The value of oblique pinhole images in pre-operative localisation with 99mTc-MIBI for primary hyperparathyroidism.

Technetium-99m labelled 2-methoxyisobutylisonitrile (MIBI) has been extensively utilised for preoperative localisation of parathyroid adenomas. Imaging techniques have varied widely, with many centres not performing routine oblique images; thus this study aimed to examine the value of routine oblique pinhole imaging. Ninety-two patients underwent pre-operative 99mTc-MIBI imaging including early and delayed anterior oblique pinhole images in addition to standard anterior pinhole images and a thyroid study prior to surgery for primary hyperparathyroidism. These studies were reviewed blindly comparing anterior and oblique images and anterior images only in relation to surgical findings. Of the 92 patients, 83 were found to have 86 parathyroid adenomas or parathyroid adenoma/hyperplasia at surgery. When compared to anterior images only, oblique views improved overall sensitivity from 76% to 88% (P<0.05), correctly localised 11 more adenomas than anterior images alone (13%) and improved the confidence of interpretation in 17 patients (20%). In conclusion, routine oblique pinhole views result in greater sensitivity and reporter confidence in pre-operative parathyroid localisation with 99mTc-MIBI.     

A study on flow properties of semisolid dosage forms

There are a wide variety of semi-solid ointments used for healing the skin diseases, whose therapeutic and skin penetration abilities may greatly differ from one another depending on the compositions of ointment vehicles. A computer optimization technique was applied to obtain the optimum formula of o/w type ointment giving the in vitro maximum absorption rate through hairless rat skin membrane. Some of the formulations were selected to find out a relationship between skin penetration of ointment and its rheological characteristics. The experimental value of absorption rate obtained from the ointment by optimum formula agreed well with the theoretical value obtained from a polynomial regression analysis. Three kinds of ointments selected among 15 formulations were obtained with a concentric cylinder type rheometer (Model; Rheolab SM-HM Physica, Germany) at 20, 30, 40 and 50°C for rheograms of rhelolgical properties of o/w type ointments. As the temperature was raised, all products showed a decrease in both shear stress and yield values. The higher skin penetration, the lower shear stress showed.     

No news is not good news: information preferences of patients with cancer

Many patients express dissatisfaction with clinicians' information-giving. When the information is complex or potentially upsetting, clinicians may deliberately withhold information, especially if they lack the skills to handle patients' emotional reactions. Others underestimate the amount of information patients require. In this study, a heterogeneous sample of 101 patients participating in a trial assessing the benefits of receiving audio-taped recordings of their ‘bad news’ consultations, completed a questionnaire similar to Cassileth's Information Styles Questionnaire. This questionnaire assessed patients' preferences for both general and specific information about their disease and its treatment. Of the sample, 94% expressed a desire for as much information as possible from their oncologist, be it good or bad; 4% wished for information only if it was good news and 2% declined extra information, preferring to leave things up to the doctor. Patients wanting less specific or no extra information were older and had poorer prognoses than those wanting full disclosure. Although precise information needs varied between patients, this study showed that patients with cancer in general wish to be well-informed about diagnosis, prognosis, therapeutic options and side-effects.     

Effects of Anemarrhena asphodeloides on IgE-mediated passive cutaneous anaphylaxis,compound 48/80-induced systemic anaphylaxis and mast cell activation

BackgroundWe investigated the effect of Anemarrhena asphodeloides Bunge (Liliaceae) water extract (AAWE) on mast cell-mediated anaphylactic reactions. Mast cell-mediated anaphylactic reaction is involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, AAWE is known to have antioxidant and anticancer activity. However, its specific effect on mast cell-mediated anaphylactic reactions is still unknown.MethodsWe examined whether or not AAWE could inhibit IgE-mediated passive cutaneous anaphylaxis (PCA), compound 48/80-induced systemic anaphylaxis, and mast cell activation.ResultsOral administration of AAWE inhibited compound 48/80-induced systemic anaphylaxis in mice. AAWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl IgE antibody in rats. AAWE reduced compound 48/80-induced degranulation of rat peritoneal mast cells (RPMCs). Moreover, AAWE inhibited histamine release and calcium uptake of RPMCs induced by compound 48/80 in a dose-dependent manner. AAWE also significantly inhibited secretion of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in phorbol 12-myristate 13-acetate plus calcium ionophores A23187-stimulated RPMCs.ConclusionsThese results suggest that AAWE suppresses compound 48/80-induced mast cell activation by inhibition of cellular mechanisms in signaling pathways, and would be beneficial for treatment of mast cell-mediated anaphylactic response.     

Performance of an Early Infant Diagnostic Test,AmpliSens DNA-HIV-FRT,Using Dried Blood Spots Collected from Children Born to Human Immunodeficiency Virus-Infected Mothers in Ukraine

An accurate accessible test for early infant diagnosis (EID) is crucial for identifying HIV-infected infants and linking them to treatment. To improve EID services in Ukraine, dried blood spot (DBS) samples obtained from 237 HIV-exposed children (≤18 months of age) in six regions in Ukraine in 2012 to 2013 were tested with the AmpliSens DNA-HIV-FRT assay, the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 Qual test, and the Abbott RealTime HIV-1 Qualitative assay. In comparison with the paired whole-blood results generated from AmpliSens testing at the oblast HIV reference laboratories in Ukraine, the sensitivity was 0.99 (95% confidence interval [CI], 0.95 to 1.00) for the AmpliSens and Roche CAP/CTM Qual assays and 0.96 (95% CI, 0.90 to 0.98) for the Abbott Qualitative assay. The specificity was 1.00 (95% CI, 0.97 to 1.00) for the AmpliSens and Abbott Qualitative assays and 0.99 (95% CI, 0.96 to 1.00) for the Roche CAP/CTM Qual assay. McNemar analysis indicated that the proportions of positive results for the tests were not significantly different (P > 0.05). Cohen''s kappa (0.97 to 0.99) indicated almost perfect agreement among the three tests. These results indicated that the AmpliSens DBS and whole-blood tests performed equally well and were comparable to the two commercially available EID tests. More importantly, the performance characteristics of the AmpliSens DBS test meets the World Health Organization EID test requirements; implementing AmpliSens DBS testing might improve EID services in resource-limited settings.     

Effects of a Medical Aid program on medical utilization patterns for low-income patients with affective disorder in Seoul

Mental illness has been increasing globally and its global burden of disease has reached a significant level, and urban dwellers have more chances of having worse mental health status due to high population density, isolated social networks. In Korea''s medical security system, Medical Aid (MA) program and National Health Insurance (NHI), patients covered by MA pay much smaller out-of-pocket payments for outpatient services because of exempt from hospitalization fees. However, as a result of focusing on improving access to medical services for the urban poor due to lower out-of-pocket payment, their healthcare costs have greatly increased, while their health management has thus far been inadequate. In light of the background, this study investigated the differences in patterns of medical utilization among affective disordered patients covered by the MA program and the NHI system respectively.Data used for this study were extracted from customized health information data from the National Health Insurance Service (NHIS). The data source used in this study, customized claims data from the NHIS, is census data, which strengthens the representativeness and reliability of the study results. A total of 6754 inpatients (MA: 3327 and NHI 20%: 3327) diagnosed with the affective disorder were retrieved by Propensity Scores Matching (PSM).The length of stay of MA beneficiaries was found to be longer than that of NHI enrollees. However, the rate of hospital emergency room visits by NHI enrollees was higher than that of MA beneficiaries.Overall, community-based interventions are required to prevent and treat mental health by providing primary medical care in the community, and linking with mental health centers. Such policies will ultimately improve the financial sustainability of medical security systems.     

Lysosomal cathepsin D mediates endogenous mucin glycodomain catabolism in mammals

Mucins are functionally implicated in a range of human pathologies, including cystic fibrosis, influenza, bacterial endocarditis, gut dysbiosis, and cancer. These observations have motivated the study of mucin biosynthesis as well as the development of strategies for inhibition of mucin glycosylation. Mammalian pathways for mucin catabolism, however, have remained underexplored. The canonical view, derived from analysis of N-glycoproteins in human lysosomal storage disorders, is that glycan degradation and proteolysis occur sequentially. Here, we challenge this view by providing genetic and biochemical evidence supporting mammalian proteolysis of heavily O-glycosylated mucin domains without prior deglycosylation. Using activity screening coupled with mass spectrometry, we ascribed mucin-degrading activity in murine liver to the lysosomal protease cathepsin D. Glycoproteomics of substrates digested with purified human liver lysosomal cathepsin D provided direct evidence for proteolysis within densely O-glycosylated domains. Finally, knockout of cathepsin D in a murine model of the human lysosomal storage disorder neuronal ceroid lipofuscinosis 10 resulted in accumulation of mucins in liver-resident macrophages. Our findings imply that mucin-degrading activity is a component of endogenous pathways for glycoprotein catabolism in mammalian tissues.

Mammalian cells append glycans to the majority of their secreted and cell surface proteins (1). These extracellular glycoproteins are broadly categorized as Asn-linked N-glycoproteins and Ser/Thr-linked O-glycoproteins, both of which are typically elaborated into branching structures with many monosaccharide units strung together. Therefore, catabolism of a given extracellular protein typically involves hydrolase-mediated breakdown of both its peptide backbone and one or more complex glycans.Much of our current understanding of glycoprotein catabolism arises from the study of human mutations that cause N-glycoprotein degradation pathways to go awry. Analysis of accumulation products in lysosomal storage disorders such as mannosidosis, aspartylglucosaminuria, sialidosis, Schindler (types I and II), galactosialidosis, and fucosidosis have provided a framework to understand N-glycoprotein catabolism (2). In brief, N-glycoproteins are extensively proteolyzed such that there are free alpha carboxyl and amino groups on the asparagine residue bearing the glycan. After fucose is removed by lysosomal α-L-fucosidase, N-glycanase aspartylglucosaminidase hydrolyzes the glycan-peptide bond. The free glycan can then be broken down from both reducing and nonreducing ends by a variety of hydrolases (2).Lysosomal degradation of O-glycoproteins is understudied relative to that of N-glycoproteins, in part due to unique difficulties associated with structural analysis of O-glycopeptides (3), and is typically assumed to occur analogously to N-glycoprotein catabolism (2, 4). Mucins are a class of extracellular O-glycoproteins that have challenged this assumption. Mucins are characterized by repeating domains bearing a high frequency of N-acetylgalactosamine (GalNAc)-linked serine and threonine residues, such that the biomolecule as a whole can exceed 50% glycosylation by mass (5). The densely spaced glycans in mucin glycodomains endow them with unique properties, including a rigid, extended secondary structure and resistance to proteolysis (6). As such, mucin catabolism has been suggested to proceed in the reverse order of N-glycan catabolism, involving removal of glycans followed by proteolysis of the peptide backbone (2), or through shedding from cell surfaces into luminal spaces (7). Meanwhile, major histocompatibility complex (MHC) I and MHC II peptides bearing mucin-type O-glycans have been repeatedly observed (8–11), indicating that mucin domains can, under some circumstances, be proteolyzed with their glycans intact.We and others have characterized proteases from the bacterial kingdom that cleave within densely O-glycosylated mucin domains without prior deglycosylation, termed mucinases (3, 12–14). The existence of bacterial mucinases indicates that access to the peptide backbone through densely spaced O-glycans is not impossible for a proteolytic enzyme. Given the biological ubiquity and clinical significance of mucins (15–20), we set out to systemically evaluate if mammals encode enzyme(s) with proteolytic activity toward glycosylated mucin domains. At the outset, we considered sequence and structure-based approaches to identify candidates from mammalian genome sequences. However, as bacterial mucinases share poor sequence homology (12, 21), we turned to a biochemical strategy.     

Effect of chitosan oligosaccharide on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in mice

The abilities of two types of chitosan oligosaccharides, chitosan oligosaccharide I (1-kDa相似文献   

Long-term results of total hip arthroplasty with a cemented custom-designed swan-neck femoral component for congenital dislocation or severe dysplasia: a follow-up note

BACKGROUND: This follow-up study updates the results in a consecutive series of nineteen cemented total hip replacements with a swan-neck femoral component in patients with congenital dislocation or severe hip dysplasia. The series was previously reported on in 1993. METHODS: The patients were petite, with an average height of 152 cm and an average weight of 50 kg, and the femoral canals could not accommodate an off-the-shelf femoral component. Sixteen of the nineteen hips were available for follow-up at an average of 13.3 years (range, eleven to twenty years). Fourteen hips had up-to-date clinical and radiographic examinations. RESULTS: At the time of the latest follow-up, thirteen hips were rated as excellent; two, as good; and one, as a failure because of loosening of both components requiring revision eleven years after the index operation. Another hip required acetabular revision because of loosening fifteen years after the index operation. The rates of femoral and acetabular component revision were 6% and 12.5%, respectively. Radiographic analysis demonstrated that no femoral component was loose. One cup was definitely loose at 19.5 years, and three cups were possibly loose at an average of fourteen years. The radiographic rate of acetabular loosening was 33%. The total rate of cup failure (radiographic loosening and revision) was 43%. CONCLUSIONS: The excellent clinical and radiographic results associated with the swan-neck femoral component, and the 94% rate of survival, at an average of 13.3 years (range, eleven to twenty years) indicate that the biomechanical objectives of this custom-designed prosthesis for patients with congenital dislocation or severe hip dysplasia were met. On the basis of this favorable long-term experience, we still use this prosthesis when the anatomic abnormality cannot be adequately addressed by use of a commercially available prosthetic component.