Long-term potentiation in the dentate gyrus of the anaesthetized rat is accompanied by an increase in extracellular glutamate: real-time measurements using a novel dialysis electrode.

We have used a glutamate-specific dialysis electrode to obtain real-time measurements of changes in the concentration of glutamate in the extracellular space of the hippocampus during low-frequency stimulation and following the induction of long-term potentiation (LTP). In the dentate gyrus, stimulation of the perforant path at 2 Hz for 2 min produced a transient increase in glutamate current relative to the basal value at control rates of stimulation (0.033 Hz). This activity-dependent glutamate current was significantly enhanced 35 and 90 min after the induction of LTP. The maximal 2 Hz signal was obtained during post-tetanic potentiation (PTP). There was also a more gradual increase in the basal level of extracellular glutamate following the induction of LTP. Both the basal and activity-dependent increases in glutamate current induced by tetanic stimulation were blocked by local infusion of the N-methyl-D-aspartate receptor antagonist D-APV. In areas CA1 and CA3 we were unable to detect a 2 Hz glutamate signal either before or after the induction of LTP, possibly owing to a more avid uptake of glutamate in the pyramidal cell fields. These results demonstrate that LTP in the dentate gyrus is associated with a greater concentration of extracellular glutamate following activation of potentiated synapses, either because potentiated synapses release more transmitter per impulse, or because of reduced uptake by glutamate transporters. We present arguments favouring increased release rather than decreased uptake.

Suprarenal intraarterial infusion of alloxan and streptozotocin during balloon occlusion of the juxtarenal abdominal aorta: a simple technique for inducing diabetes mellitus in canines with reduced mortality.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the mortality and morbidity associated with a simple technique for inducing diabetes in dogs--suprarenal intraarterial infusion of alloxan and streptozotocin during balloon occlusion of the juxtarenal abdominal aorta. MATERIALS AND METHODS: The authors attempted to induce diabetes in six purpose-bred dogs. After the dogs were fasted for 12 hours, the abdominal aorta at the level of the origin of the renal arteries was occluded with an angioplasty balloon introduced by means of a femoral approach. A 3-F microcatheter (n = 1) or infusion wire (n = 5) was introduced via the percutaneous transluminal angioplasty catheter and positioned at the level of the celiac axis, and a mixture of streptozotocin (20-25 mg/kg) and alloxan (20-25 mg/kg) was infused. Diabetes was considered to have been induced if the dogs experienced sustained hyperglycemia. RESULTS: There were no deaths during the follow-up period (range, 7 months to 2 1/2 years). A diabetes-like state was induced in five of the six dogs, and no nephrotoxicity was seen. Diabetes was not induced in one dog owing to caudal migration of an undersized balloon during the infusion; this also resulted in reversible renal damage. CONCLUSION: This simple technique is effective for inducing diabetes in dogs, and morbidity and mortality rates are lower than those reported in the literature with other described techniques.

A prospective study of laboratory and clinical measures of postural stability to predict community-dwelling fallers.

BACKGROUND: The identification of specific risk factors for falls in community-dwelling elderly persons is required to detect early changes and permit a preventative approach to management. This study determines the ability of various laboratory measures and clinical tests of postural stability to prospectively predict fallers in community-dwelling elderly women. METHODS: One hundred elderly women (65-86 years, mean age 73 +/- 5 years) performed a reaction-time step task, a limits of stability, and a quiet stance balance task. Postural muscle timing and movement speed were recorded during the step task. Center of pressure (COP) motion was recorded in quiet stance and at the limits of stability. Four common clinical balance tests were performed, and balance confidence, medical and activity history questionnaires were completed. Subjects were followed up regularly for a 6-month period following testing to determine the frequency and characteristics of any falls that occurred. Predictive capabilities of the balance measures to determine fallers were determined through logistic regression models. RESULTS: The clinical balance tests investigated were not able to predict fallers in this community-dwelling elderly population. A combination of variables from the laboratory tasks provided the best overall prediction rate (77%) of fallers (sensitivity 51%) and nonfallers (specificity 91%) from laboratory measures. Of these, step movement time and gluteus medius onset times were the factors best able to predict fallers. Alone, measures of COP motion in quiet stance and at the limits of stability had a poor ability to predict fallers, although they could correctly identify most nonfallers. Prediction was not significantly improved when clinical balance test results were added to the most predictive laboratory measures. CONCLUSIONS: Not all older adults with a reduction in balance ability reported a fall over a 6-month period. Of those who did, a combination of measures reflective of different aspects of mediolateral postural stability during a rapid step task, quiet stance, and movement to the limits of stability were best able to predict faller status, with nonfallers better predicted than fallers. These results emphasize the importance of the multifactorial nature of falls in the community-dwelling elderly population in that the clinical and laboratory measures did not predict a high proportion of fallers.

Lateral reach: a clinical measure of medio-lateral postural stability.

BACKGROUND AND PURPOSE: Medio-lateral postural instability has recently been identified as a risk factor for falls in the elderly community-dwelling population. However, few clinical tests involve challenges to stability limits in the medio-lateral direction. A lateral reach test was thus developed. Preliminary evaluation of the symmetry, accuracy, test-retest repeatability, and construct validity of the lateral reach test was undertaken to ensure its validity and repeatability prior to clinical application. METHOD: Sixty healthy older female subjects (aged 72.5 +/- 5 years) participated in this study which involved two tasks. The first was the clinical test: a maximal lateral reach to the right and left, recorded by a clinical measure (observation of hand excursion) and a laboratory measure (3D analysis of hand marker excursion). The second was the recording of centre of pressure (COP) stability limits in the lateral direction by use of a dual force platform system. Eighteen subjects returned for repeatability testing. RESULTS: No significant differences in the measures were found between the sides. Lateral reach as measured by the clinical measure was significantly (p < 0.05) correlated with both the laboratory measure of reach (r = 0.650) and with COP stability limits (r = 0.331). The clinical measure of reach was not significantly different (p > 0.01) from the laboratory measure. High test-retest repeatability (r > 0.94) was found for all measures. CONCLUSIONS: The clinical lateral reach test was found to be an accurate measure of lateral reach ability. As it was significantly correlated with COP excursion it was deemed a valid indicator of lateral stability limits. In addition, the lateral reach test had high test-retest repeatability and was symmetrical between the sides. These promising results support both it's use where a clinical indicator of medio-lateral postural stability is desired and further investigation of the lateral reach test in clinical populations.

Ascorbate and glutamate release in the rat hippocampus after perforant path stimulation: a "dialysis electrode" study.

Excitatory amino acids have been proposed to play a critical role in the development and maintenance of epileptic seizures and in the development of neuronal damage. Previous animal studies of glutamate during seizures, however, have often failed to measure any rise in glutamate. We have overcome many of the problems of these studies by using an animal model in which epileptic afterdischarges are induced by stimulation of the perforant path, and glutamate and ascorbate are measured using a newly developed microdialysis electrode that combines the advantages of microdialysis and in vivo electrochemistry. We have successfully shown (1) a rise in glutamate after an epileptic afterdischarge, (2) a concomitant initial fall and then a later rise in ascorbate, and (3) progressive dwindling of this effect when afterdischarges are repeated within minutes, despite similar electroencephalographic responses. The possible mechanisms of these effects are discussed and include ascorbate/glutamate heteroexchange, reversal of the glutamate uptake mechanism, and augmentation of glutamate uptake after a seizure.

Measurement in vitro of human plasma glycerol with a hydrogen peroxide detecting microdialysis enzyme electrode.

Human plasma glycerol was determined with a microdialysis electrode, containing the enzymes glycerol kinase and glycerol phosphate oxidase held stationary within the electrode. A microdialysis electrode is essentially a conventional microdialysis probe, with a platinum working electrode inserted into the tip of the dialysis fiber and reference and counter electrodes contained in the upper compartment. The linear range of response to glycerol was directly dependent on the concentration of ATP. At 4 mM ATP, the linear range was 0.5-500 microM. A fast response time of 20 s was obtained. Two types of interferences were observed when plasma glycerol was measured: direct oxidation of interferents at the electrode and attenuation of response to glycerol by reaction with hydrogen peroxide and/or poisoning of the platinum electrode. Ascorbate, urate, and acetaminophen were removed from plasma samples by a pretreatment step involving peroxidase and catalase. Any remaining interferent current was reduced by electropolymerizing o-phenylenediamine onto the platinum electrode. Adsorption of plasma proteins on the dialysis fiber was minimal and was not reduced by the preadsorption of human serum albumin. Very good correlation was obtained between the electrode and the standard spectrophotometric technique for the variation in glycerol concentration with time.

Changes in medical referrals to an outpatient physiotherapy department.

The information provided in 10 per cent of all written medical referrals received by a teaching hospital physiotherapy outpatient department in each of the years 1982 and 1989 was systematically analysed to identify any demonstrable changes in emphasis. Significant between year differences indicated fewer referrals containing a diagnosis in 1989 than in 1982, less emphasis on requests for physiotherapy modalities and a significant increase in more generalised requests and inclusion of aims of treatment. These results suggest that greater clinical autonomy is expected of physiotherapists by medical practitioners in this particular hospital setting, The method used in this study could be applied in future to monitor referral to physiotherapy to examine whether these results represent a real trend.

A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility.

The efficacy and safety of a new veno-active flavonoid fraction (S 5682) consisting of micronized diosmin (90%) and hesperidin (10%) have been studied in 100 patients with symptomatic capillary fragility in a double-blind, randomized, placebo-controlled trial. Treatment lasted 6 weeks and consisted of 2 daily tablets of either S 5682 or placebo. Patients were examined at weeks 0, 2, 4 and 6. Compared to placebo, capillary resistance, assessed by the negative suction cup method, was significantly higher in the S 5682 group at week 4 (219 +/- 10 mmHg versus 159 +/- 8 mmHg; p < 0.001) and week 6 (261 +/- 12 mmHg versus 163 +/- 9 mmHg; p < 0.001). This resulted in a significant improvement of symptoms of capillary fragility (spontaneous ecchymosis, epistaxis, purpura, petechiae, gingivorrhagia, metrorrhagia and conjunctival haemorrhage) in S 5682 treated patients (p < 0.001). S 5682 was well tolerated. The rate of side-effects spontaneously volunteered by the patients was similar in both groups. We, therefore, conclude that S 5682 increases to a large extent the capillary resistance in patients with abnormal capillary fragility without significant side-effects.

[Depression in elderly patients. Value of tianeptine in 140 patients treated for 1 year]. / La dépression du sujet âgé. Intérêt de la tianeptine chez 140 patients traités pendant 1 an.

An open multicenter study of the efficacy and acceptability of tianeptine, a new antidepressant structurally related to tricyclic antidepressants, was conducted by 36 gerontologists. There were 228 patients in the study; 140 were treated for one year. The patients' overall MADRS score started to decrease on day 14 and continued to decline to month 3. An improvement in depression was again observed near the end of the treatment period from month 9 to month 12. This pattern of improvement was also found with the HARS, the first item on the CGI scale and the Zung self-evaluation scale. These findings demonstrate the beneficial effect of long-term treatment in depressed elderly patients. Ten patients (4.4 percent) dropped out because of side effects: mainly drowsiness, anxiety or gastrointestinal disorders. The benefit/risk ratio (CGI, item 3), an expression of treatment effectiveness and acceptability, was very satisfactory even in these elderly patients. Regularly performed laboratory tests and clinical examinations (including weight and blood pressure) revealed no significant changes. Finally, somatic disorders, essentially cardiovascular and neurological diseases often occurring in depressed patients, remained remarkably quiescent throughout the entire treatment period.

Pharmacokinetics of the antidepressant tianeptine at steady state in the elderly.

The pharmacokinetics of tianeptine, an antidepressant with an original serotoninergic neurochemical action, was investigated in elderly patients. Kinetic profiles were developed in 12 elderly patients (age range: 72-81 yr) after single (12.5 mg) dose and multiple oral dosages (12.5 mg tid for 17 days). Multiple dosing of tianeptine was well tolerated; no accumulation of the unchanged drug was observed. Tianeptine and its MC5 metabolite (C5 acid analogue of tianeptine) reached maximum plasma levels after 1.81 +/- .99 and 2.96 +/- 1.44 hr, respectively, with values of 353 +/- 198 and 81 +/- 20 ng/mL, respectively, after a single dose and of 405 +/- 202 and 175 +/- 85 ng/mL, respectively, after multiple dosing. Minimum plasma concentrations of tianeptine were about half those of its MC5 metabolite (68 +/- 41 and 121 +/- 64 ng/mL-1 on day 5), and for each compound, they were not statistically different from day 5 to day 18 of the chronic administration. This finding is compatible with the terminal half-lives that were observed after the single dose that was 2.8 +/- .9 hr for tianeptine and 12.3 +/- 7 hr for the MC5 metabolite. For both compounds, the area-under-the-plasma levels time curve at steady state was as predicted from the initial single dose that showed no deviation from linearity with time. The kinetics of tianeptine in elderly patients were similar to those reported for young adults. However, MC5 metabolite plasma levels were higher in elderly patients than in younger patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological study of the aging human peripheral nerve.

The superficial peroneal nerve from 46 elderly patients was studied by light and electron microscopy. Like most elderly people, these patients displayed evidence of varying degrees of peripheral nervous system dysfunction, but they were not suffering from any disease known to alter the peripheral nerve. A quantitative study showed that myelinated fiber loss predominated in the large diameter group. In the majority of cases, clusters of regenerating myelinated fibers were numerous. On the other hand, Wallerian-like degeneration aspects, segmental demyelination figures and axonal organelle accumulation were relatively rare. Unmyelinated fibers were also notably damaged in most cases. There was moderate reduplication of endoneurial vascular basement membrane.

[Short-stay hospitalization of elderly persons: first step toward institutionalization?]. / L'hospitalisation en court-séjour des personnes âgées: premier pas vers l'entrée en institution?

One month outcome after hospitalization was studied in 1695 persons aged 75 and over, living in the community and admitted to acute care medical units: only 9.6% of them were then institutionalized. Returning home requires a high level of independence for feeding, mental status and continence. The level of dependence of institutionalized patients was particularly high for dressing or bathing, technical care, mental status and security. A multivariate analysis showed that the only independent predictors of institutionalization were: sex, living alone, mental status and hospital type. The role played by physical disability must be counterbalanced by the effective physical assistance, brought to the elderly by institutional or informal home care after hospitalization. These results allow early identification of persons at high risk of institutionalization.

Antihypertensive efficacy and acceptability of rilmenidine in elderly hypertensive patients.

Elderly hypertensive patients (older than 70 years, with a diastolic blood pressure [BP] between 95 and 114 mm Hg) were entered into a study after a 2-week wash-out period and randomized to 2 parallel groups: rilmenidine (n = 28) and methyldopa (n = 30). The initial dose (rilmenidine, 1 mg once daily A.M. or methyldopa, 250 mg twice daily) was doubled (1 mg twice daily or 500 mg twice daily, respectively) on day 21 if supine diastolic BP remained greater than 90 mm Hg. After a 6-week treatment period (days 0 to 42, with weekly examinations), the effects of treatment withdrawal (day 42) were evaluated twice daily (days 43 to 45), with a final examination on day 49. Most of the 58 patients (70%) (aged 81.5 +/- 0.8 years) with a mean diastolic BP of 100.2 +/- 0.7 mm Hg remained treated with the initial dose in both groups. Efficacy in both groups was identical on day 42: decrease in systolic and diastolic BP of approximately 18 mm Hg, with 85% of patients having BP levels normalized (supine diastolic BP less than or equal to 90 mm Hg). Compared with the reference period, no increase in adverse effects was noted apart from a moderate dryness of mouth in 15% of patients in both groups; no orthostatic hypotension was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension in the elderly.

The incidence of definite hypertension increases with advancement of age, and one third of the elderly population is affected. Isolated systolic hypertension is frequent in this population (10 to 12 percent in subjects between 65 and 74 years of age). The role of hypertension as a cardiovascular risk factor has been confirmed in the elderly population by the increase in cerebrovascular accidents, and by the incidence of myocardial infarction with the rise in blood pressure. The relationship between elevated diastolic and systolic blood pressure and mortality rates in the elderly is also well documented (Framingham). Effective treatment of hypertension significantly reduces the risk of associated complications: cardiovascular death, congestive heart failure, and stroke. However, the goal of antihypertensive therapy in the elderly should be not only to reduce morbidity and mortality rates, but also to do so without adverse effects on the functional well-being of patients.

[Factors related to length of hospitalization of elderly patients during short stay]. / Facteurs liés à la durée d'hospitalisation des personnes âgées en court séjour.

Length of stay of elderly patients in hospitals can be subdivised into a medical stay followed by a social stay. The average length of stay of 2134 patients aged 75 and over, admitted to 23 medical or geriatric acute wards in Aquitaine, was 13.6 days; 18% of the patients experienced a social stay of at least one day. The mean social stay was almost null (1 day) when the patient returned home, but could reach 5 days when he was discharged to a long term care facility. The kind of hospital, domicile in a rural area, the social network, and the grounds for hospitalization were significantly related to the total length of stay, but explained only 5% of variance if diagnosis was not taken into account. This percentage rose to 29% in the group with "bronchitis" as a main diagnosis. The length of social stay was related to the grounds for hospitalization, but also to recent family modifications; it did not depend on the kind of hospital. These results suggest a lack of accessibility to nursing-homes, following acute hospitalization.