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Biomedical subjects

M Stevenson

Publications and source records attributed to M Stevenson.

At least 19 recordsLinked to original sources

A study of the physical rehabilitation and psychological state of patients who sustained limb loss as a result of terrorist activity in Northern Ireland 1969-2003.

OBJECTIVE: To benchmark the psychological state and physical rehabilitation of patients who have sustained limb loss as a result of terrorist activity in Northern Ireland and to determine their satisfaction with the period of primary prosthetic rehabilitation and the artificial limb. METHOD: All patients who sustained limb loss as a result of the Troubles and were referred to our rehabilitation centre were sent a questionnaire. The main outcome measures were the SIGAM mobility grades, the General Health Questionnaire (GHQ12) and three screening questions for Post Traumatic Stress Disorder (PTSD). RESULTS: Out of a 66% response rate, 52 (69%) patients felt that the period of primary prosthetic rehabilitation was adequate; 32 (54%) lower limb amputees graded themselves SIGAM C or D; 45 (60%) patients stated that they were still having significant stump pain. Significant stump pain was associated with poorer mobility. Nine (56%) upper limb amputees used their prosthetic limb in a functional way; 33 (44%) patients showed "psychiatric caseness" on the GHQ 12 and 50 (67%) had symptoms of PTSD. CONCLUSIONS: Most patients felt that the period of physical rehabilitation had been adequate; those who did not were more likely to be having ongoing psychological problems. A high percentage of patients continue to have psychological problems and stump pain.

Adolescent↗

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells.

Non-human adenovirus vectors have attractive immunological properties for gene therapy but are frequently restricted by inefficient transduction of human target cells. Using chicken embryo lethal orphan (CELO) virus, we employed a nongenetic mechanism of polymer coating and retargeting with basic fibroblast growth factor (bFGF-pc-CELOluc), a strategy that permits efficient tropism modification of human adenovirus. bFGF-pc-CELOluc showed efficient uptake and transgene expression in chick embryo fibroblasts (CEF), and increased levels of binding and internalization in a variety of human cell lines. Transgene expression was also greater than unmodified CELOluc in PC-3 human prostate cells, although the specific activity (RLU per internalized viral genome) was decreased. In CEF, the specific activity of bFGF-pc-CELOluc was considerably higher than in the human prostate cell line PC-3. Retargeted virus was fully resistant to inhibition by human serum with known adenovirus-neutralizing activity in vitro, while in mice CELOluc was cleared less rapidly from the blood than Adluc following i.v. administration in the presence of adenovirus neutralizing serum. Polymer coating and retargeting with bFGF further reduced rates of clearance for both viruses, suggesting protection against both neutralizing and opsonizing factors. The data indicate that CELO virus may be retargeted to infect human cells via alternative, potentially disease-specific, receptors and resist the effects of pre-existing humoral immunity.

ATPases Associated with Diverse Cellular Activitie↗

How should we diagnose suspected deep-vein thrombosis?

BACKGROUND: Many different approaches are used to diagnose suspected deep-vein thrombosis (DVT), but there has been little formal comparison of strategies. AIM: To identify the most cost-effective strategy for the UK National Health Service (NHS). DESIGN: Systematic review, meta-analysis and cost-effectiveness analysis. METHODS: We identified 18 strategies and estimated the diagnostic performance of constituent tests by systematic review and meta-analysis. Outcomes of testing and treatment were estimated from published data or by an expert panel. Costs were estimated from NHS reference costs and published data. We built a decision-analysis model to estimate, for each strategy, the overall accuracy, costs, and outcomes (valued as quality-adjusted life-years, QALYs), compared to a 'no testing, no treatment' alternative. Probabilistic analysis estimated the net benefit of each strategy at varying thresholds for willingness to pay for health gain. RESULTS: At the thresholds for willingness to pay recommended by the National Institute for Clinical Excellence (20,000 pounds sterling-30,000 pounds sterling per QALY), the optimal strategy was to discharge patients with a low or intermediate Wells score and negative D-dimer, limiting ultrasound to those with a high score or positive D-dimer. Strategies using radiological testing for all patients were only cost-effective at 40,000 pound sterling per QALY or more. DISCUSSION: The optimal strategy for DVT diagnosis is to use ultrasound selectively in patients with a high clinical risk or positive D-dimer. Radiological testing for all patients does not appear to be a cost-effective use of health service resources.

Cost-Benefit Analysis↗

Public road transport crashes in a low income country.

OBJECTIVE: To assess the safety of government versus non-government public road transportation. DESIGN: Descriptive study. SETTING: Kandy Municipality Area, Sri Lanka. SUBJECTS: All road traffic crashes reported to the Kandy Police from 1 October 1998 to 30 September 1999. MAIN OUTCOME: Involvement in a road traffic crash reported to the Kandy Police in which a government bus, private bus, or a three-wheeler was involved. RESULTS: During the study period, 132 government buses, 243 private buses, and 115 three wheelers were involved in 437 police reported road crashes. Of these crashes, eight (1.8%) were fatal and 132 (30.2%) were crashes resulting in injury requiring hospitalization. The majority of road crashes involved vehicle-vehicle interaction (63.4%) and vehicle-pedestrian interaction (17.8%), while the remainder consisted of vehicle-passenger and vehicle-road structure crashes. The research highlights an increased risk associated with travel on privately owned buses (RR = 2.0, 95% CI 1.6 to 2.5) and three wheelers (RR = 2.2, 95% CI 1.7 to 2.8) compared to travel on government buses. The disparity in crash rates between government and privately owned transportation modes can be explained, in part, by fewer safety requirements being imposed on the deregulated public transportation system. CONCLUSIONS: Recommendations are made in order to address the differential in crash rates between public and private vehicle ownership used for public transportation in Sri Lanka.

Accidents, Traffic↗

Effect of ruminally protected methionine on splanchnic metabolism of amino acids in lactating dairy cows.

The effect of ruminally protected Met (RPM) on splanchnic metabolism was measured in 3 primiparous and 3 multiparous Holstein cows. Doses of RPM (0, 36, and 72 g/d) were tested in a replicated 3 x 3 Latin square design, over 3 consecutive 14-d experimental periods. A mixed ration was fed in 12 equal meals per d (average dry matter intake: 17.5 +/- 0.08 kg/d). Indwelling catheters were surgically implanted in the mesenteric artery and the portal and hepatic veins for blood collection, as well as in 2 distal branches of the mesenteric vein for infusion of p-aminohippurate to determine blood flow. On d 14 of each period, a temporary catheter was inserted into a mammary vein and 6 hourly blood samples were collected to determine plasma concentrations of metabolites, hormones, and their respective fluxes across the splanchnic bed and mammary glands. Yields of milk (32.8, 32.0, and 32.9 +/- 0.92 kg/d) and protein (1,028, 1,053, and 1,075 +/- 28.7 g/d) were unaffected by level of RPM. However, the true protein content in milk from primiparous cows increased linearly (2.92, 3.09, and 3.34 +/- 0.077%). The addition of RPM linearly increased the net flux of Met across the portal-drained viscera, which resulted in increased arterial Met concentrations (25, 29, and 40 +/- 1.1 microM). Although it had no significant effect on net portal and hepatic fluxes of other essential amino acids, RPM resulted in a linear increase in the total splanchnic output of Ile, Leu, Phe, and Thr. These results suggest that feeding RPM triggered a homeostatic response resulting in less utilization of certain essential amino acids through the gastrointestinal tract and liver. Net mammary uptake of Met did not change with the addition of RPM. However, mammary extraction of Met decreased in a linear fashion in response to increased arterial inflow.

Amino Acids↗

Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis.

OBJECTIVES: To estimate the diagnostic accuracy of non-invasive tests for proximal deep vein thrombosis (DVT) and isolated calf DVT, in patients with clinically suspected DVT or high-risk asymptomatic patients, and identify factors associated with variation in diagnostic performance. Also to identify practical diagnostic algorithms for DVT, and estimate the diagnostic accuracy, clinical effectiveness and cost-effectiveness of each. DATA SOURCES: Electronic databases (to April 2004). A postal survey of hospitals in the UK. REVIEW METHODS: Selected studies were assessed against validated criteria. A postal survey of hospitals in the UK was undertaken to describe current practice and availability of tests, and identify additional diagnostic algorithms. Pooled estimates of sensitivity, specificity and likelihood ratios were obtained for each test using random effects meta-analysis. The effect of study-level covariates was explored using random effects metaregression. A decision-analytic model was used to combine estimates from the meta-analysis and estimate the diagnostic performance of each algorithm in a theoretical population of outpatients with suspected DVT. The net benefit of using each algorithm was estimated from a health service perspective, using cost--utility analysis, assuming thresholds of willingness to pay of pound 20,000 and pound 30,000 per quality-adjusted life-year (QALY). The model was analysed probabilistically and cost-effectiveness acceptability curves were generated to reflect uncertainty in estimated cost-effectiveness. RESULTS: Individual clinical features are of limited diagnostic value, with most likelihood ratios being close to 1. Wells clinical probability score stratifies proximal, but not distal, DVT into high-, intermediate- and low-risk categories. Unstructured clinical assessment by experienced clinicians may have similar performance to Wells score. In patients with clinically suspected DVT, D-dimer has 91% sensitivity and 55% specificity for DVT, although performance varies substantially between assays and populations. D-dimer specificity is dependent on pretest clinical probability, being higher in patients with a low clinical probability of DVT. Plethysmography and rheography techniques have modest sensitivity for proximal DVT, poor sensitivity for distal DVT, and modest specificity. Ultrasound has 94% sensitivity for proximal DVT, 64% sensitivity for distal DVT and 94% specificity. Computed tomography scanning has 95% sensitivity for all DVT (proximal and distal combined) and 97% specificity. Magnetic resonance imaging has 92% sensitivity for all DVT and 95% specificity. The diagnostic performance of all tests is worse in asymptomatic patients. The most cost-effective algorithm discharged patients with a low Wells score and negative D-dimer without further testing, and then used plethysmography alongside ultrasound, with venography in selected cases, to diagnose the remaining patients. However, the cost-effectiveness of this algorithm was dependent on assumptions of test independence being met and the ability to provide plethysmography at relatively low cost. Availability of plethysmography and venography is currently limited at most UK hospitals, so implementation would involve considerable reorganisation of services. Two algorithms were identified that offered high net benefit and would be feasible in most hospitals without substantial reorganisation of services. Both involved using a combination of Wells score, D-dimer and above-knee ultrasound. For thresholds of willingness to pay of pound 10,000 or pound 20,000 per QALY the optimal strategy involved discharging patients with a low or intermediate Wells score and negative D-dimer, ultrasound for those with a high score or positive D-dimer, and repeat scanning for those with positive D-dimer and a high Wells score, but negative initial scan. For thresholds of pound 30,000 or more a similar strategy, but involving repeat ultrasound for all those with a negative initial scan, was optimal. CONCLUSIONS: Diagnostic algorithms based on a combination of Wells score, D-dimer and ultrasound (with repeat if negative) are feasible at most UK hospitals and are among the most cost-effective. Use of repeat scanning depends on the threshold for willingness to pay for health gain. Further diagnostic testing for patients with a low Wells score and negative D-dimer is unlikely to represent a cost-effective use of resources. Recommendations for research include the evaluation of the costs and outcomes of using the optimal diagnostic algorithms in routine practice, the development and evaluation of algorithms appropriate for specific groups of patients with suspected DVT, such as intravenous drug abusers, pregnant patients and those with previous DVT, the evaluation of the role of plethysmography: interaction with other diagnostic tests, outcome of low-risk patients with negative plethysmography and measurement of the costs of providing plethysmography, and methodological research into the incorporation of meta-analytic data into decision-analytic modelling.

Adult↗

Accurate, practical and cost-effective assessment of carotid stenosis in the UK.

OBJECTIVES: To determine whether less invasive imaging tests [ultrasound (US), magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and contrast-enhanced MRA (CEMRA)], alone or combined, could replace intra-arterial angiography (IAA), what effect this would have on strokes and deaths, endarterectomies performed and costs, and whether less invasive tests were cost-effective. DATA SOURCES: Electronic databases covering the years 1980-2003 inclusive, updated to April 2004. Key journals from 1990 to the end of 2002. REVIEW METHODS: The authors constituted a panel of experts in stroke, imaging, vascular surgery, statistics and health economic modelling. The accuracy of less invasive carotid imaging was systematically reviewed using Standards for Reporting of Diagnostic Accuracy (STARD) methodology, supplemented by individual patient data from UK primary research and audit studies. A systematic review of the costs of less invasive tests, outpatient clinics, endarterectomy and stroke was performed, along with a microcosting exercise. A model of the process of care following a transient ischaemic attack (TIA)/minor stroke was developed, populated with data from stroke epidemiology studies in the UK, effects of medical and surgical interventions, outcomes, quality of life and costs. A survey of UK stroke prevention clinics provided typical timings. Twenty-two different carotid imaging strategies were evaluated for short- and long-term outcomes, quality-adjusted life-years (QALYs) and net benefit. RESULTS: In 41 included studies (2404 patients, median age 60-65 years), most data were available on 70-99% stenosis. CEMRA was the most accurate [sensitivity 0.94, 95% confidence interval (CI) 0.88 to 0.97; specificity 0.93, 95% CI 0.89 to 0.96], compared with US, MRA and CTA, which were all similar (e.g. for US: sensitivity 0.89, 95% CI 0.85 to 0.92; specificity 0.84, 95% CI 0.77 to 0.89). Data for 50-69% stenoses and on combinations of tests were too sparse to be reliable. There was heterogeneity between studies for all imaging modalities except for CTA. The individual patient data (2416 patients) showed that the literature overestimated test accuracy in routine practice and that, in general, tests perform with higher sensitivity and specificity in asymptomatic than in symptomatic arteries. In the cost-effectiveness model, on current UK timings, strategies allowed more patients to reach endarterectomy very quickly, and where those with 50-69% stenosis would be offered surgery in addition to those with 70-99%, prevented most strokes and produced greatest net benefit. This included most strategies with US as first or repeat test, and not those with IAA. However, the model was sensitive to less invasive test accuracy, cost and timing of endarterectomy. In patients investigated late after TIA, test accuracy is crucial and CEMRA should be used before surgery. CONCLUSIONS: In the UK, less invasive tests can be used in place of IAA if radiologists trained in carotid imaging are available. Imaging should be carefully audited. Stroke prevention clinics should reduce waiting times at all stages to improve speed of access to endarterectomy. In patients presenting late after TIA, test accuracy is very important and US results should be confirmed by CEMRA, as patients with 50-69% stenosis are less likely to benefit. More data are required to define the accuracy of the less invasive tests, with improvements made in the data collection methods used and how data are presented. Consideration should also be given to the use of new technologies and randomised trials.

Angiography↗

Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon.

Metallothionein (MT) crypt-restricted immunopositivity indices (MTCRII) are colonic crypt stem cell mutation markers that may be induced early and in abundance after mutagen treatment. Metallothionein is the endogenous reporter gene for MTCRII, but is not typically implicated in the classical pathway of colorectal tumorigenesis. Hence, the oncological relevance of MTCRII is unclear. This study tests the hypothesis that MTCRII induced by N-methyl-N-nitrosourea (MNU) and lambda carrageenan (lambdaCgN) associate with aberrant crypt foci (ACF) in mouse colon. Undegraded lambdaCgN and MNU were tested alone and in combination against MTCRII and ACF in Balb/c mice, at 20 weeks after the start of treatment. MTCRII were unaffected by lambdaCgN alone. Combined lambdaCgN/MNU treatments induced greater MTCRII (P < 0.01) as well as greater number (P < 0.001) and crypt multiplicity (P < 0.01) of ACF than MNU alone. MTCRII were approximately 10-fold more numerous than ACF, although linear correlations were observed between these parameters (r = 0.732; P < 0.01). MTCRII are induced by lambdaCgN/MNU interactions in sufficient numbers to provide statistical power from relatively small sample sizes and correlate with ACF formation. MTCRII could thus provide the basis for a novel medium-term murine bioassay relevant to early-stage colorectal tumorigenesis.

Animals↗

The influence of lower face vertical proportion on facial attractiveness.

This study investigated the influence of changing lower face vertical proportion on the attractiveness ratings scored by lay people.Ninety-two social science students rated the attractiveness of a series of silhouettes with normal, reduced or increased lower face proportions. The random sequences of 10 images included an image with the Eastman normal lower face height relative to total face height [lower anterior face height/total anterior face height (LAFH/TAFH) of 55 per cent], and images with LAFH/TAFH increased or decreased by up to four standard deviations (SD) from the Eastman norm. All the images had a skeletal Class I antero-posterior (AP) relationship. A duplicate image in each sequence assessed repeatability. The participants scored each image using a 10 point numerical scale and also indicated whether they would seek treatment if the image was their own profile. The profile image with normal vertical facial proportions was rated by the lay people as the most attractive. Attractiveness scores reduced as the vertical facial proportions diverged from the normal value. Images with a reduced lower face proportion were rated as significantly more attractive than the corresponding images with an increased lower face proportion. Images with a reduced lower face proportion were also significantly less likely to be judged as needing treatment than the corresponding images with an increased lower face proportion.

Adolescent↗

The effect of high altitude commercial air travel on oxygen saturation.

Air travel has increased steadily over the last decade, and its effect on the health of passengers has been the subject of much debate. There is a paucity of evidence on the effects of air travel on oxygen saturation in general populations. The peripheral oxygen saturation and pulse rate of 84 passengers, aged 1-78 years, were measured by pulse oximetry at round level and altitude during air travel. There was a statistically significant reduction in oxygen saturation in all passengers travelling long haul and short haul flights (p < 0.05). The mean [range] (SD) SpO(2) for all flights at ground level was 97% [93-100] (1.33) and at cruising altitude 93% [85-98] (2.33). Fifty-four per cent of passengers had SpO(2) values of 94% or less at cruising altitude. This is a value which may prompt physicians to administer supplemental oxygen in hospital patients.

Adolescent↗

A prospective cohort study comparing hospital admission for gastro-enteritis with home management.

OBJECTIVES: To compare physical and psychological outcomes in children presenting at Accident and Emergency Departments (A&E), diagnosed with gastro-enteritis and admitted to hospital with those of a similar age, sex and severity of illness discharged home. The physical and psychological well-being of children in these two groups, in the month after the episode, were compared as was further use of health care services. DESIGN: A prospective cohort study. METHODS: A comparison of 116 children aged 1-6 years with gastro-enteritis, presenting at A&E over a 6 months period. Admitted children were compared with children discharged, of a similar age, sex and illness severity (triage score) with follow-up at 1 week and 1 month. Clinical history, psychosocial factors, investigations and outcomes were recorded at presentation and physical, psychological and family outcomes at 1 week and 1 month. RESULTS: Of 116 children, 112 (97%) completed the study (56 in each group). No differences were detected in psychosocial factors, socio-economic status, family factors, time of arrival at A&E or waiting times. Parental perception of illness was greater in the admitted group (P < 0.005), but was recorded after the decision on admission was made. At 1 week follow-up admitted children had increased separation anxiety compared with children who were discharged (P < 0.05), but this difference disappeared at 1 month. Clinical outcomes were the same for both groups, although admitted children had more investigations (91% vs. 39%). Parents were equally satisfied with their child's treatment, but one-third of children in both groups sought further consultation with a health professional in the following week. CONCLUSIONS: There is no statistically significant difference in socio-demographic data, time of arrival at A&E, waiting times, clinical and psychosocial outcomes in children with acute gastro-enteritis admitted to hospital compared with a group of children of similar age, gender and severity of illness managed at home. However, parents seek reassurance and follow-up of acutely ill children, even if the child is admitted to hospital, which has service and resource implications.

Child↗

Use of ecological study designs for injury prevention.

This paper provides an overview of the ecological study design and its application to injury prevention. The advantages and disadvantages of ecological designs are described and the principle characteristics of the ecological design are highlighted. The paper concludes by highlighting the pivotal role that ecological studies can have in our understanding of the complex interaction between the environment and injury, and the application of this design in elucidating key population based strategies for injury prevention.

Data Collection↗

The validity of a four week self-recall of sports injuries.

The ability of sports injury studies to provide reliable incidence estimates depends on accurate injury data. One of the most commonly used methods of collecting injury data is through self-report, but the validity of such information is largely unknown. This study validated a four week self-report sports injury recall against a range of external sources including hospital records, health practitioner records, and third parties. Cases were drawn from the larger, Western Australian Sports Injury Study (WASIS). This study demonstrates acceptable to good levels of agreement between self-report and more objective data in relation to details such as the nature and body part injured, and the level of injury treatment sought (kappa = 0.48 to 0.78). However, self-reported injury severity did not agree with the Injury Severity Score classification of severity.

Adolescent↗

A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis.

OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of selective oestrogen receptor modulators, bisphosphonates and parathyroid hormone (subject to licensing) for the prevention and treatment of osteoporosis and the prevention of osteoporotic fractures in postmenopausal women. DATA SOURCES: Electronic databases. REVIEW METHODS: Studies that met the review's entry criteria were eligible for inclusion in the meta-analyses provided that they reported fracture incidence in terms of the number of patients suffering fractures. Meta-analysis was carried out using the random-effects model. A model was constructed to estimate the cost-effectiveness of osteoporosis interventions. The model calculated the number of fractures that occurred and provided the costs associated with osteoporotic fractures, and the quality-adjusted life-years (QALYs). In addition, the conditions of breast cancer and coronary heart disease (CHD) were modelled, as some interventions have been shown to affect the risk of these conditions. RESULTS: Ninety randomised controlled trials (RCTs) met the inclusion criteria. They related to the five interventions (alendronate, etidronate, risedronate, raloxifene and teriparatide) and to five comparators (calcium, calcium plus vitamin D, calcitriol, hormone replacement therapy and exercise), as well as placebo or no treatment. All five interventions have been shown to reduce the risk of vertebral fracture in women with severe osteoporosis with adequate calcium intakes. However, none of these drugs has been demonstrated, by direct comparison, to be significantly more effective than either each other or the other active interventions reviewed in this report. The intervention costs of treating all osteoporotic women, for a period of 5 years, were in the region of pound 900-1500 million for alendronate, etidronate, risedronate and raloxifene. The cost per QALY ratios fell dramatically with age. Assuming the risks of a woman with severe osteoporosis at the threshold of osteoporosis, no treatment had a cost per QALY below pound 35,000 at 50 years of age. At 60 years of age, the cost per QALY of raloxifene was pound 26,000 assuming no impact on hip fractures, and pound 31,000 assuming an adverse effect. However, these results are driven by the effect on breast cancer and the assumptions made regarding this disease state. No other intervention had a cost per QALY below pound 35,000. When analyses were conducted assuming that the fracture risk is doubled at each site, alendronate and risedronate had cost per QALY ratios below pound 30,000 at all ages. For women at the threshold of osteoporosis, without a prior fracture and aged 70 years, the cost per QALY of the three bisphosphonates ranged from pound 34,000 to pound 41,000. Raloxifene had a cost per QALY of pound 23,000, assuming no effect on hip fracture, given assumptions regarding breast cancer. At 80 years of age, the cost per QALY of alendronate and risedronate was below pound 20,000. This was true for etidronate when incorporating observational data, but the value rose to pound 69,000 when only RCT data were used. No other intervention had a cost per QALY below pound 35,000. It was assumed that doubling the risk of fracture for women without a prior fracture would give results similar to patients at the threshold of osteoporosis with a prior fracture. CONCLUSIONS: Of the five interventions, only raloxifene appeared to reduce the risk of vertebral fracture in postmenopausal women unselected for low bone mineral density (BMD). However, as the full data have not been made public, there is some uncertainty regarding this result. None of the five interventions has been shown to reduce the risk of non-vertebral fracture in women unselected for low BMD. All of the proposed interventions provided gains in QALYs compared with no treatment in women with sufficient calcium and vitamin D intakes. The size of the QALY gain for each intervention was strongly related to the age of the patient. The estimated costs varied widely for the interventions. These net costs were markedly different by age, with some interventions becoming cost-saving at higher age ranges in patients with a prior fracture. Areas for future research include: the evidence base for the efficacy of fracture prevention in the very elderly, reanalysis of raloxifene using a dedicated breast cancer and CHD model, and more trials considering the cost-effectiveness of teriparatide.

Age Factors↗

An algorithm to predict pregnancy in assisted reproduction.

BACKGROUND: Male fertility potential cannot be measured by conventional parameters for the assisted reproduction technique; ICSI. This study determines the relationship between testicular and ejaculated sperm mitochondrial (mt) DNA deletions, nuclear (n) DNA fragmentation, and fertilization and pregnancy rates in ICSI. METHODS: Ejaculated sperm were obtained from 77 men and testicular sperm from 28 men with obstructive azoospermia undergoing ICSI. Testicular sperm were retrieved using a Trucut needle. mtDNA was analysed using a long PCR. The alkaline Comet assay determined nDNA fragmentation. RESULTS: Of subjects who achieved a pregnancy (50%) using testicular sperm, only 26% had partners' sperm with wild-type (WT) mtDNA. Of pregnant subjects (38%) using ejaculated sperm, only 8% had partner sperm with WT mtDNA. In each, the successful group had less mtDNA deletions and less nDNA fragmentation. There were inverse relationships between pregnancy and mtDNA deletion numbers, size and nDNA fragmentation for both testicular and ejaculated sperm. No relationships were observed with fertilization rates. An algorithm for the prediction of pregnancy is presented based on the quality of sperm nDNA and mtDNA. CONCLUSION: In both testicular and ejaculated sperm, mtDNA deletions and nDNA fragmentation are closely associated with pregnancy in ICSI.

Algorithms↗

Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults.

BACKGROUND: The Burkholderia cepacia complex (BCC) is one of the most important groups of organisms infecting cystic fibrosis (CF) patients. The aim of the study was to examine how infection with BCC affects clinical outcome. METHODS: Nineteen CF adults infected with BCC and 19 controls infected with Pseudomonas aeruginosa were studied over a 4-year period. The best forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) for each year were recorded and annual rate of decline calculated. RESULTS: The BCC infected group displayed a significantly greater reduction of FEV(1) and BMI compared to the P. aeruginosa infected group (p=0.001 and p=0.009, respectively). Sixteen patients infected with a single Burkholderia cenocepacia strain had a significantly greater rate of FEV(1) decline compared to those infected with Burkholderia multivorans (n=3) or P. aeruginosa (p=0.01 and p<0.0001, respectively). The rate of BMI decline was significantly greater in patients infected with B. cenocepacia compared to those with P. aeruginosa (p=0.007), but not significantly different in those with B. multivorans (p=0.29). CONCLUSION: BCC infection is associated with an accelerated decline in pulmonary function and BMI. Infection with a single B. cenocepacia strain was associated with a more rapid decline in lung function than those infected with either B. multivorans or P. aeruginosa.

Adult↗