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Inflammation in Cystic Fibrosis is higher than bacterial clearance needs and contributes significantly to the deterioration of lung tissue and vital prognosis. Its physiology remains controversial and is more complex than the cycle infection-obstruction-inflammation previously described with many interactions and potentiating of the responsible different mechanisms (Mechanical factors, cells, protease/anti-protease, oxidative stress, leukotriens...). This perpetual inflammatory spiral is an important therapeutic target due to its crucial prognosis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Adrenal lesions are discovered in acromegaly more frequently than in general population, without relationship with primary disease. Some patients, carriers of aryl hydrocarbon receptor interacting protein (AIP) gene mutations, developed an adrenal neoplasm., Aim: To evaluate the role of metabolic and genetic aspects and the follow-up of adrenal nodules in acromegaly., Material and Methods: We studied 69 acromegalic patients (30 male and 39 female, 56 ± 15 yr) who had been referred to the Endocrinology Unit of Padua. In all patients we determined body mass index (BMI) and waist-to-hip ratio (WHR); we performed an oral glucose tolerance test (OGTT) whenever possible. If adrenal computed tomography revealed a lesion, the patient underwent an endocrine and genetic study., Results: Adrenal lesions were identified in 14 patients and were not related to gender, duration of disease, GH or IGF-I concentrations, basal and after-OGTT glucose and insulin levels, log(HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) values, whereas BMI and WHR were higher in patients with adrenal lesions. Baseline endocrine and radiological study revealed benign lesions; during mean 4-yr follow-up none of the patients showed hormone excess, even though some lesions increased in size. We did not find any mutation in AIP gene, except heterozygous silent alteration (T48T)., Conclusions: The frequency of non-functioning adrenal lesions in acromegaly is not associated with the considered aspects, except BMI and WHR. The prolonged follow-up showed that these lesions have a tendency to increase in size independently of the control of acromegaly, so a morphological follow- up is recommended.

Background: The concurrence of intracranial aneurysms and acromegaly has been reported and debated previously. Our study in a large number of patients aimed to verify whether acromegaly patients carry a higher risk of harboring intracranial saccular aneurysms and to evaluate the possible relationship using clinical, laboratory, and imaging techniques., Materials and Methods: A total of 152 of 161 consecutive acromegaly patients (median age, 55.7 yr; 82 females) underwent neuroimaging evaluation of the circle of Willis. Clinical data (disease duration and disease control, hypertension, smoking history, diabetes and dyslipidemia, previous surgery or radiotherapy, previous or current pharmacological therapy), laboratory findings (GH and IGF-I at onset and shortly before examination), and pituitary adenoma imaging features (size and invasiveness of the cavernous sinus) were recorded., Results: Twenty-six patients (17.3%) harbored 40 newly diagnosed intracranial aneurysms; two other patients had previously undergone aneurysm clipping due to subarachnoid hemorrhage. Ten patients had multiple aneurysms; most of the aneurysms were located in the intracranial tract of the internal carotid artery (67.5%); no aneurysms belonged to the vertebrobasilar circulation. The presence of intracranial aneurysms correlated with GH serum values at disease onset (P < 0.05) and showed a trend to a positive correlation with poor disease control (P = 0.06); no other laboratory, clinical, and radiological findings correlated with the presence of intracranial aneurysms., Conclusions: GH serum excess seems to carry an increased risk of developing intracranial aneurysms. A neuroradiological evaluation of the intracranial circulation might therefore be considered in the diagnostic work-up of patients affected with acromegaly.

Objective: To examine the main clinical and laboratory data of patients initially diagnosed with polymyalgia rheumatica (PMR), which then developed another conditions., Material and Methods: We reviewed the clinical records of patients diagnosed with PMR in three hospitals in Argentina. Patients had a diagnosis of PMR if they met the following criteria: age ≥ 50 years, erythrocyte sedimentation rate (ESR) at the time of diagnosis > 40 mm, persistent pain and stiffness of at least one month of evolution in two of the following areas: neck, shoulders or proximal arms, hips or proximal lower limbs. Special attention was paid to symptoms or signs of "alarm" (beginning or during disease progression) for suspecting the presence of other non PMR disease within a period of ≤ 12 months., Results: Sixteen of the 200 patients (8%) had other diseases during follow up. Malignancies (n=4) and rheumatic diseases (n=4) were the most common entities, in addition to infective endocarditis (n=1), narrow cervical canal (n=1), Parkinson's disease (n=1), statin-related myalgia (n=1), hypothyroidism (n=1), vitamin D deficiency (n=1) and Calcium Pyrophosphate Deposition Disease (CPDD) (n=2). The average length change of diagnosis was 4.5±3 months. Ten patients had no response to steroids and two had persistently elevated ESR., Conclusion: In this study we highlight the importance of recognizing signs and symptoms along with laboratory data and lack of response to treatment as suspects for the diagnosis of other disease manifestations in patients with PMR symptoms., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Objective: The aim of the present study is to describe the general characteristics of a cohort of patients with early arthritis in Argentina., Methods: CONAART (Consorcio Argentino de Artritis Temprana--Argentine Consortium for Early Arthritis) is an initiative of seven rheumatology centres across Argentina. Patients were included if they had at least one or more swollen joints and <2 years of disease duration. Social, demographic, familiar, hereditary, clinical and laboratory data were recollected. At first visit and every year, X-rays of hands and feet were performed and working characteristics and pharmaco-economic data were re-collected., Results: A total of 413 patients were included. Of them, 327 (79.2%) were women with a median age of 49 years and a median disease duration of 6 months. Of the total, 183 (44.3%) had RA (ACR 1987) and 167 (40.4%) undifferentiated arthritis (UA). Other diagnoses included: 12 crystalics, 11 PsA, 6 uSpA, 6 other CTD, 1 AS and 27 other diagnosis. As 85% of our population had RA and UA, we only compared these two groups of patients. Patients with RA had significantly worse activity parameters of the disease (DAS of 28 joints), functional capacity (HAQ) and quality of life (Rheumatoid Arthritis Quality of Life) than patients with UA. The frequency of RF and anti-CCP, and symmetrical distribution were also significantly higher in patients with RA compared with UA patients. All patients with RA initiated early specific treatment, in a period no longer than 6 months from the beginning of the disease., Conclusion: Early arthritis clinics are a useful tool to identify and treat patients with different forms of joint involvement.

Background: Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene have been described in about 15% of kindreds with familial isolated pituitary adenomas and in a minority of early onset sporadic pituitary adenomas (PA). Among the AIP mutations reported so far, the R304X (AIPR304X) represents, together with the "Finnish mutation" Q14X, the most common one., Methods: Three AIPR304X Italian families, including a newly reported kindred, have been genotyped for 12 genetic markers surrounding the AIP gene in order to look for a potential founder effect in Italy. Disease penetrance and genotype-phenotype correlations were also addressed., Results: Analysis of chromosome 11' genetic markers revealed a common haplotype in 2 AIPR304X kindreds originating from central Italy. Overall, 17 mutations carriers were identified, including 7 patients and 10 unaffected subjects, respectively, arguing in this case for a disease penetrance of 41%. Mean age at diagnosis was 19.1±6.7 yr old, with females tending to be older than males. Though most PA were somatotropinomas (6/7), a great variability in disease severity was observed, even between subjects sharing the same at-risk haplotype., Conclusion: These data provide strong evidence for a new founder effect of the AIPR304X mutation in central Italy and the observed variations in disease severity point out the role of additional genetic or environmental factors in such kindreds.

Background: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27(KIP1) encoding gene CDKN1B have been associated with two well-defined hereditary conditions, familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 4 (MEN4). Somatotropinomas are present in most AIP mutated FIPA kindreds, as well as in two-thirds of MEN4 patients who carry pituitary tumors., Methods: Germline DNA samples of 131 Italian sporadic acromegalic patients including 38 individuals with multiple tumors, and of six FIPA families (four homogeneous for prolactinomas and two heterogeneous with prolactin/nonfunctioning pituitary adenomas) were collected in a multicentric collaborative study. The prevalence of AIP and CDKN1B gene point mutations and copy number variations were evaluated., Results: Two novel (IVS3+1G>A and c.871G>A) and one previously described (c.911G>A) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49+/-18, range 30-67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871G>A substitution was detected in a patient who also carried a MEN1 mutation suggesting that she is a double heterozygote. The possible pathogenic effect on AIP splicing of the silent substitution c.144G>A found in another patient was ruled out using a minigene-based approach. CDKN1B mutations/rearrangements were neither identified in patients with multiple neoplasia nor in FIPA families., Conclusion: AIP is mutated in about 3% of apparently sporadic acromegalic patients. The relatively high age at diagnosis, as well as its sporadic presentation, suggests that these patients are carriers of mutations with reduced pathogenicity. p27(KIP1) is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.

A 30-year-old woman was referred on April 2002 for a plaque that involved the internal aspect of the right leg, an erythema nodosum-like lesion on the lower extremities, and periarthritis on her left ankle. Subsequently, the patient developed anular, atrophic, growing, porcelain-white papules, with a thin rim of erythema and telangiectases over her upper and lower extremities. Clinically and histologically, these lesions were the characteristics of Degos disease. Despite arthritis and myositis that required treatment, low level C3 and C4, positive antinuclear antibodies, and elevated anticardiolipin antibodies only once, in a follow-up of 6 years the patient never developed a specific connective tissue disease or other systemic involvement. In conclusion, because clinical and histological findings of Degos disease might mimic connective tissue diseases, rheumatologists must be aware that this reaction pattern can be seen in a wide clinical spectrum of diseases.

Objective: This study seek to establish the prevalence of calcification of the transverse ligament of the atlas (TLA) and of crowned dens syndrome (CDS) in patients with articular chondrocalcinosis. It also seeks to assess the main computed tomography appearances of these calcifications., Patients and Methods: Twenty-eight patients with articular chondrocalcinosis were prospectively evaluated for evidence of calcifications of the transverse ligament of the atlas. A group of patients with gout, fibromyalgia, and osteoarthritis were used as control., Results: Twenty-eight patients with articular chondrocalcinosis were prospectively evaluated for evidence of calcifications of the transverse ligament of the atlas. Twenty of the patients (71%) showed this calcification by computed tomography, disclosing 3 patterns of calcification: curvilinear in shape, thick, and forming a double band and mottled. Calcifications were not found in the controls (P < 0.0001). Nine patients were symptomatic (crowned dens syndrome). Patients with chondrocalcinosis and calcification of the transverse ligament of the atlas were older than the rest of the patients. Unlike the patient group, the majority of the patients in the control group were male (P = 0.02)., Conclusion: The presence of calcifications of the transverse ligament of the atlas in patients with chondrocalcinosis occurs more frequently than that reported earlier. The CT scan is the most sensitive method to detect it. Taking into account that calcifications of TLA may manifest as CDS in a high percentage of these patients, such possibility should be considered in all patients with neck pain, stiffness, fever, and inflammatory response so as to avoid invasive diagnostic methods and more aggressive treatments than the use of nonsteroidal anti-inflammatory drugs.

Background: We aimed to evaluate the use of central catheters introduced by a peripheral vein (PICC) in children with CF., Methods: A descriptive study in patients in whom a PICC (Beckton Dickinson) was inserted., Results: 24 children aged (median (range) 10.2 years (0.3-17.3) undergoing 44 procedures were included. PICC was successfully inserted in 93.2% (41/44) of cases. Total procedure duration was (median (range)) 32.5 (10-105) minutes. The operators encountered few difficulties, median (range) 2 (1-10) (1 (absence) to 10 (maximal)); median (range) 1 (1 to 5) attempt per child). No major side effects or infections were observed. PICC obstruction in 5 (12%) cases was successfully unblocked in 4 cases (urokinase). The catheter was functional throughout the antibiotic course in 40/41 cases. A final Doppler scan (30 cases) showed total permeability of the central veins in all cases. Satisfaction index of the operators and the patients were high: median (range) 9.5 (1-10) and 8.0 (6-10) (scale: 1 (worse) to 10 (best)), respectively., Conclusion: PICCs are simple to use, and may be safely inserted in the ward. Such catheters are well tolerated, may increase the well-being of children with CF and prove an effective means by which to deliver IV therapy in this population.

Calciphylaxis is the tissue sensitivity to calcification, described mainly in patients with chronic renal insufficiency, renal transplant of parathyroid dysfunction. There is only one case described in a patient with rheumatoid arthritis, without renal dysfunction, nor hyperparathyroidism. We present the second case in a woman with inactive rheumatoid arthritis.

Objectives: The purpose of this open multicenter study was to evaluate the value of a new starch-thickened formula in infants with regurgitations in ambulatory pediatric practice., Population and Methods: The study population comprised full-term infants with an age at inclusion of 1-90 days, who were bottle-fed and presented regurgitations. The formula tested was an infant formula-thickened with starch (2g/100mL). The primary endpoint was the frequency of bottles regurgitated, expressed in percentage of meals per day after 15 days of feeding with the preparation studied. Secondary endpoints were the assessment of regurgitations using the Vandenplas' score, as well as the daily increase in weight, height, and cranial circumference, overall and gastrointestinal tolerance, and formula acceptability., Results: Sixty-four infants presenting regurgitation were included. The frequency of bottles regurgitated estimated at 80.3% at inclusion significantly decreased at D3, D15, and D30 to 40.1, 40.2 and 37.2% (P<0.0001), respectively. Thirty percent of infants did not present regurgitations at all at D30. Similarly, a significant decrease in the Vandenplas' score was observed from 1.9 at D0 to 0.9 at D30 (P<0.0001). Infant growth was similar to the French and European growth curves., Conclusion: The results showed rapid and lasting improvement in decreasing the frequency of feeding-bottles regurgitated by 50% from the first 3 days of using this new starch-thickened formula (2g/100mL). These satisfying results encourage the use of the tested formula in cases of infant regurgitation, in line with the European Society of Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommendations.

Adult-onset GH deficiency (GHD), mostly due to organic lesions of the pituitary-hypothalamic region, is frequently associated with multiple anterior pituitary deficiencies that need long-term substitutive treatment. The GH-IGF-I axis may play an important role in modulating peripheral metabolism of hormones (adrenal, thyroid, and sex hormones) and these interactions may have clinically significant implications on the phenotypes of adult GHD patients and on the effects of the combined replacement hormonal treatment of this condition. By accelerating the peripheral metabolism of cortisol, GH therapy may precipitate adrenal insufficiency in susceptible hypopituitary patients; estrogen replacement blunts the response to GH in women whereas in men with androgen substitution the responsivity increases over time. Endocrinologists should be mindful of these phenomena when starting patients with hypopituitarism on GH replacement therapy.

Chronic intestinal pseudo-obstruction (CIPO), a recently recognized manifestation of systemic lupus erythematosus (SLE) with only 23 cases reported in the English literature, may appear as a complication or as the initial presentation of SLE and usually occurs during the setting of an active lupus. The pathogenic mechanism in SLE is unknown. We describe four additional cases with clinical, radiological, and manometric features of CIPO. As SLE-related CIPO usually responds to treatment with high doses of corticosteroids and/or immunosuppressive and prokinetic agents, a high level of awareness of this complication is needed to avoid unnecessary surgical intervention.

This report describes the coexistence of three patients with rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis) and infections because of Histoplasma capsulatum. Connective tissue diseases and histoplasmosis share several clinical findings. Therefore, histoplasmosis could be misdiagnosed as connective tissue disease or a flare of these diseases. Such cases highlight the importance of awareness of histoplasmosis in immunocompromised patients, particularly in those originating from endemic areas.

There are clinical difficulties to differentiate elderly-onset rheumatoid arthritis (EORA) patients from those with polymyalgia rheumatica (PMR), especially when dealing with EORA-like PMR-onset, seronegative EORA, and PMR with peripheral synovitis, which constitute the subgroups presenting the greatest difficulties. Serum samples were obtained from two groups of patients, one with EORA diagnosis and another with a PMR diagnosis. Anticyclic citrullinated peptide (anti-CCP) antibodies (enzyme-linked immunosorbent assay method) and rheumatoid factor (RF; latex technique) were determined. Of the 16 EORA patients, 9 presented anti-CCP antibodies, 4 of whom tested positive for RF. Of the 12 EORA patients who remained negative to RF, 5 were positive for anti-CCP antibodies. Eight of the EORA patients started with polymyalgic symptoms. Three of these patients showed positive titles of anti-CCP antibodies with negative RF. All PMR patients presented negative anti-CCP antibodies, except one with weak positive titles, and all were negative for RF. Of 15 patients with PMR, 7 presented oligoarticular synovitis at the onset. After a mean follow-up of 3 months, two patients developed RA. When evaluating them for RF and anti-CCP antibodies, one tested negative, while the other was positive for both antibodies. We observed a tendency to higher values of anti-CCP antibodies in patients with extraarticular manifestations, radiological damage, and disease-modifying antirheumatic drugs. When compared to the PMR group, EORA patients presented positive anticitrulline antibodies at the beginning of the disease in a statistically significant amount. One third of the seronegative EORA patients presented positive anti-CCP antibodies at the onset.

Objectives: The objectives of this study were to evaluate the frequency and characteristics of the peripheral musculoskeletal manifestations in polymyalgia rheumatica (PMR), evaluate if PMR with peripheral synovitis represents a subset with a more severe disease, and examine for clinical and laboratory characteristics at onset of PMR that might later predict rheumatoid arthritis (RA)., Patients and Methods: Patients were diagnosed with PMR according to the 1982 Chuang criteria. Patients were followed up between 1990 and 2002. The following musculoskeletal manifestations at onset and during the follow up were considered: peripheral synovitis, distal extremity swelling with pitting edema, carpal tunnel syndrome, and distal tenosynovitis., Results: Thirty-eight of the 74 patients (51%) showed distal musculoskeletal symptoms: 29 (39%) had peripheral synovitis, 4 (5%) presented pitting edema, 4 (5%) experienced carpal tunnel syndrome, and one (1.3%) had distal tenosynovitis. These manifestations resolved completely after corticosteroid therapy was initiated. Peripheral synovitis was oligoarticular and often transient. The joints most frequently involved were the wrist, metacarpophalangeal, and knee. Erythrocyte sedimentation rate (ESR) was normal in 7 patients. When comparing patients with PMR with and without peripheral synovitis, no statistically significant differences were found in the studied variables. Through the first year of follow up, 7 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 2 patients developed giant cell arteritis, and 3 had associated malignancy. Patients who developed RA had statistically significantly increased presence of persistent synovitis and a smaller decrease in mean ESR after treatment with corticosteroids., Conclusion: Fifty-one percent of the patients with PMR presented distal musculoskeletal manifestations, with peripheral synovitis being the most frequent one. Patients with PMR with peripheral synovitis did not represent a high-risk subgroup with more severe disease. Seven patients who developed criteria for seronegative RA within the first year of follow up had presented statistically significant persistent synovitis compared with those who continued as PMR and also showed a smaller initial decrease in mean ESR after steroid treatment was initiated. The absence of persistent arthritis and the benign course of the arthritis permit the distinction of PMR from other inflammatory arthropathies.

Atlanto-axial luxation in uncommon in chronic arthritis in childhood, especially early in the course of the disease. One case is described in which atlanto-axial luxation occurred early. Computed tomographic myelography showed the cervico-medullary compression which was treated by transoral anterior decompression and posterior occipito-cervical fusion.

A case of typhlitis in a 3,5 year old girl, during induction therapy for acute lymphoblastic leukemia is reported. This typhlitis, or necrotizing enterocolitis involving the coecum and right colon resulted in stercoral peritonitis during the neutropenic phase. After surgery, the patient had a favorable outcome with complete recovery. Knowledge about this uncommon but severe complication of hemopathies leads to follow clinical, microbiologic and radiologic rules of prophylaxis and screening. Typhlitis requires early treatment by supportive care and surgical cure if necessary.

A case of arteriovenous malformation of the spinal canal in a 8 year-old girl is reported. This child complained of night abdominal pain for several months, without diagnosis. Plain X-ray showed an enlargement of the lumbar spinal canal. Magnetic resonance imaging diagnosed a spinal vascular malformation, which was confirmed by angiography. Interest of MRI in such a case is emphasized.