Federica Guaraldi

Effect of Breast and Formula Feeding on Gut Microbiota Shaping in Newborns

The gastrointestinal microbiota is a complex and dynamic ecosystem consisting of several hundreds of different microbes, mainly bacteria (1011–12 bacteria/g of colonic content, forming 60% of total fecal mass; Eckburg et al., 2005; O’Hara and Shanahan, 2006). Total number of bacteria exceeds 10 times the number of human cells, and the collection of microbial genome (microbiome) contains 100 times more genes than the human genome (Vael and Desager, 2009). Gut microbiota influence the growth and differentiation of gut epithelial cells, and play pivotal nutritive, metabolic, immunological, and protective functions (O’Hara and Shanahan, 2006). Its deregulation is involved in the pathogenesis of immunological, cardiovascular, and metabolic diseases (Hammer, 2011; Maslowski and MacKay, 2011; Harris et al., 2012). The investigation on microbiota composition started in 1900 (Tissier, 1900) and has been performed by culturing methods since the recent advent of DNA sequence-based methods, that, thanks to their ability to identify a large number of species that cannot be cultivated, have allowed a more complete and rapid assessment of the gastrointestinal ecosystem (Palmer et al., 2007; Adlerberth and Wold, 2009). On the basis of 16S ribosomial – RNA encoding gene, more than 7000 distinct phylotypes have been detected in the human distal gut (Vael and Desager, 2009), with high inter-individual and age variability, but belonging to a limited number of broad taxonomic divisions (mainly the anaerobes Bacteroides, Eubacterium, Clostridium; Hayashi et al., 2002; Eckburg et al., 2005; Zoetendal et al., 2008). In a very recent study, Arumugam et al. (2011), by combining fecal metagenomes of individuals from different countries, identified three different enterotypes (with the prevalence of Bacteroides, Prevotella, and Ruminococcus species, respectively) that are not nation or continent specific, and showed that intestinal microbiota variation is stratified, not continuous, indicating further the existence of a limited number of well-balanced host-microbial symbiotic states. These enterotypes do not seem to differ in functional richness and apparently do not correlate with nationality, gender, age, or body mass index; at the same time, they seem to characterize and be quite stable in individuals, so that they can be restored after perturbations. Gut microbiota composition and concentration physiologically varies throughout the gastrointestinal tract (increasing gradient from the stomach to the colon and characteristic gut-compartment distribution of microflora) and life stages, progressing from the newborn sterility to the extremely variable and dense colonization of adult gut, under the influence of various internal host-related and external factors (Mackie et al., 1999; Palmer et al., 2007).

Efficacy of Ultrasound-guided Intra-articular Injections of Platelet-rich Plasma Versus Hyaluronic Acid for Hip Osteoarthritis

Intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA) represent efficacious medical treatments for osteoarthritis (OA), although no comparative study on long-term efficacy in hip OA exists. The goals of the current study were to compare the clinical efficacy of PRP vs HA at 12 months of follow-up in patients with hip OA and evaluate the influence of the type of infiltration and patient age, sex, body mass index, and degree of OA on temporal clinical evolution. One hundred patients with chronic unilateral symptomatic hip OA were consecutively enrolled and randomly assigned to 1 of 2 groups: group A received PRP and group B received HA administered via intra-articular ultrasound-guided injections. Patients were evaluated at baseline and after 1, 3, 6, and 12 months using the Harris Hip Score (HHS) and visual analog scale (VAS). An overall improvement was detected in both groups between 1- and 3-month follow-up. Despite a slightly progressive worsening between 6- and 12-month follow-up, the final clinical scores remained higher compared with baseline (P<.0005), with no significant differences between PRP and HA. Regarding clinical temporal evolution, multivariate analysis showed that HHS was not influenced by the type of infiltration, patient age, sex, body mass index, or degree of OA, whereas a significant association was detected between OA grade IV and VAS evolution (P<.0005). Intra-articular injections of PRP are efficacious in terms of functional improvement and pain reduction but are not superior to HA in patients with symptomatic hip OA at 12-month follow-up.

Cushing Syndrome: Maybe Not So Uncommon of an Endocrine Disease

Background: Cushing syndrome (CS) is the result of extended exposure to excessive glucocorticoids from endogenous or exogenous sources. Traditionally, the most common cause of endogenous CS is a pituitary adenoma (Cushing disease). Less common causes are adrenocortical tumors and extrapituitary adrenocorticotropin-producing neoplasias. Objectives: This review provides updated information regarding the potential for increased prevalence of CS in specific patient populations. Here the authors provide to family physicians clinical guidance for recognition of CS by presenting a case, discussing the advantages/disadvantages of the diagnostic tests, and discussing information about the treatment options. Results: CS is expected to have an incidence of 10 to 15 people per million; however, studies of patients with diabetes, obesity, hypertension, and osteoporosis found a high prevalence of CS among these populations. The clinical manifestations of CS range from the distinctive clinical features (purple striae, facial plethora, proximal myopathy) to common conditions such as hypertension, obesity, and diabetes. Clinical practice guidelines recommend biochemical tests to screen patients for CS; however, the sensitivity and specificity of these tests vary, so a careful analysis must be performed to avoid misdiagnosis. Conclusion: CS is challenging to diagnose. Nevertheless, with a systematic approach to testing patients and an increased awareness of the high-risk patient populations, the disease can be identified in a timely manner.

Glucose metabolism in patients with subclinical Cushing’s syndrome

This clinical review will summarize the available data regarding the effect of either physiological or increased glucocorticoid concentrations on glucose metabolism and insulin-sensitivity, in order to clarify the role, if any, of subclinical Cushing’s syndrome (SCS), a status of altered hypothalamic–pituitary–adrenal axis secretion in the absence of the classical signs or symptoms of overt cortisol excess, in patients with adrenal incidentalomas (AI) and diabetes mellitus type 2. Focusing on patients with SCS associated to AI, while there is convincing evidence in the literature that even a mild hyper cortisolemia is associated with alterations of glucose metabolism, evidence is insufficient to conclude that the simple correction of chronic, even mild, hypercortisolism can completely revert metabolic, mainly glycemic alterations. At the same time, considering the variability of the prevalence of Cushing’s syndrome in patients with diabetes mellitus type 2 reported in the literature, no agreement does exist whether screening for CS can be useful and recommended in those patients.

Detection of Pituitary Antibodies by Immunofluorescence: Approach and Results in Patients With Pituitary Diseases

CONTEXT Pituitary antibodies have been measured mainly to identify patients whose disease is caused or sustained by pituitary-specific autoimmunity. Although reported in over 100 publications, they have yielded variable results and are thus considered of limited clinical utility. OBJECTIVES Our objectives were to analyze all publications reporting pituitary antibodies by immunofluorescence for detecting the major sources of variability, to experimentally test these sources and devise an optimized immunofluorescence protocol, and to assess prevalence and significance of pituitary antibodies in patients with pituitary diseases. STUDY DESIGN AND OUTCOME MEASURES: We first evaluated the effect of pituitary gland species, section fixation, autofluorescence quenching, blockade of unwanted antibody binding, and use of purified IgG on the performance of this antibody assay. We then measured cross-sectionally the prevalence of pituitary antibodies in 390 pituitary cases and 60 healthy controls, expressing results as present or absent and according to the (granular, diffuse, perinuclear, or mixed) staining pattern. RESULTS Human pituitary was the best substrate to detect pituitary antibodies and yielded an optimal signal-to-noise ratio when treated with Sudan black B to reduce autofluorescence. Pituitary antibodies were more common in cases (95 of 390, 24%) than controls (3 of 60, 5%, P = .001) but did not discriminate among pituitary diseases when reported dichotomously. However, when expressed according to their cytosolic staining, a granular pattern was highly predictive of pituitary autoimmunity (P < .0001). CONCLUSION We report a comprehensive study of pituitary antibodies by immunofluorescence and provide a method and an interpretation scheme that should be useful for identifying and monitoring patients with pituitary autoimmunity.

Acylated ghrelin as a provocative test for the diagnosis of GH deficiency in adults

OBJECTIVE Insulin tolerance test (ITT) is the test of reference for the diagnosis of adult GH deficiency (GHD), although GHRH in combination with arginine (ARG) or GH secretagogues are considered equally reliable tests. Testing with GH secretagogue alone is, anyway, a potent stimulus exploring the integrity of hypothalamic pathways controlling somatotropic function. We therefore aimed to determine the diagnostic reliability of testing with ghrelin, the natural GH secretagogue. METHODS We studied the GH response (every 15 MIN from 15 TO +120 MIN) to acylated ghrelin (1G/KG I.V. AT 0MIN) IN 78 patients with a history of pituitary disease (49 male, 29 female; age (MEANS.D.): 52.1±18.7 years; BMI: 26.7±5.3 kg/m(2)). The lack of GH response to GHRH+ARG and/or ITT was considered the gold standard for the diagnosis of GHD. The best GH cut-off to ghrelin test, defined as the one with the best sensitivity (SE) and specificity (SP), was identified using the receiver-operating characteristic curve analysis. RESULTS The best GH cut-off to ghrelin test was 7.3 μg/l in lean subjects (SE 88.2%, SP 90.9%), 2.9 μg/l in overweight subjects (SE 92.6%, SP 100%) and 0.6 μg/l in obese subjects (SE 50%, SP 100%). The diagnostic accuracy was 89.3, 94.1 and 62.5% respectively. CONCLUSIONS Our data show that testing with acylated ghrelin represents a reliable diagnostic tool for the diagnosis of adult GHD, in lean and overweight subjects, if appropriate cut-off limits are assumed. Obesity strongly reduces GH response to ghrelin, GH weight-related cut-off limit and diagnostic reliability of the test.

WTX R353X mutation in a family with osteopathia striata and cranial sclerosis (OS-CS): case report and literature review of the disease clinical, genetic and radiological features

Osteopathia striata with cranial sclerosis (OS-CS) or Horan-Beighton syndrome is a rare X-linked dominant inherited bone dysplasia, characterized by longitudinal striations of long bones and cranial sclerosis. Patients can be asymptomatic or present with typical facial dysmorphism, sensory defects, internal organs anomalies, growth and mental retardation, depending on the severity of the disease. WTX gene (Xq11) has been recently identified as the disease causing gene. Aim of this article is to present the case of a 6 year old girl initially evaluated for bilateral hearing loss. Patient’s head CT scan pointed out sclerosis of skull base and mastoid cells, and abnormal middle-ear ossification. Clinical examination of the patient and her mother were suspicious for OS-CS. The diagnosis was confirmed by X-rays examination showing typical longitudinal striation. Genetic analysis allowed the identification of maternally transmitted heterozygous nonsense c.1057C>T (p.R353X) WTX gene mutation. We also provide a systematic review of currently available knowledge about clinical, radiologic and genetic features typical of the OS-CS.

Paediatric Pituitary Adenomas: A Decade of Change

Pituitary adenomas, although rare in the paediatric age range and mostly benign, represent very challenging disorders for diagnosis and management. The recent identification of genetic alterations in young individuals with pituitary adenomas has broadened the scope of molecular investigations and contributed to the understanding of mechanisms of tumorigenesis. Recent identification of causative mutations of genes such as GNAS, PRKAR1A, MEN1 and AIP has introduced the concept of molecular screening of young apparently healthy family members. Population-based studies have reported a significantly higher number of affected subjects and genetic variations than expected. Radiological techniques have advanced, yet many microadenomas remain undetectable on scanning. However, experience with transsphenoidal and endoscopic pituitary surgery has led to higher rates of cure. Prolactinomas, corticotroph and somatotroph adenomas remain the most prevalent, with each diagnosis presenting its own challenges. As paediatric pituitary adenomas occur very infrequently within the paediatric age range, paediatric endocrine units cannot provide expert management in isolation. Consequently, close co-operation with adult endocrinology colleagues with experience of pituitary disease is strongly recommended.

An unusual cause of external snapping hip

The external snapping hip syndrome is a condition characterized by palpable or audible snap on the lateral region of the hip occurring during movements and sometimes associated with pain. It is typical of young adults and athletes and can be favored by the abnormal sliding of the iliotibial band or of the gluteus maximus muscle over the greater trochanter. We present a case of external snapping hip syndrome occurring in a young woman secondary to a dysmorphic sickle-shaped myotendinous junction of the gluteus maximus muscle. Diagnosis was allowed by an integrated clinical and radiological approach, based on dynamic ultrasound and magnetic resonance imaging (MRI).

Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

Background: Traumatic brain injury (TBI) is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A). The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.