The electrophysiological effects of thyrotropin-releasing hormone are similar in human TSH- and prolactin-secreting pituitary cells.

We studied the electrophysiological properties of individually characterized TSH-secreting cells cultured from pituitary fragments surgically removed from three patients, two who had primary TSH-secreting adenomas and one who had chronic TSH hypersecretion (hyperplasia) secondary to primary hypothyroidism. The TSH-secreting cells were excitable and had calcium-dependent action potentials. More than 80% of the cells cultured from the two patients with TSH-secreting adenomas were spontaneously active, whereas fewer cells (20%) cultured from the hypothyroid patient were spontaneously active. TRH (50 nmol/L) induced a complex pattern of electrical changes. The initial response was transient hyperpolarization (activation of potassium conductance), followed by increased low amplitude voltage fluctuations occasionally leading to action potentials. These TRH-induced electrophysiological changes were similar to those reported in rat and human PRL-secreting adenoma cells. These results suggest that TRH may have an identical mode of action in tumoral PRL and TSH cells. In the cells from the hypothyroid patient, the initial response to TRH cells was similar, but the second phase response was greater. The findings that the cells cultured from these patients behaved differently with regard to their electrophysiological characteristics (action potentials) and responses to TRH may reflect the different clinical conditions from which they were derived.

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.

Thallium-201 imaging in the follow-up of differentiated thyroid carcinoma.

Since thallium-201 imaging has been reported as a potential means of follow-up of patients with differentiated thyroid carcinoma (DTC) during ongoing thyroid suppression therapy, the authors evaluated the diagnostic sensitivity of this procedure in 31 patients known to have metastases or local recurrence. Among 51 tumor sites 201TI imaging had a detection rate of 45% whereas 84% was noted for imaging with 131I administered in therapeutic doses. Thus, even though the effectiveness of the two radionuclides is not strictly comparable due to the difference in the administered doses, Thallium imaging cannot be recommended as the only modality for the follow-up of patients with DTC. Six of the eight tumor sites negative with 131I were positive with 201TI (especially metastatic cervico-mediastinal lymph nodes). So 201TI imaging may particularly be helpful in localizing metastases or recurrences in patients with a negative 131I scan and abnormal levels of serum thyroglobulin.

Hemorheological changes in elderly subjects--effect of pentosan polysulfate and possible role of leucocyte arachidonic acid metabolism.

The effects of pentosan polysulfate (PPS) on various hemorheological parameters were studied in a group of very elderly subjects in good general health. Alterations in blood viscosity and filterability were detected in these patients, without any concomitant changes in factors which are known to affect these parameters: notably hematocrit, fibrinogen and plasma lipid levels. The hemorheological abnormalities were considerably improved by twice daily treatment with 50 mg of PPS (i.m.). Apart from its anticoagulant activity, PPS has been shown to have an anti-inflammatory action. We were interested to investigate its effects on metabolism of exogenous arachidonic acid (AA) by both platelets and leucocytes. It is becoming increasingly recognized that metabolites of AA via the 5 LO pathway appear to play a role in inflammatory processes. In this study, PPS was found to inhibit leucocyte 5 LO activity. Reduction in the levels of these metabolites may therefore have an effect on whole blood rheology.

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)

Prevalence of diabetes and effect on quality of life in older French living in the community: the PAQUID Epidemiological Survey.

OBJECTIVES: To evaluate the prevalence of diabetes mellitus in older French subjects and to examine the different aspects of quality of life in an older diabetic population. DESIGN: From a random sample of 2792 people older than age 65 living in the community, a diabetic sample was selected using three items from a questionnaire: Are you diabetic? Are you on a diabetic diet? What kind of medications do you take daily? Validation of the questionnaire was carried out previously to correct the observed prevalence. MEASUREMENTS: The questionnaire assessed social and demographic aspects, physical, mental, and subjective health, and functional disabilities. Because quality of life assessment was mainly subjective, demented subjects were excluded. RESULTS: The diabetic group consisted of 237 subjects from the older sample of 2792 (8.5%). No age difference was demonstrated between the two groups (mean, distribution), but the male/female ratio was significantly higher in those with diabetes (49.4% vs 39.3%, P = .003). Corrected prevalence of diabetes was 10.3%. After exclusion of demented subjects, 230/2726 people were investigated. Diabetic subjects were heavier (P < .001), had higher systolic blood pressure (P < .001), and had more frequent symptoms of ischemic heart disease (P < .001) and painful peripheral arterial disease (P < .001) and dyspnea (P < .001), but antecedents of stroke were similar in both groups. Diabetics were more often lacking in autonomy according to the IADL Lawton scale (P < .001), Rosow and Breslow scale (P < .001), and Mobility scale (P = .043), but not according to the Katz ADL scale. They more often exhibited symptoms of depression on the CES-D self-rating scale (21.3% vs 12.7%, P < .001), but evaluation of cognitive function was similar in both groups. Thirteen percent of diabetics, compared with 7.6% of non-diabetics, were unsatisfied with their own situation (P = .002). Health was rated as fair, bad, or very bad by 67.8% of diabetics compared with 49% of non-diabetics (P < .001). Diabetics rated themselves as feeling worse than others (15.3% vs 9.2%, P < < .001) and worried more about their health status (78% vs 63%, P < < .001). CONCLUSION: The observed prevalence of diabetes in older French people living in the community was 8.5%. Quality of life in older diabetics was poorer than that of other people of the same age.

31P magnetic resonance spectroscopy of human liver in elderly patients: changes according to nutritional status and inflammatory state.

Magnetic resonance spectroscopy (MRS) was used to determine the phosphorylated metabolite content in the liver of elderly patients in various nutritional states: normal, with protein deprivation, and with acute inflammatory syndrome. 31P-MRS investigations were performed at 1.5 T, and localized liver spectra were recorded using a two-dimensional chemical shift imaging sequence. Comparison to control spectra recorded on 10 healthy volunteers (age, 30.5 +/- 2.1 years) showed that the aging process does not significantly modify 31P-MRS liver spectra. Patients with protein deprivation exhibited a higher value than controls for the phosphomonoesters/nucleoside triphosphates (PME/NTP) ratio (P < .05). This increase was not due to the decrease of NTP, since the ratio of inorganic phosphate to NTP (Pi/NTP) remained constant. A decrease in the phosphodiesters to NTP (PDE/NTP) ratio (P < .04) contributed to the observed increase in the PME/PDE ratio (P < .01). In contrast, no significant difference in 31P-MRS spectra was found between elderly patients with hypoalbuminemia associated with inflammatory syndrome and the control group. We conclude that elderly patients with protein deprivation displayed changes in the level of phosphorylated metabolites in the liver that were not observed in the case of inflammatory syndrome despite lower serum albumin (Alb) concentrations.

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)

Standard heparin but not LMW heparin induces a concomitant increase of t-PA and PAI-1 without modification of global fibrinolysis: study after 60 days treatment.

The relationship between heparin and fibrinolysis is strongly suggested. We have studied the influence on fibrinolysis of standard heparin (SH), Calciparin and low molecular weight heparin (LMWH), Fraxiparin, given preventively in an elderly population. Patients were randomized into two groups (SH, LMWH). We investigated fibrinolytic parameters (ECLT, t-PA antigen, PAI-1 activity and antigen, t-PA/PAI-1 complexes) before treatment (D0) and at D30 and D60, before and after venous occlusion (VO). Values at D0, D30 and D60 were compared within each group. A significant and marked increase in t-PA and t-PA/PAI-1 complexes at D30 and D60 before and after VO was noted only in the SH group. The mechanism and clinical relevance of this increase remains to be established.

Study of insulin metabolism in hyperthyroid patients.

Hyperthyroidism is associated with degradation of carbohydrate metabolism. The insulin metabolism in 12 hyperthyroid patients is compared with 10 control subjects. The patients were connected to an artificial beta cell (Biostator GCIIS Miles) for two hours of insulin infusion (40 mU/m2/mn) while glycemia was maintained at its basal level by a modulated glucose infusion. Blood samples were taken, every 15 minutes for insulin and C peptide dosage. In control subjects the insulin steady state level was 93.3 +/- 5 microU/ml whereas this ranged from 42 +/- 3.4 microU/ml to 68 +/- 3.9 microU/ml in hyperthyroid patients. After treatment the insulin level was not quite normal, and ranged from 52 +/- 4.8 microU/ml to 82.2 +/- 9 microU/ml. A glucose intake not corresponding to the same insulin steady state is not therefore to be interpreted. Here there is no evidence of a correlation between the percentage decrease in the insulin test level and the thyroid hormone levels. An impairment of insulin metabolism is suggested in hyperthyroid patients, which might contribute to the decrease in carbohydrate tolerance.

A multi-center trial of the effects of oral nutritional supplementation in critically ill older inpatients. GAGE Group. Groupe Aquitain Geriatrique d'Evaluation.

The purpose of this study was to assess the effect of nutritional supplementation on dietary intake and on pressure ulcer development in critically ill older patients. The multi-center trial involved 19 wards stratified according to specialty and recruitment for critically ill older patients; 9 wards were randomly selected for nutritional intervention (nutritional intervention group), consisting of the daily distribution of two oral supplements, with each supplement containg 200 kcal, for 15 d. Pressure ulcer incidence was prospectively recorded for grades I (erythema), II (superficial broken skin), and III (subcutaneous lesion) for 15 d. Nutritional intake was monitored by using estimates in units of quarters validated by comparison with weight measurement. There were 672 subjects older than 65 y, and 295 were in the nutritional intervention group versus 377 in the control group. The patients were similar for age, sex ratio, and C-reactive protein. In comparison with the control group, the nutritional intervention group included more patients with stroke, heart failure, and dyspnea and fewer with antecedent falls, delirium, lower limb fractures, and digestive disease. The nutritional intervention group had a lower risk of pressure ulcers according to the Norton score but was less dependent (Kuntzman score) and had a lower serum albumin level. During the trial, energy and protein intakes were higher in the nutritional intervention group (day 2: 1081 +/- 595 kcal versus 957 +/- 530 kcal, P = 0.006; 45.9 +/- 27.8 g protein versus 38.3 +/- 23.8 g protein in the control group, P < 0.001). At 15 d, the cumulative incidence of pressure ulcers was 40.6% in the nutritional intervention group versus 47.2% in the control group. The proportion of grade I cases relative to the total number of cases was 90%. Multivariate analysis, taking into account all diagnoses, potential risk factors, and the intra-ward correlation, indicated that the independent risk factors of developing a pressure ulcer during this period were: serum albumin level at baseline, for 1 g/L decrease: 1.05 (95% confidence interval: 1.02 to 1.07, P < 0.001); Kuntzmann score at baseline, for 1-point increase: 1.22 (0.32 to 4.58, P = 0.003); lower limb fracture: 2.68 (1.75 to 4.11, P < 0.001); Norton score < 10 versus > 14: 1.28 (1.01 to 1.62, P = 0.04); and belonging to the control group: 1.57 (1.03 to 2.38, P = 0.04). In conclusion, it was possible to increase the dietary intake of critically ill elderly subjects by systematic use of oral supplements. This intervention was associated with a decreased risk of pressure ulcer incidence.

Effects of early electrical stimulation of the lateral hypothalamus on the delayed acquisition of approach and avoidance learning tasks in the rat.

Three experiments indicated the effects of an early bilateral stimulation of the lateral hypothalamus on later learning behaviour of male rats. The animals were stimulated at 15 days of age and tested during the sixth week of life. Stimulated rats showed an improvement of performances in acquisition of a food-reinforced operant conditioning, but their performance was impaired in two avoidance tests, an inhibitory avoidance response and a two-way avoidance test. These results cannot be interpreted in terms of handling or early experience. An hypothesis of a modified synaptic competition favouring circuits which assure the regulation of approach behaviours is formulated.

[Measurement of the intestinal clearance of alpha 1-antitrypsin and the exchangeable potassium pool in elderly patients treated with anthraquinone glycosides]. / Mesure de la clairance intestinale de l'alpha 1-antitrypsine et du pool potassique échangeable chez des patients âgés, traités par des glucosides anthraquinoniques.

In order to check the long-term tolerance of a laxative treatment, the authors supervised during six months a group of 14 elderly people (12 women and 2 men) with a mean age of 81.3 years suffering from long-standing constipation without any organic cause. The laxative was given in a daily dosage corresponding to 20 mg of sennosides. Alpha 1-antitrypsin (alpha 1-AT) clearance and exchangeable potassium pool (PPE) were measured, at the beginning (T0), and at the end of the third (T3) and the sixth (T6) months of the study. No abnormal variation of intestinal protein loss (alpha 1-AT: T0, 6.74 +/- 3.16; T3, 2.96 +/- 1.35; T6, 4.15 +/- 1.45 ml/24 h; T0-T3; p less than 0.05, T0-T6, T3-T6: NS) and exchangeable potassium pool (PPE: T0, 19.54 +/- 2.55; T3, 20.29 +/- 3.46, T6, 23.56 +/- 4.92 mEq/kg; T0-T3, T0-T6, T3-T6: NS) was observed. In opposition to current views, all long-term laxative treatments do not necessarily induce significant intestinal protein and potassium losses.

Filterability and cerebro-vascular disease.

800 mg of pentoxifylline 400 was administered daily to two groups of elderly patients (average age 80 years) with the aim of increasing cerebral efficiency. Fifty patients (Group I) were treated for 30 days and of these, 25 patients (Group II) were treated for a further, 60 days. The programme included a battery of psychometric tests (Rey's R.P.M. Recit of Barbizet, coupled image tests, immediate memory test) two geriatric scales (Geriatric Rating Scale and Nosie 30) and study of the deformability of red cells. Results at the 30th and 90th day were compared with pre-experimental results: corrected filterability was increased (Group I and II, P less than 0.05), memory tests showed significant improvement (Group I and II, P less than 0.005), geriatric rating scale showed no modification. There was no correlation between changes in corrected filterability and improvement in psychometric tests.

[Hypothyroid neuropathy]. / Neuropathie hypothyroïdienne.

Two cases of polyneuropathy in patients with hypothyroidism are reported. In both cases, the polyneuropathy involved the lower limbs and was predominantly distal. It was sensorimotor in the first patient and purely sensory in the second one. Electrophysiological findings were consistent with an axonopathy. Symptoms and electrophysiological parameters improved with thyroid therapy. Neuropathy in such cases is probably related to the duration of hypothyroidism.

[Malaise and loss of consciousness in the elderly patient: prospective evaluation of methods of investigation]. / Malaises et pertes de connaissance du sujet âgé: évaluation prospective des méthodes d'investigation.

60 consecutive patients (mean age: 80,7 yrs; s.d.: 6,1 yrs; range 70-94 yrs) referred to a geriatric medicine department with syncope or dizziness were proposectively compared with 40 age and sex matched controls. A battery of non-invasive investigations including tilt-test, glycemia, 12 lead ecg., eeg, 24 hour ambulatory ecg recording,. M--mode echocardiogram and cervical Doppler velocimetry was applied blindly to patients and controls. The proportion of abnormalities was similar in both groups having sick sinus syndrom or complete atrio-ventricular block versus no control (p less than 0.05). By contrast history-case was of great predictive value: 6 of 13 patients reporting abrupt syncope had a 24 ecg recording showing sick sinus syndrom or complete atrio ventricular block, versus 2 of 47 other patients (p less than 0,01); 11 of 14 patients reporting orhostatic dizziness or syncope had a tilt-test consistent with orthostactic hypotension versus 6 of 46 other patients (p less than 0,01).

[Plasma, red cell, and cerebrospinal fluid folate in Alzheimer's disease]. / Variations des folates plasmatiques, intraérythrocytaires et intrarachidiens, dans la démence sénile de type Alzheimer.

This study compares plasma, red cell, and cerebrospinal fluid (CSF) folate levels in subjects with mild or moderate Alzheimer's disease (AD) of senile onset and in non-demented control subjects. Twelve subjects with mild or moderate (Folstein's Mini-Mental-State-MMS--between 10 and 23) AD (DSM3 R criteria) and 12 control subjects without dementia and with MMS above 23 were included. To avoid any change in plasma folate levels due to dehydration, all dehydrated subjects were excluded. Were also excluded all subjects obviously suffering from malnutrition or alcoholism, or taking drugs likely to interfere with folate metabolism. Changes in folate levels due to posture or prolonged venous occlusion were carefully avoided. Patients with AD were 5 males and 7 females aged (Mean +/- SD) 80.2 +/- 5.7 years, MMS 14.8 +/- 2.6; controls were 7 males and 5 females aged 78.9 +/- 7.2 y, MMS 28.3 +/- 1.5. The two groups were not statistically different for these variables, except for the MMS. Plasma folate levels were lower (p < 0.006) in patients with AD (4.5 +/- 1.5 micrograms/l) compared with controls (7 +/- 2.2 micrograms/l). Red cell folate levels were lower (p < 0.007) in patients with AD (183.7 +/- 91.1 micrograms/l) compared with controls (300.4 +/- 96.1 micrograms/l). CSF folate levels were lower in AD (18.9 +/- 9.7 micrograms/l) than in controls (21.9 +/- 8.2 micrograms/l) but the difference was not statistically significant (p > 0.05). Our results indicate poorer nutrition in patients with AD.

[Effect of LH-RH infusion on plasmatic testosterone level in normal man and in pathologic cases (author's transl)]. / Effets de la perfusion prolongée de LH-RH sur le taux de la testostérone chez l'homme normal et en pathologie.

LH-RH INFUSION with 250 microgram in eight hours increases testosterone level in normal man by 40% (alpha less than 0,01). Results in hypogonadic patients and in pituitary tumours are presented. No correlation is found between LH-RH responses and pituitary enlargement.

[Value of the corticoliberine test in the etiologic diagnosis of Cushing's syndrome]. / Intérêt du test à la corticolibérine dans le diagnostic étiologique du syndrome de Cushing.

Several studies have demonstrated that the corticotropin-releasing factor test (CRF) is useful for the aetiological diagnosis of Cushing's syndrome: in Cushing's disease, as opposed to ectopic ACTH secretion syndrome, the hypothalamus-pituitary-adrenal (HPA) axis can still be stimulated by CRF. In the present study, we compared the CRF test with the reinforced dexamethasone suppression test in 18 patients: 11 with Cushing's disease, 6 with ectopic ACTH secretion and 1 with adrenal gland adenoma. We obtained 2 false-negative results with the CRF test and 1 false-positive result with the dexamethasone suppression test. Our study, together with published data, suggests that the CRF test is useful in the exploration of Cushing's syndromes of uncertain origin. However, the results obtained with this test must be compared with those of other methods used to explore the HPA axis and which are still necessary.

[Indications and limitations of anticoagulant treatment in elderly patients]. / Indications et limites des traitements anticoagulants chez les personnes âgées.

Anticoagulants constitute the rational treatment of thromboembolic accidents occurring in elderly people, but they are often not prescribed because of the risk of haemorrhage. The chronological age by itself is not a contra-indication, the limitations being the diseases associated with ageing. Anticoagulants may be used as curative treatment in atrial fibrillation with dilated left atrium (greater than 45 mm at echocardiography), in myocardial infarction, embolic strokes and complicated arteritis. They may also be used as preventive and curative treatment in phlebitis and pulmonary embolism. The complications of anticoagulant therapy will be better prevented by using the international normalized ratio and by prescribing doses that are adequate for each indication.