Alendronate medication possession ratio and the risk of second hip fracture: an 11-year population-based cohort study in Taiwan.

Alendronate is effective in preventing second hip fracture in osteoporotic patients. However, no consensus exists on the duration that is effective in preventing a second hip fracture. Our study demonstrated that risk can be reduced when the prescription is ≥ 6 months for the year following the index hip fracture. INTRODUCTION: Alendronate is effective in preventing second hip fracture in osteoporotic patients. However, no consensus exists on the accurate medication possession ratio (MPR) that is effective in preventing a second hip fracture. Our objective was to compare the risk of second hip fracture in patients treated with different MPR of alendronate. METHODS: In this population-based cohort study, data from National Health Insurance Research Database of Taiwan were analyzed. Patients 50 years and older who had an index hip fracture and were not receiving any osteoporotic medications before their fracture during 2000-2010 were included. The cohort consisted of 88,320 patients who were new alendronate users (n = 9278) and non-users (n = 79,042). Those without alendronate were matched 4:1 as the control group. Patients were subdivided into those with no medication, MPR < 25%, MPR 25-50%, MPR 50-75%, and MPR 75-100%. Cox proportional hazard models were used to calculate the adjusted hazard ratios for different MPRs of alendronate. RESULTS: After matching, 38,675 patients were included in this study; 20,363 (52.7%) were women, and 30,940 (80%) patients were without medication of alendronate. During follow-up on December 31, 2012, 2392 patients had a second hip fracture, for an incidence of 1449/100,000 person-years. Patients with alendronate MPR 50-75% had a lower risk of a second hip fracture compared to non-users (hazard ratio 0.66). When the MPR increased to 75-100%, the hazard ratio decreased to 0.61. CONCLUSIONS: In this population-based cohort study, risk of a second hip fracture can be reduced when the alendronate MPR is ≥ 50% for the year following the index hip fracture. As the MPR increases, the risk of a second hip fracture decreases.

Continuous-flow system and monitoring tools for the dielectrophoretic integration of nanowires in light sensor arrays.

Although nanowires (NWs) may improve the performance of many optoelectronic devices such as light emitters and photodetectors, the mass commercialization of these devices is limited by the difficult task of finding reliable and reproducible methods to integrate the NWs on foreign substrates. This work shows the fabrication of zinc oxide NWs photodetectors on conventional glass using transparent conductive electrodes to effectively integrate the NWs at specific locations by dielectrophoresis (DEP). The paper describes the careful preparation of NW dispersions by sedimentation and the dielectrophoretic alignment of NWs in a home-made system. This system includes an impedance technique for the assessment of the alignment quality in real time. Following this procedure, ultraviolet photodetectors based on the electrical contacts formed by the DEP process on the transparent electrodes are fabricated. This cost-effective mean of contacting NWs enables front-and back-illumination operation modes, the latter eliminating shadowing effects caused by the deposition of metals. The electro-optical characterization of the devices shows uniform responsivities in the order of 106 A W(-1) below 390 nm under both modes, as well as, time responses of a few seconds.

Greater risk of hip fracture in hemodialysis than in peritoneal dialysis.

UNLABELLED: Several differences may have existed between patients treated with peritoneal dialysis and hemodialysis because of the difference in dialysis modality. This nationwide population-based cohort study demonstrated that patients on hemodialysis had an increased risk of hip fracture compared to patients on peritoneal dialysis; the hazard ratio was 1.52. INTRODUCTION: Numerous debates on which dialysis modality is "superior" have taken place in recent decades. However, no large-scale study has ever mentioned about the relationship between dialysis modality and risk of hip fracture. METHODS: We identified 64,124 incident end-stage renal disease patients from the National Health Insurance Research Database in Taiwan between 1998 and 2008, including 59,457 (92.72%) hemodialysis (HD) and 4,667 (7.28%) peritoneal dialysis (PD) patients. After 8:1 propensity score matching, 31,554 patients, of whom 28,048 were HD and 3,506 were PD patients, were included in the study. We conducted the Cox proportional hazards model to examine the effects of dialysis modality and other variables on hip fracture risk. RESULTS: A total of 2,587 hip fractures were identified in 64,124 dialysis patients. The incidence rate of hip fracture was 13.60 per 1000 patient-years in the HD group and 6.25 in the PD group. Dialysis modality, sex, age, presence of cardiovascular disease, diabetes, medication with antiepileptic drugs, diuretics, steroids, and vitamin D had statistically significant associations with hip fracture. Patients on HD had an increased risk of hip fracture compared to patients on PD; the hazard ratio (HR) was 1.52 (95% CI: 1.09-2.12, P = 0.02). CONCLUSIONS: In this population-based cohort study, HD had a greater hip fracture risk compared to PD; the HR was 1.52. We should focus more on reducing the risk of hip fractures in hemodialysis patients.

Conducting properties of nearly depleted ZnO nanowire UV sensors fabricated by dielectrophoresis.

ZnO nanowires (NWs) with different radii (rNW) have been aligned between pre-patterned electrodes using dielectrophoresis (DEP) for the fabrication of high gain UV sensors. The DEP conditions (voltage amplitude and frequency) and electrode material, geometry and size were optimized to enhance the efficiency during the DEP process. To understand the alignment mechanism of the ZnO NWs, the dielectrophoretic force (FDEP) was analyzed as a function of the DEP conditions and NW dimensions. These studies showed that the DEP alignment process tends to trap NWs with a smaller radius. The effects of NW size on device performance were analyzed by means of I-V measurements in darkness and under illumination (200 nm < λ < 600 nm). In darkness, the NW resistance increases as rNW decreases due to the reduction of the conduction volume, until saturation is reached for rNW < 65 nm. On the other hand, the NW spectral photoresponse shows high values around 10(8) A W(-1) (measured at 5 V and λ < 370 nm) and follows a linear trend as a function of the NW cross section. In addition, the cut-off wavelength depends on rNW, presenting a clear blue-shift for NWs with a lower radius (rNW < 50 nm). Transient photoresponse studies show that NWs with lower radii have longer rise times and shorter decay times mainly due to surface trapping effects. Regardless of NW size, passivation of the surface using a dielectric capping layer of SiO2 reduces the dynamic range of the photoresponse due to a strong increase of the dark current.

Idiotype-like determinants on human T lymphocytes alloactivated in mixed lymphocyte culture.

T cells alloactivated in 5-d MLC with an HLA-DR-different stimulator acquire the capacity of stimulating the autologous mixed lymphocyte response (AMLR). We have demonstrated that activation of AMLR by allosensitized T cells is determined by the expression of the idiotype receptor for the stimulating HLA-DR alloantigen. This has been shown in experiments in which purified, OKT-3-positive T cell suspensions were first primed for 9 d with AMLR-activated T lymphoblasts, then tested in secondary AMLR with autologous lymphoblasts sensitized to various HLA-DR alloantigens. Accelerated memory responses were induced only by autologous lymphoblasts that had been sensitized against the same HLA-DR specificity as the primary AMLR stimulators. This response was not inhibited by a mouse monoclonal antibody recognizing Ia-like determinants, and was not triggered by human allogeneic resting peripheral blood lymphocytes. Thus, recognition of alloactivated T lymphoblasts in secondary AMLR seems to be specific for the idiotype-like determinants expressed by the autologous stimulators.

Murine terminal deoxynucleotidyl transferase: cellular distribution and response to cortisone.

The mouse thymus contains two forms of terminal deoxynucleotidyl transferase (TdT) which are distinguishable by the salt concentration necessary to elute them from a phosphocellulose column, by their distrubtion among the thymocyte subpopulations, and by their sensitivity to cortisone treatment. In the whole thymus the later eluting peak (peak II) is the predominant one with about 3-10% of the total activity appearing in peak I. Both peak I and peak II activities are most sensitively assayed by the polymerization of dGMP onto an oligo(dA) primer. The minor population of thymocytes which is less dense and cortisone-resistant contains a higher specific activity of peak I TdT. The majority of TdT activity is, however, found in the major population of thymocytes which occurs in the center region of a bovine serum albumin gradient and is cortisone-sensitive. A very low level of an activity indistinguishable from peak II TdT activity is also detected in the mouse bone marrow. Other tissues, such as spleen, liver, heart, and brain lack detectable amounts of TdT activity.

Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population.

In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.

Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression.

The nature of Ia antigens which appear on human T cells after activation and the stimuli required for their expression was examined utilizing a monoclonal antibody reactive with the Ia antigen framework. T cells were purified using monoclonal antibodies directed either at the entire T-cell population (OKT3) or the T-cell inducer subset (OKT4). By indirect immunofluorescence, it was shown that the human T-cell population contains no detectable Ia+ cells in the resting state. In contrast, in excess of 60% of the T-cell population expresses Ia antigen after alloactivation in the mixed lymphocyte culture. Moreover, these Ia antigens are expressed within both the OKT4+ and OKT4- subsets. Similarly, phytohemagglutinin and concanavalin A induced approximately 20% of peripheral T cells to express Ia antigen and the expression of these antigens is not restricted to either OKT4 subset. In contrast, only the inducer T-cell population which proliferates maximally to soluble antigen expresses Ia antigens after activation by tetanus toxoid. Thus, the expression of human Ia antigens on unique T-cell subsets depends upon the activation stimuli utilized and ability of the individual subset to respond to a given stimulus. Additional studies indicated that Ia antigens appear on previously Ia- T cells after activation and do not result from clonal expansion of a small subset of Ia+ T cells.

Monoclonal antibodies defining distinctive human T cell surface antigens.

Three novel nonoclonal antibodies (designed OKT1, OKT3, and OKT4) were generated against surface determinants of human peripheral T cells. Both OKT1 and OKT3 reacted with all human peripheral T cells and 5 to 10 percent of thymocytes but differed in their reactivities with T cel- lines. By contrast, OKT4 reacted with 55 percent of human peripheral T cells and 80 percent of thymocyted in that they did not react with normal B cells, null cells, monocytes, or granulocytes.

Chronic obstructive pulmonary disease and allied conditions is a strong independent risk factor for osteoporosis and pathologic fractures: a population-based cohort study.

BACKGROUND: Chronic obstructive pulmonary disease and allied conditions (COPD) is frequently associated with various comorbidities. This study examined the association between osteoporosis and pathologic fractures in a sample of patients with COPD. METHODS: In this cohort study, claims data from the National Health Insurance Research Database of Taiwan were used to evaluate the risk between COPD and osteoporosis. Using data from the Longitudinal Health Insurance Database 2000, we conducted a retrospective cohort study by investigating patients aged 20 years and older who were newly diagnosed with COPD and comparing them with controls without COPD during 2000-2010. In addition, we used univariable and multivariable Cox proportional hazards regression models to measure the association between COPD and the risk of osteoporosis. RESULTS: Our results revealed that COPD was significantly associated with a high risk of osteoporosis, regardless of whether the patients with COPD were corticosteroid users and irrespective of age and sex. After adjustment for covariates, the COPD patients exhibited a 1.54-fold higher risk of developing osteoporosis (hazard ratio 1.54, 95% confidence interval 1.44-1.64). COPD was a stronger risk factor for osteoporosis in men. Moreover, patients with severe COPD had a higher risk of osteoporosis or pathologic fractures. CONCLUSION: This study revealed that COPD, which shares the characteristics of inflammatory diseases, is associated with a higher risk of osteoporosis after adjustment for comorbidities.

The relationship between T lymphocyte subsets and Ia-like antigen positive nonlymphoid cells in early stages of cutaneous T cell lymphoma.

Immunofluorescence studies were carried out in cutaneous T cell lymphoma (mycosis fungoides) in order to analyse the microanatomical relationship of the different T lymphocyte subsets (inducer and suppressor/cytotoxic cell populations) to large nonlymphoid Langerhans-type and so-called "indeterminate" or interdigitating cells. The conventional and mouse (monoclonal) antibodies were used in various combinations using fluorescein and rhodamine labeled second layers. In 5 of the 7 cases studied the dermal infiltrate consisted of numerous T (HuTLA+) lymphocytes, 80-90% of which expressed the inducer phenotype (HuTLA+,OKT4+). Most of these cells formed close contact with large cells exhibiting large amounts of Ia-like antigens. These cells corresponded to the interdigitating and indeterminate cells in the sections. By contrast, only small numbers (10-20%) of T cells of suppressor/cytotoxic type (HuTLA+,OKT8+) were seen. These did not show a close affinity to the Ia-like antigen positive nonlymphoid component but appeared to have a predilection for the epidermis. Epidermal Langerhans cells, also strongly Ia-like antigen positive, were further defined by 2 monoclonal antibodies reacting with a cortical thymocyte antigen HTA-1. Although Langerhans cells are probably related to the Ia-like antigen positive dermal cells only a few of the abundant latter population were HTA-1+. In the remaining 2 cases, larger populations of OKT8+ (suppressor/cytotoxic) cells were seen and could be heralding a particularly benign course. These observations indicate a close functional relationship between the lymphoid and Ia-like antigen positive dermal cells during the pre-malignant phase of cutaneous T cell lymphoma.

Immunoelectron microscopic identification of Langerhans cells using a new antigenic marker.

The specificity of a monoclonal antibody (OKT6) for epidermal Langerhans cells was examined by immunoelectron microscopy. Peroxidase-labeled OKT6 bound to 1-5% of suspended human epidermal cells, as determined by light microscopy. Electron microscopic examination of peroxidase-labeled cells revealed that all Birbeck granule-containing Langerhans cells bound OKT6. In addition, a small population of indeterminate cells, lacking the Birbeck granule, was also labeled with OKT6. The ultrastructural studies confirm the specificity of OKT6 for Langerhans cells and suggest that the indeterminate cell represents a related cell population.

Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma.

Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

Structure-activity relationships of novel 2-substituted quinazoline antibacterial agents.

High-throughput screening of in-house compound libraries led to the discovery of a novel antibacterial agent, compound 1 (MIC: 12-25 microM against S. pyogenes). In an effort to improve the activity of this active compound, a series of 2-substituted quinazolines was synthesized and evaluated in several antibacterial assays. One such compound (22) displayed improved broad-spectrum antibacterial activity against a variety of bacterial strains. This molecule also inhibited transcription/translation of bacterial RNA, suggesting a mechanism for its antibiotic effects. Structure-activity relationship studies of 22 led to the synthesis of another 24 compounds. Although some of these molecules were found to be active in bacterial growth assays, none were as potent as 22. Compound 22 was tested for its ability to cure a systemic K. pneumonia infection in the mouse and displayed moderate effects compared with a control antibiotic, gentamycin.

A critical analysis of serum and urine interleukin-2 receptor assays in renal allograft recipients.

A component of the interleukin 2 receptor (IL-2R) is released in soluble form during T cell activation and can be detected in the blood during acute renal allograft rejection. This study evaluates the diagnostic utility of a sandwich enzyme immunoassay test for serum and urine IL-2R in renal allograft recipients. A rise in serum IL-2R during the week prior to the clinical diagnosis of rejection correlated better with rejection than did isolated serum IL-2R levels or urine values. For the diagnosis of acute rejection, a rise in serum IL-2R (sensitivity 73%, specificity 87%) was comparable in overall test performance to a rise in serum creatinine (sensitivity 70%, specificity 84%). Overall, the two tests had equivalent receiver operating characteristic curves. Because the etiology of false positives in creatinine and IL-2R assays differed (primarily cyclosporine toxicity and infection, respectively), the predictive value of the combined tests was superior to either alone.

Idiotypic receptors for soluble antigens on human T lymphocyte clones.

T lymphoblasts sensitized in vitro to tetanus toxoid (TT) in 6 day cultures, acquire the capacity of stimulating the blastogenic response of "resting" autologous T lymphocytes in primary AMLC reactions. The response of lymphocytes primed against autologous-TT-sensitized-lymphoblasts (ATTSL) seems to be specific for idiotypic receptors for TT, expressed by ATTSL. Evidence to this effect derive from restimulation experiments in which anti-ATTSL primed lymphocytes (PL) were shown to display memory responses only when challenged with ATTSL, and not when exposed to the antigen alone, or to autologous lymphoblasts that had been sensitized to other antigens. Memory responses were induced, however, by allogeneic lymphoblasts primed to TT, even when the latter shared no HLA-DR antigen with the responding anti-ATTSL-PL. This indicated that the recognition of idiotypic receptors for TT is not DR-restricted. By generating T cell clones reacting to PPD and anti-idiotypic T cell clones which respond to anti-PPD sensitized blasts, we have been able to analyze the idiotype-anti-idiotype T cell interreaction at the clonal level. We found that anti-idiotypic T cell clones discriminate between determinants expressed by various autologous anti-PPD clones. Certain idiotypic determinants seem to prevail, however, as they were recognized in concert by the same cluster of anti-idiotypic clones.

Enhancement of idiotype-anti-idiotype T cell interactions by monoclonal OKT11A antibody.

We have demonstrated that OKT11A, a mouse monoclonal antibody recognizing the E receptor on human T lymphocytes, strongly enhances the autologous mixed lymphocyte culture (AMLC) response induced by T lymphoblasts, while inhibiting the AMLC response induced by B lymphoblasts as well as the T cell response to alloantigens and soluble antigens. This antibody seems to enhance the idiotype-anti-idiotype interaction between resting and activated T lymphocytes.

Antigenic polymorphism of the T4 differentiation antigen expressed on human T helper/inducer lymphocytes.

The human TH lymphocyte population has been established to express a differentiation antigen (T4) which appears to function in cellular collaboration and T cell recognition of Class II MHC alloantigens. Because we observed altered immunofluorescence staining of the TH cells of some individuals using the OKT4 mAb, a systematic investigation on both the epitopic structure of the T4 glycoprotein molecule and possible polymorphism of these epitopes was undertaken. From competitive blocking assays using eight murine anti-T4 mAbs coupled with quantitative flow cytometry, at least five and possibly seven different epitopes can be recognized on the T4 molecule. Population studies showed some individuals had a reduced phenotypic expression of the OKT4 reactive determinant to one-half that of normal and others completely lacked this epitope. The OKT4 reactive epitope variations are common but have so far been racially restricted to American Blacks and do not appear related to the stage of TH cell differentiation, any identifiable immune abnormality in vitro, or a definable disease process. The OKT4 epitope cannot be unmasked by neuraminidase treatment or T cell stimulation with lectins, soluble antigens, or allogeneic lymphocytes. Coupled with a family study, the alterations in OKT4 phenotype are best explained by autosomal, codominant expression of the T4 gene product. The significance of this polymorphism on TH cell function remains unclear.

Infrared hall effect in high- T(c) superconductors: evidence for non-fermi-liquid hall scattering

Infrared ( 20-120 and 900-1100 cm(-1)) Faraday rotation and circular dichroism are measured in high- T(c) superconductors using sensitive polarization modulation techniques. Optimally doped YBa2Cu3O7 thin films are studied at temperatures in the range ( 15

Identification, display, and use of symmetry elements in atomic and electronic structure models.

Crystallographic symmetry plays an important role in structure determination from diffraction or scattering data, in spectroscopy and in simulations. It is convenient and insightful to integrate the display and use of such symmetry data with data analysis and modeling methods. We outline the integration of a suite of crystallographic algorithms, closely coupled with interactive graphical displays. These include techniques for identifying the unit cell of a solid, for automatically determining space and point group symmetries, for generalized displays of symmetry elements overlaid on structural models, and for construction, editing, and transformation of models subject to symmetry constraints. In addition, electron densities derived from periodic density functional calculations can be symmetrized and displayed with the corresponding symmetry elements. Applications of these various capabilities in crystallographic research are illustrated by topical examples.