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By M. Arokkh. Cumberland College.

Cut away all avascular scar tissue order 5mg prednisolone visa, until you reach a and suture the proximal portion to its donor site cheap 20mg prednisolone amex. Make sure the ulcer site is free of when the base of the ulcer is covered with suitable infection before you attempt such a flap purchase prednisolone 10 mg with visa. It is found in West and Central of the flap and making sure it will cover the ulcer when the Africa prednisolone 5 mg low price, India, China, Indonesia and Australia knee is flexed. Infiltrate the flap area with dilute causative organism, mycobacterium ulcerans which causes lignocaine/adrenaline solution. Debride the ulcer necrosis of skin and deep fascia through the action of thoroughly to produce fresh clean granulation tissue. These result in localized skin and on the limbs, and is often near a joint, although the site sepsis arising from apocrine glands (so do not develop in is variable. You will only achieve a lasting cure by excising the occurs, and a foul slough forms. Early on, use streptomycin and rifampicin patches or plaques, pulmonary infiltration and skin for 8wks; healing continues after completing the course of nodules (though these are often absent). If the lesion is ulcerated, control secondary The nodules do not occur in areas subject to sustained pyogenic infection with antibiotics, and irrigate with warm pressure (e. Use a single oral dose of Chemotherapy (doxorubicin, vincristine, or bleomycin) azithromycin 30mg/kg. Typically it occurs on the foot, but may affect the hand, particularly in those working in the fields in arid zones with short rainy seasons especially in latitudes between 15S and 30N. It begins slowly to form a circumscribed, rubbery or cystic, painless lobulated mass. A, mycetoma of the hand, spreading through the carpal tunnel into the forearm (unusual). B, advanced become secondarily infected, but this secondary infection mycetoma of the thigh 20yrs after infection had begun in the foot. This is the typical early lesion but simultaneous involvement of both feet is rare. This may be part of a dumb-bell lesion extending from the sole between the metatarsals. Flood the operative field at the end of the deep fat between the tendons, along the lumbrical canals, operation with iodine to minimize risks of contamination. Mycetomas never is appropriate provided you can clear the disease regress spontaneously. Regional lymph nodes are usually not enlarged, but may be affected by secondary sepsis and occasionally by If there is a lesion of the hind foot with severe bone and lymphatic spread of mycetoma. Try to find the granules, because without them all a pathologist can say is that there is a If there is a lesion of the hindfoot with minor bone granulomatous infection with multiple micro-abscesses. Make sure there is no somaliensis medium-sized yellow, actinomyces madurae response to medical treatment. If you cannot see the grains with the naked eye, get an aspiration specimen for cytology. Once the periosteum is breached, the (2),Follow the patient up carefully, and make sure he tarsal and metatarsal bones are rapidly destroyed. New bone in the walls of abscesses forms buttresses When he does, this is an indication for urgent amputation projecting outwards at angles to the shaft of a long bone. The centre of an infected bone has a honeycomb appearance, and a good film shows tiny cystic areas of bone destruction, each the site of a micro-abscess. Oedema due to venous obstruction For actinomyces, use streptomycin 14mg/kg od with becomes solid late, and eventually reaches a stage where it dapsone 15mg/kg bd for 1yr at least; you can replace fails to pit. Rifampicin can replace streptomycin and sulfadoxine- In most areas, the causes of lymphatic obstruction pyrimethamine (Fansidar), and ciprofloxacin can replace (lymphoedema), in decreasing order of frequency are: cotrimoxazole in resistant cases. If a lesion is localized, and is confined to the soft (5) Block dissection of the glands, usually for carcinoma. Take great care not to rupture the capsule of eumyces as you will otherwise transfer the fungus to Other causes include: adjacent areas, and recurrence will be inevitable. The site involved indicates the probable cause: regions with Wuchereria bancrofti and less often to Brugia Breast and arm, or vulva tuberculosis, filariasis malayi, or B. Elephantiasis due to filariasis is difficult to influence chronic non-specific inflammation. Microfilariae found in bilateral asymmetrical swelling of the feet and lower legs. This causes the lymphatics to fibrose, and obstruct, and the femoral nodes to enlarge. Lymph may ooze with persistent itching of the 1st and 2nd toe clefts, through the skin, which may be secondarily infected by and plantar oedema of the forefoot. Acute recurrent attacks of causing multiple excrescences on the feet, notably lymphangitis. Lines of hyperpigmentation on the skin Elevation, elastic stockings, and long leather boots help in indicating previous lymphangitis. If you see a patient early, persuade him to wear boots or shoes which Suggesting tuberculosis (17. The main preventive many superficial nodes (inguinal, axillary, and cervical); measure is wearing fully protective shoes rather than a history of prolonged illness in the past, with fever and sandals or open shoes from childhood. Suggesting malignant disease: firm mass in the groin or axilla; typical purplish raised lesions of Kaposi sarcoma. Each episode usually affects the same leg, and the second leg does not usually become involved until the first one shows clear signs of disease. Although the burning area of the leg may be tender, few patients seek help at this stage. Thickening of the skin (pachydermia), from constant scratching, is a common presentation. When the toes start swelling, the itchy area precedes the upper level of the swelling, and indicates progression of the disease. Early oedema of the left forefoot affecting the plantar aspect of the metatarsal pad, as well as the toes, which appear rigid, as if they were wooden and nailed on to the forefoot. They may be lifted off the floor by plantar oedema, and lack the usual curve of normal toes. C,D, increased skin markings, which become more evident if the toes are compressed. Press with your thumb on the sole over the head as fever, lymphangitis, tender lymphadenopathy, of the first metatarsal. The forefoot shows an excessive deposit of keratin on the In males, the spermatic cord, epididymis and testes are dorsum at the base of the first or second toe cleft. The chronic effects are the result of lymphatic obstruction, commonly in the retroperitoneum. They have no sensory nerves, so you can diffuse, resembling a varicocoele (34-12E), or encysted remove them without anaesthesia. Do not try to remove redundant tissue unless rigorous (6),Lymphatic varix (hygroma). Microscopic examination of the fluid rarely tropics and subtropics Wuchereria bancrofti is the cause in reveals the filaria. The hydrocele fluid shows a and microfilariae then migrate to the lymphatics via the mottled echogenicity. Add a single dose albendazole 400mg, and then a single dose of ivermectin (at dose according to weight, 34. Diethylcarbamazine is no longer recommended especially in areas endemic for onchocerciasis of loaiasis. Reduce lymphoedema by prolonged firm bandaging; then prevent further swelling by supporting the tissues permanently. Alternatively, insist on bed rest and bandage the leg with crepe bandages from the foot upwards, using sponge rubber to protect the tissues from too tight bandaging. When you have reduced the swelling, fit a graduated compression stocking, which will be useful despite the discomfort in hot moist climates. If the disease is advanced, mobilize the oedema fluid by initial elastic compression, and then consider surgery; this is not easy. The operation is a 2-stage process; excise half the circumference of the swollen tissues at a time. The deep fascia must be included in the excision to allow drainage through the deep muscle compartments of the leg. The Charles operation where only the oedematous A, extensive filarial involvement of the leg. After the operation she subcutaneous tissue is removed, and the fascia covered could walk without support. B, East African woman with an axillary swelling; needle puncture showed that this was a lymphatic varix. They all arise from mesenchyme, are commonest from the 2nd to the 4th decades, and vary considerably in malignancy. They spread by local infiltration, and lymphatic spread is usually late but may be present in up to 10%. In less differentiated tumours blood dissemination may occur early, especially to the lung. The results of radical local excision are at least as good as very radical surgery involving amputation. Chemotherapy is an expensive supplement to surgery, and is not nearly so effective as with lymphoma or nephroblastoma. There are basically 4 histological types; there is no proper capsule, and recurrence will be well differentiated (hard to distinguish from a lipoma), inevitable. If you are going to operate, make sure you can mixed (commonest), round cell (most malignant), excise the tumour with a margin of normal tissue. Do not try to excise such a tumour unless you know differentiated) tend to recur locally; round cell ones (rare) the full extent of its spread. In the thigh, distinguish a liposarcoma from pyomyositis by aspiration of pus in the latter. The patient, who is usually 30-50yrs, presents with a firm to hard mass which is This presents as a solid swelling like a ganglion; because usually painless in its early stages. Fibrosarcomas are of its position next to tendons, excision is usually moderately malignant, and spread by local infiltration. Make sure you use a tourniquet when removing these tumours and use a meticulous technique. This starts as an intradermal plaque and extends slowly Take skin snips if you suspect leprosy. This usually occurs on the extremities arising in Correct the nutritional deficit; these patients need subcutaneous tissue or in the fascia, where the prognosis is high-protein, high-calorie diets even just for healing. It probably Clean and dress the sores, initially twice daily, and treat arises from fibroblasts. You have to be radical with the removal These develop from neural sheath tissue often in of ischaemic tissue, otherwise sepsis will continue and long-standing neurofibromas in Von Recklinghausens necrosis will extend. The aim of getting successful skin disease (neurofibromatosis type 1) where the chance of cover is to remove the pressure point, so do not be afraid malignant transformation is 15%. Sudden hypotension may be It takes <1hr to produce ischaemic changes in the skin catastrophic!

The following trials of antioxidants need then to be rigorous cheap prednisolone 20mg visa, identifying not only any positive patient outcomes generic 10 mg prednisolone free shipping, but also the underlying mecha nism prednisolone 20mg free shipping, and of course any deleterious outcome buy prednisolone 10 mg amex. Glutathione is synthesized in the body by three amino acids by the catalysing of intracellular enzymes gamma-glutamylcysteine synthetase and glutathione synthetase. L-glutamic acid and gly cine are two precursors of glutathione that are biologically and readily available. However, the limiting precursor to glutathione biosynthesis and the third amino acid, L-cysteine, is not readily available in a human diet. Vitamin E incorporates into the phospholipid bilayer halting lipid peroxidation chain reactions. A benefit of -tocopherol is its ability to restore its antioxidant capacity from its oxidized form following free radical scavenging, and incorpo rate back into the plasma membrane. This is a prime example of a cellular antioxidant net work prone to dysregulation. The bene ficial effects of -tocopherol are not limited to its antioxidant properties, and recently atten tion has focused on its blood oxygenising and endogenous cell signalling functions [113]. Vitamin E foodstuffs primarily consist of -tocotreinol, an isoform of -tocopherol which has higher antioxidant efficacy in biological membranes. Despite this, the uptake and distri bution of -tocotreinol is far less than -tocopherol. Therefore, the basis of vitamin E supple mentation is to enhance -tocopherol levels in cell plasma membranes to prevent lipid peroxidation and resultant oxidative stress. One drawback of -tocopherol is that it takes several days of pre-treatment to exhibit antioxidant effects [114]. Vitamin E therapy has been extensively researched for renal and cardiovascular benefits in human disease populations. Nevertheless, confounding reports mean there is a lack of con sensus as to whether vitamin E therapy induces an overall benefit. A large scale trial concluded that vita min E supplementation to cardiovascular high-risk patients over 4. They suggest that vitamin E supplementa tion significantly increases the risk of prostate cancer for young healthy men [116]. However, this study was highly criticized owing to a bias in data analysis and numerous methodological flaws [121-130]. The appa rent lack of clarity surrounding vitamin E supplementation and associated renal and cardio vascular outcomes appears to stem largely from differences in trial design and failure to specify the form of tocopherol used. Coenzyme Q - Maintaining mitochondrial health10 The heart and kidneys contain the highest endogenous levels of co-enzymes (Co)Q and9 CoQ compared to all other organs [131, 132]. This is likely due to the respective reliance on10 aerobic metabolism and high density of mitochondria in the intrinsic functioning cells from these organs. It is imperative that endogenous CoQ levels are maintained to ensure mito10 chondrial health, and this forms the rationale for CoQ therapy. CoQ is a fundamental lip10 10 id-soluble component of all cell membranes including those enclosing subcellular compartments. The continual oxi2 2 dation-reduction cycle, and existence of CoQ in three different redox states, explains its ac10 tions as an important cellular redox modulator through its pro-oxidant and antioxidant actions. The reduced form of CoQ10 2 10 is able to give up electrons, thereby scavenging free radicals. The intermediate of ubiqui none and ubiquinol is the univalently-reduced ubisemiquinone (CoQ -H ) which acts as a+ 10 pro-oxidant to form O - and, subsequently, H O. Ubiquinol is able to donate a hydrogen atom and thus quench peroxyl radicals, preventing lipid peroxidation chain reactions. CoQ and -toco10 pherol co-operate as antioxidants through the actions of CoQ -H restoring -tocopheroxyl10 2 back to -tocopherol [109, 139]. This is in accordance with in vivo studies investigating the effects of CoQ supplementation10 which have primarily found a limited antioxidant capacity. Nonetheless, many in vitro studies demonstrate antioxidant properties of CoQ in single cells, and benefits of CoQ supplementation in humans are at10 10 tributed to its ability to maintain efficient mitochondrial energy metabolism and thus pre vent mitochondrial dysfunction, rather than act as a direct cellular antioxidant. CoQ10 supplementation in vivo reduced protein oxidation in skeletal muscle of rats but had no ef fect on mitochondrial H O production in the kidney [142]. However, Ishikawa and collea2 2 gues (2011) demonstrated a decrease in kidney O - levels in hemi-nephrectomised rats on a 2 CoQ supplemented diet, and increased renal function compared with rats on a control diet10 [143]. Recently, CoQ supplementation improved left ventricular diastolic dysfunction and10 remodelling and reduced oxidative stress in a mouse model of type 2 diabetes [144]. Omega-3 poly-unsaturated fatty acids Inflammation and oxidative stress Inflammation and fibrosis are causes, as well as consequences, of oxidative stress [145, 146]. Direct targeting of inflammatory and fibrotic pathways with more specific modifying com pounds presents a way to indirectly decrease oxidative stress in chronic pathologies. Recently, a highly beneficial outcome of fish oil supplementation was found with heart failure patients with co-morbid diabetes [155]. Clinical studies have found fish oil treatment modulates lipid levels [156, 157], and has anti- thrombotic [158, 159] and anti-hypertensive effects due to its vascular and endothelial ac tions [160]. Allopurinol A xanthine oxidase inhibitor Allopurinol treatment aims is to inhibit xanthine oxidase to decrease serum uric acid and its associated toxic effects. Allopurinol and its metabolite, oxypurinol, act as competitive sub strates for xanthine oxidase. They enhance urinary urate excretion and block uric acid reab sorption by urate transporters in the proximal tubule, thereby facilitating enhanced uric acid excretion [161-163]. Allopurinol treatment of diabetic mice attenuated hyperuricaemia, albu minuria, and tubulointerstitial injury [164]. Bardoxolone methyl is a triterperoid derived from natural plant products that has un dergone oleanolic acid-based modification [173]. Its mechanism of action is largely un known, however, it induces an overall antioxidative protective effect with anti- inflammatory and cytoprotective characteristics [174, 175]. L-Carnitine Improving cardiovascular health in dialysis Carnitine is an essential cofactor required for the transformation of free fatty acids into acyl carnitine and its subsequent transport into the mitochondria for -oxidation [177]. Acylcarnitine is also essential for the removal of toxic fat metabolism by-products. Carnitine is obtained primari ly from food stuffs, however it can be synthesised endogenously from the amino acid L-ly sine and methionine [177]. L-carnitine sup plementation offsets renal anemia, lipid abnormalities and cardiac dysfunction in hemodialysis patients [179]. Left ventricular hypertrophy regressed in hemodialysis patients receiving 10mg/kg of L-carnitine immediately following hemodialysis for a 12 month peri od. Other measures of cardiac morbidity such as reduced left ventricular ejection frac tion and increased left ventricular mass also significantly improved following low dose L- carnitine supplementation [181]. Interestingly, oxidative stress is a major characteristic of hemodialysis patients [183]. They suggest that this anti-apoptotic mechanism may also explain the demonstrated re duction in morbidity from cardiomyopathies in L-carnitine supplemented hemodialysis pa tients. The addition of L-aspartic acid or L-glutamic acid with L-citrulline and arginiro succinic acid synthase as the rate determining enzyme forms L-arginine [188]. These disparate findings highlight the need to measure L-arginine levels in patients before com mencing L-arginine supplementation. Combination antioxidants Compounds commonly used to alleviate oxidative stress exhibit different antioxidant ac tions, and so there exists the potential for different antioxidants to work together to improve whole cell and organ function through a targeted polypharmaceutical approach to decrease oxidative stress. However, most clinical studies investigating the effects of combination anti 248 Oxidative Stress and Chronic Degenerative Diseases - A Role for Antioxidants oxidants have demonstrated confounding results. The short2 period of time (2 months) of the intervention may explain this result and longer trials need to be carried out. Despite this, long-term treatment in with the antioxidants vitamin C, vitamin E, CoQ and selenium10 has been shown to reduce multiple cardiovascular risk factors [201]. Stages 2 and 3 are best to target to slow or stop further development of the disease. Given the complex nature of oxidative stress and its mo lecular pathways, antioxidants may need to be given as a polypharmacotherapy to target each aberrant pathway, with the aim of reducing the burden of these chronic diseases. The role of inflammation in the cardio-renal syn drome: a focus on cytokines and inflammatory mediators. Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative. Weight and inflammation are the major deter minants of vascular dysfunction in the aortae of db/db mice. Review: Serum and urine biomarkers of kidney disease: A pathophysio logical perspective. Contribution of im paired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic op portunities. Renin-angiotensin- aldosterone system intervention in the cardiometabolic syndrome and cardio-renal protection. Aging increases oxida tive stress and renal expression of oxidant and antioxidant enzymes that are associat ed with an increased trend in systolic blood pressure. Apoptosis in mitotic competent undifferentiated cells is induced by cellular redox imbalance independent of reactive oxygen species production. Reactive Oxygen Species and Thiol Redox Signaling in the Mac rophage Biology of Atherosclerosis. Age-related in creases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes. Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease. Nanotransducers in cellular re dox signaling: modification of thiols by reactive oxygen and nitrogen species. Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial func tion culminating in increased apoptosis. Age-related changes in mitochondrial function and antioxidative enzyme activity in fischer 344 rats. Hitchhiking of Cu/Zn superoxide dis mutase to peroxisomes-evidence for a natural piggyback import mechanism in mam mals. Visualization of the compartmentalization of glutathione and protein-glutathione mixed disulfides in cultured cells. Seg ment-specific overexpression of redoxins after renal ischemia and reperfusion: pro tective roles of glutaredoxin 2, peroxiredoxin 3, and peroxiredoxin 6. Ex pression pattern of human glutaredoxin 2 isoforms: identification and characteriza tion of two testis/cancer cell-specific isoforms. Both thi oredoxin 2 and glutaredoxin 2 contribute to the reduction of the mitochondrial 2-Cys peroxiredoxin Prx3. Pathways of glutathione metabolism and transport in isolated proximal tubular cells from rat kidney. Per oxisome proliferator-activated receptor-gamma activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Identification and dissection of the Nrf2 mediated oxidative stress pathway in human renal proximal tubule toxicity.

Introduction Mosquito abatement methods may be either long term or temporary programs directed against larvae or adults generic prednisolone 5 mg fast delivery. Larvae management includes using larvicides and eliminating breeding sources by improving water drainage or using other methods of water management 5mg prednisolone amex. Ditching purchase prednisolone 5mg on line, pumping generic prednisolone 20 mg on line, filling and similar measures can take much time, labor and equipment to give long-term results. Installations should not begin such long-term measures without first obtaining assistance from experienced entomologists. Shallow sluggish streams and ponds containing plant growth provide excellent conditions for 71 mosquito breeding. Increase the water flow rate and reduce its surface area to decrease mosquito breeding; this is often less expensive than other methods. Obtain instruction from maintenance engineers to plan and carry out this operation. Where existing drainage control includes small dams, it may be possible to use these systems for mosquito abatement. To do this, periodically release collected water, either manually or by automatic siphon, to flush the stream below the dam. The stream must have sufficient capacity (with high banks) to prevent the stream from flooding over its banks. This can be a very effective means of abatement if it is possible to flush a stream more often than it takes for the specific mosquito species breeding in it to complete its aquatic development. Mosquito abatement in impounded water depends on reservoir preparation, water level fluctuation and proper shoreline maintenance. Clear reservoirs to provide clean water surface after impoundment between maximum and minimum water levels. Fill or alter depressions between minimum and maximum water levels to drain during water level fluctuations of the lake or pond. Lower the water level at intervals not to exceed 10 days to strand eggs, larvae and pupae at the margin, strand protective debris, and expose larvae to predators. Changes to water levels may involve a cyclical fluctuation, a seasonal recession, or a combination of these methods. Shoreline drainage, removing and burning driftwood, and controlling growth of shoreline vegetation 72 should all be a part of this action so water level fluctuation will not cause an increased breeding area for another pest species. Aquatic vegetation protects mosquito larvae and pupae protection from wave action and natural enemies and, in some cases, may seriously interfere with larvicidal applications on the water surface. If such vegetation is a serious problem, its elimination becomes an essential part of mosquito abatement. Either chemical or mechanical removal may be the proper procedure, depending on the type of vegetation, size of area, and how the water is used. Give consideration to soil erosion and effects of any vegetation management techniques on fish and wildlife. To manage mosquitoes in these areas, alter the salt content of water in the marsh, or use dikes and tide gates designed to control flooding. Planners need a thorough knowledge of the species and habits of the mosquitoes present to effectively conduct this type of management. Salt content in the water may seriously affect or limit the breeding of some species. Opening channels to let sea water enter breeding areas, or excluding sea water to reduce salt content may measurably reduce mosquito breeding. Use tide gates to prevent salt water from leaking in natural water courses or ditches. Surface feeding fish are sometimes used as a supplementary control measure against mosquito larvae. Use pumps to drain water when the area to be drained is at or below the water level of an adjacent body of water. Several standing pools may be drained into one, and the water pumped from this pool to the selected outfall. Fill and grade shallow pools to prevent mosquitoes from breeding in such places as beneath buildings, on improved grounds, or beside roadways. Cracks and low areas are likely to form as the fill settles, and will afford breeding places when flooded; pest managers can effectively treat these areas with mosquito larvicides. Adequate ditching should remove water so ground surfaces become dry and ditch levels return to normal within 4-7 days (depending on climate and species) after the ditch is filled by heavy rainfall or irrigation. In designing drainage systems, care is needed to prevent creating mosquito breeding areas in new locations. Larvicides and adulticides are the most important temporary mosquito abatement methods. Pest managers should use such temporary measures to give immediate relief from mosquitoes and when more permanent measures are lacking or in planning. Temporary methods are often much less costly than permanent measures and, in some instances, may be used at less expense than permanent systems, provided they do not adversely effect people or the environment. Also, it is often vital to take such temporary methods to rapidly reduce disease vectors during an arthropod-borne disease epidemic or during short-term operations an endemic disease area. To temporarily manage mosquito breeding, treat water surfaces with insecticides, or eliminate small water accumulations in temporary containers. All such water-holding containers must be treated for effective management to be achieved. Solutions, emulsions, suspensions, dusts or granules may be applied with ground-operated equipment. Solicit the help of all people in the area to eliminate temporary water containers. Adequately screening occupied structures is also essential where mosquitoes occur. Use space sprays to manage mosquitoes indoors where immediate reduction is needed. These sprays have little or no residual effect and must be reapplied whenever new mosquitoes enter the area. Where frequent reentry is a problem, or where disease-bearing species are present, apply residuals to all surfaces where mosquitoes are likely to rest (unless otherwise prohibited, such as in a food service area or hospital). Screens with apertures equivalent to 18 x 16 mesh are essential to keep disease-bearing and pest mosquitoes, flies, and other insects from entering buildings. Such repetitive treatments are usually very expensive and pose some risk to people or the environment; avoid them except in the most unusual conditions. Exterior residual sprays have a limited value in protecting single residences or small camps. Mosquitoes are generally the most important arthropods managed in contingency operations because of the number, types and distribution of diseases they transmit. These actions are essential to effectively combat such mosquito-borne diseases: (1) Individual protective measures. For additional protection, they should wear the uniform properly with sleeves down and buttoned and pants tucked into the boots. In areas where malaria is endemic, preventive drug treatments (chemoprophylaxis) should be started before deployment and rigidly enforced as long as people are in the area and for a prescribed period of time after leaving the area as directed by the command surgeon or preventive medicine officer. The main unit effort should focus on training people in protective measures and then strictly enforcing them, especially the regular use of malaria chemoprophylaxis as directed by the command surgeon or preventive medicine officer. Since Air Force and Navy units normally operate from established bases, their units normally receive direct unit support from the preventive medicine or pest management engineering units described in Army and Marine Corps units operate more diversely and as a result must have an increased pest management capability in each unit. Unit field sanitation teams give this support before deployment, using 2-gallon pesticide sprayers and selected premixed pesticides, such as those normally included in self-help programs on fixed installations. Pest management support beyond this level is given by preventive medicine or engineering units. Area protective measures are those carried out by preventive medicine or engineering units with specially trained technicians using special equipment and controlled or restricted-use pesticides. These are the only military units with the equipment and training needed to conduct a large scale pest management operation. You should be aware of the life cycle of mosquitoes so you can take steps to avoid rearing mosquito larvae in water containers on your property. Water gardens or small fountains should be treated with larvicides or contain mosquito eating fish to prevent emerging adult mosquitoes. Maintenance of screen doors and windows will prevent adult mosquitoes from entering homes. Remember, any container that will hold water for 5 to 7 days is a potential breeding site for mosquito larvae. If it is not possible to drain areas, then treating them with larvicides if they are supporting larvae is an alternative. Many mosquito larvicides on the market are very host specific and only disrupt the larval stage of mosquitoes and do not harm non target species. They can also avoid being outside at dawn, early evening, and dusk when the majority of biting 81 female mosquitoes are active. This type of control is not usually effective in Oklahoma because it is very rare for conditions to be conducive for fogging adult mosquitoes. Adult mosquitoes must come into contact with the pesticide, so timing of application is critical. Since different mosquito species are active during different periods throughout a 24hr day it is critical to fog at exactly the proper time to get effective control of the target species. Extensive behavioral knowledge of the species to be controlled must be utilized and the spray applied only when adults are active. Weather conditions must be considered, as windy conditions usually present in the spring in Oklahoma may cause pesticides to drift out of an area so that they never reach their intended target. Pesticide label rates and recommendations must be followed according to the manufacturers instructions for all pesticides applied. Mosquito control products available for consumer use are typically sold through local home and garden supply stores. Product availability may vary according to location and state regulation Review Questions 1. Write at least three distinguishing features of mosquito from other biting dipteras. Describe the medical importance, and control methods for anopheles, culex, and aedes 3. Justify the reasons why malaria is still the most prevalent disease in the tropics. There are more than 1300 known species of black flies (or "buffalo gnats," as they are sometimes called) in the family Simulidae. As their vernacular name indicates they are usually black in colour but many have contrasting patterns of white, silvery or yellowish hairs on their bodies and legs, and others may be predominantly or largely orange or bright yellow. Black flies have a pair of large compound eyes, which in females are 85 separated on the top of the head ( a condition known as dichoptic); in the males the eyes occupy almost all of the head and touch on top of it and in front, above the bases of the antennae ( a condition known as holoptic). The mouth parts are short and relatively inconspicuous but the five-segmented maxillary palps, which arise at their base, hang downwards and are easily seen. The arrangement and morphology of the mouth parts in similar to those of the biting midges (Ceratopogonidae) the mouthparts, being stout and broad, do not penetrate very deeply into the hosts tissues.

Patients who received the ginger extract had more gastrointestinal complaints (59 vs 21%) cheap prednisolone 40mg on-line, but the symptoms were mild buy 20mg prednisolone amex. Based on these measurements the efficacy was ibuprofen ginger extract placebo purchase 5mg prednisolone with mastercard. However buy prednisolone 20mg, statistically significant effect of ginger extract was seen only by explorative statistical methods in the first period of treatment before crossover (79). Its long history of use dates back to 16th- century China, when its roots, leaves, and flowers were used for medicinal purposes. The modern-day medicinal form of the herb is derived from the root, not the flower or the vine (45). The therapeutic and adverse effects are likely due to diterpenoid compounds with epoxide structures. These compounds have been shown to have immunosuppressive and anti-inflammatory effects in in vitro and in vivo studies. Patients were randomized to placebo, low-dose (180 mg per day), or high-dose (360 mg per day) of Tripterygium extract. Beneficial effect was also seen in the low-dose group when compared with the placebo group (80). The number of patients who withdrew because of side effects was similar in both groups. Considerable toxicity has been associated with the use of Thunder God Vine in anecdotal reports. This herb has been used as an antipyretic and anti- inflammatory folk remedy for centuries. Its use dates back to ancient Greek civilization when it was prescribed to treat inflammations and hot swellings (45). The leaves can be chewed fresh or dried and made into tablets, which are available in the United States and Europe. It inhibits, in a dose-dependent fashion, the production of prostaglandins and leukotrienes by human polymorphonuclear leukocytes. Both crude feverfew extracts and purified parthenolide can inhibit adhesion molecule expression on rheumatoid synovial fibroblasts. Feverfew has an additional molecular mechanism of inhibiting the release of nuclear factor- B, an important transcription factor in the expression of multiple genes involved in the inflammatory process (45). Feverfew may increase bleeding time, thus, it should be avoided in patients with coagulopathy or on warfarin. This compound has produced beneficial results in laboratory studies, as well as in clinical trials. Significant improvements were seen in pain and functional parameters in the groups 1 and 2 compared with group 3, and there was a trend toward greater improvement with higher dose. Further subgroup analysis divided the subjects into two groups based on baseline severity of radiographic joint disease. It has also been used as a medicinal agent for centuries in these regions of the world. Curcumin is the principle curcuminoid compound that gives turmeric its yellow color and is considered the most active constituent. Curcumin has been shown to have anti-oxidant, anti-inflammatory, and anti-cancer activities. It blocked cyclooxygenase and lipoxygenase activities in cultured cells, reducing inflam- matory mediators including prostaglandins, thromboxane, and leukotrienes (87). Synovial fibroblast-like adherent cells were incubated with curcumin and celecoxib alone or in combination. Curcumin also synergistically potentiated the growth inhibition and apoptosis of the synovial cells induced by celecoxib. Two small preliminary unblinded studies showed an anti-inflammatory effect of curcumin (90,91). No large, double- blind, placebo-controlled studies have been performed to evaluate the clinical efficacy of this agent in rheumatic diseases. A Phase I clinical trial of curcumin in patients with premalignant disease in Taiwan showed that curcumin is well tolerated even in doses up to 8 g per day (89). Patient interest and use are high, as are the number of available products and practitioners, as well as the costs. The discussion in this chapter highlighted the evidence as it pertains to only a fraction of this vast topic: diets, dietary supplements, and herbal products and their role as therapies in rheumatic diseases. Scientific evidence does not support a substantial role of special diets or dietary manipulations in the treatment of the majority of patients suffering from arthritis and rheumatic diseases. The level of available evidence has not yet risen to the standards expected for pharmacological interventions However, taken broadly, vegetarian diets and those high in n-3 fatty acids are more likely to be beneficial than the traditional American diet. Laboratory data indicate that long-chain fatty acids play a role in inflam- mation, suggesting a credible pathophysiological pathway through which beneficial effects in inflammatory diseases might be mediated. However, the role of vitamin supplementation is not clear in the treatment of rheumatic diseases. There have not been adequate prospective observations to support the notion that vitamin supplementation beyond current federal recommendations is warranted in rheumatology patients. A considerable amount of work has been published regarding the effects of glucosamine and chondroitin. A variety of small, short-term trials of a variety of herbal supplements have appeared in the literature. Results of short-term trials may only reflect fluctuations in natural disease activity rather than representing true differences in long-term outcome. Unconventional medicine in the United States: prevalence, costs, and patterns of use. Trends in alternative medicine use in the United States, 19901997: results from a national survey. Advance Data From Vital and Health Statistics, Centers for Disease Control and Prevention 2004;343:120. Glucosamine, chondroitin sulfate and the two in combination for painful knee osteoarthritis. Placebo-controlled, blind study of dietary manipulation therapy in rheumatoid arthritis. Epidemiological studies in the Upernavik district, Greenland: incidence of some chronic diseases 19501974. Eicosapentaenoic acid inhibits antigen-presenting cell function of murine splenocytes. Effects of high-dose fish oil on rheumatoid arthritis after stopping non-steroidal anti-inflammatory drugs. Pathological indicators of degradation and inflammation in human osteoarthritis cartilage are abrogated by exposure to n-3 fatty acids. Effects of fish oil supplementation on non-steroidal anti-inflammatory requirement in patiens with mild rheumatoid arthritisa double-blind placebo-controlled trial. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Gammalinolenic acid treatment of fatigue associated with primary Sjogrens syndrome. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham study. Vitamin D is inversely associated with rheumatoid arthritis: results from the Iowa Womens Health Study. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Experimentally induced osteoarthritis in guinea pigs: metabolic responses in articular cartilage to developing pathology. Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model. Do antioxidant micronutrients protect against the devel- opment and progression of knee osteoarthritis? Review: oxygen and reactive oxygen species in cartilage degredation: friend or foes? A case-control study of serum tocopherol levels and the alpha- to gamma-tocopherol ratio in radiographic knee osteoarthritis: the Johnston County Osteoarthritis Project. Coordinated expression of matrix Gla protein is required during endochondral ossification for chondrocyte survival. Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness. Effects of glucosamine and chondroitin sulfate on mediators of osteoarthritis in cultured equine chondrocytes stimulated by use of recombinant equine interleukin-1b. Long-term effects of glucosamine sulphate on osteoarthrtitis progression: a randomized, placebo-controlled clinical trial. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind multicenter study versus placebo. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Advising patients who seek complementary and alternative medical therapies for cancer. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Ginger extract components suppress induction of chemokine expression in human synoviocytes. A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes. Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip. Structural effects of avocado/soybean unsaponifiables on joint-space loss in osteoarthritis of the hip. Modulation of arachidonic acid metabolism by curcumin and related b-diketone derivatives: effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase. Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells.

The X chromosome with most of the genes turned off is called the inactive X chromosome prednisolone 10 mg visa. If a somatic cell contains more than one X chromosome cheap prednisolone 5 mg, all but one are inactivated order prednisolone 10 mg. X inactivation occurs early in embryogenesis among all cells of the bastocyst at about the th 16 day of embryonic life order prednisolone 40mg. Either the X chromosome inherited from the mother (called Xm) or the X chromosome inherited from the father (called Xp) may be inactivated with equal likelihood. Once X inactivation occurs in an embryonic cell, the same X chromosome remains inactivated in all of the progeny of that cell. On average, half of the cells in a female have an inactive Xm & the other half of the cells have an inactive Xp. However, some tissues (& some women ) may have substantially more cells with one or the other X chromosome active by chance. Some essential genes must be expressed in 2 copies from both X chromosomes for normal growth & development. So if one of these essential genes is absent (as occurs in Turner syndrome), it results in abnormal growth & development. Likewise, the presence of an extra X chromosome (as occurs in Klinefelter syndrome) leads to abnormal phenotype. The inactive X-chromosome may be visible in an interphase cell as a condensed mass of chromatin called the Barr body (X chromatin). The maximum number of Barr bodies seen in a cell is equal to the number of inactivated X chromosomes (i. Counting the number of Barr bodies in somatic cells (usually in smears of buccal mucosa) is the basis of the sex chromatin test for sex chromatin aneuplody. This test is no longer used in the Western countries because karyotyping is much more accurate. And most of the genes on the X chromosome do not have homologues on the Y chromosome. Despite the fact that females have double doses of most X-linked genes in comparison to males, the amount of X linked products is usually about the same in males & females. A female who carries an X-linked recessive mutation on one of her 2 X chromosomes may express the mutant phenotype if most of her cells happen to have inactivated the X chromosome carrying the normal gene. A female carrier of an X-linked recessive disease may not detectable by gene product assays (e. Trisomy of the sex chromosomes produces phenotypic changes because of the triple dosage of the essential genes on the X chromosomes (1 copy of these essential genes on the active X chromosome & 2 copies of the activated escapee essential genes on the inactivated X chromosome). Points 3 & 4 above illustrate that aneuploidy of the sex chromosomes is better tolerated than the aneuploidy of the autosomes. Klinefelter syndrome - is a disorder that occurs when there are at least 2 X chromosomes & 1 or more Y chromosomes. In addition, it also shows increased plasma estradiol levels (by unknown mechanism). Turner syndrome - is a disorder that occurs when there is a complete or partial monosomy of the X chromosome. This karyotypic heterogeneity associated with Turners syndrome is responsible for significant variations in phenotype. Disorders of sexual differentiation (Sexual ambiguity) - are said to be present when genetic sex, gonadal sex, or genital sex of an individual are discordant. No matter how many X chromosomes are present, the presence of a single Y chromosome leads to testicular development & a genetic male. The gene responsible for the development of the testes is localized to the Y chromosome. Ductal sex - depends on the presence of derivatives of the Mullerian or Wolffian ducts. Sexual ambiguity is present whenever there is discordance among these various criteria for determining sex. A female pseudohermaphrodite has a ovaries but male external genitalia (or the external genitalia are not clearly male). Female pseudohermaphroditism - is caused by exposure of the fetus to increased androgenic hormones during the early part of gestation as occurs in congenital adrenal hyperplasia, androgen-secreting ovarian or adrenal tumor in the mother, or hormones administered to the mother during pregnancy. Male pseudohermaphroditism - has a Y chromosome & only testes but the genital ducts or the external genitalia are either ambiguous or completely female. Disorders with multifactorial inheritance - are more common than mendelian disorders. The disease clinically manifests only when the combined influences of the genes & the environment cross a certain threshold. The risk of expressing a multifactorial disorder partly depends on the number of inherited mutant genes. Hence, if a patient has more severe expression of the disease, then his relatives have a greater risk of expressing the disease (because they have a higher chance inheriting a 135 greater number of the mutant gene). In addition, the greater the number of affected relatives, the higher the risk for other relatives. The risk of recurrence of the disorder is the same for all first degree relatives of the affected individual & this is in the range of 2-7%. Hence, if parents have had one affected child, then risk that the next child will be affected is between 2 & 7%. The risk of recurrence of the phenotypic abnormality in subsequent pregnancies depends on the outcome in previous pregnancies. When one child is affected, the chance that the next child will be affected is 7%. When 2 children are affected, then the chance that the next child will be affected increases to 9%. Single gene disorders with nonclassic inheritance - are rare & are briefly mentioned here. Diseases associated with gonadal mosaicism Gonadal mosaicism can explain unusual pedigrees seen in some autosomal dominant disorders such as osteogenesis imperfecta in which phenotypically normal parents have more than one affected children. Fragile X syndrome - is the second most frequent cause of hereditary mental retardation next to Down syndrome. List the various types of mutations & discuss their effects by giving examples for each type. Explain the criteria, the pathogenesis, & give clinical examples for the 3 main mendelian patterns of inheritance. Explain the general pathogenesis of mendelian disorders associated with enzyme defects. Describe the karyotypes & the clinical features of Turner syndrome Hypofunction of which organ can explain these clinical features? Describe the cause, the karyotypes, & the clinical features of Klinefelter syndrome. Tesfaye is married to an unrelated woman called Tenagne, & has a 2 year old daughter, Mimi. Beletechs sister who is called W/ro Kelemuwa is the mother of W/ro Almazs husband, Ato Worku, who is 25 years old. What is the pattern of transmission of the of disease X, & what is the risk of disease X for W/ro Almazs next child? Have birds eye view concept on immunodeficiency states Before reading this chapter, the student is advised to review his/her immunology text or lecture note. Hypersensitivity Reactions The purpose of the immune response is to protect against invasion by foreign organisms, but they often lead to host tissue damage. An exaggerated immune response that results in tissue injury is broadly referred to as a hypersensitivity reaction. One leading to mast cell degranulation with discharge of preformed (primary) mediators and the other involving denovo synthesis and release of secondary mediators. Initial phase (response): Characterized by vasodilatation, vascular leakage, and depending on the location, smooth muscle spasm or glandular secretions. Mast cells are bone marrow driven cells widely distributed in tissues around blood vessels, and sub epithelial sites where type I reaction occurs. Morphology: Histamine and leukotriens are released rapidly from sensitized mast cells and are responsible for intense immediate reaction characterized by edema, mucous secretions and smooth muscles spasms. Three different antibody-dependent mechanisms are involved in this type of reaction 141 (i) Complement-dependent reaction i. Direct lysis: a) It is effected by complements activation, formation of membrane attack complex (C5 9). This membrane attack complex then disrupts cell membrane integrity by drilling a hole. In anucleated cells once and in nucleated cells many attacks of the complex are needed for cell lysis, because the latter ones have abilities to repair cell membrane injuries rapidly. Examples include red blood cells, leukocytes and platelets disorders: Transfusion reaction; haemolytic anemia; Agranuloytosis; Thrombocytopenia; Certain drug reaction ii. The target cells coated with IgG antibodies are killed by a variety of nonsensitized cells that have Fc receptors. Antibody-mediated cellular dysfunction In some cases, antibodies directed against cell surface receptors impair or dysregulated function without causing cell injury or inflammation. For example: In Myasthenia Gravis, antibodies reactive with acetylcholine receptors in the motor end plates of skeletal muscles impair neuromuscular transmission and cause muscle weakness. Exogenous origin Bacteria streptococcus (infective endocarditis) Viruses Hepatitis B virus (Polyarteritis nodosa) Fungi Actinomycetes (farmers lung) Parasites plasmodium species (glomerulonephritis) Drugs quinidin (hemolytic anemia) Foreign serum (serum sickness) b. Endogeneous origin Nuclear components (systemic lupus erythematosis) Immunoglobulins (rheumatoid arthritis) Tumour antigen (glomerulonephritis) Therefore, autoimmune diseases are hypersensitivity diseases in which the exaggerated immune response is directed against the self antigens as exemplified by the above three diseases. Formation of Ag-Ab complex Introduction of an antigen into the circulation, then Production of specific antibodies by immuno-competent cells and subsequent antigen antibody formation b. Deposition of immune complexes The mere formation of antigen-antibody complex in the circulation does not imply presence of disease. Inflammatory reaction After immune complexes are deposited in tissues acute inflammatory reactions ensues and the damage is similar despite the nature and location of tissues. Neutorphiles and macrophages can be activates by immune complexes even in absence of complements. With either scenario, phagocytosis of immune complexes is effected with subsequent release of chemical mediators at site of immune deposition and subsequent tissue necrosis. Morphology of immune complex-mediated hypersensitivity reaction The morphologic consequences are dominated by acute necrotizing vasculitis with intense neutrophilic exudation permiting the entire arterial wall. Affected glomeruli are hyper cellular with proliferation of endothelial and mesengial cells accompanied by neutrophillic and mononuclear infiltration. Classification of immune complex-mediated diseases: Immune complex-mediated diseases can be categorized into systemic immune complexes diseases (e.