Characterization of erythromycin-resistant Streptococcus pneumoniae in Korea, and In Vitro activity of telithromycin against erythromycin-resistant Streptococcus pneumoniae

To characterize the phenotypes and genotypes of erythromycin-resistant clinical isolates of Streptococcus pneumoniae in Korea and to evaluate the in vitro activity of telithromycin against these erythromycin-resistant isolates, we tested a total of 676 isolates of S. pneumoniae collected from 1997 to 2002 in a tertiary hospital in Seoul, Republic of Korea. MICs for erythromycin and telithromycin were determined by the agar dilution method. The macrolide resistance phenotypes of erythromycin-resistant isolates were determined by the erythromycin- clindamycin-rokitamycin triple disk (ECRTD) and MIC induction tests, whereas their macrolide resistance genotypes were determined by PCR for the erm(B), erm(A), subclass erm(TR), and mef genes. To discriminate between mef(A) and mef(E), PCR-restriction fragment length polymorphism (RFLP) analyses were performed. Of the 676 S. pneumoniae isolates, 459 (67.9%) were resistant to erythromycin. Of the 459 erythromycin-resistant isolates, 343 (74.7%) were assigned to the cMLS phenotype, 48 (10.4%) to the iMcLS phenotype, 4 (0.9%) to the iMLS phenotype, and 64 (14.0%) to the M phenotype. The erm(B) gene was detected in 251 (54.6%) isolates, the mef gene was detected in 64 (14.0%), and both the erm(B) and mef genes were detected in 144 (31.4%) isolates. All of the mef genes detected were identified as mef(E). Of the 459 erythromycin- resistant isolates, all but one were susceptible to telithromycin. The MIC(50)/MIC(90) to telithromycin of isolates carrying erm(B), mef(E), and both genes was 0.06/0.5 microg/ml, 0.03/0.125 microg/ml, and 0.5/1.0 microg/ml, respectively. Although the MICs of telithromycin for the erythromycin-resistant isolates varied according to genotype, telithromycin was very active against these erythromycin-resistant S. pneumoniae.     

Stereoselective determination of cetirizine and studies on pharmacokinetics in rat plasma

Enantiomers may confer benefits over racemates in therapeutic uses and we developed a chiral separation method of cetirizine enantiomers, a second generation H1 histamine receptor antagonist, in rat plasma. alpha1-Acidglycoprotein based chiral stationary phase(AGP-CSP), monitored with UV at 230 nm was used to separate the enantiomers. Observed enantioselectivity (alpha) was 2.0. The AGP-CSP was also used at a preparative scale to isolate the enantiomers with an optical purity of greater than ee 99%. In addition, an analysis was carried out for the cetirizine enantiomers in rat plasma to study the differences of enantiomers in pharmacokinetics. Both (+)- and (-)-cetirizine were separated using a reversed-phase column of AGP, and were detected at the range of 2.5-200 microg ml(-1) in plasma. Although there was no recognizable differences in pharmacokinetics between the enantiomers in rat, the method appears to be useful for their pharmacokinetic studies.     

Integration of human papillomavirus type 16 into cellular DNA of cervical carcinoma: preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames

The integration patterns of human papillomavirus (HPV) type 16 in the cellular DNA of six cervical carcinoma samples were analyzed by the Southern blot procedure. None of the HPV integrants retained the entire viral genome. Double HPV integration was found in one case while all other cases were single integrants. In some samples, internal deletion and selective amplification of the viral sequences were observed. On integration, the E2 open reading frame (ORF) was invariably lost but the E6/E7 ORFs and the long control region of the HPV-16 genome were retained in all seven integrations analyzed and may play a role in cellular transformation and/or maintenance of the transformed phenotype.     

Relative incidence of needle EMG abnormalities in the anterior tibial and gastrocnemius muscles

Foot drop resulting from weakness of the anterior tibial muscle is commonly encountered in clinical practice. We analyzed the incidence of needle electromyographic (EMG) abnormalities in the anterior tibial and gastrocnemius muscles from traumatic injuries to the sciatic nerve and also from different non-traumatic lower motor neuron conditions. In both traumatic and non-traumatic cases, the anterior tibial muscle showed relatively more EMG abnormalities compared to the gastrocnemius. It appears that the anterior tibial muscle is more susceptible to injury from a variety of pathologic conditions, as opposed to the gastrocnemius muscle.     

Prevalence and Associated Factors of Sarcopenia in Singaporean Adults—The Yishun Study

ObjectivesTo describe the normative values of sarcopenia among community-dwelling adults (≥21 years of age); compare the prevalence of sarcopenia using Asian Working Group for Sarcopenia criteria, 2014 (AWGS2014), Asian Working Group for Sarcopenia criteria, 2019 (AWGS2019), and European Working Group on Sarcopenia in Older People criteria, 2018 (EWGSOP2) guidelines; and identify factors associated with sarcopenia.DesignParticipants were recruited through random sampling. Sarcopenia assessments were performed using a dual-energy x-ray absorptiometry scan (muscle mass), handgrip test (muscle strength), and usual walking test (physical performance). Questionnaires were administered to evaluate lifestyle and cognition.Setting and ParticipantsIn total, 542 community-dwelling Singaporeans were recruited (21?90 years old, 57.9% women).MethodsWe assessed anthropometry, body composition, and questionnaire-based physical and cognitive factors, and estimated sarcopenia prevalence according to the AWGS2014, AWGS2019, and EWGSOP2 recommendations, and examined associations using logistic regression.ResultsAccording to AWGS2019, the Singapore population-adjusted sarcopenia prevalence was 13.6% (men 13.0%; women 14.2%) overall, and 32.2% (men 33.7%, women 30.9%) in those aged 60 years and above. The cut-offs derived from young adult reference group for low appendicular lean mass index were 5.28 kg/m2 for men and 3.69 kg/m2 for women (lower than AWGS recommended cut-off); for gait speed it was 0.82 m/s, (AWGS2019 recommended cut-off 1.0 m/s, AWGS2014 cut-off was 0.8 m/s); and for handgrip strength it was 27.9 kg/m2 for men and 16.7 kg/m2 for women (close to AWGS2019 recommendation). Age, sex, marital status, alcoholism, physical activity, body mass index, waist circumference, and global cognition were associated with sarcopenia (P < .05).Conclusions and ImplicationsThis is the first study to provide reference values of muscle mass, strength, and gait speed across the adult lifespan of Singaporeans. Using AWGS2019 criteria, sarcopenia is prominent in older age (32.2% in ≥60 years old), but it is already nontrivial (6.9%) among young and middle-age persons. Multidomain lifestyle modifications addressing muscle strength, cognition, and nutrition over the adult lifespan are important to delay the development of sarcopenia.     

Clinical Concept-Based Radiology Reports Classification Pipeline for Lung Carcinoma

Rising incidence and mortality of cancer have led to an incremental amount of research in the field. To learn from preexisting data, it has become important to capture maximum information related to disease type, stage, treatment, and outcomes. Medical imaging reports are rich in this kind of information but are only present as free text. The extraction of information from such unstructured text reports is labor-intensive. The use of Natural Language Processing (NLP) tools to extract information from radiology reports can make it less time-consuming as well as more effective. In this study, we have developed and compared different models for the classification of lung carcinoma reports using clinical concepts. This study was approved by the institutional ethics committee as a retrospective study with a waiver of informed consent. A clinical concept-based classification pipeline for lung carcinoma radiology reports was developed using rule-based as well as machine learning models and compared. The machine learning models used were XGBoost and two more deep learning model architectures with bidirectional long short-term neural networks. A corpus consisting of 1700 radiology reports including computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) reports were used for development and testing. Five hundred one radiology reports from MIMIC-III Clinical Database version 1.4 was used for external validation. The pipeline achieved an overall F1 score of 0.94 on the internal set and 0.74 on external validation with the rule-based algorithm using expert input giving the best performance. Among the machine learning models, the Bi-LSTM_dropout model performed better than the ML model using XGBoost and the Bi-LSTM_simple model on internal set, whereas on external validation, the Bi-LSTM_simple model performed relatively better than other 2. This pipeline can be used for clinical concept-based classification of radiology reports related to lung carcinoma from a huge corpus and also for automated annotation of these reports.

     

Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy volunteers.

OBJECTIVE--To investigate changes in the electrocardiographic QT interval during rapidly induced, sustained hypocalcaemia in healthy volunteers. DESIGN--Serial rate corrected QT measurements were made during and after a variable rate trisodium citrate infusion designed to "clamp" the whole blood ionised calcium concentration 0.20 mmol/l below baseline for 120 min. SUBJECTS--12 healthy teetotallers aged 19- 36 years who were not receiving medication known to influence calcium homoeostasis. MAIN OUTCOME MEASURES--Whole blood ionised calcium concentration and QaTc intervals (onset of the Q wave to T wave apex divided by the square root of the RR interval). RESULTS--Mean (SD) ionised calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10 min before returning to a stable level from 15 to 120 min (0.334 (0.023) and 0.330 (0.023) s0.5 respectively). The change from baseline of both variables expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid induction of hypocalcaemia (at 5 and 10 min) than at other times during and after the infusion (P < 0.02). CONCLUSIONS--The disproportionate prolongation of QaTc interval during prompt induction of hypocalcaemia suggests rate dependency which can be represented by a hysteresis relation between (ionised calcium, QaTc) coordinates. This finding may have clinical implications.     

K-ras mutation in colorectal carcinomas from singapore

54 sporadic colorectal cancers were analyzed for aberrations in the K-ras oncogene. DNA was extracted from frozen tissues obtained from surgical resection and analyzed for mutations in codons 12, 13 and 61 of the K-ras oncogene using single strand conformation polymorphism analysis (SSCP) and direct sequencing. Point mutations in the K-ras oncogene were found in 26/54 (48%) cases, all of which resulted in amino acid substitutions. No other types of mutations (e.g. insertions or deletions) were found. 4 of the mutations were at codon 12, 22 in codon 13 and only 1 was a codon 61 mutant. G-->A transitions were found to be predominant. A remarkable finding was the high preponderance of (13)Gly-(13)Ser mutations (54%). No correlation was observed between K-ras mutations and tumor location, Dukes' stage, differentiation levels, age or sex of the patient.