Demineralization Inhibition by Two Calcium-releasing Restorative Materials.

OBJECTIVE: To compare the ability of two calcium-releasing restorative materials to inhibit root dentin demineralization in an artificial caries model. METHODS AND MATERIALS: Preparations were made at the cementum-enamel junction of extracted human molars (40, n=10/material) and restored with two calcium-releasing materials (Experimental composite, Pulpdent Corporation and Cention N, Ivoclar Vivadent), a resin composite (Filtek Supreme Ultra, 3M Oral Care), and a resin-modified glass ionomer (RMGI) (Fuji II LC, GC). All materials (other than the RMGI) were used with an adhesive (Scotchbond Universal Adhesive, 3M Oral Care) in the self-etch mode, which was light cured for 10 seconds. All restorative materials were light cured in 2-mm increments for 20 seconds and then finished with a polishing disc. Teeth were incubated (37°C) for 24 hours in water. An acid-resistant varnish was painted onto the teeth around the restoration, leaving a 2-mm border of uncovered tooth. A demineralization solution composed of 0.1 M lactic acid, 3 mM Ca3(PO4)2, 0.1% thymol, and NaOH (to adjust pH=4.5), and a remineralization solution composed of 1.5 mM Ca, 0.9 mM P, and 20 mM Tris(hydroxymethyl)-aminomethane (pH=7.0) were prepared. Specimens were placed in the demineralization solution for 4 hours, followed by the remineralization solution for 20 hours and cycled daily for 30 days. The specimens were embedded, sectioned into 100-µm sections, and the interface between the restorative material and root dentin was viewed with polarized light microscopy. A line was drawn parallel with the zone of demineralization for each tooth. The area of "inhibition" (defined as the area external to the line) or "wall lesion" (defined as the area internal to the line) was measured with image evaluation software. Areas of inhibition were measured as positive values, and areas of wall lesions were measured as negative areas. RESULTS: A one-way analysis of variance (ANOVA) found significant differences between materials for "inhibition/wall lesion" areas in root dentin (p<0.001). Tukey post hoc analysis ranked materials (µm2, mean ±SD): Fuji II LC (5412±2754) > Cention N (2768±1576) and experimental composite (1484±1585) > Filtek Supreme Ultra (-1119±1029). CONCLUSION: The experimental composite and Cention N materials (used with an adhesive) showed net areas of inhibition greater than a reference resin composite, albeit at a lower level than a reference RMGI material (used with no adhesive).

[Clinical analysis of 11 cases of sub-acute arsenic poisoning].

Objective: To investigate the clinical manifestations, treatments and prognosis of subacute arsenic poisoning. Methods: In January 2020, a retrospective analysis was carried out on 11 patients hospitalized with subacute arsenic poisoning caused by arsenic contaminated drinking water. We observed manifestations, treatments and prognosis. Results: The main clinical presentations of subacute arsenic poisoningin were gastroenteritis in early phase, some of them had other organ damage, such as skin, blood, liver, kidney, cardiovascular and so on. The later phase was mainly peripheral nervous system damage. The treatment was mainly to chelate arsenic, protect target organs and treat toxic peripheral neuropathy. Most were significantly recoveried, but the recovery of severe toxic peripheral neuropathy was tardy. Conclusion: Acute gastroenteritis is the mainly early manifestation of subacute arsenic poisoning caused by digestive tract, and toxic peripheral neuropathy in the later phase. The prognosis is good, but the recovery of severe toxic peripheral neuropathy is tardy.

Higher Variability of Tacrolimus Trough Level Increases Risk of Acute Rejection in Kidney Transplant Recipients.

BACKGROUND: Tacrolimus is the most commonly prescribed immunosuppressive drug after kidney transplantation (KTx). The trough level of tacrolimus (T0) is currently used for routine monitoring after KTx. The purpose of this study was to examine the association between the variability of T0 and acute rejection. METHODS: All kidney transplant recipients (KTR) with tacrolimus-based regimen and episode of biopsy-proven acute rejection (BPAR) between January 2012 and October 2014 were enrolled in the acute rejection (AR) group. KTR with tacrolimus-based regimen and without episode of AR were enrolled in the control group. All of the results of T0 within 6 months before episode of acute rejection were used for the calculation of within-patient variability of T0. The percent coefficient of variation, which is calculated as (standard deviation of mean/mean) × 100%, was used to represent the concentration variability of tacrolimus. RESULTS: In all, 25 KTR with AR and another 136 KTR without BPAR were enrolled in the study. The mean age of all 161 patients was 50.1 ± 10.4 years, and the mean duration after KTx was 4.3 ± 4.7 years. The average daily dose of tacrolimus was 5.7 ± 2.6 mg, and T0 was 5.4 ± 1.8 ng/mL. Age, sex, duration after KTx, daily dose of tacrolimus, and T0 were similar in both groups. Compared with the control group, the percent coefficient of variation of T0 was significantly higher in patients with BPAR 12.1% ± 7.9% vs 39% ± 15.6%, P<.001. CONCLUSIONS: The study results suggest that, in KTR, higher variability of tacrolimus trough level is associated with higher risk of acute rejection.

[Application of standardization of medical care model for chronic mild lead poisoning].

OBJECTIVE: To standardize the treatment and evaluate the clinical application effectiveness of clinical pathway (CP) in chronic mild lead poisoning. METHODS: 60 patients with chronic mild lead poisoning hospitalized from Jan. 2014 to Dec.2014 were enrolled for the study group, 60 patients with chronic mild lead poisoning hospitalized from Jan.2013 to Dec.2013 were enrolled for the control group. The study group were cared according to clinical pathway, the control group received routine therapy; the clinical application effectiveness were compared between the two groups. RESULTS: No adverse drug reactions occurred in both groups. The curative ratio was significantly higher in the study group than in the control group (96.7% vs 86.0%, P<0.05) , the rate of patients' satisfaction to medical care significantly higher in the study group (98.3% vs 88.3%, P<0.05) , the rate of health education awareness higher in the study group (95.0% vs 81.7%, P<0.05) , the course of treatment shorter in the study group (3.2±0.6 vs 3.4±0.7, P<0.05) , the medical cost less in the study group (5773.5 yuan±1242.1 yuan vs 6354.7 yuan±1177.0 yuan, P<0.05) , the length of hospitalization was shorter in the study group (21.9 d±6.7 d vs 24.6 d±7.9 d, P<0.05). The variation rate of clinical pathway was 13.3% in clinical pathway group. CONCLUSION: The implementation of clinical pathway could improve the curative ratio, satisfaction, and health education awareness. The course of treatment, length of hospital stay and costs of hospitalization in the study group could be obviously shorter and less, and there is a little variation rate in the clinical pathway.

Additional chromosomal abnormalities in core-binding factor acute myeloid leukemia.

Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c-KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML.

Novel Approaches to the Prevention and Treatment of Rabies.

Rabies is a highly lethal disease caused by the neurotropic rabies virus (RABV), and it remains an important public health problem globally. Effective vaccines have been developed for pre- and post-exposure prophylaxis (PEP). PEP is only effective if it is initiated promptly after recognizing exposure. Once neurological symptoms develop, however, it is widely accepted that there is no effective treatment available. Recent studies indicate that the presence of RABV-specific immunity (i.e. Virus neutralizing antibodies, VNA) and the transient enhancement of the BBB permeability are absolutely required for effective virus clearance from the CNS. In principle, it has been shown in mice using various live-attenuated RABVs or recombinant RABVs expressing three copies of the G or expressing chemokine/cytokines, which can induce high levels of VNA in the serum and also capable of transiently enhancing the BBB permeability that it is possible to clear the virus from CNS. Also, it has been demonstrated that, intravenous administration of VNA together with MCP-1 (shown to transiently open up BBB) can clear RABV from the CNS in both immunocompetent and immunocompromised mice, as late as 5 days after lethal challenge. Novel therapeutic approaches aimed at allowing the peripheral VNA to cross the BBB by administration of the VNA in combination with biological or chemical agents that can transiently open up the BBB would be useful to establish an effective therapy for rabies in humans. In this review, we focus on the some of the approaches that can be used to meet the challenges in the field of rabies treatment.

DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model.

Mutant Kras (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is observed in more than 20% of non-small-cell lung cancers; however, no effective Kras target therapy is available at present. The Kras DNA vaccine may represent as a novel immunotherapeutic agent in lung cancer. In this study, we investigated the antitumor efficacy of the Kras DNA vaccine in a genetically engineered inducible mouse lung tumor model driven by Kras(G12D). Lung tumors were induced by doxycycline, and the therapeutic effects of Kras DNA vaccine were evaluated with delivery of Kras(G12D) plasmids. Mutant Kras(G12D) DNA vaccine significantly decreased the tumor nodules. A dominant-negative mutant Kras(G12D)N17, devoid of oncogenic activity, achieved similar therapeutic effects. The T-helper 1 immune response was enhanced in mice treated with Kras DNA vaccine. Splenocytes from mice receiving Kras DNA vaccine presented an antigen-specific response by treatment with peptides of Kras but not Hras or OVA. The number of tumor-infiltrating CD8(+) T cells increased after Kras vaccination. In contrast, Kras DNA vaccine was not effective in the lung tumor in transgenic mice, which was induced by mutant L858R epidermal growth factor receptor. Overall, these results indicate that Kras DNA vaccine produces an effective antitumor response in transgenic mice, and may be useful in treating lung cancer-carrying Ras mutation.

Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.

Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel ß3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.

Adult T-cell leukaemia/lymphoma can mimic other lymphomas in a non-endemic area: dilemmas in diagnosis and treatment.

BACKGROUND: The diagnosis of Adult T-cell leukaemia/lymphoma (ATL) in non-endemic regions is challenging. AIM: This study analyses the clinicopathologic features and diagnostic processes of ATL patients in Taiwan. METHODS: ATL patients diagnosed and treated at Taipei Veterans General Hospital from 1998 through 2010 were retrospectively identified. The diagnosis of ATL was confirmed by in situ detection of human T-cell leukaemia virus type 1 (HTLV-1) when necessary. Patients' data were reviewed and analysed. RESULTS: Fourteen ATL patients were identified, among whom six (42.9%) had an antecedent diagnosis of other malignant lymphomas before the ATL diagnosis, including two diagnosed with Hodgkin disease (HD), one with peripheral T-cell lymphoma, two with chronic lymphocytic leukaemia and one with angioimmunoblastic T-cell lymphoma. Of the 14 patients, eight (57%) were subclassified as the acute type, three (21.4%) as the lymphoma type, and three (21.4%) as the chronic type ATL. Five of six (83.3%) patients with initial non-ATL misdiagnosis were diagnosed with non-acute type ATL. In particular, a patient with an antecedent diagnosis of HD presented with typical Reed-Sternberg (RS)-like cells harbouring Epstein-Barr virus genomes in affected lymph nodes. The patient progressed to acute type ATL 3 years after the initial diagnosis, and HTLV-1 genomes were identified in the previous RS-like cells. CONCLUSION: In non-endemic areas, such as Taiwan, ATL, particularly the non-acute type, may mimic other lymphomas and easily be misdiagnosed. HTLV-1 serology should be routinely screened in all malignant lymphoma patients. In situ detection of HTLV-1 is helpful in cases with diagnostic dilemmas.

A retrospective analysis of the factors associated with hypercalcaemia in patients with advanced cancer.

Hypercalcaemia, a common complication of advanced cancer, causes multiple clinical symptoms, deteriorates patients' quality of life, and is associated with poor prognoses. This study aimed to identify the factors that may be associated with hypercalcaemia in advanced cancer by retrospectively reviewing the medical records of patients (n = 404) admitted to the palliative ward of the Kaohsiung Medical University Hospital, Taiwan, from 2006 to 2008. Patients' demographics, clinical data and symptoms were recorded. Seventy-nine of 404 patients had hypercalcaemia (19.6%), predominant in cases of head-and-neck cancer and haematological malignancies (P < 0.05), but not in those of bone metastases. Hypercalcaemia was associated with consciousness disturbances and leucocytosis (P < 0.05). We recommend that ionised (corrected) calcium levels be monitored clinically in patients with advanced cancer especially when consciousness disturbances are noted, or when head-and-neck or haematological malignancies are present. Testing of free calcium levels is also recommended in patients with leucocytosis.

Comparison of physiological responses to spontaneous breathing trials with a T-tube and low-level pressure support.

Previous studies have shown that spontaneous breathing trials (SBT) with a T-tube or low-level pressure support are comparable. However, low-level pressure support may overestimate the ability of a patient to sustain spontaneous breathing, resulting in premature extubation. Understanding factors contributing to different responses by patients to the two SBT methods aids in clarifying the limitation of using low-level pressure support for SBT. We performed a prospective observational study in 80 consecutive adult patients with mechanical ventilation to identify the factors contributing to different responses of a patient to the two SBT methods. The 80 patients underwent both a T-tube trial and pressure support ventilation of 6 cmH2O (PS-6) on the day of extubation. Stratified analysis was used to evaluate the effects of age, respiratory compliance and resistance, PaO2/FiO2 ratio and underlying disease on post-SBT responses. Comparing the responses to a T-tube trial and PS-6, the patients with old age, poor pulmonary compliance (≤40 ml/cmH2O) and chronic obstructive pulmonary disease had a higher heart rate (difference [95% CI]: 4 [0,8], 5 [2,9], 5 [0,10] beats/minute, respectively) and systolic blood pressure (10 [4,16], 11 [5,16], 7 [0,13] mmHg, respectively) after the T-tube trial. In conclusion, this research shows that old age and impaired respiratory mechanics contribute to different responses to spontaneous breathing trials with a T-tube and low-level pressure support. Further studies are needed to compare the effectiveness of the two SBT methods in predicting successful extubation in such patient groups.

Impact of non-tuberculous mycobacteria on pulmonary function decline in chronic obstructive pulmonary disease.

OBJECTIVE: Although chronic obstructive pulmonary disease (COPD) is a common form of structural lung disease associated with pulmonary non-tuberculous mycobacteria (NTM) infection, no longitudinal studies have investigated the role of NTM in COPD disease progression. DESIGN: From 2000 to 2008, spirometry-confirmed COPD patients with sputum specimens sent for mycobacterial cultures were included. Analysis of clinical, microbiological and pulmonary function data was performed. RESULTS: The 251 patients were divided into three groups according to the number of NTM isolates: multiple (n = 47), single (n = 63), and no (n = 141) isolates. Mycobacterium avium complex was the most common species in multiple isolates (36.2%) and single isolate (28.6%) groups. Overall, 24.7% of COPD patients had been admitted for exacerbations at least once a year, and patients with multiple and single NTM isolates were more than twice as likely as those with no isolate to experience such exacerbations (38.3% vs. 31.7% vs. 17.0%). After controlling for confounders, patients with multiple NTM isolates had a greater decline in forced expiratory volume in one second than those with single or no isolates (-79.4 ± 32.8 ml vs. -61.6 ± 31.9 ml and -56.2 ± 31.5 ml). CONCLUSION: This study suggests that NTM may play a role in disease progression and deterioration of pulmonary function in COPD patients.

Skin and soft-tissue infection caused by non-tuberculous mycobacteria in Taiwan, 1997-2008.

The aim of this study was to investigate the clinical, microbiological, and pathological characteristics and the outcomes of skin and soft-tissue infection (SSTI) caused by non-tuberculous mycobacteria (NTM). Medical records of 50 patients with SSTI caused by NTM identified from 2005 to 2008 and 63 patients previously reported in a medical centre from 1997 to 2004 were reviewed. The annual incidence (per 100,000 outpatients and in-patients) ranged from 0·57 in 2005, 0·38 in 2007, to 1·1 in 2008, with an average of 0·62/100,000. From 1997 to 2008, the average incidence was 1·39/100,000 patients. The average annual incidence of SSTI caused by NTM was 0·62/100,000 outpatients and in-patients during 2005 and 2008. Of the total of 113 patients identified during the 12-year period, patients infected with Mycobacterium fortuitum and M. marinum were younger than those infected with M. avium-intracellulare complex (MAC) (36 and 44 years vs. 55 years, P=0·004 and P=0·056, respectively), and were more likely to have previous invasive procedures than those infected with MAC and M. abscessus (81·8% and 72·0% vs. 27·8% and 54·8%, P=0·007), and less likely to have associated immunosuppression (9·1% and 24% vs. 66·7% and 45·2%, P=0·006). Granuloma was more often observed in immunocompetent patients (60·1% vs. 40%, P=0·019), and in M. marinum-infected specimens (78·3%). There were significant differences in the demographic and clinical features of patients with NTM SSTI, including immunosuppression, trauma experience, and depth of tissue infections.

HMGB1-derived peptide acts as adjuvant inducing immune responses to peptide and protein antigen.

There is a need for new adjuvants that will induce immune responses to subunit vaccines. We show that a short peptide, named Hp91, whose sequence corresponds to an area within the endogenous molecule high mobility group box (HMGB1) protein 1 potentiates cellular immune responses to peptide antigen and cellular and humoral immune responses to protein antigen in vivo. Hp91 promoted the in vivo production of the immunomodulatory cytokines, IFN-γ, TNF-α, IL-6, and IL-12 (p70), as well as antigen-specific activation of CD8+ T cells. These results demonstrate the ability of a short immunostimulatory peptide to serve as an adjuvant for subunit vaccines.

Cryptococcosis and tuberculosis co-infection at a university hospital in Taiwan, 1993-2006.

BACKGROUND: The human immunodeficiency virus (HIV) epidemic and increasing use of immunosuppressive agents have increased the prevalence of both cryptococcosis and tuberculosis (TB). However, the status of co-infection with both pathogens remains unknown. METHODS: This study retrospectively reviewed patient records of cryptococcosis and TB co-infection from 1993 to 2006. The temporal sequence of co-infection was defined as either concurrent or sequential. Data collected included patient demographics, HIV status, co-morbidities, clinical manifestations, treatment strategies, and outcome at 1-year follow-up. RESULTS: There were 23 patients with cryptococcosis and TB co-infection, representing 5.4% of cryptococcosis or 0.6% of TB cases. Eleven (48%) patients were HIV-infected, and no underlying disease or immunocompromised state could be identified in six (26%) patients. Twelve (52%) patients presented with concurrent infection, but diagnosis of co-infection could be achieved simultaneously in only three (13%). Constitutional symptoms, particularly fever and weight loss, were the most common presenting symptoms, developing in more than two-thirds of the patients. The majority (83%) of the patients made a good recovery following dual antifungal and anti-TB therapy. There were three mortalities at the 1-year follow-up, which might be attributable to a delay in diagnosis and treatment of co-infection. The outcomes of HIV-infected and non-HIV-infected patients were not significantly different. CONCLUSIONS: Cryptococcosis and TB co-infection, although rare, develops in both immunocompromised and healthy individuals. Early diagnosis and treatment may improve patient prognosis. There should be a high index of suspicion in order to achieve a timely diagnosis in a TB endemic area.

Genitourinary infections caused by nontuberculous mycobacteria at a university hospital in Taiwan, 1996-2008.

Genitourinary infections caused by nontuberculous mycobacteria (NTM) are rarely reported. The medical records of all patients with genitourinary NTM infections treated at National Taiwan University Hospital from 1996-2008 were retrospectively reviewed. Fifteen patients were identified, of whom 10 (67%) were male. More than two-thirds of patients had underlying conditions, the most common of which was chronic renal disease. Only one patient had AIDS. Acid-fast smears of urine were negative in all patients. Eleven isolates were available for further confirmation by sequencing of the 16S rRNA gene. Mycobacterium avium complex was the most common (n = 5, 33%), followed by both Mycobacterium abscessus (n = 2; 13%) and Mycobacterium fortuitum (n = 2; 13%). Of the 12 patients receiving anti-NTM treatment, only four received adequate prescribed regimens and none died of NTM infections. Two patients died of refractory urosepsis before the urinary NTM infections were diagnosed. The clinical characteristics of the 15 patients were also compared with 43 previously reported patients with genitourinary tuberculosis. Patients with genitourinary NTM infections were more likely to report constitutional symptoms, seek medical help within 1 month after the onset of symptoms and develop leukocytosis. Patients with genitourinary tuberculosis were more likely to have ureteral strictures and abnormal chest radiographs associated with active or inactive tuberculosis. Although rare, genitourinary NTM infections pose a significant threat to life and should be considered in the differential diagnosis of genitourinary infections, especially when patients are unresponsive to conventional antibiotic treatment.

The A1166C polymorphism of angiotensin II Type 1 receptor as a predictor of renal function decline over 4 years follow-up in an apparently healthy Chinese population.

AIM: The angiotensin II Type 1 receptor (AT1R) A1166C (rs5186) genez polymorphism is equivocally associated with the patients' susceptibility to chronic kidney disease or end-stage renal disease. We conducted a prospective study to investigate the influence of AT1R A1166C gene polymorphism on the quantitative changes of renal function. METHOD: Of 1500 people screened, 112 non-diabetic normotensive elderly Chinese were recruited and received biochemistry examination at the baseline, at the second and fourth year follow-up. Serum creatinine and calculated renal parameters, using Cockroft-Gault (CG) formula, Modification of Diet in Renal Disease (MDRD) Study and abbreviated MDRD (abMDRD) equation, were used to evaluate renal function and their progression. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULT: Age was 71.9 +/- 3.7 years (range 60 - 81). Serum creatinine, CG creatinine clearance (CrCl), MDRD and abMDRD glomerular filtration rate (GFR) were significantly decreased at the 2 and 4-year follow-up (all p < 0.001). The magnitude of 4-year decline of above four renal parameters was significantly higher in subjects carrying the AT1R AA genotype than C-allele carriers (p = 0.014, 0.033, 0.008 and 0.014 for creatinine, CG CrCl, MDRD and abMDRD GFR, respectively). This association was still significant in multivariate analyses (p = 0.019, 0.045, 0.035 and 0.018, respectively). CONCLUSION: This longitudinal study showed that the aging process was associated with decline of renal function in the healthy elderly. The AT1R A1166C gene polymorphism might modulate these changes in the Chinese. This provides further knowledge essential in the assessment of renal disease and determination of renal function in the older subjects.