By Q. Brontobb. Mountain State University. 2018.
Mechanism Transcription involves 3 stages i) Initiation ii) Elongation iii) Termination Three phases of transcription 1 100 mg nizagara with mastercard. This complex enzyme discount nizagara 50 mg with visa, called the holoenzyme is needed to initiate transcription since the s factor is essential for recognition of the promoter discount nizagara 50mg on line. It is common for prokaryotes to have several s factors that recognize different types of promoter (in E order 100 mg nizagara visa. The holoenzyme binds to a promoter region about 40-60 bp in size and then initiates transcription a short distance downstream (i. With in the promoter lie two 6 bp sequences that are particularly important for promoter function and which are therefore highly conserved between species. Using the convention of calling the frst nucleotide of a transcribed sequence as +1, there 2 promoter elements 98 lie at position -10 and -35, that is about 10 and 35 bp respectively, downstream of where transcription will begin. The most common termination signal is a G ≡ C rich region is a palindrome, followed by an A = T rich sequence. Those that lack such a structure require an additional protein, called rho protein (r) to help recognize the termination site and stop transcription. The product of transcription in eukarryotes are called as primary transcripts and they undergo modifcation by a process called post transcriptional modifcation. Okasaki fragments are present in i) both the parental strands ii) both the daughter strands iii) leading strand iv) lagging strand c. G-C rich region followed by A-T rich region is a signal for i) initiation ii) elongation iii) termination iv) primer formation d. One among the following is not a modifed base i) pseudo uridine ii) isopentyl adenine iii) methyl guanosine iv) deoxy thymine e. The metabolism of our body comprises two major balanced activities: anabolism (synthesis) and catabolism (degradation). Whether the metabolic changes are exergonic or endergonic, most of them have to be catalysed by enzymes. If one particular enzyme is defcient or absent then that leads to a block in the pathway of biochemical reactions leading to metabolic abnormalities which are present throughout the life and handed over to the progeny. The absence or defciency of an enzyme will cause an abnormal accumulation of the intermediate products of metabolism in the body and increased excretion in urine as such or their degradation products. For example, in the following reaction a c b d R B C D P R is the reactant, B, C and D are intermediates and P is the product and a, b, c and d are enzymes catalyzing various steps of the reactions. In this reaction pathway, if any one of the enzyme is defcient or absent, the previous intermediate accumulates and produces toxicity. It also affects the amount of product (P) formation which may be essential biologically and there by leads to pathological diseases. Beadle and Tatum put forth their theory of one gene one enzyme hypothesis which states that one gene controls the synthesis of a single enzyme. Galactosemia, Von-Gierke’s disease, hemophilia, albinism, alkaptonuria and Tay-Sach’s disease are some of the important diseases due to inborn errors of metabolism. Due to the enzyme defect galactose accumulates in blood and is reduced by aldose reductase in the eye to the corresponding galactitol which causes cataract. The general condition is more severe if it is due to a defect in galactose 1 - phosphate uridyl tranferase, since galactose 1- phosphate accumulates and depletes the liver of inorganic phosphate. After 2 - 3 months of age the liver may show fatty infltration and lead to cirrhosis (non functioning of liver cells). Galactosemia at this age is associated with mental retardation due to accumulation of galactose and galactose 1 - phosphate in cerebral cortex. In this, the enzyme which is defcient is glucose 6-phosphatase that converts glycogen to glucose 6-phosphate and then to glucose. Massive enlargement of the liver, pronounced hypoglycemia in between meals, failure of blood glucose to rise on administration of glycogen and convulsion are seen in this condition. Since glucose 6- phosphate cannot leave liver cells, there is compensatory increase in glycolysis leading to increased levels of pyruvic acid and lactic acid. If any one or more of these factors are not synthesised adequately and properly that results in defect in blood clotting and thereby hemorrhage.
It receives blood from most of the superficial tis- • Arterial supply: is from the posterior tibial artery which divides into sues of the foot via digital and communicating branches nizagara 25 mg generic. The latter branch contributes the saphenous vein commences from the medial end of the arch and the major part of the deep plantar arch (p buy cheap nizagara 50mg online. The shaft of the • The greater trochanter of the femur lies approximately a hands- fibula is mostly covered but is subcutaneous for the terminal 10 cm order 25mg nizagara visa. It is made more prominent by adducting • The popliteal pulse is difficult to feel as it lies deep to the tibial nerve the hip order nizagara 50mg visa. It is best felt by palpating in the popliteal fossa with • The ischial tuberosity is covered by gluteus maximus when the hip the patient prone and the knee flexed. The lat- the anterior superior iliac spine and the symphysis pubis (mid-inguinal eral is more elongated and descends a little further than the medial. The femoral head lies deep to the femoral artery at the mid- • When the foot is dorsiflexed the tendons of tibialis anterior, extensor inguinal point. The femoral vein lies medial, and the femoral nerve lat- hallucis longus and extensor digitorum are visible on the anterior eral, to the artery at this point. The hernial sac always lies below and • Passing behind the medial malleolus lie: the tendons of tibialis pos- lateral to the pubic tubercle (cf. The tendon of peroneus brevis inserts onto the tuberosity on • The sciatic nerve has a curved course throughout the gluteal region. Consider two linesaone connects the posterior superior iliac spine and • The heel is formed by the calcaneus. The tendocalcaneus (Achilles) the ischial tuberosity and the other connects the greater trochanter and is palpable above the heel. The division of the sciatic nerve into tibial and • The tuberosity of the navicular can be palpated 2. The tendon of tibialis posterior lies above the sustentaculum tali • The common peroneal nerve winds superficially around the neck of and the tendon of flexor hallucis longus winds beneath it. Footdrop can • The dorsalis pedis pulse is located on the dorsum of the foot be- result from fibular neck fractures where damage to this nerve has tween the tendons of extensor hallucis longus and extensor digitorum. The • The patella and ligamentum patellae are easily palpable with the small saphenous vein drains the lateral end of the arch and passes pos- limb extended and relaxed. The ligamentum patellae can be traced to its terior to the lateral malleolus to ascend the calf and drain into the attachment at the tibial tuberosity. The great saphenous vein passes anterior to the medial • The adductor tubercle can be felt on the medial aspect of the femur malleolus to ascend the length of the lower limb and drain into the above the medial condyle. This vein can be accessed consistently by ‘cutting down’ • The femoral and tibial condyles are prominent landmarks. With the anterior to, and above, the medial malleolus following local anaesthe- knee in flexion the joint line, and outer edges of the menisci within, are sia. Surface anatomy of the lower limb 119 53 The autonomic nervous system Visible Sympathetic Parasympathetic Sympathetic ganglion Cranial outflow 3, 7, 9, 10/11 Parasympathetic T1 Spinal cord Microscopic ganglion Fig. The former initiates the ‘fight or flight’ reac- ramus and are then distributed with the branches of that nerve. B They may pass to adjacent arteries to form a plexus around them Both systems have synapses in peripheral ganglia but those of the sym- and are then distributed with the branches of the arteries. Other pathetic system are, for the most part, close to the spinal cord in the gan- fibres leave branches of the spinal nerves later to pass to the arter- glia of the sympathetic trunk whereas those of the parasympathetic ies more distally. The fibres leave these spinal nerves as the white rami Loss of the supply to the head and neck will produce Horner’s syn- communicantes and synapse in the ganglia of the sympathetic trunk. There will be loss of sweating (anhidrosis), drooping of the • Parasympathetic outflow: this comprises: upper eyelid (ptosis) and constriction of the pupil (myosis) on that side. The trunk constrictor pupillae and the ciliary muscle, synapsing in the ciliary continues upwards into the carotid canal as the internal carotid nerve. Synapses occur in minute ganglia in the cardiac and pulmonary 2 They may pass straight through the corresponding ganglion and travel plexuses and in the walls of the viscera. One exceptional group of supply the pelvic viscera, synapsing in minute ganglia in the walls of fibres even pass through the coeliac ganglion and do not synapse the viscera themselves. Region Origin of connector fibres Site of synapse Sympathetic Head and neck T1–T5 Cervical ganglia Upper limb T2–T6 Inferior cervical and 1st thoracic ganglia Lower limb T10–L2 Lumbar and sacral ganglia Heart T1–T5 Cervical and upper thoracic ganglia Lungs T2–T4 Upper thoracic ganglia Abdominal and pelvic T6–L2 Coeliac and subsidiary ganglia viscera Parasympathetic Head and neck Cranial nerves 3, 7, 9, 10 Various parasympathetic macroscopic ganglia Heart Cranial nerve 10 Ganglia in vicinity of heart Lungs Cranial nerve 10 Ganglia in hila of lungs Abdominal and pelvic Cranial nerve 10 Microscopic ganglia in walls of viscera viscera (down to transverse colon) S2, 3, 4 Microscopic ganglia in walls of viscera The autonomic nervous system 121 54 The skull I Coronal suture Parietal Squamous Frontal temporal Sphenoid, greater wing Ethmoid Lambda Lacrimal Metopic suture (uncommon) Occipital Supraorbital foramen Nasal Position of frontal air sinus Zygomatic Maxilla Frontal External Ethmoid auditory meatus Lacrimal Orbital plate External occipital of frontal Styloid Optic canal Sphenoid, protuberance process Superior lesser wing Fig.
Dantrolene is Analysis of an arterial blood sample will orange in colour and supplied in vials containing demonstrate: 20mg (plus 3g mannitol) buy nizagara 100 mg otc; it requires 60mL water •aprofound metabolic acidosis (low pH and for reconstitution and is very slow to dissolve cheap nizagara 25mg visa. Correction buy nizagara 50mg otc, using episode buy nizagara 25mg with amex; the following techniques, may allow recovery •ensure that appropriate monitoring and without the need for further intervention. A sequence of actions is performed in which the airway, breathing and circulation are supported without the use of any equipment other than a simple protective shield interposed between the mouths of the rescuer and patient (e. At the same time, broken, loose or partial dentures should be re- moved, but well-fitting ones may be left in place (see later). Expired-air ventilation (rescue breathing or mouth-to-mouth ventilation) • There must be a clear path, with no leaks, be- Figure 4. The tips of the thumbs can • Keep the victim’s airway patent by performing a be used to open the mouth. Mouth-to-nose ventilation This technique is used where mouth-to-mouth ventilation is unsuccessful, for example if an ob- struction in the mouth cannot be relieved, or when the rescuer is a child. Circulation • The fingers of the lower hand are then used to Check for evidence of a circulation: perform a chin lift, and if necessary open the vic- •Look, listen and feel for normal breathing, tim’s mouth (Fig. To optimize compression and reduce rescuer (a) fatigue chest compressions are best performed with the rescuer leaning well forward over the patient, arms straight and hands, elbows and shoulders ex- tended in a straight line. This allows use of the res- cuer’s upper body weight to achieve compression, rather than the arm muscles, which will rapidly tire and reduce efficiency (Fig. Common errors Wrong hand position: • too high: the heart is not compressed; (b) • too low: the stomach is compressed and risk of Figure 4. Overenthusiastic effort: • Central arteries are more reliable than periph- • causes cardiac damage; eral ones as a pulse will be palpable even with a • fractures ribs which may damage underlying very low cardiac output. Failure to release between compressions: Chest compressions • prevents venous return and filling of the heart. This technique only results in a maximum cardiac When a collapsed person is not breathing and has output 30% of normal, and in order to achieve this no spontaneous circulation, they will require both the position of the hands is critical: rescue breathing and chest compressions; this is • The rescuer positions him/herself on one side of often referred to as cardiopulmonary resuscitation the victim. A ratio of 15 chest compressions to 2 breaths • The victim’s chest is exposed and the xiphister- should be used, irrespective of the number of per- num identified. If the heel of the other hand is placed adjacent to two or more healthcare professionals are present, them on the sternum (Fig. The 102 Management of perioperative emergencies and cardiac arrest Chapter 4 same ratio of 15:2 must still be used. The shoulder is pulled • Defibrillate if appropriate; do not delay for venti- towards the rescuer whilst at the same time the lations or chest compressions. The most important first step is to identify agement is summarized in the Universal Treatment the cardiac arrest rhythm, which can belong to one Algorithm (Fig. Defibrillation Defibrillation (and cardioversion) depolarizes a critical mass of the myocardium, allowing the nat- Figure 4. Defibrillators have a power source, either mains or battery, which charges a capacitor to a predetermined level. A manual de- diameter, placed on the patient’s chest wall (see fibrillator must only be charged when the paddles below). Success depends on the current flow are on the patient’s chest and must not be moved through the myocardium and therefore to reduce between defibrillator and patient whilst charged. This is often referred to as with the patient or trolley, directly or indirectly ‘manual defibrillation’. Increasingly, ‘hands free’ (via spilt electrolyte solution), when the defibrilla- systems consisting of two large, self-adhesive tor is discharged. Any nitrate patches The paddles or self-adhesive electrodes are should be removed from the patient’s chest placed anterolateral: one to the right of the ster- along with any high-flow oxygen to eliminate num, just below the clavicle; and the other over the risk of fire. Al- ally a shout of ‘stand back’, and a visual check of though the paddles are marked positive and nega- the area are mandatory before discharging the tive, each can be placed in either position (Fig. An alternative is to place them anteroposterior to If further shocks are required, the paddles should the heart. A •Shout ‘stand back’ and make a visual check of precordial thump can be used under the same cri- the area. In general, the outcome from asystole is Epinephrine (adrenaline) poor unless there are ‘p’ waves present that may re- This is a naturally occurring catecholamine, ad- spond to cardiac pacing. This leads to an in- Atropine crease in the peripheral vascular resistance that tends to divert blood flow to the vital organs An anticholinergic acting at muscarinic receptors, (heart, brain).
This was particularly evident in three-arm trials in which p-values for comparisons of interest for this review were not the primary comparisons in the trial order nizagara 100mg with mastercard. It may be that in some cases the reporting of the evidence buy 50mg nizagara overnight delivery, rather than the evidence itself generic 25 mg nizagara, is insufficient to make any conclusion about the comparative effectiveness of two treatments order 100 mg nizagara with mastercard. The seven comparisons are listed below with the proportion of drugs represented in each class indicated in parentheses. Similarly, only one of two oral decongestants was studied (pseudoephedrine), the one that is most commonly used. In four comparisons, intranasal corticosteroid alone or in combination was poorly represented: In two (versus nasal antihistamine and versus oral leukotriene receptor antagonist), only fluticasone propionate and budesonide were studied. In the other two (combination intranasal corticosteroid plus nasal antihistamine versus each component), only fluticasone propionate was studied. Comparative effectiveness conclusions therefore apply to the specific drugs in each comparison; how well they generalize to other drugs in the same class is uncertain. The other two meta- analyses assessed oral selective antihistamine in comparison to intranasal corticosteroid (row 3). In approximately half of the trials identified for this comparison, treatment effects for nasal and eye symptoms were not reported. Therefore, the evidence was imprecise and insufficient to support a comparative effectiveness conclusion of superiority or equivalence for these outcomes. All other “Insufficient” cells indicate insufficient evidence to support only superiority conclusions. Summary of findings and strength of evidence for effectiveness in 13 treatment comparisons: Key Question 1–adults and adolescents a Asthma Comparison Representation Nasal Symptoms Eye Symptoms Quality of Life Symptoms 1. Entries indicate comparative efficacy conclusions supported by the evidence, or insufficient evidence to form a conclusion. For the comparison of oral selective antihistamine to intranasal corticosteroid (row 3), evidence was insufficient to form conclusions of superiority or equivalence for nasal and eye symptoms. For all other outcomes, “Insufficient” indicates insufficient evidence for conclusions of superiority; equivalence was not assessed. For comparisons involving combination therapy (rows 9 through 13), the proportion of the drug class studied as monotherapy is the same as the proportion of that drug class studied in combination therapy. For example, in row 9, two of five oral selective antihistamines (40 percent) were studied as monotherapy, and the same two antihistamines were studied in combination therapy. Moderate strength evidence for comparable effectiveness of oral selective antihistamine and oral leukotriene receptor antagonist for nasal and eye symptoms and for improved quality of life at 2-4 weeks. Moderate strength evidence for the use of oral leukotriene receptor antagonist over oral selective antihistamine for reduced asthma rescue medication use at 2-4 weeks. Low strength evidence for the use of combination oral selective antihistamine plus intranasal corticosteroid over oral selective antihistamine monotherapy for improved quality of life at 2-4 weeks. Oral selective antihistamine versus oral decongestant: eye symptoms at 2 weeks o Original conclusion: Insufficient evidence to support the use of one treatment 103, 107 over the other based on two good quality trials (N=890) with low risk of bias and consistent but imprecise treatment effects favoring oral selective antihistamine. Because approximately half of patients would still be in 103 the trial with imprecise results, the body of evidence would remain imprecise. Intranasal corticosteroid versus nasal antihistamine: nasal congestion at 2 weeks o Original conclusion: High strength of evidence for comparable effectiveness 115-119, 121 (equivalence) of the treatments based on eight trials (N=2443) with low risk of bias and consistent and precise results. Because this trial represented 2 percent of patients reporting this outcome, its impact on the overall precision of the body of evidence was minimal, and the body of evidence would remain imprecise. Intranasal corticosteroid versus nasal cromolyn: rhinorrhea at 2 weeks o Original conclusion: Insufficient evidence to support the use of one treatment 122 over the other based on one poor quality trial (n=43) with high risk of bias and an imprecise treatment effect favoring intranasal corticosteroid. If this were considered a precise result, the strength of evidence would remain insufficient to support the use of one treatment over the other due to the high risk of bias and unknown consistency of the body of evidence. Because the majority of patients would still be in 90, 130 the trials with imprecise results, the body of evidence would remain imprecise. If this were considered a precise result, the strength of evidence to support the use of combination oral selective antihistamine plus oral decongestant over oral selective antihistamine monotherapy would be moderate. Responder Analysis To demonstrate clinically meaningful treatment effects, the preferred analysis is a responder analysis, in which the outcome of interest is the proportion of patients who reached a predefined minimum threshold of improvement. In meta-analyses of three trials that compared combination intranasal corticosteroid plus nasal antihistamine to both intranasal corticosteroid and nasal antihistamine monotherapy (total N=3150), responder analyses were 115 included. Resolution was defined as reduction in all individual nasal symptom scores to less than 1.