The Effect of Pre-operative use of Antiplatelets and Anticoagulants on Time to Surgery in Hip Fracture Patients.

Introduction: Hip fractures are a major health concern resulting in significant morbidity worldwide. They are the leading cause of fall-related injuries amongst the elderly with high risk of death, and numbers are expected to rise with the growing elderly population. Expedited surgical repair has been proven to improve patient outcomes, however there are often multiple barriers to early surgery especially in the elderly. The use of antiplatelets and anticoagulation is a significant contributory factor to surgical delay. Materials and methods: We conducted a retrospective, single centre study on hip fracture patients admitted to an acute care orthogeriatric unit over a 12-month period, aimed at determining the impact of pre-operative use of antiplatelets and anticoagulants on time to surgery (TTS) and its impact on one-year mortality rates. Results: Amongst 404 eligible patients, 102 were on antiplatelets, 23 on anticoagulants and 279 were neither on antiplatelets or anticoagulants. Our study showed that patients taking clopidogrel (p<0.001) and DOACs (p=0.001) were more likely to have delayed surgery compared to those who were not on these agents. In addition, all patients on warfarin experienced surgical delay. Warfarin group also had highest mortality rates compared to other group and 10 times more likely to die within a year (p=0.001). Conclusion: The results from this study are consistent with existing literature, suggesting that the use of clopidogrel and anticoagulants have a negative impact on TTS in hip fracture patients. Strategies should be developed for patients on these medications to enhance their TTS.

Case series of haemothorax secondary to avulsed bullae vessel.

Haemothorax refer to the bleeding in the pleural space. It is commonly due to iatrogenic, blunt or penetrating chest trauma. Non-traumatic haemothorax is a rare entity that can potentially lead to life threatening complications. The initial management of both traumatic and non-traumatic haemothorax includes resuscitation and stabilisation of the patient. We would like to present two cases of non-traumatic haemothorax secondary to an avulsed bullae vessel.

Endometriosis - A rare cause of primary spontaneous pneumothorax.

Catamenial pneumothorax is a rare condition. We report a case of a 36-year-old female who presented with dyspnoea every time before she had her regular menses. Further investigation confirmed that she had catamenial pneumothorax. With this case we wish to highlight this rare diagnostic entity that every clinician should keep in mind.

Cross-sectional study on knowledge of chronic kidney disease among medical outpatient clinic patients.

BACKGROUND: Chronic kidney disease (CKD) is a major health concern worldwide. There are limited studies which look into the actual knowledge level of CKD among the general population both locally and internationally. This study aims to assess the knowledge level of CKD among patients in a secondary hospital in Malaysia. METHODS: Consecutive sampling of patients attending the Medical Outpatient Clinic was performed in this crosssectional study. Respondents were given self-administered questionnaires which contain questions on demographic characteristics and knowledge on CKD. RESULTS: Out of 300 respondents, 78.6% (n=236) of the respondents completed the questionnaire. Majority of respondents (73.7%, n=174) scored less than 4 out of 7 marks on knowledge on CKD. Respondents who were younger, males, having higher education status, professionals/executives and earned higher monthly income were more likely to have a higher mean knowledge score of CKD. Respondents who have heard of CKD were also significantly associated with higher mean knowledge score of CKD. CONCLUSION: The study findings suggest that our Malaysian population is still inadequately informed on CKD, especially those who are at risk of developing CKD and its complications, and also among those of the lower socioeconomic group. In order for successful primary and secondary prevention of CKD, more importance should be placed on increasing awareness on CKD among these atrisk groups.

P53 expression in colorectal carcinoma: the University of Malaya Medical Centre's experience.

Loss of P53 function is regarded as one of the critical steps in colorectal carcinogenesis. This study determines the P53 expression pattern of colorectal carcinoma in a cohort of 116 local patients. There was no significant relationship between overexpression of P53 with tumour stage (p=-0.209, chi square test) and grade (p=0.877, chi square test). Survival analysis using Kaplan-Meier procedure did not show significant relationship between P53 positivity with overall recurrence-free and survival outcome (p=0.3322 and 0.921 respectively; log rank test). Long-term follow-up may give a better evaluation on the prognostic value of P53 overexpression in colorectal carcinoma.

Rapid differentiation of "Mycobacterium canettii" from other Mycobacterium tuberculosis complex organisms by PCR-restriction analysis of the hsp65 gene.

A total of 102 isolates of the Mycobacterium tuberculosis complex, including available "M. canettii" isolates, were studied by PCR-restriction analysis of a 441-bp fragment of the hsp65 gene. PRA upon HhaI enzyme digestion (GCGC) allowed easy differentiation of "M. canettii" from other members of the M. tuberculosis complex (three bands of 260, 105, and 60 bp for "M. canetti," compared to four bands of 185, 105, 75, and 60 bp for other members of the M. tuberculosis complex). Sequencing of the 441-bp hsp65 fragment of "M. canettii" isolates showed the disappearance of an HhaI site at position 235 due to a C-to-T transition that corresponded to position 631 of the homologous hsp65 gene of M. tuberculosis H37Rv. Considering that "M. canettii" may also exist as a stable rough morphotype, we suggest that the true number of "M. canettii" isolates may be underestimated in clinical microbiology laboratories.

Description of a novel Mycobacterium simiae allelic variant isolated from Caribbean AIDS patients by PCR-restriction enzyme analysis and sequencing of hsp65 gene.

A sudden upsurge in the isolation of Mycobacterium simiae from terminally ill AIDS patients was recently reported on the Caribbean island of Guadeloupe. Identification of these M. simiae isolates was achieved using biochemical tests and further confirmed by PCR-restriction analysis (PRA) of a 439-bp fragment of hsp65. A novel PRA profile III (three Bst EII fragments of 240/125/80 bp and four Hae III fragments of 145/125/40/25 bp) was observed in four blood isolates from two patients. The 16 S rRNA gene sequencing of the hypervariable A region confirmed that all the pattern III isolates were indeed M. simiae species, and the hsp65 sequencing confirmed the existence of a new hsp65 allele in these caribbean isolates. A hsp65 sequence-based phylogenetic tree was also created for 39 species including M. simiae and related mycobacterial species as well as other rapid and slow growing mycobacteria, and may serve as an useful tool for identification of mycobacteria to species level.

Activity of rifapentine and its metabolite 25-O-desacetylrifapentine compared with rifampicin and rifabutin against Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis and M. bovis BCG.

The in vitro activity of rifapentine and its metabolite, 25-O:-desacetylrifapentine, as compared with that of rifampicin and rifabutin, was determined against Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis and M. bovis BCG. MICs were determined radiometrically and by the 1% proportional method using Middlebrook 7H11 agar. The bactericidal effect of the drugs was determined in parallel at selected concentrations. For drugsusceptible isolates of M. tuberculosis, the Bactec MICs of rifapentine and 25-O:-desacetylrifapentine were 0.03-0.06 mg/L and 0. 125-0.25 mg/L, respectively. Similar MICs were obtained for M. africanum (0.03-0.125 and 0.125-0.50 mg/L, respectively), and M. bovis (0.063-0.25 and 0.125-1.0 mg/L, respectively), but MICs were considerably lower for M. bovis BCG (0.008-0.063 mg/L for rifapentine and 0.016-0.125 mg/L for its metabolite). In general, MICs determined using 7H11 agar medium were usually one or two dilutions higher than those obtained using Bactec broth. When compared with rifampicin and rifabutin, the inhibitory activity of rifapentine for drug-susceptible isolates was roughly equal to that of rifabutin, and the inhibitory activity of 25-O:-desacetylrifapentine was comparable to that of rifampicin; however, rifapentine was somewhat more bactericidal than rifabutin at equal concentrations. Clinical isolates of M. tuberculosis with a high degree of resistance to rifampicin (MIC >/= 32 mg/L) were also highly resistant to rifabutin, rifapentine and 25-O:-desacetylrifapentine, although the MICs of rifabutin in this case were somewhat lower than the MICs of rifapentine.

Evaluation and validation of a commercial ELISA for diazinon in surface waters.

The performance of a commercially available microtiter plate ELISA kit for the determination of diazinon was evaluated for sensitivity, selectivity, intra-assay repeatability, accuracy, and matrix effects in fortified distilled water and filtered and unfiltered environmental surface water samples. Repeatability and reproducibility studies show that the kit satisfies current EPA criteria for the assessment of analytical methods. Mean recoveries from spiked samples averaged 80.3, 95.5, and 103.5% from distilled, unfiltered surface, and filtered surface waters, respectively. The experimentally determined method detection limit (MDL) for the commercial diazinon microtiter plate format (0.0159 microg L(-)(1)) was comparable to the least detectable dose (LDD) established by the manufacturer (0.022 microg L(-)(1)). Specificity studies indicate that the diazinon polyclonal antibody can readily distinguish the target compound from other structurally similar organophosphorus analogues, with the exception of diazoxon. Cross-reactivity with the oxon was approximately 29%, while reactivity with pirimiphos-methyl, pirimiphos-ethyl, and chlorpyrifos-ethyl was negligible. A slight matrix effect was discovered to be present in both filtered and unfiltered environmental water matrixes, but its effect on the immunoassays is insignificant within experimental error. For validation of the microtiter plate ELISA format, environmental surface and storm runoff water samples were collected, split, and analyzed directly by ELISA and by liquid-liquid extraction followed by GC (California State Department of Food and Agriculture method EM 46.0). Results of the two analytical methods were then compared statistically. A close correlation was found between methods for unspiked and untreated river water samples (r = 0.969) while a much less robust correlation was obtained for runoff waters (r = 0.728). Results from runoff waters exhibit a particularly high positive bias for the ELISA method relative to the GC method. Cross-reactivity of diazoxon and probably other unidentified cross-reacting components may be responsible for the exaggerated account of the target analyte in surface and runoff waters. While excellent for screening purposes, further study is required to elucidate and quantify the factors responsible for the consistent overestimation of ELISA results before the kit can be employed routinely for regulatory compliance monitoring.

In vitro activities of the ketolides telithromycin (HMR 3647) and HMR 3004 compared to those of clarithromycin against slowly growing mycobacteria at pHs 6.8 and 7.4.

The in vitro activities of HMR 3647 (telithromycin) and HMR 3004, two novel semisynthetic ketolides, were investigated and compared with that of the reference macrolide drug, clarithromycin, against 34 strains of slowly growing mycobacteria at pHs 6.8 and 7.4, as determined radiometrically. The MICs at pH 7.4 were about 1 to 2 dilutions lower than those observed at pH 6.8. In terms of the highest to the lowest activity, the three antibiotics could be classified as follows: clarithromycin > HMR 3004 > HMR 3647. Among the species tested, Mycobacterium bovis BCG, M. ulcerans, M. avium, and M. paratuberculosis were moderately susceptible to HMR 3004 and HMR 3647 (MICs at pH 7.4, < or =5.0 and < or =20.0 microg/ml, respectively, versus < or =1.25 microg/ml for clarithromycin), whereas M. tuberculosis, M. africanum, M. bovis, and M. simiae were resistant (MICs, > or =10.0 and > or =40.0 microg/ml, respectively, at pH 7.4). Although not more active than clarithromycin in vitro, the high level of intracellular accumulation of the two ketolides inside phagocytes warrants further screening in experimental animal models.

Species-specific identification of Mycobacterium leprae by PCR-restriction fragment length polymorphism analysis of the hsp65 gene.

PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene present in all mycobacteria was used in the present investigation to characterize Mycobacterium leprae. Bacilli were extracted and purified from different organs from experimentally infected armadillos and nude mice (Swiss mice of nu/nu origin). A total of 15 samples were assayed in duplicate, and the results were compared with those obtained for a total of 147 cultivable mycobacteria representing 34 species. Irrespective of its origin or viability, M. leprae strains from all the samples were uniformly characterized by two fragments of 315 and 135 bp upon BstEII digestion and two fragments of 265 and 130 bp upon HaeIII digestion. PRA is a relatively simple method and permits the conclusive identification of M. leprae to the species level.

Follow up of Mycobacterium tuberculosis transmission in the French West Indies by IS6110-DNA fingerprinting and DR-based spoligotyping.

A total of 115 Mycobacterium tuberculosis isolates from 80 patients were typed using IS6110-DNA fingerprinting and DR-based spoligotyping to describe the active transmission of tuberculosis in a Caribbean setting over a 2-year period. A total of 61 different pattern types were observed by IS6110-RFLP and 10 clusters containing between two and 15 patients could be defined. By spoligotyping, 45 different pattern types were observed with 12 clusters containing two to 11 patients. Thirty-two patients could be included in eight spoligotype-defined clusters and in nine RFLP-defined clusters when strictly concordant matching results were put together. In conclusion, about 40% of the patient isolates were clustered by DNA fingerprinting suggesting recent transmission of tuberculosis in our region. This study confirmed the increased accuracy and discriminatory power of the association of IS6110-RFLP and spoligotyping for studies on the molecular epidemiology of M. tuberculosis, and suggests that despite good implementation of tuberculosis control programs in Guadeloupe, active transmission of tuberculosis may be far more important than suspected.

Synergistic activities of antituberculous drugs with cerulenin and trans-cinnamic acid against Mycobacterium tuberculosis.

The recent upsurge in the incidence of tuberculosis with significant emergence of multidrug-resistant cases has focused on the priority of discovering effective new drugs and on the strategies to augment the potential of existing drugs against Mycobacterium tuberculosis. In the present study, we investigated cerulenin and trans-cinnamic acid, which have recently been shown to augment the activity of various antibiotics against Mycobacterium avium [Antimicrob. Agents Chemother. 38 (1994) 2287-2295], to enhance the activity of isoniazid, rifampin, ofloxacin, amikacin and clofazimine against M. tuberculosis. The synergy observed was compared with identical combinations using ethambutol, a cell wall-inhibiting drug used in standard antituberculous chemotherapy. The results showed that ethambutol resulted in synergistic activity in 12/30 drug combinations, as compared to 15/36 for cerulenin and 101/18 for trans-cinnamic acid. This increase in drug activity was even observed with drug-resistant isolates. Use of novel antimicrobials and understanding of their mechanisms of action may be an effective strategy to determine previously undescribed targets for future drug development.

Antimycobacterial activity of chemically defined natural substances from the Caribbean flora in Guadeloupe.

Eight chemically defined, naturally occurring compounds were extracted from the tropical flora of the Caribbean island of Guadeloupe: pilocarpine, an alkaloid from Pilocarpus racemosus; heraclenol and isomeranzin, coumarins from Triphasia trifolia; lochnerin, an indole alkaloid from Rauwolfia biauriculata; ibogaine and voacangine, indole alkaloids from Tabernaemontana citrifolia; texalin, an oxazole from Amyris elemifera; and canellal, a sesquiterpene dialdehyde from Canella winterana. An essential oil fraction from Canella winterana was also tested. The antimycobacterial activity of these substances was tested against Mycobacterium tuberculosis, M. avium and M. kansasii using the Middlebrook 7H11 agar medium, the Bactec 460-TB radiometric methodology, and determination of bacterial viable counts. Three compounds, namely ibogaine, voacangine and texalin, showed antimycobacterial activity. Investigations on the structure-modification and structure-activity relationships of these compounds may help determine new targets for future drug development.

Spoligotyping followed by double-repetitive-element PCR as rapid alternative to IS6110 fingerprinting for epidemiological studies of tuberculosis.

A total of 129 clinical isolates of Mycobacterium tuberculosis representing 91 patients were typed by a combination of direct-repeat (DR)-based spoligotyping and an inter-IS6110-PGRS (polymorphic GC-rich region)-PCR, also designated double-repetitive-element PCR (DRE-PCR). During the first phase of this investigation, 72 clinical strains representing 52 patients were initially typed by IS6110-restriction fragment length polymorphism (RFLP) and DR-RFLP, followed by spoligotyping and DRE-PCR. In the second phase of this investigation, the discriminating ability of spoligotyping plus DRE-PCR was studied for 57 isolates from 39 patients who were suspected to be epidemiologically linked, and the typing results were later confirmed by IS6110-RFLP and DR-RFLP analyses. The molecular clustering of the isolates remained identical irrespective of the methods used. These results show that the association of two PCR-based fingerprinting techniques for molecular epidemiology of tuberculosis has a discriminating ability similar to the IS6110-RFLP reference method.

Rapid identification of mycobacteria to species level by PCR-restriction fragment length polymorphism analysis of the hsp65 gene and proposition of an algorithm to differentiate 34 mycobacterial species.

PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene (A. Telenti, F. Marchesi, M. Balz, F. Bally, E. C. Böttger, and T. Bodmer, J. Clin. Microbiol. 31:175-178, 1993) was applied to 108 mycobacterial isolates representing 34 species to evaluate its potential as a rapid reference method. A total of 49 distinct patterns were obtained; 25 species were characterized by a single PRA pattern, while 9 species gave more than one specific pattern. An algorithm describing these 34 species (which includes five additional species and new subgroups of Mycobacterium kansasii, M. abscessus, and M. peregrinum) is proposed. A relatively simple and inexpensive method, PRA may be particularly helpful in routine clinical microbiology laboratories.

Molecular fingerprinting of Mycobacterium tuberculosis on a Caribbean island with IS6110 and DRr probes.

Because of a substantial increase in human immunodeficiency virus (HIV) infection and HIV-linked tuberculosis in the Caribbean, a molecular fingerprinting study of clinical isolates of Mycobacterium tuberculosis isolated at the Pasteur Institute of Guadeloupe from 1994 to 1995 was undertaken with the insertion sequence IS6110 and the direct repeat DRr probes. We present the results for 72 isolates from 51 patients. A major cluster (cluster A) representing isolates from 12 patients (24%) was detected upon PvuII-IS6110 fingerprinting, which revealed a pattern of four bands among these isolates. Homogeneity was retained when the isolates were further analyzed with the DRr probe or further characterized by AluI and SmaI-DRr restriction fragment length polymorphism analysis. The isolates of cluster A, from 10 men and 2 women, was present in people of all ages and of different ethnic and geographical backgrounds, and infection with these isolates was independent of the HIV status of the patients (except for 2 HIV-positive patients from the same ward from whom the tubercle bacilli were isolated at the same time). The percentage of reactivation versus active transmission events could not be precisely determined in this study. These results are discussed on the basis of the genetic advantage of predominant clusters and/or specific characteristics of the settings from which a similar cluster of isolates with four bands has so far been reported, which include South Africa, French Polynesia, and Guadeloupe.