[Measuring the handgrip strength of geriatric patients]. / Het meten van handgreepsterkte bij geriatrische patiënten.

The handgrip strength of geriatric patients can be measured when the patient is hospitalized. This article elaborates on the intrinsic and extrinsic factors which have a direct or indirect influence on handgrip strength. For the best results the tests need to be taken in the best circumstances with attention to individual differences and the age of the patient. Handgrip strength as determination of biological vitality is a key concept. Besides the physical characteristics there are many psychological factors (cognition, psyching-up, test attitude…) influencing the results. These are barely mentioned or not mentioned at all in the usual procedures. Research of handgrip strength testing theories is mostly focused on young, healthy adults and less on elderly patients. The main goal of this article is stimulating experimental research on the measurement of handgrip strength with elderly people and involving them more actively with the procedure. It is not enough to acquire insight in function and predicting characteristics of handgrip strength. Next to the aiming for the best test performance is 'working interactively with elderly patients' a goal on itself in the modern vision of health care.

[Nutritional assessment in oncogeriatrics]. / Nutritionele screening bij de oncogeriatrische patient.

Geriatric patients are not defined by their age but by their general profile. Ageing is characterized by loss of organ function together with a reduced capability for adapting to changes in the environment (loss of homeostatic mechanisms) leading to frailty. In the older patient with cancer, there can be problems of dietary intake next to the effects of ageing per se. On top of this situation, the deleterious effects of the inflammatory processes induced by the tumour are superimposed. When these changes are translated into nutritional concepts, it is clear that, in the older cancer patient, there is a strong overlap of starvation, sarcopenia, and cachexia. Nutritional assessment should be part of the routine preliminary evaluation of the older oncology patient. Difference should be made between assessment of risk and actual nutritional status, which should be assessed with specific malnutrition indices. Body weight assessment with specific attention to unintended weight loss is essential in this evaluation. One should recognise the fact that body mass index (BMI) should be interpreted with caution, but that a low value for BMI still heralds an increased malnutrition risk. This increased alertness for nutritional problems has a lot to offer in the willingness for early intervention. The nutritional assessment, however, must be framed in a larger comprehensive geriatric assessment addressing several functional domains.

[A screening tool to identify older people at risk of adverse health outcomes at the time of hospital admission]. / Een screeningsinstrument om de geriatrische liaison in het ziekenhuis op te starten: de Voorlopige indicator voor Plaatsing (VIP).

The proportional increase of the ageing population results in an ever growing percentage of elderly among hospitalised patients. Older patients have complex medical, social and psychological problems that could benefit from coordinated care or case management. Identification of high-risk older adults is mandatory to initiate a liaison geriatric management program. A simple screening tool is presented to identify older people at the time of admission who are at increased risk of adverse health outcomes. The instrument was validated during a period of 6 months when all (n = 618) older adults (> 70 year) hospitalised in non-geriatric departments of a general hospital were screened. This "Variable Indicative of Placement risk" (VIP) shows a good sensitivity (81%) and specificity (86%) and has a high Negative Predictive Value (97%). Furthermore, it shows a significant positive correlation with the length of stay (p < 0.001). The questionnaire turned out to be a very useful tool in the emergency department as well as in other wards because it probes premorbid frailty components with three simple questions. Due to its simplicity a nurse without geriatric training can complete it. Patients who are not at risk of an adverse outcome are easily recognised. A positive score indicates loss of functional independence and a risk of increased length of stay. Further geriatric assessment and intervention seem then appropriate.

The relationships between the cortisol responses to dexamethasone and to L-5-HTP, and the availability of L-tryptophan in depressed females.

In order to investigate the relationships between the hypothalamic-pituitary-adrenal (HPA)-axis activity, the central serotonergic neurotransmission, and the peripheral metabolism of l-tryptophan (L-TRP), the authors measured the following: the postdexamethasone cortisol values, the cortisol responses to 125 mg 5-hydroxy-L-tryptophan (L-5-HTP) orally, and the total L-TRP/competing amino acids (CAA) ratio in 64 depressed females. Severely depressed females showed significantly lower values for L-TRP/CAA, significantly higher postdexamethasone cortisol values, and cortisol responses to L-5-HTP as compared with minor depressives. Dexamethasone nonsuppressors showed significantly lower L-TRP/CAA values as compared with suppressors. The cortisol responses to dexamethasone were significantly and negatively correlated with the availability of L-TRP. The cortisol responses to L-5-HTP were not related to either the availability of L-TRP or to the postdexamethasone cortisol values.

Effects of dexamethasone on the availability of L-tryptophan and on the insulin and FFA concentrations in unipolar depressed patients.

Several authors have shown that the availability of L-tryptophan (L-TRP) in the serum is lower in patients with major depression than in controls. It has recently been reported that the administration of a dose of dexamethasone sufficient to cause cortisol suppression also caused significant decrements in the availability of L-TRP. In order to elucidate the putative pathophysiological mechanisms underlying this decreased L-TRP disposition, the authors examined 37 depressed women categorized according to the DSM-III. L-TRP, the sum of five competing amino acids (CAA), the L-TRP/CAA ratio, and insulin and free fatty acid (FFA) levels were determined both before and after oral administration of 1 mg dexamethasone. The availability of L-TRP was significantly lower in depressed women with melancholia compared with simple major and minor depressives. The baseline disposal of L-TRP was related neither to insulin nor to FFA concentrations Dexamethasone administration significantly reduced the L-TRP and L-TRP/CAA values and increased FFA and insulin levels. Postdexamethasone L-TRP and FFA levels were significantly and positively correlated.

Creatinine arm index as alternative for creatinine height index.

Nutritional assessment of elderly people is limited due to a lack of age-corrected standards. The objective of this study was to develop a new, more age-independent index for nutritional assessment by correcting the creatinine height index (CHI) for the age-induced changes in its variables. This might improve the differentiation between physiological reduction in muscle mass in elderly people and the changes induced by malnutrition. Seventy-four elderly and 100 young healthy volunteers were compared by anthropometric and biochemical-assessment variables. From the high correlation between total arm length and body length (r = 0.86; P less than 0.001) and the use of an alternative formula to calculate ideal body weight (IBW) from height and wrist circumference, a relatively age-independent estimate of IBW was determined. Creatinine arm index, as an adapted index of CHI, is proposed based on this age-independent IBW estimation and a specific creatinine coefficient for different age groups.

Biological heterogeneity of melancholia: results of pattern recognition methods.

In this study, we have measured the following biological variables in 78 depressed inpatients: adrenocorticotrophic hormone (ACTH) responses to corticotropin releasing factor (CRH: 100 micrograms intravenously), postdexamethasone cortisol and ACTH values, and circulating concentrations of L-tryptophan (L-TRP). Patients were categorized according to the DMS-III as (1) minor depression, (2) simple major depression, and (3) major depression with melancholia/psychotic features. By means of various pattern recognition methods, we determined whether these diagnostic groups constitute discrete biological classes or form relevant stages (i.e., continuous categories) in a continuum of progressing biological dysfunction. We established that unipolar depression constitutes one biological continuum characterized by a progression of lower CRH-induced ACTH responses, lower L-TRP levels, and higher postdexamethasone cortisol and ACTH values along the diagnostic spectrum. However, the biological differences in these markers between melancholia and minor depression are quantitatively prominent to the extent that they become qualitative. These findings support the biological heterogeneity hypothesis of melancholia. Simple major depression is a heterogeneous class with regard to the biological markers employed.

The decreased availability of L-tryptophan in depressed females: clinical and biological correlates.

1. The plasma levels of L-tryptophan (L-TRP) and the sum of five competing amino acids (CAA) namely tyrosine, phenylalanine, valine, leucine, isoleucine, were determined in 79 depressed females categorized according to the DSM-III. 2. In these patients the authors measured several parameters known to affect the availability of the above amino acids, i.e. triidothyronine (FT3) and thyroxine (FT4), vanilylmandelic acid (VMA), noradrenaline and adrenaline in 24 hr urine, the sex hormonal and nutritional state. 3. The 1 mg dexamethasone suppression test was performed and the pre and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) levels were determined at 8 a.m. 4. L-TRP and the ratio L-TRP/CAA were significantly lower in severely depressed females (296.X3, 296.X4) as compared with minor (300.40, 309.00) and simple major depressives (296.X2). The ratio L-TRP/CAA performed well as a clinical tool separating melancholic from minor depression. 5. FT3, FT4, VMA and noradrenaline were significantly increased in the severely depressed females, but these data did not correlate with the availability of L-TRP. Neither baseline cortisol nor the sex hormonal, nor the nutritional state related to the L-TRP data. The ratio L-TRP/CAA was significantly and negatively correlated with the postdexamethasone cortisol and ACTH values.

Disturbances in acute phase plasma proteins during melancholia: additional evidence for the presence of an inflammatory process during that illness.

1. Leukocyte enumeration through flow cytometry has revealed that severe depression may be accompanied by a systemic immune activation, indicative of an inflammatory response. The latter condition allegedly involves an important modification of acute phase plasma protein (APP) equilibrium. 2. In order to elucidate whether the state of severe depression is represented by alterations in APPs, the authors measured: alpha 1 antitrypsin (alpha 1 AT), alpha 2 macroglobulin (alpha 2 M), haptoglobin (Hp), alpha 1 acid glycoprotein (alpha 1 S), transferrin (Tf), complement component 4 (C4) and C-reactive protein (CRP). Interleukin-1-beta (II-1 beta) and interleukin-6 (II-6) circulating levels were determined. 3. Hyperhaptoglobinemia and hypotransferrinemia are hallmarks for major depression and depression per se, respectively. The disorders in Hp and Tf circulating levels are highly sensitive to (83%) and specific for (100%) melancholia as opposed to the healthy state. 4. Disorders in both APPs are significantly related to the absolute number of blood monocytes. 5. The authors observed a trend towards lower alpha 2M and higher alpha 1S values in severely depressed subjects. Severity of depression was significantly related to Hp and alpha 1S (both positively) and to alpha 2M and Tf (both negatively) values. 6. No significant intercategory differences in C4 could be established, whilst only a few subjects exhibited measurable CRP, II-1 beta and II-6 circulating levels. 7. Our findings may support the hypothesis that depression is accompanied by an inflammatory response.

A revised interpretation of the TRH test results in female depressed patients. Part I: TSH responses. Effects of severity of illness, thyroid hormones, monoamines, age, sex hormonal, corticosteroid and nutritional state.

Thyrotropin secreting hormone (TSH) levels were recorded in baseline conditions and 20 and 60 min after thyrotropin releasing hormone (TRH) administration (200 micrograms i.v.) in 60 depressed females categorized according to DSM-III. Basal TSH (TSHB) and peak TSH responses (TSHP) were measured using ultrasensitive RIA assays. The use of delta max TSH (TSHP minus TSHB) had no advantage over the use of TSHP since both factors were almost linearly (r = 0.98) correlated. TSHP was largely (72% of the variance) predicted by TSHB. It was suggested that TSHP consisted of two components. The first part was a relative deduction from TSHB. The second part was the newly proposed concept of the residual TSH (TRHR). This part was computed by partialling out the relative effects of TSHB on TSHP by means of regression analysis. In clinical practice two relevant factors should be used to evaluate the hypothalamic-pituitary-thyroid (HPT) axis: (1) TSHB reflecting the setpoint of the HPT axis and (2) TSHR reflecting the latent capacity of the HPT axis to respond to overwhelming amounts of exogenous TRH. TSHB was significantly reduced in severely depressed patients (296.X3, 296.X4) as compared with minor depressives (300.40, 309.00). These differences could be attributed to significantly increased free thyroxine levels and to noradrenergic hyperactivity in the severely depressed females. TSHR correlated significantly and negatively with follicle stimulating hormone levels, age, body mass index and the post-dexamethasone cortisol values. TSHR was significantly reduced in the post-menopausal state.

Suppressive effects of dexamethasone on hypothalamic-pituitary-thyroid axis function in depressed patients.

This study investigated the effects of dexamethasone (1 mg orally) on the function of the hypothalamic-pituitary-thyroid (HPT) axis. We determined pre- and post-dexamethasone thyroid-secreting hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse T3 and cortisol levels in 61 depressed inpatients. Dexamethasone had a pronounced suppressive effect on basal TSH and FT3 levels. It had a significant stimulating effect on rT3 levels. No differences were found between melancholic and minor depressives in the effects of dexamethasone on basal TSH, FT3 and rT3. Cortisol non-suppressors were characterized by less suppression of basal TSH values.

A revised interpretation of the TRH test results in female depressed patients. Part II: Prolactin responses. Relationships with sex hormones, corticosteroid state, age, monoamines and amino acid levels.

Prolactin (PRL) levels were recorded in baseline conditions and 20 and 60 min after thyrotropin releasing hormone (TRH) administration (200 micrograms i.v.) in 60 depressed females categorized according to DSM-III. Peak PRL responses were significantly (r = 0.727, P less than 0.001) correlated with their baseline levels. Consequently, the PRL responses to TRH were largely predicted by baseline PRL levels. It was suggested that the PRL responses to TRH consisted of two parts. The first component was a relative exaggeration of basal PRL, reflecting the basal activity of the hormone. The second component was the residual response. This part was estimated by partialling out the relative effects of basal PRL on peak PRL responses by means of regression analysis. Basal PRL and residual PRL responses were uninformative for major depression. Post-menopausal females showed significantly reduced basal PRL levels. There was a significant negative correlation between basal PRL and follicle stimulating hormone levels, age and post-dexamethasone cortisol values. The residual PRL responses were negatively correlated with free triiodothyronine levels and positively with serotonergic variables, i.e., 5-hydroxyindoleacetic acid in 24-h urine and the ratio L-tryptophan/competing amino acids.

Anthropometric and biochemical assessment of the nutritional state in depression: evidence for lower visceral protein plasma levels in depression.

Severe depression is characterized by anorexia and weight loss, symptoms that could endanger the patient's nutritional state. In order to investigate the nutritional state of depressed patients we determined the following in 113 healthy controls and depressed inpatients: (1) anthropometric variables such as body weight, ideal body weight (IBW), percentage of IBW, mean arm circumference, triceps skinfold thickness and arm muscle circumference, and (2) biochemical parameters such as albumin (Alb), prealbumin (Prealb), and transferrin (Tf). We were unable to detect any differences in the anthropometric parameters between healthy controls, minor and major depressed patients. Depressed patients exhibited significantly lower Alb and Tf levels than healthy controls. The drop in both plasma proteins was highly sensitive (72%) and specific (92%) for melancholia. These results may point towards the existence of a disorder in protein homeostasis or protein malnutrition without a marasmic component.

Impaired mitogen-induced lymphocyte responses and the hypothalamic-pituitary-adrenal axis in depressive disorders.

The lymphocyte stimulation responses to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed (PWM) were investigated in 30 hospitalized depressed women undergoing a dexamethasone suppression test (DST). Patients were classified according to DSM-III as having major depression with melancholia, without melancholia, and minor depression. The Hamilton Depression Rating Scale (HDRS) and the State-Trait Anxiety Inventory (STAI) were measured. Patients with major depression showed significantly decreased lymphocyte stimulation induced by PHA, Con A, and PWM as compared to those with minor depression. These differences could not be attributed to age, body weight, weight loss, total number of leukocytes, menopausal status, sleep disturbances, concomitant use of low-dosage benzodiazepines or length of drug-free period before testing. The group mean differences in lymphocyte stimulation counts were not affected by the severity of illness or the severity of state and trait anxiety. There were no significant differences in the lymphocyte responses to PHA, Con A, and PWM between DST non-suppressors and DST suppressors. No significant correlations were established between baseline and post dexamethasone cortisol values and the lymphocyte stimulation counts.

Influence of intravenous hyperalimentation on cardiac dimensions and heart function.

Eleven severe malnourished patients, mean age 34 yrs and mean weight 66 per cent of ideal body weight, were studied to evaluate the effect of intravenous hyperalimentation on the function and size of the heart. Left ventricular size and systolic function were measured before and after a mean weight gain of 19 per cent with electro, vector, echo and phonomechanographic methods. During hyperalimentation a statistically significant increase in left ventricular mass (p<0.01) was observed. Correction for body weight showed a parallel increase between the parameters and weight gain. Echocardiographic and phonomechanographic indexes of left ventricular systolic function remained unchanged. A decrease of the amplitude of the maximal spatial QRS vector was shown by vectocardiography. These results indicate that during intravenous hyperalimentation of the severe malnourished a proportional increase in cardiac size and mass occurs with preservation of the left ventricular systolic function.

A revised interpretation of postdexamethasone ACTH and cortisol findings in unipolar depressed females.

Baseline 8 a.m. adrenocorticotropic hormone (ACTH) and cortisol levels and the postdexamethasone ACTH/cortisol values at 8 a.m. and 4 p.m. were determined in 86 depressed females diagnosed using DSM-III criteria. Postdexamethasone ACTH and cortisol values were significantly correlated with their baseline levels. We have shown that regression analysis should be used to assess dexamethasone-induced changes as the residual ACTH and cortisol responses, with the relative effects of the baseline data on the hormone responses being partialed out. The residual ACTH and cortisol values were significantly increased in the most severely depressed females as compared to minor depressives. The residual ACTH responses were markedly correlated with the residual cortisol responses. Cortisol nonsuppression during a depressive episode appeared to be determined by an augmented ACTH escape from dexamethasone suppression. The residual ACTH and cortisol responses could prove to be the most sensitive reflection of the disorder in the negative feedback by dexamethasone on the pituitary. In clinical practice, the ratio ln (postdexamethasone ACTH): ln (basal ACTH) can be used, since this ratio is linearly correlated with the residual ACTH responses.

Regional cerebral blood flow in unipolar depression measured with Tc-99m-HMPAO single photon emission computed tomography: negative findings.

Recent studies have reported that patients with unipolar major depression may show a lower whole brain cerebral blood flow (CBF) and reduced regional CBF in frontal, temporal, and parietal lobes. The present study used single photon emission computed tomography (SPECT) with the CBF marker Tc-99m-hexamethylpropyleneamineoxine (HMPAO) to measure the cortical CBF of six individual regions of interest (ROIs), total ROI, and left or right hemispheric total ROI in 43 unipolar depressed subjects and 12 normal control subjects. There were no significant differences in the distribution of Tc-99m-HMPAO uptake into total ROI, right or left global ROI, prefrontal, motor frontal, parietal, temporal, visual cortex, or associative visual cortex between patients with melancholic depression, simple major depression, or minor depression and healthy control subjects. There were also no significant differences in the right-left distribution of uptake between the patients and the control subjects. Hypoperfusion was observed in motor frontal and parietal cortex of patients who had been taking benzodiazepines during the study period. It is concluded that cortical CBF, as assessed with Tc-99m-HMPAO SPECT, is relatively intact in the present sample of patients with severe depression.

Alterations in immune functions during normal aging and Alzheimer's disease.

It is thought that aging induces immune changes, which are related to the pathophysiology of Alzheimer's disease (DAT). In this study, the total number of leukocytes, white blood cell differentiation, mitogen-induced lymphocytic proliferation, neutrophil phagocytosis and superoxide release, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood cultures were comparatively investigated between healthy adults (range 22-45 years) and healthy elderly volunteers (range 70-91 years), and between DAT patients (range 56-94 years) and age-matched control subjects. Healthy elderly volunteers showed significantly lower phytohemagglutinin (PHA)-induced lymphocyte proliferation and percentage and absolute number of basophils than young volunteers. In normal volunteers, there were significant and negative correlations between age and the number of basophils. Patients with DAT showed a trend toward significantly higher PHA-induced lymphocyte proliferation and significantly decreased percentage and absolute number of large unstained cells than healthy volunteers. In DAT patients, the total number of leukocytes and the percentage and number of neutrophils were positively correlated with age. All other immune-inflammatory variables were not significantly altered either by the aging process or DAT. The present study suggests that aging and DAT may differently affect some immune variables.

Clinical subtypes of unipolar depression: Part III. Quantitative differences in various biological markers between the cluster-analytically generated nonvital and vital depression classes.

The hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-thyroid (HPT) axis, and the availability of L-tryptophan (L-TRP) to the brain were studied in their relationships to (1) 14 depressive symptoms measured by the Structured Clinical Interview for DSM-III-R--Patient Version (SCID) and (2) the cluster-analytically generated vital/nonvital classes. The following biological parameters were measured in 100 depressed females: free thyroxine (FT4), baseline thyroid stimulating hormone (TSH), predexamethasone and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) values, the circulating levels of total L-TRP, and the L-TRP/sum of competing amino acids ratio. We found that the psychopathological correlates of disorders in the HPA/HPT axis and of a decreased availability of L-TRP were vital symptoms, i.e., distinct quality of mood, nonreactivity, early morning awakening, anorexia-weight loss, and psychomotor disorders. There was no significant relationship between those biological markers and the nonvital symptoms of the SCID inventory for depressive symptoms. However, we did not validate our SCID clustering in vital and nonvital classes by qualitative differences in the biological variables. It was concluded that our nonvital/vital clusters should be regarded as continuous categories with regard to the biological markers studied; these clusters constitute relevant stages in the continuum of progressing biological dysfunction.

Morphometric changes in microvasculature in rat myocardium during malnutrition.

BACKGROUND: Because the interrelationship between the parenchymal cell population and the microvasculature is critical in normal organ function, the effects of starvation on rat myocardium were studied morphometrically with respect to the microvasculature. METHODS: Morphometric analytical studies were performed on myocardium of adult, female Wistar rats (groups of 5-7 rats) on fasting days 0, 1, 2, 4, 6, 8 and 10. Since cardiac muscle is a tissue with a high level of anisotropy, methods based on the concept of vertical planes were used to describe quantitative alterations in the rat myocardium both at the cellular and ultrastructural level. RESULTS: Morphometric analysis of electromicrographs of myocardium showed an increase in capillary density together with a decrease in capillary lumen cross-sectional area during starvation (p < .05). There was no significant change in volume fraction of the capillaries but surface density of the myocytes increased significantly (p < .01) and the diffusion distance for oxygen from the capillary lumen to the mitochondrion decreased (p < .01). CONCLUSIONS: Malnutrition alters the interrelationship between parenchyma and vascularization in the heart. This leads to a significant decrease of the diffusion distance for metabolites. This decrease of diffusion distance may improve cellular energy supply and offers a relative protection of the metabolism in the malnourished myocyte.