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By L. Ningal. Lakeland College. 2018.

The lateral field is occupied by level of the medulla oblongata and the pons purchase amantadine 100mg, the pedunculopontine tegmental nucleus it is overlain by the cerebellum and in the (D20) generic amantadine 100 mg fast delivery. At the ventral margin of the tegmen- mesencephalon by the tectum (quadrigemi- tum lies the interpeduncular nucleus (D21) amantadine 100 mg with visa, nal plate) (A5) order amantadine 100mg free shipping. The ventral part of the brain which is rich in peptidergic neurons (pre- stem mainly contains the large tracts de- dominantly enkephalin). The habenulo in- scending from the telencephalon; they form terpeduncular tract (fasciculus retroflexus, the pyramids (A6) in the medulla oblongata, Meynert’s bundle) (p. The lateral lemniscus (D22) radiates ven- The ventricular system undergoes consider- trally into the nucleus of the inferior col- able narrowing in the midbrain, the aque- liculus (D14) (p. The fibers of the duct of the mesencephalon (cerebral aqueduct, peduncle of the inferior colliculus (D23) aqueduct of Sylvius) (A–D9). During aggregateatthelateralaspectandruntothe development, the lumen of the neural tube medial geniculate body (central auditory becomes increasingly narrowed as the teg- pathway, p. In the medial field lie the mentum of the midbrain increases in medial longitudinal fasciculus (D24) (p. The fiber plate of the basal plate lie ventrally: the nucleus of of the medial lemniscus (D26) (p. The fibers of the cerebral peduncle nucleus (eye muscles), the red nucleus (C11), (D27) are cut transversely and are inter- and the substantia nigra (C12) (consisting of spersed with a few pontine fibers running anouterreticularpartandaninnercompact across. The sensory derivatives of the alar plate lie dorsally: the tectum of the mesen- D28Periaqueductal gray substance, central cephalon (quadrigeminal plate) (C13) (syn- gray. D Cross Section Through the Inferior Colliculi of the Midbrain (D) The inferior colliculus with its nucleus (nu- cleus of inferior colliculus) (D14) (synaptic relay station of the central auditory path- way) is seen dorsally. The transitional re- gion between pons and cerebral peduncles Plane of section and the most caudal cell groups of the sub- stantia nigra (D15) lie ventrally. The magno- cellular nucleus of the trochlear nerve (D16) Kahle, Color Atlas of Human Anatomy, Vol. Structure of the Midbrain, Inferior Colliculi 133 55 44 44 99 44 88 66 11 77 22 33 A Structure of medulla oblongata, pons, and midbrain 1313 99 1010 2929 99 1111 1212 1010 B Development of the midbrain C Organization of the midbrain into basal and alar plates 1414 2323 2828 1919 99 2222 1818 2020 2424 2525 1717 1616 2626 1515 1414 2727 1919 99 2222 1818 1717 1616 2424 2121 2020 2525 2626 2121 D Cross section through the midbrain at the level of the inferior colliculi, cellular staining (Nissl) and fiber staining (myelin) Kahle, Color Atlas of Human Anatomy, Vol. The ven- The two superior colliculi (A1) are seen dor- tral aspect on both sides is formed by the sally. In lower vertebrates, they represent corticofugal fiber masses of the cerebral the most important visual center and con- peduncles (AB19). In the superficial gray layer (A2) termi- Region of the Midbrain (B) nate the fibers from the occipital fields of The pretectal region (B21) situated orally to the cortex (corticotectal tract) (A3). The the superior colliculi represents the tran- optic layer (A4), which in lower vertebrates sition from the midbrain to the dien- consists of fibers of the optical tract, is cephalon. Hence, the cross section already formed in humans by fibers from the lateral contains structures of the diencephalon: genicular body. The deeper layers of cells dorsally on each side lies the pulvinar (B22), and fibers are collectively known as stratum in the middle the epithalamic commissure lemnisci (A5). Here terminate the spinotec- (B23), and ventrally the mamillary bodies tal tract (p. The pretectal region extends dor- lateral lemnisci, and fiber bundles of the in- solaterally with the principalpretectalnucleus ferior colliculi. The latter is an important relay sta- The aqueduct is surrounded by the peri- tion for the pupillary reflex (p. It fibers of the optical tract and the fibers of contains a large number of peptidergic neu- the occipital cortical fields terminate here. The mesencephalic nucleus of the across the epithalamic commissure to the trigeminal nerve (A7) lies laterally to it, and Edinger–Westphal nucleus (accessory ventrallytoitliethenucleusoftheoculomotor oculomotor nucleus). Ventral to the aque- nerve (A8) and the Edinger-Westphal nucleus duct are the Darkshevich’s nucleus (B26) and (accessory oculomotor nucleus) (A9) the interstitial nucleus (of Cajal) (B27), the (p.

In fact buy 100mg amantadine free shipping, the follow up procedure is aimed at retrospectively assessing the (prevalent) health status at time zero trusted amantadine 100mg, as a substitute for establishing the reference standard 50 ASSESSING THE ACCURACY OF DIAGNOSTIC TESTS diagnosis of the target disorder immediately at time zero itself buy cheap amantadine 100mg online. Therefore generic 100 mg amantadine with visa, this design modification can be designated a “delayed-type cross-sectional study”, instead of a follow up study. As mentioned earlier, in such situations incorporation bias may be the result. If test data are indeed an essential part of the diagnostic criteria, one cannot avoid balancing a certain risk of incorporation bias against not being able to perform diagnostic research at all, or making a final diagnosis while ignoring an important element of the criteria. Often, one can find a practical compromise in considering that for clinical purposes it is sufficient to know to what extent the available diagnostic tests at time zero are able to predict the target disorder’s becoming clinically manifest during a reasonably chosen follow up period. This can be done while adding an extra blinding step, such as randomly rearranging the order of anonymised patient records. If there then appear to be important differences in the research conclusions, this should be transparently reported and discussed as to the clinical implications. When it is impossible to meet the principle that the reference standard should be similarly applied to all study subjects irrespective of their health or test result status, “next best” solutions can be considered. For example, to determine the accuracy of the exercise electrocardiogram (ECG) in primary care settings, it might be considered medically and ethically unjustified to submit those with a negative test result to coronary angiography. For these test negatives a well standardised clinical follow up protocol (delayed-type cross-sectional study) might be acceptable. This option is particularly important when the focus is on exercise ECG in patients who have a relatively low prior probability of coronary heart disease. For this spectrum of patients, results of a study limited to those who would be clinically selected for coronary angiography would be clearly not applicable. In order to have some validation of this procedure, for the 51 THE EVIDENCE BASE OF CLINICAL DIAGNOSIS subgroup who had an angiography one can compare the standard diagnoses based on the follow up with the angiography results. In summary, although a completely identical and “hard” reference standard for all included study subjects is the general methodological paradigm, this is not always achievable. In such situations, given the described limitations and the suggested alternative approaches, establishing a well documented and reproducible reference standard protocol – indicating the optimal procedure for each type of patient – may be not only the best one can get but also sufficient for clinical purposes. Prognostic criterion Diagnostic testing should ultimately be in favour of the patient’s health, rather than just an assessment of the probability of the presence of disease. In view of this, the reference standard procedure can sometimes incorporate prognosis or consequences for clinical management. This is especially relevant in situations where an exhaustive nosological classification is less important, and when management is based primarily on the clinical assessment (for example in deciding about physiotherapy in low back pain, or referral to a neurosurgeon in sciatica14). Sometimes making a final diagnosis is less important than a prognosis, in view of the clinical consequences (incidental fever) or the lack of a solid diagnostic consensus (the pyriformis syndrome). In establishing a “prognostic reference criterion”, a pitfall is that prognosis can be influenced by interfering treatments. In this context, methods for unbiased assessment of the impact of testing on patient prognosis are important (Chapter 4). It is to be expected that with the progress of DNA testing for disease, prognostic relevance will increasingly be the reference standard. Standard shift as a result of new insights At certain moments during the progress of pathophysiological knowledge on diagnosis, new diagnostic tests may be developed that are better than the currently prevailing reference standard. However, if this possibility is systematically ignored by reducing diagnostic accuracy research to just comparing new tests with traditional standards, possible new reference standards would never be recognised, as they would always seem less accurate than the traditional ones. Therefore, pathophysiological expertise should be involved in the evaluation of diagnostic accuracy. Examples of a shift in reference standard are the replacement of the clinical definition of tuberculosis by the identification of Mycobacterium tuberculosis, and of old imaging techniques by new ones (see also Chapter 1). The selection of patients is crucial for the study outcome and its external (clinical) validity. For example, as has already been emphasised, it is widely recognised that diagnostic accuracy is very much dependent on the spectrum of included patients and the results of relevant tests performed earlier, and may differ for primary care patients and patients referred to a hospital. For example, the study can address the diagnostic accuracy of clinical tests for sciatica in general practice, the accuracy of ECG recording in outpatients with palpitations without a compelling clinical reason for immediate referral, or the diagnostic accuracy of the MRI scan in diagnosing intracerebral pathology in an academic neurological centre.

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This environment must contain the correct con- else but water because the body has a remarkable capacity centrations of ions to maintain body fluid volume and to for adjusting the functions of its organs and tissues to pre- enable excitable cells to function order amantadine 100 mg with amex. This is readily apparent from the fact that an organic substances are continually lost from the body as a adrenalectomized animal discount 100mg amantadine free shipping, unlike its normal counterpart generic amantadine 100 mg on-line, result of perspiration 100mg amantadine with mastercard, respiration, and excretion. Under normal con- diminishes, ATP generation by the cells becomes inade- ditions, these critical constituents of the body’s extracellu- quate to support life, and the animal eventually dies. Even 607 608 PART IX ENDOCRINE PHYSIOLOGY when fed a normal diet, an adrenalectomized animal typi- Zona glomerulosa cally loses body sodium and water over time, and eventu- Zona fasciculata Cortex: 80–90% ally dies of circulatory collapse. Its death is caused by a lack Zona reticularis of certain steroid hormones that are produced and secreted by the cortex of the adrenal gland. The glucocorticoid hormones, cortisol and corticos- Medulla: 10–20% terone, play essential roles in adjusting the metabolism of carbohydrates, lipids, and proteins in liver, muscle, and adi- pose tissues during fasting, which assures an adequate sup- ply of glucose and fatty acids for energy metabolism de- spite the absence of food. The mineralocorticoid hormone aldosterone, another steroid hormone produced by the ad- renal cortex, stimulates the kidneys to conserve sodium Catecholamines and, hence, body fluid volume. The glucocorticoids also enable the body to cope with Androgens physical and emotional traumas or stresses. The physiological importance of this action of the glucocorticoids is empha- Cortisol sized by the fact that adrenalectomized animals lose their ability to cope with physical or emotional stresses. Even when Aldosterone given an appropriate diet to prevent blood glucose and body sodium depletion, an adrenalectomized animal may die when exposed to traumas that are not fatal to normal animals. These hormones are the catecholamines, ep- androgen dehydroepiandrosterone, which is related chem- inephrine and norepinephrine, which have widespread ically to the male sex hormone testosterone. The molecu- effects on the cardiovascular system and muscular system lar structures of these hormones are shown in Figure 34. Many small arteries branch from the aorta and renal arteries and enter the cortex. These vessels give rise to capillaries that course radially through the cortex and ter- FUNCTIONAL ANATOMY OF THE minate in venous sinuses in the zona reticularis and adrenal ADRENAL GLAND medulla; therefore, the hormones produced by the cells of the cortex have ready access to the circulation. The human adrenal glands are paired, pyramid-shaped or- The cells of the adrenal cortex contain abundant lipid gans located on the upper poles of each kidney. This stored lipid is functionally significant be- renal gland is actually a composite of two separate en- cause cholesterol esters present in the droplets are an im- docrine organs, one inside the other, each secreting portant source of the cholesterol used as a precursor for the separate hormones and each regulated by different mech- synthesis of steroid hormones. The outer portion or cortex of the adrenal gland completely surrounds the inner portion or medulla and makes up most of the gland. During embryonic develop- The Adrenal Medulla Is a Modified ment, the cortex forms from mesoderm; the medulla arises Sympathetic Ganglion from neural ectoderm. The adrenal medulla can be considered a modified sympa- thetic ganglion. The medulla consists of clumps and strands The Adrenal Cortex Consists of of chromaffin cells interspersed with venous sinuses. Chro- Three Distinct Zones maffin cells, like the modified postganglionic neurons that receive sympathetic preganglionic cholinergic innervation In the adult human, the adrenal cortex consists of three his- from the splanchnic nerves, produce catecholamine hor- tologically distinct zones or layers (Fig. Epi- zone, which lies immediately under the capsule of the nephrine and NE are stored in granules in chromaffin cells gland, is called the zona glomerulosa and consists of small and discharged into venous sinuses of the adrenal medulla clumps of cells that produce the mineralocorticoid aldos- when the adrenal branches of splanchnic nerves are stimu- terone. The inner layer is comprised of interlaced strands of cells called the zona reticularis. HORMONES OF THE ADRENAL CORTEX The zona fasciculata and zona reticularis both produce the physiologically important glucocorticoids, cortisol and Only small amounts of the glucocorticoids, aldosterone, corticosterone. These layers of the cortex also produce the and adrenal androgens are found in adrenal cortical cells at CHAPTER 34 The Adrenal Gland 609 Zona glomerulosa Comparison of Shared Activities of TABLE 34. However, given the amounts of these hor- mones secreted under normal circumstances and their relative activities, glucocorticoids are not physiologically important mineralocorticoids, nor does aldosterone func- tion physiologically as a glucocorticoid. As discussed in detail later, the amounts of glucocorti- coids and aldosterone secreted by an individual can vary Cortisol Corticosterone greatly from those given in Table 34. For ex- ample, in an individual subjected to severe physical or emo- tional trauma, the rate of cortisol secretion may be 10 times greater than the resting rate shown in Table 34. Certain diseases of the adrenal cortex that involve steroid hormone biosynthesis can significantly increase or decrease the Dehydroepiandrosterone amount of hormones produced. Lesser a given time because those cells produce and secrete these amounts of other androgens are also produced. In the human male, however, androgens pro- a healthy adult under resting (unstimulated) conditions.

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She is 2 cationic dye purchase 100mg amantadine mastercard, however amantadine 100 mg, suggests that there was a loss of given an intravenous infusion of hypertonic saline (1 discount 100mg amantadine fast delivery. Several days after serum albumin bears a net negative charge at physiological she had improved generic amantadine 100mg without a prescription, bronchoscopy is performed. Proteins that have leaked across the glomerular filtration sion of 1 L of 1. Assume barrier are not only excreted in the urine but are reabsorbed that her total body water is 25 L (50% of her body weight). The endocytosed proteins are digested Why is the total body water used as the volume of distribu- in lysosomes to amino acids, which are returned to the cir- tion of Na , even though the administered Na is limited to culation. The liver, which synthe- Why should the hypertonic saline be administered slowly? The endogenous creatinine (CR) clearance (an estimate of Answers to Case Study Questions for Chapter 24 GFR) equals (UCR V)/PCR (60 1. Note that the permeability of with an impaired ability to dilute the urine (note the inap- the glomerular filtration barrier to macromolecules (plasma propriately high urine osmolality), led to severe hypona- proteins) was abnormally high, but permeability to fluid tremia and water intoxication. Addition of 1 L of 308 mEq Na /L to 25 L produces an in- may be significant and may lead to a reduced fluid perme- ability and GFR. The edema is a result of altered capillary Starling forces and used in this calculation because when hypertonic NaCl is added to the ECF, it causes the movement of water out of renal retention of salt and water. The decline in plasma the cell compartment, diluting the extracellular Na. Because the brain is enclosed in a nondistensible cranium, ing fluid movement out of the capillaries into the interstitial compartment. The edema is particularly noticeable in the when water moves into brain cells and causes them to swell, intracranial pressure can rise to very high values. The abdomi- nal distension (in the absence of organ enlargement) sug- This can damage nervous tissue directly or indirectly by im- gests ascites (an abnormal accumulation of fluid in the ab- pairing cerebral blood flow. The neurological symptoms seen in this patient (headache, semiconsciousness, grand dominal cavity). The kidneys avidly conserve Na (note the low urine [Na ]) despite an expanded ECF volume. The in- though the exact reasons for renal Na retention are contro- creased blood pressure and cool and pale skin may be a consequence of sympathetic nervous system discharge re- versial, a decrease in the effective arterial blood volume sulting from increased intracranial pressure. This leads to activation of the renin-angiotensin-aldosterone system restoration of a normal plasma [Na ] can produce serious damage to the brain (central pontine myelinolysis). The physicians wanted to exclude the presence of a bron- chogenic tumor, which is the most common cause of ments of the nephron reabsorb more Na than usual be- cause of an intrinsic change in the kidneys. Rapid development of hyponatremic seizures in a 1998;338:1202–1211 psychotic patient. Goldman MB, Luchins DJ, Robertson GL Mechanisms of al- CASE STUDY FOR CHAPTER 24 tered water metabolism in psychotic patients with polydipsia Water Intoxication and hyponatremia. A 60-year-old woman with a long history of mental ill- ness was institutionalized after a violent argument with CASE STUDY FOR CHAPTER 25 her son. She experiences visual and auditory hallucina- tions and, on one occasion, ran naked through the ward Lactic Acidosis and Hemorrhagic Shock screaming. She refuses to eat anything since admission, During a violent argument over money, a 30-year-old but maintains a good fluid intake. The assailant escaped, day, she complains of a slight headache and nausea and but friends were able to rush the victim by car to the has three episodes of vomiting. The patient is unconscious, with a blood found on the floor in a semiconscious state, confused pressure (mm Hg) of 55/35 and heart rate of 165 and disoriented. The sub- Her pulse rate is 70/min and blood pressure is 150/100 ject is pale, with cool, clammy skin.

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Another reform in MICRA is the sliding contingency fee scale for plaintiff attorneys order 100mg amantadine, which assures that the greater a plaintiff’s injuries and damages buy amantadine 100mg visa, the larger the percentage of the total award that goes to the plaintiff discount amantadine 100mg with mastercard, with a corresponding reduced share to the plaintiff’s law- yer cheap amantadine 100 mg on-line. As a report of an American Bar Association commission explained long ago about this kind of provision: “[In] order to relate the attorney’s fee more to the amount of legal work and expense involved in handling a case and less to the fortuity of the plaintiff’s economic status and degree of injury, a decreasing maximum schedule of attorney’s fees, reasonably generous in the lower recovery ranges and thus unlikely to deny potential plaintiffs access to legal representation, should be set on a state-by-state basis. Chapter 2 / Litigation 19 is the time during which a suit must be filed after the injury occurs or, absent an express waiver by the defendant, it is barred. Before MICRA and analogous statutes in other states, the limitations period was prac- tically open-ended, making stale claims common and resulting in a “long-tail” for liability that prevented accurate claims forecasting and predictable premium setting. Underlying this rule is the public policy rationale that it “encourage[s] citizens to purchase and maintain insurance for personal injuries and for other eventualities.. If we were to permit [defendants] to mitigate damages with payments from plaintiff’s insurance, plaintiff would be in a position inferior to that of having bought no insurance, because his payment of premiums would have earned no benefit. Defendant should not be able to avoid payment of full compensation for the injury inflicted merely because the victim has had the foresight to provide himself with insurance. When a defendant chooses to introduce such evidence, the plaintiff may introduce evidence of the amounts he or she has paid, for example, 9 “More than a decade may pass before a suit is brought on an incident involving a minor. This further complicates the methods of establishing rates, and is inequitable since the vast majority of medial malpractice committed on infants is detectable within the normal statute of limitations. Although this modifi- cation of the collateral source rule does not specify how the jury should use such evidence, the underlying legislative presumption and the prac- tical effect is that in most cases, the jury sets plaintiff damages at a lower level because of its awareness of plaintiff net collateral source benefits. Other states have altered their collateral source for medical negligence cases to explicitly mandate a deduction of the amount of the collateral sources from the plaintiff’s award. Danzon, The Frequency and Severity of Medical Mal- practice Claims: New Evidence, Law & Contemp. Chapter 2 / Litigation 21 future damages through a “lump sum” judgment, payable at the con- clusion of the trial. Accordingly, they have advocated legislative adoption of a “periodic payment” procedure as a reform measure that would, in these com- mentators’ view, benefit both plaintiffs and defendants. Code § 6-11-3(3) (future damages of more than $150,000 to be paid periodically); Alaska Stat. In addition, they determined that the public interest is served by limiting a defendant’s obligation to those future damages that a plaintiff actually incurs, eliminating windfalls obtained by a plaintiff’s heirs when they inherit a portion of a lump sum judgment that was intended to compensate the injured person for losses he never sustained. As the California Su- preme Court stated when, against constitutional attack, it upheld that state’s periodic payment provision:20 One of the factors which contributed to the high cost of malpractice insurance was the need for insurance companies to retain large reserves to pay out sizeable lump sum awards. The adoption of a periodic payment procedure permits insurers to retain fewer liquid reserves and to increase investments, thereby reducing the costs to insurers and, in turn, to insureds. In addition, the portion of [the periodic payment statute] which provides for the termination of a significant portion of the remaining future damage payments in the event of the plaintiff’s death is obviously related to the goal of reduc- ing insurance costs. HOW THE VARIOUS RULES “FIT” WITHIN THE LEGAL HIERARCHY Notice that most of the rules discussed so far are state statutes or judge-made by courts where the liability disputes arise. Court- or judge- made rules (they are synonymous) are known as common law rules. They are derived from particular factual disputes and, after articulation of them by the court as a guiding principle for future cases, have the force of stare decisis or precedent. Precedent is to be followed by future courts unless it is has outlived its usefulness or no longer makes sense. That decision is made by an intermediate appellate court or the highest court in that state or by the legislature. When the defendant in a profes- sional liability case is the federal government or its employees, or arises under particularly defined circumstances that implicate federal law, 20American Bank & Trust Co. Chapter 2 / Litigation 23 then federal courts decide the dispute according to federal statutes and federal common law. All statutes—federal and state—must be interpreted or applied by courts to particular facts.

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