Mark Corson

By F. Berek. Canisius College.

T he expecta­ tions o f some patients about a treatm ent can alter or even reverse the action of a pharmacological agent order chloramphenicol 250mg mastercard. T he subjects did indeed overcome the drug—they experienced no stomach discomfort discount 250mg chloramphenicol mastercard. W hen disease has a clear em odonal base purchase chloramphenicol 500mg with amex, the effectiveness of the placebo appears to be enhanced. In one study, pa­ tients with bleeding pepuc ulcers were given a placebo but inform ed that it was a powerful and effective drug. O ther patients were given the same agent but were advised that it was a new and promising experim ental drug of undeter­ m ined effectiveness. T he first group scored 75 percent in their remission rate; the second only 25 percent. T houghtful observers, like Frank, The Impact of Medical Care on Patients 19 think there is m ore to it. T he healer as well as the patient m ust believe in the efficacy of the treatm ent, or at least skillfully convey a state of belief to the patient. As Frank puts it: If the effectiveness of the placebo lies in its ability to mobilize the patient’s expectancy of help, then it should work best with those patients who have favorable expectations from medicine and, in general, accept and respond to symbols of healing. T he placebo, w hether a drug or some other treat­ ment, may serve only as a material symbol of the healer’s power. The placebo effect dem onstrates that medicine can cure some patients through its symbolic presence, simply by being there. If cures can be achieved by a fusion o f the patient’s belief in the treatm ent and the manifestation o f symbols of healing, we must ask if it is possible to use equally effective but less expensive symbols. For centuries healers have adm inistered to pa­ tients, with little impact if m easured by the test of effective­ ness. But medicine worked in the past and still works today, although with mixed results. Medicine has effective technologies— technologies that link what the physician does with what happens to the patient. Most of the research was designed to ascertain optimal conditions for the production of goods. But the investigators discovered an anomaly—whatever they did, 20 The Impact of Medicine production improved. W hen workers believed that m anagem ent cared, w hether by increasing or decreasing the lighting, for example, they tried harder. Some patients given placebos respond better to the null “treatm ent” than those given active drugs. In some studies, groups of patients given placebos had better treatm ent outcomes than groups treated with active medications. One of the dangers, then, of too rigorous an examina­ tion of medicine—requiring proof beyond a reasonable doubt—is that caring might be lost in the process. In procedures such as reduction of frac­ tures; treatm ent of infectious diseases such as diphtheria, tetanus, poliomyelitis, and tuberculosis; and surgery for re­ moval of pathenogenic organs, the physician truly heals. Medical care also heals when it utilizes therapies with which The Impact of Medical Care on Health Status 21 it has been entrusted. Penicillin, sulfa drugs, and antibiotics have expanded the capacity of the medical care system to treat and heal. The capacity to deal effectively with syphilis and tuberculosis represents a milestone in human endeavor, even though full use of this potential has not yet been made. And there are, of course, other examples: the treatment of endo- crinologic disorders with appropriate hormones, the preven­ tion of hemolytic disease of the newborn, the treatment and prevention of various nutritional disorders, and perhaps just around the corner, the management of Parkinsonism and sickle-cell anemia. There are other examples, and everyone will have his favorite candidate for the list, but the truth is that there are not nearly as many as the public has been led to believe. T he Papanicolaou test for cervical cancer has proven utility,39 and the means have been found to treat some forms of skin cancer. Paradoxically, some diseases that are both preventable and treatable continue to strike large num bers of people. Allen Chase in The Biological Imperatives40 lists a num ber of preventable diseases which either kill or debilitate large num bers of people simply because resources have not been allocated to their control. Included are hookworm disease, which afflicts approxim ately 600 million people; ascariasis, 22 The Impact of Medicine another worm infestation; schistosomiasis; trachom a, which causes irreversible blindness; and endemic goiter. T he fact that most of these diseases are ram pant in underdeveloped areas does not make them irrelevant. Even in the United States there are diseases that could be m ore effectively treated, or possibly even prevented. Edward Berk, Chairm an o f the D epartm ent of Medicine at the University of California at Irvine, m ore than half of the population o f the United States registers frequent complaints about digestion. Roughly 15 to 20 percent of all illnesses reported afflict the digestive tract—the stomach, intestines, biliary passages, liver, and pancreas. Because of nonspecific symptoms, many cases of peptic ulcer and gallstones, for example, re­ main undetected. Nevertheless, digestive disease ranks second only to circulatory disorders as a cause of workdays lost per year. And research funds are disproportionately spent in other areas, particularly those that have strong lobbies, such as cystic fibrosis and muscular dystrophy.

Vascular rupture can branch of the striate arteries at the posterior angle cheap 500mg chloramphenicol, explain very early hemorrhagic infarcts and early resulting in an ovoid mass pushing the insular cortex intrainfarct hematoma (between 6 and 18 hours after laterally and displacing or involving the internal cap- stroke) buy discount chloramphenicol 500 mg online, whereas hemorrhagic transformation usually sule generic chloramphenicol 500mg fast delivery. From this initial putaminal-claustral location a develops within 48 hours to 2 weeks. They are Caudate hemorrhage, a less common form of caused by leakage from damaged vessels, due to bleeding from distal branches of lateral striate arter- increased vascular permeability in ischemic tissue or vascular rupture secondary to ischemia. Hypertension is the leading risk and the posterior limb of the internal capsule laterally. Larger hematomas often reach the corona serum cholesterol levels, have been identified. The causes the cortico-subcortical junction between gray and include small vascular malformations, vasculitis, white matter and spread along the fiber bundles brain tumors and sympathomimetic drugs (e. A variant, the midline hematoma, originates the second most frequent location (approx. Section 1: Etiology, pathophysiology and imaging Pontine hemorrhages from bleeding of small para- particularly prothrombin gene and factor V Leiden median basilar perforating branches cause medially mutations, and prothrombin mutation, as well as placed hematomas involving the basis of the pons. Later on, it is rate is higher with poor control of hypertension and replaced by fibrous tissue, occasionally with recanali- also in hemorrhages due to other causes. After hours the cortex and adjacent white matter and often are or days extracellular edema develops at the periphery hemorrhagic. After 4 to 10 days the red blood might lead only to brain edema, but usually causes cells begin to lyse, granulocytes and thereafter micro- bilateral hemorrhagic infarcts in both hemispheres. Finally, the infarcts: cytotoxic edema is absent or mild, vasogenic astrocytes at the periphery of the hematoma pro- edema is prominent, and hemorrhagic transformation liferate and turn into gemistocytes with eosinophilic or bleeding is usual. After that Cerebral venous thrombosis can lead to a venous period – extending to months – the residue of the infarct. Venous infarcts are different from arterial hematoma is a flat cavity with a reddish lining infarcts: cytotoxic edema is absent or mild, vaso- resulting from hemosiderin-laden macrophages [26]. Acute occlusion of a major brain artery causes a Hypertension is the leading risk factor, and the stereotyped sequel of morphological alterations which most common location is the putamen. The most sensitive brain cells are neurons, Thrombi of the cerebral veins and sinuses can develop followed – in this order – by oligodendrocytes, astro- from many causes and because of predisposing con- cytes and vascular cells. If blood flow decreases below the threshold of less than 10% of cases, but septic cavernous sinus energy metabolism, the primary pathology is necrosis thrombosis is still a severe, however rare, problem. In the following, densed acidophilic cytoplasm, formation of triangular primary and delayed cell death will be described nuclear pyknosis and direct contact with swollen separately. Electronmicroscopically mitochondria exhibit flocculent densities which represent denatu- Cellular pathology of ischemic stroke rated mitochondrial proteins. After 2–4 hours, ische- mic cell change with incrustrations appears, which Primary ischemic cell death has been associated with formaldehyde pigments de- In the core of the territory of an occluded brain artery posited after fixation in the perikaryon. These changes With ongoing ischemia, neurons gradually lose are potentially reversible if blood flow is restored their stainability with hematoxylin; they become before mitochondrial membranes begin to rupture. Inter- undergo irreversible necrotic changes (red neuron or estingly, neurons with ischemic cell change are mainly Light microscopical characteristics of rat brain infarction Figure 1. Light-microscopical evolution of neuronal changes after Acute ischemic changes experimental middle cerebral occlusion. In focal ischemia delayed neur- festation of ischemic cell change requires some onal death may occur in the periphery of cortical residual or restored blood flow, whereas ghost cells infarcts or in regions which have been reperfused may evolve in the absence of flow [32]. Primary ischemic cell death induced by focal Cell death is also observed in distant brain regions, ischemia is associated with reactive and secondary notably in the substantia nigra and thalamus. The most notable alteration during the ini- The morphological appearance of neurons during tial 1–2 hours is perivascular and perineuronal astro- the interval between ischemia and cell death exhibits a cytic swelling; after 4–6 hours the blood–brain barrier continuum that ranges from necrosis to apoptosis breaks down, resulting in the formation of vasogenic with all possible combinations of cytoplasmic and edema; after 1–2 days inflammatory cells accumulate nuclear morphology that are characteristic of the throughout the ischemic infarct, and within 1. In its pure form, necrosis 3 months cystic transformation of the necrotic tissue combines karyorrhexis with massive swelling of endo- occurs together with the development of a peri-infarct plasmic reticulum and mitochondria, whereas in astroglial scar. However, as this with the collateral circulation and, hence, induce method may also stain necrotic neurons, a clear dif- variations in infarct size. Disturb- branches are end-arteries which, in contrast to the ances of protein synthesis and the associated endo- cortical branches, do not form collaterals with the plasmic reticulum stress are also responsible adjacent vascular territories. As a consequence, the for cytosolic protein aggregation and the formation basal ganglia are consistently part of the infarct core of stress granules [38]. In the hippocampus, stacks whereas the cerebral cortex exhibits a gradient of of accumulated endoplasmic reticulum may become blood flow which decreases from the peripheral visible but in other areas this is not a prominent towards the central parts of the vascular territory. Depending on the steepness of this gradient, a cor- tical core region with the lowest flow values in the Severe ischemia induces primary cell death due to lower temporal cortex is surrounded by a variably necrosis of all cell elements. Transcranial occlusion of the middle cerebral artery: post- or retro-orbital transcranial approaches for middle cerebral artery occlusion are mainly used in rats and mice because in these species the main stem Pathophysiology of stroke of the artery appears on the cortical surface rather close to its origin from the internal carotid artery [40]. In Animal models of focal ischemia contrast to transorbital middle cerebral artery occlu- According to the Framingham study, 65% of strokes sion, transcranial models do not produce ischemic that result from vascular occlusion present lesions in injury in the basal ganglia because the lenticulo-striate the territory of the middle cerebral artery, 2% in the branches originate proximal to the occlusion site. In experimental flow values from the peripheral to the central parts stroke research, this situation is reflected by the of the vascular territory. A nylon later modified for use in cats, dogs, rabbits and even suture with an acryl-thickened tip is inserted into rats. The procedure is technically demanding and the common carotid artery and orthogradely requires microsurgical skills. The advantage of this advanced, until the tip is located at the origin of approach is the possibility of exposing the middle the middle cerebral artery. Modifications of the cerebral artery at its origin from the internal carotid original technique include different thread types artery without retracting parts of the brain. Vascular for isolated or combined vascular occlusion, adjust- occlusion can thus be performed without the risk ments of the tip size to the weight of the animal, of brain trauma.