CT imaging of solid renal masses: pitfalls and solutions.

Computed tomography (CT) remains the first-line imaging test for the characterisation of renal masses; however, CT has inherent limitations, which if unrecognised, may result in errors. The purpose of this manuscript is to present 10 pitfalls in the CT evaluation of solid renal masses. Thin section non-contrast enhanced CT (NECT) is required to confirm the presence of macroscopic fat and diagnosis of angiomyolipoma (AML). Renal cell carcinoma (RCC) can mimic renal cysts at NECT when measuring <20 HU, but are usually heterogeneous with irregular margins. Haemorrhagic cysts (HC) may simulate solid lesions at NECT; however, a homogeneous lesion measuring >70 HU is essentially diagnostic of HC. Homogeneous lesions measuring 20-70 HU at NECT or >20 HU at contrast-enhanced (CE) CT, are indeterminate, requiring further evaluation. Dual-energy CT (DECT) can accurately characterise these lesions at baseline through virtual NECT, iodine overlay images, or quantitative iodine concentration analysis without recalling the patient. A minority of hypo-enhancing renal masses (most commonly papillary RCC) show indeterminate or absent enhancement at multiphase CT. Follow-up, CE ultrasound or magnetic resonance imaging (MRI) is required to further characterise these lesions. Small (<3 cm) endophytic cysts commonly show pseudo-enhancement, which may simulate RCC; this can be overcome with DECT or MRI. In small (<4 cm) solid renal masses, 20% of lesions are benign, chiefly AML without visible fat or oncocytoma. Low-dose techniques may simulate lesion heterogeneity due to increased image noise, which can be ameliorated through the appropriate use of iterative reconstruction algorithms.

Negative thermal expansion in hybrid improper ferroelectric Ruddlesden-Popper perovskites by symmetry trapping.

We present new results on the microscopic nature of the ferroelectricity mechanisms in Ca3 Mn2O7 and Ca3Ti2O7. To the first approximation, we confirm the hybrid improper ferroelectric mechanism recently proposed by Benedek and Fennie for these Ruddlesden-Popper compounds. However, in Ca3Mn2O7 we find that there is a complex competition between lattice modes of different symmetry which leads to a phase coexistence over a large temperature range and the "symmetry trapping" of a soft mode. This trapping of the soft mode leads to a large uniaxial negative thermal expansion (NTE) reaching a maximum between 250 and 350 K (3.6×10^(-6) K^{-1}) representing the only sizable NTE reported for these and related perovskite materials to date. Our results suggest a systematic strategy for designing and searching for ceramics with large NTE coefficients.

Psychological wellbeing in parents of children with Down syndrome: A systematic review and meta-analysis.

We report a review examining the psychological wellbeing of parents of children with Down syndrome (DS) relative to that of parents of typically developing (TD) children. A systematic search identified 57 relevant studies, which were synthesised meta-analytically. Relative to their counterparts with TD children, mothers and fathers of children with DS reported higher levels of parenting stress (mothers: g = 0.57, 95% CI [0.33, 0.81]; fathers: g = 0.40, [0.24, 0.56]), depressive symptoms (mothers: g = 0.42, [0.23, 0.61]; fathers: g = 0.25, [0.02, 0.48]) and psychological distress (mothers: g = 0.45, [0.30, 0.60]; fathers: g = 0.63, [0.26, 0.99]). Small effects were found for anxiety for mothers (g = 0.16, [0.03, 0.29]), with no differences for fathers (g = 0.03, [-0.25, 0.32]). No group differences were found for positive impact of parenting (mothers: g = -0.09, [-0.25, 0.07]; fathers: g = -0.04, [-0.30, 0.22]), while evidence concerning other positive wellbeing outcomes was limited. No significant moderating effects of child age range, country income level, or group differences in parental education level were identified, but limited subgroup analyses were possible. Raising a child with DS may be associated with elevated stress, depressive symptoms, and psychological distress for mothers and fathers. However, levels of parenting reward appear equivalent to those experienced by parents raising TD children.

Joint tenderness and swelling in biologic-treated inflammatory arthritis patients - a tricky trade off?

OBJECTIVE: To compare the pattern of joint responses in patients with rheumatoid arthritis and psoriatic arthritis treated with TNF inhibitor (TNFi) therapy. METHODS: A total of 182 PsA/Rheumatoid arthritis (RA) patients attending the rheumatology unit of a tertiary referral centre in Ireland were recruited and prospectively followed up by the attendant rheumatologists. Clinical progress of the patients was noted at baseline and 6 months after starting TNFi therapy. RESULTS: A total of 114 RA and 68 PsA patients were assessed; 20% of the patients had one of either tender joints or swollen joints after 6 months of therapy. Rheumatoid arthritis patients had a significantly higher proportion of non-tender swollen joints compared with PsA patients, whereas PsA patients had a higher proportion of tender non-swollen joints (p < 0.05). CONCLUSION: Residual joint swelling was found more commonly in RA patients than in PsA patients following TNFi therapy, whereas residual tender joints occurred more frequently in PsA; this may reflect enthesiopathy or periostitis.

Scale transformation of magnetic "bubble" arrays: coupling of topological disorder and polydispersity.

The evolution of disorder in response to period adaptation in a hexagonal magnetic bubble array is shown to arise from the proliferation of dislocations and to proceed by means of intermediate states of steadily decreasing hexatic order to an amorphous final state. Remarkably, each dislocation core imposes a size adjustment on bubbles decorating its constituent pair of five- and sevenfold coordinated sites. Topological disorder thus induces intrinsic polydispersity and converts the initially unimodal size distribution into a trimodal one. This intimate interplay between geometry and topology provides an explicit mechanism by which structural disorder arises as a result of frustration.

Magnetic flux-line lattices and vortices in the copper oxide superconductors.

A variety of recent experiments on both the static and the dynamic properties of vortices and flux-line lattices in the mixed state of the copper oxide superconductors are discussed. The experiments are of two basic types: (i) experiments that image the magnetic flux patterns either with magnetic decoration or neutrons and give information about static structures, and (ii) experiments that explore the dynamics of vortices either through the resistivity or other electrodynamic responses of the material. Results of these experiments argue in favor of the existence of a true phase transition in the high-field vortex state from a low-temperature superconducting vortex glass phase into a disordered high-temperature vortex fluid phase. The vortex glass phase transition model does a good job of explaining high-precision measurements of the dynamics at the transition. At low fields and temperatures, very long range hexatic order in the flux-line lattice is observed.

Synthesis and structure of Zr(iv)- and Ce(iv)-based CAU-24 with 1,2,4,5-tetrakis(4-carboxyphenyl)benzene.

Two new MOFs denoted as M-CAU-24 (M = Zr, Ce) based on 1,2,4,5-tetrakis(4-carboxyphenyl)benzene (H4TCPB) were obtained under mild reaction conditions within 15 min. The MOFs with composition [M6(µ3-O)4(µ3-OH)4(OH)4(H2O)4(TCPB)2] crystallise in the scu topology, a connectivity hitherto unreported for Zr-MOFs with tetracarboxylate linker molecules. Zr-CAU-24 exhibits UV/blue ligand-based luminescence.

Interleukin-1 beta inhibits glutamate release in hippocampus of young, but not aged, rats.

The proinflammatory cytokine, interleukin-1, is synthesized in neuronal and glial cells and is released in response to stress/injury. IL-1 exerts profound effects on the central nervous system, which include an inhibitory effect on synaptic activity in hippocampus, a brain area expressing a high density of IL-1 receptors. We report that IL-1 beta has an inhibitory effect on KCl-stimulated release of glutamate and KC1-stimulated [45Ca] influx in synaptosomes prepared from hippocampus of 4-month-old rats. These effects were inhibited by the endogenous receptor antagonist, IL-1ra, and by the phospholipase A2 (PLA2) inhibitor, quinacrine, suggesting that IL-1 receptor activation is coupled to PLA2. An inhibitory effect of IL-1 beta on protein kinase C activity was also observed. KC1-induced calcium-dependent release and calcium influx, and protein kinase C activity were significantly decreased in hippocampal synaptosomes prepared from 22-month-old compared to 4-month-old animals. In contrast to the inhibitory effect of IL-1 beta in synaptosomes prepared from young adult animals, no effect was observed on release, calcium influx, or protein kinase C activity in synaptosomes prepared from aged animals. We report that there is an age-related increase in expression of IL-1 beta in hippocampus and propose that this change may underlie the attenuated responses to IL-1 beta in hippocampus of aged animals.

Age-related changes in oxidative mechanisms and LTP are reversed by dietary manipulation.

Aged rats exhibit an impaired ability to sustain long-term potentiation in dentate gyrus which correlates with a decrease in arachidonic acid concentration. Here we confirm the previous finding that dietary supplementation with arachidonic acid and its precursor, gamma-linolenic acid, reversed the impairment in LTP in aged rats and report that there is a significant correlation between membrane arachidonic acid concentration and response to tetanic stimulation. We observed that age was associated with decreases in the concentration of vitamins C and E and increased activity of superoxide dismutase, indicative of a compromise in antioxidative defenses; these changes were paralleled by increases in interleukin-1beta (IL-1beta) concentration and lipid peroxidation. Dietary manipulation restored polyunsaturated fatty acid concentrations to values observed in tissue prepared from young rats and reversed the age-related changes in vitamins E and C, IL-1beta concentration and superoxide dismutase activity. We propose that these changes reverse the increase in lipid peroxidation and thereby the age-related change in polyunsaturated fatty acids.

Analysis of the effect of membrane arachidonic acid concentration on modulation of glutamate release by interleukin-1: an age-related study.

Aging is associated with a change in membrane composition that includes a decrease in membrane polyunsaturated fatty acids, including arachidonic acid, and an increase in membrane cholesterol. Alterations in membrane structure are likely to impact on transmitter release, which relies on the fusion of synaptic plasma and synaptic vesicle membranes, and it may therefore be the underlying cause of the age-related decrease in glutamate release in hippocampal preparations. Recent evidence indicates that interleukin-1, by binding with its receptor, inhibits glutamate release in hippocampal synaptosomes prepared from young but not aged rats. The age-related attenuated effect may be due to impaired ligand-receptor interactions arising from the change in membrane composition, which should theoretically be reversed by increasing membrane polyunsaturated fatty acid concentration. To test this hypothesis, we have investigated the effect of a diet supplemented with arachidonic acid and its precursor, gamma-linolenic acid, on membrane arachidonic acid concentration, glutamate release and on the release response to interleukin-1 in hippocampal tissue prepared from aged and young rats. We report that dietary supplementation reversed the age-related changes in membrane arachidonic acid and expression of IL-1beta. We also present data that indicate that the age-related decrease in glutamate release from hippocampal synaptosomes was reversed in aged animals that had been fed on the experimental diet. The data support the view that changes in membrane composition contribute to certain age-related deficits, in particular the decrease in glutamate release observed in hippocampal synaptosomes.

Mitogenic effects and nuclear localisation of procorticotrophin-releasing hormone expressed within stably transfected fibroblast cells (CHO-K1).

To investigate the intracellular localisation and biological activity of procorticotrophin-releasing hormone (proCRH), we have established stably transfected CHO-K1 cells expressing the rat pre-proCRH cDNA. Using immunoblot analysis of cell lysates of transfected CHO-K1 cells, we detected a major CRH immunoreactive band with an apparent molecular weight of approximately 19 kDa. This 19 kDa band could account for full length proCRH molecule which has not undergone post-translational modifications. Metabolic labelling followed by immunoprecipitation, SDS-PAGE and autoradiography indicated that no endoproteolytic processing of proCRH takes place within the transfected CHO-K1 cells. Immunofluorescence staining localises the CRH precursor to both the cytoplasm and to the nucleus in transfected CHO-K1 cells. This result was confirmed using subcellular fractionation techniques on radiolabelled CHO-K1 cells expressing immunoreactive CRH. A major CRH-immunoreactive band of 19 kDa was detected both in the microsomal and secreted fractions, indicating the presence of proCRH within the secretory pathway of these cells. This was also evident in the nuclear fraction, therefore confirming the nuclear localisation of proCRH. Analysis of DNA concentration, cell number and DNA synthesis showed that stably transfected CHO-K1 cells expressing proCRH have a higher proliferation and DNA synthesis rate than wildtype CHO-K1 cells or CHO-K1 cells transfected with pEE14 alone. Our results therefore suggest a mitogenic role for the intact proCRH molecule within CHO-K1 cells. Furthermore, treatment of mouse corticotrophic tumour cells (AtT20/D16-16) with conditioned medium from transfected CHO-K1 cells expressing proCRH, stimulated both DNA synthesis and cell proliferation above basal levels. Our results constitute the first reported direct evidence of a mitogenic role for proCRH acting on a corticotrophic cell population.

Procorticotrophin-releasing hormone: endoproteolytic processing and differential release of its derived peptides within AtT20 cells.

Procorticotrophin-releasing hormone (proCRH) is expressed mainly in the hypothalamus and in the placenta, where it undergoes tissue-specific endoproteolysis. Our results show that within stably transfected AtT20/D16V cells proCRH is cleaved to generate two fragments of approximately 8 and 3 kDa which could account for proCRH(125-194) and proCRH(125-151), respectively, and a 4.5 kDa product which could account for mature IR-CRH(1-41). The immunofluorescence staining patterns for IR-CRH and IR-ACTH and their response of secretagogues indicate targeting of proCRH and POMC to the secretory pathway in transfected AtT20 cells. In this work, we have used a unique set of specific RIAs and IRMAs to the full length POMC and proCRH molecules and several products of endoproteolytic processing to assess if they could be released differentially in response to stimulation. Although the release of both IR-ACTH and IR-CRH peptides from transfected AtT20 cells is stimulated in response to exposure to high potassium stimulation (51 mM KCl/SmM CaCl2), the sorting index (SI) suggests that mature ACTH is sorted to the regulated secretory pathway 2.1-fold more efficiently than mature CRH(1-41). Mature ACTH is also sorted to the regulated secretory pathway 9-fold more efficiently than IR-proCRH(125-151). Also, mature CRH(1-41) is sorted to the regulated secretory pathway 3-fold more efficiently than IR-proCRH(125-151). These results therefore indicate that the intracellular mechanisms for the storage and release of POMC, proCRH and their endoproteolytic products differ and would sustain the hypothesis that within mammalian peptidergic cells, different biologically active peptides originating from the same or different precursor molecules, could be differentially released in response to specific stimuli. This would give these cells the capacity to finely regulate neurotransmitter release in response to environmental and physiological demands.

Corticotrophin-releasing hormone receptor type 1: generation and characterization of polyclonal antipeptide antibodies and their localization in pituitary cells and cortical neurones in vitro.

Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide which plays a major role in regulating the endocrine response to stress. CRH acts by first binding to specific receptors on the plasma membrane of target cells. A CRH receptor from a human corticotroph adenoma and rat brain has recently been cloned (CRH-R1). In this paper, we have chosen three different peptide sequences within the CRH-R1 molecule which bear no similarity to other members of this receptor subfamily (or indeed any known protein) and which are likely to be exposed on the surface of the native protein, for antibody production. Some of these fragments produced antipeptide antibodies of good titre which cross-reacted with the CRH-R1 receptor expressed in transiently transfected COS-7 cells and in tissue extracts from rat cerebellum, cortex, pituitary gland and human myometrium, both in Western blots and in liquid-phase radioimmunoassay. We used immunofluorescence techniques to localize the CRH receptor in transiently transfected COS-7 cells, primary cultures of rat anterior pituitary (AP) cells, the corticotroph-tumour cells AtT20 D16-16 and cortical neurons in primary culture. Our results indicate IR-CRH-R1 receptors have a punctate distribution on the plasma membrane of AP cells and AtT20 D16-16 cells. Whilst in AP cells their appearance is a fine punctate pattern, in AtT20 cells, they appear as large patches which could account for receptor clusters. Within primary cortical neurons, their distribution does not appear to be polarized. Our results suggest that distribution of CRH-R1 receptors within the different cell-types investigated depends not only on the amino acid sequence but also on cellular factors.

Histopathological patterns of melanoma metastases in sentinel lymph nodes.

AIMS: Sentinel lymph node biopsy (SLNB) is an important component in the staging and treatment of cutaneous melanoma (CM). The medical literature provides only limited information regarding melanoma sentinel lymph node (SLN) histology. This report details the specific histological patterns of melanoma metastases in sentinel lymph nodes (SLNs) and highlights some key factors in evaluating SLNs for melanoma. METHODS: From 281 SLNB cases between June 1998 and May 2002, 79 consecutive cases of SLN biopsies positive for metastases from CM were retrospectively reviewed. The important characteristics of the SLNs and the metastatic foci are described. RESULTS: The median size of positive SLNs was 17 mm (range, 5-38). SLNs had a median of two metastatic foci (range, 1-11), with the largest foci being a median of 1.1 mm in size (range, 0.05-24). S-100 and HMB-45 staining was positive in 100% and 92% of the detected metastatic foci, respectively. The metastatic melanoma cells were epithelioid, spindled, and mixed in 86%, 5%, and 9% of cases. Metastatic foci were most often (86%) found in the subcapsular region of the SLN. Benign naevic cells were found coexisting in 14% of positive SLNs. CONCLUSIONS: Staining for S100 is more sensitive than HMB-45 (100% v 92%), but HMB-45 staining helped to distinguish benign naevic cells from melanoma. The subcapsular region was crucial in SLN evaluation, because it contained the metastases in 86% of cases. Evaluation of the subcapsular space should not be compromised by cautery artefacts or incomplete excision of the SLN.

Generation and characterization of an antiserum reactive with a proteolytic processing site within rat procorticotrophin-releasing hormone.

In this paper we report the generation of an antibody specific for the cleavage site within procorticotrophin-releasing hormone (proCRH) at the N-terminus proCRH/CRH (1-41) junction. Using radioimmunoassay techniques were show that the antibody generated (781) cross-reacts specifically with the proCRH (137-150) Tyr fragment, corresponding to the cleavage site within the full length precursor molecule. The anti-cleavage site antibody does not crossreact with the endoproteolytic products originated from the CRH precursor molecule, i.e. CRH (1-41) or proCRH (125-151) or with any of the CRH-immunoreactive fragments tested i.e. CRH (36-41), CRH (1-20) and CRH (30-41). It also shows no cross-reactivity with CRH-related substances from other species, i.e. urotensin I (fish) and sauvagine (frog). The cleavage site antibody (781), recognizes the full length proCRH molecule in Western blotting and in liquid phase radioimmunoassay from transfected CHO-K1 cells expressing the full length pre-proCRH cDNA. Using immunofluorescence and immunoprecipitation techniques followed by SDS-PAGE and autoradiography, we confirm the presence of the intact CRH precursor molecule within the nucleus and the cytoplasm of stably transfected CHO-K1 cells expressing immunoreactive proCRH. The immunofluorescence studies using primary cultures of hypothalamic neurons, show that immunoreactive (IR) proCRH is localized within the perinuclear region and was also seen along the neuronal processes where it accumulates at their tips. Our results, therefore, show that this antibody will be an invaluable tool in the study of intracellular trafficking in relation to the endoproteolytic processing of the CRH precursor molecule.

The treatment of esophageal perforation with delayed recognition and continuing sepsis.

Five patients, recently treated for esophageal ruptures, provided a spectrum of "late" perforations. Treatment was individualized for each patient and ranged from suture closure of the perforation to esophagectomy. Four of the 5 patients survived and now have no dietary restrictions. The goals of treatment should be: (1) elimination of sources of chemical and bacterial soilage; (2) drainage of infected areas; (3) augmentation of host defenses by antibiotics; and (4) provision of adequate nutrition. Several treatment adjuncts, alone or in combination, may be used to accomplish these goals. The selection of treatment methods should be influenced by the site of perforation, the extent of local inflammation, the status of the residual esophagus, the overall status of the patient, and the chronicity of the perforation. As the risk of uncontrolled sepsis increases, the surgeon should take more aggressive and definitive steps, up to and including esophagectomy in certain cases, to prevent further soilage.

Traumatic rupture of ascending aorta and left main bronchus.

A 14-year-old male pedestrian was hit by a truck and admitted with respiratory distress and subcutaneous emphysema. Aortography revealed disruption of the ascending aorta. Bronchoscopy revealed rupture of the left main bronchus at the carina. Both lesions were repaired using a median sternotomy, cardiopulmonary bypass, and a transpericardial approach for the bronchial repair. To our knowledge, this is the first report of successful repair of a combined rupture of a major bronchus and the ascending aorta.

Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro.

The effects of the cytokine, interleukin-1 beta (IL-1 beta), and its receptor antagonist IL-1ra, were studied on long-term potentiation in the dentate gyrus of rat hippocampal slices. Field excitatory postsynaptic potentials were recorded extracellularly in the molecular region of the dentate gyrus in response to stimulation of the medial perforant path. Low frequency synaptic transmission was unaffected by IL-1 beta (1 ng/ml), but pre-treatment with IL-1 beta completely blocked induction of long-term potentiation. Co-application of IL-1 beta and IL-1ra (100 ng/ml) attenuated the inhibitory effect of IL-1 beta. In parallel with these findings, we demonstrate that IL-1 beta also inhibited 45Ca influx into the slices. The inhibitory effect of IL-1 beta on induction was mimicked by tumour necrosis factor (TNF; 4.5 ng/ml) and lipopolysaccharide (LPS; 10 micrograms/ml). These results indicate a modulatory role for cytokines in hippocampus and suggest that the inhibitory effect of IL-1 beta on long-term potentiation may relate to its inhibitory effect on calcium channel activity.

Dielectric relaxations in ultrathin isotactic PMMA films and PS-PMMA-PS trilayer films.

The local and cooperative dynamics of supported ultrathin films ( L = 6.4 - 120 nm) of isotactic poly(methyl methacrylate) (i-PMMA, Mn = 118 x 10(3) g/mol) was studied using dielectric relaxation spectroscopy for a wide range of frequencies (0.1 Hz to 10(6) Hz) and temperatures (250 - 423 K). To assess the influence of the PMMA film surfaces on the glass transition dynamics, two different sample geometries were employed: a single layer PMMA film with the film surfaces in direct contact with aluminum films which act as attractive, hard boundaries; and a stacked polystyrene-PMMA-polystyrene trilayer film which contains diffuse PMMA-PS interfaces. For single layer films of i-PMMA, a decrease of the glass transition temperature T(g) by up to 10 K was observed for a film thickness L < 25 nm (comparable to R(EE)), indicated by a decrease of the peak temperature T(alpha) in the loss epsilon(")(T) at low and high frequencies and by a decrease in the temperature corresponding to the maximum in the apparent activation energy E(a)(T) of the alpha-process. In contrast, measurements of i-PMMA sandwiched between PS-layers revealed a slight (up to 5 K) increase in T(g) for PMMA film thickness values less than 30 nm. The slowing down of the glass transition dynamics for the thinnest PMMA films is consistent with an increased contribution from the less mobile PMMA-PS interdiffusion regions.

Shoulder hemiarthroplasty for proximal humeral fractures.

Shoulder hemiarthroplasty is a well-accepted surgical procedure for the treatment of specific subtypes of proximal humeral fractures, including four-part fractures, three-part fractures associated with severe osteopenia, head-splitting and severe articular impression fractures. Careful patient assessment and meticulous surgical technique are essential to prevent complications. The results are satisfactory in approximately 80% of cases. The results are better in younger patients and in acute versus chronic fractures. There are a significant number of complications that are related to technical details of the procedure. Careful placement of the prosthesis and secure reattachment of the tuberosities to the shaft reduce the chance of complication following surgery. Good to excellent results in terms of range of motion and pain relief can be expected in most patients.