An insulinoma presenting with hypochondriac delusions and food refusal

ABSTRACT The authors report a case of a 68-year-old man with an unrecognized insulinoma manifesting with neuropsychiatric symptoms. For two years, he presented with unspecified behavior changes, autonomic and neuroglycopenic symptoms, which led him to be misdiagnosed with a neurologic and psychiatric disorder before the insulinoma was recognized. Following neurological alterations in context of hypoglycemia, subsequent to longstanding food refusal, he was admitted in the psychiatric ward. Despite good global response and normal food intake, hypoglycemic episodes were still occurring and led to a careful evaluation which permitted the definitive diagnostic. This case highlights the diagnostic difficulties of medical disorders presenting with clinical features overlapping neurological and psychiatric syndromes. It also reflects the diagnostic difficulties in rare clinical entities, particularly in patients previously followed in psychiatry and underlines the need for a constant dialogue and updating of clinicians

Behavioral and Psychological Symptoms of Dementia

Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors occurring in subjects with dementia. BPSD constitute a major component of the dementia syndrome irrespective of its subtype. They are as clinically relevant as cognitive symptoms as they strongly correlate with the degree of functional and cognitive impairment. BPSD include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite changes. It is estimated that BPSD affect up to 90% of all dementia subjects over the course of their illness, and is independently associated with poor outcomes, including distress among patients and caregivers, long-term hospitalization, misuse of medication, and increased health care costs. Although these symptoms can be present individually it is more common that various psychopathological features co-occur simultaneously in the same patient. Thus, categorization of BPSD in clusters taking into account their natural course, prognosis, and treatment response may be useful in the clinical practice. The pathogenesis of BPSD has not been clearly delineated but it is probably the result of a complex interplay of psychological, social, and biological factors. Recent studies have emphasized the role of neurochemical, neuropathological, and genetic factors underlying the clinical manifestations of BPSD. A high degree of clinical expertise is crucial to appropriately recognize and manage the neuropsychiatric symptoms in a patient with dementia. Combination of non-pharmacological and careful use of pharmacological interventions is the recommended therapeutic for managing BPSD. Given the modest efficacy of current strategies, there is an urgent need to identify novel pharmacological targets and develop new non-pharmacological approaches to improve the adverse outcomes associated with BPSD

Tympanoplasty in children: A review of 91 cases

OBJECTIVES: There is a marked diversity in the reported success rates for achieving an intact tympanic membrane following tympanoplasty. Controversy exists about the factors thought to influence surgical outcome. These facts have important implications for the selection of patients who would benefit the most. This study reviews the factors thought to determine the anatomical and functional success of tympanoplasty in children. MATERIALS AND METHODS: Retrospective study of the anatomical and functional results of 91 tympanoplasties performed in children. Age, gender, size and site of perforation, status of operated and contralateral ear, underlying cause of the perforations, surgical technique, pre-operative and post-operative hearing levels, post-operative follow-up time and post-operative complications were recorded. We divided our population into two groups according to the expected eustachian tube maturity (younger group (N=24): ≤10 years old, older group (N=67): >10 years old). All patients were evaluated in terms of anatomical and functional outcome and complications. RESULTS: Anatomical success was achieved in 85.7% and functional success was 76.9% after a mean follow-up of 25.6 ± 17.1 months. Anatomical success (intact tympanic membrane) was achieved in 83% of younger vs 87% of older patients (p=n.s.). Functional (air bone gap closure) success was 75% in the younger group vs 78% in the older group (p=n.s.). There were no significant differences in post-operative gain at different frequencies (500, 1000, 2000 and 3000 Hz) between the two groups. A previous adenoidectomy in children older than 10 years seems to be an independent predictor of functional success The incidence of minor and major complications were 29% in patients aged ≤10 and 21% in those older than 10 (p=n.s.). We report 12.9% minor post-operative complications in successful cases: injury to the chorda tympani nerve (5.7%), wound infection (2.9%), otitis externa (2.9%) and transient vertigo (1.4%). Among the 21 reperforations observed, 92.3% occurred before 1 year. CONCLUSIONS: This study shows that tympanoplasty is a valid treatment modality for tympanic membrane perforation in the pediatric population. A tympanic membrane perforation can be closed at any age. There is no age limit below which perforation should not be closed. A previous adenoidectomy in children older than 10 years seems to be an independent predictor of functional success

The neuroinflammatory hypothesis of delirium

Delirium is a neuropsychiatric syndrome characterized by a sudden and global impairment in consciousness, attention and cognition. It is particularly frequent in elderly subjects with medical or surgical conditions and is associated with short- and long-term adverse outcomes. The pathophysiology of delirium remains poorly understood as it involves complex multi-factorial dynamic interactions between a diversity of risk factors. Several conditions associated with delirium are characterized by activation of the inflammatory cascade with acute release of inflammatory mediators into the bloodstream. There is compelling evidence that acute peripheral inflammatory stimulation induces activation of brain parenchymal cells, expression of proinflammatory cytokines and inflammatory mediators in the central nervous system. These neuroinflammatory changes induce neuronal and synaptic dysfunction and subsequent neurobehavioural and cognitive symptoms. Furthermore, ageing and neurodegenerative disorders exaggerate microglial responses following stimulation by systemic immune stimuli such as peripheral inflammation and/or infection. In this review we explore the neuroinflammatory hypothesis of delirium based on recent evidence derived from animal and human studies

The Cholinergic System and Inflammation: Common Pathways in Delirium Pathophysiology

OBJECTIVES: To investigate whether delirium is associated with an unbalanced inflammatory response or a dysfunctional interaction between the cholinergic and immune systems. DESIGN: Cohort observational study. SETTING: General hospital orthopedic ward. PARTICIPANTS: One hundred one individuals aged 60 and older with no previous cognitive impairment undergoing elective arthroplasty. MEASUREMENTS: Incidence of postoperative delirium, plasma cholinesterase activity (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) and inflammatory mediators (C-reactive protein (CRP), interleukin (IL)-1 beta, tumor necrosis factor alpha, IL-6, IL-8, IL-10) before and after surgery. RESULTS: Thirty-seven participants developed postoperative delirium and had greater production of CRP and proinflammatory to anti-inflammatory ratio after surgery. In participants with delirium, but not in controls, preoperative levels of plasma cholinesterase activity correlated with ΔCRP (AChE: ρ = 0.428, P = .008 and BuChE: ρ = 0.423, P = .009), ΔIL-6 (AChE: ρ = 0.339, P = .04), and ΔP/A ratio (AChE: ρ = 0.346, P = .04). CONCLUSION: Delirium was associated not only with an unbalanced inflammatory response, but also with a dysfunctional interaction between the cholinergic and immune systems. Comprehensive understanding of the relationship between the cholinergic and immune systems is crucial to developing new insights into delirium pathophysiology and novel therapeutic intervention

Low preoperative plasma cholinesterase activity as a risk marker of postoperative delirium in elderly patients.

BACKGROUND: delirium is a frequent neuropsychiatric syndrome affecting medical and surgical elderly patients. Cholinergic dysfunction has been implicated in delirium pathophysiology and plasmatic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities are suppressed in patients with delirium. In this cohort study, we investigated whether these changes emerge during delirium or whether they are present before its onset. METHODS: plasma activities of AChE and BuChE were measured pre- and postoperatively in consecutive patients ≥60 years old undergoing elective total hip replacement surgery. In addition to a comprehensive clinical and demographic baseline evaluation, venous blood samples were collected from each subject in the morning of hospital admission's day and in the morning of the first postoperative day. Delirium was screened daily with confusion assessment method (confirmed with diagnostic and statistical manual of mental disorders (DSM-IV)-TR). RESULTS: preoperatively, plasma esterase activity was significantly lower in patients who developed delirium compared with the remaining subjects. Following surgery BuChE activity was lower in the delirium group but this difference disappeared after controlling for preoperative values. Plasma cholinesterase activity correlated positively with calcium and haemoglobin and negatively with total bilirubin and international normalised ratio. CONCLUSION: plasma cholinesterase activity can be a useful candidate biomarker to identify subjects at greater risk of developing postoperative delirium

The Stress Response to Surgery and Postoperative Delirium: Evidence of Hypothalamic—Pituitary—Adrenal Axis Hyperresponsiveness and Decreased Suppression of the GH/IGF-1 Axis

Introduction: The aim of this study is to determine whether postoperative delirium is associated with dysregulation of hypothalamic—pituitary—adrenal and growth hormone/insulin-like growth factor 1 (GH/IGF-1) responses following acute systemic inflammation. Methods: Plasma levels of cortisol, IGF-1, C-reactive protein, interleukin (IL)-6, IL-8, and IL-10 were measured before and after surgery in 101 patients 60 years without dementia undergoing elective hip arthroplasty. Participants were assessed with confusion assessment method and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) postoperatively and 37 patients fulfilled the DSM-IV-TR criteria for delirium. Results: Preoperative plasma cortisol levels were similar in delirium and nondelirium groups (405.37+189.04 vs 461.83+219.39; P ¼ .22). Participants with delirium had higher postoperative cortisol levels (821.67 + 367.17 vs 599.58 + 214.94; P ¼ .002) with enhanced postoperative elevation in relation to baseline (1.9- vs 1.5-fold; P ¼ .004). The plasma levels of IGF1 did not differ in delirium and nondelirium groups before (18.12 + 7.58 vs 16.8 + 7.86; P ¼ .477) and following surgery (13.39 + 5.94 vs 11.12 + 6.2; P ¼ .639), but the levels increased in relation to baseline more frequently in patients who developed delirium (24.3% vs 7.8%; P ¼ .034). The magnitude of postoperative cortisol elevation correlated with DIL-6 (P ¼ .485; P ¼ .002), DIL-8 (P ¼ .429; P ¼ .008), and DIL-10 (P ¼ .544; P < .001) only in patients with delirium. Conclusions: Hypothalamic—pituitary—adrenal axis hyperresponsiveness and a less frequent suppression of the GH/IGF-1 axis in response to acute stress are possibly involved in delirium pathophysiology

Ethoprophos fate on soil–water interface and effects on non-target terrestrial and aquatic biota under Mediterranean crop-based scenarios

The present study aimed to assess the environmental fate of the insecticide and nematicide ethoprophos in the soil–water interface following the pesticide application in simulated maize and potato crops under Mediterranean agricultural conditions, particularly of irrigation. Focus was given to the soil–water transfer pathways (leaching and runoff), to the pesticide transport in soil between pesticide application (crop row) and non-application areas (between crop rows), as well as to toxic effects of the various matrices on terrestrial and aquatic biota. A semi-field methodology mimicking a “worst-case” ethoprophos application (twice the recommended dosage for maize and potato crops: 100% concentration v/v) in agricultural field situations was used, in order to mimic a possible misuse by the farmer under realistic conditions. A rainfall was simulated under a slope of 20° for both crop-based scenarios. Soil and water samples were collected for the analysis of pesticide residues. Ecotoxicity of soil and aquatic samples was assessed by performing lethal and sublethal bioassays with organisms from different trophic levels: the collembolan Folsomia candida, the earthworm Eisenia andrei and the cladoceran Daphnia magna. Although the majority of ethoprophos sorbed to the soil application area, pesticide concentrations were detected in all water matrices illustrating pesticide transfer pathways of water contamination between environmental compartments. Leaching to groundwater proved to be an important transfer pathway of ethoprophos under both crop-based scenarios, as it resulted in high pesticide concentration in leachates from Maize (130 µg L−1) and Potato (630 µg L−1) crop scenarios, respectively. Ethoprophos application at the Potato crop scenario caused more toxic effects on terrestrial and aquatic biota than at the Maize scenario at the recommended dosage and lower concentrations. In both crop-based scenarios, ethoprophos moved with the irrigation water flow to the soil between the crop rows where no pesticide was applied, causing toxic effects on terrestrial organisms. The two simulated agricultural crop-based scenarios had the merit to illustrate the importance of transfer pathways of pesticides from soil to groundwater through leaching and from crop rows to the surrounding soil areas in a soil–water interface environment, which is representative for irrigated agricultural crops under Mediterranean conditions.This studywaspartlysponsoredbytheEuropeanFundfor Economic andRegionalDevelopment(FEDER)throughthePro- gram OperationalFactorsofCompetitiveness(COMPETE)and National FundsthroughthePortugueseFoundationofScience and Technology(Ph.D.granttoSaraLeitão – SFRH/BD/42306/2007, Ciência 2007 – POPH andQREN,andTerbAzineBiorem – PTDC/ AAC-AMB/111317/2009)