control study. Fedorowski A, Hedblad B, Engstrom G, Gustav Smith J, Melander O (2010) Orthostatic hypotension and long-term incidence of atrial fibrillation: the Malmo Preventive Project. Fedorowski A, Burri P, Melander O (2009) Orthostatic hypotension in genetically related hypertensive and normotensive individuals. Leonetti G (1989) the clinical performance of nicardipine in elderly hypertensive patients with concomitant diseases. Haiat R, Piot O, Gallois H, Hanania G (1999) Blood pressure response to the first 36 hours of heart failure therapy with perindopril versus captopril. Fedorowski A, Engstrom G, Hedblad B, Melander O (2010) Orthostatic hypotension predicts incidence of heart failure: the Malmo preventive project. Lepor H, Jones K, Williford W (2000) the mechanism of adverse events associated with terazosin: an analysis of the Veterans Affairs cooperative study. Formulation(s) and strength(s) proposed for inclusion; including adult and paediatric dosing 4 6. Whether listing is requested as an individual medicine or as a representative of a pharmacological class 7. Review of benefits: summary of comparative effectiveness in a variety of clinical settings 10. It has played a key role in the elimination programmes of these two neglected tropical diseases and was more recently approved for the treatment for Strongyloides infections. Effective treatment of patients with scabies using ivermectin has been reported in many different clinical environments from individual patients to institutions and in older persons. There have been a number of clinical trials where it has been found to have clinical and parasitological efficacy in both those with the conventional forms of scabies and those with crusted scabies, a more severe form often seen in the immunocompromised (Rosumeck et al 2018). There have been three largescale public health programmes using ivermectin in the control of endemic of scabies in Fiji (Romani et al 2015), Australia (Kearns et al 2015) and an ongoing major outbreak in Ethiopia. At present, scabies is often treated with topical anti mite agents such as permethrin, benzyl benzoate, crotamiton and sulphur containing pastes or soaps (Strong and Johnston 2006). The use of gamma benzene hexachloride has been almost universally discontinued because of concerns over potential neurotoxicity. These topically applied treatments, while effective in individual cases, have major disadvantages when treating large numbers of individuals or patients with severe infestations such as crusted scabies or scabies in older persons. These include the need to apply topical preparations over the entire body, often more than once, as well as the need to simultaneously treat all other family members whether or not symptomatic. Poor compliance with treatment regimens is a major issue in management of endemic scabies. Formulation(s) and strength(s) proposed for inclusion; including adult and paediatric dosing 5. The proposed formulation of ivermectin is a tablet (scored) in 3 mg doses, to be administered in a single-dose of 200 µg ivermectin/kg body weight. This is the proposed dosing regimen for adults and children over the age of 5 or with a minimum body weight of 15 kg. Pharmacology, treatment details, public health relevance and evidence appraisal and synthesis Pharmacology and mode of action of Ivermectin in Human Scabies Ivermectin is absorbed after oral administration. A 12 mg dose in an adult male results in a Cmax of 24-30 ng ml -1 and tmax of 5-10 h. After an initial peak if plasma levels there is a second rise in these levels between 6 and 12 h suggesting enterohepatic recycling. Ivermectin is bound to fat containing tissue and plasma proteins but is also present in skin peaking at 8 h after oral administration. These studies have been carried out in healthy volunteers and patients with onchocerciasis. There have been few studies in breast-feeding women but the maximum recorded concentration in breast milk was 14. Current recommendations advise that ivermectin should not be used in pregnant women or those currently breast feeding. The principal targets of the drug are the glutamate-gated chloride ion channels which occur in invertebrate (including Sarcoptes) nerve and muscle cells (Mounsey et al 2007). This leads to membrane hyperpolarisation and failure of intermuscular signal transmission. In turn this leads to functional failure in locomotion, feeding and sensory input and death of adult mites. Ivermectin does not destroy mite ova and hence a second dose is often used to eliminate newly hatched larvae and adults. This dose schedule is for individuals over the age of 5 or with a minimum body weight of 15 kg. Repeated therapy every 1 week for up to 8 weeks is recommended for immunocompromised individuals with crusted scabies. Ivermectin is indicated as a drug of choice for scabies by the certain countries including Australia and France and as second line therapy in other countries. It is also recommended in the national guidelines of Japan and by the United States Centers for Disease Control and Prevention.
Non-parametric statistical methods and stepwise multiple logistic regression analysis were utilized to study the independent effects of the variables on mortality underlying depression definition discount amitriptyline 25mg online. There were no differences in demographic data depression test francais cheap 25 mg amitriptyline with mastercard, insurance mood disorder lupus generic amitriptyline 50mg on line, screening colonoscopy tropical depression weather definition buy amitriptyline 25mg with mastercard, cancer stage at diagnosis depression documentary generic amitriptyline 25mg without a prescription, treatment and early deaths related to severity of disease burden on presentation depression definition journal amitriptyline 50 mg line, between study groups. The high mortality despite similar clinical features may be attributable to highly aggressive tumor behavior among African Americans that has been recently reported in literature. Purpose: Constipation affects approximately 25% of the population in the United States. Methods: this case-control study involved consecutive patients who underwent diagnostic colonoscopy for constipation at Digestive Disease Institute. The control group consisted of consecutive patients with an average risk for colon cancer who underwent routine screening colonoscopy. History of smoking was associated with colon adenoma in the univariable analysis, but the association was not significant in the multivariable analysis. Other incidental findings on colonoscopy in the study group included diverticulosis in 138 (30. Conclusion: this case-control study showed that patients undergoing diagnostic colonscopy for constipation had a lower prevalence of colon adenoma, as compared with patients undergoing routine screening colonoscopy. Therefore, these patients had no more than average risk for colon adenoma and only routine screening colonoscopy is indicated. Demographic, clinical and laboratory data were obtained from electronic records and statistically anaiysed. Other laboratory data such as levels of white blood cell count, serum creatinine, and serum albumin were not predictive of recurrence. Among co-morbid conditions, there was a trend towards recurrence among those who had gastroesophageal reflux disease (p=0. In-patient medication utilization, including number and type of antibiotic, was not associated with increased recurrence. To our knowledge, this has not been described as a known predictor for recurrence. Although its mechanism remains unclear, thrombocytosis greater than 300,000 may signify a brisk inflammatory response with possibly a similar mechanism not unlike that seen with leukocytosis. Purpose: A glucagonoma, a glucagon secreting tumor of the pancreas, can be a devastating diagnosis resulting in metastasis and thromboemoblism. Surgical pathology revealed a well-differentiated pancreatic neuroendocrine tumor, positive for glucagon by immunohistochemistry. Nonspecific symptoms such as anemia, diarrhea, and thromboembolism may also occur. Surgical resection is curative; however disease is frequently metastatic at presentation. Our patient lacked typical features of presentation and only complained of chronic diarrhea. Purpose: Rumination syndrome is the effortless regurgitation of recently ingested food which is not preceded by retching. Objective confirmation of the findings has been shown using antroduodenal manometry or esophageal manometry-impedance, but the sensitivities and availability in clinical practice of these modalities are lacking. Methods: A 23 year old female was referred with complaints of worsening regurgitation for 6 years. The patient indicated that regurgitated material comes up after nearly every meal without retching or nausea and that episodes began immediately after or sometimes during a meal. On colonoscopy, an 8mm pedunculated polyp with a long stalk was seen in the ascending colon,along with a 1 cm sessile polyp in the sigmoid colon. Histopathological examination revealed a tubular adenoma in which two discrete ova with chronic inflammation could be seen in the lamina propria. High power demonstrated the ova were oval in shape, one showing the characteristic lateral spine of Schistosoma mansoni, and both contained viable miracidia. Further history revealed the patient had lived in Liberia for most of her life where she had bathed and drank water from a lake. She continues to remain symptom free and her immigrated family members were recommended surveillance. During their life cycle, the larvae penetrate the skin, migrate to the lungs through venous circulation and mature into adult worms in the liver. They migrate to the mesenteric vessels of bowel or bladder where the female worms lay eggs. Eggs retained in the intestinal wall cause an inflammatory response leading to hyperplasia, ulceration, microabscess, and granuloma formation. Clinically they may present as colicky abdominal pain, change in bowel habits, or occult gastrointestinal bleeding. Some studies suggest an increased risk of colorectal cancer in patients with schistosoma egg induced polyps particularly those with atypical hyperplasia. Conclusion: this patient demonstrates how uncommon diseases are being seen frequently with an increase in migration. A keen vigilance should be kept on history, and labs which may suggest parasitic infection in an asymptomatic individual that comes for routine screening. Purpose: To draw attention to mucosal tears as an unusual but important endoscopic presentation of collagenous colitis. Methods: Case report of patient with collagenous colitis and mucosal tear on colonoscopy. Results: A 60-year-old woman with a history of constipation presents with a complaint of rectal pain, watery, non-bloody diarrhea, and a 6-pound weight loss over one year. Random colon biopsies showed diffuse, irregular thickening of the subepithelial collagen table accompanied by focal denudation of the surface epithelium and increased intraepithelial lymphocytes, diagnostic of collagenous colitis (Figure B, right). Biopsies of the mucosal tear showed granulation tissue with acute inflammation consistent with a nonspecific ulcer (Figure B, left). The patient was treated with Pepto-Bismol, budesonide, mesalamine enemas, metronidazole, and ciprofloxacin. After three days, the diarrhea and rectal pain resolved and after three weeks, all medications, except budesonide, were stopped. At two years, the patient remained asymptomatic with normal colonoscopy and biopsies. Conclusion: Mucosal tears have been reported previously in 12 patients with collagenous colitis. The cause is unclear but may be related to underlying inflammation with mucosal friability. In microscopic colitis, the mucosa is endoscopically normal, but histology shows characteristic abnormalities. We propose that mucosal tears may be a characteristic and significant endoscopic abnormality in collagenous colitis. Standard treatment for collagenous colitis appears adequate for management of mucosal tears. Purpose: Although combination therapy with bevacizumab (a monoclonal antibody against vascular endothelial growth factor) and paclitaxel has shown improvement in progression-free survival in patients with metastatic breast cancer, bevacizumab has been linked to an increased risk of severe bowel complications. Three months prior to this presentation, she was found to have liver and bone metastases, and was started on bevacizumab and paclitaxel therapy. Her past medical history was also significant for a history of paroxysmal atrial fibrillation for which she was on warfarin therapy. Her physical exam was otherwise normal except for tenderness to palpation in the left lower quadrant. Colonoscopy revealed focal ischemia within the sigmoid colon spanning approximately 8 cm with surrounding ulceration and edema. Her rectal bleeding was of a self limited nature with no further episodes of bleeding during the hospitalization and stable hemoglobin prior to discharge. Although ischemic colitis has been reported in treatment for metastatic cancer in patients who have received prior radiation therapy, to our knowledge, this is the first documented case of ischemic colitis in the treatment of metastatic cancer in the absence of radiation. However, treatment with bevacizumab has also been shown to increase the risk of arterial thromboembolism which could also potentially lead to bowel ischemia. Other known complications of bevacizumab therapy include abdominal pain, vomiting, gastrointestinal hemorrhage, and perforation. New abdominal symptoms must be taken seriously in patients treated with bevacizumab and caution must be used when prescribing this therapy to patients. Purpose: Muir-Torre syndrome is a rare autosomal dominant condition characterized by the combination of sebaceous gland tumors and at least one visceral cancer especially colonic. Early recognition of the syndrome in patients with sebaceous gland tumors should facilitate early detection of subsequent malignancies if the patients and their relatives are entered into appropriate screening programs. Case presentation: A 46 years old asymptomatic male was referred by his dermatologist and primary care physician for screening colonoscopy before the age 50. The patient had no gastrointestinal symptoms and had no previous history of inflammatory or any other bowel disease. His paternal grandmother had colon cancer at old age but he denied any other family history of cancer. However, he recently had an excision of a sebaceous cyst from the nose and the histology showed sebaceous carcinoma. Histological findings of sebaceous carcinoma raised concerns about the possibility of Muir-Torre Syndrome which involves an increased risk of concomitant visceral malignancy especially colonic carcinoma in such patients and indicates regular colonic screening. Based on this clinical concern the patient was referred for screening colonoscopy. Patient had colonoscopy performed which showed an ulcerated circumferential mass at the level of the cecum, biopsies confirmed the diagnosis of moderately and poorly differentiated adenocarcinoma of the colon. Staging investigations were normal and patient was referred for surgical colonic resection. Conclusion: Patients with Muir-Torre Syndrome are probably more common than is recognized, but sebaceous gland tumors are rare and the diagnosis of such a tumor should suggest the possibility of the syndrome and prompt a search for associated malignancies especially colonic carcinoma and to investigate for the underlying genetic mutation. Timely diagnosis of colonic malignant neoplasm in this subset of patients, before the screening age of 50 can cure the disease and save many lives. Purpose: To increase awareness among physicians of antibiotic-associated hemorrhagic colitis caused by Klebsiella oxytoca. Results: Case 1: A 30 year-old man with no significant past medical history presented with right-sided abdominal pain and bloody diarrhea one week after receiving amoxicillin following a routine dental procedure. Multiple stool studies were negative for the presence of Clostridium difficile toxin. Stool studies were negative for the presence of Clostridium difficile toxin; however Klebsiella oxytoca was isolated from stool cultures. Conclusion: Colitis following administration of an antibiotic is a well-recognized complication, with Clostridium difficile traditionally implicated as the most common culprit. Antibiotic-associated hemorrhagic colitis caused by Klebsiella oxytoca is a separate entity from C. The colitis associated with Klebsiella oxytoca usually displays an abrupt onset and involves the right colon. The colitic symptoms are typically self-limited and resolve after discontinuation of the offending antibiotic without the need for additional treatment. Our series of patients emphasize the importance of pursuing specific studies for the diagnosis of K. Greater awareness of Klebsiella oxytoca associated colitis is needed among gastroenterologists and primary care physicians in order to avoid misdiagnosis and unwarranted therapy. A repeat colonoscopy revealed diffuse petechiae, ecchymosis and ulceration in the sigmoid descending colon region (Fig 1). Results: Biopsies were obtained and the pathology revealed amyloid deposition in the muscularis mucosa on Congo Red staining showing the apple green biferengent appearance under polarized light (Fig 2). Biopsies with amyloid staining is critical for making the diagnosis, as early diagnosis reduces risk of critical systemic end organ damages. Purpose: Lymphomas may appear in the colon as primary malignancy or as a part of systemic disease. Knowledge of the forms of presentation is therefore important in order to suspect the disease and reach an early diagnosis. Additionally, colonic lymphoma often requires a multidisciplinary treatment approach. Methods: A 59 years old male was admitted with a chief complaint of left sided dull, non-radiating abdominal pain associated with 20lbs of weight loss over the last 2 months. On physical examination, his abdomen was soft with normal bowel sounds and mild tenderness in the left lower quadrant without any rebound. A firm mass with an irregular margin, about 10x12 cm in size was palpable in left lower quadrant of the abdomen. He had had an unremarkable screening colonoscopy about 18months prior to this visit. A colonoscopy showed a 15cm long circumferential, ulcerated, friable, nearly obstructing lesion in the descending colon 60 cm from the anal verge. Results: Histopathological examination of surgical specimen confirmed the diagnosis of large B cell lymphoma. At six months the patient has not shown any evidence of recurrence of his disease. We found our case unique because of the large size of tumor, the rapidity of growth and the lack of traditionally described risk factors for the development of lymphoma. Our case illustrates that treatment involving a multidisciplinary approach including surgery and chemotherapy is considered ideal. Reservoirs include a variety of water environments and vegetable produce with an increase in isolation during warm weather months. Originally thought of as a pathogen in the immunocompromised host only, these organisms are now recognized as a cause of a spectrum of disease in immunocompetent humans. The following is a case of diffuse colitis with deep ulcers secondary to Aeromonas sobria. A 76-year-old, previously healthy female presented with complaints of 2-3 months of nightly fevers up to 102 degrees Fahrenheit associated with sweats. She also complained of crampy abdominal pain and diarrhea intermittently associated with the passage of bright red blood over the previous two weeks and a 15 pound weight loss over the same time period.
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