Calcium/phosphate ratio: an additional tool for the clinical management of asymptomatic primary hyperparathyroidism?

PURPOSE: Serum calcium/phosphate ratio (Ca/P) has been recently proposed as an additional tool to identify primary hyperparathyroidism (PHPT), especially in patients with subclinical presentation, with a proposed cut-off of 3.3 when both values are expressed in mg/dL. No data are available on the relationship between Ca/P and the clinical presentation of PHPT. We thus evaluated this relationship in a large, single-center, unselected series. METHODS: 515 consecutive PHPT patients (mean age 65 ± 13.15 years, 77.1% females) were retrospectively evaluated at diagnosis. RESULTS: Mean Ca/P was 4.54 ± 1.5 (range 2.36-13.9), being higher than 3.3 in 88.5% of patients. Ca/P was significantly higher in (1) males, (2) symptomatic PHPT, (3) patients with 25-hydroxy vitamin D levels lower than 20 µg/L, (4) patients with osteitis fibrosa cystica, (5) patients with T score < - 2.5 at the radial site. In a multivariate regression analysis, Ca/P resulted significantly associated with PTH levels. After the exclusion of 57 patients with asymptomatic PHPT (aPHPT) patients and serum Ca higher than 1 mg/dL above the upper limit of normal range, no differences were found in Ca/P between aPHPT meeting or not surgical criteria. CONCLUSIONS: In PHPT Ca/P ratio is associated with increased biochemical and clinical severity of disease and represents a direct indicator of clinical bone damage. However, it does not seem an additional tool to identify aPHPT patients reaching surgical indication.

Fitting parameters and therapies of ODE tumor models with senescence and immune system.

This work is devoted to introduce and study two quasispecies nonlinear ODE systems that model the behavior of tumor cell populations organized in different states. In the first model, replicative, senescent, extended lifespan, immortal and tumor cells are considered, while the second also includes immune cells. We fit the parameters regulating the transmission between states in order to approximate the outcomes of the models to a real progressive tumor invasion. After that, we study the identifiability of the fitted parameters, by using two sensitivity analysis methods. Then, we show that an adequate reduced fitting process (only accounting to the most identifiable parameters) gives similar results but saving computational cost. Three different therapies are introduced in the models to shrink (progressively in time) the tumor, while the replicative and senescent cells invade. Each therapy is identified to a dimensionless parameter. Then, we make a fitting process of the therapies' parameters, in various scenarios depending on the initial tumor according to the time when the therapies started. We conclude that, although the optimal combination of therapies depends on the size of initial tumor, the most efficient therapy is the reinforcement of the immune system. Finally, an identifiability analysis allows us to detect a limitation in the therapy outcomes. In fact, perturbing the optimal combination of therapies under an appropriate therapeutic vector produces virtually the same results.

Clinical presentation and management of patients with primary hyperparathyroidism in Italy.

PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13  years), the remaining 38 (6.3%, age 41 ± 17  years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

Quality assurance in cardiovascular CT: a practical guide.

Cardiovascular computed tomography (CCT) is a cutting-edge imaging technique providing important, non-invasive, diagnostic information. Concerns exist regarding radiation exposure to patient populations, but achieving optimal image quality at the lowest doses can be challenging. This guide provides practical advice about how quality can be assured in any CCT unit or radiology department. Illustrated by real-world vignettes and data analysis from our own experience, we highlight a multidisciplinary team approach to each stage of the patient journey, the effectiveness of regular dose audit overseen by a CT optimisation group, and the importance of underused systolic scanning techniques, in order to drive significant dose reduction without loss of image quality or clinical confidence.

The safe practice of CT coronary angiography in adult patients in UK imaging departments.

Computed tomography coronary angiography is increasingly used in imaging departments in the investigation of patients with chest pain and suspected coronary artery disease. Due to the routine use of heart rate controlling medication and the potential for very high radiation doses during these scans, there is a need for guidance on best practice for departments performing this examination, so the patient can be assured of a good quality scan and outcome in a safe environment. This article is a summary of the document on 'Standards of practice of computed tomography coronary angiography (CTCA) in adult patients' published by the Royal College of Radiologists (RCR) in December 2014.

Mild primary hyperparathyroidism as defined in the Italian Society of Endocrinology's Consensus Statement: prevalence and clinical features.

BACKGROUND: Mild primary hyperparathyroidism (PHPT) was recently clearly defined for the first time. Our study was thus aimed to pinpoint proportion and clinical characteristics of this kind of patients. DESIGN AND PATIENTS: We retrospectively evaluated our series of 360 consecutive patients with PHPT, selecting those with all features allowing a correct classification (serum total and ionized calcium, phosphate, creatinine, PTH, 25OHD, urinary calcium, renal and neck ultrasound, MIBI scintiscan, and DEXA at lumbar spine, femoral neck, and distal third of radius). Patients were defined asymptomatic (aPHPT) when bone or kidney was not involved and no hypercalcemic symptom occurred; mild PHPT was defined as aPHPT not meeting updated surgical criteria. RESULTS: Seventy-five patients among 172 classified as aPHPT had all available data required for surgical evaluation and could be evaluated. Sixty/75 met surgical criteria and the remaining 15 were classified as mild. Mild PHPT patients had lower total and ionized calcium, urinary calcium, and PTH levels than aPHPT meeting surgical criteria, while vitamin D levels and BMD were similar. CONCLUSIONS: Mild PHPT strictly defined according to the last consensus represents a small subgroup with a less active form of the disease.

Quality of life and hormones after sex reassignment surgery.

BACKGROUND: Transpeople often look for sex reassignment surgery (SRS) to improve their quality of life (QoL). The hormonal therapy has many positive effects before and after SRS. There are no studies about correlation between hormonal status and QoL after SRS. AIM: To gather information on QoL, quality of sexual life and body image in transpeople at least 2 years after SRS,to compare these results with a control group and to evaluate the relations between the chosen items and hormonal status. SUBJECTS AND METHODS: Data from 60 transsexuals and from 60 healthy matched controls were collected. Testosterone,estradiol, LH and World Health Organization Quality of Life (WHOQOL-100) self-reported questionnaire were evaluated. Student's t test was applied to compare transsexuals and controls. Multiple regression model was applied to evaluate WHOQOL's chosen items and LH. RESULTS: The QoL and the quality of body image scores intranspeople were not statistically different from the matched control groups' ones. In the sexual life subscale,transwomen's scores were similar to biological women's ones, whereas transmen's scores were statistically lower than biological men's ones (P = 0.003). The quality of sexual life scored statistically lower in transmen than intranswomen (P = 0.048). A significant inverse relationship between LH and body image and between LH and quality of sexual life was found. CONCLUSIONS: This study highlights general satisfaction after SRS. In particular, transpeople's QoL turns out to be similar to Italian matched controls. LH resulted inversely correlated to body image and sexual life scores.

Spectroscopic, structural, and conformational properties of (Z)-4,4,4-trifluoro-3-(2-hydroxyethylamino)-1-(2-hydroxyphenyl)-2-buten-1-one, C12H12F3NO3: a trifluoromethyl-substituted ß-aminoenone.

The (Z)-4,4,4-trifluoro-3-(2-hydroxyethylamino)-1-(2-hydroxyphenyl)-2-buten-1-one (C(12)H(12)F(3)NO(3)) compound was thoroughly studied by IR, Raman, UV-visible, and (13)C and (19)F NMR spectroscopies. The solid-state molecular structure was determined by X-ray diffraction methods. It crystallizes in the P2(1)/c space group with a = 12.1420(4) Å, b = 7.8210(3) Å, c = 13.8970(5) Å, ß = 116.162(2)°, and Z = 4 molecules per unit cell. The molecule shows a nearly planar molecular skeleton, favored by intramolecular OH···O and NH···O bonds, which are arranged in the lattice as an OH···O bonded polymer coiled around crystallographic 2-fold screw-axes. The three postulated tautomers were evaluated using quantum chemical calculations. The lowest energy tautomer (I) calculated with density functional theory methods agrees with the observed crystal structure. The structural and conformational properties are discussed considering the effect of the intra- and intermolecular hydrogen bond interactions.

Southern Ocean sea-ice extent, productivity and iron flux over the past eight glacial cycles.

Sea ice and dust flux increased greatly in the Southern Ocean during the last glacial period. Palaeorecords provide contradictory evidence about marine productivity in this region, but beyond one glacial cycle, data were sparse. Here we present continuous chemical proxy data spanning the last eight glacial cycles (740,000 years) from the Dome C Antarctic ice core. These data constrain winter sea-ice extent in the Indian Ocean, Southern Ocean biogenic productivity and Patagonian climatic conditions. We found that maximum sea-ice extent is closely tied to Antarctic temperature on multi-millennial timescales, but less so on shorter timescales. Biological dimethylsulphide emissions south of the polar front seem to have changed little with climate, suggesting that sulphur compounds were not active in climate regulation. We observe large glacial-interglacial contrasts in iron deposition, which we infer reflects strongly changing Patagonian conditions. During glacial terminations, changes in Patagonia apparently preceded sea-ice reduction, indicating that multiple mechanisms may be responsible for different phases of CO2 increase during glacial terminations. We observe no changes in internal climatic feedbacks that could have caused the change in amplitude of Antarctic temperature variations observed 440,000 years ago.

[Intracranial dural sinus hypodensity as a sign of acute thrombosis: an unusually atypical radiological manifestation]. / Hipodensidad de senos durales intracraneales como signo de trombosis aguda: una manifestación radiológica extraordinariamente atípica.

TITLE: Hipodensidad de senos durales intracraneales como signo de trombosis aguda: una manifestación radiológica extraordinariamente atípica.

Transcriptional networks of knockout cell lines identify functional specificities of H-Ras and N-Ras: significant involvement of N-Ras in biotic and defense responses.

We characterized differential gene expression profiles of fibroblast cell lines harboring single or double-homozygous null mutations in H-ras and N-ras. Whereas the expression level of the individual H-, N- and K-ras genes appeared unaffected by the presence or absence of the other ras loci, significant differences were observed between the expression profiles of cells missing N-ras and/or H-ras. Absence of N-ras produced much stronger effects than absence of H-ras over the profile of the cellular transcriptome. N-ras(-/-) and H-ras(-/-) fibroblasts displayed rather antagonistic expression profiles and the transcriptome of H-ras(-/-) cells was significantly closer to that of wild-type fibroblasts than to that of N-ras(-/-) cells. Classifying all differentially expressed genes into functional categories suggested specific roles for H-Ras and N-Ras. It was particularly striking in N-ras(-/-) cells the upregulation of a remarkable number of immunity-related genes, as well as of several loci involved in apoptosis. Reverse-phase protein array assays demonstrated in the same N-ras(-/-) cells the overexpression and nuclear migration of tyrosine phosphorylated signal transducer and activator of transcription 1 (Stat1) which was concomitant with transcriptional activation mediated by interferon-stimulated response elements. Significantly enhanced numbers of apoptotic cells were also detected in cultures of N-ras(-/-) cells. Our data support the notion that different Ras isoforms play functionally distinct cellular roles and indicate that N-Ras is significantly involved in immune modulation/host defense and apoptotic responses.

Tumour-suppression function of KLF12 through regulation of anoikis.

Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell adhesion. Knockdown of KLF12 in parental cells results in decreased apoptosis following cell detachment from matrix. KLF12 regulates anoikis by promoting the cell cycle transition through S phase and therefore cell proliferation. Reduced expression levels of KLF12 results in increased ability of lung cancer cells to form tumours in vivo and is associated with poorer survival in lung cancer patients. We therefore identify KLF12 as a novel metastasis-suppressor gene whose loss of function is associated with anoikis resistance through control of the cell cycle.

Primary hyperparathyroidism and Klinefelter's syndrome in a young man.

UNLABELLED: We report the association of primary hyperparathyroidism (PHPT) and Klinefelter's syndrome (KS) in a 22-year-old male complaining of worsening fatigue. PHPT was asymptomatic at the diagnosis, but the patient had worsening hypercalcemia and osteoporosis, and developed acute renal colic. He then underwent parathyroidectomy with resection of a single adenoma and normalization of calcium and parathyroid hormone levels. Clinical and therapeutic implications of this rare association are discussed. LEARNING POINTS: The coexistence of KS and PHPT is very uncommon.Patients with mild PHPT often have nonspecific symptoms that may be confused and superimposed with those of hypogonadism.KS patients, especially when young and already osteoporotic at diagnosis, should be screened for other causes of secondary osteoporosis, in particular PHPT.

The use of ciclosporin in paediatric inflammatory bowel disease: an Italian experience.

AIM: To asses the efficacy and safety of ciclosporin in a paediatric population with inflammatory bowel disease. PATIENTS AND METHODS: Twenty-three Italian children treated with ciclosporin were studied retrospectively. The indications for treatment were severe unresponsive colitis, chronic active colitis or severe fistulizing Crohn's disease. The treatment duration, follow-up and causes of drug discontinuation were assessed. RESULTS: Sixteen patients were treated intravenously for a mean time of 10 +/- 7 days (1-24 days) and 19 orally for a mean time of 133 days (17-660 days). The mean follow-up of all patients was 13.2 months. Ciclosporin was totally ineffective, being discontinued for surgery, in nine of 23 patients (39%); it was discontinued for partial response in three patients (13%). During treatment, clinical remission was achieved in eight children (35%) and maintained after drug withdrawal in four (17%). In severe unresponsive colitis, urgent colectomy was avoided in 12 (85%) of 14 patients who tolerated the drug. Side-effects appeared in six of 23 patients (26%), and three (13%) required ciclosporin to be discontinued due to neurotoxicity. CONCLUSIONS: Ciclosporin shows disappointing long-term results in the treatment of refractory inflammatory bowel disease, but can play an important role in preventing urgent surgery in unresponsive severe colitis. Severe side-effects can occur.

Hepatitis A vaccine in pediatric patients affected by metabolic liver diseases.

Twenty children with a variety of metabolic liver diseases were given two doses of hepatitis A vaccine. Adverse reactions were mild. All subjects responded to vaccine with seroconversion to hepatitis A virus antibodies after the first dose, regardless of transaminase values, and had a booster effect from the second doses.

7Beta-oxygenated limonoids from Trichilia elegans ssp. elegans.

Five 7beta- and 7alpha-oxygenated obacunone-type limonoids were obtained on reinvestigation of the seeds of Trichilia elegans ssp. elegans: 7-deoxo-7beta-acetoxykihadanins A and B, 7-deoxo-7beta-hydroxykihadanins A and B and 7-deoxo-7alpha-hydroxykihadanin A, the last three being isolated after acetylation procedures as their mono- and/or diacetate derivatives. This is the first report of the natural occurrence of C-7 beta-substituted limonoids without any oxygenated function at C-6. The structures of these compounds have been established on the basis of 1D- and 2D-NMR spectral techniques, ESI-mass spectrum and X-ray crystallographic data.

99mTc-white cell scanning to detect gut inflammation in children with inflammatory bowel diseases or spondyloarthropathies.

OBJECTIVE: Gut inflammation is a common feature shared by inflammatory bowel diseases (IBD) and the spondyloarthropathies (SpA). The aim of the present study was to compare the reliability of a number of non-invasive investigations for the detection of an inflammatory process of the intestine. METHODS: Forty-two children were studied: (i) patients with a previous diagnosis of IBD (group A); (ii) patients with suspected IBD (group B); and (iii) patients with predominantly rheumatological manifestations associated with gastrointestinal symptoms (group C). All the patients were studied using 99mTechnetium-HMPAO labelled white cell scanning (99mTc-WCS), and abdominal ultrasound (US). In addition the ESR, serum class A immunoglobulins, faecal occult blood (OB) and faecal alpha 1-antitripsin level (F alpha 1-AT) were determined. Colonoscopy plus multiple biopsies and radiological study of the intestine were used as gold standards. RESULTS: 99mTc-WCS showed the highest sensitivity (85%) and specificity (100%) in detecting the presence of gut inflammation. This was followed by ESR and faecal occult blood (63% sensitivity, 44% specificity), F alpha 1-AT (43% sensitivity, 44% specificity) and IgA (42% sensitivity, 88% specificity). Ultrasound was informative in 28% of the active/affected patients, with a specificity of 75%. CONCLUSION: Although ileo-pancolonscopy remains the gold standard for the histological characterisation of gut inflammation, 99mTc-WCS represents the most reliable non-invasive test for its detection.

Structure, Single Crystal EPR Spectra, and Exchange Interactions in [Cu(L-proline)(2)](2).5H(2)O and Cu(D,L-proline)(2).2H(2)O.

A new copper(II) compound, [Cu(L-proline)(2)](2).5H(2)O (C(20)Cu(2)H(42)N(4)O(13)) (called compound I) was synthesized and crystallized, and its structure was solved using X-ray methods. It is monoclinic, space group P2(1), with a = 11.187(1) Å, b = 12.172(3) Å, c = 11.661(1) Å, beta = 114.96(1) degrees, and Z = 2. There are two chemically different copper molecules (labeled A and B), both with the copper atom in a N(2)O(2) square planar coordination. Molecule type A has one water molecule in an apical position. Molecule B has water molecules in each of the two apical positions. Single-crystal EPR measurements have been performed in I and also in Cu(D,L-proline)(2).2H(2)O (compound II). From the similar angular variations of the position of the single resonance observed in both compounds, we evaluated the molecular g tensors. Interpretation of the molecular g tensors resulted in d(x)()()2(-)(y)()()2 orbital ground states. From the angular variations of the line width we calculated the magnitude of the exchange interactions coupling neighbor copper ions in each compound. In I copper ions type A at 7.25 Å are arranged in chains coupled through axial-equatorial bonds. The exchange coupling within these chains is |J/k| = 118 mK. The coupling between copper ions type B is weaker. However, the interactions between copper ions type A and B generate a three-dimensional magnetic network. Our data in compound II indicate that a superexchange pathway containing a weak hydrogen bond C-H- - -O is the path for an exchange interaction with |J'/k| = 48 mK between coppers in neighbor layers at 9.75 Å.

On the lability of dimethylsulfoxide (DMSO) coordinated to the [Ru(II)-NO(+)] species: X-ray structures of mer-[RuCl(3)(DMSO)(2)(NO)] and mer-[RuCl(3)(CD(3)CN)(DMSO)(NO)].

The syntheses of nitrosyl-dimethylsulfoxide-ruthenium(II) complexes with general formula mer-[RuCl(3)(L)(DMSO)(NO)] (L=DMSO or CD(3)CN) is reported. The mer-[RuCl(3)(DMSO)(2)(NO)] (1) complex was obtained from the reaction of [RuCl(3)(NO)] with the sulfoxide ligand in acetone. The mer-[RuCl(3)(CD(3)CN)(DMSO)(NO)] (2) compound was obtained from mer-[RuCl(3)(DMSO)(2)(NO)] maintained in deuterated acetonitrile. These data suggest a slow kinetic reaction due the low lability of the DMSO ligand coordinated to the [Ru(II)-NO(+)] species. The crystal and molecular structures of (1) and (2) have been determined from X-ray studies. Crystal data: for (1), monoclinic, P2(1)/c, a=8.8340(2) A, b=12.0230(3) A, c=13.7064(4) A, beta=114.546(2) degrees, Z=4, R1=0.0429; for (2), monoclinic, P21/n, a=10.0180(7) A, b=9.5070(7) A, c=13.3340(9) A, beta=102.264(4) degrees, Z=4, R1=0.0472. The spectroscopic characterization of (1), in solid state (infrared spectrum) and in solution (nuclear magnetic resonance and cyclic voltammetry) is also described.

A girl with severe fistulizing Crohn's disease.

We report the case of a girl with a severe perianal fistulizing Crohn's disease who during intravenous infusion of cyclosporine developed headache, general seizures and cortical blindness. Head magnetic resonance imaging showed spread, cortical-subcortical nonenhancing signal changes. Full neurological recovery was achieved in 24 hours. Cyclosporine was stopped and a single dose of infliximab was infused with rapid improvement of the fistula that at 7 months' follow-up is still closed.