Regulation of neurotransmitter enzyme by quisqualate subtype glutamate receptors in cultured cerebellar and hippocampal neurons

The possible involvement of ionotropic and metabotropic quisqualate (QA) receptors in neuronal plasticity was studied in cultured glutamtergic cerebellar or hippocampal cells in terms of the specific activity of phosphate-activated glutaminase, an enzyme important in the synthesis of the putative neurotransmitter pool of glutamate. When cerebellar of hippocampal neurons were treated with QA, it elevated the specific activity of glutaminase in a dose-dependent manner. The half-maximal effect was obtained at about 0.1 μM, the maximum increase was at about 1 μM, but levels higher than 10 μM QA produced progressive reduction in glutaminase activity. In contrast, QA had little effects on the activities of lactate dehydrogenase and aspartate aminotransferase and the amount of protein, indicating that the increase in glutaminase was relatively specific. The QA-mediated increase in glutaminase was mimicked by the ionotropic QA receptor agonist -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; EC₅₀, about 0.5 μM), but not by the metabotropic QA receptor agonist trans-(±)-1-aino-cyclopentyl-1,3,dicarboxyalte (t-ACPD; up to 0.5 mM). The specific ionotropic QA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited QA- and AMPA-mediated increases in glutaminase activity in a dose-dependent manner, whereas other glutamate receptor antagonists, -2-amino-5-phosphonovalerate, γ- -glutamyl aminomethyl sulphonic acid and γ- -glutamyl diethyl ester were ineffective. The elevation of neurotransmitter enzyme was Ca²⁺-dependent. The increase in Ca²⁺ influx essentially through the activation of L-type voltage-operated Ca²⁺ channels, and not the mobilization of internal Ca²⁺ stores, was responsible for these QA receptor-mediated long-term plastic changes in hippocampal and cerebellar neurons.     

Cerebral Effects in Superior Vena Caval Cannula Obstruction: The Role of Brain Monitoring

A pediatric cardiac case of transient obstruction of the superior vena cava by the venous cannula before cardiopulmonary bypass is presented. With venous obstruction and increase in central venous pressure, reduced cerebral blood flow velocities and absence of diastolic Doppler flow were detected. This was followed by regional cerebral venous oxygen desaturation and global electroencephalographic slowing. Reposition of the venous cannula led to the recovery of these physiologic indicators and a noncomplicated clinical outcome.     

The Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) evaluated in insulin glargine trials shows greater responsiveness to improvements than the original DTSQ

Background  

The results of using status measures to identify any changes in treatment satisfaction strongly suggest a need for specific change instruments designed to overcome the ceiling effects frequently observed at baseline. Status measures may leave little room to show improvement in situations where baseline ceiling effects are observed. A change version of the DTSQ (DTSQc) is compared here with the original status (now called DTSQs) version to test the instruments' comparative ability to demonstrate change.     

An evaluation of the mechanical failure modalities of a rotating hinge knee prosthesis

The clinical and metallurgical performance of 12 retrieved Noiles total knee prostheses was investigated. Clinical histories and serial roentgenograms were used in conjunction with the American Society for Testing and Materials (ASTM) standard implant retrieval and analysis techniques to assess device performance. All of the devices were removed because of implant loosening with pain, while two devices also had a late infection. The average time in situ for all devices was four years. Roentgenographically, all of the devices showed signs of progressive radiolucencies. Ten (83%) of the devices migrated proximally within the femur. A marked varus drift was observed in eight (67%) of the retrieved prostheses. Hypertrophy of the femoral cortex was observed in eight (67%) of the cases. Seventy-three percent of the polyethylene tibial stems exhibited extensive wear on the anterior and medial aspects of the articulating surface. Extensive wear was also seen on the anterior and extreme posterior aspects in 92% of the polyethylene tibial plateau bearings. This wear was a consequence of the migration of the femoral component leading to buttressing of the plastic components against bone or bone cement. This study indicates serious design flaws in the Noiles knee prosthesis that unless corrected would question the use of the device in either primary or revision knee surgery.     

Impairments in vasopressin-stimulated inositol lipid metabolism in hepatocytes of septic rats

Vasopressin (VP)-stimulated 32P-inositol lipid metabolism was studied in hepatocytes obtained from rats rendered septic by cecal ligation and puncture. Basal 32P-phosphatidylinositol (PI) labeling, as well as its hormone-stimulated turnover, were greatly reduced in septic rats compared with sham-operated rats. The earliest VP-induced degradation of 32P-polyphosphoinositides (poly-PI) was greatly attenuated in septic rats. Moreover, while 32P-poly-PI labeling reached its lowest value by 60 sec of VP stimulation in cells from sham-operated rats, maximal changes in 32P-phosphatidylinositol 4,5-bisphosphate (32PIP2) occurred within 30 sec in septic rats. In contrast, the recovery of 32PIP2 labeling was more active in cells from septic rats, overcoming the impairment in its resynthesis triggered by surgical trauma in cells from sham-operated rats. The lower uptake of 32P into phosphatidic acid (PA) at the different time points analyzed was a sensitive indicator of the lower production of diacylglycerols from the VP-induced degradation of inositol phospholipids in septic rats. These observations support the idea that sepsis is associated with perturbations in the earliest events of the hepatocyte signal transmission pathway, namely, at the level of a receptor coupled to inositol lipid metabolism. Such perturbations are likely to be involved in the previously reported defective cell physiologic response to external hormone stimulation.     

Management of acute visual loss in children.]

Acute or rapidly progressive visual loss in children needs urgent attention and treatment. It may be unilateral orbilateral. Etiology depends upon the involved areas: eye ball, optic nerve, retro-chiasmatic pathways. Psychogenic origin is quite common in school-age children, however, it has to be considered last. Unilateral visual loss may be overlooked. Acute total transitory visual loss may be due to epilepsy or to migraine. Rapidly progressive visual loss may be due to retinal disease, optic neuritis or cortical blindness. Management of visual loss depends on clinical features, associated symptoms, and aspect of the optic disc. It needs collaboration between ophthalmologist,pediatrician and neuropediatrician. Retinal hemorrhages first call to mind a traumatic origin. Swelling of the optic disc may be due to increased intracranial pressure or due to optic neuritis. When the optic disc is normal it is necessary to rule out organic diseases before establishing the diagnosis of a psychogenic vision disturbance. In emergency, brain neuroimaging is the best way to diagnose intracranial mass and visualize optic pathways.     

Paramedic and emergency department care of stroke: baseline data from a citywide performance improvement study.

BACKGROUND: Rapid diagnosis and transport by paramedics and efficient, effective emergency management are essential to improving care of acute stroke patients. OBJECTIVES: To measure the performance of paramedics and emergency departments providing care for patients with suspected acute stroke. METHODS: Two stroke centers and 4 other hospitals where most patients with acute stroke in Houston, Tex, are admitted participated. Hospital and paramedic performance data were collected prospectively on 446 patients with suspected acute stroke transported by paramedics between September 1999 and February 2000. RESULTS: Paramedics had a sensitivity of 66%, specificity of 98%, and overall accuracy of 72% in diagnosing stroke. For patients with suspected stroke, 58.5% arrived in the emergency department within 120 minutes of symptom onset; in confirmed cases, that percentage was 67%. Mean total transport time was 42.2 minutes and was significantly longer (P < .001) to inner-city hospitals (44 minutes) than to suburban, community-based centers (39 minutes). Door to computed tomography times were significantly (P < .001) shorter for the 2 stroke centers than the other hospitals. Overall thrombolysis treatment rate among patients with confirmed ischemic stroke was 7.4% (range, 0-19.4%); treatment rates at the 2 stroke centers were 5.9% and 19.4%. CONCLUSIONS: More than half of patients with suspected stroke arrive at hospitals while thrombolytic treatment is still feasible. Although the current rate for thrombolytic treatment in Houston exceeds the national rate, performance of paramedics and hospitals in treating acute stroke can be improved by increasing efficiency and standardizing medical practices.     

Rotational ablation of coronary artery lesions using single,large burrs

Previous clinical use of the Rotablator^(TM) In coronary artery disease has involved a sequential increase in burr sizes up to 2 mm in diameter and has often utilized balloon adjunct to achieve an optimal result. We report our experience and describe our technique using a single, large burr (2.25, 2.5, or 2.75 mm diameter) without balloon assistance. The burr size was selected to approximate 70–90 percent of the apparent normal lumen diameter. Thirty-one patients with 36 lesions of complex morphology (eccentric, irregular, calcified, ulcerated, at bends, at bifurcations, completely occluded, as well as balloon failures) were successfully treated with the Rotablator^(TM). Results were assessed by computerized quantitative angiography. The percent diameter stenosis (mean ± SD) for the group was reduced from 69.8 ± 11.3% to 30.9 ± 10% (p < 0.001). The mean absolute diameter stenosis increased from 0.9 ± 0.3 mm to 2.2 ± 0.3 mm (p < 0.001). Angiographically visible dissections were seen in 4 patients and were uncomplicated in 2. One patient had a non-Q-wave myocardial infarction. A fourth patient had a presumed acute occlusion 36 hr after the procedure, necessitating emergency bypass surgery, but without Q waves on the electrocardiogram or wall-motion abnormalities on the echocar-diogram. Nitroglycerin was infused through the Rotablator^(TM) catheter and has considerably lowered the degree and frequency of spasm. No other acute complications occurred. The mean procedure time using a single burr was shorter than when multiple burrs were used: 56.5 vs. 97.3 min, respectively (p < 0.05). The use of a single, large-size Rotablator^(TM) burr is an effective method of treating complex coronary stenoses without balloon assistance and has an encouragingly low complication rate and short procedure time. © 1992 Wiley-Liss, Inc.     

Prognostic implications of the proliferative potential of low-grade astrocytomas

The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3 1/2 years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.     

Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.