Bone in Anorexia.

Anorexia nervosa is a feeding disorder involving intentional weight loss. Restricted dietary intake leads to disturbed bone metabolism due to various factors, notably endocrine, that affect bone microarchitecture and incur risk of fracture. Mild to moderate anorexia shows a paradoxical increase in bone marrow adipose tissue, whereas severe forms show gelatinous transformation known as serous atrophy of bone marrow (SABM). Imaging assessment of the mineralized and adipose components uses several techniques: dual-energy X-ray absorptiometry, computed tomography, chemical shift magnetic resonance imaging (MRI), and single-voxel MR spectroscopy. SABM induces MRI bone signal disturbances that can be hard to interpret and may hinder visualization of the fracture line.

Cancer anorexia: hypothalamic activity and its association with inflammation and appetite-regulating peptides in lung cancer.

BACKGROUND: Energy homeostasis is mediated by the hypothalamus, whose inflammation-induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non-anorexic (NA) cancer patients, and in controls (C). METHODS: Lung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used. RESULTS: Thirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all-time points, anorexic patients showed lower hypothalamic activity compared with NA (P < 0.001) (T0: 585.57 ± 55.69 vs. 667.92 ± 33.18, respectively; T1: 536.50 ± 61.70 vs. 624.49 ± 55.51, respectively; T2: 556.44 ± 58.51 vs. 615.43 ± 71.50, respectively). Anorexic patients showed greater BOLD signal reduction during T0-T1 than NA (-8.5% vs. -6.80%, P < 0.001). Independently from the presence of anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL-1 and ghrelin (P < 0.001). CONCLUSIONS: Hypothalamic activity in A cancer patients is reduced respect to NA and responds differently to oral challenges. This suggests a central control of appetite dysregulation during cancer anorexia, before, and after oral intake.

Are patterns of bone loss in anorexic and postmenopausal women similar? Preliminary results using high resolution peripheral computed tomography.

This study intended to compare bone density and architecture in three groups of women: young women with anorexia nervosa (AN), an age-matched control group of young women, and healthy late postmenopausal women. Three-dimensional peripheral quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal radius, a technology providing measures of cortical and trabecular bone density and microarchitecture, was performed in the three cohorts. Thirty-six women with AN aged 18-30 years (mean duration of AN: 5.8 years), 83 healthy late postmenopausal women aged 70-81 as well as 30 age-matched healthy young women were assessed. The overall cortical and trabecular bone density (D100), the absolute thickness of the cortical bone (CTh), and the absolute number of trabecules per area (TbN) were significantly lower in AN patients compared with healthy young women. The absolute number of trabecules per area (TbN) in AN and postmenopausal women was similar, but significantly lower than in healthy young women. The comparison between AN patients and post-menopausal women is of interest because the latter reach bone peak mass around the middle of the fertile age span whereas the former usually lose bone before reaching optimal bone density and structure. This study shows that bone mineral density and bone compacta thickness in AN are lower than those in controls but still higher than those in postmenopause. Bone compacta density in AN is similar as in controls. However, bone inner structure in AN is degraded to a similar extent as in postmenopause. This last finding is particularly troubling.

Neuropsychology and anorexia nervosa. Cognitive and radiological findings.

INTRODUCTION: Research into neuropsychological impairments present in the patients suffering from anorexia nervosa (AN) has advanced considerably, in the past decades. It now provides neuropsychologists with a wide field of knowledge of the changes found in the cerebral and cognitive capabilities of these patients, as well as their reversible or static features, thereby yielding a characteristic profile of neuropsychological impairment in AN. DEVELOPMENT: We present a review updated to December 2010 of the results delivered by studies of both morphological and cognitive changes, providing us with an updated theoretical and practical framework for conducting future research. CONCLUSIONS: The studies to date show morphological and functional cerebral changes in the patients diagnosed with AN, but have yet to clarify whether these changes occur after the onset of the disease or if, as more recent research shows, they are one of its causes and could be the basis for a tendency toward developing anorexic symptomatology. Later studies show a neuropsychological network with impairments in the prefrontal and right parietal cortices as a characteristic feature, meaning that those capacities and their related cerebral areas would play major role in the onset and development of the illness. These studies have completely changed classic theories about AN.

Establishment of a new murine model of hypercalcemia with anorexia by overexpression of soluble receptor activator of NF-κB ligand using an adenovirus vector.

Hypercalcemia is a significant complication of certain human malignancies that is primarily caused by the release of calcium from bone due to marked bone resorption by osteoclast activation. Osteoclast differentiation and activation is mediated by receptor activator of NF-κB ligand (RANKL). Transgenic mice overexpressing murine soluble RANKL (sRANKL) that we generated previously exhibited severe osteoporosis accompanied with enhanced osteoclastogenesis, but never exhibited hypercalcemia. To analyze the relationship between serum concentration of sRANKL and hypercalcemia and generate a simple and quick hypercalcemia model, an adenovirus vector harboring murine sRANKL cDNA (Ad-sRANKL) was injected i.p. into male C57BL/6 mice. Sera were collected to measure the levels of sRANKL, calcium and biochemical markers of bone turnover. Food intake and body weight were measured every 3 or 4 days. All the mice were killed 2 weeks after the injection, and femurs were collected to measure bone structure and bone mineral density (BMD). Serum sRANKL and calcium increased, peaking on day 7. Food intake and body weight significantly declined on day 7. These results indicated that the mice had anorexia as a symptom of hypercalcemia. Increases in bone resorption and formation markers with a marked decrease in BMD were observed on day 14. These results reflect accelerated bone formation following activation of osteoclasts, indicating coupling between bone formation and resorption. In conclusion, a new murine model of hypercalcemia with anorexia was established by overexpressing sRANKL. This model would be useful for studies of hypercalcemia and coupling between bone formation and resorption.

Clinical application of Patlak plot CT-GFR in animals with upper urinary tract disease.

Glomerular filtration rate (GFR), an important parameter of renal function, is difficult to assess clinically. Serum creatinine and blood urea nitrogen measurements lack sensitivity, whereas radionuclide determination of GFR is not always available and requires postinjection patient isolation. GFR can be determined using computed tomography (CT), most commonly via Patlak plot analysis. Four adult cats, two adult dogs, and a foal underwent abdominal CT under general anesthesia for various diseases of the upper urinary tract. CT-GFR was measured with a single-slice dynamic acquisition and Patlak plot analysis. In five animals, the total CT-GFR appeared to be below normal, corresponding with mild (two animals) and moderate (two animals) increases of serum creatinine in four. In the two animals with normal or increased CT-GFR, serum creatinine was within the reference values. A significant negative logarithmic relationship was found between CT-GFR and serum creatinine values (P = 0.008; r2 = 0.75). No complications occurred during or following CT-GFR. CT examination provided clinically relevant information in 3/5 patients with possible ureteral obstruction and in 3/3 patients with suspected ureteral calculi. Single-slice dynamic CT-GFR was practical and provided clinically useful information in this small series of patients undergoing CT of the upper urinary tract. There was a significant relationship between CT-GFR and serum creatinine values, which supports the clinical potential of CT-GFR and justifies further investigation of this technique.

Simple diagnostic approach to childhood fecal retention using the Leech score and Bristol stool form scale in medical practice.

BACKGROUND AND AIM: To assess fecal retention, plain abdominal radiography is frequently used to complement the clinical history and physical examination, and three scoring systems have been proposed by Barr, Blethyn, and Leech on a single abdominal radiography. The aim of the present study was to find simple and useful diagnostic tools for an approach to fecal retention by correlation of the three scoring systems with the clinical characteristics. METHODS: This study included 76 children (5.6-15.4 years, male : female = 33:43) who presented with various gastrointestinal complaints and 20 healthy children from the years 2004-2008. Defecation characteristics, abdominal pain, anorexia and nausea, the Bristol stool form scale, and colonic transit time were studied. Plain abdominal radiographs were independently scored with the three scoring systems by a pediatrician and a radiologist. RESULTS: The k-value of the Leech score (0.912) between two of the observers was higher than the others (Barr 0.870 and Blethyn 0.670), and the correlation coefficients of the Leech scoring system by a pediatrician in relation to the colonic transit time (r = 0.861, P < 0.001) and the Bristol stool form scale (r = -0.818, P < 0.001) were highest in the constipated children. Furthermore, there were statistically significant associations between the Leech scoring system and the defecation frequency per week (r = -0.569 and -0.625 in two observers) or abdominal pain (r = 0.574 and 0.567). CONCLUSIONS: The Leech score and the Bristol stool form scale may be simple and useful diagnostic tools for pediatricians to access childhood fecal loading in outpatient clinics along with a thorough clinical history.

A functional neuroimaging study of appetite loss in Alzheimer's disease.

BACKGROUND: Alzheimer's Disease (AD) is frequently associated with changes in appetite. This study investigated the relationship between regional cerebral perfusion and appetite loss in AD. METHODS: 64 patients with possible or probable AD were characterized as being with (n=22) or without (n=44) appetite loss based on the Neuropsychiatric Inventory (NPI) Appetite subscale. 99mTc-ECD SPECT scans were coregistered to a standardized template in Talairach space generating mean ratios of uptake referenced to the cerebellum. Regions of interest (ROIs) included anterior cingulate cortex (ACC), middle mesial temporal cortex (MTC-m), inferior mesial temporal cortex (MTC-i), insula (INS), orbitofrontal cortex (OFC) and thalamus-hypothalamus (THAL). RESULTS: Backward stepwise logistic regression analysis of these ROIs showed hypoperfusion in the L-ACC (p=0.015) and L-OFC (p=0.015), relative sparing of perfusion in the R-ACC (p=0.010), R-OFC (p=0.010) and L-MTC-m (p=0.006), and greater anxiety (p=0.005) independently predicted loss of appetite (chi(2)=22.24, p=0.001, Nagelkerke R(2)=0.41). CONCLUSIONS: Hypoperfusion in the left anterior cingulate and left orbitofrontal cortices, and relative sparing of perfusion in the right anterior cingulate, right orbitofrontal and left middle mesial temporal cortices emerged as predictors of appetite loss in this sample of patients. These findings are consistent with impairments in the extrinsic motivational pathways of eating and impaired reward value of food as components of appetite loss in AD.

[Assessment of cortical brain blood flood by brain perfusion spect in patients with a diagnosis of eating behavior disorders]. / Valoración del flujo cortical cerebral mediante SPECT de perfusión cerebral en pacientes con diagnóstico de trastornos de la conducta alimentaria.

OBJECTIVE: To evaluate cortical brain blood flow by 99mTc-HMPAO SPECT in patients with Eating Disorders (ED): restrictive anorexia (RA) and purgative bulimia (PB). MATERIAL AND METHOD: The study included 7 women with diagnostic criteria of RA and 12 with PB. The control group was made up of 12 healthy women. All subjects underwent brain 99mTc-HMPAO SPECT. The SPECT studies were quantified, yielding semiquantitative indexes relating to cerebellar activity in different regions. Body dissatisfaction was assessed by means of the BSQ (Body Shape Questionnaire). The results were analyzed with the ANOVA variance and had a statistical significance of p < 0.05. RESULTS: Mean BSQ scores were 98.28 (range 71-159) in the RA group, 145.05 (range 73-191) in the PB group, and 57.4 (range 37-88) in the control group. All patients in the sample (i.e., both RA and PB) showed global cerebral hypoperfusion versus the controls, although the difference only reached statistical significance in the RA group in the left parietal lobe (p = 0.02) and in the right (p = 0.004) and left temporal lobes (p = 0.015). In the PB group, the significantly hypoperfused regions were the right (p < 0.001) and left (p = 0.008) superior frontal lobe, the right inferior frontal lobe (p = 0.042), the right (p = 0.042) and left (p = 0.002) parietal lobes, and the right temporal lobe (p = 0.002). CONCLUSION: The results obtained showed that patients with ED had cerebral hypoperfusion compared with healthy subjects. This pattern is common in parietotemporal regions for both PB and AR although with temporal and parietal predominance in RA and PB, respectively. In addition, patients with PB had frontal region involvement.

Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer.

Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.

Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11c]raclopride.

BACKGROUND: Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). METHODS: To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [(11)C]raclopride was used to assess DA D2/D3 receptor binding. RESULTS: The women who were recovered from AN had significantly higher [(11)C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. CONCLUSIONS: These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.

Changes in cerebral blood flow in bulimia nervosa.

Bulimia nervosa is an eating disorder of which characterized psychopathological symptoms are a recurrent episode of binge eating. The changes in cerebral blood flow (CBF) in a patient with bulimia nervosa between his or her different eating phases are presented. CBF was measured quantitatively by means of single photon emission computed tomography using I-123 N-isopropyl-p-iodoamphetamine. CBF of the global brain during a binge-eating phase was higher than that during an anorexic state phase. In the anorexic state, the CBF in the temporal, parietal, and occipital lobes on the right side was lower than that on the left side. In the binge-eating state, a lack of laterality between the right and left cerebral hemispheres was found. This finding suggests that cerebral activity differs between the two phases, and that asymmetry is dependent of the eating state.

Changes in ultrasound appearance of the internal female genital organs during treatment for eating disorders.

OBJECTIVE: To confirm that changes of the internal female genital organs in patients with eating disorders can be detected with ultrasound and that successive normalization can be followed during treatment. STUDY DESIGN: Thirty-five women with the diagnoses of eating disorders were examined with ultrasound while undergoing psychiatric treatment. The endometrial thickness and ovarian volume were measured. The sonographic picture of the ovaries was classified in four classes. RESULTS: Bulimics had changes of their ovaries in spite being of normal weight. After psychiatric treatment and a normal diet, the ovaries and the bleeding pattern normalized without a change in body weight. In anorectics, undetectable ovaries or ovaries without follicles were associated with low body mass index (BMI), but multifollicular ovaries or presence of a dominant follicle and ovarian volume had no clear relation to BMI. The endometrial thickness correlated with BMI. CONCLUSION: Ovarian morphology appeared more important than ovarian size. Changes of the ovaries appeared more related to eating patterns than to BMI. Eating disorders should be considered in women with bleeding disorders. Ultrasound examination can contribute to the differential diagnosis.

Pelvic ultrasound scanning of the ovaries in adolescent anorectic patients at low weight and after weight recovery.

In sixteen adolescent anorectic inpatients with secondary amenorrhea pelvic ultrasound examination of the ovaries was performed at lowest weight and after weight recovery. The outcome was assessed six months later at follow-up, assigning the patients to the categories of good, intermediate and poor outcome according to the modified Morgan and Russell criteria. At lowest weight all patients' ovaries were smaller than expected for age. After weight recovery the good outcome group had mature and fully developed ovaries whereas the ovarian morphology of patients with poor outcome remained prepubertal. The ovarian volume in the good outcome group was significantly higher than in the poor outcome group. From a threshold BMI of 17.8 upwards we observed a positive linear correlation between BMI and ovarian volume. At BMI 18 the probability for recovered ovaries was 53% rising to 82% at BMI 19.8, which was the highest noting in our study. Nevertheless, we could not find a clear cut-off BMI for definite prediction of recovered ovaries. Therefore, in patients with anorexia nervosa pelvic ultrasound is a very suitable method for determining the target weight required for recovery of ovarian function and resumption of menses. Normalized ovaries indicate favourable outcome and physical recovery.