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By P. Gorn. Howard Payne University.

H e tells m e that a high proportion of such references cite "data on file" and m any m ore refer to publications written discount hydrea 500mg without a prescription, edited, and published entirely by the industry. Evidence from these sources has som etim es (though by no m eans invariably) been shown to be of lower scientific quality than that which appears in independent, peer reviewed journals. In other words, you don’t need to "trash" papers about drug trials because of where they have been published, but you do need to look closely at the m ethods and statistical analysis of such trials. If these three steps are not followed (as is often the case, for exam ple in term inal care), therapeutic chaos can result. In a veiled slight on surrogate endpoints, Sackett and his team rem ind us that the choice of specific therapy should be determ ined by evidence of what does work and not on what seems to work or ought to work. If you are a practising (and non-academ ic) clinician, your m ain contact with published papers m ay well be through what gets fed to you by a drug rep. The pharm aceutical industry is a slick player at the surrogate endpoint gam e and I m ake no apology for labouring the point that such outcom e m easures m ust be evaluated very carefully. I will define a surrogate endpoint as "a variable which is relatively easily measured and which predicts a rare or distant outcome of either a toxic stimulus (for example, pollutant) or a therapeutic intervention (for example, drug, surgical procedure, piece of advice), but which is not itself a direct measure of either harm or clinical benefit". The growing interest in surrogate endpoints in m edical research reflects two im portant features of their use. In the evaluation of pharm aceutical products, com m only used surrogate endpoints include: • pharm acokinetic m easurem ents (for exam ple, concentration- tim e curves of a drug or its active m etabolite in the bloodstream ) • in vitro (i. First, a change in the surrogate endpoint does not itself answer the essential prelim inary questions "W hat is the objective of treatm ent in this patient? Second, the surrogate endpoint m ay not closely reflect the treatm ent target; in other words, it m ay not be valid or reliable. Third, the use of a surrogate endpoint has the sam e lim itations as the use of any other single m easure of the success or failure of therapy – it ignores all the other m easures! Overreliance on a single surrogate endpoint as a m easure of therapeutic success usually reflects a narrow or naïve clinical perspective.

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After local anesthesia purchase 500 mg hydrea, a skin dermatotomy is made with a scalpel blade and the 17-gauge introducer needle is then advanced along the 126 Chapter 7 Intradiscal Electrothermal Annuloplasty FIGURE 7. AP radiograph angled in craniocaudal fashion, parallel to the L4-5 intervertebral disc; the superior endplate of L5 and the inferior end- plate of L4 are seen en face. The nee- dle is advanced slowly to avoid encountering the traversing root, and if radicular symptoms are elicited, the needle is withdrawn and reori- ented to avoid the root. A tactile resistance and gritty crunching is en- countered when the needle first enters the annulus, and the fluoro- scope is then repositioned in a posteroanterior (PA) projection. Care should be taken not to advance the needle beyond the disc margins, and if there is any confusion about the position of the needle tip dur- ing advancement, the position should be checked fluoroscopically in two orthogonal planes. The patient may report transient localized back pain as the needle penetrates the annulus. Radicular symptoms are not expected and may indicate needle position too close to the descending root. The needle position is checked in the PA projection confirming the tip position just inside the annulus. Under lateral fluoroscopy, the introducer needle is then advanced minimally to achieve positioning of the tip in the nucleus pulposus just in the anterior half of the disc. Optimal positioning is with the tip between a 12 and a 3 o’clock posi- tion (Figures 7. The needle is rotated to ensure that the opening in the needle tip points medially to facilitate catheter naviga- tion. The stylet is removed from the introducer needle, and the catheter Historical Perspective 127 FIGURE 7. Lateral diagram showing angulation (arrows) necessary for parallel approach to the lumbar discs. Cau- docranial angulation is required for accessing the upper lumbar discs, and craniocaudal angulation is necessary for accessing the lower discs. Oblique lateral radiograph demonstrating projection for safe disc ac- cess at discography or annuloplasty. An- gulation is chosen parallel to the disc to be accessed, and obliquity is chosen to opti- mize access to the central disc and avoid the traversing nerve root.

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Parasitic and Rickettsial Infections 293 Cestodes Cysticercosis The features of CNS cysticercosis depend on the num- ber cheap hydrea 500mg with visa, location, and size of the cysts and the intensity of the evoked inflammatory response. Cysts can invade cerebral parenchyma and induce seizures (50% of patients), obstruct the CSF flow and produce hydro- cephalus (30% of cases), involve the meninges and produce meningitis, occlude vascular structures and cause stroke, or less frequently, involve the spinal cord and cause paraparesis Echinococcus granulosus The CNS is involved in only 1–2% of Echinococcus granulosus infections. The larvae usually produce single mass lesions within the brain parenchyma that cause headache, convulsions, personality changes, memory loss, or focal neurological deficits Taenia multiceps This can also involve the posterior fossa, leading to signs of increased intracranial pressure or obstructive hydrocephalus Diphyllobothrium Spirometra species CNS: central nervous system; CSF: cerebrospinal fluid. Nematodes Visceral larva migrans – Toxocara canis Rare but serious neurological complications occur, in- cluding headache, convulsions, or behavioral changes and hemiplegia – Toxocara cati – Baylisascaris Raccoon ascaris procyonis Eosinophilic meningitis – Angiostrongylus The lung worm of rats. Direct invasion of the CNS pro- cantonensis duces headache, vomiting, neck stiffness, fever, para- esthesias, convulsions and cranial nerve palsies (sixth or seventh nerve) The differential diagnosis of CSF eosinophilia includes:! Other parasitic infections (Paragonimus westermani, Gnathostoma spinigerum, or Schistosoma species) Tsementzis, Differential Diagnosis in Neurology and Neurosurgery © 2000 Thieme All rights reserved. Later, focal signs such as motor or cranial nerve palsy predominate, and correlate with larval encystment. Additionally, signs of cerebellar dysfunction, convulsions, or peripheral neu- ropathies may occur, indicating the broad spectrum of neurological complications of symptomatic trichinosis – Trichinella spiralis Temperate climates – Trichinella nelsoni Africa – Trichinella nativa Arctic Strongyloides stercoralis This nematode is endemic in tropical and subtropical regions, and is excreted in the stools of 0. The Strongyloides stercoralis larvae penetrate the skin and migrate to the intestines, lungs, and rarely the CNS; in the latter, they producing meningitis, infarction, or brain abscess CNS: central nervous system; CSF: cerebrospinal fluid. Trematodes (Flukes) Schistosomiasis Schistosoma species inhabit the human vascular sys- tem in the mesenteric veins (S. Central Nervous System Infections in AIDS 295 Rocky Mountain Spotted Fever Rickettsia rickettsii This is transmitted via contact with the wood tick, the dog tick, or the Lone Star tick, with an overall inci- dence of 0. The usual neurological features consist of headache, neck stiffness, altered sensorium, and convulsions. Other neurological abnormalities include ataxia, aphasia, neural hearing loss, and papilledema. The neuro- pathological findings consist of cerebral edema, peri- vascular and meningeal lymphocytic infiltration, and extensive necrotizing vasculitis Cat-Scratch Disease Afipia felis Small Gram-negative bacterium Rochalimaea henselae Neurological complications occur in 2–3% of immuno- competent patients, and the features consist of head- ache, convulsions, altered level of consciousness, status epilepticus, spinal cord involvement with paraparesis or tetraparesis, and Brown–Sequard syndrome Central Nervous System Infections in AIDS Encephalitis Most common, approximately in 60% of HIV patients Toxoplasmosis Most common opportunistic infection, in 20–40% of AIDS sufferers Cryptococcosis In 5% of cases Progressive multifocal In 1–4% of cases leukoencephalopathy (PML) Miscellaneous CNS Incidence ranges from 2% to 18% in AIDS patients tuberculosis – Neurosyphilis Present in 1–3% of HIV-infected patients – Cytomegalovirus in- fection – Herpes simplex Both HSV-1 and HSV-2 – Varicella zoster In less than 1% of immunocompromised patients AIDS: acquired immune deficiency syndrome; CNS: central nervous system. Tsementzis, Differential Diagnosis in Neurology and Neurosurgery © 2000 Thieme All rights reserved. Acute Bacterial Meningitis 297 Predisposing condition Pathogenic organism – Gram-negative organisms (isolated in 5–20% of shunt infections, particularly in infants) – Other pathogens: Pseudomonas spp.