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Treatment Treatment is supportive in conjunction with drug withdrawal and steroid therapy buy discount januvia 100 mg diabetes supplies definition. Once alveolar and interstitial damage is established order 100 mg januvia with mastercard diabetes definition canadian, progression to fibrosis is the norm discount januvia 100mg overnight delivery diabetes symptoms en espanol, and prognosis is poor generic januvia 100 mg with visa diabetes signs cats. Methotrexate Methotrexate can cause a variety of lung toxicity, but is classically associ- ated with interstitial pneumonitis (incidence 2–8%). Risk factors include high-dose therapy, daily administration, and pre-existing lung disease. There is an acute form that develops hours to days after initiation of therapy, and a chronic form that presents after weeks to years of continuous prophylactic therapy. Treatment Resolution is usually rapid after drug withdrawal, and mortality is low. Sulfasalazine Sulfasalazine is used as a disease-modifying drug in rheumatoid arthritis and in the treatment of inflammatory bowel disease. Although systemic side-effects are well described, pulmonary side-effects are relatively rare. Sputum production, rash, and chest pain have been described, but are inconsistent features. The most common histological appearances are of eosinophilic pneumonia, but fibrosis is possible. Oxygenation is often relatively preserved and any hypoxia easily reversed with supplemental oxygen. However, oxygen therapy may exacerbate hypercapnia in patients with chronic hypercapnia. These patients frequently present to secondary care with unrelated problems and are identified on the basis of abnormal investigations. This section will focus on patients who often present with an acute episode on the background of often unrecognized chronic respiratory failure. These patients may therefore be seen by intensive care, respiratory, or emergency/acute medicine physicians. Many patients with respiratory failure of extrapulmonary origin require long-term home ventilation (see b Long-term (home) ventilation, p 354). Control of respiration Normal respiratory function is controlled by a neural network located in the lower brainstem (pontine, dorsal, and ventral respiratory groups). Motor neurones project down the spinal cord to the diaphragm, inter- costal, and abdominal muscles. In patients with abnormal respiratory function, clinically significant hypov- entilation often first occurs during sleep. In general patients present in one of three ways: • As an emergency with acute decompensation, often on the background of unrecognized chronic respiratory failure. Precipitating factors include: • Respiratory tract infection • Pulmonary aspiration, as many of these patients have co-existing bulbar dysfunction • Upper airway obstruction • Other intercurrent illness or medical intervention (e. Note: It is easy to miss the usual signs of respiratory distress in muscle- wasted patients, but tachycardia and hypertension are often seen. Investigations The investigations required will be determined to some degree by the speed of onset of illness and the time available before instituting therapy. OxyHb saturation <88% for 5 min is considered evidence of significant desaturation. A value of –70cmH2O in males and –60cmH2O in females is unlikely to be associated with respiratory muscle weakness. Still more advanced • Limited (home) sleep study: measures of airflow, thoraco-abdominal movement, oximetry, heart rate. Specialized • Full polysomnography: in cases of diagnostic uncertainty (do they have coexistent sleep apnoea syndrome? Treatment: general principles Acute upper airways obstruction This requires urgent definitive control of the airway. Options include: • Deep inhalational anaesthesia with sevoflurane to facilitate intubation, avoiding muscle relaxant use 6. Ventilation In hypercapnic respiratory failure both the hypercapnia and hypoxia can be corrected by ventilatory support (assuming no coexisting lung disease). The speed of onset of respiratory failure often governs the speed with which this must be instituted. In many patients a planned approach can be undertaken as the insidious onset of respiratory failure does not necessitate rapid correction. Early in the process the patient’s views should be ascertained and ventilatory support only instituted if this is in accordance with the patient’s wishes. In patients with acute muscle denervation, suxamethonium should be avoided as it may precipitate fatal hyperkalaemia. A range of patient–ventilator interfaces exists: • Nasal mask • Nasal pillows • Full facemask. In the acute setting a full facemask is generally favoured, but is a matter of physician preference. Once hypercapnia is controlled the interface can be changed to nasal mask/pillows, depending on patient predilection. There is more detailed discussion of long-term ventilatory support in b Long-term (home) ventilation, p 354. Acute inflammatory postinfectious polyneuropathy (Guillain–Barré syndrome) • Most common cause of neuromuscular respiratory failure, with an incidence of 1–4/100000/year. The response to treatment in myotonic dystrophy is often less satisfac- tory as a result of the complexities of the issues involved. Patients with respiratory failure of non-pulmonary cause present an on-going problem because of their acute presentation, chronic hypercapnia requiring long-term respiratory support, and the need to negotiate other medical problems, e. It is prudent for the care of such patients to be brought under the aegis of a single consultant with a specific commitment to, and expertise in, the care of these challenging groups, ideally supported by a specialist team of nursing and paramedical staff. The range and complexity of available therapies is steadily increasing and there is a move away from limiting treatment on the basis of chronolog- ical age (median age at presentation is 60–70). General principles of treating haematological malignancy Chemotherapy Chemotherapy works by being more toxic to malignant cells than healthy cells. Usually given in pulses or cycles, which are timed so that, hope- fully, the patient’s bone marrow and other susceptible healthy tissues have regenerated between cycles, but the malignancy has not. This gradually reduces tumour burden without progressive deterioration in healthy tissue. Chronic myeloid leukaemia • Long-term disease control generally possible with continuous daily administration of well-tolerated oral agents. Low-grade lymphoma and chronic lymphocytic leukaemia • May be aggressive but generally indolent. These cells are re-infused after chemo- therapy has been completed and eliminated from the body. This technique is used to give very large doses of chemotherapy in myeloma and relapsed high-grade lymphoma. Donor marrow is infused after the chemotherapy is completed and elimi- nated from the patient’s system.

Patients should be monitored closely for signs of bleeding (reduced blood pressure 100 mg januvia visa diabetes y sus consecuencias, increased heart rate discount 100mg januvia free shipping blood glucose monitoring chart, bruises januvia 100 mg otc blood glucose 48, petechiae discount januvia 100mg on line diabetes death, hematomas, red or black stools, cloudy or discolored urine, pelvic pain, headache, and lumbar pain). Of note, compared with warfarin, the newer oral anticoagulants— apixaban, rivaroxaban, and dabigatran—pose a significantly lower risk for serious bleeds. Candidates for treatment must be carefully screened for risk factors (see “Warnings and Contraindications”). When a patient is incapable of accurate self-medication, a responsible individual must supervise treatment. Patients should be advised to make a record of each dose, rather than relying on memory. Patients anticipating elective procedures should discontinue warfarin several days before the appointment. If an emergency procedure must be performed, injection of vitamin K can help suppress bleeding. Fetal Hemorrhage and Teratogenesis From Use During Pregnancy Warfarin can cross the placenta and affect the developing fetus. In addition, warfarin can cause gross malformations, central nervous system defects, and optic atrophy. Women of childbearing age should be informed about the potential for teratogenesis and advised to postpone pregnancy. Long-term warfarin use (more than 12 months) may weaken bones and thereby increase the risk for fractures. Drug Interactions General Considerations Warfarin is subject to a large number of clinically significant adverse interactions—perhaps more than any other drug. As a result of interactions, anticoagulant effects may be reduced to the point of permitting thrombosis, or they may be increased to the point of causing hemorrhage. Patients must be informed about the potential for hazardous interactions and instructed to avoid all drugs not specifically approved by the prescriber. As indicated, the interactants fall into three major categories: (1) drugs that increase anticoagulant effects, (2) drugs that promote bleeding, and (3) drugs that decrease anticoagulant effects. The major mechanisms by which anticoagulant effects can be increased are (1) displacement of warfarin from plasma albumin, (2) inhibition of the hepatic enzymes that degrade warfarin, and (3) decreased synthesis of clotting factors. The major mechanisms for decreasing anticoagulant effects are (1) acceleration of warfarin degradation through induction of hepatic drug-metabolizing enzymes, (2) increased synthesis of clotting factors, and (3) inhibition of warfarin absorption. The interaction does mean, however, that the combination must be used with due caution. The potential for harm is greatest when an interacting drug is being added to or withdrawn from the regimen. The interaction of heparin with warfarin is obvious: being an anticoagulant itself, heparin directly increases the bleeding tendencies brought on by warfarin. By blocking aggregation, aspirin can suppress formation of the platelet plug that initiates hemostasis. Therefore, when the antifibrin effects of warfarin are coupled with the antiplatelet and ulcerogenic effects of aspirin, the potential for hemorrhage is significant. Accordingly, patients should be warned specifically against using any product that contains aspirin, unless the provider has prescribed aspirin therapy. Like aspirin, other antiplatelet drugs can increase the risk for bleeding with warfarin. In fact, acetaminophen was routinely recommended as an aspirin substitute for patients who needed a mild analgesic. Unlike aspirin, which promotes bleeding by inhibiting platelet aggregation, acetaminophen is believed to inhibit warfarin degradation, thereby raising warfarin levels. At this time, the interaction between acetaminophen and warfarin has not been proved. Warnings and Contraindications Like heparin, warfarin is contraindicated for patients with severe thrombocytopenia or uncontrollable bleeding and for patients undergoing lumbar puncture, regional anesthesia, or surgery of the eye, brain, or spinal cord. In addition, warfarin is contraindicated in the presence of vitamin K deficiency, liver disease, and alcoholism—conditions that can disrupt hepatic synthesis of clotting factors. Vitamin K for Warfarin Overdose1 The effects of warfarin overdose can be overcome with vitamin K1 (phytonadione). If vitamin K fails to control bleeding, levels of clotting factors can be raised quickly by infusing fresh whole blood, fresh-frozen plasma, or plasma concentrates of vitamin K–dependent clotting factors. Like medicinal vitamin K, dietary vitamin K can reduce the anticoagulant effects of warfarin. Dietary sources include mayonnaise, canola oil, soybean oil, and green leafy vegetables. Patients do not need to avoid these foods but instead should keep intake of vitamin K constant. If vitamin K intake does increase, then warfarin dosage should be increased as well. Conversely, if vitamin K intake decreases, the warfarin dosage should decrease too. Contrasts Between Warfarin and Heparin Although heparin and warfarin are both anticoagulants, they differ in important ways (Table 44. Although both drugs decrease fibrin formation, they do so by different mechanisms: heparin inactivates thrombin and factor Xa, whereas warfarin inhibits synthesis of clotting factors. Heparin and warfarin differ with respect to time course of action: effects of heparin begin and fade rapidly, whereas effects of warfarin begin slowly but persist several days. Finally, these drugs differ with respect to management of overdose: protamine is given to counteract heparin; vitamin K is given to counteract warfarin. Dosage Basic Considerations Dosage requirements for warfarin vary widely among individuals, and hence dosage must be tailored to each patient. Dosage reductions based on this information can be determined using the calculator at www. Preparations Warfarin sodium [Coumadin, Jantoven] is available in tablets (1, 2, 2. In addition, warfarin is available in a formulation for parenteral dosing, which is not commonly done. Direct Thrombin Inhibitors The anticoagulants discussed in this section work by direct inhibition of thrombin. Hence they differ from the heparin-like anticoagulants, which inhibit thrombin indirectly (by enhancing the activity of antithrombin). Dabigatran Etexilate Dabigatran etexilate [Pradaxa, Pradax ] is an oral prodrug that undergoes rapid conversion to dabigatran, a reversible, direct thrombin inhibitor. Compared with warfarin—our oldest oral anticoagulant—dabigatran has five major advantages: rapid onset; no need to monitor anticoagulation; few drug-food interactions; lower risk for major bleeding; and, because responses are predictable, the same dose can be used for all patients, regardless of age or weight.

Ofodile and Bokhari reported the mean It is important to recognize that patients of African descent nasal labial angle of the Black American nose to be ~91 degrees in women and 84 degrees in men purchase januvia 100 mg on-line diabete 2 sintomi,13 compared with ranges of seeking rhinoplasty procedures are often those whose alar base width extends beyond the medial canthi and approaches the 95 to 100 degrees and 90 to 95 degrees in Caucasian women and men discount 100 mg januvia fast delivery blood glucose measurement, respectively buy cheap januvia 100 mg on line diabetes symptoms low iron. Tip rotation is determined by contour of the tip should be continuous with the brow-tip aes- examining the relationships between the dorsum buy 100mg januvia amex diabetes type 2 virus, lobule, and thetic, or dorsal ciliary lines and the lateral borders of the tip columella on the lateral view. The transition from the dorsum should transition smoothly into the curvilinear contour of the to the columella should be smooth, except for the possible pres- alar lobule. The supratip break defining points, distinct light reflexes, and smooth dorsal ciliary point is created by the separation of the septum from the dorsal lines as seen in the leptorrhine nose, may not be realistic for line and a subtle convexity of the alar cartilages, and the colum- some patients with noses of African descent. Nonetheless, the ellar break point separates the most anterior segment of the rhinoplasty surgeon operating upon the patient of African columella from the infralobule. These goals can be achieved by executing surgical prone patients rarely have untoward scarring issues in this area. On the other hand, the endonasal approach is associated with less soft tissue disruption, less edema, and more rapid recovery. However, it is also associated with decreased visualization of tip anatomy and greater complexity in making precise changes to 75. In the final analysis, the decision to per- Access to the nasal tip can be accomplished by using either an form tip rhinoplasty through an open or endonasal approach open or endonasal approach. Depending upon the surgical should be based upon the patient’s individual needs and sur- goals, both approaches offer unique advantages and disadvan- geon’s experience with the chosen approach. Mobilizing the lateral crura the base of the nose supplied by the premaxilla and anterior from the underlying vestibular lining allows the surgeon to uti- nasal spine. These bones are commonly hypoplastic in patients lize cartilage from the lateral crura to add projection to the of African descent, and consequently the nasal tip is often nasal tip. Additionally, the lateral crus can also be released from underprojected in these patients. Tip definition refers to the its most lateral portion, allowing for even more movement degree of refinement of the underlying cartilaginous structures toward the dome. If the lateral crus is released at its most lateral of the tip, smooth transitions between the tip and its surround- segment, it is critical that this area be reconstituted and sup- ing aesthetic subunits, and how well the skin envelope drapes ported with a lateral aural strut to provide support to the alar over the underlying framework. These strat- jection and definition in either an intradomal or interdomal egies include cartilage mobilization with suture fixation techni- fashion. Intradomal sutures are hor- improve tip projection and definition can be accomplished izontal mattress sutures that are placed through the domal through both endonasal and open techniques. The patient of African tion and fixation technique options that can be used to improve descent with wide domal arches will benefit greatly with intra- domal sutures. Interdomal sutures attach the posterior medial aspect of the domes to one another; this technique serves to Table 75. Defect Surgical Pearls Cartilage mobilization and suture fixation techniques such as Inadequate tip projection Domal sutures, lateral crural steal, col- the lateral crural steal and domal sutures are generally well and definition umellariseptal extension graft, nasal onlay suited for improving nasal projection and enhancing tip defini- grafts (septa) donor site preferred) tion. To obtain Minimize external incisions, alar base Alar flare more significant changes in nasal tip projection, cartilage- excision+lateral crural strut, rim grafts grafting techniques are often necessary. The septum is the pre- Increased interalar width Alar base excision+alar base cinch ferred choice for autologous cartilage. The placement of ing the risk of saddling, supratip depression, and airway col- a columellar strut is a logical starting point when attempting to lapse. Furthermore, a strong columellar strut provides the or costal cartilage can be harvested and used as grafts within long-term stability needed to support other grafts that may be the nasal tip. Harvesting of conchal cartilage in patients of Afri- placed more anteriorly on the tip for improved projection and can descent should be approached with caution as the periaur- definition. In comparison with the leptorrhine nose, columellar icular region is a high-risk area for keloid formation. Irradiated costal cartilage is readily available in sufficient malposition of the strut along the premaxilla if it is placed low quantities and its reported long-term use has been favorable. If additional nasal length is In general, we discourage the use of synthetic grafts for nasal needed along with tip projection, a septal extension graft may tip or dorsal augmentation to minimize long-term complica- prove useful and obviate the need for a columellar strut. The septal extension graft can be secured to the caudal septum When considering techniques that improve upon nasal tip in end-to-end or overlapping fashion and fixated with perma- projection and definition in noses of African descent, the uti- nent or slowly resorbing suture. The columellar strut is extension grafts provide structural support to the nasal tip and essential for creating support to the nasal tip in addition to decrease the risk of tip ptosis postoperatively. Once strut or 597 Ethnic Rhinoplasty septal extension graft placement is complete, the nasal tip be performed judiciously, as excessive defatting can lead to should be reassessed and additional grafting techniques devascularization and necrosis of the soft tissue envelope. In the patient with significant defi- often relatively thick, allowing generous grafts to be used. In ciency of the premaxilla, a cartilaginous onlay graft can be addition, the use of grafts to enhance tip projection also results placed in the premaxillary regions. Due to the generous volume in improved tip definition, a frequent request of patients of of this graft that may be required, it is best to use costochondral African descent seeking nasal tip refinement. This premaxillary graft should be carefully crafted to Debulking the fibrofatty soft tissue can be considered in straddle the region of the anterior nasal spine while not patients of African descent in an attempt to add additional defi- extending laterally beyond the alar base. The premaxillary graft nition to the nasal tip region following the use of suture fixation serves as a foundation to build upon and corrects the anatomic or grafting techniques and can be performed by gently remov- deficiency of the premaxilla often seen in the underrotated ing small lobules of fat in the region of the middle crura, taking African nose. This graft can be deployed through a hemitrans- care not to injure the subdermal plexus. Alar base excision and suture techniques can be anterior nasal spine and premaxilla; by doing so it softens the localized to the base, the nostril sill, or a combination of both nasal labial angle and creates the illusion of tip rotation. If a significant amount of soft tissue excision tip to be secured into the position of desired rotation. The lat- is required to correct excessive interalar base width, the alar eral crural overlay technique described by Kridel and Konior cinch technique, which involves releasing and repositioning the can be effective in correcting the underrotated nose. In this technique, vertically ori- technique, the lateral crura are cut across their midportions, ented incisions are placed within the nasal sill and the tissue then overlapped and fixed with horizontal mattress sutures. Once this tissue is removed, the alae are cinched at the midline with a straight Keith needle. Although these techniques are extremely helpful in to stiffen the alar side wall and create the appearance of addressing increased base width, they also contribute to exter- decreased alar flare. When treating the alar base, it is important nal scars, hyperpigmentation, and an unnatural transition to to avoid placing incisions directly in the alar-facial groove and the cheek or upper lip. We have found that the use of cartilage to bevel the incisions to allow for inversion of the skin edges grafts placed adjacent to the rim or as lateral crural struts can during closure. It is also important to place deep sutures during serve to stiffen the rim, decrease mild to moderate alar flare closure to minimize scar widening postoperatively. When considering alar Close attention to the aftercare is critical to achieving successful base excision techniques, it is important to correctly diagnose outcomes when performing rhinoplasty in the patient of Afri- alar flare and recognize that it is a different entity from can descent. Alar flare refers to the maximum hypertrophic scarring occur less commonly around the nose Fig. Ana- the possibility of an extended period of splinting if necessary, tomic basis and clinical implications for nasal tip support in open versus because prolonged edema is common in patients of African closed rhinoplasty.

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