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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 19 recordsLinked to original sources
PubMed2006

Kinetics of the immune response to the (F1+V) vaccine in models of bubonic and pneumonic plague.

Protection against aerosol challenge with > 300 MLD of Yersinia pestis was observed 7 days after a single immunisation of mice with the F1+V vaccine. At day 60, mice were protected against injected challenge (10(7)MLD) in a vaccine dose-related manner. Recall responses to rV in splenocytes ex vivo at day 98 correlated significantly (p<0.001) with the immunising dose-level of V antigen; no memory response or anti-V serum IgG was detected in killed whole cell vaccine (KWCV) recipients. This may explain the susceptibility of KWCV recipients to aerosol challenge and the enhanced protection conferred by the F1+V sub-unit vaccine, particularly since the anti-F1 responses induced by either vaccine were similarly IgG1-polarised.

Animals↗
PubMed2006

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↗
PubMed2006

Accuracy of needle placement in ACJ injections.

Localization of the Acromioclavicular joint (ACJ) even at arthroscopic surgery may be difficult because of its small size, osteophytes, variable anatomy of the joint and capsule. Therefore injection of the ACJ in the clinic may well be inaccurate. The aim of this study was to review the clinical accuracy of needle placement in ACJ injections, if performed without the aid of image intensification. Sixty patients with 66 shoulders were injected in the Day Unit in our department. The joint was palpated clinically, and the needle was placed in the site thought to be in the AC Joint. An image intensifier was then used to check the position of the needle in the AP and axillary views. The needle was considered correctly placed if between the bony boundaries of the acromion and clavicle. This was found in only 26 injections (39.4%). The remaining 40 injections (60.6%) were misplaced, either laterally in 21 injections (31.8%), medially in 13 (19.8%), anteriorly in 3 (4.5%) and inferiorly in 3 injections (4.5%). Theses were then reinserted under image intensifier guidance. The misplaced injections would have lead to inaccurate clinical outcomes, and decision making. This study is similar to other studies in that X-ray guidance improves the accuracy of injections and surgery. However the potential error rate for the small, anatomically variable AC joint is high. There is a 60% potential for ACJ injections to be out of the joint if performed by palpation alone, and we recommend the routine use of image intensification guidance.

Acromioclavicular Joint↗
PubMed2006

Managing aggression in a psychiatric hospital using a behaviour plan: a case study.

This paper focuses on the critical role of nursing in implementing a behaviour plan in a psychiatric hospital. The plan was implemented with a 40-year-old man with a long history of aggression towards others and self. The study used a single-subject research design with baseline and intervention phases (AB Design). Data were collected on (1) frequency of incidents of aggression towards others and self; (2) use of restrictive interventions to manage aggression (i.e. restraints, pro re nata medication, 1:1 special observation); and (3) frequency of staff injury. The data show a decrease in frequency of aggression towards others and self, a concurrent reduction in the use of restrictive interventions to manage aggression, and a decrease in incidents of staff injury. The behaviour plan helped staff maintain a safe and therapeutic milieu. The behaviour plan has given the patient an opportunity to learn positive replacement behaviours and skills, and the opportunity eventually to leave the hospital to live in a less restrictive community home.

Adult↗
PubMed2006

CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients.

A randomized controlled trial of CMV-IVIG (cytomegalovirus-intravenous immunoglobulin) for prevention of Epstein Barr virus (EBV) posttransplant lymphoproliferative disease (PTLD) in pediatric liver transplantation (PLTx) recipients was begun in Pittsburgh and subsequently expanded to four additional sites. Protocol EB viral loads were obtained in a blinded fashion; additional loads could be obtained for clinical indications. Patients were followed for 2 years post-LTx. Eighty-two evaluable patients (39 CMV-IVIG, 43 placebo) developed 18 episodes of EBV disease (7 CMV-IVIG, 11 placebo) including nine cases of PTLD (three CMV-IVIG, six placebo). No significant differences were seen in the adjusted 2-year EBV disease-free rate (CMV-IVIG 79%, placebo 71%) and PTLD-free rate (CMV-IVIG 91%, placebo 84%) between treatment and placebo groups at 2 years (p > 0.20). The absence of significant effect of CMV-IVIG may be explained by a lack of efficacy of the drug or limitations of sample size.

Adolescent↗
PubMed2005

Resonance contributions to anti-Stokes/Stokes ratios under surface enhanced Raman scattering conditions.

Anti-Stokes/Stokes asymmetries under surface enhanced Raman scattering (SERS) conditions are studied for a wide variety of SERS-active media and different analytes. Evidence is provided for the existence of underlying resonances that create these asymmetries. We show here that these resonances are associated with the electromagnetic coupling between the analyte (probe) and the metal. The work demonstrates the use of the anti-Stokes/Stokes ratio as a tool to understand the hierarchy of resonances in the SERS problem, which is essential for quantification purposes.

Journal Article↗
PubMed2005

Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors.

BACKGROUND: ZD6474 selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor and epidermal growth factor receptor. The safety, tolerability and pharmacokinetics of ZD6474 were assessed in a phase I dose-escalation study of patients with advanced solid tumors. PATIENTS AND METHODS: Adult patients with tumors refractory to standard treatments received once-daily oral ZD6474 (50-600 mg) in 28-day cycles, until disease progression or unacceptable toxicity was observed. RESULTS: Seventy-seven patients were treated at doses of 50 mg (n=9), 100 mg (n=19), 200 mg (n=8), 300 mg (n=25), 500 mg (n=8), and 600 mg (n=8). Adverse events were generally mild, and the most common dose-limiting toxicities (DLT) were diarrhea (n=4), hypertension (n=4), and rash (n=3). The incidence of most adverse events appeared to be dose-dependant. In the 500 mg/day cohort, 3/8 patients experienced DLT and this dose was therefore considered to exceed the maximum tolerated dose. Pharmacokinetic analysis confirmed that ZD6474 was suitable for once-daily oral dosing. CONCLUSIONS: Once-daily oral dosing of ZD6474 at 300 mg/day is generally well tolerated in patients with advanced solid tumors, and this dose is being investigated in phase II trials.

Administration, Oral↗
PubMed2005

Diallyl sulfide inhibits diethylstilbesterol-induced DNA adducts in the breast of female ACI rats.

Diethylstilbestrol (DES) is metabolized to reactive intermediates that produce DNA adducts and ultimately cancer. Diallyl sulfide (DAS) has been shown to inhibit the metabolism of several procarcinogens. The ability of DES to produce DNA adducts in microsomal, mitochondrial, and nuclear in vitro metabolic systems and in the breast of female ACI rats, as well as ability of DAS to inhibit DNA adducts were investigated. Microsomes, mitochondria, and nuclei isolated from breast tissue of female ACI rats were used to catalyze oxidation reactions. Female ACI rats were treated i.p. as follows: (1) corn oil, (2) 200mg/kg DES, (3) 200mg/kg DES/200mg/kg of DAS, (4) 200mg/kg DES/400mg/kg DAS. DES produced DNA adducts in each metabolic system. The relative adduct levels were 2.1 x 10(-4), 6.2 x 10(-6), and 2.9 x 10(-7) in microsomal, mitochondrial, and nuclear reactions, respectively. DAS inhibited DNA adducts in each metabolic system. The percent inhibition ranged from 86% in microsomes to 93% in nuclei. DES produced DNA adducts in mtDNA and nDNA. DAS completely inhibited the DES-induced mtDNA adducts and caused a dose dependent decrease in nDNA adduct formation. These findings suggest that DAS could inhibit DES-induced breast cancer by inhibiting its metabolism.

Allyl Compounds↗
PubMed2004

Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain.

In order to evaluate the immunogenicity and protective efficacy of anthrax vaccine candidates a suitable small animal model is required. The inbred A/J strain of mouse has been selected as a potential model, and its immune response to immunisation with recombinant protective antigen (rPA) vaccine characterised, by assessment of rPA specific antibody production, and protection against injected challenge, with the unencapsulated STI strain of Bacillus anthracis. Studies were conducted to determine the time required post immunisation to develop a protective immune response, to define the minimum protective dose of vaccine required and to assess the long-term immune response to immunisation. From the results of these studies it was possible to establish that the A/J mouse is a consistent and robust small animal model for rPA vaccine testing. A comparison of the immune response to rPA vaccine immunisation in the Turner Outbred (TO) mouse strain was also conducted. Both inbred and outbred mouse strains displayed a predominantly Th2 biased immune response and showed a comparable antibody response to rPA immunisation. An assessment of protection in the TO mouse against aerosol challenge with the fully virulent strain of B. anthracis, Ames, was also made.

Animals↗
PubMed2004

DNA adduct analysis and histopathological biomarkers in European flounder (Platichthys flesus) sampled from UK estuaries.

The presence of genotoxic and potentially carcinogenic chemical contaminants in the estuarine and coastal marine environment is well documented. In this study, European flounder (Platichthys flesus) sampled from eight UK estuaries were analysed for hepatic DNA adducts, using the 32P-postlabelling assay and liver histopathology as part of an on going survey to establish the health status of UK estuaries. Fish were collected from the estuaries Tyne, Mersey, Thames, Alde (reference site), Belfast, Forth, Clyde and Southampton. At the majority of contaminated sites (Southampton, Thames, Clyde, Tyne and Mersey) the predominant DNA adduct profile consisted of diagonal radioactive zones (DRZs). In contrast, flounder collected from the Forth, Alde and Belfast lacked DRZs with only background levels of DNA damage being observed. Statistically significant differences were observed between several of the sites sampled with the hepatic DNA adduct levels detected in flounder from Southampton, Thames and Clyde statistically elevated (P < 0.05) over those levels detected at the Tyne (Southampton and Thames only), Forth, Alde and Belfast. Histological analysis of these samples revealed a range of lesions including foci of cellular alteration, hepatocellular fibrillar inclusions, nuclear pleomorphisms along with non-toxicopathic changes/alterations, such as those associated with cell turnover (apoptosis, necrosis, regeneration) and immune-related functions (melanomacrophage aggregates, inflammation). Although it is difficult to associate higher prevalence of these lesion types with specific sites, generally, the lowest prevalence was seen in flounder captured from the Alde estuary, with higher prevalence (particularly of melanomacrophage aggregates, inflammation and necrotic foci) seen in fish from the contaminated sites.

Animals↗
PubMed2004

Expression of intercellular adhesion molecules in the bladder of patients with interstitial cystitis.

OBJECTIVES: To study the presence of intercellular adhesion molecule-1 (ICAM-1), P-selectin, and E-selectin, as well as the cytoskeletal components talin and vinculin that bind to cellular adhesion molecules (CAMs), in bladder biopsies from patients with interstitial cystitis (IC) and controls. IC is a sterile, bladder disorder characterized by urinary frequency and pelvic floor pain. The pathologic bladder findings include defective urothelium, activated mast cells, and variable inflammation. Mast cells can induce the expression of CAMs necessary for initiation of inflammation. METHODS: Fresh frozen biopsies were analyzed immunocytochemically from 2 female normal bladders, 10 female IC bladders, 1 clear margin of transitional cell carcinoma of female bladder, 1 normal foreskin, 1 transitional cell carcinoma of foreskin, and 1 inflamed male finger. RESULTS: Of the 10 IC samples, 9 were positive for ICAM-1, 6 for P-selectin, 6 for vinculin, 5 for talin, and 4 for E-selectin, all exclusively perivascular. Both normal bladders were negative for ICAM-1 and P-selectin and faintly positive for E-selectin, and one was weakly positive for talin and vinculin; the normal foreskin was negative. The "control" samples from the transitional cell carcinoma of the bladder and foreskin, as well as the inflamed finger skin, were positive only for ICAM-1. An increased number of activated mast cells associated with ICAM-1 was noted in IC. CONCLUSIONS: These results showed that ICAM-1 is expressed in IC, with variable expression of the other markers studied, supporting the different degrees of bladder inflammation noted in patients with IC.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2004

Treatment of dairy wastewater using a vertical bed with passive aeration.

The aim of this research was to investigate the feasibility of treating liquid dairy wastes by a vertical bed equipped with an innovative passive aeration system. The vertical bed (32 liter) was operated by recirculating consecutive batches of liquid waste in the column. Batches of liquid waste were applied at two different rates: 1) each batch was recirculated for 72 hours, and 2) each batch was recirculated for 24 hours. Settled liquid dairy wastes (5000 mg l(-1) COD, 2000 mg l(-1) BOD and 2500 mg l(-1) TSS) were used in the experiments. When the reactor operated with each batch recirculating for 72 hours, the BOD and COD reduction were 66% and 40%, respectively. The vertical bed operated successfully without the need for an additional rest period. The main removal was observed to take place during the first 20 hours. No biomass or solids accumulation was observed indicating that the remaining 52 hours of recirculation were actually used for bed regeneration, i.e. integrated rest period. When the reactor operated with each batch recirculating for 24 hours, the system clogged after 21 days. An additional 24 day rest period was needed in order to free 94% of the initial void space. In this mode, the BOD and COD reduction were 67% and 47%, respectively. The overall COD removal in a complete operational cycle (feeding period followed by a rest period) was 467 g COD m(-3) d(-1) (996 g COD m(-2) d(-1)). This value is 1.4 higher than the COD removal obtained in the 72 hour per batch mode and shows the advantage of conventional vertical bed operation of intensive feeding followed by rest period rather than a rest period integrated into the feeding cycle.

Air Movements↗
PubMed2004

A phase II study of escalated-dose docetaxel with granulocyte colony-stimulating factor support in patients with advanced breast cancer.

PURPOSE: Docetaxel is highly active in the treatment of patients with breast cancer. The principal dose-limiting toxicities of the 3-weekly regimen are neutropenia and febrile neutropenia. In a previous phase I dose-escalation study with granulocyte colony-stimulating factor (G-CSF) support, the recommended dose was determined to be docetaxel 160 mg/m(2) 3-weekly. The objectives of this phase II study were to determine the response rate and toxicity of this dose and schedule, given as first-line in patients with advanced breast cancer. Mobilisation of peripheral blood stem cells (PBSCs) was also investigated. PATIENTS AND METHODS: Eligible women had metastatic breast cancer and were aged 18-75 years with ECOG performance status < or =2. Strict criteria for liver function were followed, and adjuvant chemotherapy must have been completed at least 6 months previously. Treatment was docetaxel 160 mg/m(2) over 60-90 min every 21 days with G-CSF 5 micro g/kg/day until neutrophil recovery, for up to six cycles. A 3-day corticosteroid prophylaxis was given. Bloods samples to determine PBSC levels [CD34+, granulocyte-macrophage colony-forming cells (GM-CFC) and burst-forming units-erythroid (BFU-E)] were taken on days 6, 8, 9 and 11 following docetaxel. RESULTS: Twenty-five women with median age 50 years (range 35-66) were included. Seventeen (68%) had previously received adjuvant chemotherapy. In total, 112 cycles were delivered (median four per patient), with dose reductions required in 12.5% of cycles. G-CSF was given for a median of 6 days. The median neutrophil nadir was 0.5 x 10(9)/l and occurred a median 5 days after treatment. The median duration of grade 3 or 4 neutropenia was 2 days (range 1-7). Grade 4 neutropenia occurred in 44% of patients, but there was only one episode of febrile neutropenia. Five patients were taken off study due to toxicities that included oedema, neurosensory toxicity and asthenia. Confirmed partial response was seen in nine patients (37.5%; 95% confidence interval 19% to 59%). CD34+ cells, GM-CFC and BFU-E levels peaked at day 8 following docetaxel administration. The median CD34+ cell peak was 6.5 x 10(4)/ml, with only 20% of patients <2 x 10(4)/ml, a level below which leukapheresis is not usually attempted. CONCLUSIONS: Docetaxel 160 mg/m(2) was delivered with G-CSF support with a very low rate of febrile neutropenia. Non-haematological toxicity was significant, causing five patients to go off study. Effective mobilisation of PBSCs was seen. The response rate of 37.5% was less than that obtained in first-line studies using standard-dose docetaxel 100 mg/m(2), suggesting that there is no additional benefit in dose escalation of this cytotoxic agent in breast cancer patients using this schedule.

Adult↗
PubMed2004

Non-invasive ventilation in surgical patients in a district general hospital.

We have retrospectively audited the use of non-invasive ventilation (NIV) in surgical patients. We analysed the case notes of 38 surgical patients who received NIV over a 9-month period. Twenty-three patients received NIV following emergency surgery, eight after elective surgery, and seven did not have an operation. Co-morbidity was common. The commonest reasons for starting NIV were chest infection, acute respiratory distress syndrome and pulmonary oedema. NIV was often only one aspect of treatment in surgical patients with complex medical problems. With intensive support from the critical care outreach team, NIV can be safely delivered on a surgical ward, and may sometimes prevent intensive care unit admission. Use of NIV on the intensive care unit may obviate the need for tracheal intubation in some patients. In very ill surgical patients with a poor prognosis, NIV was frequently used as the ceiling of respiratory support.

Adult↗