Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method.

This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl2), concentrations of sodium alginate and CaCl2 solutions, collection distance, flow rate, stirring speed, syringe needle diameter and hardening time to fabricate the microcarriers, the Taguchi method was applied. Using different conditions, a total of 18 groups were prepared. The average size of microspheres from different groups was estimated as ~ 2 mm (range 1.1 to 1.6 mm). Signal-to-noise ratio analysis showed the optimal spherical integrity (F1) achieved when the above parameters were designed as 0.1, 2.5 wt%, 6 wt%, 8 cm, 30 mL/h, 150 rpm, 0.25 mm and 2 h, respectively. The best (F1), middle (F2) and worst (F3) groups were used for further experiments. Fourier-transform infrared spectroscopy spectrum showed that F1, F2 and F3 conformations were distinct from original sodium alginate. Drug-loaded calcium alginate microcarriers demonstrated rougher surfaces compared to microspheres without drug under transmission electron microscopy. Compared to pH 7.4, swelling rates in PBS were decreased at pH 6.5. Encapsulation and loaded efficiencies of the Dox-loaded microcarriers were estimated as ~ 40.617% and ~ 3.517%. In vitro experiments indicated that the F1 Dox-loaded microcarriers provide a well sustained-release efficacy for about two weeks at 37 °C in PBS. Treatments of calcium alginate microcarriers without the Dox in two distinct hepatocellular carcinoma-derived cell lines, Huh-7 and Hep-3B, indicated that these microcarriers were non-toxic. The Dox-loaded microcarriers displayed sustained-release capacity and reduced cell viabilities to ~ 30% in both cell lines on Day 12.

Sjögren's syndrome associated with protein losing gastroenteropathy manifested by intestinal lymphangiectasia successfully treated with prednisolone and hydroxychloroquine.

Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine.

Direct observation therapy with appropriate treatment regimens was associated with a decline in second-line drug-resistant tuberculosis in Taiwan.

The resistance of Mycobacterium tuberculosis (MTB) to second-line drugs (SLDs) is growing worldwide; however, associations between the appropriateness of treatment for tuberculosis (TB) and whether the directly observed treatment, short course (DOTS)/DOTS-plus programs had an impact on the prevalence of SLD-resistant MTB are still uncertain. We performed a retrospective analysis of resistance profiles among MTB isolates obtained from 6,035 consecutive patients from 2004 to 2011 at two TB referral hospitals in Taiwan. There was a significant decrease (all p-values <0.01) in the prevalence of MTB isolates that were resistant to fluoroquinolones, injectable SLDs, and orally administered SLDs, and multidrug-resistant (MDR) and extensively drug-resistant (XDR) MTB isolates over time. There was a significant increase in the coverage rate of DOTS/DOTS-plus programs and that of administering appropriate first-line and second-line regimens (all p < 0.01). Compared with isoniazid-susceptible isolates, high-level (1.0 mg/L) isoniazid-resistant and MDR isolates showed extensive cross resistance to ofloxacin (5.9%, p < 0.01 and 33.6%, p < 0.01), levofloxacin (9.6%, p < 0.01 and 38.1%, p < 0.01), moxifloxacin (11.1%, p < 0.01 and 26.5%, p < 0.01), kanamycin (6.8 %, p < 0.01 and 16.7 %, p < 0.01), ethionamide (6.4%, p < 0.01 and 16.2%, p < 0.01), and para-aminosalicylic acid (13.1%, p < 0.01 and 20.4%, p < 0.01), but not to capreomycin (2.0%, p = 0.06 and 1.6%, p = 0.08). The decline in prevalence of resistance to SLDs was negatively correlated with the rise in rates of administering appropriate regimens as well as the DOTS/DOTS-plus programs, but not with the increase in usage of second-line regimens. The implementation of DOTS/DOTS-plus programs with appropriate regimens was associated with a decrease in the prevalence of SLD-resistant and XDR TB.

Epidemiological investigation of a case of nosocomial Legionnaires' disease in Taiwan: implications for routine environmental surveillance.

An epidemiological investigation with Legionella and molecular subtyping was conducted to determine the source of a case of nosocomial Legionnaires' disease (LD) who was hospitalized in three hospitals within a month. Legionella pneumophila serogroup 3, an uncommon serogroup for infection, was isolated from the patient's sputum. Environmental surveillance revealed Legionella colonization in all three hospitals; the patient isolate matched the isolate from the first hospital by molecular typing. Culturing the hospital water supply for Legionella is a pro-active strategy for detection of nosocomial LD even in hospitals experiencing no previous cases.

Blood surveillance and detection on platelet bacterial contamination associated with septic events.

The objective of this study was to evaluate the risk of transfusion-associated septic events in Taiwan. In Taiwan, most blood components are provided from blood centres; so platelet (PLT) bacterial contaminations are rarely reported. The study's aim is to investigate the prevalence of PLT bacterial contamination in Kaoshiung Armed Forces General Hospital by using BacT/ALERT system for routine screening. A total of 82 apheresis and 2256 whole blood-derived PLT units were tested. A measured quantity of 1 mL aliquots were taken as samplings from all blood bag tubing of PLT units, and then further incubated in a bacterial detection system (BacT/ALERT). The subcultures of true-positive bottles underwent bacterial identification by using Vitek system, microscopic observation and culture-based methods. Eight units (0.34%, 8 of 2338) were found to have bacterial contamination. The true-positive rate of the whole blood-derived and apheresis PLTs was 0.31% (7 of 2256) and 1.22% (1 of 82), respectively. Six microorganisms were identified with the most dominate being Staphylococcus epidermidis. One case of transfusion-associated sepsis was confirmed; in addition, the holding period of PLTs (F = 4.522, P = 0.034) and positive detection of PLT bacterial contamination (F = 46.605,P < 0.001) were associated with post-transfusion sepsis. Thus, in this study, although the transfusion-associated septic event was rarely found and PLT units were provided from blood centres, bacterial screening was necessary to safely quarantine the transfusion. The holding period of PLT units should be no more than 4 days in order to avoid possible bacterial contamination.

Hepatocellular carcinoma with metastasis to right atrium--a report of three cases.

Hepatocellular carcinoma (HCC) is one of the most common neoplasma in Taiwan. The tumor itself has the tendency of extension into the venous system, such as to the portal vein, hepatic vein and inferior vena cava (IVC), but intra-atrial metastasis is unusual. Antemortem diagnosis was difficult before the availability of two-dimensional echocardiography (2-DE). Sometimes, the first symptoms and signs are cardiogenic manifestations such as dyspnea on exertion, syncope, edema of the lower legs, and shock. Clinicians may mistakenly make the wrong diagnosis of heart failure. Because of this, we hereby report three cases of HCC with right intra-atrial metastasis to raise the physician's awareness. All three cases initially presented as right side heart failure. Imaging study revealed hepatocellular carcinoma with right intra-atrial metastasis. Two of the three cases died within one month after diagnosis.