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Coma.

Ann N Y Acad Sci. 2009 Mar;1157:32-47

Authors: Young GB

Coma is a state of unarousable unconsciousness due to dysfunction of the brain’s ascending reticular activating system (ARAS), which is responsible for arousal and the maintenance of wakefulness. Anatomically and physiologically the ARAS has a redundancy of pathways and neurotransmitters; this may explain why coma is usually transient (seldom lasting more than 3 weeks). Emergence from coma is succeeded by outcomes ranging from the vegetative state to complete recovery, depending on the severity of damage to the cerebral cortex, the thalamus, and their integrated function. The clinical and laboratory assessments of the comatose patient are reviewed here, along with an analysis of how various conditions (structural brain lesions, metabolic and toxic disorders, trauma, infections, seizures, hypothermia, and hyperthermia) produce coma. Management issues include the determination of the cause and reversibility (prognosis) of neurological impairment, support of the patient, definitive treatment when possible, and the ethical considerations for those situations where marked disability is predicted with certainty.

PMID: 19351354 [PubMed - indexed for MEDLINE]

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Febrile neutropenia.

Ann N Y Acad Sci. 2008 Sep;1138:329-50

Authors: Ellis M

This review summarizes the current status and diagnostic-therapeutic challenges in febrile neutropenia. Patients with neutropenia-associated infections have a poor prognosis. A large meta-analysis of trials assessing prophylactic antibiotics has shown significant survival benefits; clinical significance of resistance is unclear. Administering broad-spectrum antibiotics to established febrile neutropenic patients has become selective, vancomycin is withheld unless absolutely necessary, and low-risk patients are identified with biological markers. Such patients are now managed with oral antibiotics at home or even without antibiotics. Protracted prolonged neutropenia is the setting par excellence for invasive fungal infections. Conventional amphotericin B administered to such risk patients reduces the incidence of fungal infections. New antifungal drugs have heightened efficacy and lowered toxicity. Novel antifungal diagnostic tests include imaging, particularly the CT “halo” sign (aspergillosis), and serology (glucan, galactomannan), and provide earlier diagnosis and treatment and better outcomes. Negative tests may indicate withholding antifungal therapy. High intermittent dosing of liposomal amphotericin B seems as safe and as effective as standard dosing regimens, but at half the drug acquisition cost. The use of nonantibiotic agents has offered alternative management strategies. Recombinant interleukin-11 reduces bacteremia, through a cytoprotective mechanism on the gut. rhIL-11 releases C-reactive protein and causes shedding of soluble TNF receptor-1, modulating the immunological milieu and the systemic inflammatory response. Other candidate molecules include RANTES and long-pentraxin 3. Recombinant growth factors reduce febrile episodes, permitting completion of chemotherapy, increase overall survival, and minimize infection mortality.

PMID: 18837909 [PubMed - indexed for MEDLINE]

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Related Articles

Cancer pain and analgesia.

Ann N Y Acad Sci. 2008 Sep;1138:278-98

Authors: Christo PJ, Mazloomdoost D

Pain ranges in prevalence from 14-100% among cancer patients and occurs in 50-70% of those in active treatment. Cancer pain may result from direct invasion of tumor into nerves, bones, soft tissue, ligaments, and fascia, and may induce visceral pain through distension and obstruction. Cancer pain is multifaceted. Clinicians may describe cancer pain as acute, chronic, nociceptive (somatic), visceral, or neuropathic. Despite implementation of the WHO guidelines, reports of undertreatment of cancer pain persist in various clinical settings and in spite of decades of work to reduce unnecessary discomfort. Substantial obstacles to adequate pain relief with opioids include specific concerns of patients themselves, their family members, physicians, nurses, and the healthcare system. The WHO analgesic ladder serves as the mainstay of treatment for the relief of cancer pain in concert with tumoricidal, surgical, interventional, radiotherapeutic, psychological, and rehabilitative modalities. This multidimensional approach offers the greatest potential for maximizing analgesia and minimizing adverse effects. Primary therapies are directed at the source of the cancer pain and may enhance a patient’s function, longevity, and comfort. Adjuvant therapies include nonopioids that confer analgesic effects in certain medical conditions but primarily treat conditions that do not involve pain. Nonopioid medications (over-the-counter agents) are useful in the management of mild to moderate pain, and their continuation through step 3 of the WHO ladder is an option after weighing a drug’s risks and benefits in individual patients. Symptomatic treatment of severe cancer pain should begin with an opioid, regardless of the mechanism of the pain. They are very effective analgesics, titrate easily, and offer a favorable risk/benefit ratio. Cancer pain remains inadequately controlled despite the diagnostic and therapeutic means of ensuring that patients feel comfortable during their illness. Therefore, all practitioners need to make control of cancer pain a professional duty, even if they can only use the most basic and least expensive analgesic medications, such as morphine, codeine, and acetaminophen, to reduce human suffering.

PMID: 18837907 [PubMed - indexed for MEDLINE]

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Detecting awareness in the vegetative state.

Ann N Y Acad Sci. 2008;1129:130-8

Authors: Owen AM, Coleman MR

The assessment of residual brain function in the vegetative state, is extremely difficult and depends frequently on subjective interpretations of observed spontaneous and volitional behaviors. For those patients who retain peripheral motor function, rigorous behavioral assessment supported by structural imaging and electrophysiology is usually sufficient to establish a patient’s level of wakefulness and awareness. However, it is becoming increasingly apparent that, in some patients, damage to the peripheral motor system may prevent overt responses to command, even though the cognitive ability to perceive and understand such commands may remain intact. Advances in functional neuroimaging suggest a novel solution to this problem; in several recent cases, so-called “activation” studies have been used to identify residual cognitive function and even conscious awareness in patients who are assumed to be vegetative, yet retain cognitive abilities that have evaded detection using standard clinical methods.

PMID: 18591475 [PubMed - indexed for MEDLINE]

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