
By H. Goose. Willamette University.
Bicarbonate and Hemoglobin in the Red Blood Cell [A ] pH pKa log [HA] The bicarbonate buffer system and hemoglobin in red blood cells cooperate in [HCO ] buffering the blood and transporting CO2 to the lungs discount 90mg dapoxetine amex. Although no car- [HCO ] bonic anhydrase can be found in blood plasma or interstitial fluid effective 90 mg dapoxetine, the red blood 3 pH 6. As the carbonic acid dissociates (circle 3), the H released is also buffered by combination with hemoglobin (Hb, where [CO2(d)] is the concentration of dis- solved CO the [HCO ] is expressed as circle 4). The side chain of the amino acid histidine in hemoglobin has a pKa of 6. The bicarbonate anion is transported out of the stant of 0. As the red blood cell approaches the lungs, the direction of the equilibrium reverses. CO2 is released from the red blood cell, causing more carbonic acid to dissociate into The partial pressure of CO2 (PaCO2) in Di Abietes’ arterial blood was 28 mm Hg (reference range 37 43), and her serum bicarbonate level was 8 mEq/L (ref- erence range 24 28). Elevated levels of ketone bodies had produced a ketoacidosis, and Di Abietes was exhaling increased amounts of CO2 by breathing deeply and frequently (Kussmaul’s breathing) to compensate. Ketone bodies are weak acids that partially dissociate, increasing H levels in the blood and the interstitial fluid surrounding the “metabolic” respiratory center in the hypothal- amus that controls the rate of breathing. As a result of the decrease in pH, her respira- tory rate increased, causing a fall in the partial pressure of arterial CO2 (PaCO2). As bicar- bonate and increased protons combined to form carbonic acid and produce more CO2, her bicarbonate concentration decreased (HCO H S H CO S CO H O). As 3 2 3 2 2 shown by Di’s low arterial blood pH of 7. CHAPTER 4 / WATER, ACIDS, BASES, AND BUFFERS 49 TCA carbonic – cycle 1 anhydrase H2PO4 Fuels CO2 CO2 CO2 + H2O H2CO3 2 6 Acetoacetate –2 8 HPO4 Fatty Acetoacetate 3 H+ H+ + acids H Pr HCO – 4 HPO –2 3 Hb 7 4 5 HbH HCO – HPr 6 3 H PO– H2CO3 2 4 Cl– Hepatic cell Blood Red blood cell Fig. CO produced from cellular metabolism is converted to bicarbonate and H in the red blood cells. Within 2 the red blood cell, the H is buffered by hemoglobin (Hb) and phosphate (HPO 2). The bicarbonate is transported into the blood to buffer H gen- 4 erated by the production of other metabolic acids, such as the ketone body acetoacetic acid.

The man with whom she has shared “dirty” needles to inject drugs accom- panies Ivy to the clinic and requests that he be tested for the presence of HIV discount dapoxetine 60 mg fast delivery. RECOMBINANT DNA TECHNIQUES Techniques for joining DNA sequences into new combinations (recombinant DNA) were originally developed as research tools to explore and manipulate genes but are now also being used to identify defective genes associated with disease and to cor- rect genetic defects generic dapoxetine 90mg on line. Even a cursory survey of the current literature demonstrates that these techniques will soon replace many of the current clinical testing proce- dures. At least a basic appreciation of recombinant DNA techniques is required to understand the ways in which genetic variations among individuals are determined CHAPTER 17 / USE OF RECOMBINANT DNA TECHNIQUES IN MEDICINE 299 and how these differences can be used to diagnose disease. RESTRICTION FRAGMENTS EcoRI Enzymes called restriction endonucleases enable molecular biologists to cleave seg- ments of DNA from the genome of various types of cells or to fragment DNA obtained from other sources. A key feature of restriction enzymes is their specificity. Most of the DNA sequences recognized by restriction enzymes are "Sticky" ends palindromes, that is, both strands of DNA have the same base sequence when read in a 5 to 3 direction. The cuts made by these enzymes are usually “sticky” (that is, Fig. Note that the DNA sequence shown is a palindrome; the products are single-stranded at the ends, with one strand overhanging the other). Hundreds of restriction enzymes with different specificities of this sequence by EcoRI produces single- have been isolated (Table 17. Not shown Restriction fragments of DNA can be used to identify variations in base sequence is an example of an enzyme that generates in a gene. However, they also can be used to synthesize a recombinant DNA (also blunt ends (see Table 17. The sickle cell mutation causes the -globin gene to restriction enzyme recognition lose this MstII restriction site. Therefore, because Will Sichel is homozygous for the sickle sequence? Sequences Cleaved by Selected Restriction Enzymes* (B) (5’) T A C G A T (3’) A T G C T A Restriction Enzyme Source Cleavage Site (C) (5’) C T G A G (3’) AluI Arthrobacter luteus 5 - A G C T - 3 3 - T C G A - 5 G A C T C (D) (5’) A T C C T A (3’) BamHI Bacillus amyloliquefaciens H 5 - G G A T C C - 3 3 - C C T A G G - 5 T A G G A T EcoRI Escherichia coli RY13 5 - G A A T T C - 3 3 - C T T A A G - 5 HaeIII Haemophilus aegyptius 5 - G G C C - 3 3 - C C G G - 5 Restriction endonucleases were 5 - A A G C T T - 3 discovered in bacteria in the late HindIII Haemophilus influenzae Rd 3 - T T C G A A - 5 1960s and 1970s. These enzymes 5 - C C G G - 3 were named for the fact that bacteria use MspI Moraxella species 3 - G G C C - 5 them to “restrict” the growth of viruses (bac- MstII Microcoleus 5 - C C T N A G G - 3 teriophage) that infect the bacterial cells.

The first report with clear generic dapoxetine 30 mg otc, consistent indications buy discount dapoxetine 90mg line, a consistent procedure, and that followed with rigid outcomes criteria was published in 1985. A fair outcome was a hip whose MP was between 25% and 40% (Case 10. A poor outcome was any individual whose MP was 40% or greater (Case 10. These criteria were used to evaluate 74 children who had 147 adduc- tor lengthenings performed at an average age of 4. Hip abduction was limited to 25° bilaterally; how- he developed slight pelvic obliquity that caused his right ever, the radiograph showed normal hips with less than hip to reduce and the left hip remain stable. One year later, the hip the hip adduction had again decreased to 25° on the left abduction was 20° bilaterally and the hip radiograph and 35° on the right (Figure C10. This is an example showed definite left hip subluxation with 40% migration of the intermediate outcome in which the child is left with (Figure C10. He had bilateral adductor longus teno- a definite abnormal hip including mild subluxation and tomy, gracilis tenotomy, and iliopsoas and proximal ham- acetabular dysplasia; however, in a nonambulatory indi- string lengthening. A radiograph 18 months later revealed vidual, this may remain stable throughout a lifetime. There improved hip position on the left with a 29% migration is little research evidence to guide treatment decision mak- (Figure C10. This type of hip does need age, the hip migration was slightly increased at 33% and monitoring, and if the hip develops progressive subluxa- 30%, and he had developed definite acetabular dysplasia tion or becomes painful, it should be treated. Twenty-nine hips that had adductor lengthenings had a preoperatively nor- mal MP, meaning less than 24%, and at final follow-up, 76% of these hips had a good rating, 10% were fair, and 14% were poor outcomes. Seventy- seven percent of the hips were initially mildly subluxated, meaning they had an MP between 25% and 40%, for a mean MP of 31%. At final follow-up, 56% of these hips had good outcomes, 36% had fair outcomes, and 8% had poor outcomes. There were 32 moderately subluxated hips with an MP between 40% and 60%, for a mean of 46%.

This thinking allows correcting pelvic malalignments Figure 9 dapoxetine 60 mg sale. This 15-year-old boy with quad- riplegic involvement had severe kyphosis during spinal instrumentation dapoxetine 30 mg with visa. Because he had a fixed Pelvic Obliquity cervical lordosis that was not recognized preoperatively, this neck extension was now The definition and measurement of pelvic obliquity depends on whether chil- fixed and he could no longer look forward. Often, pelvic obliquity has been defined based This boy required a surgical release of the on the horizontal plane of the space in which the children are placed. This cervical lordosis followed by orthotic control definition works well for flexible pelvic obliquity, especially in standing (B). This case illustrates the importance of children in whom the radiograph is made with them standing upright, or examining the mobility of the cervical spine before correcting kyphosis. However, the definition does not work well for children 510 Cerebral Palsy Management Case 9. A radio- walked a long distance or at the end of the day. A physical graph demonstrated a chronic spondylolisthesis with a examination showed no significant contractures except grade 1 to 2 slip (Figure C9. His gait pattern showed the high variability of the athetoid movement disorder. After treatment with a lumbar flexion lumbosacral or- thosis for 5 months, the pain immediately returned. He then had an in situ fusion of L4 to the sacrum (Figure C9. The pelvis-to-room horizontal plane may be much more reflective of how the technician seated a child for the radiograph than any real meas- ure of pelvic obliquity as defined by the pelvis’s position relative to the spine and trunk.

Also dapoxetine 60 mg discount, as these children are mobilized cheap dapoxetine 60 mg on line, they may complain of a period of neuritic pain in the lower extremity, and several children have complained of areas of numbness. This neuritic pain is probably caused by the extensive nerve stretch that occurs when lumbar lordosis is corrected as the posterior neuronal structures undergo some lengthening. All patients have overcome this neuritic pain syndrome and the numbness has resolved; however, it occasionally requires up to 1 year. Spine 465 Complications of Spine Surgery Complications of posterior spinal fusion in children with CP are common. Most of these complications are relatively self-limiting and resolve with ap- propriate management. From an extensive review of 107 spinal fusions in children with CP, the best predictor for risk of complication is severity of the neurologic disability. The level of the neurologic involvement is defined based on a score that combines the ability to speak, walk, eat, presence of seizures, and intelligence. Based on assessing these five areas, there was such a strong correlation to neurologic disability that the presence of additional risk fac- tors such as tracheostomy, tracheal diversion, gastrostomy tubes, seizure drugs, or malnutrition were not correlated with additional risk. At this time, we believe the overriding risk factor for complications following spine surgery is the severity of the children’s neurologic disability. It is difficult to know how to use this information to counsel families, but physicians have to be honest with this risk. For families who want to aggressively pursue medical care, this risk is usually not a significant concern because the alternative of the child becoming bedfast is difficult for them to manage as well. Children or adolescents who have a spinal fusion for severe scoliosis usually also have many other multiple system problems. These problems, com- bined with the large magnitude of the surgical procedure, mean that these children are at risk for almost any medical problem that can be imagined. This discussion of complications will focus only on serious complications that have been encountered or that are encountered frequently. In reality, this covers almost every complication encountered in the 340 children with CP in whom we have done a spine fusion. Several notable areas are missing from this complication list, mainly thromboembolic disease.