Hypothermia does not influence liver damage and function in a porcine polytrauma model.

BACKGROUND: Previous studies revealed evidence that induced hypothermia attenuates ischemic organ injuries after severe trauma. In the present study, the effect of hypothermia on liver damage was investigated in a porcine long term model of multi-system injury, consisting of blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shockMETHODS: In 30 pigs, a standardized polytrauma including blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shock of 45% of total blood volume was induced. Following trauma, hypothermia of 33∘C was induced for 12 h and intensive care treatment was evaluated for 48 h. As outcome parameters, we assessed liver function and serum transaminase levels as well as a histopathological analysis of tissue samples. A further 10 animals served as controls. RESULTS: Serum transaminase levels were increased at the end of the observation period following hypothermia without reaching statistical significance compared to normothermic groups. Liver function was preserved (p⩽ 0.05) after the rewarming period in hypothermic animals but showed no difference at the end of the observation period. In H&E staining, cell death was slightly increased hypothermic animals and caspase-3 staining displayed tendency towards more apoptosis in hypothermic group as well. CONCLUSIONS: Induction of hypothermia could not significantly improve hepatic damage during the first 48 h following major trauma. Further studies focusing on multi-organ failure including a longer observation period are required to illuminate the impact of hypothermia on hepatic function in multiple trauma patients.

Ab initio calculation of energy levels for phosphorus donors in silicon.

The s manifold energy levels for phosphorus donors in silicon are important input parameters for the design and modeling of electronic devices on the nanoscale. In this paper we calculate these energy levels from first principles using density functional theory. The wavefunction of the donor electron's ground state is found to have a form that is similar to an atomic s orbital, with an effective Bohr radius of 1.8 nm. The corresponding binding energy of this state is found to be 41 meV, which is in good agreement with the currently accepted value of 45.59 meV. We also calculate the energies of the excited 1s(T 2) and 1s(E) states, finding them to be 32 and 31 meV respectively.

Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model.

BACKGROUND: Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma. MATERIALS & METHODS: Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA. RESULTS: Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h. CONCLUSION: A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application.

A porcine polytrauma model with two different degrees of hemorrhagic shock: outcome related to trauma within the first 48 h.

BACKGROUND: An animal polytrauma model was developed, including trunk and extremity injuries combined with hemorrhagic shock and a prolonged post-traumatic phase. This could be useful for the assessment of different therapeutic approaches during intensive care therapy. METHODS: A standardized polytrauma including lung contusion, liver laceration and lower leg fracture was applied in 25 pigs. They underwent controlled haemorrhage either with a blood volume loss of 45 % and a median arterial pressure (MAP) <30 mmHg/90 min (group L, n = 15) or a 50 % blood loss of and an MAP <25 mmHg/120 min (group H, n = 10). Five non-traumatized pigs served as a control (group C). Subsequently, intensive care treatment was given for an observational period of 48 h. RESULTS: Both trauma groups showed signs of shock and organ injury (heart rate, MAP and lactate). The frequency of cardiopulmonary resuscitation (CPR) and lung injury was directly related to the severity of the haemorrhagic shock (CPR-group L: 4 of 15 pigs, group H: 4 of 10 pigs; Respiratory failure-group L: 3 of 13, group H: 3 of 9. There was no difference in mortality between trauma groups. CONCLUSION: The present data suggest that our model reflects the mortality and organ failure of polytrauma in humans during shock and the intensive care period. This suggests that the experimental protocol could be useful for the assessment of therapeutic approaches during the post-traumatic period.

[Cognitive and affective theory of mind in Lewy body dementia: A preliminary study]. / Théorie de l'esprit cognitive et affective dans la démence à corps de Lewy : une étude préliminaire.

INTRODUCTION: 'Theory of Mind' refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component), to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge no studies investigating theory of mind in dementia with Lewy Bodies (DLB) have been published. The aim of our study was to search theory of mind deficits in patients with DLB. METHODS: Seven patients with DLB (DLB group), at the stage of mild dementia or mild cognitive impairments, and seven healthy elderly adults (control group) were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition test to assess the cognitive component of theory of mind, and the Reading the Mind in the Eyes test for the assessment of affective component. RESULTS: We found a significant difference between the two groups for the Faux Pas test with an average score of 35.6 for the DLB group and 48.3 for the control group (P=0.04). Scores were particularly low in the DLB group for the last question of the test concerning empathy (42.9% versus 85%, P=0.01). There was not a significant difference between the two groups for the Reading the Mind in the Eyes test (P=0.077). DISCUSSION: This preliminary study showed early impairments of theory of mind in the DLB. The cognitive component seems more affected than the affective component in this pathology. This pattern is consistent with the pattern found in Parkinson's disease, but differs from other neurodegenerative diseases as Alzheimer's disease or frontotemporal lobe dementia. These patterns may help to differentiate DLB from these diseases. Further study is needed to confirm these results and to compare with other dementias.

Prediction of adverse drug reactions using decision tree modeling.

Drug safety is of great importance to public health. The detrimental effects of drugs not only limit their application but also cause suffering in individual patients and evoke distrust of pharmacotherapy. For the purpose of identifying drugs that could be suspected of causing adverse reactions, we present a structure-activity relationship analysis of adverse drug reactions (ADRs) in the central nervous system (CNS), liver, and kidney, and also of allergic reactions, for a broad variety of drugs (n = 507) from the Swiss drug registry. Using decision tree induction, a machine learning method, we determined the chemical, physical, and structural properties of compounds that predispose them to causing ADRs. The models had high predictive accuracies (78.9-90.2%) for allergic, renal, CNS, and hepatic ADRs. We show the feasibility of predicting complex end-organ effects using simple models that involve no expensive computations and that can be used (i) in the selection of the compound during the drug discovery stage, (ii) to understand how drugs interact with the target organ systems, and (iii) for generating alerts in postmarketing drug surveillance and pharmacovigilance.

RB1 and TP53 pathways in radiation-induced sarcomas.

The tumour suppressor genes, TP53 and RB1, and four genes involved in their regulation, INK4a, ARF, MDM2 and MDMX, were analysed in a series of 36 post-radiotherapy radiation-induced sarcomas. One-third of the tumours developed in patients carrying a germline mutation of RB1 that predisposed them to retinoblastoma and radiation-induced sarcomas. The genetic inactivation of RB1 and/or TP53 genes was frequently observed in these sarcomas. These inactivations were owing to an interplay between point mutations and losses of large chromosome segments. Radiation-induced somatic mutations were observed in TP53, but not in RB1 or in the four other genes, indicating an early role of TP53 in the radio-sarcomagenesis. RB1 and TP53 genes were biallelically coinactivated in all sarcomas developing in the context of the predisposition, indicating that both genes played a major role in the formation of these sarcomas. In the absence of predisposition, TP53 was biallelically inactivated in one-third of the sarcomas, whereas at least one allele of RB1 was wild type. In both genetic contexts, the TP53 pathway was inactivated by genetic lesions and not by the activation of the ARF/MDM2/MDMX pathway, as recently shown in retinoblastomas. Together, these findings highlight the intricate tissue- and aetiology-specific relationships between TP53 and RB1 pathways in tumorigenesis.

Arginase acts as an alternative pathway of L-arginine metabolism in experimental colon anastomosis.

L-Arginine is the substrate for the nitric oxide synthase (NOS) pathway that is essential for gastrointestinal wound healing. L-Arginine is also the substrate for the enzyme arginase which metabolizes L-arginine to ornithine and subsequently to proline and polyamines both known to interact in cell proliferation and collagen synthesis. Two distinct isoforms of arginase exist. The temporal expression of the L-arginine metabolism in experimental colon anastomosis was investigated. Male Lewis rats underwent laparotomy. A left-sided colotomy was performed and the colon reanastomosed using 6-0 prolene. Sham operation was performed in controls. On days 2, 5, 10, 14, and 28 after the surgery the anastomosis was excised. The tissue at the anastomosis (ANAST) as well as above and below the anastomosis (PDC) and from sham colon was harvested and analyzed for distinct arginase isoform I (AI) and arginase isoform II (AII) activity, protein and mRNA expression as well as immunohistochemistry. iNOS protein and mRNA expression were investigated in parallel. A mean of 3 to 4 separate rats were analyzed per time point. Statistical analysis was performed by student's t-test, significance was reached when P < 0.05. AI activity, protein, and mRNA expression were significantly upregulated at the anastomosis compared to sham controls and PDC colons at all time points. The maximum was achieved at days 10 to 14 after wounding, and decreased to baseline levels thereafter. Inflammatory cells stained positive for AI. AII protein was not detectable. However RT-PCR showed low baseline expression. iNOS expression was upregulated early but for a shorter time period after wounding and reverted quickly to undetectable levels. In anastomotic healing, AI upregulation suggests a prolonged metabolism of arginine via arginase to polyamines and proline to provide substrate for collagen synthesis and cell proliferation. The functional implication of this arginase pathway further needs to be elucidated.

Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women.

BACKGROUND: Urinary tract infections are common in elderly patients. Authors of non systematic literature reviews often recommend longer treatment durations (7-14 days) for older patients than for younger women, but the scientific evidence for such recommendations is not clear. OBJECTIVES: To determine the optimal duration of antibiotic treatment for uncomplicated symptomatic lower urinary tract infections in elderly women. SEARCH STRATEGY: We contacted known investigators and pharmaceutical companies marketing antibiotics used to treat urinary tract infections, screened the reference list of identified articles, reviews and books, and searched the following data bases: MEDLINE, EMBASE, CINAHL, Healthstar, Popline, Gerolit, Bioethics Line, The Cochrane Library, Dissertation Abstracts International, Index to Scientific & Technical Proceedings. SELECTION CRITERIA: All randomized controlled trials in which different treatment durations of oral antibiotics for uncomplicated symptomatic lower urinary tract infections in elderly women were compared. We excluded patients with fever or flank pain and those with complicating factors. Trials with treatment durations longer than 14 days or designed for prevention of urinary tract infection were also excluded. No language restriction was applied. DATA COLLECTION AND ANALYSIS: The quality of all selected trials was assessed and data extracted by the reviewers. Main outcome measures were persistence of urinary symptoms (short-term and long-term efficacy), effect on mental and functional status and adverse drug reactions. To compare the different treatment durations, we defined the following categories of duration: single dose, short course (3-6 days) and long course (7-14 days). Relative risk (RR) and 95% confidence intervals (CI) were calculated for each trial and outcome and were then combined using a random effects model. MAIN RESULTS: Thirteen trials were included in this review. Six trials compared single dose with short-term treatment (3-6 days), three studies single dose with long-term treatment (7-14 days) and four trials short-term with long term treatment. Eight trials also included younger patients, but provided a subgroup analysis for elderly women. The methodological quality of all trials was low. All trials reported results of bacteriological cure rate; less often clinical outcomes (e.g. improvement or cure of symptoms) were analyzed. Only five trials compared the same antibiotic given for a different length of time. We performed a separate analysis for these trials. The rate of persistent bacteriuria rate at short-term (two weeks post-treatment) was better in the longer treatment group (3-14 days) than in the single dose group (RR 1.84, 95% CI 1.18 to 2.86). However, the rate of persistent bacteria at long term and the clinical cure rate showed no statistically significant difference between the two groups. Patients showed a preference for single dose treatment (RR 0.73, 95% CI 0.66 to 0.88), however this was based on only one trial comparing the same antibiotic. The comparison of short (3-6 days) and longer treatments (7-14 days) did not show any significant difference, but the number of included studies and sample size were low. REVIEWER'S CONCLUSIONS: This review suggests that single dose antibiotic treatment is less effective but may be better accepted by the patients than longer treatment durations (3-14 days). In addition there was no significant difference between short course (3-6 days) versus longer course (7-14 days) antibiotics. The methodological quality of the identified trials was poor and the optimal treatment duration could not be determined. We therefore need more appropriately designed randomized controlled trials testing the effect, - on clinical relevant outcomes -, of different treatment durations of a given antibiotic in a strictly defined population of elderly women.

Microdissection techniques for cancer analysis.

One difficulty in studying molecular changes of tumours has been the inability to isolate DNA and RNA from a homogeneous cell population. The combination of several new technologies should help overcome these hurdles. Microdissection is a technique for rapid and easy procurement of a pure cellular subpopulation away from its complex tissue milieu. Laser-assisted microdissection has recently been identified as a quick, simple and effective method by which microdissection of complex tissue specimens can be routinely performed for molecular analysis. With the advent of laser microdissection, cDNA libraries can be developed from pure cells obtained directly from stained neoplastic tissue, and microarrays of thousands of genes can now be used to examine gene expression in microdissected tumour tissue samples. This review will concentrate on the application of different microdissection techniques in the area of cancer research.

[Droperidol and dimenhydrinate alone or in combination for prevention of postoperative nausea and vomiting]. / Droperidol und Dimenhydrinat alleine und in Kombination zur Prophylaxe von Ubelkeit und Erbrechen in der postoperativen Phase.

BACKGROUND: Droperidol and dimenhydrinate are inexpensive antiemetic drugs. Droperidol, especially, has been studied extensively in the past, but there are no studies that used the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). Thus, the aim of this randomised controlled and double-blinded study was to evaluate the antiemetic efficacy and the side effects of such a combination therapy. METHODS: 240 inpatients undergoing ENT surgery under general anaesthesia were randomised to receive one of four antiemetic regimes: placebo, dimenhydrinate (1 mg x kg-1), droperidol (15 micrograms x kg-1), or the combination of both drugs (droperidol 15 micrograms x kg-1 + dimenhydrinate 1 mg x kg-1) was administered after induction of anaesthesia and repeated 6 hours after the first administration. For general anaesthesia a standardised technique including benzodiazepine premedication, propofol, desflurane in N2O/O2, vecuronium, and a continuous infusion of remifentanil was used. Postoperative analgesia and antiemetic rescue medication were standardised. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hours. The main goal of the study was to increase the number of patients who were completely free from PONV (chi 2-test with Fisher-Yates' correction). Furthermore, the severity of PONV was analysed using a standardised scoring algorithm. RESULTS: Data of 227 patients could be analysed. The incidence of patients who suffered from PONV was 41.3% (95%-confidence interval: 29-55%) in the placebo-group. Dimenhydrinate alone reduced PONV to 34.5% (95%-CI: 22-48%). This marginal effect and the effect of droperidol (PONV: 26.4% (95%-CI: 15-40%)) could not be proven statistically, since the power of the study was too small. The combination of both drugs decreased PONV to 19.6% (95%-CI: 10-32%) and also reduced the severity of the symptoms to a clinically acceptable level. CONCLUSION: Dimenhydrinate failed to reduce the incidence and severity of PONV. The efficiency of droperidol given alone was within the ranges previously known from metaanalytic data. The combination of both drugs showed a moderate synergistic effect.

[Analgesic effects of topical opioids: are they effective?]. / Effet analgésique des opiacés en usage cutané: quelle est leur efficacité?

Recent research has revealed the presence of opioid receptors in inflamed peripheral tissues. This gives rise to the possibility of treating the pain caused by wounds with the advantage of reducing the secondary effects related to the use of opioids and at the same time rendering their use more efficacious. The theory of a peripheral analgesic action of opioids has been tested in a variety of situations, in particular in brachial plexus blocks and intra-articular injections. In addition, the analgesic effect of opioids has been tested by cutaneous application for various conditions but on only a limited number of patients. On the basis of these case reports, we cannot conclude that the peripheral use of opioids is efficacious and the topical use of opioids cannot be recommended unless done within the framework of a controlled clinical trial.

Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma.

Genome alterations of seven secondary tumors (five osteosarcomas, one malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring in the field of irradiation of patients treated for bilateral retinoblastoma have been studied. These patients were predisposed to develop radiation-induced tumors because of the presence of a germ line mutation in the retinoblastoma gene (RB1). Tumor cells were characterized by a high chromosome instability whereas microsatellites and minisatellites were found to be stable. In all tumors, the normal RB1 allele was lost with the corresponding chromosome 13, whereas the germ line mutated allele was retained. The two alleles of TP53 were inactivated, one by deletion of the short arm of chromosome 17, the other by mutation. As compared with non-radiation-induced tumors, the observed panel of TP53 mutations was uncommon with sites not recurrently found otherwise and a high rate of deletions (3/7). In these predisposed patients, the loss of the single normal allele of RB1 is rather due to the radiation-induced chromosome instability than a direct effect of ionizing radiation.

Midazolam sedation for upper gastrointestinal endoscopy in older persons: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: To investigate the benefits and risks of using midazolam for sedation during upper gastrointestinal endoscopic procedures in older persons. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: A 304-bed geriatric university hospital. PATIENTS: Sixty-five geriatric inpatients (mean age 84 +/- 7) undergoing gastroscopy. INTERVENTION: Sedation with either midazolam (30 microg/kg IV) or saline (placebo). All patients received supplemental oxygen during the procedure (2 L/minute). MEASUREMENTS AND RESULTS: Patients' recall of their tolerance to the exam (categorical scale) and pain score were significantly in favor of midazolam at 2 and 24 hours. Multivariate analysis at 2 hours showed that midazolam increased the probability of good tolerance (odds ratio (OR) = 19.3; 95% confidence interval (CI) 2.2-170.4, P = .008). Circumstantial amnesia occurred at 24 hours in 84% (midazolam) versus 27% (placebo) (P < .001). With midazolam, mean sedation time was 83 +/- 13 minutes and mean arterial pressure (MAP) was about 10 mm Hg lower without clinically significant hypotension. Hypoxemia (SaO2 < 92%) was more frequent in the midazolam group after endoscopy (44% vs. 18%, P = .033), but no major desaturation was observed. Cognitive function (Mini-Mental State Exam, MMSE) was similar before and 2 and 24 hours after the exam in both groups. Acute confusion was observed in two patients (1 midazolam, 1 placebo). In multivariate analysis, midazolam was associated with a higher risk of hypoxemia after endoscopy (OR = 3.5; 95% CI 1.1-10.8, P = .029) but not of confusion. CONCLUSIONS: Under adequate surveillance, the benefits in terms of tolerance to the procedure of low-dose midazolam for upper gastrointestinal endoscopic sedation outweigh the risks in older people.

What's the basis for treating infections your way? Quality assessment of review articles on the treatment of urinary and respiratory tract infections in older people.

OBJECTIVE: To assess the quality of readily available review articles on urinary and respiratory tract infections in older people. METHODS: Data sources were articles identified by MEDLINE search (1988-1998), review of the bibliographies of identified publications, textbooks from the library of a geriatric university hospital, and booklets with general guidelines on antibiotic therapy. Selection was made of review articles or book chapters about urinary and/or respiratory tract infections in older people that were readily available, ie, in Swiss medical libraries. Quality was assessed according to clinical applicability of the recommendations, methodology of the review, type of literature cited in the bibliography, and age of the population included in these reference articles. RESULTS: Only 13 of 29 (45%) review articles about urinary tract infections and seven of 29 (24%) articles about respiratory tract infections satisfied our criteria of applicability. Specifically, dosage, route of administration, and treatment duration were often not described. The overall methodological quality was low (mean score 1.9 +/- 1.0 on a scale of 9). No review specified the methods used to identify, select, and validate included information. Authors of the review articles quoted an important number of other review articles and only a small number of clinical trials. Less than one-quarter of these clinical trials actually comprised primarily an older population. CONCLUSIONS: Review articles on treatment of common infectious diseases in older people are often neither clinically applicable nor of good methodological quality. Therefore, more systematic review articles regarding treatment of older patients, as well as evidence-based practice guidelines, are needed.

DNA methylation and chromosome instability in lymphoblastoid cell lines.

In order to gain more insight into the relationships between DNA methylation and genome stability, chromosomal and molecular evolutions of four Epstein-Barr virus-transformed human lymphoblastoid cell lines were followed in culture for more than 2 yr. The four cell lines underwent early, strong overall demethylation of the genome. The classical satellite-rich, heterochromatic,juxtacentromeric regions of chromosomes 1, 9, and 16 and the distal part of the long arm of the Y chromosome displayed specific behavior with time in culture. In two cell lines, they underwent a strong demethylation, involving successively chromosomes Y, 9, 16, and 1, whereas in the two other cell lines, they remained heavily methylated. For classical satellite 2-rich heterochromatic regions of chromosomes 1 and 16, a direct relationship could be established between their demethylation, their undercondensation at metaphase, and their involvement in non-clonal rearrangements. Unstable sites distributed along the whole chromosomes were found only when the heterochromatic regions of chromosomes 1 and 16 were unstable. The classical satellite 3-rich heterochromatic region of chromosomes 9 and Y, despite their strong demethylation, remained condensed and stable. Genome demethylation and chromosome instability could not be related to variations in mRNA amounts of the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B and DNA demethylase. These data suggest that the influence of DNA demethylation on chromosome stability is modulated by a sequence-specific chromatin structure.

Minocycline-induced pericardial effusion.

OBJECTIVE: To describe a reversible hypersensitivity reaction characterized by pericardial effusion and acute mixed liver injury in a woman treated with minocycline. CASE SUMMARY: A 39-year-old white woman developed dyspnea and chest pain with pericardial effusion on echocardiography approximately 20 days after starting minocycline treatment. Additional manifestations consisted of eosinophilia and liver injury. No lung, skin, or joint involvement was noted; antinuclear antibody testing was negative. DISCUSSION: Minocycline has been associated with rare but severe hypersensitivity reactions and autoimmune disorders, generally involving the lungs, skin, or joints. We observed a patient with an unusual minocycline-induced reaction with pericardial effusion and acute mixed liver injury. The number of spontaneously reported cases in national and international databases indicates that minocycline-induced pericardial effusion is very rare as a main clinical manifestation. CONCLUSIONS: Clinicians should be aware of the possibility of pericardial effusion without lung, skin, or joint involvement as an adverse effect of minocycline.

[Susceptibility of the elderly patient to hyponatremia induced by selective serotonin reuptake inhibitors]. / Susceptibilité du sujet âgé à l'hyponatrémie induite par les inhibiteurs sélectifs du recaptage de la sérotonine.

Numerous spontaneous reports of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have followed the increased use of selective serotonin reuptake inhibitors (SSRI). It has been estimated that 1 in 200 patients treated per year developed SIADH, age and low body weight being particular risk factors. No clear gender effect has been detected when confounding factors such as body weight or antidepressant consumption are taken into account. Age-related susceptibility to hyponatraemia may be explained by physiological changes in renal and endocrine function. The high prevalence of polymedication and pluripathology in the elderly may be a contributing factor as well. To date, no study has demonstrated how SSRIs affect the regulation of fluid/sodium balance nor whether they have an independent effect on this regulation in depressed subjects.