[Medical-scientific research in the elderly in The Netherlands; historic milestones and methodological problems]. / Medisch-wetenschappelijk onderzoek bij ouderen in Nederland; historische mijlpalen en methodologische problemen.

OBJECTIVE: To describe the methodological development of medical research regarding elderly subjects in the Netherlands. DESIGN: Descriptive. SETTING: Nijmegen University, the Netherlands. METHOD: All research on aging published in the Netherlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) starting from its first volume in 1857 up to 1983 was studied. Selected were those articles in which new research methods were introduced. Next, six pioneering researchers in geriatrics were interviewed on the methodological development of geriatric research and on the problems they encountered in their own research. RESULTS: Research started with studies on age-associated diseases such as prostatism, presbyacusis and senile dementia. It was only after a considerable delay that new diagnostic instruments such as electrocardiography and new research designs such as randomized trials found their way into research on elderly patients. The development of a questionnaire on the health of the elderly, the introduction of the concept of activities of daily living and of diagnostic instruments in the field of psychogeriatrics were important steps that made possible current geriatric research. From the outset, researchers encountered methodological problems still relevant in current research and caused by characteristics of geriatric patients: frailty, high prevalence of comorbidity, coexistence of physical, psychological and social problems, and large interindividual differences.

Nasal absorption of hydroxocobalamin in healthy elderly adults.

AIMS: To investigate the nasal absorption of hydroxocobalamin in 10 healthy elderly adults. METHODS: In a cross-over study, blood samples were collected before administration of the drug and after 10, 20, 30, 40, 60, 120, 180 and 240 min. The plasma cobalamin concentration was determined by competitive radioisotope binding technique. RESULTS: The maximal plasma cobalamin concentration (Cmax) after nasal administration of 750 microg hydroxocobalamin was 1900 +/- 900 pmol l(-1) (mean +/- s.d.). The maximal plasma cobalamin concentration was reached in 35 +/- 13 min (t[max]). The Cmax after nasal administration of 1500 microg hydroxocobalamin was 3500 +/- 2500 pmol l(-1) with a t(max) of 28 +/- 16 min. Both the AUC(0,240 min) and AUC(0,00) increased significantly with an increase of the dose from 750 microg to 1500 microg (P = 0.037 and P = 0.028, respectively). The nasal spray was well tolerated. No signs of irritation or local sensitivity were noted. CONCLUSIONS: The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid, high and well tolerated.

[Reduction of the number of falls in hospitalized patients using a risk index and through preventive measures]. / Reductie van het aantal valpartijen bij opgenomen patiënten door gebruik van een risico-index en door preventieve maatregelen.

OBJECTIVE: To investigate the effect of early identification of hospitalised patients with an increased risk of falling and of preventive measures on the frequency of falling. SETTING: Ten medical units (two neurology, five internal medicine, three surgery; 276 beds) in the St. Radboud Hospital in Nijmegen. METHODS: In a first case control study (5 months), a slightly modified falling risk index of Innes and Turman was validated. In a following (5.5 months) study period the index was computed for every hospitalised patient. Preventive measures were used in patients with a high score. The numbers of falls in both study periods were compared. All falls were carefully documented. RESULTS: High scores on the index were significantly associated with falls (p < 0.001). In both study periods (1 and 2) sensitivity (87% and 89%) and specificity (82% and 74%) of the index were high. A significant reduction in fall rate, 86 falls in period 1 versus 66 in period 2, was achieved, (corrected for number of patients and patient days). CONCLUSION: The modified index is a useful instrument for early identification of patients with a substantial risk of falling in the hospital. Early risk identification and preventive measures were successful in reducing the number of falls.

Postprandial blood pressure reduction.

Recently it has been shown that, after a meal, blood pressure may fall in the elderly, in patients with autonomic failure and in patients on haemodialysis. This review deals with the available data on postprandial blood pressure reduction, the clinical significance and some pathophysiological hypotheses. The mechanism is not fully understood, but postprandial blood pressure reduction seems to be related to glucose related factors, since blood pressure only falls after oral glucose loading, but not after oral fructose, fat or protein loading. Vasoactive gastrointestinal peptides may play a role in the glucose induced vasodilation of splanchnic vasculature, but attempts to identify such peptides have been unsuccessful. The role of insulin in postprandial blood pressure reduction remains to be elucidated, but it does not appear to have any influence on systemic vasodilation or baroreflex response. Although the clinical significance of postprandial blood pressure reduction remains uncertain, patients can be advised in several ways on how to avoid this symptom. Treatment of hypertension, small carbohydrate meals, caffeine and treatment with the somatostatin analogue SMS 201-995 may have a beneficial effect. Patients on haemodialysis with symptomatic hypotension should not consume meals during the procedure.

The effect of oral glucose, protein, fat and water loading on blood pressure and the gastrointestinal peptides VIP and somatostatin in hypertensive elderly subjects.

In elderly subjects blood pressure (BP) may fall after a meal. It can be reproduced by oral glucose, but the effect of fat and protein ingestion on postprandial BP has not been reported. Furthermore, we hypothesized that vasoactive gastrointestinal peptides are involved in this phenomenon. We studied 10 hypertensive elderly subjects (mean age 74 +/- 3 years) for the effects of oral glucose, fat, protein and water loading on BP in relation to plasma concentrations of vasoactive intestinal polypeptide (VIP), somatostatin and insulin. Glucose loading resulted in a decrease of mean arterial pressure by 14 +/- 2 mmHg (P less than or equal to 0.001). In contrast, the ingestion of fat, protein or water had no significant effect on BP. Somatostatin increased after fat and protein loading, whereas VIP increased only after fat loading. These data indicate that postprandial BP reduction in the elderly is related to glucose-related factors. The gut peptide VIP does not seem to play a role in this phenomenon.

Somatostatin analog octreotide (SMS 201-995) prevents the decrease in blood pressure after oral glucose loading in the elderly.

In elderly subjects blood pressure (BP) may fall after a meal. The mechanism of this phenomenon is unknown, but it has been suggested that it may be mediated by insulin and/or vasoactive gut hormones. We studied in normo- and hypertensive elderly subjects the effects of the synthetic long-acting somatostatin analog octreotide (SMS 201-995) on the BP reduction that follows oral glucose administration in subjects who are recumbent and on their postglucose plasma vasoactive intestinal polypeptide (VIP) and insulin concentrations. After placebo treatment, mean arterial pressure fell by 15 +/- 1 mm Hg (P less than 0.001) in the 10 hypertensive subjects and by 7 +/- 2 mm Hg (P less than 0.01) in the 10 normotensive subjects. In contrast, when 50 micrograms octreotide were given sc, BP did not change significantly in either group. Oral glucose did not induce a rise in plasma VIP after either octreotide or placebo administration. The postglucose rises in plasma glucose concentrations were similar after octreotide and placebo treatments in both groups. After placebo administration the postglucose plasma insulin levels increased from 79 to 519 pmol/L in the hypertensive subjects and from 63 to 464 pmol/L in the normotensive subjects, whereas after octreotide treatment plasma insulin increased little in either group. These data indicate that treatment with octreotide holds promise for patients with symptomatic postprandial hypotension, and that VIP does not seem to play a role in this phenomenon.

Atypical Cogan's syndrome: an autoimmune disease?

A 22-year-old woman is described with gastrointestinal complaints, sclerokeratitis, and a bilateral progressive hearing loss. The clinical picture, the outcome of lymphocyte stimulation tests against S antigen (retina soluble antigen), outer rod segment, and scleroprotein, and the successful administration of corticosteroids after a partial spontaneous hearing improvement, are suggestive of an autoimmune disease.

Adrenal scintigraphy in primary aldosteronism. Improved visualization after long-term pre-treatment with dexamethasone.

Dexamethasone-modified adrenal scintigrams were performed on 13 patients with an aldosterone-producing adenoma and on one patient with an aldosterone-producing carcinoma. Adrenal scintigrams using 131I-19-Iodocholesterol were obtained after short pre-treatment with dexamethasone, while 131I-6 beta-Iodomethyl-19-Nor-Cholesterol scintigrams were performed after long-term pre-treatment with dexamethasone during 9-21 days. Using the former procedure the adrenal scintigrams correctly identified the adenoma in 3 of 8 patients, while with the latter procedure the adrenal scintigrams localized the adenomas in 8 out of 9 patients, including 3 patients in whom the former procedure had failed. The adrenal carcinoma was not visualized with 131I-6 beta-Iodomethyl-19-Nor-Cholesterol. Thus, the sensitivity of 131I-19-Iodocholesterol scintigrams to detect aldosterone-producing adenomas was only 37.5%. Uptake of radioactivity in the normal contralateral adrenal gland accounted for the low detection rate. On the other hand, the 131I-6 beta-Iodomethyl-19-Nor-Cholesterol scintigrams, performed after long-term pre-treatment with dexamethasone, had a sensitivity of 89%. It is suggested that long-term pre-treatment with dexamethasone contributed to the improved sensitivity by a more effective suppression of radioactivity uptake in the normal adrenal gland.

Nocturnal, daytime, and postural changes of plasma aldosterone before and during dexamethasone in adenomatous and idiopathic aldosteronism.

The relative importance of ACTH and the renin angiotensin system for control of aldosterone was studied in eight patients with adenomatous primary (APA) and four with idiopathic aldosteronism (IHA). Plasma aldosterone (PA) and cortisol (PC) were measured in blood collected during the night at 15-min intervals between 0500--0800 h by integrated sampling on day 1 and in casual samples during the daytime while patients were in the upright and in the supine position (days 1 and 2, at 1200, 1600, and 2000 h). PRA was measured in all daytime samples. On days 3, 4, and 5, 2 mg dexamethasone were given, and the same protocol for blood sampling was repeated on days 4 and 5. During the night, mean PA in IHA patients was markedly lower than that in APA patients. PA patients correlated with PC in both groups. Dexamethasone reduced the mean nocturnal PA in both groups to equal proportions. In the daytime, the mean recumbent PA in IHA patients was also significantly lower than that in APA patients but was equal in both groups while subjects were in the upright posture. Daytime PA significantly correlated with PC in APA patients and with PRA in IHA patients. During upright posture, dexamethasone did not reduce daytime PA in either group. In the supine position, dexamethasone reduced daytime PA values in APA but not in IHA patients. Thus, short time fluctuations of PA during the night are equally influenced by ACTH in APA and IHA patients, though at markedly different levels of aldosterone production. During the daytime, the influence of ACTH on PA remains apparent in the group with APA. However, the renin-angiotensin system seems to play a predominant role in the control of PA during the daytime in patients with IHA. During dexamethasone and ACTH suppression, PA in APA patients rises in response to upright posture as it does in IHA patients.

Pituitary-thyroid function in spironolactone treated hypertensive women.

Four weeks high dose spironolactone treatment (Aldactone Searle, 100 mg q. i. d.) significantly enhanced the TSH (delta max. 8.5 +/- 4.1 vs. 4.6 +/- 3.1 microunits/ml, P less than 0.05) and T3 (delta max. 32 +/- 27 vs. 11 +/- 16 ng/100 ml, P less than 0.05) responses to an intravenous TRH/LH-RH bolus injection in 6 eumenorrhoeic euthyroid hypertensive women, without affecting basal serum TSH, T3 or T4 levels or the basal and stimulated LH, FSH and prolactin values (P greater than 0.10). The mean serum testosterone, 17-hydroxyprogesterone and oestradiol levels were also similar before and during therapy. Spironolactone, possibly by virtue of its antiandrogenic action, may exert its enhancing effect on pituitary-thyroid function by modulating the levels of receptors for TRH in the thyrotrophs or by altering the T3 receptor in the pituitary permitting a greater response to TRH.