食管球囊联合超细胃镜扩张贲门失弛缓症1例

对1例中年贲门失弛缓症患者于超细胃镜直视下应用食管球囊预扩张一次的基础上,将胃镜插至胃底反转对球囊定位后再次扩张.扩张口径满意,无穿孔；症状缓解,随访1mo无复发.     

CB7-02: Medicare Part D Cost-sharing and Antipsychotic Drug Use in Two Medicare Advantage Systems

Background/Aims The Affordable Care Act phases out the Medicare Part D coverage gap over the next decade; however, beneficiaries will continue to face substantial cost-sharing even after 2020. Higher cost-sharing has been associated with reductions in necessary drug use. Non-adherence to antipsychotics, a mainstay of schizophrenia treatment, is associated with worse clinical outcomes. We investigated the impact of Part D cost-sharing on antipsychotic spending and adherence for beneficiaries with schizophrenia, focusing on within-person cost-sharing increases associated with the gap. Methods We included Medicare Advantage (MA) beneficiaries enrolled in plans linked with an integrated delivery system (IDS, N=999) and non-integrated systems (non-IDS, N=3,878) who received 1+ inpatient or 2+ outpatient schizophrenia diagnoses during 2006-2007 and antipsychotics in 2006. We examined total and out-of-pocket antipsychotic spending and adherence based on the proportion of days covered (PDC) using Part D drug event data. We examined changes in monthly costs and adherence before and after beneficiaries reached the gap using within-person fixed effects models to account for unmeasured, time-stable confounders across comparison groups. Results Overall, 34% of subjects faced a gap in 2007; most remaining beneficiaries received low- income subsidies (LIS) that covered the gap. Among gap subjects, 45% (IDS) and 55% (non-IDS) reached the gap threshold of $2,400 in total drug spending. Monthly out-of-pocket spending increased substantially in both systems during vs. before the gap (IDS: $139 [$118 to $159]; non-IDS: $84 [$79 to $91]). Total monthly antipsychotic costs and adherence decreased after reaching the gap among non-IDS beneficiaries (costs: -$163 [-$179 to -$146]; adherence: -14.7 percentage points [-16.2 to -13.1]). Among IDS beneficiaries, changes in total costs and adherence pre- vs. post-gap were not significant (costs: -$82 [-$179 to $15]; adherence: 3.1 pp [-0.6 to 6.8]). For LIS beneficiaries with no gap, adherence did not decrease after reaching the gap spending threshold. Discussion Antipsychotic adherence decreased during the gap among non-IDS MA beneficiaries, but did not among IDS beneficiaries or among LIS recipients without a gap. Cost-related non- adherence to antipsychotics among beneficiaries with schizophrenia could result in adverse clinical outcomes. Work is needed to explore potential system-level characteristics that influence patients' responses to cost-sharing.     

NIA0004Unsaturated fatty acids diminish the detrimental effects of saturated fatty acids on insulin signalling in human muscle by decreasing de novo ceramide production

Insulin resistance in skeletal muscle is associated with impaired oxidative capacity and reduced size, number and function of mitochondria. Insulin‐resistant individuals have lower adiponectin concentrations, a characteristic predating the development of type‐2 diabetes (T2D). The aim of this study was to test the potential role of adiponectin in mitochondrial bioenergetics in individuals predisposed to develop T2D, in adiponectin KO mice and in primary muscle cell culture. Individuals with a family history of T2D displayed lower plasma adiponectin concentration (P = 0.03), reduced PGC1β (P = 0.04) and mtFAM (P = 0.03) mRNA, lower mitochondrial content (P = 0.006), citrate synthase (P = 0.02) and (‐HAD (P = 0.03) activity, suggesting defective mitochondrial bioenergetics in skeletal muscle. In addition, AdipoR1 was the principle correlate of mitochondrial content (r² = 0.81), suggesting an important role in mitochondrial biogenesis. Knock out of adiponectin in mice was associated with low PGC1α and PPARδ mRNA (both, P < 0.05), reduced mitochondrial content (P < 0.05) and COX II activity (P < 0.05) and markers for type‐1 oxidative fibers in skeletal muscle. This suggests that mitochondrial function is dependent on circulating adiponectin. In primary cultures of human myotubes, treatment with adiponectin induced AMPKK/ AMPK activity, PGC1α protein, mitochondrial biogenesis (P < 0.05), palmitate oxidation (P < 0.05), citrate synthase (P < 0.05) and SOD activity (P < 0.05), and reduced mitochondrial membrane potential and the production of ROS (P < 0.05). The inhibition of adiponectin receptor expression by siRNA or of AMPK by a pharmacological agent blunted the induction in mitochondrial function. Our findings indicate a novel pathway in skeletal muscle by which adiponectin increase mitochondrial number and function and exerts an insulin sensitizing effect.     

Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon [see comments]

In 13 patients with severe steroid-refractory idiopathic immune thrombocytopenia (ITP), a short course of recombinant alpha 2b interferon (IFN), given at a dose of 3 MU for 12 doses, caused a significant increase in platelet count in 11 patients. The rise in platelet count occurred following completion of the short course of IFN in 10 patients and occurred during therapy in one patient. Three patients showed an increase to normal platelet counts within 14 days of discontinuing the drug, eight showed a partial response, with a platelet count increase from 30 to 100 x 10(9)/L, and two patients showed minimal response. One complete responder relapsed at 5 months from initial response, and a further course of alpha 2b IFN caused a second prompt response with a rise of platelet count to supranormal levels. Short-course alpha 2b IFN can be recommended as a therapy for severe ITP. Responses are seen in splenectomized and nonsplenectomized subjects, and thrombocytopenia is not exacerbated during treatment.     

Improvement in airway responsiveness and asthma severity during pregnancy. A prospective study

In the myometrium and gut, smooth muscle becomes less contractile during pregnancy, probably because of the effect of progesterone and estrogen. It is not known whether these hormones cause similar changes in airway smooth muscle, and therefore, this study examined airway responsiveness during the large hormonal changes of pregnancy and evaluated whether changes in responsiveness are associated with changes in (1) progesterone and estrogen and (2) the clinical severity of asthma. Twenty nonpregnant asthmatic women were assessed every 3 months until conception. In the 16 who conceived, assessments were repeated once during the second and third trimesters and 1 month after delivery. Data collected preconception and from those who did not conceive within 1 yr were used for control subjects. There was a 2-fold improvement in airway responsiveness during pregnancy from a preconception mean PC20 0.35 to 0.72 mg/ml during the second trimester and 0.58 mg/ml during the third (p = 0.03). Post-delivery responsiveness (0.48 mg/ml) was not significantly different from preconception. The improvements during pregnancy were greater than the 3 monthly fluctuations when not pregnant (p = 0.04) and were greatest in those who were most hyperresponsive initially (p = 0.01). There was an associated improvement in clinical asthma severity as indicated by a reduction in minimum medication requirements (p = 0.03) and this was not at the expense of good symptoms control; both symptoms and spirometry remained unchanged during pregnancy. Changes in responsiveness were not closely related to progesterone or estriol, suggesting that other nonhormonal factors may also contribute to the improvement during pregnancy and that the control of asthmatic airway smooth muscle may not be exactly the same as that of the myometrium and gut.     

Effect of methotrexate and sulphasalazine on UMR 106 rat osteosarcoma cells

Methotrexate is commonly used in the treatment of rheumatoid arthritis. An osteopathy has been described in children treated with methotrexate for leukaemia, consisting of bone pain, osteoporosis and fractures. Animals given short-term high-dose and long-term low-dose methotrexate have both reduced bone formation and increased resorption on histomorphometry. As patients with rheumatic diseases have numerous risk factors for osteoporosis, possible additional risk from low-dose methotrexate is of relevance to the rheumatologist. To investigate further the mechanism of osteoporosis in animals and man, in vitro studies were carried out on an osteoblast cell line, using concentrations found in patients with rheumatic disease. UMR 106 rat osteoblast-like osteosarcoma cells were incubated with methotrexate, and also with sulphasalazine, an anti-rheumatic drug with no known effect on bone, for comparison. A dose-dependent toxic effect of methotrexate on the cell line was observed using concentrations found in patients with rheumatic disease. This was not observed with sulphasalazine. The reduced bone formation observed in animals and man may be due to a direct effect of methotrexate on the osteoblast.      

In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site

Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast- rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.     

Aerosols for systemic delivery of macromolecules

During the past 50 years, aerosol therapy with small molecules has become the mainstay for managing lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. During the past decade, a new therapeutic paradigm has evolved-the delivery of macromolecules into the systemic circulation through the lung. Systemic pulmonary therapy with proteins and peptides resulted from major developments in dry powder drug formulations and aerosol delivery technology. These new technologies will enable the treatment of systemic disease, such as diabetes mellitus, noninvasively by means of the deep lung. Within a decade, it is likely that many medications will be administered in this way.     

Standardization of inhalation provocation tests: Influence of nebulizer output,particle size,and method of inhalation

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 μm aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 μm AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV₁) by 20% (PC₂₀). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC₂₀. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.     

Quantitative determination of bone marrow transplant engraftment using fluorescent polymerase chain reaction primers for human identity markers

We have developed a quantitative, nonisotopic method using variable number tandem repeat (VNTR) and short tandem repeat (STR) markers for monitoring donor cell engraftment in marrow transplant recipients. Posttransplant DNA from the recipient is amplified with fluorescent polymerase chain reaction (PCR) primers for polymorphic markers that distinguish donor alleles from recipient alleles. The fluorescent PCR products are then separated on agarose or acrylamide gels on the Applied Biosystems 373A Sequencer (Foster City, CA). Using GeneScan 672 software (Applied Biosystems) to analyze the separated alleles, we can correlate allele peak areas to the percentage of donor or recipient DNA. We quantitate engraftment in a mixed chimeric sample by mixing pretransplant recipient and donor DNAs in a range of percentages and amplifying the mixtures to produce a standard curve. By amplifying and analyzing the posttransplant sample DNA(s), we can determine the extent of engraftment by interpolating the percent peak area of the informative allele(s) from this standard curve. This approach provides a precision of measurement ranging, depending on the marker, from 3.5% to 8.0% (percent coefficient of variation) and an accuracy of engraftment determination ranging from 97% to 99%, with a sensitivity of detection of 1% donor or recipient DNA. We retrospectively analyzed a panel of 32 patients and found seven to be informative for some degree of mixed chimerism, indicative of either residual normal host cells or leukemic relapse. An analysis of different cell lineages obtained posttransplant showed different degrees of engraftment in myeloid and T-cell populations. In summary, this method can provide an accurate, quantitative assessment of mixed chimerism in patients posttransplant. Such information may be useful in the future in guiding early implementation of additional treatment designed to circumvent graft failure or suppress relapse.