Exercise tolerance in systemic sclerosis patients without pulmonary impairment: correlation with clinical variables.

OBJECTIVES: In systemic sclerosis (SSc) patients pulmonary vasculopathy (PV) is present in the early stage of disease and impairs dilation of affected pulmonary blood vessels, impeding pulmonary blood flow during exercise. Abnormal gas exchange findings were early investigated by cardiopulmonary exercise test (CPET). METHODS: A total of 34 female and 6 male [median age 49 (20-63) years] SSc patients with normal chest imaging and pulmonary function tests were enrolled. Twenty healthy controls age and sex matched [16 female and 4 male; median age 51 (35-73) years] were also recruited. All subjects underwent a full clinical examination, including a nailfold video capillaros copy (NVC). An incremental symptom-limited CPET was performed with estimation of minute ventilation (VE), workload (WR), peak oxygen uptake (pVO22), and ventilatory efficiency (VE/VCO2 slope). RESULTS: A reduced exercise tolerance (pVO2<80% of predicted) was documented in 18 out of 40 subjects (45%). Six out of 18 patients with a reduced exercise tolerance showed indirect signs of ventilation perfusion mismatch (VE/ VCO2 slope >34). Patients with digital ulcers (DUs) history showed VE/VCO2slope values significantly higher [31.4 (18-39.6)] than in patients without DUs history [26.9 (22-29.4)] (p<0.0001). VE/VCO2slope values also significantly differed between the three capillaroscopic groups: early [26.3 (18-29.4)], active [28 (26.8-39.6)], and late [32.9 (22.4-39)] (p<0.0001). A positive correlation was found between the VE/ VCO2slope and both Disease Activity Index (p<0.0001, r=0.59) and Disease Severity Scale (p<0.0001, r=0.73). CONCLUSIONS: In SSc patients without evidence of pulmonary and cardiac involvement, CPET might be useful in disclosing an early PV.

Defecatory disorders in anorexia nervosa: a clinical study.

BACKGROUND: Defecatory disorders in patients with eating disorders have been overlooked. We evaluated the prevalence and type of defecatory disorders in patients with anorexia nervosa. METHODS: The aim of our questionnaire-based study was to determine the prevalence of constipation and faecal incontinence (FI) in patients with anorexia nervosa attending our dedicated eating disorders outpatient clinics and whether length of illness and low body mass index (BMI) exacerbate both constipation and FI. The Wexner constipation score (WCS), Altomare's obstructed defecation score (OD score) and the faecal incontinence severity index (FISI) were used to evaluate constipation and incontinence. A WCS ≥5, OD score ≥10 and a FISI ≥10 were considered clinically relevant. RESULTS: Eighty-five patients (83 females; mean age 28 years ± 13) with anorexia nervosa (study group) and mean BMI of 16 ± 2 kg/m(2) (range 14-19 kg/m(2)) were studied. This group was compared to 57 healthy volunteers (control group) with mean BMI of 22 ± 3 kg/m(2) (range 20-27 kg/m(2)). In the study group, 79/85 (93%) patients suffered from defecatory disorders defined as at least one abnormal score, either WCS, OD score or FISI, compared to 7/57 (12%) controls (p < 0.001). Constipation (defined as WCS ≥5) was present in 70/85 (83%) patients with anorexia and in 7/57 (12%) controls (p = 0.001), while obstructed defecation syndrome (defined as OD score ≥10) was present in 71/85 (84%) patients with anorexia and 7/57 (12%) controls (p < 0.001). In patients with anorexia, the mean WCS score was 10 ± 5 standard deviation (SD) (3 ± 2 SD in controls; p < 0.001), and the mean OD score was 12 ± 4 SD (3 ± 4 SD in controls; p < 0.001). Overall, 62/85 (73%) patients with anorexia had FI defined as FISI score ≥10, and the mean FISI score in anorexia patients was 12 ± 9 SD. A combination of constipation and FI (either both WCS and FISI abnormal or both OD score and FISI abnormal) was present in 55/85 (64%) and 8/85 (9%) presented with FI alone. Moreover, all results are influenced by the severity of the disease measured by BMI and duration. The percentage of defecatory disorders rises from 75 to 100% when BMI is <18 kg/m(2) and from 60 to 75% when the duration of illness is ≥5 years (p < 0.001 and p = 0.021, respectively). CONCLUSIONS: Defecatory disorders are associated with anorexia nervosa and increased with the duration and severity of the illness.

Body composition phenotype: Italian Mediterranean Diet and C677T MTHFR gene polymorphism interaction.

OBJECTIVES: Strategies to improve weight maintenance are focused on considering the genetic makeup and its interaction with dietary intake, with the aim to identify vulnerable individuals that will benefit from a variety of more personalized dietary recommendations. The aim of the study was to examine the impact of the C677T MTHFR gene Polymorphism on body composition changes induced by a balanced hypocaloric Italian Mediterannean diet (IMD). SUBJECTS AND METHODS: Participation in the study included a complete screening of anthropometry and body composition by Dual-energy X-ray absorptiometry (DXA), and a genotyping for the C677T MTHFR polymorphism. 70 Italian Caucasian obese were enrolled and 56 of them completed the screening at baseline and 12 weeks after the nutritional intervention. RESULTS: T(+) carriers had a higher content of Total Body Fat (TBFat), and Lean (TBLean), reflecting on higher weight and BMI, than T(-) carriers. After IMD, the 28.6% and 71.4% of total subjects decreased weight and TBFat (Kg), respectively. The relative changes were: delta % = -9.09±3.85 for weight; delta % = -15.79±8.51 for TBFat; delta % = -3.80±5.60 for TBLean. The 5.3% of subjects who reached the end point of intervention, and the 8.9% who reduced TBFat (%) below the cut-off of preobesity, were T(-) carriers. A loss of TBLean (Kg) was observed in the 5.1% and 23.5% of T(-) and T(+) carriers. CONCLUSIONS: MTHFR genetic variations analysis would be an innovative tool for the nutritional assessment, in order to predict the therapeutic response of obese subjects, in terms of fat and lean mass loss.

Rapid and easy assessment of insulin resistance contributes to early detection of polycystic ovary syndrome.

AIMS: Polycystic ovary syndrome (PCOS) is frequently observed in women of reproductive age, and is associated with disturbances in both reproductive and metabolic function. Insulin resistance (IR) is key to the pathophysiology of PCOS, and early detection may improve outcomes in this patient group. Rapid and straightforward laboratory tests may contribute towards early detection. METHODS: A retrospective chart review of 185 women presenting for the first time to a gynecology clinic was carried out. Of this group, 77 met the inclusion criteria. The sample was divided according to insulin sensitivity (IS) given by the Matsuda Index, and the two groups were compared using correlation analysis. Furthermore, the sensitivity and specificity of the Matsuda, homeostasis model assessment of IR (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) indexes were compared. RESULTS: Although bodu mass index (BMI) was higher in the insulin resistant group than the insulin sensitive group, the mean age of the IR group was actually lower. HOMA-IR and QUICKI correlated well with the Matsuda index in both groups. The HOMA-IR test showed the highest sensitivity and specificity in the detection of IR when compared to the Matsuda Index, and no added benefit was derived from using a combination of both QUICKI and HOMA- 1R. CONCLUSIONS: In a group of 77 women diagnosed with PCOS, 49 (63.6%) had IR according to the Matsuda index. The HOMA-IR index, which is based on fasting serum insulin and glucose, correlated closely with the Matsuda index, indicating it may be a reliable substitute in the detection and subsequent early intervention required to improve outcomes in PCOS.

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Amenorrhea after weight recover in anorexia nervosa: role of body composition and endocrine abnormalities.

UNLABELLED: Hypothalamic amenorrhea in anorexia nervosa often precedes weight loss and may persist after re-feeding and restoration of a stable normal weight. AIM: To assess the rate of persistent amenorrhea in anorexia nervosa (AN) after re-feeding and the relations of this condition with body composition changes and other endocrine parameters. METHODS: A cohort of 250 female outpatients was studied to assess persistent amenorrhea prevalence after stable weight recovery. Among these, we selected 20 AN female patients (age 16.5-35), 10 with amenorrhea (group 1) and 10 with normal menses (group 2). We collected data such as age, age at menarche, age at onset of AN, actual body mass index (BMI) and at onset of AN, duration of disease. Physical activity has been evaluated as minute per day. The following data were obtained: prolactin, growth hormone, estradiol, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, free urinary cortisol, serum calcium and phosphates, urinary calcium, phosphaturia and alkaline phosphatase. Body composition was assessed with a dual energy x-ray absorptiometry (DEXA). RESULTS: Thirty-five patients (14%) over a cohort of 250 where still amenorrhoic after stable weight recovery. No significance was found in the evaluation of blood biochemical tests of the 2 groups. Free urinary cortisol was significantly higher in amenorrhoic patients (58.14+/-0.4 vs 15.91+/-9.5), p=0.02. The analysis of body composition has shown a percentage of fat of 22.23+/-5.32% in group 1 and of 26.03%+/-9.1% in group 2, respectively, showing no significant differences. Amenorrhoic patients carried on doing a significantly heavier physical activity than eumenorrhoic patients. CONCLUSIONS: An adequate body composition and a well represented fat mass are certainly a necessary but not sufficient condition for the return of the menstrual cycle. Such menstrual cycle recovery would probably need other conditions at present being studied and evaluated to occur, such as secretory patterns of leptin and its correlations with adrenal function.

Densitometric evaluation in women with anorexia nervosa.

Anorexia nervosa (AN) is classified as a high-risk factor for osteoporotic fractures. Dual X-ray absorptiometry (DXA) is the most popular method for measuring bone loss, but it is less sensitive than quantitative computed tomography (QCT). We compared DXA and QCT in measuring the lumbar spine of 17 female patients with AN and 27 healthy subjects. We found discordance between DXA and QCT using World Health Organization (WHO) criteria with the T-score. With QCT as a reference method because of its sensitivity, we found one false-negative, one false-positive, and two misdiagnosed cases. We suggest some correction factors to improve DXA evaluation and screening of bone loss in AN.

Osteoporosis and anorexia nervosa: relative role of endocrine alterations and malnutrition.

BACKGROUND AND AIM: Anorexia nervosa (AN) is a psychiatric disorder characterised by self-induced starvation or a very reduced caloric intake, and frequently by severe life-threatening protein calory malnutrition. Its physiological consequences include amenorrhea, estrogen deficiency and osteoporosis. Osteoporosis may develop as a consequence of a lack of estrogens, low calcium or vitamin D intake, hypercortisolemia or the duration of the illness. The aim of this study was to identify the best endocrinological and nutritional indicators of bone density. SUBJECTS AND METHODS: The study involved 49 young females with AN and malnutrition and 24 age-matched normal controls in whom AN had been excluded on the basis of a clinical evaluation using DSM IV criteria. We studied bone density in early osteopenia, a condition in which the potential risk of fractures is certainly high and traditionally related to a variety of endocrinological and nutritional factors. RESULTS: Bone density was significantly lower in the AN than the control group in all of the examined bone districts: bone mineral density (BMD) spine 0.89 +/- 0.19 vs 1.27 +/- 0.2 (p<0.0001), BMD neck 0.75 +/- 0.14 vs 1.08 +/- 0.17 (p<0.001), BMD Ward 0.74 +/- 0.17 vs 1.12 +/- 0.11 (p<0.0001). Non-significant differences were found in the patients who had undergone previous estrogen medication. Body mass index (BMI) correlated with bone density, but caloric and calcium intake were not significant predictors. IGF-1, a known nutritionally dependent trophic bone factor, was significantly reduced in our patients but did not correlate with BMD. Like other authors, we found a close correlation between lean body mass and BMD in neck and spine. Physical exercise, urinary free cortisol osteocalcin and type I collagen-telopeptide (NTX) did not significantly correlate with the degree of osteopenia. CONCLUSIONS: Our data suggest the importance of nutritional factors (particularly lean body mass and BMI) in determining bone mass, and the relatively limited importance of endocrinological factors with the exception of the duration of amenorrhea as an indirect indicator of endocrinological status.

Regression of microalbuminuria in type II diabetic, hypertensive patients after long-term indapamide treatment.

The influence of hypertension on the progression of persistent microalbuminuria in type II diabetes has not yet been clarified. We have studied the effects of 36 months of indapamide treatment (2.5 mg once daily) on blood pressure (BP), albumin excretion rate (AER), urinary immunoglobulin G4 (IgG4), and glomerular filtration rate (GFR) in 10 patients who were mildly hypertensive and had type II microalbuminuric diabetes (AER greater than 30 mg/24 hours and less than 300 mg/24 hours). BP, AER, and IgG4 significantly decreased after 6 months until the end of the study. Mean GFR was 94.4 +/- 7.5 ml/min/1.73 m2 in the baseline and did not change significantly throughout the course of the antihypertensive therapy. AER and IgG4 were directly related (r = 0.57; p less than 0.004), whereas BP did not relate to GFR, AER, or IgG4. The nephropathy index (45.5 +/- 4 in the baseline) significantly decreased at 12 months (38.7 +/- 2.1), 24 months (35.4 +/- 1.6), and 36 months (36.5 +/- 1.5) (at least p less than 0.01). Long-term indapamide treatment reduced BP and urinary protein loss without affecting GFR. These results indicate a potential role of this drug in the long-term renal protection of patients with type II diabetes, mild hypertension, and microalbuminuria.

Pancreatic polypeptide response to a protein-rich meal in diabetic patients with and without neuropathy.

A protein-rich meal and insulin-induced hypoglycemia (ITT) are two of the most important stimuli on pancreatic polypeptide (PP) secretion in diabetic patients. Previous studies have shown a reduced PP response to ITT in diabetic patients with autonomic neuropathy (AN). Twelve patients without AN (mean age 44 +/- 10.8 yr, mean duration of diabetes 11 +/- 5.6 yr), 9 with AN (51.4 +/- 6 yr, 15.8 +/- 6.9 yr) and 9 controls (N) were studied. AN was assessed by the evaluation of the beat-to-beat variation of the heart rate during deep breathing. PP secretion was stimulated by a protein-rich meal (200 g meat, 150 g milk). All insulin-dependent diabetic (IDD) patients lacked circulating PP antibodies. All diabetic patients showed a significant reduction in the early vagal phase compared to controls. This behavior was more evident in diabetic patients with AN and the secondary phase of these two groups overlapped with the response of controls. These data may be explained by the initial alterations of vagal functions not detectable by current methods.