Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While all delirious patients have clouding of consciousness (alteration of attention) and cognitive dysfunction, the level of alertness of different patients may range from stuporous to hyperalert. We, therefore, developed an analog scale to rate the alertness of delirious patients, and a separate scale to rate the severity of their clouding of consciousness. Based on these scales, patients were categorized overall as relatively "activated" (relatively alert despite clouding of consciousness), or "somnolent" (relatively stuporous along with clouding of consciousness). Cognitive function was estimated using the Mini-Mental Status Exam. Separate ratings were made of hallucinations, delusions, illusions, and agitated behavior. Activated and somnolent patients had similar ages, overall severity of delirium, and Mini-Mental Status Exam scores. Activated patients, however, were more likely to have hallucinations, delusions, and illusions than somnolent patients, and were more likely to have agitated behavior. Patients with hepatic encephalopathy were more likely to have somnolent delirium, while patients with alcohol withdrawal appeared more likely to have activated delirium. These data indicate that phenomenologic subtypes of delirium can be defined on the basis of level of alertness. These subtypes are validated in part by their differing associations with symptoms unrelated to alertness. These subtypes may have different pathophysiology, and thus, potentially different treatments.
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PMID:Delirium: phenomenologic and etiologic subtypes. 181 69

To determine the clinical significance of thyroid function abnormalities in patients maintained on lithium, the authors evaluated the relationships of thyroid function tests to clinical response to lithium and side effects from lithium in 20 outpatients meeting DSM-III criteria for major affective disorder. No significant relationships were found between baseline thyroid function tests and clinical response. Thyroxine (T4) and triiodothyronine uptake ratio (T3UR) within the normal range were found to be associated with complaints of lethargy and cognitive impairment. Thirteen subjects were followed prospectively for 6 months with monthly evaluations of affective state, side effects, and occurrence of relapse. Thyroid function tests were repeated at the final visit. Final and mean T3 levels within the normal range were found to be significantly lower in patients who relapsed, and mean T3 level was inversely correlated with affective state as measured by mean scores on the Hamilton Rating Scale for Depression and the Young Mania Rating Scale.
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PMID:Thyroid function in patients maintained on lithium. 314 59

We conducted a phase I trial of caracemide, a new chemotherapeutic agent, which is active in the MX1 (mammary) and CX1 (colon) human tumor xenografts. Using a 5-day bolus schedule, dose-limiting toxicity consisting of burning perioral pain associated with flushing, nasal stuffiness, and excess lacrimation was seen at 650 mg/m2/day. Using a 5-day continuous-infusion schedule, dose-limiting toxicity in the form of changes in affect, lethargy, disorientation, and cognitive dysfunction with electroencephalogram abnormalities was noted at 800 mg/m2/day. The recommended phase II dose levels are 525 mg/m2/day using the 5-day bolus schedule and 650 mg/m2/day using the continuous-infusion schedule. Because of venous pain at the site of infusion, the drug must be delivered via central venous access. The pathophysiology of both the peripheral and central side effects of caracemide may be related to increased cholinergic activity.
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PMID:Phase I trial of caracemide using bolus and infusion schedules. 354 56

A patient presenting with a severe subacute encephalopathy was shown to be infected with a stealth virus. Although the patient partially recovered, he remained lethargic with cognitive impairment and worsening headaches. Ten months after the onset of his illness, his clinical condition further deteriorated with seizures, coma and death. A brain biopsy revealed vacuolated degenerate neural cells consistent with a stealth viral encephalopathy. Focal perivascular lymphocytic inflammation was present within the leptomeninges and to a lesser extent within the parenchyma of the brain. Vasculitis may occasionally contribute to the complex symptomatology of stealth viral encephalopathy.
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PMID:Stealth viral encephalopathy: report of a fatal case complicated by cerebral vasculitis. 888 69

Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages over the "old" drugs. The second purpose is to teach those interested in clinical pharmacology about the use of Web-based information access to answer a neurology/clinical pharmacology problem: to compare the efficacy and side effects of topiramate versus lamotrigine versus phenobarbital using odds ratios. Cost of all three AEDs was also compared. A number of new AEDs, including topiramate and lamotrigine, have been developed for chronic focal and secondarily generalized epileptic seizures. Efficacy of these drugs as anticonvulsants does not seem to be superior to that of traditional anticonvulsants such as phenobarbital. However, the advantage of the new drugs is a different spectrum of possible adverse events. Newer AEDs may or may not induce sedation and may minimize noncompliance by reducing side effects of lethargy and cognitive impairment. The difficulty in achieving therapeutic dosage because of side effects makes one consider whether these agents are "better" than the oldest and most side effect-prone AED, phenobarbital. The new AEDs have less frequent interactions, leading to improved tolerability with comedication. This exercise compares two "new" AEDs, topiramate and lamotrigine, with phenobarbital by evaluating efficacies and side effects using relative odds ratios, a method commonly used in drug development research. Development of new algorithms and/or new knowledge will bring beneficial tools to all clinical pharmacologists.
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PMID:Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios. 1275 Dec 70

Six severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1). a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2). a pharmacodynamic mechanism due to a direct toxicity of TPM in at-risk epileptic patients.
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PMID:Drug induced encephalopathy in six epileptic patients: topiramate? valproate? or both? 1507 54

Sickness behaviors are a set of adaptive responses to infection that include lethargy, anorexia, and, of direct relevance to this work, learning and memory impairments. The proinflammatory cytokine, interleukin-1 beta (IL-1beta) has been proposed as the primary peripheral mediator of these sickness behaviors, though few studies have investigated the effects of peripheral IL-1beta on learning and memory. We used three different versions of the Morris water task (Morris water task), a spatial learning and memory task, to separately assess the effects of peripheral IL-1beta on acquisition, consolidation, and retention of spatial location information. Using a dose that induced anorexia, assessed as a significant reduction in body weight, we observed no performance impairments in the IL-1beta-treated rats across the different versions of the task, suggesting that peripheral IL-1beta alone is insufficient to induce spatial learning and memory impairments in the rat. The observed dissociation of anorexia and cognitive dysfunction suggests that, either spatial learning and memory are not principal components of the sickness response, or cognitive dysfunction requires different or additional peripheral mediator(s).
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PMID:Interleukin-1beta induces anorexia but not spatial learning and memory deficits in the rat. 1662 Oct 55

Primary hyperparathyroidism (PHPT) is classically thought of as the somatic manifestation of hypercalcemia in which patients suffer from a variety of complaints including abdominal pain, nephrolithiasis, osteopenia, and mental status changes. Contemporary PHPT patients are generally free of somatic manifestations and are most often diagnosed when routine biochemical testing shows an elevated serum calcium level. The modern day patient may present with much more subtle neurocognitive symptoms including fatigue, lethargy, muscle weakness, depression, and cognitive impairment. Advances in imaging technology, intraoperative parathyroid hormone measurement, and surgical technique now allow parathyroidectomy to be performed using a focused approach without the absolute need of a four-gland exploration. Minimally invasive techniques allow the procedure to be accomplished under local anesthesia on an outpatient basis. This brief review summarizes the presentation, biochemical evaluation, operative intervention, and follow-up care of the modern day PHPT patient.
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PMID:Primary hyperparathyroidism. 1760 56

Recent studies suggest that activation of the peripheral immune system elicits a discordant central (i.e., in the brain) inflammatory response in aged but otherwise healthy subjects compared with younger cohorts. A fundamental difference in the reactive state of microglial cells in the aged brain has been suggested as the basis for this discordant inflammatory response. Thus, the aging process appears to serve as a "priming" stimulus for microglia, and upon secondary stimulation with a triggering stimulus (i.e., peripheral signals communicating infection), these primed microglia release excessive quantities of proinflammatory cytokines. Subsequently, this exaggerated cytokine release elicits exaggerated behavioral changes including anorexia, hypersomnia, lethargy, decreased social interaction, and deficits in cognitive and motor function (collectively known as the sickness behavior syndrome). Whereas this reorganization of host priorities is normally adaptive in young subjects, there is a propensity for this response to be maladaptive in aged subjects, resulting in greater severity and duration of the sickness behavior syndrome. Consequently, acute bouts of cognitive impairment in elderly subjects increase the likelihood of poor self-care behaviors (i.e., anorexia, weight loss, noncompliance), which ultimately leads to higher rates of hospitalization and mortality.
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PMID:Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. 1849 85

It is well-established that total testosterone (TT) in men decreases with age and that bioavailable testosterone (bio-T) falls to an even greater extent. The clinical relevance of declining androgens in the aging male and use of testosterone replacement therapy (TRT) in this situation is controversial. Most studies have been short term and there are no large randomized placebo-controlled trials. Testosterone has many physiological actions in: muscles, bones, hematopoietic system, brain, reproductive and sexual organs, adipose tissue. Within these areas it stimulates: muscle growth and maintenance, bone development while inhibiting bone resorption, the production of red blood cells to increase hemoglobin, libido, enhanced mood and cognition, erectile function and lipolysis. Anabolic deficits in aging men can induce: frailty, sarcopenia, poor muscle quality, muscle weakness, hypertrophy of adipose tissue and impaired neurotransmission. The aging male with reduced testosterone availability may present with a wide variety of symptoms which in addition to frailty and weakness include: fatigue, decreased energy, decreased motivation, cognitive impairment, decreased self-confidence, depression, irritability, osteoporotic pain and the lethargy of anemia. In addition, testosterone deficiency is also associated with type-2 diabetes, the metabolic syndrome, coronary artery disease, stroke and transient ischemic attacks, and cardiovascular disease in general. Furthermore, there are early studies to suggest that TRT in men with low testosterone levels may improve metabolic status by: lowering blood sugar and HbA1C in men with type-2 diabetes, reducing abdominal girth, ameliorating features of the metabolic syndrome, all of which may be protective of the cardiovascular system. The major safety issue is prostate cancer but there is no evidence that supports the idea that testosterone causes the development of a de novo cancer. So on balance in a man with symptoms of hygonadism and low or lowish levels of testosterone with no evidence of prostate cancer such as a normal PSA a therapeutic (4-6 months) trial of TRT is justified. Treatment and monitoring of this duration will determine whether the patient is responsive.
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PMID:Testosterone and the aging male: to treat or not to treat? 2015 46


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