By C. Einar. Roanoke College. 2018.
In fact this approach has proved valuable in treating the peripheral neuro- muscular disorder of myasthenia gravis which presents as a muscle weakness caused by insufficient cholinergic activity at skeletal neuromuscular junctions cheap toprol xl 50mg with visa. The function of ACh can be increased and the symptoms alleviated toprol xl 50 mg visa, without central side-effects order toprol xl 50mg with amex, by reducing the destruction of ACh by giving the anticholinesterase drug neostigmine toprol xl 100 mg on-line, which does not cross the blood±brain barrier. Of course, nothing is perfect and anti- muscarinic drugs may be needed to overcome the accompanying increased peripheral parasympathomimetic effects of ACh. Despite all these problems there has been considerable progress in the treatment of disease states through NTmanipulation. Before the advent of levodopa therapy in Parkinsonism the treatment of neurological and psychiatric disorders had little 298 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION scientific basis but the initial and striking success with levodopa in Parkinsonism perhaps raised false expectations. In respect of drug therapy, Parkinsonism presented with a number of advantageous features that are unlikely to be repeated in other conditions. It involves a relatively specific degeneration of one particular NT(DA) pathway, DA has a precursor (levodopa) that readily crosses the blood±brain barrier and its peripheral metabolism to DA can be stopped by decarboxylase inhibitors that themselves do not cross the blood±brain barrier. Although DA is used elsewhere in the brain, nowhere is it concentrated to the same extent as in the striatum, where the degeneration occurs, and it has few peripheral effects. Fortunately DA also appears to be synthesised from levodopa even in the absence of DA neurons and it does not appear to have to be released synaptically in a physiological way in order to control striatal activity and reduce the symptoms of rigidity and akinesia. Even so, long-term therapy with levodopa has not been without its problems and disappointments and highlights the difficulties of replacement therapy. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 15 iseases of the Basal anglia R. The main features are: (1) Slowness and loss of movements known as bradykinesia or akinesia (2) Muscle stiffness and rigidity (3) Tremor of the limbs mainly at rest (but not in sleep) These result in a shuffling gait, an inability to initiate even simple movements like turning, a stooped posture and micrographia (small handwriting). It is a slowly pro- gressing degenerative disease affecting, at most, some 1% of the population above 55 years. PATHOLOGY It was known for most of the twentieth century that the brains of PD patients lacked the dark pigmentation characteristic of neurons in the substantia nigra. Such colouring is caused by melanin granules in their cell bodies and although its role is uncertain it is only found in humans and primates and they alone can develop the symptoms of PD. The substantia nigra (SN) is also characterised by round eosinophilic intraneuronal inclusions known as Lewy bodies, which are increased in PD. Neither neuromelonin nor Lewy bodies are confined solely to the SN but it is the neurons of the SN which degenerate in PD. This was first detected in post-mortem studies in 1960 by Hornykiewicz and numerous studies since have shown that not only is PD associated with and presumably caused by a loss of striatal DA, but at death that loss actually reaches more than 80%. Within the striatum DA loss is greater in the putamen which has predominantly motor links with the cortex than in the caudate mucleus with its connections to cortical association areas. Recently PET studies with 6-fluorodopa, which is taken up by DA nerve terminals in the striatum and is therefore presumably a measure of both the number of functional DA neurons in the nigrostriatal tract to it as well as its DA content, show that this is more like 50% of normal at the start of symptoms, not the 80% observed at PM (see Neurotransmitters, Drugs and Brain Function. Webster &2001 John Wiley & Sons Ltd 300 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Fig. In fact sequential PET measurements in selected patients as the disease progresses followed by extrapolation backwards suggests that DA loss may start some 5 years before symptoms first appear. Nevertheless it is surprising that in all PM studies of normal and PD brains the concentration of striatal DA is either normal or only 10- 20% of it. There is some loss (40±60%) of DA in the nucleus accumbens of the mesolimbic system in the ventral tegmentum (A10) and cortex at post-mortem but nowhere is it as marked as in the striatum. Some loss of NA, 5-HT, CCK and the enkephalins and of the markers GAD and ChAT (for GABA and ACh) have been reported in the striatum, SN and other areas but these rarely exceed 50% and could be secondary to DA loss. The ability of the striatum to apparently function normally until it has lost much of its DA can be ascribed in part to denervation supersensitivity, the degeneration of the DA input resulting in an increase in postsynaptic DA receptors and partly to the remaining neurons producing more DA. This is supported by measurements in humans which show that the HVA:DA ratio, a measure of DA turnover, is much greater in Parkinsonism patients and by microdialysis in rats with 6-OHDA lesions of the nigrostriatal tract, when the reduction in perfusate (released) DA is very much less than that of neuronal (stored) DA. Thus initially the nigrostriatal tract is able to compensate for the loss of neurons but eventually this fails and the symptoms of PD emerge. ANIMAL MODELS Since PD is caused by a relatively specific degeneration of the DA nigrostriatal tract and as there are specific toxins, for DA neurons, i. Tremor and akinesia can be seen, however, in primates after such toxins and these are being more widely used in experimental studies of PD and drug evaluation.
After infantryman became unsteady and order 100mg toprol xl with amex, after a few more steps buy toprol xl 25mg on-line, the end of the infusion he is sent back to his unit with in- sat on the ground generic toprol xl 100 mg otc. He told his comrades that he was dizzy structions to consume salt with dinner purchase toprol xl 100 mg overnight delivery, drink at least three and had a headache. When they urged him to drink from quarts of fluid before going to bed, and to return for fol- his canteen, he took a few swallows and said that he was low-up in the morning. What is the likely basis of the patient’s nausea, which also his rectal temperature is 38. If we assume that the patient’s total body water was 36 L CASE STUDY FOR CHAPTER 30 when he came for treatment, it can be shown that giving the patient 3 L of water without salt (by mouth and/or as an in- A Patient With Dyspnea During Exercise travenous infusion of glucose in water) would reduce serum A 56-year-old man complained of shortness of breath and [Na ] to 144 mmol/L. Such treatment would improve the pa- chest pain when climbing stairs or mowing the lawn. How might the medical offi- subjected to a stress test, with noninvasive monitoring of cer argue the case for giving 2 L of normal saline? What other (and relatively unusual) condition could produce and cardiac electrical activity. Did the medical officer rule this beats/min; blood pressure, 118/75 mm Hg; arterial blood possibility out by appropriate means? The patient’s nausea is probably a result of constriction of terminated because of the subject’s severe dyspnea. His the splanchnic vascular beds, which is part of the homeo- heart rate is 119 beats/min (his age and sex-adjusted pre- static cardiovascular response that helps maintain cardiac dicted maximal heart rate is 168 beats/min), blood pressure output and blood pressure when central blood volume is re- is 146/76 mm Hg, arterial blood oxygen saturation is 88%, duced. Central blood volume, in turn, was reduced by the and the ECG is normal (Fig. What are three lines of evidence for ventilatory limitation to constriction of the renal vascular beds, which, in turn, con- this subject’s exercise? Why did arterial blood oxygen saturation fall during exer- tion of the renin-angiotensin system) to scanty urine pro- cise? Why would endurance exercise training likely increase this large amounts of sweat, and losing correspondingly large individual’s exercise capacity? Ventilatory limitation is evidenced by severe dyspnea as a next morning without correcting the salt deficit, he is likely primary symptom in exercise, falling arterial blood oxy- to have further difficulties in the heat. Even if the medical genation, and exercise termination at relatively low heart officer has guessed incorrectly about the patient’s salt bal- rate. Arterial blood oxygen saturation fell during exercise be- fluid intake should be able to excrete any excess salt result- cause increased cardiac output (increased pulmonary blood ing from the treatment. Hyponatremia can produce symptoms similar to the pa- tent (a result of increased skeletal muscle oxygen extrac- tient’s symptoms. However, the medical officer was able to tion) increase demands for oxygenation in lungs with inade- exclude hyponatremia (although not necessarily some de- quate diffusing capacity. Exhaustion occurred before a maximal heart rate was Giving a hyponatremic patient large volumes of fluid with- reached because lung disease creates severe dyspnea even out an equivalent of salt (which would have been a reason- in mild exercise. The pulse pressure rose during exercise because sympa- thetic stimulation and enhanced venous return increase the would worsen the hyponatremia, perhaps to a dangerous stroke volume at constant arterial compliance. Endurance exercise training would have little effect on any Reference aspect of lung function. Clinical complications of body fluid and elec- adaptations within exercising muscle that would increase trolyte balance. Body Fluid Bal- muscle oxidative capacity and reduce lactic acid production. Boca Raton, FL: CRC Press, By reducing the ventilatory demands of exercise, these 1996;297–317. PART IX Endocrine Physiology CHAPTER Endocrine Control Mechanisms Daniel E. Hormones are chemical substances, involved in cell-to-cell transported in the bloodstream bound to carrier proteins, communication, that promote the maintenance of home- whereas most peptide and protein hormones are soluble in ostasis. Steroid hormones and thyroid hormones are generally docrine abnormalities. The word “hormone” is derived gan systems by a group of specialized chemical substances from the Greek hormaein, which means to “excite” or to “stir called hormones.
If there were others involved in the incident of treatment about which plaintiff com- plains buy cheap toprol xl 25 mg line, make some notes as to who they were buy toprol xl 25 mg low price, what role they played in that treatment buy toprol xl 25 mg lowest price, and how you know that they were involved or witnessed the treatment cheap toprol xl 25mg otc. What legal theories, other than negligence, is the plaintiff relying on? What are the necessary elements to those theories and how does your lawyer think the plaintiff will try to satisfy them? Are the theories asserted in the complaint’s various causes of action supported in law? Now, there are two things any good malpractice defense attorney will do to best represent a client: put together a discovery plan and a 32 Hiestand litigation strategy. The two go hand-in-hand, and although not all attorneys put them in writing, you will want a commitment from your attorney to do so for you. These are privileged documents, so your opponent will not be able to force you to disclose them. To be sure, both the initial discovery plan and litigation strategy will change as new information is learned and as there are rulings on motions filed by the parties that affect the course of the litigation. That is understand- able, but it is important for you to have each revised plan because it will keep you informed as to how your defense is progressing, what needs to be done, by when, and whether the case is likely to be resolved without the necessity of trial. Your attorney will also likely work a little harder and maybe smarter for a client who shows interest in his or her own defense. As already mentioned, your objective is to get rid of the case against you at the earliest opportunity, certainly before trial. Ask your attor- ney to explain his litigation strategy for accomplishing that goal. Is the plaintiff asserting any claims that are outside the MICRA defenses available to you? Can those claims be disposed of by legal motions or are you stuck with defending hybrid claims? What evidence must be assembled to file a motion for summary judgment or summary adjudication? Does the discovery plan track with the litigation strategy so as to avoid time barriers that might otherwise preclude those motions from being filed? Once you have a sense of the theories the plaintiff is relying on in suing you, it will be important to find out what evidence the plaintiff has, or must get, to tie you into each theory. Your attorney will develop a discovery plan that seeks to find out what you don’t know and con- firm what you do know. That discovery plan should set forth the facts essential to prove the elements of any theory of liability asserted and of any defense you will assert. Your attorney should seek a stipulation with opposing counsel as to material facts that you believe will not be disputed and put that stipulation in writing. The discovery plan should indicate the discovery device(s) that will be used to prove or disprove the existence of each element of all claims and defenses and the source of proof for each fact pertinent to those elements. The extent of claimed damages is something that you will want to nail the plaintiff down on. Do the local court rules limit the number of experts and, if so, does this hurt your defense? What experts has Chapter 2 / Litigation 33 plaintiff’s counsel used in the past for medical malpractice cases? In doing this, your sense of how the rules and players interact and can affect the outcome of the litigation game will make you a more valuable contributor in preparing to win. Chapter 3 / Risk Reduction 35 3 Risk Reduction From a Plaintiff Attorney’s Perspective David Wm. Horan, MD, JD SUMMARY This chapter looks at malpractice litigation from the unique view- point of the plaintiff attorney. What aspects of the doctor– patient relationship most affect the likelihood of litigation?