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619 records · Page 35Linked to original sources
PubMed2003

Transient hypohidrosis induced by topiramate.

PURPOSE: Hypohidrosis during topiramate (TPM) treatment was recently reported in children. We describe an adult epilepsy patient who developed inability to sweat as well as heat intolerance while undergoing treatment with TPM. METHODS: To detect the site of the sweat block, patient underwent examination of sweat gland function, cardiovascular autonomic test, and body temperature rhythm determination. RESULTS: During TPM treatment, cardiovascular autonomic function and circadian rhythm of body core temperature were normal, whereas thermoregulatory sweat test (TST) showed anhydrosis. This adverse drug effect was quickly resolved after drug discontinuation. CONCLUSIONS: Because of normal cardiovascular autonomic function and central and peripheral thermoregulatory mechanisms, we hypothesize that hypohidrosis during TPM treatment could be due to a carbonic anhydrases (CA) block at the level of sweat gland.

Adult↗
PubMedDate not supplied

Using a cutoff of <10 ppm for breath hydrogen testing: a review of five years' experience.

To assess the clinical use of the breath hydrogen test in a large community hospital using a <10 ppm cutoff, we reviewed 222 tests performed over a 5-year period to evaluate patients for disaccharidase deficiency or bacterial overgrowth of the small intestine. Of these, the vast majority (195) were for lactose malabsorption, although fructose (17), sucrose (8) and lactulose (2) were also occasionally administered. One hundred eleven tests (50 percent) were positive, with an increase of at least 10 ppm hydrogen above the fasting level and a maximum value most commonly observed (42.3 percent of the time) at 3 hours post-administration. Only 34 patients (15.3 percent) had symptoms noted during the test, as compared with 185 (83.3 percent) who had experienced persistent intestinal problems prior to the test. Recent conditions which may have caused intestinal distress, such as transient disaccharidase deficiency, infections, surgery or other disorders like Crohn's disease, ulcerative colitis or food poisoning, were recorded in only 14 cases. Patterns consistent with bacterial overgrowth of the small intestine were observed in only 3 cases. Of 111 positives, 9 cases had increases between 10 and 20 ppm hydrogen and 7 showed the increase in the 3-hour sample, possibly reflecting a delayed transit through the intestine. Final diagnoses in 6 of these where information was available were for conditions other than malabsorption. We conclude that using a rise of 10 ppm to interpret a positive test does not contribute significantly to an increased frequency of false positives, but that patients with increases between 10 and 20 ppm probably are not lactase deficient.

Adolescent↗
PubMedDate not supplied

Clinical and electroencephalographic effects of topiramate in patients with epilepsy and healthy volunteers.

Although topiramate, one of the newer drugs used in treating epilepsy, is effective in reducing seizure frequency and has a wide spectrum of action, it often induces intolerable adverse effects, predominantly related to the central nervous system. Information that would help document adverse reactions early, thus allowing topiramate doses to be adjusted during the drug titration and maintenance phases, could be obtained from electroencephalogram (EEG) studies. We studied the clinical effects and EEG changes induced by topiramate in patients with refractory partial epilepsy receiving the drug as add-on therapy. To exclude effects related to the other drugs and to epilepsy itself, we compared data from patients and healthy volunteers. After receiving topiramate, 22.6% of patients became seizure free and 29% had their seizures reduced by 50% or more. Topiramate nevertheless induced noteworthy adverse reactions, the main problems being sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose of topiramate induced mild adverse reactions, mainly affecting concentration and attention, with difficulties in speech and writing. In patients with epilepsy, the EEG changes induced by topiramate consisted of increased delta and theta activities and decreased activity in the rapid bands. This recognizable topiramate-induced EEG pattern was again evident in the healthy volunteers, in whom we also detected a significant reduction in the alpha frequency rhythm. Our results confirm that topiramate needs to be introduced gradually while patients undergo close neuropsychologic and neurophysiologic monitoring to detect adverse sedative and cognitive reactions early. The EEG correlate of these events seems to be increased activity in the slower frequency bands.

Adult↗
PubMed2006

Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia.

Hepatic insulin resistance is one of the characteristics of type 2 diabetes and contributes to the development of hyperglycemia. How changes in hepatic glucose flux lead to insulin resistance is not clearly defined. We determined the effects of decreasing the levels of hepatic fructose 2,6-bisphosphate (F26P(2)), a key regulator of glucose metabolism, on hepatic glucose flux in the normal 129J mice. Upon adenoviral overexpression of a kinase activity-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, the enzyme that determines F26P(2) level, hepatic F26P(2) levels were decreased twofold compared with those of control virus-treated mice in basal state. In addition, under hyperinsulinemic conditions, hepatic F26P(2) levels were much lower than those of the control. The decrease in F26P(2) leads to the elevation of basal and insulin-suppressed hepatic glucose production. Also, the efficiency of insulin to suppress hepatic glucose production was decreased (63.3 vs. 95.5% suppression of the control). At the molecular level, a decrease in insulin-stimulated Akt phosphorylation was consistent with hepatic insulin resistance. In the low hepatic F26P(2) states, increases in both gluconeogenesis and glycogenolysis in the liver are responsible for elevations of hepatic glucose production and thereby contribute to the development of hyperglycemia. Additionally, the increased hepatic gluconeogenesis was associated with the elevated mRNA levels of peroxisome proliferator-activated receptor-gamma coactivator-1alpha and phosphoenolpyruvate carboxykinase. This study provides the first in vivo demonstration showing that decreasing hepatic F26P(2) levels leads to increased gluconeogenesis in the liver. Taken together, the present study demonstrates that perturbation of glucose flux in the liver plays a predominant role in the development of a diabetic phenotype, as characterized by hepatic insulin resistance.

Adenoviridae↗
PubMed2003

Safety of available agents used to treat bipolar disorder: focus on weight gain.

BACKGROUND: Pharmacotherapeutic management of bipolar disorder has advanced considerably since the introduction of lithium therapy nearly 50 years ago. The sizable percentage of patients who do not respond adequately to lithium and/or are intolerant to its side effects has served as an impetus for identifying alternative pharmacotherapeutic agents. Recent advances in the understanding of the neurotransmitter systems and their receptors as it applies to treatment of bipolar disorder has, in part, led to progress in delineating applications of anticonvulsant/antiepileptic drugs (AEDs) in this area. Although the efficacy of many drugs has been evaluated in patients with this disorder, medication tolerability and adherence issues related to unfavorable side effect profiles are substantial impediments to the development of novel pharmacotherapies. The potential for excessive weight gain as a side effect of certain psychopharmacologic agents remains a concern to both clinicians and patients. METHOD: English-language literature from 1985-2001 in MEDLINE was searched for the terms bipolar disorder, anticonvulsant, antiepileptic, lithium, antipsychotic, weight, and compliance. This article reviewed current therapeutic options for bipolar disorder, including newer AEDs and atypical antipsychotic drugs, with emphasis on the issue of weight gain and possible approaches to minimizing this risk. RESULTS: Certain newer AEDs are characterized by more favorable safety and tolerability profiles that include weight loss as a desirable side effect. Because bipolar disorder is associated with unacceptably high rates of relapse, recurrence, and morbidity, the concept of pharmacotherapeutic efficacy logically not only includes symptom relief but also necessarily encompasses issues related to regimen tolerability and adherence. CONCLUSION: There is a need for guidelines to help physicians carefully formulate and individualize management plans to reach safe, effective, and cost-efficient patient outcomes. Monitoring the weight of patients with bipolar disorder and educating them regarding this issue should be standard components of any treatment plan.

Anticonvulsants↗
PubMed2006

Topiramate in essential tremor: a double-blind, placebo-controlled trial.

BACKGROUND: Essential tremor is most prevalent and most disabling in older patients. Additional therapies are required for patients with an inadequate response or intolerable side effects. In small trials, topiramate appeared to be beneficial in essential tremor. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-design trial, patients with moderate to severe essential tremor of the upper limbs were randomized to 24 weeks of treatment with placebo or topiramate (target dose, 400 mg/day) as monotherapy or as an adjunct to one antitremor medication. The primary efficacy variable was the final visit tremor score based on the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). RESULTS: The intent-to-treat population was 208 patients (topiramate, 108; placebo, 100). The final visit score (last observation carried forward) was lower in the topiramate group than with placebo (p < 0.001). Mean percentage improvement in overall TRS scores was 29% with topiramate at a mean final dose of 292 mg/day and 16% with placebo (p < 0.001). Topiramate was associated with greater improvement in function and disability (p = 0.001). A between-group difference (p < 0.001) was observed at the first on-treatment visit at 4 weeks when the target topiramate dose was 100 mg/day (mean achieved dose, 62 +/- 9 mg/day). The most common treatment-limiting adverse events in topiramate-treated patients were paresthesia (5%), nausea (3%), concentration/attention difficulty (3%), and somnolence (3%). Adverse events were treatment limiting in 31.9% of topiramate patients and 9.5% of placebo patients. CONCLUSIONS: Topiramate was effective in the treatment of moderate to severe essential tremor. Tremor reduction was accompanied by functional improvements, such as in motor tasks, writing, and speaking.

Adult↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗