Therapeutic apheresis in Asia: An Indonesia single center experience

In developing countries, like Indonesia, apheresis is still a relative new procedure. Nowadays, therapeutic apheresis procedures are performed in the field of hematology and neurology, especially in the teaching hospitals in Indonesia. Therapeutic apheresis procedure, that is, leukocytapheresis, therapeutic plasma exchange (TPE), and thrombocytapheresis are already performed. In the period 2009–2013, 204 apheresis procedures in 137 patients to reduce the leukocytes, 72 TPE procedures in 17 patients, and 14 thrombocyte reductions were performed in the Sardjito hospital, Yogyakarta, Indonesia. In the future, to improve the therapeutic apheresis implementation, it is important to increase the insurance coverage and also should be considered to introduce the apheresis medicine into the curriculum of appropriate physician programs in Indonesia. Especially in Indonesia, a lot of efforts are still being needed to improve implementation of therapeutic apheresis. J. Clin. Apheresis 30:139–140, 2015. © 2014 Wiley Periodicals, Inc.     

Expression of gastrin-releasing peptide (GRP) in the bovine uterus during the estrous cycle

Gastrin-releasing peptide (GRP) has been proposed as a novel regulatory peptide in the reproductive tract. We previously demonstrated that GRP immunoreactivities are found predominantly in the uterine gland epithelial cells of nonpregnant and pregnant cows. The present study focused on the distribution of GRP immunoreactivity and the expression of GRP mRNA in the bovine endometrium during the estrous cycle. Tissues were collected from 21 uterine horns and bodies during the estrous cycle. RT-PCR showed the expected GRP mRNA fragments (284 bp) in the tissues from all stages of the cycle. In situ hybridization results ascertained the expression of the GRP mRNA in the uterine gland epithelial cells and superficial epithelial cells of the endometrium. Positive staining of GRP immunoreactivity in the uterine gland epithelial cells was detected in both the uterine horn and body from all stages of the cycle. In metestrus and diestrus stages, GRP was also detected in the superficial epithelial cells of horn, but not in the body. The degrees of GRP mRNA expression and intensities of GRP immunoreactivity in the endometrium increased from proestrus to diestrus stages. These findings suggest that GRP may be important both in the endometrial remodeling during the estrous cycle and in the implantation and development of blastocysts.     

Diagnostic value of serum human Galactomannan aspergillus antigen and 1,3‐beta‐D‐glucan in immunocompromised patient suspected fungal infection

BackgroundThe prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3‐beta‐D‐glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells.MethodA cross‐sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman''s correlation coefficient, ROC curve analysis and 2 × 2 contingency table.ResultsSerum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut‐off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut‐off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection.ConclusionsThe immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels.     

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia

Background  

Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.     

Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship.

PURPOSE/OBJECTIVE: To assess the relationship between the radiation therapy (RT) dose received by the muscular components of the swallowing (sw) apparatus and - dysphagia related - quality of life (QoL) in oropharyngeal cancer. MATERIALS/METHODS: Between 2000 and 2005, 81 patients with SCC of the oropharynx were treated by 3DCRT or IMRT, with or without concomitant chemotherapy (CHT); 43 out of these 81 patients were boosted by brachytherapy (BT). Charts of 81 patients were reviewed with regard to late dysphagia complaints; 23% experienced severe dysphagia. Seventeen patients expired. Fifty-six out of 64 (88%) responded to quality of life (QoL) questionnaires; that is, the Performance Status Scales of List, EORTC H&N35, and the M.D. Anderson Dysphagia Inventory. The superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeus muscle and the inlet of the esophagus, are considered of paramount importance for swallowing. The mean dose was calculated in the muscular structures. Univariate analysis and multivariate analysis were performed using the proportional odds model. RESULTS: Mean follow-up was 18 months (range 2-34) for IMRT, and 46 months for 3DCRT (range 2-72). At 3-years, a LRC of 84%, DFS of 78% and OS of 77% were observed. A significant correlation was observed between the mean dose in the scm and mcm, and severe dysphagia complaints (univariate analysis). A steep dose-effect relationship, with an increase of the probability of dysphagia of 19% with every additional 10 Gy, was established. In the multivariate analysis, BT (dose) was the only significant factor. CONCLUSION: A dose-effect relationship between dose and swallowing complaints was observed. One way to improve the QoL is to constrain the dose to be received by the swallowing muscles.     

SMN2 and NAIP gene dosages in Vietnamese patients with spinal muscular atrophy

Background: The SMN1 gene is now recognized as a spinal muscular atrophy (SMA)-causing gene, while SMN2 and NAIP have been characterized as a modifying factor of the clinical severity of SMA. Gene dosage of SMN2 is associated with clinical severity of SMA. But the relationship between gene dosage of NAIP and clinical severity of SMA remains to be clarified, although complete deletion of NAIP is frequent in type I patients.
Methods: To evaluate the contribution of the SMN2 and NAIP gene dosages to SMA, quantitative real-time polymerase chain reaction was used to measure copy numbers of SMN2 and NAIP in 34 Vietnamese SMA patients lacking SMN1 (13 type I, 11 type II and 10 type III patients).
Results: The SMN2 copy number in type I patients was significantly lower than that in type II–III patients, which was compatible with the previous reports. In contrast, 25 out of 34 patients had only zero or one copy of NAIP , while 50 out of 52 controls had two or more copies. For NAIP (+) genotype, six out of 13 type I patients, eight out of 11 type II patients and six out of 10 type III patients carried one NAIP copy.
Conclusions: The SMN2 copy number was related to the clinical severity of SMA among Vietnamese patients. The presence of one NAIP copy, that is, heterozygous NAIP deletion, was common in Vietnamese SMA, regardless of clinical phenotype.     

Human subcutaneous tissue distribution of fluconazole: comparison of microdialysis and suction blister techniques

AIMS: To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS: A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were induced on the lower arm using gentle suction prior to ingestion of a single oral dose of fluconazole (200 mg). Microdialysate, blister fluid and blood were sampled over 8 h. Fluconazole concentrations were determined in each sample using a validated HPLC assay. In vivo recovery of fluconazole from the microdialysis probe was determined in each subject by perfusing the probe with fluconazole solution at the end of the 8 h sampling period. Individual in vivo recovery was used to calculate fluconazole concentrations in subcutaneous interstitial fluid. A physiologically based pharmacokinetic (PBPK) model was used to predict fluconazole concentrations in human subcutaneous interstitial fluid. RESULTS: There was a lag-time (approximately 0.5 h) between detection of fluconazole in microdialysate compared with plasma in each subject. The in vivo recovery of fluconazole from the microdialysis probe ranged from 57.0 to 67.2%. The subcutaneous interstitial fluid concentrations obtained by microdialysis were very similar to the unbound concentrations of fluconazole in plasma with maximum concentration of 4.29 +/- 1.19 microg ml(-1) in subcutaneous interstitial fluid and 3.58 +/- 0.14 microg ml(-1) in plasma. Subcutaneous interstitial fluid-to-plasma partition coefficient (Kp) of fluconazole was 1.16 +/- 0.22 (95% CI 0.96, 1.35). By contrast, fluconazole concentrations in blister fluid were significantly lower (P < 0.05, paired t-test) than unbound plasma concentrations over the first 3 h and maximum concentrations in blister fluid had not been achieved at the end of the sampling period. There was good agreement between fluconazole concentrations derived from microdialysis sampling and those estimated using a blood flow-limited PBPK model. CONCLUSIONS: Microdialysis and suction blister techniques did not yield comparable results. It appears that microdialysis is a more appropriate technique for studying the rate of uptake of fluconazole into subcutaneous tissue. PBPK model simulation suggested that the distribution of fluconazole into subcutaneous interstitial fluid is dependent on tissue blood flow.     

Assessment of in vitro and in vivo recovery of gallamine using microdialysis

The application of microdialysis technique for the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of probe performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investigation of the pharmacokinetics and pharmacodynamics of the neuromuscular blocker, gallamine. In vitro recovery of gallamine from the microdialysis probe when different perfusion flow rates were employed was evaluated leading to selection of a flow rate of 2 microl/min with 15-min sampling intervals for the subsequent studies. In vitro recovery of gallamine from the microdialysis probe was independent of concentration, stable over an 8-h period and reproducible. Comparable in vitro recoveries were obtained by different established approaches including recovery estimation by gain, loss and the zero-net flux (ZNF) method. Recovery by loss was used to study the in vivo recovery of gallamine from rat muscle tissue. The in vivo recovery was stable over a 5.5-h sampling period. In vitro performance of the probe subsequent to the in vivo study remained stable supporting reusage of the probe. These data highlight the importance of a systematic examination of microdialysis probe validation.     

Prophylactic effect of allopurinol mouthwash against stomatitis induced by the chemotherapy (PMUE regimen) for gastrointestinal malignancies

For prevention of the chemotherapy-induced stomatitis we administered allopurinol mouthwash to 15 out of 38 patients who underwent PMUE regimen. The severity of stomatitis was graded on five scales according to the criteria of Japan Society For Cancer Therapy. The incidence of stomatitis was defined as patients number with stomatitis above Grade 2/all patients number. Six of 23 patients which were not given allopurinol mouthwash (control group) developed stomatitis of Grade 1 (three patients), Grade 3 (two), or Grade 4 (one). Only one patient given allopurinol mouthwash (AMW group), however, suffered from Grade 1 stomatitis. The incidence of stomatitis was 13.0% for a control group and 0% for an AMW group. The average graded toxicity was 0.07 for the AMW group significantly lower than 0.57 for the control group. There was no significant difference between the two groups in other clinical adverse effects or abnormal laboratory data. These results suggested that allopurinol mouthwash regimen was well tolerated and effective for prevention of the chemotherapy induced stomatitis.