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Background: The reason for the high prevalence of mild cobalamin (vitamin B-12) deficiency in the elderly is poorly understood., Objective: We aimed to determine the reason for this high prevalence., Design: We examined cobalamin intake, the presence and severity of atrophic gastritis, the presence of Helicobacter pylori infection, and plasma cobalamin and methylmalonic acid (MMA) concentrations in 105 healthy, free-living, older subjects aged 74-80 y., Results: Mild cobalamin deficiency, ie, low to low-normal plasma cobalamin concentrations (< 260 pmol/L) and elevated plasma MMA concentrations (> 0.32 micromol/L), were found in 23.8% of subjects; 25.7% of subjects were not cobalamin deficient (plasma cobalamin > or = 260 pmol/L and plasma MMA < or = 0.32 micromol/L). Six subjects (5.8%), including 1 with mild cobalamin deficiency, had dietary cobalamin intakes below the Dutch recommended dietary intake of 2.5 microg/d. Mildly cobalamin-deficient subjects had lower total (diet plus supplements) cobalamin intakes (median: 4.9 microg/d; 25th and 75th percentiles: 3.9, 6.4) than did non-cobalamin-deficient subjects (median: 6.3 microg/d; 25th and 75th percentiles: 5.4, 7.9) (P = 0.0336), mainly because of less frequent use of cobalamin supplements (8% compared with 29.6%; chi2 = 3.9, P = 0.048). Atrophic gastritis was found in 32.4% of the total study group: mild to moderate in 19.6% and severe in 12.7%. The prevalence of severe atrophic gastritis, but not mild-to-moderate atrophic gastritis, was higher in mildly cobalamin-deficient subjects (25%) than in non-cobalamin-deficient subjects (3.7%) (chi2 = 4.6, P = 0.032). The prevalence of immunoglobulin G antibodies to H. pylori was similar in mildly cobalamin-deficient subjects (54.2%) and in non-cobalamin-deficient subjects (44.4%) (chi2 = 0.5, P = 0.5)., Conclusions: The high prevalence of mild cobalamin deficiency in healthy, free-living, older Dutch subjects could be explained by inadequate cobalamin intake or severe atrophic gastritis in only 28% of the study population. Other mechanisms explaining mild cobalamin deficiency in older people must be sought. more...

Background: Diuretics are frequently used by elderly patients and overprescription has been suggested. However, the present withdrawal patterns of these medications in clinical practice elderly patients are unclear., Methods: Retrospective medical record analysis of all 584 patients aged 75 years or older admitted to a 240-bed nursing home facility in the years 1990-1994. One-year follow-up by record review and collection of updated information from nursing home physicians., Results: Two hundred and twenty patients (37.7%) used diuretics, and use increased with age (p < 0.05). Reported indications for prescription were heart failure (n = 77), hypertension (n = 38), ankle edema without heart failure (n = 21), or not reported (n = 84). Diuretics were withdrawn in 82 of 220 patients (37.3%), but a doubtful actual indication for diuretic use was found in 72 of the remaining 138 patients (52.2%). After withdrawal, the probability of remaining free from diuretics for at least one year was 0.47. There were no reports of life-threatening or fatal incidents after withdrawal. Mortality rates for the patients whose diuretics were withdrawn did not differ from patients continuing on diuretics., Conclusions: Withdrawal of diuretics was frequently performed and often successful. In addition, doubtful indications for diuretics were found in half of the patients continuing on these medications, suggesting additional opportunities for diuretic withdrawal. more...

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. more...

The conduct of research in geriatric medicine differs from that in other medical specialties in a number of ways. In geriatric research it is almost impossible to study a large, homogeneous group of subjects, suffering solely from the problem to be studied. Moreover, measurements and questionnaires should be short, simple and not very troublesome. These differences are due to the heterogeneity of geriatric patients and the high prevalence of multimorbidity, often resulting in impaired physical, psychological and social performance. In this article a number of issues which are important for successful recruitment and selection of subjects for geriatric research are discussed. First, a review of relevant literature is given, and subsequently, experiences concerning recruitment and selection appreciated in the Nijmegen geriatric research programme' are described. This programme was part of the governmental Netherlands Programme for Research on Ageing (NESTOR). According to the literature the efficacy of recruitment may be improved by: personal contact between researcher and subject in view, introduction of the selection criteria already at the time of subjects' recruitment, a balance between research burden and profit, sufficient rewards for participation, both financially and non-financially, maximal effort in the subjects' transport, and also piloting of the recruitment procedure. In the NESTOR-studies the average number of subjects who were recruited and who completed the studies was low (23%), because a lot of the recruited subjects did not meet the selection criteria or considered participation as too troublesome. Subjects who agreed to participate showed high research compliance. more...

Objective: To study the effect of theophylline use on the vitamin B-6 status., Design: Descriptive., Setting: Department of Geriatric Medicine of Nijmegen Academic Hospital and Department of Pulmonary Diseases, University of Nijmegen, the Netherlands., Patients and Methods: Vitamin B-6 status was determined by measuring pyridoxal-5'-phosphate (PLP) in whole blood (using a high performance liquid chromatography method, reference values: 35-107 mumol/l) in 141 patients from the Geriatric department (84 non-chronic obstructive pulmonary disease (COPD), 40 COPD patients without theophylline and 17 COPD patients with theophylline) and in 25 non-geriatric COPD patients on theophylline., Results: Of the 84 geriatric non-COPD patients (mean age: 82 years; SD: 6) 56% had a subnormal vitamin B-6 status, of the 40 geriatric COPD patients without theophylline (82 years; SD: 6) 70%, of the 17 geriatric COPD patients on theophylline (80 years; SD: 5) 94% and of the 25 non-geriatric COPD patients on theophylline (62 years; SD: 11) 96%., Conclusion: In patients who used theophylline a higher prevalence of subnormal vitamin B-6 status was found than in patients who did not. more...

Objectives: Multi-Frequency Bioelectrical Impedance Analysis (MFBIA) is a quick, simple, and inexpensive method to assess body fluid compartments. This study aimed at determining the validity of MFBIA in detecting clinically relevant changes of fluid balance in geriatric patients., Design: A prospective, observational study., Setting: The 22-bed Geriatric Department of the University Hospital Nijmegen., Participants: Hospitalized patients were eligible if they did not have a pacemaker, were not suffering from terminal illnesses, and did not have psychogeriatric diseases likely to interfere with capacity to consent or comply. During a 16-months period, 218 patients were admitted, of whom 78 patients were eligible and 53 consented to participate., Measurements: Each subject's fluid balance was diagnosed twice a week as dehydrated, overhydrated, or euvolemic, based on standardized physical examination, laboratory tests, and weight evaluation. Changes in fluid balance were quantified by measuring total body water (TBW) and extracellular fluid (ECF) applying deuterium- and bromide-dilution techniques. Impedance at 1, 5, 50, and 100 kHz and body weight were measured daily. Sensitivity and Guyatt's responsiveness indexes of MFBIA in detecting dehydration and overhydration were determined., Results: In total, 1071 MFBIA measurements were performed, during which 14 transitions from dehydration to euvolemia and 13 transitions from overhydration to euvolemia were monitored. Rehydration of dehydrated patients caused an increase in TBW and ECF of 3.4 +/- 1.8 L and 1.9 +/- 1.9 L, respectively, which resulted in significant decreases in impedance of 133 +/- 67 omega at 1 kHz and 93 +/- 61 omega at 100 kHz (P = .001). Treatment of overhydrated patients caused a TBW and ECF loss of 3.8 +/- 4.2 L and 3.1 +/- 3.8 L, respectively, which resulted in significant increases in impedance of 104 +/- 72 omega at 1 kHz and 81 +/- 68 omega at 100 kHz (P < .001). Sensitivity of a single MFBIA in diagnosing dehydration and overhydration was 14% and 17%, respectively. Responsiveness indexes of weighing and MFBIA for dehydration and overhydration were similar at all frequencies and greater than one., Conclusion: The sensitivity of a single impedance measurement in detecting dehydration and overhydration was low. However, responsiveness of serial measurements to intra-individual changes in fluid balance was good. Therefore, this noninvasive technique may be used in clinical practice to improve monitoring fluid balance in geriatric patients, especially when daily weighing is difficult. more...

Objectives: To describe diuretic usage and withdrawal patterns in a population of very old geriatric patients and to evaluate the long-term probability of remaining free from diuretic therapy after withdrawal., Design: Retrospective analysis of medical records and 1-year follow-up study., Setting: University Hospital Nijmegen and Rijnstate Hospital Arnhem, a non-academic teaching hospital, The Netherlands., Participants: All 1547 patients, aged 75 years or older, visiting geriatric medicine departments in the two hospitals for the first time in the years 1990 through 1993., Measurements: Data on medical history, physical examinations, and medication use were obtained from medical records. Diuretic withdrawal and motivation was recorded as reported. Record review indicating diuretic withdrawal prompted a 1-year follow-up investigation and collection of additional updated information from family care and/or nursing-home physicians., Results: A total of 593 three patients (38.3%) were using diuretics. Use of diuretics increased with age from 33.6% in patients aged 75 to 79 years to 47.4% in patients aged 90 years or older (P < .05). Diuretics were withdrawn in 218 patients (36.8%), in 101 patients because of doubts about the initial or persistent indication for diuretic use and in 91 patients because of adverse effects. No reasons for withdrawal were reported in 26 patients. Withdrawal of diuretics was attempted more often in cases of diuretic prescriptions for unknown reasons (51.2%) or ankle edema without heart failure (45.0%) than when prescriptions were for heart failure (28.5%) or hypertension (35.4%). The overall probability of remaining free of diuretic therapy for 1 year was 0.41. Success of diuretic withdrawal was significantly less when congestive heart failure was the initial indication for prescription (probability 0.24). We did not find other clinical parameters related to the success of withdrawal., Conclusions: Our study demonstrates that diuretic therapy can be withdrawn for at least a 1-year period in a substantial number of very old geriatric patients receiving these medications, regardless of the initial indications for prescription. However, withdrawal is performed without application of uniform criteria. Future prospective studies should be directed at developing clear guidelines for diuretic withdrawal in order to facilitate identification of eligible patients and to further improve the success of withdrawal attempts. more...

Objective: To compare the results of open with endoscopic release of the carpal tunnel in patients with the carpal tunnel syndrome., Design: Randomised prospective study., Setting: General hospital Zeeuws-Vlaanderen, Oostburg and Terneuzen, the Netherlands., Method: 178 patients were randomised for open or endoscopic release. The symptom severity score and functional status score were completed before and three months after the procedure. One week after the operation the patients' postoperative pain was measured on a 10-point visual analogue scale. Differences were analysed using the Chi-square test or the t-test., Results: Randomisation failed in two patients; 85 patients had an endoscopic release and 91 patients had an open release. The postoperative pain was significantly less in the endoscopic group. Improvement in symptom severity score and functional status score was the same in both groups. There was no difference in absence from work. Two local complications occurred in the endoscopically treated group. Of the patients 25% were not or only slightly satisfied with the results., Conclusion: Endoscopic release of the carpal tunnel is as effective as the open release but it gives less postoperative pain. Because of the risk of complications and the additional costs, the endoscopic release is not the preferred method for treatment of the carpal tunnel syndrome, however. more...

Objective: To study free- and protein-bound cobalamin absorption and the correlation with atrophic gastritis in healthy middle-aged and older subjects., Design: A cross-sectional study., Participants: Fifty-two healthy subjects, aged 26 to 87 years, apparently free from conditions known to influence the cobalamin status. Middle-aged subjects were defined as those younger than 65 years of age (median age 57 years) and older subjects as those 65 years and older (median age 75 years)., Measurements: Protein-bound cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of scrambled egg yolk, labeled in vivo with 57 Co-cobalamin by injecting a hen with 57 Co-cyanocobalamin. The percentage of 57 Co-cobalamin bound to protein was 65%. Free cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of crystalline 57 Co-cyanocobalamin. Plasma cobalamin, folate and fasting plasma gastrin, and pepsinogen A and C concentrations were determined., Results: The median urinary excretion of egg yolk 57 Co-cobalamin in middle-aged subjects was 12.3% (25th and 75th percentiles 10.5%-14.5%) compared with 11.7% (25th and 75th percentiles 9.8%-13.6%) in older subjects (P = .283). The median urinary excretion after administration of free 57 Co-cobalamin in middle-aged subjects was 25.7% (25th and 75th percentiles 20.6%-30.7%) compared with 27.9% (25th and 75th percentiles 21.4%-34.5%) in older subjects (P = .694). Neither egg yolk nor free 57 Co-cobalamin excretion correlated with age. A ratio of pepsinogen A to pepsinogen C less than 1.6, indicating atrophic gastritis, was found in 13 subjects. Within the atrophic gastritis group, 11 subjects had a pepsinogen A concentration greater than or equal to 17 micrograms/L, indicating mild to moderate atrophic gastritis, and two subjects had a pepsinogen A concentration less than 17 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. All subjects had normal fasting plasma gastrin concentrations. Free and egg yolk 57 Co-cobalamin excretions were not reduced in the atrophic gastritis group when compared with the non-atrophic gastritis group. Median plasma cobalamin concentration was not significantly lower in older subjects (P = .205). Nonetheless, plasma cobalamin concentration correlated negatively with age (r = -.36; P = .008)., Conclusions: We demonstrated no significant difference in either free or protein-bound cobalamin absorption between healthy middle-aged and older adults. In addition, no alteration in cobalamin absorption was found in subjects identified as having mild to moderate atrophic gastritis. Therefore, based on our results, the high prevalence of low cobalamin levels in older people cannot be explained by either the aging process or mild to moderate atrophic gastritis. more...

Background: Charles Bonnet's Syndrome (CBS), characterised by the presence of complex visual hallucinations in psychologically normal people, was considered for a long time to be rare. Systematic research on CBS has been limited. However, it has been realised that CBS occurs frequently in elderly, visually handicapped patients, and we have been able to study the syndrome in a large number of patients., Methods: After screening 505 visually handicapped patients, 60 were found to meet proposed diagnostic criteria for CBS (generally, the existence of hallucinations without delusions or loss of insightful cognition.) Psychopathological characteristics, personal meaning, and the emotional impact of hallucinations, as well as factors influencing the hallucinations, were analysed., Findings: Although diagnostic criteria demand merely "partial insight", all patients had full insight into the unreal nature of their hallucinations. Other characteristics varied. In 46 (77%) patients, hallucinations lacked a personal meaning. Sensory deprivation and a low level of arousal seemed to favour the occurrence of hallucinations. CBS caused considerable distress in only 17 (28%) patients. However, all patients were glad to be told that their hallucinations were not due to mental disease. The proper diagnosis had been made in only one of the 16 patients who had consulted a doctor., Interpretation: Although largely unrecognised in clinical practice, CBS should be considered as a diagnosis in patients who complain of hallucinations and who meet defined diagnostic criteria. There is no proven treatment, but many patients will benefit from reassurance that their hallucinations do not imply mental illness. more...

The decision whether a potential subject is competent or incompetent is a necessary and crucial part of conducting medical research in the elderly. The assessment of competency is required by the legal and ethical frameworks in which this research has to take place. The state of play in the national and international discussions of bills for legislation of this topic will be summarized. Especially the practical consequences of this forthcoming legislation for researchers will be explained. The ethical framework for medical research with elderly subjects will be described from a historical point of view. By means of a review of relevant literature the legal definition of competency will be operationalized and tests for its assessment will be discussed. Competency of consent is assessed by asking several questions about the essential elements of the study. The introduction of a try out of the study for a subject before asking consent ('experienced consent') is propagated as a method to optimize this consent of elderly subjects. Special conditions for giving the required information to elderly subjects, for the informed consent by proxy and for the inclusion of nursing-home residents, are discussed. more...

An automated program using a Finapres device and a personal computer, using a battery of five cardiovascular reflex tests has been developed. This has been used to study cardiovascular autonomic dysfunction in 23 ambulant patients with Parkinson's disease, without disabling fluctuations, and 23 age-matched healthy controls, as a screening method to detect autonomic dysfunction. In one patient only a Finapres signal of insufficient quality due to the tremor excluded subsequent analysis. Heart rate response to forced breathing was abnormal (below the fifth percentile of 124 normals) in six (26.1%) of parkinsonian patients and in one (4.3%) healthy age- and sex-matched control, to standing up four (17.4%) versus none, and to the Valsalva manoeuvre seven (30.4%) versus two (8.7%) respectively. The blood pressure response to standing up was abnormal in two (8.7%) parkinsonian patients and in none of the controls, while the response to sustained handgrip was abnormal in five (21.7%) patients versus one (4.3%) control. Autonomic dysfunction is commonly defined as an abnormal score on two or more of the five tests. Using this arbitrary definition, five patients with Parkinson's disease (= 23%) had cardiovascular autonomic dysfunction, and none of the controls were abnormal. more...

A 58-year-old man underwent surgery for an inguinal hernia. Surgery was performed under epidural anaesthesia. The patient afterwards developed increasing low back pain. Magnetic resonance imaging showed an epidural abscess, which was drained by laminectomy. The patient recovered without neurological sequelae. more...

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. more...

Digoxin is a toxic drug with a narrow therapeutic index that is mostly used by the elderly. Although it is accepted that toxicity of digoxin occurs more frequently in elderly than in younger patients, there is dispute about its prevalence and associated mortality. A study was therefore set up to, on the one hand, find the prevalence and associated mortality of digoxin toxicity in patients admitted onto two geriatric wards in London and, on the other hand, to study the relationship between serum digoxin level and age, serum urea, serum potassium and serum calcium in geriatric patients with digoxin toxicity. Over a period of three years 1438 patients (age 75-93) were admitted of whom 452 (31%) were on digoxin. Thirty-five patients (7.7%) were diagnosed as having digoxin toxicity. Eight patients (22.9%) with digoxin toxicity died during admission. Mortality was higher although not statistically significant for the patients with toxicity than for the patients who were on digoxin without toxicity. The fatal outcome was not predicted by age, serum urea, serum potassium or serum calcium. The serum digoxin level of the eight patients who died was lower than the level of those (n = 23) who survived. Four patients (11%) had a normal serum digoxin level and clinical features of digoxin toxicity that disappeared on stopping digoxin. A hypothesis is put foreward to explain the weak association between serum digoxin level and digoxin toxicity in geriatric patients. more...

We studied the diagnostic interpretation by physicians of written histories of 118 patients with a transient loss of consciousness. Considerable disagreement about a diagnosis of either syncope or seizure was found. Overall agreement was only 31%; an erroneous diagnosis was made in 16% of cases. We concluded that the diagnosis of a seizure after a single event is often too unreliable to justify early treatment. more...

The aim of this study was to evaluate tests predicting renovascular hypertension. This was done by relating the results of renal vein renin tests, the captopril test, and renal scintigraphic tests to the blood pressure outcome 12 months after relief of renal artery stenosis by percutaneous transluminal renal angioplasty in 31 patients. Cure was seen in eight (26%). Improved blood pressure was obtained in 12 patients (39%), and in 11 patients (35%), the result for blood pressure was a failure. The accuracies of the two mathematical models used to analyze the renal vein renin assays were 44% and 60%. The captopril test showed a sensitivity of 36% and an accuracy of 43%. Renal captopril technetium Tc 99m-labeled pentetic acid scintigraphy gave a sensitivity of 60%. Stepwise logistic regression analysis of clinical variables in relation to blood pressure response revealed age as the only factor significantly related to blood pressure outcome. We conclude that the tests used are unfit for helping select patients for percutaneous transluminal renal angioplasty and that age may have an important influence on outcome. more...

Blood pressure (BP) in the elderly may decrease after a meal or oral glucose loading. The mechanism of this phenomenon is still unclear. In addition, the effect of the temperature of a meal on postprandial BP is unknown. However, it has been suggested that vasoactive gastrointestinal peptides are involved in the etiology of postprandial BP reduction. Therefore, we studied the effects of a cold and a warm glucose solution on BP, heart rate, plasma glucose, insulin, and substance-P levels in 15 healthy elderly subjects with a mean age of 74 +/- 3 (SD) years. With an interval of at least 2 days, a warm (50 degrees C) and a cold (5 degrees C) solution (75 g glucose/300 mL water) were given in random order. After the cold glucose loading mean arterial pressure increased by a maximum of 3.9 +/- 1.3 mmHg (P less than 0.01). In contrast, BP decreased after the warm solution by a maximum of 8.0 +/- 1.1 mmHg (P less than 0.001). Neither test had an influence on plasma substance-P levels. Our data suggest that postprandial blood pressure reduction in the elderly is dependent on food temperature. Substance-P does not seem to play a role in this phenomenon. more...

A 21-year-old woman is reported with aplastic anaemia, who presented with pain in the leg. Rapid loss of sciatic nerve function followed. MRI showed irregular streaks of low intensity in the muscles of the pelvic region. A diagnosis of sciatic neuritis as initial symptom of clostridial myonecrosis was made. more...

The relationship between atrial natriuretic peptide (ANP) and age was studied. In elderly subjects (65 to 84 years) higher basal ANP levels were found as compared with those found in young subjects (21 to 23 years). Volume loading (750 mL 0.9% NaCl in 60 minutes) increased ANP levels only in the aged group, and plasma renin activity decreased only in the young subjects. Plasma aldosterone levels did not change. Basal cyclic guanosine monophosphate values did not differ in either group, and rose to a similar extent during volume loading. High pressure liquid chromatography analysis did not suggest different molecular forms of immunoreactive ANP in elderly subjects. The main circulating component both basal and after stimulation corresponds to the (99-126)hANP form. more...

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. more...

Based on studies in laboratory animals and on measurements of the urinary metabolites (allo)tetrahydrocortisol and tetrahydrocortisone in human volunteers it has been claimed that liquorice-induced mineralocorticoid excess is caused by a unique defect in the conversion of cortisol to cortisone. To further evaluate this hypothesis we have investigated the influence of glycyrrhetinic acid (GA), the mineralocorticoid-active constituent of liquorice, on plasma cortisol and cortisone in 10 healthy young normotensive volunteers. Pure GA (500 mg/day), administered orally from days 3-10 of the study, exerted pronounced mineralocorticoid activity. Ingestion of GA resulted in an elevated urinary excretion of free cortisol and virtually unchanged plasma cortisol levels in the presence of markedly decreased levels of both plasma cortisone and urinary free cortisone. These results provide direct clinical support for the hypothesis that GA induces an inhibition of the activity of 11 beta-dehydrogenase, resulting in a blockade in the conversion of cortisol to cortisone. more...

A number of reports share the conclusion that the captopril test is an adequate screening procedure for the detection of renovascular disease among hypertensive patients. Therefore, we prospectively studied the value of this test in 149 consecutive hypertensive patients. The test was considered positive if plasma renin activity, after an oral dose of 25 mg of captopril, rose by more then 4.44 ng.L-1.s-1 (16.0 ng/mL per hour). The sensitivity of the test was 39%, the specificity was 96%, the positive predictive value was 81%, and the negative predictive value was 79%. No clinically important cutoff point identifying patients with renal artery stenosis could be detected in the values of baseline and stimulated plasma renin activity nor in baseline blood pressure or changes after captopril testing. The low sensitivity makes the captopril test unfit to be used as a screening procedure in an unselected hypertensive population. more...

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. more...

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. more...

Pretreatment with a somatostatin analogue, octreotide (SMS 201-995), prevents postprandial blood pressure reduction in the elderly. We hypothesized that this beneficial effect on blood pressure is caused by an octreotide-induced suppression of insulin secretion. We studied the effects of octreotide and insulin administration on the course of blood pressure after oral glucose loading in 10 healthy hypertensive old persons (mean age 73 +/- 3 years). Octreotide was given in a dose of 50 micrograms subcutaneously (sc) (time = -30 minutes). Insulin was given sc in a dose of 0.3 U/kg body weight (time = -10 minutes) and glucose was given orally in a dose of 75 g in 300 mL water (time = 0 minutes). Plasma insulin concentrations remained essentially unchanged after placebo and rose to a maximum level of 58 +/- 6 mU/L following insulin administration. The course of blood pressure was not different following glucose loading with high or low plasma insulin levels. These data indicate that the effects of octreotide on postprandial blood pressure reduction in the elderly are unrelated to the inhibition of insulin secretion. more...

It has been reported that postural hypotension in the elderly is common. However, these studies included institutionalized and more or less disabled persons. Furthermore, postural hypotension may be related to baseline blood pressure. In this study, the influence of age and blood pressure on the hemodynamic and plasma catecholamine responses to orthostatic stress was investigated in young and old normotensive and hypertensive healthy subjects. In normotensive and hypertensive elderly persons, the percentage blood pressure responses during tilt were not significantly different from that seen in young normotensives. We measured a slight decrease of systolic blood pressure and a slight increase of diastolic blood pressure. The hypertensive young patients showed an enhanced diastolic blood pressure response with no fall in systolic blood pressure, in contrast to the normotensive young subjects. Both elderly groups had a lower increase of heart rate than the young subjects. The percentage increase in norepinephrine after tilting was significantly lower in elderly hypertensives than in elderly normotensives and young hypertensives. The presence of hypertension was associated with a decrease in blood pressure, but age had no influence on the change in blood pressure during tilt. In this group of healthy elderly subjects, there was no significant orthostatic hypotension when the blood pressure course of the entire tilt test was taken into account. more...

In a group of 269 untreated hypertensive patients the effect of a single oral dose of captopril (25 mg) on blood pressure was studied for 90-120 minutes. The systolic blood pressure decreased by more than 20% in 9.5% and by more than 30% in 1.1% of the patients. In 22.6% the diastolic blood pressure decreased by more than 20%; in 4.5% it fell more than 30%. The calculated mean arterial pressure (MAP) was reduced by more than 20% in 12.3% of the patients and by more than 30% in 3%. Three patients showed transient neurological deficits. Factors related to a strong blood pressure drop were: renal artery disease and resistant hypertension. However, a potentially dangerous fall in blood pressure, i.e. an acute fall of MAP of over 30%, was also observed in the absence of these risk factors. Therefore not all patients at risk can be identified in advance, and treatment with ACE-inhibitors has to be started under well-controlled circumstances especially in elderly patients. more...

This paper is a report on a case of primary Non-Hodgkin's lymphoma of the central nervous system, diagnosed by cytological and immunological examination of the cerebrospinal fluid. The relevant literature on the subject is reviewed. The importance of examination of the cerebrospinal fluid in cases suspected of this disease is stressed. more...

Recently, it has been recognized that blood pressure (BP) in the elderly may decrease after a meal or oral glucose loading. Calcium antagonists and diuretics have been advocated as first-line drugs for the treatment of hypertension in the elderly. It is not known whether these antihypertensive drugs may further deteriorate or improve BP homeostasis after a meal. Therefore, we studied in a double-blind parallel study the effects of a 12-week treatment with nitrendipine, 20 mg once daily, and hydrochlorothiazide, 50 mg once daily, on BP homeostasis after an oral glucose loading. In addition, the effects of both agents on carbohydrate metabolism were studied. Before treatment, mean BP decreased by 13 +/- 1 mm Hg (SEM) (10%, p less than 0.001) 60 min after the glucose loading in the nitrendipine group [n = 9, age 73 +/- 3 (SD) years] and by 9 +/- 2 (SEM) mm Hg (7%, p less than 0.01) in the hydrochlorothiazide group [n = 13, age 76 +/- 4 (SD) years]. After 12 weeks of treatment, oral glucose loading resulted in mean BP reductions of 7 +/- 2 mm Hg (6%, p less than 0.01) and 4 +/- 2 mm Hg (4%, not significant) in the nitrendipine and hydrochlorothiazide groups, respectively. In the hydrochlorothiazide group, the area under the curve of plasma glucose was significantly higher after treatment than before (p = 0.03). We conclude that antihypertensive treatment with nitrendipine or hydrochlorothiazide improves BP homeostasis after an oral glucose loading. In contrast to nitrendipine, 12 weeks of treatment with hydrochlorothiazide slightly impairs carbohydrate metabolism. more...