Showing papers by "Northwick Park Hospital published in 2007"
TL;DR: The findings suggest that vitamin D contributes to protection against TB by “nonclassical” mechanisms that include the induction of antimicrobial peptides.
Abstract: Vitamin D deficiency is associated with susceptibility to tuberculosis, and its biologically active metabolite, 1alpha,25 dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), has pleiotropic immune effects. The mechanisms by which 1alpha,25(OH)(2)D(3) protects against tuberculosis are incompletely understood. 1alpha,25(OH)(2)D(3) reduced the growth of mycobacteria in infected human PBMC cultures in a dose-dependent fashion. Coculture with agonists or antagonists of the membrane or nuclear vitamin D receptors indicated that these effects were primarily mediated by the nuclear vitamin D receptors. 1alpha,25(OH)(2)D(3) reduced transcription and secretion of protective IFN-gamma, IL-12p40, and TNF in infected PBMC and macrophages, indicating that 1alpha,25(OH)(2)D(3) does not mediate protection via these cytokines. Although NOS2A was up-regulated by 1alpha,25(OH)(2)D(3), inhibition of NO formation marginally affected the suppressive effect of 1alpha,25(OH)(2)D(3) on bacillus Calmette Guerin in infected cells. By contrast, 1alpha,25(OH)(2)D(3) strongly up-regulated the cathelicidin hCAP-18 gene, and some hCAP-18 polypeptide colocalized with CD14 in 1alpha,25(OH)(2)D(3) stimulated PBMC, although no detectable LL-37 peptide was found in supernatants from similar 1alpha,25(OH)(2)D(3)-stimulated PBMC cultures. A total of 200 mug/ml of the active peptide LL-37, in turn, reduced the growth of Mycobacterium tuberculosis in culture by 75.7%. These findings suggest that vitamin D contributes to protection against TB by "nonclassical" mechanisms that include the induction of antimicrobial peptides.
385 citations
TL;DR: Genes involved in differentiation and development were significantly over-represented and approximately half of the genes identified feature in the Online Mendelian Inheritance in Man database, suggesting that they could have important implications for phenotype and, thus, be useful for association studies of complex diseases.
Abstract: The discovery of copy number variation in healthy individuals is far from complete, and owing to the resolution of detection systems used, the majority of loci reported so far are relatively large ( approximately 65%>10 kb). Applying a two-stage high-resolution array comparative genomic hybridization approach to analyse 50 healthy Caucasian males from northern France, we discovered 2208 copy number variants (CNVs) detected by more than one consecutive probe. These clustered into 1469 CNV regions (CNVRs), of which 721 are thought to be novel. The majority of these are small (median size 4.4 kb) and most have common boundaries, with a coefficient of variation less than 0.1 for 83% of endpoints in those observed in multiple samples. Only 6% of the CNVRs analysed showed evidence of both copy number losses and gains at the same site. A further 6089 variants were detected by single probes: 48% of these were observed in more than one individual. In total, 2570 genes were seen to intersect variants: 1284 in novel loci. Genes involved in differentiation and development were significantly over-represented and approximately half of the genes identified feature in the Online Mendelian Inheritance in Man database. The biological importance of many genes affected, along with the well-conserved nature of the majority of the CNVs, suggests that they could have important implications for phenotype and, thus, be useful for association studies of complex diseases.
216 citations
TL;DR: The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.
Abstract: We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.
197 citations
TL;DR: Novel therapeutic approaches such as the use of anti-tumour necrosis factor alpha (TNF-alpha) inhibitors and drug-eluting arterial stents show promise for improving the prognosis in severe disease.
Abstract: Takayasu's arteritis (TA), a rare large vessel vasculitis of unknown aetiology, remains a difficult disease to manage with diagnosis often delayed until the late occlusive stage when irreversible vascular damage has occurred. Recent studies suggest that non-invasive imaging modalities including magnetic resonance imaging, ultrasound and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) allow diagnosis of TA earlier in the disease course than standard angiography and provide a means for monitoring disease activity. Choice of appropriate therapy for TA is limited by a lack of evidence and a combination of corticosteroids and immunosuppressive drugs is most commonly used. Novel therapeutic approaches such as the use of anti-tumour necrosis factor alpha (TNF-alpha) inhibitors and drug-eluting arterial stents show promise for improving the prognosis in severe disease. In addition, strict management of traditional cardiovascular risk factors such as dyslipidaemia, hypertension and lifestyle factors is mandatory to minimize secondary cardiovascular complications, which are the major cause of death in this disease.
162 citations
TL;DR: This data indicates that the use of C‐reactive protein as a predictor of chorioamnionitis in preterm prelabour rupture of membranes (PPROM) report highly conflicting results.
104 citations
TL;DR: Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay.
Abstract: BACKGROUND: Many adults with pulmonary tuberculosis are unable to expectorate. Gastric washing, sputum induction using nebulized hypertonic saline, and bronchoscopy with bronchoalveolar lavage have all been used to obtain specimens for diagnosis, but to our knowledge, the timing and volume of induced sputum have not been well studied, and these 3 methods have not been compared. METHODS: The study recruited consecutive adult inpatients with chest radiography findings suggestive of tuberculosis who were unable to expectorate. Subjects provided 3 induced sputum samples for culture on day 1 and additional samples on days 2 and 3. In addition, gastric washing specimens were collected on days 1, 2, and 3. A proportion of subjects with negative smear results underwent bronchoalveolar lavage. RESULTS: The study recruited 140 subjects. Among 107 subjects who provided 3 gastric washing specimens and at least 3 induced sputum specimens, 43% had cultures positive for Mycobacterium tuberculosis. Use of 3 induced sputum samples detected more cases than did use of 3 gastric washings (39% vs. 30%; P=.03). Among 79 subjects with culture results for all 5 induced sputum specimens, there was no difference in yield between samples obtained by induced sputum induction performed in a single day or that performed over 3 days (34% vs. 37%; P=.63). There was no association between sputum volume and positive culture results. No additional cases were diagnosed in the 21 patients who underwent bronchoscopy. CONCLUSIONS: Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously. Use of bronchoscopy with bronchoalveolar lavage did not increase diagnostic sensitivity. Samples could be collected in 1 day, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay.
103 citations
TL;DR: Whole body vibration has been proposed as an alternative exercise stimulus to produce adaptive responses similar to resistance exercise to analyse acute hormonal responses to WBV.
Abstract: Whole body vibration (WBV) has been proposed as an alternative exercise stimulus to produce adaptive responses similar to resistance exercise. Few studies have analysed acute hormonal responses to WBV. Purpose To evaluate neuromuscular and hormonal responses to an acute bout of isometric half-squat exercise with and without superimposition of WBV. Methods Seven healthy males (22.3+/-2.7 years) performed 10 sets of half squat isometric exercise for 1 min with 1-min rest between sets. Two separate trials were conducted either with WBV [30 Hz; 3.5 g (1 g=9.81 m.s2)] or without vibration (Control). Salivary concentration of testosterone and cortisol was collected and maximal isometric unilateral knee extensions (MVC) were completed before, immediately after, 1, 2 and 24 h after treatment. Results Significant decreases in MVC were observed immediately after (229.4+/-53.2 Nm), 1 h (231.6+/-59.9 Nm), and 2 h (233.0+/-59.1 Nm) after WBV compared with baseline (252.7+/-56.4 Nm; P<0.05). No significant change in MVC was recorded in Control. Rate of torque development in the first 200 ms (RTD200 ms), and salivary testosterone and cortisol concentrations were unaffected in both conditions. However, there was a trend for change over time in cortisol (P=0.052), with an increase after WBV and decrease after Control. Conclusion A 10 min session of intermittent WBV was shown to produce an acute reduction in MVC in healthy individuals, which recovered after 24 h. No significant changes were identified in salivary concentration of testosterone and cortisol suggesting that WBV with low acceleration does not represent a stressful stimulus for the neuroendocrine system.
103 citations
TL;DR: Ultrasound contrast agents are approved for opacification of the heart chambers and to improve endocardial border definition, and the myocardial contrast enhancement is also very useful for assessing thickening of theMyocardium and myocardIAL perfusion.
Abstract: Ultrasound contrast agents are approved for opacification of the heart chambers and to improve endocardial border definition. The myocardial contrast enhancement is also very useful for assessing thickening of the myocardium and myocardial perfusion. Several multicentre and numerous single-centre trials have demonstrated the usefulness of contrast echocardiography in clinical practice. Contrast echocardiography is probably one of the best validated echocardiographic techniques. Improved accuracy of contrast-enhanced images is not restricted to patients with a poor baseline image quality. Even with an optimal baseline image quality the borders are not as well defined as after LV opacification. Usage of contrast can improve image alignment and helps to avoid off-axis scanning. Contrast studies are particularly useful when a precise measurement of LV function is needed: 1. To decide about the need of implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy (CRT), 2. Follow-up of patients with moderate valvular disease and decision for surgical treatment, 3. Selection and monitoring of patients undergoing chemotherapy with cardiotoxic drugs, 4. Assessment of LV function in patients in intensive care and coronary care units. Optimal endocardial border delineation is crucial and often can be achieved only by ultrasound contrast: 1. Assessment of LV thrombi and masses, 2. Left ventricular non-compaction/apical hypertrophy, 3. Right ventricular dysplasia, right ventricular thrombus, 4. Stress echocardiography and regional wall motion assessment. Future echocardiography will be more 3D and more quantitative than current echocardiography. And contrast echocardiography has already proven its value for both applications.
94 citations
TL;DR: The most relevant and recent evidence for the principal aetiopathogenic theories of both forms of cholesteatoma are reviewed, in the light of recent otopathological findings.
Abstract: Cholesteatoma is a non-neoplastic, keratinising lesion which has two forms: congenital and acquired. Congenital cholesteatoma develops behind a normal, intact tympanic membrane, whilst acquired cholesteatoma is associated with a defect in the tympanic membrane. The pathological substrate of cholesteatoma is keratinising stratified squamous epithelium, but the origin of this epidermal tissue in the middle ear is controversial. Here, we review the most relevant and recent evidence for the principal aetiopathogenic theories of both forms of cholesteatoma, in the light of recent otopathological findings. Congenital cholesteatoma is most plausibly explained by the persistence of fetal epidermoid formation. Conclusive 'proof' awaits the unambiguous demonstration of the metamorphosis of an epidermoid nidus into a lesion in vivo. Acquired cholesteatoma may develop by various mechanisms: immigration, basal hyperplasia, retraction pocket and/or trauma (iatrogenic or non-iatrogenic). However, squamous metaplasia of the normal cuboidal epithelium of the middle ear is a highly unlikely explanation. Chronic inflammation seems to play a fundamental role in multiple aetiopathogenic mechanisms of acquired cholesteatoma. Therefore early treatment of inflammatory conditions might reduce their sequelae, perhaps by preventing the development of hyperplastic papillary protrusions. Continued otopathological, cellular and molecular research would enhance our limited understanding of cholesteatoma and may lead to new therapeutic strategies for this erosive disease, which often defies surgical treatment.
89 citations
TL;DR: The overall 5-year relative survival rate is comparable if not better than other studies, supporting recent evidence that the prognosis in this group of patients is no worse than for colorectal cancer in the population as a whole.
Abstract: Colorectal cancer is the second most common cause of death from cancer in the UK. It is estimated that between 2 to 3 per cent of colorectal cancer occurs in patients younger than the age of 40 years. It remains unclear from the literature whether this group of patients has a worse prognosis from colorectal cancer than the population as a whole. There are no large series that report a 10-year survival in young patients diagnosed with colorectal cancer. The authors' objective was to assess patients diagnosed with colorectal cancer younger than the age of 40 years to determine whether the 5- and 10-year survival rates in a tertiary referral center compares favorably with survival rates obtained at other centers and the population as a whole. A retrospective observational study was conducted and an analysis of the patient's notes was made, specifically looking at age at diagnosis, nature and duration of symptoms, predisposing risk factors for colorectal cancer, the site within the bowel of the colorectal cancer, the type of curative resection performed, Dukes' stage, and details of 5- and 10-year follow-up to assess survival. Forty-nine patients age 40 years or younger received treatment for colorectal cancer at St. Mark's Hospital from 1982 to 1992. The overall 5- and 10-year survival was 58 per cent and 46 per cent respectively. The study provides more evidence to support the fact that young patients with colorectal cancer seem to present with more advanced disease. Despite this, the overall 5-year relative survival rate is comparable if not better than other studies, supporting recent evidence that the prognosis in this group of patients is no worse than for colorectal cancer in the population as a whole.
83 citations
TL;DR: The extent of residual myocardial viability predicted by MCE is a powerful independent predictor of hard cardiac events in patients after AMI.
TL;DR: A case of neonatal hypocalcaemic seizures secondary to vitamin D deficiency is presented and it is becoming clear that there is a positive correlation between maternal vitamin D status during pregnancy and lactation and the development of rickets both in infancy and childhood.
Abstract: Maternal vitamin D insufficiency is not uncommon. Infants born to mothers who are deficient in vitamin D and or calcium, usually due to cultural modifications in their diets or clothing habits, and in addition are breastfed, are at risk of developing vitamin D deficiency and hypocalcaemia. We present a case of neonatal hypocalcaemic seizures secondary to vitamin D deficiency. Rickets in children resulting from vitamin D deficiency is well documented. It is also becoming clear that there is a positive correlation between maternal vitamin D status during pregnancy and lactation and the development of rickets both in infancy and childhood. The correlation between maternal vitamin D, neonatal vitamin D and hypocalcaemia is not well documented.
TL;DR: The consequences of living day-to-day with CBP is described and the ‘insider’ accounts of its impact on daily life are documents and facilitated ‘adjustment’ to ‘loss’ may be more helpful than inferring the potential for a life free of pain as a result of therapeutic endeavours.
Abstract: Purpose Back-related functional limitations are largely assessed using lists of activities, each scored on a yes/no basis and the scores then summed This provides little information about how chronic back pain (CBP) patients live with their condition This study describes the consequences of living day-to-day with CBP and documents the ‘insider’ accounts of its impact on daily lifeMethod Unstructured interviews, using the ‘Framework’ approach with topic guide, were recorded and transcribed verbatim Subjects were sampled for age, sex, ethnicity and occupation from new referrals with back pain to a rheumatology outpatient clinic Eleven subjects (5 male, 6 female) were interviewed either in English (n = 9) or their preferred language (n = 2) Interviews were read in-depth twice to identify the topics Data were extracted in phrases and sentences using thematic content analysisResults Four themes emerged: sleep/rest, mobility, independence and leisure All subjects reported issues about sleep and rest
TL;DR: It was showed that WBV exercise with frequencies of 30, 40, and 50 Hz and small amplitudes does not affect muscle oxygenation of VL and GM muscles to a higher degree than a nonvibration condition.
Abstract: Purpose: The aim of this study was to investigate the effects of different whole-body vibration (WBV) frequencies on oxygenation of vastus lateralis (VL) and gastrocnemius medialis (GM) muscles during static squatting in sedentary and physically active healthy males.
Methods: Twenty volunteers (age: 24.6 ± 2.9 yr; body mass: 80.6 ± 11.8 kg; height: 178.1 ± 7.6 cm) participated in this study. Ten subjects were sedentary individuals and 10 were athletes practicing different sports. All subjects completed four trials (control, and 30-, 40-, and 50-Hz WBV) in a randomized controlled crossover design. The trials consisted of static squatting on a vibrating platform for a total duration of 110 s. Muscle-oxygenation status was recorded with near-infrared spectroscopy.
Results: The data analysis revealed no significant treatment-by-time interactions in tissue-oxygenation index (TOI) or ? total hemoglobin volume (tHb) in VL and GM muscles. A significant main effect of time in TOI of both VL and GM muscles was identified (P < 0.001). VL TOI significantly decreased by 2.8% at 90 s in the control condition and by 3.3% at 110 s in the 30-Hz condition; VL TOI significantly increased by 2.1 and 3.0% at 30 s in the 40- and 50-Hz conditions, respectively. GM TOI significantly decreased by 3.2% at 60 s, by 4.1% at 90 s, and by 4.3% at 110 s in the control condition, and by 5.5% at 110 s in the 30-Hz condition.
Conclusion: This study showed that WBV exercise with frequencies of 30, 40, and 50 Hz and small amplitudes does not affect muscle oxygenation of VL and GM muscles to a higher degree than a nonvibration condition.
TL;DR: There was no difference in cost to diagnosis between initial ETT and MPI, and in low-likelihood patients ETT was less costly, whereas there was no cost difference in intermediate- or high- likelihood patients.
TL;DR: The pre-drilled steel embedding-mould technique described here meets the conditions to construct high-quality, high-density PTMAs with inexpensive, easy-to-use equipment.
Abstract: space of about 3 h it was possible to drill up to 600 holes and to fill the PTMA with PTCBs. The technique was validated in a study on breast carcinomas (data not shown). Of 256 PTCBs (1 mm in diameter), 24% were non-informative due to loss of PTCBs (7%) during the staining process, disrupted PTCBs (1.5%), missing tumour (12.5%) and insufficient quality of the staining (3%; fluorescence in situ hybridization). This number of non-informative PTCBs is within the range (15–37%) published for the Beecher system. In summary, we looked for a way to construct high-quality, high-density PTMAs with inexpensive, easy-to-use equipment. The pre-drilled steel embedding-mould technique described here meets these conditions. Using equipment costing <$300 (£150), it was possible to construct PTMAs with up to 600 holes using conventional plastic cassettes and steel embedding moulds.
TL;DR: The additional investment in longer-stay rehabilitation in this group of complex patients was offset relatively quickly by long-term savings in the cost of care.
Abstract: Purpose: To examine the cost-efficiency of longer stay rehabilitation in patients with complex neurological disabilities.Methods: Longitudinal cohort analysis of consecutive admissions to a specialized in-patient rehabilitation unit. Selection criteria: patients who were highly dependent on admission (NPDS ≥ 25) and had a length of stay > 125 days. Serial changes in dependency and care costs were measured by the Northwick Park Dependency and Care Needs Assessment (NPDS/NPCNA), which provides a generic estimation of dependency, care hours and weekly cost of continuing care in the community.Results: Of 410 admissions over 5 years, 51 met the case-selection criteria—mean age 39 ± 17 years, male:female ratio 2:1. The mean length of stay (LOS) was 184 ± 56 days (max 312). Between 4 months and discharge (mean 58 ± 56 days later) significant changes were seen in dependency (t = 4.8, p < 0.0001) and care costs (t = 2.0, p < 0.05). The mean additional cost of rehabilitation beyond 4 months (£16 766 ± 17 334) would...
TL;DR: A 17-year-old Sri Lankan woman in her first pregnancy presented at 39 weeks and 4 days gestation with a clear history of ruptured membranes, confirmed on speculum examination, and regular painful contractions to deliver a female infant in good condition by normal vaginal delivery.
TL;DR: The Rehabilitation Complexity Scale (RCS) demonstrated clear differences between the two types of service, in terms of the complexity of case mix and of the rehabilitation inputs provided.
Abstract: New commissioning arrangements in the NHS require the identification of 'complex specialised' (CS) services, as distinct from more 'general' or 'district specialist' (DS) rehabilitation services, to determine differential cost-tariffs. In this cross-sectional postal survey representing 49 inpatient neurological rehabilitation services in the UK, no clear service characteristics that distinguished CS services (n = 20) from DS services (n = 29) could be identified. On the other hand, the Rehabilitation Complexity Scale (RCS) demonstrated clear differences between the two types of service, in terms of the complexity of case mix and of the rehabilitation inputs provided. District specialist services reported a median RCS score of 7 (interquartile range (IQR) 6-8), whereas CS services reported higher scores (median 9 (IQR 7-11)) (Mann-Whitney z = -9.3, p or = 9 appeared to be a sensitive and specific indicator of a CS service. This study represents the first reported use of the RCS. Feedback regarding the utility of the tool was generally favourable, although other more detailed instruments are likely to be required to distinguish complexity at the very top end of the scale. As NHS services tackle the challenges posed by Payment by Results for management of patients with complex needs, it is suggested that this approach may have application in other fields of clinical practice.
TL;DR: It is concluded that endurance exercise may act as a promoter for RV changes and a resultant trigger for VA, and the postulated cause and effect relationship between RV dysfunction and VA is agreed.
Abstract: We read with great interest the article by Ector et al. 1 reporting ventricular arrhythmias (VA) in highly trained endurance athletes, originating from a mild right ventricular (RV) dysfunction. Of note, the authors conclude that endurance exercise may act as a promoter for RV changes and a resultant trigger for VA. In part, we agree with the authors' findings; however, we have some comments regarding the postulated cause and effect relationship between RV dysfunction and VA.
An increased prevalence of arrhythmias in endurance-trained athletes has been noted previously, predominantly in veteran athletes.2 Several forms of idiopathic VA have been identified in athletes, which, by definition, originate in hearts without structural abnormalities.3 Unpublished observations from our laboratory …
TL;DR: Background Dendritic cells mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined.
Abstract: Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory-tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD 1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid-naive, allergen-challenged and allergen-naive subjects (atopic asthmatics, atopic non-asthmatics and non-atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA-DR + (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4 + naive T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC-dextran was enhanced in cells from asthmatics (P < 0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P < 0.05-P < 0.001), CD1c, CD1d and langerin (P < 0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24h; P < 0.05). CD11c - CD123 high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD 1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.
TL;DR: This article revisits the induction of bone by the osteogenic proteins of the transforming growth factor-beta superfamily in nonhuman and human primates and proposes that the translation in clinical contexts of the phenomenon of bone; formation by autoinduction, is predictably achievable by the binary application of relatively low doses of transforming growth factors with a recombinant human osteogenic protein.
TL;DR: Immersion warming of blood for transfusion by immersion in a water bath appears to be a reasonable alternative to using a blood‐warming coil.
Abstract: The practice of warming blood for transfusion by immersion in a water bath has been studied. Blood, 3 days after collection, with CPD-adenine anticoagulant, was warmed at 25 degrees C, 37 degrees C and 45 degrees C for up to 2 hours. The procedure was repeated after 2 and 4 weeks' storage at 4 degrees C. Only trivial biochemical and morphological changes resulted from warming. Within these limits, immersion warming of blood appears to be a reasonable alternative to using a blood-warming coil. Other aspects of immersion warming are discussed.
TL;DR: Stress MCE was superior to TIMI risk score and exercise electrocardiography in the assessment of risk in patients with suspected acute coronary syndrome, nondiagnostic electro Cardiac Echocardiographic findings, and negative troponin.
Abstract: We hypothesized that myocardial contrast echocardiography (MCE) could be used to stratify risk in patients with suspected acute coronary syndrome but a nondiagnostic electrocardiogram and negative troponin. Pretest Thrombolysis In Myocardial Infarction (TIMI) scores were determined. Exercise electrocardiographic data in those patients undergoing treadmill stress echocardiography as part of risk evaluation were analyzed independently of echocardiographic data. On a separate day, low-power MCE at rest and during vasodilator stress was performed. All patients were followed for cardiac events (cardiac death, myocardial infarction, and revascularization). Of 148 patients, 27 demonstrated abnormal myocardial contrast echocardiographic results and had higher cardiac event rates compared with those with normal myocardial contrast echocardiographic findings (59% vs 7%, p
TL;DR: The detection of myocardial perfusion during echocardiographic examinations permits simultaneous assessment of global and regional myocardia structure, function, and perfusion, enabling the optimal non-invasive assessment of coronary artery disease.
Abstract: Recent updates in the field of echocardiography have resulted in improvements in both image quality and techniques allowing echocardiography to maintain it's position as the primary non-invasive imaging modality. In particular, the development of new ultrasound contrast agents and imaging techniques have now made possible the assessment of myocardial perfusion. Myocardial contrast echocardiography utilises acoustically active gas filled microspheres (microbubbles), which have rheology similar to that of red blood cells. The detection of myocardial perfusion during echocardiographic examinations permits simultaneous assessment of global and regional myocardial structure, function, and perfusion, enabling the optimal non-invasive assessment of coronary artery disease. Myocardial contrast echocardiography is equally adept in assessing chronic coronary artery disease, acute coronary syndromes and hibernating myocardium.
TL;DR: Three hours of semi‐supine cycling resulted in no evidence of a depression inleft ventricular systolic function, while left ventricular diastolic function declined postexercise, suggesting that the maintained CVP helped to prevent cardiovascular drift in this protocol.
Abstract: This study examined whether left ventricular function was reduced during 3 h of semi-recumbent ergometer cycling at 70% of maximal oxygen uptake while preload to the heart was maintained via saline infusion. Indices of left ventricular systolic function (end-systolic blood pressure–volume relationship, SBP/ESV) and diastolic filling (ratio of early to late peak filling velocities into the left ventricle, E:A) were calculated during recovery and compared with baseline resting data. During exercise in seven healthy, trained male subjects, an arterial catheter allowed continuous assessment of arterial pressure, stroke volume (SV), cardiac output () and an index of contractility (dP/dtmax). A venous catheter assessed that central venous pressure (CVP) was maintained throughout rest, exercise and 10 min into recovery. Both systolic blood pressure and heart rate (HR) increased with the onset of exercise (from 132 ± 5 to 185 ± 19 mmHg and from 66 ± 9 to 135 ± 23 beats min−1; increases from rest to the end of the first 5 min of exercise in SBP and HR, respectively) but systolic blood pressure did not change from 30 to 180 min of exercise (∼150 mmHg), while heart rate only increased by 8 ± 9 beats min−1 (means ±s.d.; P > 0.05). The attenuated increase in HR compared with other studies suggests that the maintained CVP (∼5 mmHg) helped to prevent cardiovascular drift in this protocol. Stroke volume, and dP/dtmax were all increased with the onset of exercise (from 85 ± 8 to 120 ± 18 ml, from 5.4 ± 1.3 to 16.5 ± 3.3 l min−1 and from 14.4 ± 4 to 28 ± 8 mmHg s−1; values from rest to the end of the first 5 min of exercise for SV, and dP/dtmax, respectively) and were maintained during exercise. There was no difference in the SBP/ESV ratio from pre- to postexercise. Conversely, E:A was reduced from 2.0 ± 0.4 to 1.6 ± 0.5 postexercise (P < 0.05), returning to normal values at 24 h postexercise. This change in diastolic filling could not be fully explained (r2= 0.39) by an increased heart rate and, with CVP unchanged, it is likely to represent some depression of intrinsic relaxation properties of left ventricular myocytes. Three hours of semi-supine cycling resulted in no evidence of a depression in left ventricular systolic function, while left ventricular diastolic function declined postexercise.
TL;DR: ATRIPLA is a combination of three drugs that have been well studied and are currently approved as first-line agents internationally and the studies that demonstrate the efficacy and safety of these drugs are reviewed as well as the potential drawbacks.
Abstract: Since the first description of AIDS cases over 25 years ago, great strides have been made in the treatment of HIV infection. The pursuit of new and novel therapies is ongoing, and a particular drive to simple regimens with low toxicities has been seen over the last few years. The arrival of the first once-daily single-tablet regimen is a noteworthy milestone. ATRIPLA (Bristol-Myers Squibb, Princeton, NJ, and Gilead Sciences, Foster City, CA, USA) is a combination of three drugs that have been well studied and are currently approved as first-line agents internationally. The studies that demonstrate the efficacy and safety of these drugs are reviewed as well as the potential drawbacks. Single-tablet regimens are likely to become the therapies of choice for those commencing antiretroviral treatment, and their place in today's management is discussed.
TL;DR: The Datex ‘Normac’ infrared anaesthetic agent monitor has been evaluated for accuracy of calibration, stability and speed of response and was found to be very good for isopurane and enflurane but was slightly less accurate for halothane, due to a low signal: noise ratio.
Abstract: Summary
The Datex ‘Normac’ infrared anaesthetic agent monitor has been evaluated for accuracy of calibration, stability and speed of response. Accuracy was assessed by comparing with a gas chromatograph calibrated using volumetric standards and was found to be very good for isopurane and enflurane but was slightly less accurate for halothane, due to a low signal: noise ratio. The stability of the instrument was found to be exceptionally good. The response time is dependent on the sampling rate and we found that, in practice, the instrument would record the end expired anaesthetic concentration on patients breathing up to 15 breaths/minute. The instrument is compact and convenient for use in operating theatres.
TL;DR: A case of a young male affected by SLE who developed leg ulcers diagnosed as PG in the absence of aPL antibodies is described, where the onset of PG was associated with reactivation of SLE.
Abstract: Leg ulcerations can occur in systemic lupus erythematosus (SLE) patients with antiphospholipid (aPL) antibodies and/or vasculitis, and it has been suggested that aPL antibodies may play a pathogenetic role in skin manifestations of SLE. To our knowledge, there is only one report of an aPL antibody-negative patient who developed pyoderma gangrenosum (PG) several years before the diagnosis of SLE. We describe a case of a young male affected by SLE who developed leg ulcers diagnosed as PG in the absence of aPL antibodies, where the onset of PG was associated with reactivation of SLE. Effective treatment led to significant improvement in skin lesions and SLE activity.
TL;DR: Vibration stimulation can moderate the increase in bone resorption and reduction in bone formation caused by a metabolic acidosis, and is associated with a reduction in calcium excretion and titratable acid and urea output.
Abstract: Excess protein intake can adversely affect the bone via an increase in calcium excretion, while suitable mechanical loading promotes osteogenesis. We therefore investigated whether vibration exposure could alleviate the bone mineral losses associated with a metabolic acidosis. Ten healthy individuals aged 22 – 29 years (median = 25) underwent three 5-day study periods while monitoring their dietary intake. The study consisted of recording the participants' usual dietary intake for 5 consecutive days. Participants were then randomly divided into two groups, one of which received a protein supplement (2 g · kg−1 body mass · day−1; n = 5) and the other whole-body low-magnitude (3.5 g), low-frequency (30 Hz) mechanical vibration (WBV) delivered through a specially designed vibrating plate for 10 min each day (n = 5). Finally, for the third treatment period, all participants consumed the protein supplement added to their normal diet and were exposed to WBV exercise for 10 min per day. Daily urine samp...