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Explore and excise the track weight loss pills for menopause buy shuddha guggulu on line amex, since the tissue along the track is devitalized, lay open the investing fascia over disrupted muscle to evacuate the muscle haematoma and excise the pulped muscle, leaving healthy contractile muscle that bleeds when cut. Change the packs daily until infection is controlled and all dead tissue has been excised. Only then can skin closure be completed and the repair of damaged structures be planned. Do not attempt to repair cleanly divided muscle with stitches but simply suture the investing fascia. Plan to renew the packing daily until the wound is clean and produces no further discharge. The essential feature of the external fixator is that it provides a stable reduction of any fracture by using percutaneously introduced wires or pins in to the bone, which are then attached to an external frame. The Ilizarov and similar circular frames are beyond the scope of this chapter, but in an emergency you should be familiar with the principles involved, and the techniques of applying a simple unilateral frame. Such a frame is constructed from one or more rigid bars which are aligned parallel to the limb and to which the threaded pins that are drilled in to the fragments of bone are attached. In the simplest form, here described, the pins are held to the bar with acrylic cement (Denham type;. Once bone stability has been achieved, damaged segments of major arteries and veins should be repaired by an experienced surgeon, using grafts where appropriate. Loosely appose the ends of divided nerves with one or two stitches in the perineurium, so that they can be readily identified and repaired later when the wound is healed and all signs of inflammation have disappeared. Similarly, identify and appose the ends of divided tendons in preparation for definitive repair at a later date. Do not remove small fragments of bone that retain a periosteal attachment or large fragments whether they are attached or unattached. Excise devitalized muscle, especially the major muscle masses of the thigh and buttock. Aftercare 1 n Keep the pin tracks clean and free of scabs and incrustations by daily cleaning with sterile saline or a mild antiseptic solution. A rigorous regime will minimize the risk of pin-tract infection and premature pin loosening. Threaded bar 2 n An external fixator is essentially only a temporary measure before Plastic-coated fixed carriage 3 n Fixator removal is simple. Cut the pins with a hacksaw or bolt Portsmouth threaded pins definitive treatment can be carried out. It is seldom used as the sole method of fracture management and should, therefore, be removed at a time when the wound is healthy, at which time it may be possible to definitively stabilize the fracture. Take care in drilling the bone that the drill bit does not overheat, which may in turn cause local bone necrosis leading to the formation of ring sequestra with subsequent loosening and infection of the pins. Retain any bone that has a remaining periosteal attachment, as this bone is potentially still viable. Biomechanically, the stability of the fixator is enhanced if there are three pins in each of the major fragments, with the nearest pin being close to the fracture line. Each has a triangular or square butt, which inserts in to a chuck, and a trocar point. The Steinmann pin is uniform throughout but the Denham pin has a short length of screw thread wider than the main shaft near its centre, which screws in to one cortex of the bone and minimizes sideways slip during traction. It may be seen as a temporary measure, as definitive treatment, or as a supplement to treatment. With the more widespread use of increasingly sophisticated internal fixation devices, skeletal traction is less frequently employed as a definitive method of treating long-bone fractures. Skeletal traction requires careful supervision and adjustments to remain effective. If the 5 n Make sure that the skin is not distorted where the pin passes 6 n Dress the punctures with small squares of gauze soaked in tincture of benzoin. Remember that the effective traction is doubled as a result of the pulley arrangement. Have the traction string horizontal and apply sufficient traction weights so as to reduce the fracture and restore alignment and length of the bone. Tie the distal end of this attachment to that of the main splint with traction cord. I have found the Cone caliper easier to apply and less likely to slip than the Crutchfield device. Z Access 1 n the patient lies supine with the head carefully supported so as to 2 n Establish the insertion point for the caliper, which is at the point avoid sudden and unexpected movement. Bring the caliper back in to position and introduce the pin through the conical end of the caliper. The pins are then tightened down through the outer table to a predetermined depth. Support the calf and thigh from the side-bars of the frame with slings of Domette bandage. If you feel unable to attempt a primary repair then mark the nerve ends with a non-absorbable suture to assist their location at the time of the definitive operation. X Appraise 1 n Always assume that a peripheral nerve injury in the presence of W 488. You must therefore identify the nerve when the wound is treated and satisfy yourself as to its integrity. If it is divided, either mark or appose the ends in their correct orientation for secondary repair later. While an operating microscope may not be available, simple magnifying loupes will usually suffice. Prepare 1 n Do not attempt immediate primary nerve repair unless you have adequate magnification (loupes or operating microscope) and are sufficiently experienced in the techniques involved. If there is any doubt, it is safer to mark or appose the nerve ends for later exploration and repair. A neuropraxia (block to conduction of nerve impulses without disruption of the axon or its supporting cells) will usually recover spontaneously in days or weeks, and an axonotmesis (the axon undergoes Wallerian degeneration) in the time it takes for the axons to regenerate. Axons regenerate at a rate of 1 mm/day and so it will take approximately 90 days, for example, for re-innervation of the brachioradialis to occur following an injury to the radial nerve at the distal end of the spiral groove of the humerus. If joints were flexed to avoid tension they must only be extended gradually over the next 3 weeks, if necessary by applying serial plasters at weekly intervals, or by incorporating a hinge with a locking device to allow flexion but no more than the set amount of joint extension. When the tendon is divided within a fibrous sheath on the flexor surface of the hand, for example, the sheath is also damaged and the connective tissue from the healing sheath grows in to the healing tendon, causing adhesions. For this reason, injuries to the digital flexor tendons within the sheath should preferably be treated by experienced hand surgeons. Tendons may also require suturing as part of another procedure such as tendon transfer. Action 1 n If this is a delayed repair there may be fibrous scar tissue at the 2 n If necessary, cut transversely across fibrous scar tissue that may be 3 n Hold one end of the nerve firmly, using a special nerve-holding joining the ends together. It may be necessary to resect a centimetre or more from each end of the nerve because of the intraneural fibrosis (neuroma) caused by the initial injury. If it proves impossible to appose the nerve ends then an interposition graft may be necessary. As with nerve injuries, if it is in the vicinity of a tendon and there is no distal action, assume that the tendon is divided until it is shown to be intact on clinical examination. Cut the first pair of sutures and turn the nerve over by passing one bulldog clip suture under and the other over the nerve. These act as stay sutures and facilitate rotation of the nerve while placing further sutures. If not, delay the repair until the wound is healed and is no longer indurated, maintaining full mobility of the joints in the meantime by physiotherapy. It is not unheard of to suture the proximal end of one tendon to the distal end of another or even to the cut end of a nerve! In the case of possible 2 n Incise the skin over the most superficial aspect of the lesion, 3 n Incise the deep fascia and split the muscle in the line of its fibres infection, do not exsanguinate the limb.

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Isolated renal tubular necrosis often recovers weight loss pills contrave purchase shuddha guggulu 60caps with amex, although a period of support by haemodialysis or haemofiltration may be required. Total anuria immediately after the operation suggests the possibility of occlusion of both renal arteries. Arrange urgent Duplex ultrasound to assess renal perfusion and consider whether re-exploration is indicated, with a view to renal artery reconstruction. The insertion of a spinal drain as part of the anaesthetic preparation is helpful and allows monitoring and maintenance of the cerebrospinal fluid pressure at a low level (10 cmH2O). This helps to maintain perfusion of the spinal cord and reduces the incidence of paraplegia. This is unfortunately not uncommon following emergency operations for ruptured aneurysm, particularly if there has been massive blood loss. It usually becomes apparent within 24 hours but can develop more insidiously over a few days. Mechanical ventilatory support with a high concentration of inspired oxygen and positive endexpiratory pressure is often required to maintain adequate blood gases. Support the chest in a left lateral position but rotate the pelvis forward so that the trunk is twisted slightly. Correct positioning of the patient is vital to allow access to the chest and to the abdomen. Access 1 n For thoracic aneurysms make an incision over the fifth intercostal space. For thoracoabdominal aneurysms make an incision over the sixth or seventh space and extend it across the costal margin to the midline of the abdomen and then inferiorly to the pubis. Divide the diaphragm around its margin to permit the wound to be opened widely with a rib retractor and to preserve its function. Reflect the spleen, pancreas and left colon to the right to expose the abdominal aorta. Alternatively, the incision in the abdomen can be extended to allow access to the retroperitoneum, thereby removing the need for visceral medial rotation. Action 1 n When all dissection has been completed administer heparin to 2 n Establish left heart bypass (left atrium to left common femoral achieve full anticoagulation. In the case of extensive aneurysms isolate the proximal site of anastomosis with clamps in the first place in order to maintain uninterrupted perfusion of the viscera for as long as possible. Widely patent intercostal arteries at this level should be preserved and reimplanted in to the graft within a patch of aorta. Have a low threshold to buttress the entire anastomosis with either buttressed sutures or a ring of Teflon which is sutured concurrently with the native thoracic aorta and graft. Usually it is possible to include the coeliac axis, superior mesenteric and right renal arteries in one patch (Carrel patch), leaving the left renal artery to be implanted separately. Perfusion of the viscera can be maintained with additional cannulae from the cardiac pump, thereby reducing warm ischaemia time. As an alternative to constructing an aortic patch bearing the abdominal visceral arteries, use a graft incorporating branches of each of the visceral arteries (Coselli graft). Implant these and Two chest drains are inserted superiorly and inferiorly to drain blood and to allow lung expansion. Complications 1 n Haemorrhage, anuria, adult respiratory distress syndrome, myo- 9 n All successfully by straight endografts introduced from the groin or via the abdominal aorta or an infrarenal aortic graft. The risk of operative complications, including paraplegia and death, appears to be much lower than that associated with open repair. Fenestrated and branched endoluminal devices, which permit endovascular repair of aneurysms in the visceral or thoracoabdominal region, are only undertaken by specialist vascular units and are not the remit of this chapter. Infarction of the spinal cord is irreversible, therefore rehabilitation with moral and physical support is the essential and only appropriate response to established paraplegia. Prepare 1 n the clinical indications for endovascular repair are similar to those for open repair (see above). However, some patients who are unfit for the open operation may be able to tolerate the less-invasive endovascular procedure. The procedure itself carries a very low risk and the recovery time is much shorter than that associated with conventional open operation. Be sure that the minimal anatomical criteria, as defined by the device manufacturer, are satisfied. If regional anaesthesia is used, facilities for general anaesthesia must be immediately available in case conversion to open repair becomes necessary. Although percutaneous access is possible with some types of device, the benefit is marginal and it is recommended that the common femoral arteries are exposed on both sides. It is permissible to cross 6 n Access for the device is via the common femoral artery and it is essential that the iliac arteries can permit the passage of the introducer systems. Iliac arteries should measure 7 mm or greater and should not be too tortuous or heavily calcified. Withdraw the angiography catheter from the sheath in the common femoral artery and replace it with a catheter with a shaped end. Obtain an angiogram to determine precisely the position of the renal arteries relative to bone structures or a radio-opaque measuring scale placed under the patient. Through this catheter exchange the standard guide-wire for a long, super-stiff guide-wire (for example, a Lunderquist) and position it in the ascending aorta. Usually, fine adjustment of the position of the device is possible after deployment of the upper one or two rows of the stent and another angiogram may be obtained at this stage. However, remember to withdraw the angiography catheter in to the sac of the aneurysm before deploying the device fully. Modern modular stent-grafts are provided with a choice of limbs of different lengths and diameters. Radioopaque markers are located at strategic points on the device for 18 n Close the groin incisions and check to ensure that the peripheral circulation is satisfactory. When satisfied with the angiographic appearances remove all sheaths, catheters and guide-wires, close the femoral arteriotomies with 5/0 polypropylene sutures and restore blood flow to both limbs. Advance catheters over the wire from both groins to push the loop well up before carefully withdrawing it to position the end within the aorta. Alternatively, use a brachial approach to advance a wire through the device to the second groin. Again, use a goose-neck snare to capture the wire and withdraw it through the sheath in the groin. The presence of an endoleak indicates that the sac is still pressurized and therefore that a risk of rupture persists. Flow in the aneurysm sac visualized on completion angiography may originate from: (a) one or more of the anastomoses (type 1 endoleak); (b) retrograde perfusion from patent lumbar or inferior mesenteric arteries (type 2 endoleak); (c) incomplete seal between the modular parts (type 3 endoleak); or (d) graft porosity (type 4 endoleak). Tortuous or calcified iliac arteries may obstruct access of the introducer sheath carrying the device. It is often possible to straighten the iliac arteries by applying gentle traction upon the external iliac artery from the groin. It may be impossible to manipulate a guide-wire in to the short leg from the second groin. The patient must not be allowed to leave the operating table with a large proximal type 1 endoleak because these are the most dangerous of all. Anecdotal evidenceindicates that an unresolved proximal type 1 endoleak is associated with a higher risk of rupture than anuntreated aneurysm. Furthermore, clinical studies have demonstrated that they are rarely the cause of adverse postoperative events. Therefore no further intervention is required if a type 2 endoleak is diagnosed from the postoperative angiogram. If, for any reason the endograft cannot be deployed or it is found to be grossly malpositioned, convert the procedure to an open repair. The short saphenous vein can be harvested for use as a bypass with the patient in this position, but if the long saphenous vein in the thigh is to be used, first harvest the vein and prepare it with the patient supine. Initially, mural thrombus develops within the aneurysm and, possibly because of repeated flexion of the knee joint, fragments break away and embolize in to the distal vessels.

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In particular weight loss jewelry buy 60caps shuddha guggulu fast delivery, decide whether the tumour reaches the superficial aspect of the superficial lobe, because if it does you may need to modify the plane of your dissection. If the tumour does not reach this aspect, it is acceptable to dissect close to the gland, preserving the mandibular branch of the facial nerve in the overlying platysmal flap as described in the similar operation for sialolithiasis. If the tumour does reach this superficial aspect, perform the mobilization in a plane more remote from the gland. Try to identify the mandibular branch of the facial nerve and preserve it, provided that this does not jeopardize your margin around the tumour. Divide the facial vessels between ligatures, well above and below the posterior pole of the gland. This policy usually only entails the sacrifice of fibres from such muscles as the anterior belly of the digastric anteriorly, the intermediate tendon of the digastric and the stylohyoid muscle inferiorly, the stylomandibular ligament posteriorly and the mylohyoid, stylohyoid, hyoglossus and posterior belly of the digastric medially. Assess 1 n Carefully assess by inspection and palpation the extent of the le2 n Plan the excision taking in to account the relaxed skin tension sion and the required area of excision. Raise the skin at one 4 n At this stage you will find it easier to decide by palpation how deeply the lesion extends. Make sure that your plane of cutting is sufficiently deep to give a wide margin of normal tissue below, as well as all round, the tumour. Remember that you must achieve an adequate margin of normal tissue on the deep aspect of the lesion as well as around it. A further precaution against aspiration of blood is to have the pharynx packed with 2. Cut out a full-thickness area of skin corresponding in size and shape to the pattern, with minimal subcutaneous fat. Stitch in the graft using interrupted non-absorbable sutures, tying the knots so that they lie on the surrounding intact skin rather than on the skin graft. You should produce sufficient tension in the graft to discourage haematoma without an excess that would produce a strangulation effect on the graft with consequent necrosis. Tissues often feel different when the patient is anaesthetized, making you change your decision about the depth of penetration of the lesion. Action 1 n Form a mental picture of the exact position and shape of your 2 n the area around that to be excised or biopsied can be injected incision. It is helpful to place a stitch at one end of the specimen so that the pathologist can orientate it and provide information on any areas of inadequate tumour clearance. The stitches must traverse the tissues far enough from the incision that they will not be cut when you make the incision. Make the wound roughly oval or in the shape of an ellipse, the direction of the long axis of the oval being dictated by the need to minimize damage to neighbouring structures. Do this as speedily as possible, as you cannot control bleeding until the excision is complete. This controls the worst of the bleeding if your assistant maintains traction on the stitch ends. Does the exci7 n If excision appears complete, tie the stitches in the form of the 8 n Complete haemostasis using diathermy and further sutures if necessary while maintaining a clear field with the sucker. Access 1 n Prepare the patient as for a local excision biopsy of an intraoral lesion. Do not forget 2 n Decide the width and length of wedge that you need to remove to ensure a wide margin of normal tissue around the lesion. Plan to excise the rim of the lesion in continuity with a generous portion of the neighbouring normal tissue. In general, the excised piece is oval with its long axis at right angles to the margin of the lesion. Usually this stops all bleeding, but if it fails to do so, use diathermy or insert more sutures. Do not insert sutures in to the lesion itself, since this may spread neoplastic cells. If you use a knife, the digital pressure of your assistant and yourself minimizes bleeding. Temporarily relax the fingers, first on one side and then on the Checklist n 2 n Are you sure that the specimen has been correctly bottled and 1 Was there any blood on the deeper parts of the pharyngeal pack Remember that any such sample must be sent in a sterile container without formalin. Insert further sutures to close the mucosa along the dorsal and ventral surface of the tongue, and to stop bleeding from the superficial layers. Ultrasound scanning of lesions in this area is important in the diagnosis of the lesion and most importantly to confirm that a thyroid gland does exist (in the normal situation). When operating on a lump you have diagnosed as a dermoid cyst, always look for evidence of a track upwards towards the tongue or downwards towards the hyoid. If you find such evidence, you must alter your diagnosis to thyroglossal cyst and change your operation accordingly. Access 1 n the patient lies supine, with the upper half of the table angled sufficiently upwards to cause the external jugular veins to collapse. This position facilitates access to the front of the neck, without putting the strap muscles and the superficial tissues on stretch. Use mosqui to artery forceps and absorbable ties to control bleeding from the labial artery. Deepen this through the skin and superficial fascia, and achieve haemostasis using diathermy. Continue what should prove a relatively bloodless dissection in all directions until you expose the deep aspect of the lesion. Make sure that there are points manifest themselves and can be sealed rather than bleed after the skin is closed. If the lump moves on swallowing and on protrusion of the tongue, it is likely to be a thyroglossal cyst; if it does not, it is likely to be a dermoid cyst. Blanket stitch gives firm, sideto-side apposition along every millimetre of the incision, ensuring that the incision is airtight. The suction/drain tubing is stitched to the skin using a clove hitch to ensure that the tube cannot slip in or out. The first fixes a loop so that pulling on the end of the apparatus does not pull the tube out of the wound. Note the intimate relationship between the track and the posterior aspect of the body of the hyoid, and the angle at which the suprahyoid portion of the track inclines. Persistence backwards for a short distance before again turning downwards to the isthmus of the thyroid gland. Check that after the air has been evacuated from the wound the system is airtight. Skin apposition must be perfect along the whole length of the wound not only to promote healing, but also to create an airtight wound so that the suction drainage can work efficiently, and to achieve the best cosmetic result possible. The sinus, which is more common, is an opening in the skin near the level of the thyroid isthmus connecting with a track that proceeds upwards for a variable distance towards the foramen caecum. The most common lesion is the cyst, which may lie at any point in the track but most often in the region of the hyoid bone, and which may have associated with it a variable stretch of persistent track both upwards and downwards. The course of this migration is midline, first through the tongue itself and between the muscles of the submental region, then closely applied to the hyoid bone, or even through it; at this stage the tract loops upwards and 3 n the intimate relationship between the track and the body of the 4 n Operations are described separately for (a) a thyroglossal sinus and (b) a thyroglossal cyst lying just below the body of the hyoid. The track has been cored out to the body of the hyoid, the central portion of the bone has been detached in continuity with the track, and a cylinder of muscle is cored out in the midline from the submental muscles in a direction backwards and upwards at 45. As you ap2 n Search for any downward extension of the track as a fibrous cord in the midline. If you find one, follow it as far downwards as you can feel it, or to the isthmus of the thyroid gland, and excise it separately. Action 1 n Dissect the oval of skin and superficial fascia and the fibrous tissue around the upward track from the sinus opening, raising a tube of tissues containing the track. At this and every subsequent stage, be careful to keep a margin of tissue between your instruments and the track itself. The tract can be injected with methylene blue dye to assist in identifying its path. You will find that it is 2 n the opening of the sinus may be situated above the thyroid isth- n intimately adherent to the body of the hyoid bone in the midline. Dissect this cord and follow its lower end downwards to the thyroid isthmus to include it in your specimen. Use bone-cutting forceps to excise this segment of bone, leaving it in continuity with the track. The complete lesion is a fistula with one opening in the pharynx near the posterior pillar of the fauces and the other in the skin at the junction of the middle and lower thirds of the anterior border of the sternomastoid muscle.

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The primitive heart tube is the first organ to function as a circulatory system by beating at embryonic Day (E) 9 in mice and at Day 22 in humans to meet the requirement to deliver nutrients throughout the developing embryo weight loss pills for teens discount 60 caps shuddha guggulu with amex. From the beating tube, the shape of the heart changes to create a rightward looping of the tube, followed by the steps to form a four-chambered structure as a result of the orchestration of multiple cardiac progenitor cells that are regulated by numerous signaling molecules and transcription factors with hemodynamic changes. Maintaining the pumping function, with concomitant shape changes during development, may make the cardiovascular system relatively susceptible to a variety of mistakes. It is known that congenital heart defects are the most among human congenital anomalies that are estimated at approximately 1% of newborns. Immediately after delivery, usually at 20 days in mice and around 270 days after conception in humans, the cardiovascular system switches the course of blood circulation for an oxygen source from the placenta to the lung, which involves closure of the ductus arteriosus, ductus venosus and foramen ovale. The morphogenesis of the heart, thus, seems to be a natural art brought about by evolution in order to obtain a higher function for maintaining a higher organism. Department of Pediatrics, Division of Pediatric Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. In the first step of cardiac development, a specific subset of mesodermal cells, generated during embryonic gastrulation migrate anterolaterally to form a crescent shape on approximately E7. In the mouse embryo, this source lies medially to the cardiac crescent and then lies behind the primitive heart tube, extending in to the mesodermal layer of the pharyngeal arches. Frontal views of embryos at cardiac crescent and primitive heart tube stage, and a lateral view of embryo at looping heart stage with transverse sections, and the four-chambered heart are shown. Cardiac neural crest cells contribute to the outflow tract cushions (yellow) that eventually form the aorto-pulmonary septum. A sub-region of the cranial neural crest cells originating between the otocyst and somite 3 has been called the "cardiac neural crest cells" that migrates in to the third, fourth, and sixth pharyngeal arches and the cardiac outflow tract (Hutson and Kirby 2007). They contribute to remodeling of the six pairs of bilaterally symmetric pharyngeal arch arteries connecting to the dorsal aorta that eventually results in the formation of the thoracic aorta, and proximal subclavian, carotid, and pulmonary arteries. In addition, they also form the septum of the outflow tract that divides the embryonic single truncus arteriosus in to the aortic and pulmonary trunk. As for the development of the coronary vasculature, smooth muscle cells arise from the epicardium, and endothelial cells and capillaries are derived from the venous plexus, at the sinus venosus, which invades the heart after formation of the epicardium. Islet1 in Cardiac Progenitors Insight in to the molecular mechanism underlying the development of cardiac progenitors would provide new therapeutic approaches for cardiac repair. In the past 10 years, numerous transcription factors that function during cardiac development have been identified. Thereafter, it has been shown that a diverse set of human fetal Islet1-positive cardiovascular progenitors give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages, and that purified Islet1-positive primordial progenitors were capable of self-renewal and expansion before differentiation in to the three major cell types in the heart (Bu et al. Islet1 knockout mice showed developmental defects of the right ventricle and outflow tract (Cai et al. During development, the expression of Islet1 is first detectable in the area comprising the dorsal-medial aspect of the cardiac crescent, and then behind the forming heart tube, expanding the splanchnic mesoderm of the pharyngeal region. Such signals may be autocrine, but often arise from the adjacent endoderm or other cell lineages. Wnt Signaling for Cardiac Progenitors Canonical Wnt signaling promotes progenitor cell proliferation, in addition to playing earlier roles in mesodermal development and negative modulation of cardiac specification (Cohen et al. Canonical Wnt -catenin pathway is also required for neural crest induction (De Calis to et al. Loss of Wnt signaling reduces the number of Islet1-positive cells, leading to defects of the outflow tract and right ventricle, whereas excess Wnt signaling expands the Islet1positive population. Transcriptome analysis of these Islet1positive cells shows an up-regulation of Fgfs, which promote proliferation, when canonical Wnt signaling is increased (Kwon et al. Conditional expression of stabilized -catenin in Islet1-positive cells also shows downregulation of the gene encoding myocardin that promotes myocardial and smooth muscle differentiation. Although Islet1 had been mainly associated with proliferation, it may, at least when expressed at a high level, promote differentiation and can directly activate a regulatory element of the myocardin promoter. Differences in the levels of Islet1 in determining its effects on differentiation or proliferation are likely to be associated with the level of stabilized -catenin in cardiac progenitor cells. Non-canonical Wnt signaling is specifically required for the outflow tract development (Pandur et al. Wnt11 mutant embryos have a short outflow tract and develop alignment and septation defects likely mediated by the loss of transforming growth factor (Tgf) 2 signaling. Tgf 2 signaling is a critical regulator of the neural crest and endocardial cushion development during the outflow tract septation (Zhou et al. Mice with Fgf8 hypomorphic alleles develop outflow tract defects reminiscent of those in the mouse mutant for T-box transcription factor, Tbx1 (Abu-Issa et al. Tbx1 itself is regulated positively Lessons from Heart Development to Regeneration 65 by Shh signaling (Garg et al. Fgf signaling, probably through its effects on proliferation, increases the extent of the heart field and the consequent numbers of cardiomyocytes that eventually form the outflow tract. There has been some evidence suggesting the role of Fgf signaling for migration of neural crest cells. Fgf8 and Fgf2 have chemotactic activity for neural crest cells (Kubota and I to 2000; Sa to et al. Interestingly, cranial neural crests express a variety of ephrinB2 ligand and the Eph receptors during their migration (Smith et al. Their migratory pathways are clearly bordered by non-neural crest cells expressing ephrinB1 ligand and the EphB2 receptor. An increase in Fgf signaling might increase the cardiac progenitor pool at the level of differentiation. In addition to Fgf8 and Fgf10, Fgf15 is also implicated in the outflow tract development. Fgf15 mutants show outflow tract defects, probably at least partly as a result of abnormal development of the neural crest (Vincentz et al. Hh Signaling for Cardiac Progenitors Hh signaling is also often associated with proliferation. At the arterial pole, Shh from the endoderm affects the pharyngeal arch mesoderm with additional effects on the maintenance and deployment of the neural crest (Dyer and Kirby 2009). In the absence of Shh, the pharyngeal vasculature, as well as outflow tract development is affected. In chick embryos, Shh signaling is clearly important for maintaining progenitor cell proliferation in the critical time frame which precedes addition of cells to the heart tube (Dyer and Kirby 2009). It is also required for the survival of neural crest cells in the pharyngeal region. Lessons from Heart Development to Regeneration 67 Shh signaling in the pharyngeal mesoderm is required not only for the outflow tract development but also for the atrioventricular septation (Goddeeris et al. Bmp Signaling for Cardiac Progenitors Bmp signaling is required for cardiac mesoderm specification and differentiation (Schultheiss et al. Mouse mutants with Bmpr1a, that encodes the Bmp receptor type 1 in the early cardiac mesoderm, results in a failure to form a differentiating heart tube, although Islet1-positive cardiac progenitor cells are present (Klaus et al. Later conditional deletion of Bmpr1a in Islet1expressing cells results in an abnormal right ventricle and outflow tract with increased numbers of Islet1-positive cells, suggesting a differentiation defect as Islet1 is normally downregulated in cardiomyocytes. This is accompanied by a reduction in Tbx20 that is required to repress Islet1 in the outflow tract (Yang et al. At the time of induction, Bmp4 is homogenously expressed in the dorsal neural tube whereas the Bmp inhibitor noggin is expressed in a cranial-coudal gradient, with high expression in the presumptive cardiac neural crest in order to control the level of Bmp activity to precise concentration for induction (Sela-Donenfeld and Kalcheim 1999). A gradient of Bmp activity determined by noggin specifies the expression of downstream transcription factor, Msx genes, in the neural fold which in turn upregulates early neural crest specific markers, such as Snail1/2 and FoxD3 (Tribulo et al. For the delamination from the neural tube, neural crest cells synchronously undergo epithelial-mesenchymal transition in the S phase of the cell cycle. Delamination is disturbed by inhibition of the cell cycle transition from G1 to S (Burstyn-Cohen and Kalcheim 2002). During the outflow tract development, Bmp4 is essential for myocardium formation as well as the survival of the neural crest (Nie et al. Outflow tract elongation is reduced in embryos lacking both Bmp4 and 68 Cardiac Regeneration using Stem Cells Bmp7 (Liu et al. Different signaling thresholds may be required for an effect on proliferation or differentiation of cardiac progenitors. Bmp/Tgf signaling can also be regulated by Tbx1 through direct interaction with Smad1 (Fulcoli et al.

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Supporting structures assist the delivery of gametes, and the uterus is the site of the embryo and fetus during pregnancy. Pregnancy begins with fertilization and is a time when the fertilized ovum undergoes implantation, embryonic and fetal development, and birth. Male reproductive organs include the testes, a system of ducts (epididymis, ductus deferens, ejaculatory ducts, and urethra), accessory glands (seminal vesicles, prostate, and bulbourethral glands), and supporting structures (scrotum and penis). The scrotum is a sac that hangs from the root of the penis and consists of loose skin and underlying hypodermis; it supports the testes. The temperature of the testes is regulated by contraction of the cremaster muscle and dartos muscle, which either elevates them and brings them closer to the warmth of the pelvic cavity or relaxes and moves them farther from the pelvic cavity for cooling. The testes are paired glands in the scrotum containing seminiferous tubules, which produce sperm during spermatogenesis. The seminiferous tubules contain the spermatogenic cells that form sperm; Sertoli cells, which nourish spermatogenic cells and secrete inhibin; and Leydig cells, which produce the male sex hormone testosterone. During spermiogenesis, developing sperm form an acrosome and flagellum, shed excess cytoplasm, increase mitochondria, and become elongated sperm cells that are released in to the lumen of the seminiferous tubules. Mature sperm have a pointed head, a caplike acrosome filled with enzymes for penetrating the secondary oocyte, and a tail with a middle piece containing mitochondria that provide energy for movement toward the secondary oocyte. At puberty, the hypothalamus secretes gonadotropin-releasing hormone, which stimulates anterior pituitary secretion of luteinizing hormone and follicle-stimulating hormone. Follicle-stimulating hormone and testosterone stimulate Sertoli cells to secrete androgen-binding protein, which binds to testosterone and keeps its concentration high in the seminiferous tubule. Sertoli cells secrete inhibin, which inhibits follicle-stimulating hormone release to help regulate the rate of spermatogenesis. Testosterone stimulates development of male reproductive structures and secondary sex characteristics, development of male sexual behavior, male and female libido, bone growth, protein anabolism, and sperm maturation. Fluid from Sertoli cells pushes sperm through the testis in the straight tubules, through the rete testis, then through the epididymis in the efferent ducts. The epididymis lies along the posterior border of each testis and contains the tightly coiled ductus epididymis, the site of sperm maturation and storage. The spermatic cord passes the ductus deferens, the testicular artery and veins, autonomic nerves, lymphatic vessels, and cremaster muscle through the inguinal canal. The ducts of the ductus deferens and seminal vesicle unite to form the ejaculatory duct, the passageway for ejection of sperm and secretions of the seminal vesicles in to the first portion of the urethra, the prostatic urethra. The urethra extends from the urinary bladder to the tip of the penis and is subdivided in to the prostatic, membranous, and spongy urethra. Seminal fluid constitutes about 60% of the volume of semen and contributes to sperm viability. The prostate lies inferior to the urinary bladder and surrounds the prostatic urethra. Its secretion constitutes about 25% of the volume of semen and contributes to sperm motility and viability. Paired bulbourethral glands lie inferior to the prostate on either side of the membranous urethra. They secrete mucus for lubrication and an alkaline fluid that neutralizes acids from urine in the urethra. Semen is a mixture of sperm and seminal fluid, which consists of secretions from the seminiferous tubules, seminal vesicles, prostate, and bulbourethral glands. Semen provides the fluid in which sperm are transported, supplies nutrients for sperm, and neutralizes the acidity of the male urethra and the vagina. The penis contains the urethra and is a passageway for ejaculation of semen and excretion of urine. The body of the penis is composed of three masses of erectile tissue: two corpora cavernosa penis and a corpus spongiosum penis that contains the spongy urethra and keeps it open during ejaculation. Engorgement of the penile blood sinuses under the influence of sexual excitation is called erection. Ejaculation is the expulsion of semen from the urethra to the exterior of the body. The female organs of reproduction include the ovaries, uterine tubes (oviducts), uterus, vagina, and vulva. Mammary glands are considered part of both the integumentary and reproductive systems. The ovaries are located on each side of the uterus and held in position by the broad, ovarian, and suspensory ligaments. The ovarian cortex contains ovarian follicles with oocytes in different stages of development. A corpus luteum, the remains of a follicle after ovulation, degenerates in to the corpus albicans. The secondary oocyte is released from the ovary during ovulation and is usually swept in to the uterine tube. The uterine tubes extend laterally from the uterus and are the normal sites of fertilization. Their distal end is an open, funnel-shaped infundibulum with fingerlike fimbriae that sweep the oocyte in to the uterine tube. Ciliated cells and peristaltic contractions help move a secondary oocyte or zygote toward the uterus. The uterus functions in menstruation, implantation of a fertilized ovum, fetal development, and labor. It also is part of the pathway for sperm to reach the uterine tubes to fertilize a secondary oocyte. The uterus wall is composed of an outer perimetrium; a middle myometrium consisting of three layers of smooth muscle important during labor; and the inner endometrium that lines the lumen of the uterus. There is an extensive blood supply to support regrowth of sloughed-off lining after menstruation, implantation of the fertilized ovum, and development of the placenta. It is a receptacle for the penis during sexual intercourse, an outlet for menstrual flow, and a passageway for childbirth. The external genitals of the female are termed the vulva and include the mons pubis, labia majora, labia minora, clitoris, vestibule, vaginal orifice, urethral orifice, and bulb of the vestibule. Also part of the vulva are the paraurethral glands, which secrete mucus in to the urethra; and the greater vestibular glands, which secrete lubricating mucus in to the vestibule to facilitate intercourse. The perineum is the diamond-shaped area medial to the thighs and buttocks containing the external genitals and anus. Within each breast is a mammary gland that functions in lactation, and the production and ejection of milk. The uterine cycle is a series of concurrent changes in the endometrium of the uterus to prepare it to receive the fertilized ovum and support ovum development. Gonadotropin-releasing hormone from the hypothalamus stimulates the anterior pituitary to release follicle-stimulating hormone and luteinizing hormone, which stimulate development of follicles and secretion of estrogens by the follicles. Luteinizing hormone also stimulates ovulation, formation of the corpus luteum, and secretion of estrogens, progesterone, relaxin, and inhibin from the corpus luteum. Estrogens stimulate the development and maintenance of female reproductive structures, secondary sex characteristics, and protein anabolism, and decrease blood cholesterol levels. Progesterone works with estrogens to prepare the endometrium for implantation and the mammary glands for milk secretion.

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Group A beta-haemolytic streptococcus is the commonest cause of bacterial pharyngitis weight loss pills in pakistan buy shuddha guggulu 60caps low cost, but co-pathogens in children include Staphylococcus aureus, Haemophilus influenzae, Branhamella catarrhalis and Bacteroides fragilis. Clinically differentiation of the pathogens of pharyngitis is rarely possible and there are no reliable clinical clues to identifying streptococcal infection. Frequently no pathogens are isolated on culture, making the value of this questionable. Any non-healing lesion of the pharynx or oral cavity leads to the suspicion of neoplasia, both carcinoma and lymphoma, and early biopsy may be necessary for diagnosis. It is primarily a disease of young adults but can present in childhood and in older adults. The most common finding is tender cervical adenopathy, usually accompanied with a sore throat. The pharyngeal signs range from acute follicular tonsillitis indistinguishable from other causes of follicular tonsillitis, to a grey membrane lining the oropharynx, petechiae on the soft palate and sometimes a peritonsillar abscess, which can be bilateral. False positive monospots can occur in healthy controls as well as in mumps, systemic lupus erythematosis and sarcoidosis. Ampicillin-based antibiotics should be avoided because of the certainty of producing a rubelliform rash. Other viral diseases that may present in a similar manner include: cytomegalovirus, herpes simplex 1, herpes zoster, hand, foot and mouth disease and herpangina. Other causes of specific pharyngitis In the developing world and in vulnerable population groups, there are a number of conditions for which the clinician must be alert. It is the site of primary infection almost always in children and results in an asymptomatic primary focus in the pharynx (usually tonsil or adenoid) with cervical lymphadenopathy. In adults the pharynx may be involved in patients with widespread miliary tuberculosis. Syphilis this is an infection by the spirochaete Treponema pallidum and apart from the congenital form, is acquired by sexual intercourse. In secondary syphilis the pharynx and soft palate display hyperaemia and inflammation and there may be lesions which have been described as mucous patches or ``snail track' ulcers. Uncommon in the Western World because of widespread immunisation in children but is on the increase in the non-immunised patients. Systemic effect of the toxins can lead to myocarditis, nephritis and encephalitis. Throat Pain 91 to pathology within the tonsils themselves, or to the efficacy of any therapy employed. The evidence is now strong that a significant majority of a cohort of sufferers in the paediatric age group show improvement over 3 years with most having only minor episodes thereafter. Cohorts of children treated conservatively show similar levels of symptoms to those treated by tonsillectomy after 3 years, but there are individual cases that continue to have severe recurrent episodes resulting in significant morbidity. There is also a group of adults, typically in the teens or early 20s, who suffer recurrent or chronic sore throat symptoms with disabling morbidity from time to time. Treatment of diphtheria should start immediately and antitoxin should be given within the first 48 h of onset without confirmation of the result of the throat swab. Allergic testing to ensure no allergy against horse serum should be done before injection. Indications for tonsillectomy By definition, tonsillitis cannot occur after tonsillectomy (unless some tonsillar remnants are present). It is therefore important in considering tonsillectomy that the diagnosis of tonsil pathology is as certain as possible. Management of this includes adequate analgesia, anti-emetics when required and attention to nutrition, oral hygiene and hydration. Complications of sore throat Following streptococcal infection, complications may occur and rarely in the developed world include rheumatic fever (0. Septic complications are much commoner after both viral and bacterial tonsillitis as bacterial superinfection may occur following an initial viral infection and may result in serious and occasionally life threatening illness. Quinsy Peritonsillar abscess (quinsy) is a collection of pus between the fibrous capsule of the tonsil and the superior constrictor muscle of the pharynx. It is usually a complication of acute tonsillitis, occurs at any age, but is most often seen in young adults between 20 and 40 years. Clinically the history is progressive, usually unilateral, sore throat over 3 or 4 days, pain on swallowing (odynophagia), dysphagia for solids and eventually liquids, drooling of saliva, trismus, ipsilateral ear pain and headache associated with fever, lethargy and ipsilateral lymphadenopathy. The patient usually develops a ``plummy voice' secondary to the oropharyngeal swelling. There is limited opening of the mouth, with the tonsil displaced medially by the bulging in the region of the superior pole of the tonsil and enlarged tender lymph nodes in the upper jugulodigastric area of the neck. The differential diagnosis includes infectious, inflammatory, vascular and neoplastic pathologies (Box 16. The presence of a pointing abscess, clinical deterioration, failure to respond to intravenous antibiotic and evidence of an abscess on imaging, would all be reasonable indications for drainage either by needle aspiration or using a conventional guarded quinsy knife. Good results and minimal morbidity are reported with no increase in perioperative, primary or secondary haemorrhage and the additional advantage of avoiding recurrence and the need for elective delayed tonsillectomy. Complications of quinsy Deep neck space abscess and mediastinitis have been described. Mediastinitis has a significant mortality even when treated aggressively with powerful antibiotics. Infectious: peritonsillar cellulitis, parapharyngeal abscess, upper molar dental abscess, and infectious mononucleosis. Inflammatory: Kawasaki disease (rare) Vascular: post-traumatic internal carotid pseudo-aneurysm (rare) Malignant neoplasm: squamous cell carcinoma, lymphoma, sarcoma, metastatic disease, minor salivary gland tumour. Benign neoplasm: deep lobe parotid lesions (rare) Parapharyngeal abscess the parapharyngeal space is a potential space located on either side of the upper pharynx, from the nasopharynx to the oropharynx. Infection can spread to the parapharyngeal space from any of the other deep neck spaces including peritonsillar, retropharyngeal and submandibular space. Bacteriology of deep neck space infections seems to be changing with increasing numbers of cases due to gram-negative aerobic organisms, which do not respond to first-line penicillin treatment and thus may be contributing to the significant mortality seen in some parts of the world. Organisms such as Klebsiella pneumonia and Streptcoccus viridians are commonly grown. Presentation and examination are very similar to peritonsillar abscess except that the maximum swelling in the pharynx is more inferiorly placed and behind the tonsil, with less oedema of the palate. Not infrequently, a firm but fluctuant swelling rather than lymphadenopathy can be felt in the upper neck. Treatment is in Confirmation of the presence of pus on needle aspiration is diagnostic, but if there is doubt, or the patient is very ill and there is difficulty evaluating the anatomical region, then imaging is indicated prior to any surgical intervention. Treatment of quinsy Most patients diagnosed with a quinsy will be admitted to hospital for intravenous fluids and antibiotics until acceptable swallowing has recovered. Benzylpenicillin intravenously will cover the majority of the anaerobes as well as the streptococcal infection and is the treatment of choice, but metronidazole may also be added. Surgical drainage may be necessary if the clinical condition does not respond rapidly to intravenous antibiotics with or without steroids and if a collection is demonstrated on imaging. Retropharyngeal abscess Retropharyngeal abscess most commonly occurs in children under 6 years old, with a peak incidence between 3 and 5 years.

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If you do undertake it weight loss pills garcinia cambogia free trial discount shuddha guggulu 60caps mastercard, however, remember ations of less than 5 mm only if aqueous humour is leaking. Tie each suture while an assistant, using two pairs of plain forceps, draws the edge of the flap well over the site of the penetration. If the penetration is central, it should still be possible to cover it in this way. Give the injection by passing the needle tangentially through the conjunctiva in a horizontal direction 1 cm back from the limbus, in to the quadrant opposite to that of the penetrating injury. If you withdraw it correctly, nothing escapes from the anterior chamber even if the ocular tension is very high. Do not press for longer than a second at a time initially, since a rapid drop in intraocular pressure may re-start the bleeding. Repeat intermittent pressure until you note some clearing of the anterior chamber. This condition justifies a much more rapid evacuation of the clear normal aqueous humour. Patients with sickle cell disease or trait may have severe hyphaemata, which is very slow to resolve. Undertake it only when: n the anterior chamber is full of blood and n There is a considerable rise in the intraocular pressure, which is unresponsive to acetazolamide (Diamox) and oral glycerol or mannitol infusions over a 3-day period or n the patient is in severe pain. Have available a disposable or diamond tetracaine (amethocaine) drops given at 5-minute intervals. It is usually better, from a psychological point of view, to suture the eye as best you can then discuss removal of the eye, if it is not viable, with the patient over the next few days. Months, or even years later, the unaffected eye and the affected eye develop panuveitis with sight-threatening sequelae including glaucoma and cataract. Do not insert the needle directly at the foreign body, but enter the cornea a little to the side. Monitor the patient daily, if possible, until the conjuntiva has healed and no longer stains with fluorescein. If daily monitoring is not possible, advise the patient to use chloramphenicol ointment three times a day until symptoms resolve. Immediately concentrate on removing any matter mechanically and, in particular, copiously irrigate the eye using any harmless fluid you have at hand. If the cornea is affected, apply antibiotic/steroid ointments such as Maxitrol (containing dexamethasone 0. Keep the conjunctival fornices patent to prevent symblepharon (adhesion of the eyelids to the eyeball), by twice-daily passing a glass rod between the lids and the eyeball after anaesthetizing the eyeball with oxybuprocaine 0. Always admit patients with lime burns for observation as the effects may be delayed and you may need to institute half-hourly drops including vitamin C in high dosage. Also encourage the patient to eat citrus fruits, since vitamin C is an antioxidant and a cofactor in collagen synthesis. If there is loss of skin following a thermal burn, the ocular surface may also be severely damaged by the injury. In the longer term it will be necessary to reconstruct the lids using tissue from elsewhere, such as skin from behind the ear and hard palate grafts to recreate the tarsal plate. Metallic foreign bodies must be removed within a week because of the risk of the metallic ions causing toxicity to the retina. Be willing to 4 n A large foreign body may cause a penetrating injury that requires 1 n Remove these by everting the upper eyelid after instilling proxy- Subtarsal foreign bodies 2 n Once the eyelid is everted, keep hold of the lashes and press them metacaine, tetracaine (amethocaine) or oxybuprocaine. Grasp the upper lid lashes with the thumb and forefinger of one hand and pull the lid down and forwards. With an orange stick, press the upper edge of the tarsal plate downwards (some 4 mm from the lid margin) and then lift the lashes so as to rotate the lid over the orange stick, which pushes the tarsal plate down and under the lid margin at the same time. Remove the orange stick and use your freed hand to remove the foreign body with the cotton-wool swab. A stye is an infection of a sebaceous gland of the lid, and resolves without treatment in 36 hours. They all go away eventually but if they are persistent they may be incised and curetted. Avoid incision wherever possible but, in the presence of a tense abscess causing pain, release it. It is usually associated with fever, reduced visual acuity on the affected side, proptosis and gross eyelid swelling and reduced eye movements. The patient needs to be admitted, the organism isolated and treatment started with intravenous antibiotics. Review the patient daily, and admit for intravenous antibiotics if it deteriorates. Distinguish preseptal cellulitis from orbital cellulitis, which is a life-threatening illness. In preseptal cellulitis, even if the lid is swollen the eye is not proptosed and is fully mobile, with a normal or near normal visual acuity. Mobility of the prosthetic eye is better following evisceration than following enucleation. It may also be accompanied by pus in the anterior chamber (hypopyon); if this is unresponsive to intensive local and systemic antibiotics, you may need to perform paracentesis to obtain a specimen for microscopy and culture. Application of superglue to the thin cornea may provide emergency treatment of corneal perforation. Cut the conjunctiva close to this edge, undermine some more and proceed snipping right round the cornea. This is a lustrous grey-white colour, and you should satisfy yourself that you are really down to it by cutting away any other loose fascial planes. Test that you have caught the muscle by pulling the hook anteriorly, when it will be stopped short at the insertion and will then move the whole eye. Cut off the tendons of the superior, lateral and inferior recti flush with the globe instead of leaving a stump attached to the globe as was done with the medial rectus. B 8 n If you have any idea where the inferior and superior oblique mus- cles are, and they can be found, divide them. Usually, however, no formal search need be made for them as they can be dealt with as the globe is removed. The eyeball should now come forwards with something of a jerk; its equator will be in front of the plane of the speculum. Now slightly close the speculum and tighten its screw so that the globe is kept in its forward dislocated position. Any short, but tough, blunt-nosed scis- sors, preferably slightly curved, will do. First rotate the globe outwards by grasping the stump of the medial rectus with 2-in-3 fixation forceps. Probe the region of the optic nerve, which you cannot yet see, by passing the points of closed scissors from the nasal side to where it should be. Now withdraw the scissors about 5 mm, open the blades widely enough to flank the nerve, then advance the blades to engage it, making sure you are far enough in to section the nerve with one cut. Finally, close the conjunctiva as a separate layer with 6/0 or 8/0 synthetic absorbable sutures. While applying pressure, inspect the enucleated eye for completeness of removal, especially in the region of the optic nerve. Use a continuous 7/0 or 8/0 synthetic absorbable suture, either in a continuous keyhole or over-and-over pattern; tie at each end. Appraise 1 n If the vital internal structures of the eye are destroyed by infection, with loss of vision, evisceration (removal of the soft contents from within the sclera), is indicated rather than enucleation, since mobility is better following evisceration. Modify your technique as follows: 1 Insert sutures in to each of the rectus muscles before cutting them off the globe.

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One of the commonest disorders of respiration is the periodic (Cheyne-Stokes) type in which there is alternating hyperpnoea and apnoea weight loss pills visalia ca purchase line shuddha guggulu. This usually indicates a bilateral cerebral or high brain stem lesion or metabolic dysfunction. Other brainstem lesions of the midbrain or mid-pons cause central hyperventilation or ataxic irregular breathing patterns. The latter are most commonly seen in lesions of the medulla and lack the rhythmical waxing and waning of the Cheyne-Stokes type. The odour of acetone in the breath in diabetic comas is classical, but not detectable by many people. Pulse the pulse is: (a) Rapid and weak in haemorrhage, shock, some stages of syncope and circulatory collapse. A weak, irregular pulse is found in low brainstem lesions and a fibrillating pulse raises the possibility of cerebral embolism. Percussion of the skull in children with hydrocephalus produces a high-pitched, cracked-pot note, and in comatose infants a bulging fontanelle indicates increased intracranial pressure. If burr holes or a decompression are present, they should be palpated, because if tense and bulging this means high intracranial pressure. It may, however, indicate cerebellar tonsillar herniation at foramen magnum level, rather than frank meningitis. This is important for it would contraindicate a lumbar puncture, and the history of the onset is vital. In the earliest stages of subarachnoid haemorrhage, neck rigid ity may not have developed, sometimes is delayed even 24 hours, and if coma or collapse is profound. The tongue A common cause of coma being epilepsy, the tongue should be examined for evidence of having been bitten. The surface and the inside of the cheek, palate, fauces and pharynx should be inspected for the effects of corrosive fluids. This is done by rubbing the sternum vigorously with the knuckles, and by pressure in the supraorbital notch. There may be signs of diffuse disease or of a focal lesion in the supratentorial or subtentorial compartment. In addition to evaluation of the level of consciousness itself, and attention to the pattern of respiration, it is the examination of the pupils, ocular movements and motor func tion that forms the most crucial part of the exercise. Th e cranial nerves the ordinary routine examination is not possible, for all observa tions have to be objective, and a somewhat different approach must be adopted. The fundi these must be most carefully examined in every case, the abnor malities having the same significance as described in Chapter 7. Remember, however, that whereas true papilloedema (in the absence of marked hypertension) indicates increased intracranial pressure, its absence does not in any way exclude a space-occupying lesion. Visual fields these cannot be accurately tested, but in stuporose states, a menac ing movement towards the eye from one side and then the other will normally produce a blink (menace reflex), which may be absent when the gesture is made from the side of a hemianopia. Their presence or absence is, in fact, the single most important sign in distinguishing metabolic from structural disease. These may be primary, or secondary to central pressure herniation as in cases of tumour or haematoma in the supratentorial compartment. Be certain any dilatation is not due to the use of atropine by a previous examiner. It is commonly, but not invariably, on the side of the expanding lesion and demands prompt surgical Chapter 27 the unconscious patient action. By the time both pupils are dilated, there has usually been a secondary haemorrhage in to the brainstem, and even correction of the primary lesion may not save the patient. Ocular position and ocular movements Note the position of the eyes, any deviation from the midline, how well sustained this is, any spontaneous ocular movements and any movements on sudden noise or on command. Abnormalities of conjugate deviation have an important role in comatose states and are dealt with in Chapter 8. Remember that forced upward deviation of the eyes or oculogyric crises can be caused by toxic doses of the phenothiazine derivatives. Because the pathways controlling oculomotor vestibular reflexes lie adjacent to the reticular formation, good use can be made of testing these responses. These observa tions are of particular value in distinguishing structural lesions of the cerebral hemispheres from those of the brainstem, remember ing, of course, that the latter dysfunction is often secondary to cen tral herniation. But in the absence of secondary brainstem compres sion, cerebral hemisphere lesions do not affect either reflex. Similarly, metabolic suppression of the hemispheres and brainstem spares the oculomotor vestibular pathways until late, when their abnormality can then be used to identify the so-called brainstem death. It can be recalled from Chapter 11 that irrigation of the external auditory canal with cold (or warm) water excites nystagmus. In lesions of the diencephalon causing coma, the fast compo nent of that nystagmus is depressed, so that there is, instead, just tonic conjugate deviation of the eyes towards the irrigated ear. Midbrain or Part 6 Examinations of particular difficulty upper pontine lesions can cause various abnormalities; deviation may be confined to the ipsilateral eye, indicating a contralateral intemuclear ophthalmoplegia, or be seen only in the contralateral eye, suggesting a sixth nerve lesion on the stimulated side. Occa sionally, such absence of any ocular response is the result of bilateral end-organ poisoning by gentamycin or other related antibiotics. Flattening and smoothing of the wrinkles on one side, with uncovering of the sclera, are seen in paralysis of lower motor neuron type and sometimes in the acute stages of severe upper motor neuron paralysis. The paralyzed side will be blown out and sucked in during expiration and inspiration. Normally, this is most marked on the side stimulated, but when there is facial paralysis it is reduced on the affected side, no matter which side is stimulated. Touching the comer of the mouth may produce a sucking reflex and deviation of the comer of the mouth. This is seen in the adults in bilateral cerebral lesions of severe diffuse character. It is often bilaterally absent in deep coma or depressed if the cornea has been exposed for a long time. Painful stimulation of the skin should be carried out by pinprick or pinching, and the relative grimacing on each side compared. Great care in interpretation of corneal reflex and facial sensory tests is required in the presence of facial paralysis (see Chapter 10). Purely unilateral loss of sensation in comatose patients is usu ally part of a complete hemianalgesia and indicates a deep-seated hemisphere or upper brainstem lesion. Sensory loss on one side of the face but on the opposite side of the body indicates a lower brainstem lesion, and is especially common in the lateral medullary syndrome, traditionally due to a posterior inferior cerebellar artery thrombosis, but in fact usually a sign of vertebral artery disease. The motor system A great deal will have been learnt during the preliminary period of inspection. This applies particularly to the position of the limbs Chapter 27 the unconscious patient and the degree of movement carried out by each limb. The tone of the limbs can be tested in the normal way, but remember that in the acute stage of a severe intracranial lesion, the tone may be lost, rather than increased, on the side opposite to the lesion. Normally, the fall is checked and slowed, but in unilateral paralysis the arm will fall unchecked. Next, raise the legs in to the flexed position, so that the soles of the feet rest on the bed, and then allow them to fall back. Remember, midbrain lesions produce decerebrate posturing, and that this may at first only follow noxious stimulation, and may be unilateral if the other side is paralyzed. Th e reflexes Testing the reflexes, being an objective procedure, can be carried out in the normal way and the usual deductions can be drawn, but in states of deep coma the interpretation of the results may be different. The plantar responses may be absent, or bilaterally extensor, and so also have little localizing value, except that if there is a unilateral extensor plantar, this indi cates the side of a pyramidal system lesion. Dilata tion of the pupils, grimacing or movements of the limb will occur if sensation is present. In the former, there is usually movement of the normal limb even when the abnormal side is stimu lated. In deep coma, these tests are of little value, other than as an indication of the depth of the coma. Coordination this cannot be tested in the ordinary way, but in stuporose states the patient will often attempt to fight off interference and to brush off the painful stimuli. Essential investigations Blood Obviously, the history and clinical assessment of the case will influ ence greatly the type of investigation to be undertaken, but in every case the sample must be sent immediately for a full blood count, estimation of glucose, urea and electrolytes and often for plasma calcium and liver function tests.