Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 100
Filter
Add more filters

Publication year range
1.
Soft Matter ; 15(5): 901-916, 2019 Jan 30.
Article in English | MEDLINE | ID: mdl-30543256

ABSTRACT

Numerical modelling has emerged as a powerful and effective tool to study various dynamic behaviours of biological matter. Such numerical modelling tools have contributed to the optimisations of food drying parameters leading to higher quality end-products in the field of food engineering. In this context, one of the most recent developments is the meshfree-based numerical models, which have demonstrated enhanced capabilities to model cellular deformations during drying, providing many benefits compared to conventional grid-based modelling approaches. However, the potential extension of this method for simulating bulk level tissues has been a challenge due to the increased requirement for higher computational time and resources. As a solution for this, by incorporating meshfree features, a novel coarse-grained multiscale numerical model is proposed in this work to predict bulk level (macroscale) deformations of food-plant tissues during drying. Accordingly, realistic simulation of morphological changes of apple tissues can now be performed with just 2% of the previous computational time in microscale and macroscale simulations can also be conducted. Compared to contemporary multiscale models, this modelling approach provides more convenient computational implementation as well. Thus, this novel approach can be recommended for efficiently and accurately simulating morphological changes of cellular materials undergoing drying processes, while confirming its potential future expansion to efficiently and accurately predict morphological changes of heterogeneous plant tissues in different spatial scales.


Subject(s)
Desiccation , Models, Molecular , Plants, Edible/chemistry , Plants, Edible/cytology
2.
Can J Urol ; 25(2): 9255-9261., 2018 04.
Article in English | MEDLINE | ID: mdl-29680003

ABSTRACT

INTRODUCTION: Multimodal analgesia is an effective way to control pain and limit opioid use after surgery. The quadratus lumborum block and paravertebral block are two regional anesthesia techniques that leverage multimodal analgesia to improve postoperative pain control. We sought to compare the efficacy of these blocks for pain management following radical cystectomy. MATERIALS AND METHODS: We performed a retrospective review of radical cystectomy patients who received bilateral continuous paravertebral blocks (n = 125) or bilateral single shot quadratus lumborum blocks (n = 50) between 2014-2016. The primary outcome was postoperative opiate consumption on day 0. Secondary outcomes included self-reported pain scores and hospital length of stay. RESULTS: Quadratus lumborum block patients had similar opioid use on postoperative day 0 compared with paravertebral block patients (29 mg versus 30 mg, p = 0.90). Pain scores on postoperative day 0 were similar between quadratus lumborum block and paravertebral block groups (4.0 versus 3.8, p = 0.72); however, the paravertebral block group had lower pain scores on days 1-3 compared with the quadratus lumborum block group (all p < 0.05). Hospital length of stay was similar between groups (6.6 days versus 6.2 days, p = 0.41). CONCLUSIONS: There were no differences in opioid consumption among patients receiving bilateral single shot quadratus lumborum blocks and bilateral continuous paravertebral blocks after radical cystectomy. These data suggest that the quadratus lumborum block is a viable alternative for delivering multimodal analgesia in cystectomy patients.


Subject(s)
Analgesics, Opioid/administration & dosage , Anesthesia, Spinal/methods , Cystectomy/methods , Nerve Block/methods , Pain, Postoperative/prevention & control , Urinary Bladder Neoplasms/surgery , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Postoperative Care/methods , Retrospective Studies , Risk Assessment , Urinary Bladder Neoplasms/pathology
3.
Can J Urol ; 24(4): 8895-8901, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28832307

ABSTRACT

INTRODUCTION: To investigate the use of a high-arginine immunonutrient supplement prior to radical cystectomy for bladder cancer. MATERIALS AND METHODS: We recruited 40 patients to consume a total of four high-arginine immunonutrient shakes per day for 5 days prior to radical cystectomy. The primary outcome measures were safety, tolerability and adherence to the supplementation regimen. Ninety-day postoperative outcomes were also compared between supplemented patients and a cohort of 104 prospectively identified non-supplemented radical cystectomy patients. Multivariable logistic regression models were used to compare overall complications, infectious complications, and readmission rates between groups. RESULTS: There were no serious adverse events during supplementation. Four patients (10%) stopped supplementation due to nausea (n = 2) and bloating (n = 2). Thirty-three patients (83%) consumed all prescribed shakes. Immunonutrient supplementation was not significantly associated with overall complications (adjusted odds ratio [OR] 1.08; 95% confidence interval [CI] 0.50-2.33), infectious complications (OR 1.23; 95% CI 0.49-3.07), or readmissions (OR 1.48; 95% CI 0.62-3.51) on multivariable analyses. CONCLUSIONS: Preoperative supplementation with a high-arginine immunonutrient shake was safe and well tolerated prior to radical cystectomy. Contrary to prior reports, immunonutrient supplementation was not associated with lower postoperative infectious complications in this cohort, perhaps owing to the 5 day supplementation period. Further study is needed to identify the optimal immunonutrient supplement regimen for radical cystectomy patients.


Subject(s)
Arginine/therapeutic use , Cystectomy , Postoperative Complications/microbiology , Postoperative Complications/prevention & control , Preoperative Care/methods , Urinary Bladder Neoplasms/surgery , Aged , Cystectomy/methods , Female , Humans , Male , Middle Aged , Pilot Projects , Postoperative Complications/immunology
4.
Can J Urol ; 23(6): 8568-8575, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27995853

ABSTRACT

INTRODUCTION: Up to 25% of men with prostate cancer who undergo radical prostatectomy will recur. In this setting, salvage radiotherapy may cure patients with local recurrence, but is unable to cure those with occult metastatic disease. The objective of this study is to examine how prostate-specific antigen (PSA) response to radiotherapy predicts subsequent disease progression and survival. MATERIALS AND METHODS: Using a prospectively populated database of 3089 men who underwent open radical prostatectomy, 212 patients (7%) were identified who received early salvage radiotherapy for biochemical recurrence. The main outcome was time to disease progression after salvage radiotherapy. Patients were stratified by PSA response after radiotherapy: 1) PSA < 0.1 ng/mL, 2) persistently detectable PSA, and 3) rising PSA. RESULTS: Patients received salvage radiotherapy at a median PSA of 0.20 ng/mL (IQR 0.10-0.30 ng/mL). At a median follow up of 47.3 months, a total of 52 (25%) patients experienced disease progression. On multivariable analysis, both persistent PSA (HR 5.12; 95% CI 1.98-13.23) and rising PSA (HR 16.55; 95% CI 6.61-41.48) were associated with increased risk of disease progression compared to those with PSA < 0.1 ng/mL after adjusting for pre-radiotherapy PSA, Gleason score, margin status, stage, and time to radiotherapy. Only rising PSA was associated with an increased risk of cancer-specific and all-cause mortality. CONCLUSIONS: PSA response is associated with the risk of disease progression following salvage radiotherapy. This information can be used to counsel patients on the potential need for additional therapy and identify those at greatest risk for progression and cancer-related mortality.


Subject(s)
Neoplasm Recurrence, Local/diagnosis , Prostate-Specific Antigen/analysis , Prostatectomy/adverse effects , Prostatic Neoplasms/radiotherapy , Radiotherapy , Salvage Therapy/methods , Aged , Disease Progression , Humans , Male , Margins of Excision , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Prostatectomy/methods , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Radiotherapy/adverse effects , Radiotherapy/methods , Retrospective Studies , Time-to-Treatment , United States/epidemiology
5.
Intern Med J ; 42(12): 1324-9, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22757662

ABSTRACT

BACKGROUND: A previous study utilising oral polyethylene-glycol by Borg et al. concluded that obesity is an independent predictor of inadequate bowel preparation at colonoscopy. AIM: To compare bowel preparation quality between obese and non-obese individuals as assessed by Boston bowel preparation scale (BBPS) after using sodium picosulphate. METHODS: Prospective recruitment of patients at a day surgical unit in a New South Wales academic hospital. Bowel preparation was with Picoprep in all patients. Body Mass Index and epidemiological details were collected. Bowel preparation efficacy was assessed using the Boston Bowel Preparation Score. RESULTS: One hundred and four patients were enrolled prospectively. Five (4.8%) were excluded owing to poor mental capacity. Sixty-three (64%) were non-obese, and 36 (36%) were obese. Fifty-seven (90%) non-obese and 32 (89%) obese patients had good bowel preparation. There was no statistical difference for sodium picosulphate bowel preparation between obese and non-obese individuals (P > 0.99) using Fisher's exact probability tests. The BBPS score in the left colon predicted the overall BBPS score in all patients (P < 0.001). Three of 99 patients (3%) did not tolerate sodium picosulphate, with nausea being the most common side-effect. LIMITATIONS: Non-randomised study CONCLUSIONS: There was no difference in bowel preparation quality between obese and non-obese patients using a low-volume bowel preparation (sodium picosulphate) and without dose modification of the bowel preparation. Sodium picosulphate was a welltolerated and an effective bowel preparation for obese individuals. With an increasing incidence of obesity and expanding colonoscopic indications within Australia and other Western countries from government-sponsored programs, it is paramount that procedural quality not be compromised in the obese patient.


Subject(s)
Cathartics , Citrates/therapeutic use , Colonoscopy , Obesity , Organometallic Compounds/therapeutic use , Picolines/therapeutic use , Adolescent , Adult , Aged , Body Mass Index , Humans , Male , Middle Aged , Young Adult
6.
Water Res ; 200: 117206, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34022631

ABSTRACT

Widespread wastewater pollution is one of the greatest challenges threatening the sustainable management of rivers globally. Understanding microbial responses to gradients in environmental stressors, such as wastewater pollution, is crucial to identify thresholds of community change and to develop management strategies that protect ecosystem integrity. This study used multiple lines of empirical evidence, including a novel combination of microbial ecotoxicology methods in the laboratory and field to link pressure-stressor-response relationships. Specifically, community-based whole effluent toxicity (WET) testing and environmental genomics were integrated to determine real-world community interactions, shifts and functional change in response to wastewater pollution. Here we show that wastewater effluents above moderate (>10%) concentrations caused consistent significant shifts in bacterial community structure and function. These thresholds of community shifts were also linked to changes in the trophic state of receiving waters in terms of nutrient concentrations. Differences in the community responses along the effluent concentration gradient were primarily driven by two globally relevant bacterial indicator taxa, namely Malikia spp. (Burkholderiales) and hgcI_clade (Frankiales). Species replacement occurred above moderate effluent concentrations with abundances of Malikia spp. increasing, while abundances of hgcI_clade decreased. The responses of Malikia spp. and hgcI_clade matched gene patterns associated with globally important nitrogen cycling pathways, such as denitrification and nitrogen fixation, which linked the core individual taxa to putative function and ecosystem processes, rarely achieved in previous studies. This study has identified potential indicators of change in trophic status and the functional consequences of wastewater pollution. These findings have immediate implications for both the management of environmental stressors and protection of aquatic ecosystems.


Subject(s)
Microbiota , Wastewater , Bacteria/genetics , Ecosystem , Ecotoxicology , Rivers
7.
Sci Data ; 7(1): 158, 2020 05 27.
Article in English | MEDLINE | ID: mdl-32461582

ABSTRACT

Real-world observational datasets that record and quantify pressure-stressor-response linkages between effluent discharges and natural aquatic systems are rare. With global wastewater volumes increasing at unprecedented rates, it is urgent that the present dataset is available to provide the necessary information about microbial community structure and functioning. Field studies were performed at two time-points in the Austral summer. Single-species and microbial community whole effluent toxicity (WET) testing was performed at a complete range of effluent concentrations and two salinities, with accompanying environmental data to provide new insights into nutrient and organic matter cycling, and to identify ecotoxicological tipping points. The two salinity regimes were chosen to investigate future scenarios based on a predicted salinity increase at the study site, typical of coastal regions with rising sea levels globally. Flow cytometry, amplicon sequencing of 16S and 18S rRNA genes and micro-fluidic quantitative polymerase-chain reactions (MFQPCR) were used to determine chlorophyll-a and total bacterial cell numbers and size, as well as taxonomic and functional diversity of pelagic microbial communities. This strong pilot dataset could be replicated in other regions globally and would be of high value to scientists and engineers to support the next advances in microbial ecotoxicology, environmental biomonitoring and estuarine water quality modelling.


Subject(s)
Ecotoxicology/methods , Microbiota/drug effects , Wastewater/toxicity , Bacteria/classification , Bacteria/drug effects , Salinity
8.
Resuscitation ; 80(2): 183-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19091453

ABSTRACT

Under current resuscitation guidelines symptomatic ventricular tachycardia (VT) with a palpable pulse is treated with synchronised cardioversion to avoid inducing ventricular fibrillation (VF), whilst pulseless VT is treated as VF with rapid administration of full defibrillation energy unsynchronised shocks. The additional delay in setting up the ECG to provide accurate synchronisation has been the main reason for advocating this approach, although many current defibrillators allow accurate synchronisation via just the adhesive defibrillator pads. The aim of this study was to investigate whether the timing of defibrillatory shocks in rapid VT-affected resuscitation outcome. The timings of the shocks relative to the QRS complex were used to define whether each shock was acting as a 'synchronised' or 'unsynchronised' shock. The study was a retrospective review of all diagnostic electrophysiological studies performed at Papworth Hospital. A total of 271 studies for ventricular arrhythmias were identified, with 144 studies resulting in stable monomorphic VT being induced. Of these VT episodes, 40 stopped spontaneously, 61 cases were terminated with anti-tachycardia pacing, 1 required cardioversion for slow but incessant VT and 42 required defibrillation for severe haemodynamic compromise/cardiac arrest. The electronic recordings of the defibrillation episodes were analysed to investigate the effects of shock timing on outcome. Of the 42 patients who required defibrillation, 30 had shocks delivered within a 100 ms window of the peak of the QRS complex. Of these, 28 patients converted to a perfusing rhythm and 2 patients deteriorated from VT to VF as a result of the defibrillation shock. The remaining 12 patients received shocks outside this window, with 5 converting to a perfusing rhythm and 7 deteriorating to VF. Defibrillator shocks within the QRS complex had a success rate of 93% compared to a success rate of 42% for outside the QRS complex (p=0.0016 two-tailed Fishers' exact test, odds ratio=19.6, 95% limits=3.1-123.1). There was no significant effect of age or sex of the patient, the underlying heart disease, rate of VT or anti-arrhythmic medication on the outcome, although the number of patients was too small to definitively exclude this. Therefore, defibrillation shocks delivered shortly after the peak of the QRS complex in rapid VT do appear to offer significant advantages over defibrillation shocks at other parts of the cardiac cycle for very rapid ventricular tachycardia.


Subject(s)
Electric Countershock/methods , Electrocardiography , Outcome Assessment, Health Care , Tachycardia, Ventricular/therapy , Cardiopulmonary Resuscitation , Humans , Retrospective Studies
9.
J Mater Sci Mater Med ; 20(12): 2367-74, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19579062

ABSTRACT

Dissolution tests were carried out to compare the mechanical properties of calcium phosphate based bioceramics with different compositions, before and after ageing for various time periods in Ringer's solution (pH 7.2) or distilled water (pH 7.2 and 4.0) at 37 degrees C. The results indicate that the sample composition seems to have more of an effect on the mechanical properties than does the storage environment. No obvious decrease in mechanical properties was found after samples had been aged in the various solutions during the different time periods. This indicates that these samples could be of significant clinical interest as their good structural properties were retained.


Subject(s)
Calcium Phosphates/chemistry , Ceramics , Hydrogen-Ion Concentration , Isotonic Solutions , Materials Testing , Microscopy, Electron, Scanning , Ringer's Solution , Solubility , Water
10.
11.
FEMS Microbiol Lett ; 365(11)2018 06 01.
Article in English | MEDLINE | ID: mdl-29718203

ABSTRACT

With the launch of the teaching excellence framework, teaching in higher education (HE) is under greater scrutiny than ever before. Didactic lecture delivery is still a core element of many HE programmes but there is now a greater expectation for academics to incorporate alternative approaches into their practice to increase student engagement. These approaches may include a large array of techniques from group activities, problem-based learning, practical experience and mock scenarios to newly emerging approaches such as flipped learning practices and the use of gamification. These participatory forms of learning encourage students to become more absorbed within a topic that may otherwise be seen as rather 'dry' and reduce students engagement with, and therefore retention of, material. Here we use participatory-based teaching approaches in microbiology as an example to illustrate to University undergraduate students the potentially devastating effects that a disease can have on a population. The 'threat' that diseases may pose and the manner in which they may spread and/or evolve can be challenging to communicate, especially in relation to the timescales associated with these factors in the case of an epidemic or pandemic.


Subject(s)
Disease Outbreaks , Education, Medical/methods , Epidemiology/education , Pandemics , Behavior Therapy , Humans , Students/psychology
12.
J Clin Invest ; 107(2): 191-8, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11160135

ABSTRACT

Defective cardiac muscle relaxation plays a causal role in heart failure. Shown here is the new in vivo application of parvalbumin, a calcium-binding protein that facilitates ultrafast relaxation of specialized skeletal muscles. Parvalbumin is not naturally expressed in the heart. We show that parvalbumin gene transfer to the heart in vivo produces levels of parvalbumin characteristic of fast skeletal muscles, causes a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhances relaxation performance in an animal model of slowed cardiac muscle relaxation. Parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism. Additionally, parvalbumin gene transfer may provide a new therapeutic approach to correct cellular disturbances in calcium signaling pathways that cause abnormal growth or damage in the heart or other organs.


Subject(s)
Heart/drug effects , Parvalbumins/pharmacology , Ventricular Function, Left/drug effects , Animals , Electrocardiography , Female , Gene Targeting , Gene Transfer Techniques , Heart/physiology , Heart Ventricles , Hemodynamics , Models, Animal , Myocardial Contraction/drug effects , Parvalbumins/genetics , Rats , Rats, Sprague-Dawley
13.
Circ Res ; 86(4): 470-7, 2000 Mar 03.
Article in English | MEDLINE | ID: mdl-10700453

ABSTRACT

The goal of this study was to investigate isoform-specific functional domains of the inhibitory troponin subunit, troponin I (TnI), as it functions within the intact myofilaments of adult cardiac myocytes. Adenovirus-mediated gene transfer was used to deliver and express a TnI chimera composed of the amino terminus of cardiac TnI (cTnI) and the carboxy terminus of slow skeletal TnI (ssTnI) in adult rat cardiac myocytes. The TnI chimera, designated N-card/slow-C TnI, was expressed and incorporated into myofilaments after gene transfer, without detectable changes in contractile protein stoichiometry or sarcomere architecture. Interestingly, force at submaximal Ca(2+) levels was markedly elevated in single permeabilized myocytes expressing the N-card/slow-C TnI chimera relative to force generated in adult myocytes expressing ssTnI or cTnI. Based on these results, a hierarchy of myofilament Ca(2+) sensitivity is emerging by use of TnI chimera analysis, with the order of sensitivity being N-card/slow-C TnI>>ssTnI>>cTnI. These results also strongly suggest that independent isoform-specific domains in both the amino and carboxy portions of TnI influence myofilament Ca(2+) sensitivity. In additional studies carried out under pathophysiological ionic conditions (pH 6.2), the dramatic acidosis-induced decrease in myofilament Ca(2+) sensitivity observed in myocytes expressing cTnI was blunted in myocytes expressing N-card/slow-C TnI in a manner similar to that in ssTnI-expressing myocytes. These results demonstrate that there is a pH-sensitive domain residing in the carboxy-terminal portion of TnI. The dissection of isoform-specific functional domains under physiological and acidic pH conditions demonstrates the utility of TnI chimeras for analysis of TnI function and provides important insights into the overall function of TnI within the intact myofilament of adult cardiac myocytes.


Subject(s)
Actin Cytoskeleton/physiology , Calcium/physiology , Chimera/genetics , Myocardial Contraction/physiology , Myocardium/cytology , Troponin I/genetics , Troponin I/physiology , Amino Acid Sequence/genetics , Animals , Chimera/physiology , Female , Hydrogen-Ion Concentration , Molecular Sequence Data , Myocardium/metabolism , Rats , Troponin I/metabolism
14.
Med Eng Phys ; 27(6): 443-53, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15990061

ABSTRACT

The Foley catheter, introduced in the mid-1930s and originally manufactured from latex, is still the most commonly used device for the management of urinary incontinence (UI). Despite the passage of time, there are still problems associated with the use of these devices. It is currently estimated that the management and treatment of UI costs the UK National Health Service (NHS) in the order of 500 million pound per annum. Faced with the known demographic changes in the adult population these costs will continue to rise for the foreseeable future. This review examines the range of materials currently used to manufacture Foley catheters from both latex and silicone. It outlines the common problems associated with their clinical use-infection, encrustation and blockage. The main changes that have been made to the materials employed in response to these problems are analysed. In the first instance the use of controlled release glass and slow release polymers to introduce disinfectants and antibacterial agents is considered. Attempts to alter surface properties by using coatings based on silver, polytetrafluoroethylene (PTFE), hydrogels and silicone are then described. It can be seen that despite these approaches, problems remain with the design and materials currently used to manufacture catheters. The review concludes that changes to the materials currently used for the manufacture of commercially available catheters could potentially alleviate many of the existing problems. However, standards need to be developed in order to enable direct comparison of the mechanical and physical properties of existing and potential catheter designs to ensure their effective function in-service.


Subject(s)
Biocompatible Materials/chemistry , Catheterization/instrumentation , Equipment Contamination/prevention & control , Urinary Catheterization/instrumentation , Catheterization/methods , Catheterization/trends , Equipment Design/trends , United Kingdom , Urinary Catheterization/methods , Urinary Catheterization/trends
15.
Endocrinology ; 125(5): 2790-2, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2507299

ABSTRACT

Roles of follicle-stimulating hormone (FSH) and sex steroids in regulating the expression of mRNA species encoding the alpha-, beta A- and beta B-subunits of inhibin were studied in cultured granulosa cells from immature rat ovaries. Inhibin subunit mRNAs were detected by Northern blot analysis of total RNA extracted from granulosa cell monolayers which had been incubated for 48 h in serum-free medium containing FSH (100 ng/ml) and/or a steroid (10(-6) M): estradiol (E), testosterone (T) or 5 alpha-dihydrotestosterone (DHT). Levels of mRNA encoding each inhibin subunit in untreated (control) cultures were low. In cultures treated with FSH alone, levels of inhibin alpha-, beta A- and beta B-subunit mRNA were approximately 60-fold, 70-fold and 66-fold greater than control, respectively. In cultures treated with E alone, levels of inhibin alpha- and beta B-subunit mRNA were elevated approximately 4-fold and 2-fold, respectively, but the level of inhibin beta A-subunit mRNA was not measurably affected. Treatment with T or DHT alone had no consistent effect on the levels of any inhibin subunit mRNA. The stimulatory effects of FSH were not consistently altered by the presence of either androgen or estrogen. These results confirm the role of FSH in regulating inhibin alpha-subunit gene expression and provide direct evidence that both inhibin beta-subunit genes are inducible by FSH in granulosa cells. All three inhibin subunit mRNAs followed the same pattern, suggesting that their expression is coordinately regulated by FSH during granulosa cell differentiation.


Subject(s)
Estradiol/pharmacology , Follicle Stimulating Hormone/pharmacology , Gene Expression Regulation/drug effects , Genes/drug effects , Granulosa Cells/metabolism , Inhibins/genetics , Transcription, Genetic/drug effects , Animals , Blotting, Northern , Cells, Cultured , Dihydrotestosterone/pharmacology , Female , Granulosa Cells/drug effects , Macromolecular Substances , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , Rats , Testosterone/pharmacology
16.
Pharmacogenetics ; 3(5): 270-4, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8287066

ABSTRACT

It has been claimed that the amino acid derivative carbocisteine is predominantly metabolized by sulfoxidation and that this pathway exhibits a genetic polymorphism. Moreover, those subjects with a 'poor metabolizer' phenotype have been thought to have a genetic predisposition to developing certain diseases. We have confirmed the observations of others that this marker drug does not undergo significant S-oxidation. Furthermore, a novel urinary metabolite, S-(carboxymethylthio)-L-cysteine (CMTC) has recently been identified. To determine if a genetic polymorphism for this biotransformation pathway exists, metabolic ratios (% urinary excretion carbocisteine/% urinary excretion CMTC) for 120 healthy volunteers were assessed using high-performance thin-layer chromatography. Urinary excretion of the parent drug ranged from 6% of the dose administered to 56% (mean +/- SD, 23.4 +/- 0.8%). No cysteinyl sulfoxide metabolites were identified in the urine samples. The amount excreted as CMTC exhibited a 12-fold variation but only accounted for mean of 4.4% (1-12%) of the dose given. Two individuals initially had high metabolic ratios (> 30), however, on rechallenge both their MRs were less than 5. Therefore, carbocisteine is not an appropriate probe drug for sulfoxidation. The formation of the novel metabolite CMTC appears to exhibit polymorphism, although the considerable intra-subject variation for its formation does not allow assignment of a phenotype.


Subject(s)
Carbocysteine/metabolism , Adult , Aged , Aged, 80 and over , Biotransformation , Carbocysteine/analogs & derivatives , Carbocysteine/pharmacokinetics , Carbocysteine/urine , Female , Humans , Male , Middle Aged , Phenotype , Polymorphism, Genetic , United Kingdom , White People/genetics
17.
Arch Neurol ; 36(5): 311-3, 1979 May.
Article in English | MEDLINE | ID: mdl-220939

ABSTRACT

Clinicopathological findings for two similar patients in whom myelopathy and radiculoneuropathy developed in association with malignant lymphoma were reviewed. This pattern of neurological disease has not been reported in association with the malignant lymphoproliferative disorders, and it provides ground for speculation concerning lymphocyte function and viral infection in cases of neurological disease in association with remote neoplasm.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/complications , Mycosis Fungoides/complications , Spinal Cord Diseases/etiology , Spinal Nerve Roots , Adult , Aged , Female , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Mycosis Fungoides/pathology , Peripheral Nerves/pathology , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/pathology , Spinal Cord/pathology , Spinal Cord Diseases/pathology , Spinal Nerve Roots/pathology , Virus Diseases/complications
18.
Am J Cardiol ; 68(8): 751-5, 1991 Sep 15.
Article in English | MEDLINE | ID: mdl-1892082

ABSTRACT

Detailed analysis of the QRS complex can identify patients at risk from ventricular arrhythmias, but similar techniques applied to the atria have been disappointing. This study attempts to quantitate differences in the fine morphology of P waves in a group of 9 patients with paroxysmal atrial fibrillation (AF) versus 15 control subjects. Atrial triggered signal-averaging was combined with a detailed investigation of P-wave duration, high-frequency spatial voltage and spatial velocity. Signal-averaged P-wave duration was significantly increased in patients with paroxysmal AF (135 +/- 8 vs 126 +/- 4 ms, p less than 0.05). The root-mean-square voltage at frequencies greater than 35 Hz in these patients was also significantly greater (16 +/- 3 vs 12 +/- 1 microV, p less than 0.05). Similar observations were made at frequencies greater than 40 Hz (10 +/- 3 vs 7 +/- 1 microV, p less than 0.05). These differences appeared to be confined to the third quarter of the P wave (third quarter root-mean-square voltage at greater than 40 Hz expressed as a ratio of total P-wave root-mean-square voltage, 1.4 +/- 0.1 vs 1.2 +/- 0.1, p = 0.005). Spatial velocity was also increased in the paroxysmal AF group (peak spatial velocity 6.4 +/- 1.8 vs 4.6 +/- 0.5 mV/s, p less than 0.05). These observations support previous intracardiac data that implicate delay and fragmentation of intraatrial conduction in the pathogenesis of paroxysmal AF.


Subject(s)
Atrial Fibrillation/physiopathology , Electrocardiography , Signal Processing, Computer-Assisted , Adult , Aged , Algorithms , Echocardiography , Echocardiography, Doppler , Female , Fourier Analysis , Heart Conduction System/physiology , Humans , Male , Middle Aged
19.
Aliment Pharmacol Ther ; 8(3): 337-42, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7918930

ABSTRACT

OBJECTIVE: To determine whether flumecinol (3-trifluoromethyl-alpha-ethylbenzhydrol, Zixoryn) is effective in ameliorating pruritus of cholestasis, particularly in primary bilary cirrhosis. METHODS AND RESULTS: 50 patients (46 with primary biliary cirrhosis, PBC) took oral flumecinol 600 mg or identical placebo once weekly for 3 weeks. Patients assessed pruritus by scoring a daily 100 mm visual analogue scale (VAS; 0 = no itch, 100 = severe, continuous, day and night intolerable itch). Quality of life was similarly measured. Patients scored the VAS daily for a 7-day baseline and for a further 21 days. Subjectively, pruritus improved in 13 of 24 on flumecinol and 10 of 26 on placebo (chi 2 = 1.24, P = 0.27). Median difference in fall in VAS pruritus score between baseline week (mean score for each individual used) and the last week was 8.0 [95% confidence interval (CI) -2.1 to 20.8] and for VAS quality of life was 5.0 (95% Cl 0.4 to 13.0) both in favour of flumecinol over placebo. Later, 19 patients (all PBC) were randomised to flumecinol 300 mg or placebo daily for 3 weeks. Subjectively, pruritus improved in 7 of 10 on flumecinol and 1 of 9 on placebo (Fisher's exact test, P = 0.02). Median difference in fall in VAS pruritus score was 19.8 mm (95% CI 3.3 to 40.7 mm) in favour of flumecinol over placebo and for quality of life was 3.5 mm (95% Cl -5.9 to 24.9 mm). Flumecinol did not significantly affect liver function tests, antipyrine clearance or serum total bile acids, and was not associated with any significant side-effects. CONCLUSION: Flumecinol was safe at the above doses and short term treatment with 300 mg daily, significantly ameliorated pruritus in primary biliary cirrhosis.


Subject(s)
Benzhydryl Compounds/administration & dosage , Liver Cirrhosis, Biliary/complications , Pruritus/prevention & control , Administration, Oral , Double-Blind Method , Female , Humans , Male , Pruritus/complications , Pruritus/etiology , Quality of Life , Severity of Illness Index
20.
Biomaterials ; 11(5): 321-9, 1990 Jul.
Article in English | MEDLINE | ID: mdl-2144774

ABSTRACT

The in vivo biological and mechanical performance of four artificial anterior cruciate ligament replacements, available for clinical use, was examined in the goat over a period of 2 yr. The prostheses used in the study were manufactured from polytetrafluoroethylene, Dacron or a composite of Dacron and carbon fibres. Histologically, no device was found to perform adequately both intraosseously and intra-articularly. The breaking load for each device immediately after insertion and after 12 month was found to be lower than that of the normal anterior cruciate ligament. All devices were found to have partially or completely ruptured intra-articularly after 2 yr.


Subject(s)
Biocompatible Materials , Knee Joint/surgery , Ligaments, Articular/surgery , Materials Testing , Prostheses and Implants , Animals , Biomechanical Phenomena , Female , Fibroblasts/pathology , Goats , Knee Joint/pathology , Male , Polyethylene Terephthalates , Polytetrafluoroethylene , Prostheses and Implants/adverse effects , Synovial Membrane/pathology , Synovitis/pathology
SELECTION OF CITATIONS
SEARCH DETAIL