By X. Mortis. Dominican College.
No wonder order 160mg super p-force with mastercard, then discount super p-force 160mg fast delivery, that clinical researchers examine relationships between a wide range of more easily measured phenomena and final diagnoses. These phenomena include elements of the patient’s history, physical examination, images from all sorts of penetrating waves, and the levels of myriad constituents of body fluids and tissues. Alas, even the most promising phenomena, when nominated as diagnostic tests, almost never exhibit a one-to-one relationship with their respective target disorders, and several different diagnostic tests may compete for primacy in diagnosing the same target disorder. As a result, considerable effort has been expended at the interface between clinical medicine and scientific methods in an effort to maximise the validity and usefulness of diagnostic tests. This book describes the result of those efforts, and this chapter focuses on the specific sorts of questions posed in diagnostic research and the study architectures used to answer them. At the time that this book was being written, considerable interest was being directed to questions about the usefulness of the plasma concentration of B-type natriuretic peptide in diagnosing left ventricular dysfunction. Because real examples are far better than hypothetical ones in illustrating not just the overall strategies but also the down-to-earth tactics of clinical research, we will employ this one in the following paragraphs. To save space and tongue twisting we will refer to the diagnostic test, B-type natriuretic peptide, as BNP and the target disorder it is intended to diagnose, left ventricular dysfunction, as LVD. The starting point in evaluating this or any other promising diagnostic test is to decide how we will define its normal range. This chapter deals with the strategies (a lot) and tactics (a little) of research that attempts to distinguish patients who are “normal” from those who have a specific target disorder. Before we begin, however, we need to acknowledge that several different definitions of normal are used in clinical medicine, and we confuse them at our (and patients’) peril. Because the mean of a gaussian distribution plus or minus 2 standard deviations encloses 95% of its contents, it became a tempting way to define the normal several years ago, and came into general use. It is unfortunate that it did, for three logical consequences of its use have led to enormous confusion and the creation of a new field of medicine: the diagnosis of non-disease. First, diagnostic test results simply do not fit the gaussian distribution (actually, we should be grateful that they do not; the gaussian distribution extends to infinity in both directions, necessitating occasional patients with impossibly high BNP results and others on the minus side of zero! The third harmful consequence of the use of the gaussian definition of normal is shared by its more recent replacement, the percentile. Recognising the failure of diagnostic test results to fit a theoretical distribution such as the gaussian, some laboratorians have suggested that we ignore the shape of the distribution and simply refer (for example) to the lower (or upper) 95% of BNP or other test results as normal. Although this percentile definition does avoid the problems of infinite and negative test values, it still suggests 21 THE EVIDENCE BASE OF CLINICAL DIAGNOSIS that the underlying prevalence of all diseases is similar – about 5% – which is silly, and still contributes to the “upper-limit syndrome” of non-disease because its use means that the only “normal” patients are the ones who are not yet sufficiently worked up. This inevitable consequence arises as follows: if the normal range for a given diagnostic test is defined as including the lower 95% of its results, then the probability that a given patient will be called “normal” when subjected to this test is 95%, or 0. If this same patient undergoes two independent diagnostic tests (independent in the sense that they are probing totally different organs or functions), the likelihood of this patient being called normal is now (0. The risk factor definition is based on studies of precursors or statistical predictors of subsequent clinical events; by this definition, the normal range for BNP or serum cholesterol or blood pressure consists of those levels that carry no additional risk of morbidity or mortality. Unfortunately, however, many of these risk factors exhibit steady increases in risk throughout their range of values; indeed, some hold that the “normal” total serum cholesterol (defined by cardiovascular risk) might lie well below 3. Another shortcoming of this risk factor definition becomes apparent when we examine the health consequences of acting upon a test result that lies beyond the normal range: will altering BNP or any other risk factor really change risk? For example, although obesity is a risk factor for hypertension, controversy continues over whether weight reduction improves mild hypertension. A related approach defines the normal as that which is culturally desirable, providing an opportunity for what HL Mencken called “the corruption of *This consequence of such definitions helps explain the results of a randomised trial of hospital admission multitest screening that found no patient benefits, but increased healthcare costs, when such screening was carried out. Such a definition has the potential for considerable harm, and may also serve to subvert the role of medicine in society. Two final definitions are highly relevant and useful to the clinician because they focus directly on the clinical acts of diagnosis and therapy. The diagnostic definition identifies a range of BNP (or other diagnostic test) results beyond which LVD (or another specific target disorder) is (with known probability) present. The “known probability” with which a target disorder is present is known formally as the positive predictive value, and depends on where we set the limits for the normal range of diagnostic test results. This definition has real clinical value and is a distinct improvement over the definitions described above. It does, however, require that clinicians keep track of diagnostic ranges and cut-offs. The final definition of normal sets its limits at the level of BNP beyond which specific treatments for LVD (such as ACE inhibitors) have been shown conclusively to do more good than harm. This therapeutic definition is attractive because of its link with action. The therapeutic definition of the normal range of blood pressure, for example, avoids the hazards of labelling patients as diseased unless they are going to be treated. Thus, in the early 1960s the only levels of blood pressure conclusively shown to benefit from antihypertensive drugs were diastolic pressures in excess of 130 mmHg (phase V). Then, in 1967, the first of a series of randomised trials demonstrated the clear advantages of initiating drugs at 115 mmHg, and the upper limit of normal blood pressure, under the therapeutic definition, fell to that level. In 1970 it was lowered further to 105 mmHg with a second convincing trial, and current guidelines about which patients have abnormal blood pressures that require treatment add an element of the risk factor definition and recommend treatment based on the combination of blood pressure with age, sex, cholesterol level, blood sugar, and smoking habit. These days one can even obtain evidence for blood pressure treatment levels based on the presence of a second disease: for example, in type 2 diabetes the “tight control” of blood pressure reduces the risk of major complications in a cost effective way. Obviously, the use of this therapeutic definition requires that clinicians (and guideline developers) keep abreast of advances in therapeutics, and that is as it should be. The question is everything As in other forms of clinical research, there are several different ways in which one could carry out a study into the potential or real diagnostic usefulness of a physical sign or laboratory test, and each of them is appropriate to one sort of question and inappropriate for others. Among the questions one might pose about the relation between a putative diagnostic test (say, BNP) and a target disorder (say, LVD), four are most relevant: q Phase I questions: Do patients with the target disorder have different test results from normal individuals?
One such transporter cheap super p-force 160 mg on-line, the divalent metal transporter (DMT-1) 160 mg super p-force visa, is expressed abundantly in the duodenum. Iron Once inside the cell, heme iron is released by the action deficient of heme oxygenase and mixed with the intracellular free iron pool. Iron is either stored in the enterocyte cytoplasm bound to the storage protein apoferritin to form ferritin, or transported across the cell bound to transport proteins, which carry the iron across the cytoplasm and release it into the intercellular space. Iron is bound and transported in the blood by transferrin, a -globulin synthesized by the liver. Iron absorption is closely regulated by iron storage in en- terocytes and iron concentration in the plasma. Enterocytes are continuously shed into the lumen, and the ferritin con- tained within is also lost. Normally, iron in enterocytes is derived from the lumen and the blood (Fig. The amount of iron absorbed is regulated by the amount stored Iron loaded Lumen Enterocyte Blood Heme Heme Heme oxygenase Transport protein Iron Ferritin Apoferritin Transferrin Transferrin Fe Fe FIGURE 27. In healthy subjects, the DMT-1 amount of iron that enters enterocytes is regulated by the Ferritin Transferrin- amount of iron in the cells and circulating in the plasma. In Fe iron-deficient subjects, little iron is incorporated into entero- cytes and less is circulating in the plasma; therefore, absorption is increased and excretion is decreased. In iron-loaded subjects, the mucosal cells and transferrin are more highly saturated, lim- = Facilitated transport iting absorption and increasing excretion. CHAPTER 27 Gastrointestinal Secretion, Digestion, and Absorption 511 in enterocytes. In iron deficiency, the circulating plasma ABSORPTION OF WATER iron concentration is low, which stimulates the absorption In human adults, the average daily intake of water is about of iron from the lumen and the transport of iron into the 2 L. Moreover, in a deficient state, less iron is stored as glands, pancreas, liver, and GI tract make up the most of ferritin in the enterocytes, so the loss of iron through this the fluid entering the GI tract (about 7 L). In iron-loaded patients, there volume of fluid, only 100 mL are lost in the feces. There- is less absorption of iron because of the large amount of mu- fore, the GI tract is extremely efficient in absorbing water. Furthermore, because of the high level of sorption depends on both the region of the intestinal tract circulating plasma iron, the transfer of iron from enterocytes and the luminal osmolality. Through a combination of various ileum absorb the bulk of the water that enters the GI tract mechanisms, body iron homeostasis is maintained. Water Intake, Absorption, Because water absorption is determined by the osmolal- TABLE 27. The osmolality of blood is about 300 mOsm/kg Food and beverages 2,000 mL Salivary secretion 1,000 mL H2O. The water of a hypertonic meal is therefore Water absorbed absorbed mainly in the ileum and colon. In contrast, if a Duodenum and jejunum 4,000 mL hypotonic meal is ingested (e. REVIEW QUESTIONS DIRECTIONS: Each of the numbered protein crucial for the absorption of (D) Hydrochloric acid items or incomplete statements in this vitamin B12 by the ileum. What is this (E) Hypochlorous acid section is followed by answers or by protein? Select the (A) Intrinsic factor salivary acinar cells to release the ONE lettered answer or completion that is (B) Gastrin protease BEST in each case. Most of the following GI secretions (E) Chylomicrons (C) Kininogen have a basal output during the 4. Gastric acid secretion is stimulated (D) Kinin interdigestive period (between meals). Of the Which phase is associated with the (A) Lactoferrin various GI secretions, which is the bulk of acid secretion? After the ingestion of a meal, the pH (D) Salivary secretion (E) Colonic in the stomach lumen increases in (E) Biliary secretion 5 Carbonic anhydrase is an enzyme that response to the dilution and buffering 2. Bile acid uptake by hepatocytes is occurs in plants, bacteria, and animals of gastric acid by the arrival of food. Parietal cells in the stomach secrete a (C) Bicarbonate ion from carbonic acid (D) 9 to 10 (continued) 512 PART VII GASTROINTESTINAL PHYSIOLOGY 9. Unlike other GI secretions, salivary (A) Glucose protein has been digested and secretion is controlled almost (B) Glucose and galactose absorbed by the GI tract? Maltase hydrolyzes maltose to form (D) Free amino acids and tripeptides (C) Cimetidine (A) Glucose (E) Free amino acids, dipeptides, and (D) Aspirin (B) Glucose and galactose tripeptides (E) Omeprazole (C) Glucose and fructose 22. The chief cells of the stomach secrete (D) Galactose and fructose (A) Vitamin A (A) Intrinsic factor (E) Galactose (B) Vitamin D (B) Hydrochloric acid 17. Which sugar is taken up by (C) Vitamin K (C) Pepsinogen enterocytes by facilitated diffusion? The interaction of histamine with its (C) Fructose stimulates calcium absorption by the H2 receptor in the parietal cell results (D) Xylose GI tract? Dietary triglyceride is a major source (B) Vitamin D concentration of nutrient for the human body. It is (C) Vitamin A (B) An increase in intracellular cAMP digested mostly in the intestinal lumen (D) Vitamin K production by pancreatic lipase to release (E) Vitamin C (C) An increase in intracellular cGMP (A) Lysophosphatidylcholine and fatty 24. Which vitamin is transported in production acids chylomicrons as an ester? When the pH of the stomach lumen diglyceride (E) Vitamin B12 falls below 3, the antrum of the 19. Potassium is absorbed in the jejunum stomach releases a peptide that acts absorbed by the small intestine and by locally to inhibit gastrin release.
Paresthesias 51 52 NURSING PRACTICE IN MULTIPLE SCLEROSIS: A CORE CURRICULUM TABLE 11 buy 160mg super p-force overnight delivery. Other causes: depression super p-force 160 mg generic, deconditioning, medications, concommitant medical conditions (thyroid dysfunction, cardiovascular disease), sleep disturbance C. The most common cause of MS-related disability 54 NURSING PRACTICE IN MULTIPLE SCLEROSIS: A CORE CURRICULUM D. Question about other symptoms (pain, spasticity, bowel or bladder dysfunction) 7. Encourage the use of appropriate use of assistive devices (scooters, walkers, wheelchairs, transfer equipment) 3. Encourage the initiation of symptom management—pain, spasticity, bowel, bladder dysfunction 6. Medications used to manage MS-related fatigue: CNS stimulants (methylphenidate) aminopyridines (currently being studied in research) amantidine (SE: headache, dizziness, rash) modafinil (SE: headache, tachycardia, palpitations, con- traindicated in LMVP) pemoline (liver cautions) SSRI antidepressants unique antidepressants—buprioprion (Wellbutrin®) (SE: seizure risk) 9. Pain inadequately defined, identified, or measured by an observer CHAPTER 11: THE SYMPTOM CHAIN IN MULTIPLE SCLEROSIS 55 C. Acute pain trigeminal neuralgia tonic spasms lightning-like extremity pain painful Lhermitte’s sign optic neuritis and retrobulbar pain 2. Chronic pain with insidious onset dysesthetic extremity pain bandlike pain in torso or extremities back pain with radicolopathy headache F. Trigeminal neuralgia probably arises from transmission of nerve impulses in areas of demyelination. In the chronic phase, anticonvulsants such as carbamaze- pine and gabapentin are used. Less common is the painful tetanic posturing of an arm or leg, usually on one side of the body. Treatment consists of carbamazepine, clonazepam, tizanidine, and baclofen. Lightning-like extremity pain can be treated with carbamazepine, gabapentin, and phenytoin. Lhermitte’s sign responds to the above medications and also to tricyclic antidepressant medications. Headache has been reported to be causally related to demye- linating lesions. When associated with a relapse, treatment with steroids may cause resolution of headache. Optic neuritis is due to inflammation and demyelination occurring in and around pain-sensitive meninges surrounding the optic nerve. Gabapentin—useful in dysesthetic and paroxysmal pain; better SE profile than phenytoin 3. Accentuation of DTR and clonus occurs, with exaggeration of flexor reflexes C. Spasms and stiffness are common in the quadriceps, hamstrings, and gastrocnemious muscles D. May be heightened during an exacerbation, with underlying infection, and with noxious stimuli E. Reduce muscle hypertonia by stretching spastic muscles and by application of warm or cold packs 4. Develop and improve useful automatic movements and thus promote maximal function 6. Supply supportive aids such as walkers, wheelchairs, crutches, orthoses, and special shoes F. Screening for noxious stimuli will promote prompt treatment and reduction of spasticity. Medications for spasticity may be sedating and excessive doses may result in weakness CHAPTER 11: THE SYMPTOM CHAIN IN MULTIPLE SCLEROSIS 57 1. Surgically implanted pump for intrathecal baclofen delivery no systemic side effects expensive requires surgery reserved for patients in whom other interventions are unsuccessfulTremor, incoordination, and weakness A. Physical and occupational therapy may provide patient with education and assistive devices, but do not correct the underlying problemDysarthria A. Normal speech consists of five systems working together smoothly and rapidly: 1. Articulation—making quick, precise movements of the lips, tongue, mandible, and soft palate 5. Treatment consists of management of spasticity and tremor along with speech and language therapy (SLT) 58 NURSING PRACTICE IN MULTIPLE SCLEROSIS: A CORE CURRICULUM F. Are problematic speech and voice characteristics detracting from the message being communicated? Are speech, voice, and communication problems interfering with the patient’s quality of life? Are speech, voice, and communication problems perceived as troublesome by the patient and family? Normal swallowing involves intricate and rapid coordination of sensory and motor activity in the oral cavity, pharynx, and esophagus. Normal oromotor control for swallowing involves lip closure, facial tone and musculature, rotary lateral jaw motion, and pharyngeal swallow.
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