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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2007

Incubation period, spore egestion and horizontal transmission of Nosema fumiferanae (Microsporidia: Nosematidae) in spruce budworm (Choristoneura sp., Lepidoptera: Tortricidae): the role of temperature and dose.

Various instars of Choristoneura occidentalis were fed with a range of doses of Nosema fumiferanae and reared at 20, 24 and 28 degrees C to determine the influence of temperature and dose on the time to spore egestion and the number of spores egested in the frass. When larvae were fed in the third stadium, as few as 10(2) spores per larva initiated infection, and both onset of spore egestion and the number of spores egested were affected by a complex relationship between temperature and inoculation dose. Onset of spore egestion varied from 11 to 15 days postinoculation. At 20 degrees C, the onset was delayed and spore production decreased with increasing inoculation dose whereas at higher temperatures spores were first egested at the lowest dose and spore production increased with dose. When larvae were fed spores in the fifth and sixth stadium, no spores were egested because pupation occurred before completion of the incubation period. To assess the effect of temperature on horizontal transmission, Choristoneura fumiferana larvae fed with 10(4) N. fumiferanae spores per larva were reared with uninfected larvae at 15, 20 and 25 degrees C. At 15 degrees C, we observed the highest degree of horizontal transmission, defined by the largest change in N. fumiferanae prevalence, even though the density of spores available for horizontal transmission was the lowest. Infected adults eclosed later than uninfected adults and the time to eclosion was also dependent on sex and temperature. We relate our experimental findings to consequences for horizontal and vertical transmission of N. fumiferanae in spruce budworm populations.

Animals↗
PubMed2007

The surgical management of patients who achieve a complete pathological response after primary chemotherapy for locally advanced breast cancer.

AIMS: Our aim was to investigate the role of minimal surgery in patients with locally advanced breast cancer (LABC) who achieve a complete pathological (pCR) response to primary chemotherapy (PC) and evaluate subsequent local recurrence (LRR), disease free survival (DFS) and overall survival (OS). METHODS: Between January 2000 and April 2005, 101 patients with operable LABC (T2, T3, N0 or N1, M0) who were not suitable for conservation surgery were treated with PC. Patients were treated with doxorubicin and cyclophosphamide for four cycles (100 patients) then four cycles with paclitaxel (91 patients). Post-PC surgery consisted of multiple core biopsies and axillary clearance for patients with a complete clinical and radiological response. If a pCR was confirmed no further breast surgery was performed. The remaining patients were treated with breast conserving surgery or mastectomy and axillary clearance as appropriate. Adjuvant radiotherapy was given to all patients. RESULTS: Breast conservation was possible in 60% of patients. Overall, 20 patients achieved a pCR of which 16 were confirmed on core biopsies alone. All patients were followed-up for a mean of 33.5 months (95% CI, 30.3-36.7). There were 10 local recurrences, four following mastectomy, four after wide excision and two after core biopsies. There was no difference in DFS (chi square=0.18; p=0.67) or OS (chi square=0.67; p=0.41) between patients achieving a pCR and the remainder. CONCLUSIONS: The local recurrence rate of these poor prognosis patients is similar to other reported series but higher than in our previously reported series of patients managed according to the same protocol. Our current management therefore now includes pre-treatment marking and subsequent surgical excision.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown. AIMS: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. METHODS: A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. RESULTS: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. CONCLUSIONS: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Aged↗
PubMed2006

Oceans and human health: Emerging public health risks in the marine environment.

There has been an increasing recognition of the inter-relationship between human health and the oceans. Traditionally, the focus of research and concern has been on the impact of human activities on the oceans, particularly through anthropogenic pollution and the exploitation of marine resources. More recently, there has been recognition of the potential direct impact of the oceans on human health, both detrimental and beneficial. Areas identified include: global change, harmful algal blooms (HABs), microbial and chemical contamination of marine waters and seafood, and marine models and natural products from the seas. It is hoped that through the recognition of the inter-dependence of the health of both humans and the oceans, efforts will be made to restore and preserve the oceans.

Animals↗
PubMed2006

Electroclinical features of absence seizures in childhood absence epilepsy.

OBJECTIVE: To accurately define the electroclinical features of absence seizures in children with newly diagnosed, untreated childhood absence epilepsy (CAE). METHODS: The authors searched an EEG database for absence seizures in normal children with new onset untreated absence epilepsy. Seventy consecutive children were classified into IGE syndromes. The clinical and EEG features of the seizures in the children with CAE were analyzed using video-EEG recordings. RESULTS: The authors analyzed 339 absence seizures in 47 children with CAE. The average seizure duration was 9.4 seconds and clinical features consisted of arrest of activity, loss of awareness, staring, and 3-Hz eyelid movements, but there was individual variation. Ictal EEG predominantly showed regular 3-Hz generalized spike and wave (GSW) with one or two spikes per wave; however, disorganization of discharges was common and three or more spikes per wave occurred rarely. Postictal slowing was frequent. Interictal abnormalities included fragments of GSW, posterior bilateral delta activity, and focal discharges. Although all 47 children met the current criteria for CAE, only 5 fulfilled the recently proposed criteria for CAE. CONCLUSION: The heterogeneous nature of each clinical and EEG feature of untreated absence seizures is of critical importance when determining criteria for childhood absence epilepsy.

Canada↗
PubMed2006

Reducing variation in antibacterial prescribing rates for 'cough/cold' and sore throat between 1993 and 2001: regional analyses using the general practice research database.

OBJECTIVE: To use the General Practice Research Database (GPRD) to explore the regional variation in prescribing for single diagnostic episodes of 'cough/cold' and sore throat and how this changed between 1993 and 2001. METHODS: Data from the GPRD was used to conduct a longitudinal survey of morbidity and antibiotic prescribing data. RESULTS: Nationally there has been a substantial reduction in diagnosed episodes per 1000 patient years at risk for both diagnoses: from 104.6 (104.0-105.2) to 86.5 (86.0-86.9) for cough/cold (-17.3%) and from 102.8 (102.2-103.4) to 69.2 (68.8-69.6) for sore throat (-32.6%). In addition to the changes in diagnostic rate there have been reductions in diagnosis-related prescribing: from 41.8% to 34.8% of cough/cold episodes (-7.0%) and from 77.3% to 60.8% of sore throat episodes (-16.4%). These aggregated data conceal wide regional variations. For cough/cold the change in prescribing rate during the study varied from -16.0% to +5.3% and for sore throat from -28.3% to -7.3%. CONCLUSIONS: In addition to a substantial reduction in diagnosis of cough/cold and sore throat, there has been a reduction in diagnosis-related prescribing episodes in almost all regions. Although there continues to be regional variation in diagnosis-related prescribing this has reduced substantially over the 9-year study period.

Anti-Bacterial Agents↗
PubMed2006

Pupil findings in a consecutive series of 150 patients with generalised autonomic neuropathy.

AIM: To detect and characterise the pattern and extent of pupil abnormalities in patients with generalised autonomic failure. METHODS: A consecutive series of 150 patients referred for investigation of symptomatic generalised autonomic failure underwent pupil investigations. Infra-red video pupillography was used to measure resting pupil diameters in light and dark, the light reflex response, the miosis associated with an accommodative effort, and responses to topical administration of various pharmacological agents. The results were compared with data recorded under identical conditions from a cohort of 315 age-matched and sex-matched healthy controls. RESULTS: Overall, two thirds of patients had abnormal pupils (66%) with sympathetic deficit occurring twice as often as parasympathetic deficit. However, the prevalence and type of pupil abnormality showed wide variation according to aetiology--for example, almost all patients with amyloidosis had abnormal pupils, two thirds with pure autonomic failure but less than a quarter with multiple system atrophy. In most patients (85%), pupil abnormalities were bilateral and symmetrical, none had a Horner's syndrome in one eye and a tonic pupil in the other. No significant correlation between the type of pupil abnormality and the predominant type of systemic autonomic deficit was seen in most conditions. CONCLUSIONS: The pupils are often affected in autonomic neuropathy, although this is not always apparent either to the patient or to their doctors. Considerable care is needed not only to detect these abnormalities but also to interpret correctly the results of pupil tests in this group of patients.

Adolescent↗
PubMed2006

Hydroponic uptake of atrazine and lambda-cyhalothrin in Juncus effusus and Ludwigia peploides.

Phytoremediation encompasses an array of plant-associated processes known to mitigate contaminants from soil, sediment, and water. Modification of pesticides associated with agricultural runoff includes processes directly associated with aquatic macrophytes in addition to changes in soil geochemistry and associated rhizospheric degradation. Remediation attributes of two vegetative species common to agricultural drainages in the Mississippi Delta, USA, were assessed using atrazine and lambda-cyhalothrin. Concentrations used in 8-d hydroponic exposures were calculated using recommended field applications and a 5% runoff model from a 0.65-cm rainfall event on a 2.02-ha field. While greater atrazine uptake was measured in Juncus effusus, greater lambda-cyhalothrin uptake occurred in Ludwigia peploides. Maximum pesticide uptake was reached within 48h for each exposure and subsequent translocation of pesticides to upper plant biomass occurred in macrophytes exposed to atrazine. Sequestration of 98.2% of lambda-cyhalothrin in roots of L. peploides was measured after 8d. Translocation of lambda-cyhalothrin in J. effusus resulted in 25.4% of pesticide uptake partitioned to upper plant biomass. These individual macrophyte remediation studies measured species- and pesticide-specific uptake rates, indicating that seasonality of pesticide applications and macrophyte emergence might interact strongly to enhance mitigation capabilities in edge-of-field conveyance structures.

Agriculture↗
PubMed2006

Vaccines for preventing influenza in healthy children.

BACKGROUND: In children and adults the consequences of influenza are mainly absences from school and work, however the risk of complications is greatest in children and people over 65 years old. OBJECTIVES: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children; assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness) and document adverse events associated with receiving influenza vaccines. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005); OLD MEDLINE (1966 to 1969); MEDLINE (1969 to December 2004); EMBASE (1974 to December 2004); Biological Abstracts (1969 to December 2004); and Science Citation Index (1974 to December 2004). We wrote to vaccine manufacturers and a number of corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years old. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Fifty-one studies involving 263,987 children were included. Seventeen papers were translated from Russian. Fourteen RCTs and 11 cohort studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live vaccines showed an efficacy of 79% (95% confidence interval (CI) 48% to 92%) and an effectiveness of 33% (95% CI 28% to 38%) in children older than two years compared with placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% (95% CI 41% to 71%) than live vaccines but similar effectiveness: 36% (95% CI 24% to 46%). In children under two, the efficacy of inactivated vaccine was similar to placebo. Thirty-four reports containing safety outcomes were included, 22 including live vaccines, 8 inactivated vaccines and 4 both types. The most commonly presented short-term outcomes were temperature and local reactions. The variability in design of studies and presentation of data was such that meta-analysis of safety outcome data was not feasible. AUTHORS' CONCLUSIONS: Influenza vaccines are efficacious in children older than two years but little evidence is available for children under two. There was a marked difference between vaccine efficacy and effectiveness. That no safety comparisons could be carried out emphasizes the need for standardisation of methods and presentation of vaccine safety data in future studies. It was surprising to find only one study of inactivated vaccine in children under two years, given recent recommendations to vaccinate healthy children from six months old in the USA and Canada. If immunisation in children is to be recommended as public-health policy, large-scale studies assessing important outcomes and directly comparing vaccine types are urgently required.

Adolescent↗
PubMed2006

Hip, knee, and ankle kinematics of high range of motion activities of daily living.

Treatment of joint disease that results in limited flexion is often rejected by patients in non-Western cultures whose activities of daily living require a higher range of motion at the hip, knee, or ankle. However, limited information is available about the joint kinematics required for high range of motion activities, such as squatting, kneeling, and sitting cross-legged, making it difficult to design prosthetic implants that will meet the needs of these populations. Therefore, the objective of this work was to generate three-dimensional kinematics at the hip, knee, and ankle joints of Indian subjects while performing activities of daily living. Thirty healthy Indian subjects (average age: 48.2 +/- 7.6 years) were asked to perform six trials of the following activities: squatting, kneeling, and sitting cross-legged. Floating axis angles were calculated at the joints using the kinematic data collected by an electromagnetic motion tracking device with receivers located on the subject's foot, shank, thigh, and sacrum. A mean maximum flexion of 157 degrees +/- 6 degrees at the knee joint was required for squatting with heels up. Mean maximum hip flexion angles reached up to 95 degrees +/- 27 degrees for squatting with heels flat. The high standard deviation associated with this activity underscored the large range in maximum hip flexion angles required by different subjects. Mean ankle range of flexion reached 58 degrees +/- 14 degrees for the sitting cross-legged activity. The ranges of motion required to perform the activities studied are greater than that provided by most currently available joint prostheses, demonstrating the need for high range of motion implant design.

Activities of Daily Living↗
PubMed2006

Clinical pathways for patients with newly diagnosed hepatitis C - what actually happens.

Management of hepatitis C virus (HCV)-infected individuals requires referral to specialist care. To determine whether patients newly diagnosed as anti-HCV positive are appropriately referred for further investigation and management, and if not, to determine why not. We studied patients tested for antibodies to HCV by Nottingham Public Health Laboratory in a 2-year period (2000-2002). The progress of newly diagnosed anti-HCV positive patients into specialist clinics for further management was documented. For patients not referred for specialist care, a questionnaire was sent to the clinician requesting the initial anti-HCV test, to identify reasons for nonreferral. Eleven thousand one hundred and seventy-seven patients were tested for anti-HCV. Two hundred and fifty-six (2.3%) were newly diagnosed as being anti-HCV positive. Two per cent of samples sent from primary care were anti-HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison, drug and alcohol units, and secondary care, respectively. About 64.3% of positive patients diagnosed in primary care were referred to specialist care, compared to 18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One hundred and twenty-five (49%) newly diagnosed patients were referred appropriately for further management. 68 of these attended clinic, 45 underwent liver biopsy and 26 (10%) began treatment. One hundred and thirty-one patients (51%) were not referred. In 54 cases, there was no evidence that the anti-HCV positive result reached the patient. In 15, referral was considered but rejected, and 20 patients were referred to non-HCV-specialists (their general practitioners or to genito-urinary medicine). Hence less than 50% of newly diagnosed anti-HCV positive patients are referred to an appropriate clinic for further investigation and management. Reasons for this are multifarious and complex, reflecting both systems failure and patient choice. Unless these are understood and addressed, the Department of Health Hepatitis C Strategy (2002) and Action Plan for England (2004) will fail to achieve their intended objectives.

Adolescent↗
PubMed2006

Instructional design and the emergency department.

This paper studies the effectiveness of different educational programmes. A number of cohorts of junior doctors received one of two different induction training packages. These programmes differed principally in the length of time over which they were administered. The junior doctors were then assessed using a structured questionnaire. There was a noticeable difference in the factual recall between the cohorts depending on what programme they had attended. Those attending the programme delivered over an extended period showed better performance on assessment. The interpretations and implications of these findings are discussed.

Education, Medical, Graduate↗
PubMed2006

Chemical phosphorus removal to extremely low levels: experience of two plants in the Washington, DC area.

Chemical phosphorus removal using metal (iron and aluminium) salts is frequently used to control effluent soluble phosphorus levels in wastewater treatment plants. In the Washington DC area effluent phosphorus requirements are extremely stringent to protect the Chesapeake Bay. Full-scale data from two plants in the area were analysed to establish phosphate behaviour in the presence of iron. Titration experiments and mathematical modelling were performed to determine the role of ferric phosphate and hydroxide precipitation and other mechanisms that may potentially be involved in phosphorus removal. Iron addition is described in the model using a chemical equilibrium approach extended with surface charges and adsorption. The model verifies key observations from full-scale data: (a) extremely low orthophosphate levels can be achieved over a wide range of pH values, (b) a mixture of ferric phosphate and ferric hydroxide precipitate is forming with the hydroxide acting as sorbent, (c) molar ratios of Fe/P (iron dosed to phosphate removed) vary widely (1.0-3.9) based on the technology used and residual phosphate levels. The model will be a useful tool for engineers to optimise preliminary, simultaneous and tertiary P removal, both for design and plant operation.

District of Columbia↗
PubMed2005

Influence of vegetation in mitigation of methyl parathion runoff.

A pesticide runoff event was simulated on two 10 m x 50 m constructed wetlands (one non-vegetated, one vegetated) to evaluate the fate of methyl parathion (MeP) (Penncap-M). Water, sediment, and plant samples were collected at five sites downstream of the inflow for 120 d. Semi-permeable membrane devices (SPMDs) were deployed at each wetland outflow to determine exiting pesticide load. MeP was detected in water at all locations of the non-vegetated wetland (50 m), 30 min post-exposure. MeP was detected 20 m from the vegetated wetland inflow 30 min post-exposure, while after 10d it was detected only at 10 m. MeP was measured only in SPMDs deployed in non-vegetated wetland cells, suggesting detectable levels were not present near the vegetated wetland outflow. Furthermore, mass balance calculations indicated vegetated wetlands were more effective in reducing aqueous loadings of MeP introduced into the wetland systems. This demonstrates the importance of vegetation as sorption sites for pesticides in constructed wetlands.

Biomass↗
PubMed2005

Ciprofloxacin suppresses bacterial overgrowth, increases fasting insulin but does not correct low acylated ghrelin concentration in non-alcoholic steatohepatitis.

BACKGROUND: Insulin resistance and oxidative stress induced by products of small intestinal bacterial activity are putative factors in the pathogenesis of non-alcoholic steatohepatitis. Acylated ghrelin is the biologically active form of an orexigenic gastric hormone that modifies insulin sensitivity and body composition. AIM: To investigate the effect of ciprofloxacin on small intestinal bacterial activity, ethanol, ghrelin and insulin in non-alcoholic steatohepatitis patients. METHODS: Twelve non-alcoholic steatohepatitis patients and 11 controls were studied before and after ciprofloxacin 500 mg b.d. for 5 days. After an overnight fast, 75 g glucose was ingested and blood was sampled every 20 min for 120 min. Acylated and total ghrelin, ethanol and insulin were measured. Small intestinal bacterial activity was detected by glucose hydrogen breath test. RESULTS: Mean (range) integrated plasma acylated ghrelin which was 102 (21-241) and 202 (88-366) pg/mL . 2 h in non-alcoholic steatohepatitis and controls respectively (P = 0.015). This difference persisted after correction for body mass index and was unaffected by ciprofloxacin treatment. One of six non-alcoholic steatohepatitis patients positive for small intestinal bacterial activity remained positive after ciprofloxacin. In contrast, the one healthy control positive for small intestinal bacterial activity remained positive after ciprofloxacin (P = 0.025). Ethanol was detected in two subjects in each group, becoming immeasurable after ciprofloxacin. In non-alcoholic steatohepatitis patients median (range) fasting insulin increased from 113 (10-223) to 152 (32-396) pmol/L (P < 0.02), after ciprofloxacin. This was accompanied by similar changes in insulin resistance. CONCLUSIONS: Small intestinal bacterial activity is common in non-alcoholic steatohepatitis. Low acylated ghrelin in non-alcoholic steatohepatitis cannot be attributed to small intestinal bacterial activity. Changes in fasting insulin and ethanol following ciprofloxacin suggest that these parameters may be influenced by small intestinal bacterial activity.

Adult↗