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Biomedical subjects

D Hart

Publications and source records attributed to D Hart.

At least 19 recordsLinked to original sources
PubMed2007

Analysis of multidisciplinary lung cancer practice.

BACKGROUND: The aim of this study was to describe the activity of a lung cancer multidisciplinary clinic (MDC) and examine whether this model of clinical practice results in adherence to best-practice guidelines. METHODS: Prospective analysis of demographic and clinical data in 431 patients referred to a lung cancer MDC for the management of known or suspected thoracic malignancy. Adherence was documented to clinically relevant guideline recommendations concerning timely and evidence-based lung cancer management. RESULTS: Of 431 patients, 257 were diagnosed with primary lung cancer, mean age 68 years, 70% men and 90% current smokers or ex-smokers. Only 21% were referred with known malignancy and 28% were asymptomatic. Overall, 51% had stages I and II non-small-cell lung cancer, with this bias towards early-stage disease greatest in patients from rural areas. Histological confirmation of lung cancer was obtained in 92%. There was a high rate of adherence to international guideline recommendations concerning timely lung cancer diagnosis, staging and treatment implementation. Similarly, there was adherence to selected key evidence based recommendations for lung cancer management contained in national guidelines. CONCLUSION: Within a MDC, patients receive timely diagnosis, staging and treatment according to evidence-based guideline recommendations. The high proportion of patients receiving active treatment has implications for resource allocation. There is a referral bias towards patients with early non-small-cell lung cancer, particularly in rural patients, suggesting that further education about advances in metastatic lung cancer management is required. This study would support the establishment of regional lung cancer services with links to fully resourced MDC.

Adult↗
PubMed2006

Implementation of semi-automated cloning and prokaryotic expression screening: the impact of SPINE.

The implementation of high-throughput (HTP) cloning and expression screening in Escherichia coli by 14 laboratories in the Structural Proteomics In Europe (SPINE) consortium is described. Cloning efficiencies of greater than 80% have been achieved for the three non-ligation-based cloning techniques used, namely Gateway, ligation-indendent cloning of PCR products (LIC-PCR) and In-Fusion, with LIC-PCR emerging as the most cost-effective. On average, two constructs have been made for each of the approximately 1700 protein targets selected by SPINE for protein production. Overall, HTP expression screening in E. coli has yielded 32% soluble constructs, with at least one for 70% of the targets. In addition to the implementation of HTP cloning and expression screening, the development of two novel technologies is described, namely library-based screening for soluble constructs and parallel small-scale high-density fermentation.

Amino Acid Sequence↗
PubMed2006

Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Surgery is considered the treatment of choice for patients with resectable stage I and II (and some patients with stage IIIA) non-small cell lung cancer (NSCLC), but there have been no previously published systematic reviews. METHODS: A systematic review and meta-analysis of randomised controlled trials was conducted to determine whether surgical resection improves disease specific mortality in patients with stages I-IIIA NSCLC compared with non-surgical treatment, and to compare the efficacy of different surgical approaches. RESULTS: Eleven trials were included. No studies had untreated control groups. In a pooled analysis of three trials, 4 year survival was superior in patients undergoing resection with stage I-IIIA NSCLC who had complete mediastinal lymph node dissection compared with lymph node sampling (hazard ratio estimated at 0.78 (95% CI 0.65 to 0.93)). Another trial reported an increased rate of local recurrence in patients with stage I NSCLC treated with limited resection compared with lobectomy. One small study reported a survival advantage among patients with stage IIIA NSCLC treated with chemotherapy followed by surgery compared with chemotherapy followed by radiotherapy. No other trials reported significant improvements in survival after surgery compared with non-surgical treatment. CONCLUSION: It is difficult to draw conclusions about the efficacy of surgery for locoregional NSCLC because of the small number of participants studied and methodological weaknesses of the trials. However, current evidence suggests that complete mediastinal lymph node dissection is associated with improved survival compared with node sampling in patients with stage I-IIIA NSCLC undergoing resection.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

[HTA in the decision-making processes of health care institutions. Current state and relevant questions of regulatory health law].

The development of the German HTA system and the corresponding HTA law began in 2000 and was concluded for the time being with the coming into force of the law on the modernisation of statutory health insurance on 1 January 2004. This law has established the Federal Joint Committee (G-BA) and the Institute for Quality and Efficiency in Health Care (IQWiG) as "new institutions" of statutory health insurance, restructured the procedures for the assessment of health services and formulated more precise assessment criteria than hitherto provided. There are other institutions in the health care system concerned with HTA which are not dealt with here.

Biomedical Technology↗
PubMed2006

Immature platelet fraction measurement: a future guide to platelet transfusion requirement after haematopoietic stem cell transplantation.

summary. The decision to prophylactically transfuse platelets is dependent on the platelet count, careful regular clinical assessment and agreed local protocol. The ability to predict when platelet recovery will occur should allow a more reasoned approach to platelet transfusion. An increase in reticulated platelets demonstrates impending platelet recovery. A new rapid automated method to assess reticulated platelets, the immature platelet fraction (IPF), is described, and its clinical utility assessed. The IPF is identified by flow cytometry with the use of a nucleic acid specific dye in the reticulocyte channel on the Sysmex XE-2100. Fifty healthy adult volunteers were used to establish the normal range. Patients where platelet marrow production or destruction might be abnormal were studied, and some patients followed serially during treatment. Thirty patients receiving cytotoxic chemotherapy were tested, and 13 of these patients followed serially. Fifteen patients post-autologous or allogeneic transplant were followed daily for platelet count and IPF percentage to monitor platelet recovery. The method demonstrates good reproducibility and stability. The recovery phase of thrombocytopenia in most chemotherapy and transplant patients was preceded by a rise in IPF percentage several days prior to platelet recovery. In particular, patients undergoing autologous transplantation (n = 8) using peripherally collected stem cells have a characteristic IPF percentage motif, with a rise one or two days prior to engraftment. The automated IPF is a useful parameter in the clinical evaluation of the thrombocytopenic patient and has the potential to allow optimal transfusion of platelet concentrates.

Adult↗
PubMed2005

Myofascial trigger point development from visual and postural stressors during computer work.

The mechanism of musculoskeletal pain underlying low level static exertions, such as those experienced during computer work, is poorly understood. It was hypothesized that static postural and visual stress experienced during computer work might contribute to trigger point development in the trapezius muscles, resulting in myofascial pain. A study was conducted to observe the development of myofascial trigger points while 16 female subjects used a computer under conditions of high and low postural and visual stress. Trigger point development was monitored via expert opinion, subject self-report, and electromyographic activity. Only the high visual stress conditions resulted in greater trigger point sensitivity as reported by subjects and the myofascial specialist. Cyclic trends in median frequency of the EMG signal were assessed for the trapezius muscle. When high visual stress was combined with low postural stress condition there were significantly fewer cycles (1.6 cycles) as compared to the condition of low visual and low postural stress (2.8 cycles), and the condition of high visual and high postural stress (3.5 cycles). These significant differences between conditions were found for the right trapezius but not for the left. The findings suggest that high visual stress may be involved in the development of the myofascial pain response.

Adult↗
PubMed2005

The diversity of Banana streak virus isolates in Uganda.

In a study of the variation among isolates of Banana streak virus (BSV) in Uganda, 140 sequences were obtained from 49 samples by PCR across the conserved reverse transcriptase/RNaseH region of the genome. Pairwise comparison of these sequences suggested that they represented 15 different species and phylogenetic analyses showed that all species fell into three major clades based on 28% sequence difference. In addition to the Ugandan sequences, clade I also contained BSV species that are known as both integrated sequences and episomal viruses; clade II also contained integrated BSV sequences but which have not previously been identified as episomal viruses. Clade III comprised of Sugarcane bacilliform virus isolates and Ugandan BSV sequences and for which there is no evidence of integration. The possible reasons for the extraordinary levels of virus sequence variation and the potential origins and epidemiology of these viruses causing banana streak disease are discussed.

Amino Acid Sequence↗
PubMed2005

Surgery for early stage non-small cell lung cancer.

BACKGROUND: Surgical resection (usually lobectomy) is considered the treatment of choice for individuals with stage I and II non-small cell lung cancer (NSCLC) and for some patients with resectable stage IIIA NSCLC. However much of the evidence supporting surgery is observational. OBJECTIVES: To determine whether, in patients with early stage non-small cell lung cancer, surgical resection of cancer improves disease-specific and all-cause mortality compared with no treatment, radiotherapy or chemotherapy. To compare the effectiveness of different surgical approaches (e.g. lobectomy versus limited resection) in improving disease-specific or all-cause mortality in patients with early stage lung cancer. SEARCH STRATEGY: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE (1966 to December 2003)), bibliographies, handsearching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing surgery alone (or in combination with other therapy) with non-surgical therapy and randomised trials comparing different surgical approaches. DATA COLLECTION AND ANALYSIS: A pooled hazard ratio was calculated where possible. Tests for statistical heterogeneity were performed. MAIN RESULTS: Eleven trials were included with a total of 1910 subjects. There were no studies with an untreated control group. In a pooled analysis of three trials, four-year survival was superior in patients with resectable stage I to IIIA NSCLC who underwent resection and complete mediastinal lymph node dissection compared with those undergoing resection and lymph node sampling, the hazard ratio was estimated to be 0.78 (95% CI 0.65-0.93, P = 0.005). A further trial found an increased rate of local recurrence in patients with stage I NSCLC treated with limited resection compared with lobectomy. One small trial found a survival advantage in favour of chemotherapy followed by surgery compared to chemotherapy followed by radiotherapy in patients with stage IIIA NSCLC. However none of the other trials included in the review demonstrated a significant improvement in survival in patients treated with surgery compared with non surgical therapy. Several of the included trials had potential methodological weaknesses. AUTHORS' CONCLUSIONS: Conclusions about the efficacy of surgery for local and loco-regional NSCLC are limited by the small number of participants studied to date and potential methodological weaknesses of trials. Current evidence suggests that lung cancer resection combined with complete mediastinal lymph node dissection is associated with a small to modest improvement in survival compared with lung cancer resection combined with systematic sampling of mediastinal nodes in patients with stage I to IIIA NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

[Risk-benefit evaluation of medicinal products. An element of Health Technology Assessment].

This paper aims to further develop and specify the method and the process of risk-benefit evaluation for determining the safety of medicinal products in national and European pharmaceutical law. The term "safety" (Unbedenklichkeit=the relationship between efficacy and harmfulness) is one of the central categories of national and European pharmaceutical law. The guaranteeing of the safety of pharmaceuticals is not a static but a dynamic and process oriented objective. It aims to preserve what has been approved on the one hand, and to increase the standard of safety by innovation on the other. A medicinal product is only found to be safe if the result of the risk-benefit evaluation is a positive risk-benefit balance. Safety must be guaranteed permanently through the entire lifecycle of the medicinal product. One must differentiate between absolute safety, which is related to the individual product, and relative safety, which is related to already available medicinal products of the same indication. The process of risk-benefit evaluation is determined by the indication of the medicinal product. The different types of medicinal products or their different mechanisms of action require different risk-benefit evaluations. The established, estimated and evaluated benefit has to be compared with the established, estimated and evaluated risks of the medicinal product. The comparative risk-benefit evaluation requires a procedural optimisation of benefits as well as minimisation of risks and a reciprocal optimisation of both requirements. If the comparison of the benefits and risks of the product results in a negative risk-benefit balance, the product is rated absolutely unsafe. The product is relatively unsafe if its standard of safety is lower than that of already available pharmaceuticals of the same indication and the existing safety gap (increased benefit or lesser risks) is deemed considerable. Differences in benefit and/or differences in risk between the medicinal products compared in the risk/benefit evaluation render the assessment more difficult and require differentiation. Such differentiation, based on indication, has to be appropriate from the doctor's perspective and desirable from the perspective of the patient. Both perspectives have to be considered in the risk/benefit evaluation under the aspect of risk acceptance ("justifiable").

Adverse Drug Reaction Reporting Systems↗
PubMed2005

The accuracy of EUS-FNA in assessing mediastinal lymphadenopathy and staging patients with NSCLC.

Optimal management of nonsmall cell lung cancer (NSCLC) depends on tissue diagnosis and accurate staging. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is minimally invasive and provides cytological confirmation of malignant mediastinal disease. The aim was to assess the accuracy of EUS-FNA in cases of enlarged mediastinal lymphadenopathy (LN) of unknown aetiology and in the staging of NSCLC. A total of 52 consecutive patients with stage I-IIIb NSCLC or enlarged mediastinal LN of unknown aetiology underwent EUS-FNA. Negative results were confirmed with a surgical procedure: mediastinoscopy, video-assisted thoracic surgery (VATS) or lobectomy with systematic mediastinal lymph node dissection. In total, 34 patients had EUS-FNA performed for diagnosis, whilst the remaining 18 had EUS-FNA for staging. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (95% confidence interval) were 93% (77-99), 100% (78-100), 100% (87-100), 88% (63-99) and 95% (84-99), respectively. When EUS-FNA was used in patients with NSCLC, the sensitivity, specificity, PPV, NPV and accuracy were 92% (73-99), 100% (69-100), 100% (85-100), 83% (51-98) and 94% (80-99), respectively. For mediastinal LN of unknown aetiology, no malignant disease was missed. Endoscopic ultrasound-guided fine-needle aspiration is an accurate tool for assessing mediastinal lymph node involvement in nonsmall cell lung cancer and in the diagnosis of unexplained mediastinal lymphadenopathy. Endoscopic ultrasound-guided fine-needle aspiration is a minimally invasive procedure that can be used as an adjunct or alternative to mediastinoscopy.

Aged↗
PubMed2004

Pregnancy-related thrombosis in a woman with congenital afibrinogenemia: a report of two successful pregnancies.

We managed two pregnancies in a woman with congenital afibrinogenemia with increasing amounts of cryoprecipitate to achieve a pre-infusion fibrinogen level of 60 mg/dL. The first pregnancy resulted in placental abruption at 36 weeks, in spite of recent cryoprecipitate infusion. Both placentas showed infarction. Post-partum ovarian and renal vein thromboses complicated the second pregnancy. Mean FVIII (344%) and vWF Antigen (323%) were elevated prior to cryoprecipitate infusion, with mean post-infusion levels of 367% and 363%. The clearance of fibrinogen after cryoprecipitate infusion increased during the course of pregnancy. A paradoxical prothrombotic state with embolization may play a role in the observed complications of pregnancy.

Afibrinogenemia↗
PubMed2004

UK population dose from medical X-ray examinations.

OBJECTIVE: To assess the annual per caput and collective effective dose to the United Kingdom population from medical and dental X-ray examinations. METHOD: The results of a detailed survey of the frequency of X-ray examinations during the financial year 1997/1998 were combined with contemporary data on the effective doses typically received by patients. The resulting per caput and collective dose for 1997/1998 was updated to 2001/2002 by using annual statistics on the total numbers of computed tomography (CT), interventional and conventional examinations collected by the English Department of Health. RESULTS: The annual per caput effective dose for the UK in 2001/2002 was estimated at 0.38 mSv. Over the last 10 years CT has more than doubled its contribution and is now responsible for 47% of the collective dose from medical X-rays. The contribution from conventional radiographic and fluoroscopic examinations has nearly halved to about 34%. Interventional and angiographic procedures together contribute the remaining 19%. CONCLUSIONS: The annual per caput effective dose of 0.38 mSv is low in comparison with other countries having similarly developed systems of health-care. This is due to both a lower frequency of X-ray examinations per head of population and generally lower doses in the UK than in other developed countries.

Angiography↗
PubMed2003

Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins.

BACKGROUND: Osteoarthritis (OA) is a disorder of the whole synovial joint organ. There is growing evidence of the importance of bone turnover in OA, and human studies have demonstrated that the subchondral bone is metabolically active in OA. The aim of this study was to assess the relationships of radiographic knee OA with altered bone turnover and calcium regulation. METHODS: We performed a matched and unmatched case-control study using twins assessed for OA. The subjects were 1644 female Caucasian twin pairs (266 monozygotic and 556 dizygotic) aged 24-79 yr from the St Thomas' UK Adult Twin Registry. Assays for measures of bone turnover [bone-specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline (DPD)] and calcium regulation [serum parathyroid hormone (PTH), 25-hydroxyvitamin D, serum calcium, serum magnesium and serum phosphate] were performed. The radiological features of knee OA were graded on a four-point scale (0-3) for osteophytes and a five-point scale (0-4) for Kellgren and Lawrence classification. Adjustment for age, body mass index (BMI) and relatedness was made. Conditional logistic regression analysis was also used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for having radiological features of knee OA per standardized unit difference of serum variable between twins. RESULTS: Of the 1644 women studied, 474 (28.8%) had radiological evidence of knee osteophytes. There was evidence of increased bone turnover, increased PTH levels and decreased vitamin D levels in this group compared with those without osteophytes. No association was seen with joint space loss. After adjusting for age, BMI and relatedness, all of the differences disappeared except for a significant increase 10% in urinary DPD (P = 0.04). Discordant twin pair analysis (performed on a subgroup of 229 pairs) confirmed modest increases in bone resorption indicated by urinary DPD (OR 1.67, 95% CI 0.88-3.16) and a significant decrease in serum magnesium (OR 0.65, 95% CI 0.46-0.92) in the co-twins with OA. CONCLUSION: Bone resorption is increased in women with knee OA, consistent with metabolically active subchondral bone. However, bone formation, vitamin D and calcium regulation were not different after adjusting for age and BMI. The results suggest that bone resorption is increased in the presence of OA. Although we cannot clearly differentiate a cause or effect relationship, these results suggest that this is related to disease mechanisms and point to potential diagnostic or therapeutic avenues for bone resorption in OA.

Adult↗
PubMed2003

Molecular characterization of the fish-pathogenic fungus Aphanomyces invadans.

Aphanomyces invadans (Saprolegniaceae) is a peronosporomycete fungus associated with the serious fish disease, epizootic ulcerative syndrome (EUS), also known as mycotic granulomatosis. In this study, interspecific relationships were examined between A. invadans isolates and other aquatic animal pathogenic Saprolegniaceae, and saprophytic Saprolegniaceae from EUS-affected areas. Restriction fragment length polymorphisms and sequences of ribosomal DNA confirmed that A. invadans is distinct from all other species studied. A sequence from the internal transcribed spacer region ITS1, unique to A. invadans, was used to design primers for a PCR-based diagnostic test. Intraspecific relationships were also examined by random amplification of polymorphic DNA using 20 isolates of A. invadans from six countries. The isolates showed a high degree of genetic homogeneity using 14 random ten-mer primers. This provides evidence that the fungus has spread across Asia in one relatively rapid episode, which is consistent with reports of outbreaks of EUS. Physiological distinctions between A. invadans and other Aphanomyces species based on a data set of 16 growth parameters showed remarkable taxonomic congruence with the molecular phylogeny.

Animals↗
PubMed2003

CMRF44+ dendritic cells from peripheral blood stem cell harvests of patients with myeloma as potential cellular vectors for idiotype vaccination.

The optimal conditions required to harvest dendritic cells (DC) for immunotherapy were investigated in a series of preliminary investigations using peripheral blood stem cell (PBSC) harvests and blood from patients with myeloma. There was no difference in the number of DC (CMRF44+, CD19-, CD14-) in PBSC mobilized with G-CSF (mean 0.28%, n = 7) compared with GM-CSF (mean 0.24%, n = 6) and apheresis itself did not concentrate DC. In longitudinal studies (n = 10), the peak DC count (day 12 post PBSC harvest) did not correlate with the peak CD34+ cell count or white cell count. A simple affinity purification of DC resulted in a mean 63-fold purification. Affinity enriched suspensions from normal blood contained more DC (mean = 18.8%; n = 5) than those from patients with myeloma (mean = 9.9%; n = 13). The percentage of DC with a lymphoid phenotype (CD11c-, CDw123hi+) was significantly higher in G-CSF mobilized PBSC harvests (22.7%; n = 6) than in peripheral blood samples from patients with myeloma (7.0%; n = 13; p = 0.01). DC endocytosis was normal and did not change throughout the course of the disease. Neither DC numbers nor subsets changed significantly between days 1 and 3 of culture. Current mobilization procedures, optimized for PBSC, need to be altered when harvesting DC.

Antibodies, Monoclonal↗