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Biomedical subjects

S Roberts

Publications and source records attributed to S Roberts.

At least 19 recordsLinked to original sources

Case of adolescent with Paget-Schroetter syndrome and underlying thrombophilia due to an elevated lipoprotein (A).

Upper extremity deep vein thrombosis (UEDVT) is a rare disorder in children and is most often associated with a central venous catheter (CVC), cancer, or an underlying thrombophilia. In adults, repetitive or strenuous upper extremity activity has been linked to mechanical compression of the thoracic outlet resulting in subclavian vein thrombosis, also known as Paget-Schroetter Syndrome (PSS). We present the case of a 14 year old female who was found to have an UEDVT consistent with PSS. On subsequent thrombophila screening, she was noted to have a significantly elevated lipoprotein (a) level of 83 (normal: <30 mg/dL). She underwent 3 months of anticoagulation therapy prior to her first rib resection and in follow-up was noted to have complete patency of her subclavian vein. This case illustrates the necessity for thrombophilia screening in the pediatric patient with UEDVT despite evidence of anatomic abnormality or mechanical venous compression.

Adolescent↗

A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network.

AIMS: Combined modality therapy (with chemotherapy+/-radiotherapy) has become a standard treatment for locally advanced oesophageal cancer. However, there appears to be no compelling evidence for one treatment type or combination to suit all and at this time the clinical multi-disciplinary team (MDT) forms an important role in selecting optimal therapies for the individual. This prospective comparison in one cancer network, looks at the outcomes of this decision making process. METHODS: Over a five year period 1998-2003, data were prospectively collected on all 330 consecutive patients, referred to a tertiary specialised MDT for whom curative treatment was the planned intent. Patients were managed according to an agreed local protocol and allocated to receive one of 5 treatments: surgery alone (S), pre-operative chemotherapy (C+S), pre-operative chemo-radiotherapy (CRT+S), definitive chemo-radiotherapy (CRT) and radiotherapy alone (RT). RESULTS: The 2 and 5 year survival for all patients receiving potentially curative treatment were 49% and 26% respectively. With 2 and 5 year survival for S, CRT+S, C+S, CRT and RT being 53,21; 57,40; 37,27; 50,27; 23,0 months respectively. Of the surgical therapies, mortality was highest in the CRT+S group, versus C+S and S; 12.5%, 1.6%, 4.5% respectively (p=0.025). Non-surgical based therapies had more than double the incidence of local relapses compared to surgical based therapies; however the CRT group had an overall survival comparable with S alone. The commonest sites of distant relapse were liver (56%), lung (38%), bone (32%) and non-regional lymph nodes (24%). CONCLUSION: The results suggest that in patients who are deemed unfit for surgical intervention, definitive chemoradiotherapy remains a viable alternative; they also lend further support to selected case triple modality therapy. These areas should be further examined in the context of randomised controlled phase III trials.

Aged↗

Lactate threshold does not influence metabolic responses during exercise in cyclists.

The purpose of this study was to compare plasma markers of metabolic stress and other physiological parameters during prolonged endurance exercise of different intensity in trained subjects possessing a "high" or "low" lactate threshold (LT) expressed as a percentage (%) of peak power output (PPO). Fifteen trained male cyclists completed an incremental exercise test for determination of PPO and the LT (% PPO). Each subject then completed a 90-min and 20-min exercise trial at an intensity representing 75 and 85 % of PPO, respectively. Blood lactate (La), as well as plasma hypoxanthine (Hx) and uric acid (UA) were measured during each exercise trial. The responses in two groups, one (n = 8) with a LT approximately 65 % PPO (LT (low)), the other group (n = 7) with a LT approximately 75 % (LT (high)) (p < 0.01), were then compared. With the exception of UA, La and Hx increased significantly (p < 0.01) throughout each exercise trial compared to rest. However, there were no significant differences in each trial between the two groups of cyclists. There were also no significant differences in the other physiological parameters in each exercise trial between the subjects in LT (low) and LT (high). This study demonstrates that in trained cyclists homogeneous in terms of PPO, plasma markers of metabolic demand during prolonged exercise are not influenced by the LT when measured in an incremental exercise test.

Adult↗

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

Adult↗

v-Myb represses the transcription of Ets-2.

The v-Myb oncogene causes monoblastic leukemia and transforms only myelomonocytic cells in culture. The v-Myb protein is nuclear and binds to specific DNA sequences. To identify genes regulated by v-Myb, we utilized primary cells transformed by a retrovirus encoding a v-Myb-estrogen receptor (ER) fusion protein. The Ets-2 gene was not expressed in v-Myb-ER transformed cells in the presence of estradiol, but was expressed within 4 h after estradiol withdrawal. The expression of Ets-2 also increased dramatically following phorbol ester-induced differentiation of the v-Myb-transformed BM2 cell line. Conversely, CRYP-alpha, encoding a transmembrane tyrosine phosphatase, was expressed in the presence but not the absence of estradiol in v-Myb-ER transformed cells. CRYP-alpha was downregulated during the phorbol ester-induced differentiation of BM2 cells. Although LIM-3 expression was estradiol-inducible in v-Myb-ER transformed monoblasts, LIM-3 was expressed neither in primary yolk sac cells transformed by unfused v-Myb nor in BM2 cells. We conclude that although v-Myb has been intensively studied as a transcriptional activator, v-Myb can repress biologically relevant genes such as Ets-2, which promotes macrophage differentiation. In addition, we have shown that some genes that are regulated by a v-Myb-ER fusion protein may not be relevant to the biological function of the unfused v-Myb protein.

Animals↗

Senescence in human intervertebral discs.

Intervertebral discs demonstrate degenerative changes relatively early in life. Disc degeneration, in turn, is associated with back pain and disc herniation, both of which cause considerable clinical problems in the western world. Cell senescence has been linked to degenerative diseases of other connective tissues such as osteoarthritis. Thus we investigated the degree of cell senescence in different regions of discs from patients with different disc disorders. Discs were obtained from 25 patients with disc herniations; from 27 patients undergoing anterior surgery for either back pain due to degenerative disc disease (n = 25) or spondylolisthesis (n = 2) and from six patients with scoliosis. In addition, four discs were obtained post-mortem. Samples were classified as annulus fibrosus or nucleus pulposus and tissue sections were assessed for the degree of cell senescence (using the marker senescence-associated-beta-galactosidase (SA-beta-Gal)) and the number of cells present in clusters. There were significantly more SA-beta-Gal positive cells in herniated discs (8.5% of cells) than those with degenerative disc disease, spondylolisthesis, scoliosis, or cadaveric discs (0.5% of cells; P < 0.001). There was more senescence of cells of the nucleus pulposus compared to those of the annulus fibrosus and in herniated discs a higher proportion of cells in cell clusters (defined as groups of three or more cells) were SA-beta-Gal positive (25.5%) compared to cells not in clusters (4.2%, P < 0.0001). This study demonstrates an increased degree of cell senescence in herniated discs, particularly in the nucleus where cell clusters occur. These clusters have been shown previously to form via cell proliferation, which is likely to explain the increased senescence. These findings could have two important clinical implications: firstly, that since senescent cells are known to behave abnormally in other locations, they may lead to deleterious effects on the disc matrix and so contribute to the pathogenesis and secondly, cells from such tissue may not be ideal for cell therapy and repair via tissue engineering.

Adolescent↗

Quality of hospital care in African American and white patients with ischemic stroke and TIA.

OBJECTIVE: To examine whether differences exist in the in-hospital diagnostic evaluation and treatment of African American and white patients with ischemic stroke (IS) and TIA. METHODS: The authors used a state-wide hospital-based stroke registry prototype designed to measure and track the quality of acute stroke care. Weighted descriptive statistics for each racial group are reported for the following variables, which were deemed to be potential confounders of the association between race and the quality of stroke care: age, gender, insurance status, emergency medical services arrival, functional status on presentation, modified Rankin score at discharge, stroke subtype, neurologist involved in care, and stroke pathway utilization. The magnitude and significance of the associations between race and each quality indicator of in-hospital acute stroke care were determined by separate multiple logistic regression models, adjusting for all potential confounding variables. RESULTS: Among patients admitted with IS and TIA who were alive at discharge (n = 1,837), 340 (18.5%) were African American and 1497 (81.5%) were white. After multivariate analysis, African Americans were less likely to have a door-to-CT time of less than 25 minutes (odds ratio [OR] 0.13 [CI 0.049 to 0.32]), obtain cardiac monitoring (OR 0.54 [CI 0.29 to 1.03]), undergo dysphagia screening (OR 0.69 [CI 0.50 to 0.95]), and receive smoking cessation counseling (OR 0.27 [CI 0.17 to 0.42]). CONCLUSIONS: Quality of hospital care for African American and white patients with acute ischemic stroke and TIA was similar in many respects. However, African Americans were less likely to receive a CT within 25 minutes of arrival, cardiac monitoring, dysphagia screening, and smoking cessation counseling.

Adolescent↗

Gender differences among medical students in attitudes to learning about complementary and alternative medicine.

OBJECTIVES: To explore gender differences in attitudes to CAM among Year 1, 2 and 3 medical students. DESIGN: Survey; seven-item self-administered questionnaire. SETTING: Plenary lectures at the start of semester 2 of the academic year at the University of Birmingham Medical School. RESULTS: 35.6% of 662 students were male and 64.4% female. Females were more likely than males to feel CAM has an important role in healthcare (p < 0.001). This difference increased through the medical course (p < 0.05). Females gave a more positive rating than males to the use of five therapies in healthcare (p < 001). Females were more positive than males about learning the theory (p < 0.001) and practice (p < 0.001) of CAM and a greater amount of CAM curriculum time (p < 0.001). CONCLUSIONS: If CAM teaching is optional females may be more likely to choose it. An unexpected consequence of more women than men entering medical school may be a positive impact on the development of integrated medicine.

Attitude↗

Effect of antiretroviral treatment and counselling on disclosure of HIV-serostatus in Johannesburg, South Africa.

This prospective non-randomized study of clinic attendees, compares self-reported HIV disclosure patterns in relation to access to antiretroviral access and counselling. It was carried out in public sector hospital HIV clinics in Johannesburg, South Africa, and 144 HIV-positive men and women attending the HIV clinics participated in the study.The results showed that there was no correlation between being on antiretroviral therapy and disclosure of HIV status. There was also no correlation between disclosure of HIV status and with different levels of counselling and access to support groups. Disclosure levels were high (92% told at least one person), however, there was a high level of delayed (15% greater than a year) or non-disclosure (21%) to partners. Family members and partners provided most moral support after disclosure. Having access to antiretroviral therapy and support groups and available counselling did not seem to affect disclosure patterns. It is possible that a patients beliefs about their treatment plays a more important role for disclosure than the actual treatment itself. Other factors are also likely important for disclosure, such as the patient's social network especially with their families, and knowledge of the disease.

Adult↗

Intra-operative parathyroid hormone monitoring in secondary hyperparathyroidism: is it useful?

OBJECTIVES: To assess the use of intra-operative parathyroid hormone (PTH) level monitoring as a predictor of persistent hypoparathyroidism after total parathyroidectomy in renal hyperparathyroidism. SETTING: University Teaching Hospital Otorhinolaryngology and Head and Neck Surgery Unit. PARTICIPANTS: All patients with renal hyperparathyroidism undergoing parathyroidectomy between January 2004 and July 2005. Twenty-nine patients were identified. MAIN OUTCOME MEASURES: Comparison is made between pre- and intra-operative PTH levels (ioPTH) in patients who at 3 months postoperatively maintained hypoparathyroidism and patients who did not. Results were analysed to see whether ioPTH predicts maintenance of the hypoparathyroid state. RESULTS: The mean preoperative PTH level was 932 pg/L (range: 58-1808). The mean postoperative PTH level was 147 pg/L (range: 16-498). The mean 3-month PTH level was 47 pg/L (range: <1-515). The mean postoperative PTH level for patients with a persistently high PTH level at 3 months was 286 pg/L (range: 272-299), compared with 63 pg/mL (16-160) in patients remaining normparathyroid, and 159 pg/L (range: 39-498) for patients with persistent hypoparathyroidism. If the normoparathyroid state is strictly considered to be failure following total parathyroidectomy, ioPTH is not predictive of hypoparathyroidism. However, ioPTH is indicative of biochemical resolution of the hyperparathyroid state (normo- or hypoparathyroidism). CONCLUSION: We conclude that the use of ioPTH monitoring in the surgical management of secondary hyperparathyroidism fails to predict persistent hypoparathyroidism following total parathyroidectomy, but does predict biochemical resolution of hyperparathyroidism.

Adult↗

Applying a moving total mortality count to the cities in the NMMAPS database to estimate the mortality effects of particulate matter air pollution.

OBJECTIVES: To apply a new method for estimating the association between daily ambient particulate matter air pollution (PM) and daily mortality to data from over 100 United States cities contained in the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) database and to see whether the results from the 90 cities NMMAPS analysis are robust to this different modelling approach. This new method has recently been shown to provide improved estimates for the association between PM and daily mortality when every-day PM data are unavailable. It avoids the need for selecting a lag of PM at which the mortality effects of PM are to be investigated. METHODS: With the aid of analytical methods and databases developed for NMMAPS, Poisson log linear models controlling for long term trends and weather effects were used to estimate the association between PM and mortality for cities in the NMMAPS database using the new method. A two stage Bayesian hierarchical model was then used to combine city specific estimates to form a national average PM mortality effect estimate. RESULTS: A 10 microg/m3 increase in PM was associated with a 0.12% increment in total mortality and a 0.17% increment in cardiovascular and respiratory mortality. These results are consistent with those found in the NMMAPS analysis. CONCLUSIONS: There is a statistically significant association between short term changes in PM and mortality on average for the cities contained in the NMMAPS database. These findings are further evidence that this widespread pollutant adversely affects public health.

Adult↗

Mercury in traditional Tibetan medicine - panacea or problem?

UNLABELLED: Symptoms of mercury toxicity, biochemical changes, and blood/urine mercury levels were evaluated in a small group of patients. Six patients attending Delek Hospital, Dharamsala, India, taking mercury-containing traditional Tibetan medicine (TTM) (Group I), were compared with three patients taking non-mercury containing TTM (Group II) and healthy volunteers(Group II). Quantitative estimation of mercury ingestion based on chemical analysis was compared with US regulatory standards. RESULTS: Group I were significantly older (mean 55 years+/-SE 6.4) range 26-69 years, than Group II (26.7 years+/-SE 5) range 17-34 years and Group III (32.5 years +/-SE 0.5) range 33-34 years (P =0.05). Group I took TTM on average for 51 months and had a mean of 2.5 non-specific, mercury-related symptoms. Group I had higher mean diastolic pressures (85 mmHg) than Group II (73 mmHg) (P=0.06) and more loose teeth. Mean daily mercury intake for Group I was 674 microg, estimated as 10 microg/kg per day. (Established reference dose for chronic oral exposure: 0.3 microg/kg per day.) Blood mercury levels were non-detectable, but mean urinary mercury levels for Group I were 67 microg/L (EPA levels <20 microg/L). Renal and liver function tests were not significantly different between groups and within normal clinical range. CONCLUSIONS: Prolonged ingestion of mercury containing TTM is associated with absent blood levels, but relatively high urinary levels. Further studies are needed to evaluate toxicity and therapeutic potential.

Adolescent↗

Bristol COPD Knowledge Questionnaire (BCKQ): testing what we teach patients about COPD.

Health professionals recommend education of patients about COPD. There is no satisfactory instrument to measure their knowledge and therefore to assess the results of education. A multiple-choice questionnaire (BCKQ) has been designed and tested. Each of 13 topics contains five statements for which there is a right or wrong answer. Its validity and consistency has been assessed, and the test re-test reliability and responsiveness measured after an interval of eight weeks. A copy of the multiple-choice questionnaire is given in the Appendix. The questionnaire was judged by patients and health professionals to have good content and face validity. It has good internal consistency for the 65 items. (Cronbach's alpha 0.73). It can be completed and scored within twenty minutes. The average score in subjects who had not received prior education was 54.7%. In a group not receiving education there was good test-retest reliability (r = 0.71). Following an eight-week education programme there was a significant improvement of 18.3 percentage points, and most of the increase was maintained for six months without any further formal education. BCKQ is suitable for both clinical and research purposes. It will test knowledge that is appropriate for COPD patients and can be used as an assessment tool for individual patients, or as a broad cross-sectional survey instrument. It will enable the effectiveness of education to be assessed and will be of value in developing and comparing different educational interventions.

Aged↗

Outbreak of E. coli O157 infection in the south west of the UK: risks from streams crossing seaside beaches.

In August 2004 seven cases of Escherichia coli O157 infection were identified in children on holiday in Cornwall, southwest England, all of whom had stayed at different sites in the area. Isolates from all seven cases were confirmed as E. coli serogroup O157 phage type 21/28. We carried out a case-control study among holidaymakers who visited the beach. A standardised questionnaire was administered by telephone to parents. They were asked where on the beach the children had played, whether they had had contact with the stream that flowed across the beach, and about their use of food outlets and sources of food eaten. Cases were more likely to have played in the stream than controls (OR [1.72- undefined]). The time spent in the stream by cases was twice spent there by controls. Cases and controls were equally exposed to other suspected risk factors. PFGE profiles for all the cases were indistinguishable. Increased numbers of coliforms were found in the stream prior to the outbreak. Cattle were found grazing upstream. We suggest that the vehicle of infection for an outbreak of acute gastrointestinal illness caused by E. coli O157 was a contaminated freshwater stream flowing across a seaside beach. The onset dates were consistent with a point source. Heavy rainfall in the days preceding the outbreak might have lead to faeces from the cattle potentially contaminated by E. coli O157 contaminating the stream, thereby leading to the outbreak. Control measures included fencing off the part of the stream in which children played, and putting up warning signs around the beach.

Bathing Beaches↗

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia.

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.

Adult↗

Anaesthetic management of a neonate with congenital cyst adenoid malformation.

We report the anaesthetic management of a male neonate with congenital cyst adenoid malformation (CCAM) of the lung who underwent thoracotomy for resection of CCAM 24 h after birth and again at 24 days. The initial operation involved a 10-day admission to a paediatric intensive care unit (PICU) requiring ventilation, and was complicated by a pneumothorax. This report concentrates on the anaesthetic management for the second thoracotomy. The combination of intra-operative remifentanil infusion and the use of ultrasound to confirm correct placement of epidural catheter allowed on-table tracheal extubation and a shorter stay in PICU. The use of one-lung ventilation (OLV) allowed for better surgical access and enabled complete resection of the lesion.

Anesthesia, Epidural↗

Early versus delayed surgical treatment of open tibial fractures: effect on the rates of infection and need of secondary surgical procedures to promote bone union.

The purpose of this study was to evaluate whether there was any significant difference in the rates of infection and of secondary surgical procedures to promote bone union, between early(6 h or less after arrival to hospital) and delayed(more than 6 h) surgical treatment of open tibial fractures. Three hundred and eighty-three open tibial fractures were evaluated. 184 fractures had early and 199 had delayed surgical treatment. The rates of infection and secondary surgical procedures to promote bone union of the two groups were compared with univariate and multivariate statistical methods. There was no statistically significant difference between early and delayed treatment groups with respect to overall infection (53/184 versus 51/199 infection rates, P = 0.96), deep infection (8/184 versus 8/199 infection rates, P = 1.0), and rates of secondary surgical procedures to promote bone union (24/184 versus 20/198, P = 0.77). We were unable to demonstrate any significant difference in infection rates or need of secondary procedures to promote bone union, between early and delayed surgical treatment of open tibial fractures.

Adolescent↗

Diagnosis and management of Staphylococcus aureus infections of the skin and soft tissue.

Infections involving the skin and soft tissue are common and range from superficial, localized and sometimes self-limiting infections to deep, rapidly spreading and potentially life-threatening infections. Skin infections caused by Staphylococcus aureus include primary pyodermas, while those involving the soft tissues include cellulitis and pyomyositis. Surgical site infections and infections in intravenous drug users are also commonly caused by S. aureus. The severity of the infection determines the choice of treatment. There are few studies that have critically appraised the use of antibiotics in skin and soft tissue infections, and most guidelines are based on expert opinion. The beta-lactam group of antibiotics are the mainstay of treatment for methicillin-susceptible S. aureus infections. For methicillin-resistant S. aureus (MRSA) infections, both with community-acquired and hospital-acquired strains--which are becoming an increasing problem--the antibiotic choice is determined by local susceptibility patterns. Macrolides, clindamycin and cotrimoxazole are options for community-acquired MRSA, while vancomycin is reserved for treatment of infections caused by multiresistant MRSA strains and for patients with suspected endocarditis or severe sepsis. Although a number of the newer antibiotics such as linezolid and quinopristin/dalfopristin have been shown to have good activity against MRSA, these agents should only be used with specialist advice.

Anti-Bacterial Agents↗