A COMPARISON OF KETOPROFEN SR AND SULINDAC IN THE ELDERLY WITH RHEUMATOID ARTHRITIS

The elderly (age >65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.     

Long-Term Subdural Strip Electrocorticographic Monitoring of Ictal Déjà Vu

Summary: We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right-handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left-handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experiential phenomenon appears to lateralize to the hemisphere nondominant for handedness.     

Effects of Ethanol on the Contractile Function of the Heart: A Review

Chronic ethanol consumption leads to a number of alterations in the contractile function of the heart and is a leading cause of cardiomyopathy. Ethanol also has an acute negative inotropic effect mediated by direct interaction with cardiac muscle cells, although this action is often masked by indirect actions resulting from enhanced release of catecholamines in vivo. This article reviews the effects of ethanol on the contractile function of the heart. The specific targets affected by ethanol in cardiac muscle cells are discussed in terms of potential mechanisms underlying the depressions of contractility resulting from both acute and chronic actions of ethanol.     

Hyperexcitability associated with localizable lesions in epileptic patients

Intracellular recordings from neurons were carried out in cortical slices obtained from tissue removed from patients suffering from intractable seizures. The patients were divided into two groups based on the presence or absence of an anatomical abnormality that could be imaged preoperatively. The lesion or its surround was the presumptive epileptogenic area. The tissue removed from the patients without lesions was removed either for biopsy purposes or for access to epileptic tissue and was not considered epileptogenic. All neurons from patients without an imageable lesion, and some (19%) from patients with an imageable lesion, responded to orthodromic stimuli with a sequence of synaptic excitation followed by inhibition; these properties resembled those of normal rodent cortical slices. Different responses, classified as abnormal, were observed in 81% of the neurons in tissue specimens obtained near lesions. The most common was prolonged synaptic excitation with no noticeable inhibition, even at high stimulus strengths. In three resections, long latency all-or-none depolarization shifts were observed that resemble the classic paradoxical depolarization shift seen in in vivo extracellular recordings. Loss of specific inhibitory systems within the cortex may contribute in part to these abnormal responses.     

Dietary Vitamin E Modulation of Cytokine Production by Splenocytes and Thymocytes from Alcohol-Fed Mice

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably afffecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and inter-feron-γ by concanavalin A (Con A)-stimulated splenocytes and in terleukin-6 and tumor necrosis factor-a by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccha-ride-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleu-kin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin- 4 and interferon-γ production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supple-mentation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.     

The effects of norepinephrine transporter inactivation on locomotor activity in mice.

BACKGROUND: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. METHODS: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. RESULTS: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. CONCLUSIONS: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.     

Frontotemporal dementia and parkinsonism linked to chromosome 17 with the N279K tau mutation

We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course.     

Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver.

Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for detection by MRS. In this study, three independent signal-to-noise ratio (SNR) optimizations were combined to enable chemical shift imaging (CSI) as a localization method in the detection of 5FU and its metabolites in tumor tissue. First, the hardware was optimized by using circularly polarized coils together with integrated preamplifiers. Second, the optimal pulse angle (Ernst angle) was determined on the basis of T(1) relaxation time measurements of 5FU. Finally, averaging of CSI phase-encoding steps was optimized by using the applied Hamming filter as a weighting function. The combination of these three methods enables the in vivo detection of 5FU and alpha-fluoro-beta-alanine (FBAL) by (19)F MRS, localized in three dimensions in tumor and liver tissue at a time resolution of 4 min at 1.5 Tesla.