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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 91 records · Page 5Linked to original sources
PubMed2002

Pseudomonas fluorescens pseudobacteraemia: a cautionary lesson.

OBJECTIVES: To describe an outbreak of pseudobacteraemia caused by Pseudomonas fluorescens in a paediatric population. To document and highlight the effect this outbreak had on clinical management and the steps taken to determine the source. METHODS: A clinical and microbiological investigation was carried out into a cluster of 38 pseudobacteraemias caused by Pseudomonas fluorescens in paediatric patients over a 10 month period. RESULTS: The source of the outbreak of pseudobacteraemia was found to be contaminated lithium heparin tubes, which were being filled prior to the filling of the blood culture bottle. Cultures of the same tubes yielded Pseudomonas fluorescens. As a result of the initial positive blood cultures, clinical management was altered in 18 cases. A staff education programme was instituted and eventually resulted in a cessation of the pseudobacteraemia. CONCLUSIONS: Pseudobacteraemias are a major cause of potentially inappropriate therapy in febrile children. Attention to detail in the collection of blood cultures can help reduce this outcome. Staff involved in the collection of blood cultures need to be aware of this potential source of contamination.

Adolescent↗
PubMed2002

Phase I and pharmacokinetic study of docetaxel in combination with epirubicin and cyclophosphamide in advanced cancer: dose escalation possible with granulocyte colony-stimulating factor, but not with prophylactic antibiotics.

BACKGROUND: The objective of this phase I trial was to determine the maximally tolerated doses of the combination of docetaxel, epirubicin and cyclophosphamide. PATIENTS AND METHODS: Patients with advanced cancer, World Health Organization (WHO) performance status 0 to 2, who had received up to one prior chemotherapy regimen were treated with docetaxel, epirubicin and cyclophosphamide repeated every 21 days. The cyclophosphamide dose was fixed at 600 mg/m(2) and the dose levels studied were: docetaxel/epirubicin; 60/60, 75/60, 75/75, 75/90, 85/90 and 85/105 mg/m(2). There was provision for the addition of prophylactic ciprofloxacin and granulocyte colony-stimulating factor (G-CSF) in separate steps if dose-limiting toxicity (DLT) was neutropenia related. RESULTS: Forty-three patients were entered and all were assessable for toxicity. Dose-limiting toxicity, predominantly febrile neutropenia, was surprisingly seen at the first dose level. The addition of prophylactic ciprofloxacin did not permit dose escalation, but dose escalation was possible with the addition of G-CSF. The highest administered dose level with G-CSF was docetaxel 85 mg/m(2) and epirubicin 105 mg/m(2) with DLTs in five of six patients. Treatment was well tolerated in 10 patients treated at the recommended dose level (85/90) with only one patient experiencing DLT. Responses were seen in a range of malignancies including breast and anaplastic thyroid cancers. No significant pharmacokinetic interaction was observed, but a transient increase in epirubicinol plasma concentration occurred during and after docetaxel infusion. CONCLUSIONS: The recommended dose level of docetaxel 85 mg/m(2), epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) with G-CSF support has a favorable toxicity profile and is suitable for further investigation in phase II and III trials.

Adult↗
PubMed2002

Evaluation of Brucella abortus strain RB51 and strain 19 in pronghorn antelope.

Free-roaming elk and bison in the Greater Yellowstone Area remain the only wildlife reservoirs for Brucella abortus in the United States, and the large number of animals and a lack of holding facilities make it unreasonable to individually vaccinate each animal. Therefore, oral delivery is being proposed as a possible option to vaccinate these wild ungulates. One of the main problems associated with oral vaccination is the potential exposure of nontarget species to the vaccines. The purpose of this study was to determine the effects of two Brucella vaccines, strain 19 (S19) and the rough strain RB51 (SRB51), in pregnant pronghorn antelope. We conclude that S19 and SRB51 rarely colonize maternal and fetal tissues of pregnant pronghorn and were not associated with fetal death. Oral delivery of either vaccine at this dose appears to be nonhazardous to pregnant pronghorn.

Abortion, Veterinary↗
PubMed2002

Evidence for the role of demyelination, HLA-DR alleles, and cytokines in the pathogenesis of parvovirus B19 meningoencephalitis and its sequelae.

OBJECTIVE: To review the clinical and pathological features of parvovirus B19 meningoencephalitis and its sequelae in 12 previously published cases, and to perform additional tests to determine the pathogenesis of the disease. METHODS: Cases were reviewed and available serum and cerebrospinal fluid (CSF) tested for antiganglioside antibodies and a range of cytokines. In situ hybridisation for parvovirus B19 DNA was performed on postmortem brain tissue in two cases. HLA-DRB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: Cerebellar involvement was suggested either clinically or pathologically in four cases. In the two cases with postmortem histology, there was marked atrophy of the molecular and granular layers of the cerebellum with focal loss of Purkinje cells. Brain scanning by MRI or CT was done in six cases during the acute phase. Three were abnormal with evidence of demyelination. Three had markedly enlarged ventricles, in two of which there was high signal intensity from the white matter on both T1 and T2 weighted images. The three cases with abnormal brain scans had long term neurological sequelae (mental retardation, personality change, altered affect). In situ hybridisation on available postmortem brain tissue was negative in the two cases tested. All cases in which HLA-DR alleles were determined carried at least one of the following alleles: HLA-DRB1*01, *04, *07, *09, *15, *16. Available serum and CSF was tested for antiganglioside antibodies (all negative) and for a panel of cytokines, which had a similar profile in both serum (n = 5) and CSF (n = 1) during the acute phase. Cytokines that were consistently detectable were IL-6 (mean 726.20 pg/ml), TNFalpha (50.64 pg/ml), IFNgamma (39.64 pg/ml), GM-CSF (216.12 pg/ml), and MCP-1 (154.43 pg/ml); IL-1beta, IL-5, and IL-13 were undetectable. CONCLUSIONS: HLA-DR associations, an increased cytokine response, and benefit from immunomodulatory treatment (in one case) support a role for the immune response in the pathogenesis of parvovirus B19 meningoencephalitis.

Adolescent↗
PubMed2002

Increased central arterial stiffness in hypothyroidism.

Hypothyroidism is associated with cardiovascular dysfunction. It is increasingly apparent that stiffening of central arteries may lead to increased afterload and cardiac dysfunction. We noninvasively studied the peripheral and central pressure waveforms in 12 untreated hypothyroid patients as well as in 12 age-, sex-, and body mass index-matched controls using the technique of pulse wave analysis from recordings at the radial artery. Indexes of arterial stiffness, augmentation index (AI) and augmentation of central arterial pressure (AG), were derived as well as time of travel of the reflected wave (TR), a direct estimate of aortic pulse wave velocity. At baseline, there were no significant differences between the 2 groups in brachial and aortic blood pressures. Hypothyroid patients had significantly higher AI than controls (mean +/- SEM[SCAP], 32.0 +/- 3.4% vs. 17.0 +/- 2.4%; P < 0.0005) even when corrected for heart rate (AI(C); 28.0 +/- 3.2% vs. 17.0 +/- 2.4%; P < 0.006) and AG (13.0 +/- 2.2 vs. 7.0 +/- 2.1 mm Hg; P < 0.03) together with a lower TR (132.0 +/- 4.1 vs. 142.0 +/- 1.5 msec; P < 0.03). After 6 months of therapy with T(4), all patients were euthyroid. AI(C) had decreased in the patient group (23.0 +/- 3.2% vs. 28.0 +/- 3.2%; P < 0.01) as had AG (9.0 +/- 1.5 vs. 13.0 +/- 2.2 mm Hg; P < 0.008), but TR was significantly higher (142.0 +/- 3.0 vs. 132.0 +/- 4.1 msec; P < 0.008). AI correlated with age in all groups (hypothyroid group: r = 0.937; P < 0.0005; control group: r = 0.804; P < 0.0005), but correlated with TSH level only among controls (r = 0.591; P < 0.05). This study confirms that hypothyroidism is associated with increased cardiovascular risk, as evidenced by increased augmentation of central aortic pressures and central arterial stiffness. Furthermore, these abnormalities are reversed after adequate T(4) replacement.

Adult↗
PubMed2002

The effects of thyrotoxicosis and its treatment on central arterial stiffness.

OBJECTIVE: To assess central arterial stiffness in thyrotoxicosis using the technique of pulse wave analysis. DESIGN: Case control study designed to determine the effect of thyrotoxicosis on central arterial stiffness and at 6 months after radioiodine treatment. PATIENTS: Twenty (18 women and 2 men) thyrotoxic patients and 20 age- and sex-matched controls were studied at baseline. Thyrotoxic patients were re-studied at 6 months following treatment of thyrotoxicosis with 555 MBq (131)I with no additional therapy for the six-month period. MEASUREMENTS: Using the sphygmocor apparatus, peripheral pressure waveforms were recorded non-invasively from the radial artery and central pressure waveforms were generated from these. Indices of arterial stiffness, central augmentation index (AI), augmentation of central arterial pressure (AG) and central blood pressures were derived. AI corrected for heart rate (AIc) was calculated. RESULTS: Thyrotoxic patients recorded a significantly lower AI (means+/-s.e.m.) compared with controls (15.0+/-2.1 vs 28.0+/-2.1%; P<0.0005) even when corrected for differences in heart rate AIc (20.0+/-2.1 vs 28.0+/-2.1%; P<0.005) as well as AG (6.0+/-0.8 vs 10.0+/-1.1 mmHg; P<0.002) but higher pulse pressure (58.0+/-3.5 vs 47.0+/-2.0 mmHg; P<0.02). At 6 months following treatment, a significant rise in AIc (27.0+/-1.8 vs 20.0+/-2.1%; P<0.005) and AG (11.0+/-1.0 vs 6.0+/-0.8 mmHg; P<0.005) was noted. Lipid profiles were comparable between the groups. CONCLUSIONS: These data suggested that subjects with untreated thyrotoxicosis have a decreased augmentation of central arterial pressure or lowered central arterial stiffness that would not appear to contribute to any excess cardiovascular risk in that condition.

Blood Pressure↗
PubMed2002

High-speed plasmid isolation using 96-well, size-exclusion filter plates.

The accelerating pace of genomics analysis has necessitated the abbreviation of DNA sample preparation protocols. We have developed a size-exclusion-based system for the rapid isolation ofplasmid DNA in a 96-well microplate format. This high-speed protocol employs a modified alkaline lysis methodfor the preparation of the bacterial lysate, followed by three short vacuum filtration steps. Unlike traditional bind/wash/elute methods, there is no need to use chaotropic salts or ethanol. The samples are recovered from the top side of the MultiScreen96 PLASMID plates. Starting with bacterial cell pellets, the entire prycedure for purifying the plasmid DNA can be performed in 30 min with a multichannel pipettor. The high yields, reproducibility, and quality of the plasmids make this system a good choice for any cloning or DNA sequencing operation.

Base Sequence↗
PubMed2002

Equine surgical colic: risk factors for postoperative complications.

The reason for undertaking this study was that postoperative complications of colic surgery lead to patient discomfort, prolonged hospitalisation and increased cost. Potential risk factors for the 6 most common postoperative complications (jugular thrombosis, ileus, re-laparotomy, wound suppuration, incisional herniation and colic) were evaluated using multivariable models. Jugular thrombosis was associated significantly with heart rate greater than 60 beats/min and with increased packed cell volume (PCV) at admission. The risk of postoperative ileus also increased with increasing PCV at admission and was higher in horses recovering from pedunculated lipoma obstruction. Incisional herniation was strongly associated with wound suppuration and with increasing heart rate at admission. The emergence of cardiovascular parameters as risk factors for several postoperative complications is consistent with the hypothesis that endotoxaemia is important in the development of these complications. Early referral of colic cases, prior to the development of severe endotoxaemic shock, may minimise the risk of some postoperative complications. Horses that have suffered epiploic foramen entrapment, are more than 4 times as likely to undergo re-laparotomy than other horses. Horses that have suffered postoperative ileus have a similarly increased risk of undergoing re-laparotomy. The risk of postoperative colic is significantly associated with horses recovering from large colon torsion (>360 degrees) and with having undergone re-laparotomy. Hazard ratios (with 95% confidence intervals) for these last two effects are 3.1 (1.7, 5.7) and 3.4 (1.9, 6.2), respectively. Knowledge of the risk factors for postoperative complications allows more accurate prognostication postoperatively and suggests ways in which the risk of postoperative complications can be minimised.

Animal Welfare↗
PubMed2002

Survey of faecal parasites in patients from western Kenya.

Faecal specimens were collected from patients complaining of diarrhoea and abdominal or epigastric discomfort at two hospitals. Information obtained by questionnaires completed at the time of specimens collection, included demographic and clinical data. Specimens were preserved in 10% formalin and polyvinyl alcohol (PVA) and examined, as wet mounts and stained with Wheatley's Trichrome, Weber, modified acid-fast and hot safranin stains. One hundred patients were examined, in 30 of them parasites were detected. The most common organism identified was Cryptosporidium parvum, in specimens of five patients, followed by Entamoeba histolytica/E. dispar in four patients. The recently described "emerging parasites" were detected. Helminth eggs were found in two patients only. HIV status was not known for most of the patients, and the parasites commonly proliferate in the immuno-compromised individuals were not frequently found.

AIDS-Related Opportunistic Infections↗
PubMed2001

The surgical management of women with ovarian cancer in the south west of England.

The surgical management of epithelial ovarian cancer in the South West of England was studied in the two years 1997-1998 in order to determine the factors that influence the outcome of surgery and to provide a baseline from which to assess the effect of centralisation of cancer services. All hospitals in the South West region of England participating in the Regional Cancer Organisation's longitudinal study of outcomes in gynaecological malignancies are included. Six hundred and eighty-two patients with epithelial ovarian cancer were registered with the RCO in the two-year study period. Five hundred and ninety-five women were offered primary cytoreductive surgery of which 438 were said to be optimally cytoreduced. Applying multivariate models to analyse the outcome of surgery, older patients (OR = 0.82 per 5-year increase in age, P = 0.0003), patients treated in hospitals managing fewer than ten cases of ovarian cancer per year (OR = 1.92, P = 0.02) and patients with FIGO stage 3 (OR = 0.02, P < 0.0001) or 4 (OR = 0.002, P < 0.0001) disease were less likely to be optimally cytoreduced. Gynaecological oncologists were 2.06 times more likely to attain optimal cytoreduction when compared to general gynaecologists and this was statistically significant (P = 0.01). The results from this study support the argument that limiting surgery for ovarian malignancy to specialised surgeons improves the extent of cytoreductive surgery.

Adult↗
PubMed2001

The influence of DNA double-strand break structure on end-joining in human cells.

DNA end-joining is the major repair pathway for double-strand breaks (DSBs) in higher eukaryotes. To understand how DSB structure affects the end-joining process in human cells, we have examined the in vivo repair of linearized plasmids containing complementary as well as several different configurations of non-complementary DNA ends. Our results demonstrate that, while complementary and blunt termini display comparable levels of error-free rejoining, end-joining fidelity is decreased to varying extents among mismatched non-complementary ends. End structure also influences the kinetics of repair, accurately recircularized substrates for blunt and complementary termini being detected significantly earlier than for mismatched non-complementary ends. These results suggest that the end-joining process is composed of an early component, capable of efficiently repairing substrates requiring a single ligation event, and a late component, involved in the rejoining of complex substrates requiring multiple processing steps. Finally, these two types of repair events may have different genetic requirements as suggested by the finding that exposure of cells to wortmannin, a potent inhibitor of phosphatidylinositol 3-related kinases (PI 3-related kinases), blocks the repair of complex substrates while having little or no effect on those requiring a simple ligation event.

Androstadienes↗
PubMed2001

A preliminary evaluation of a prospective study of pulmonary function studies and symptoms of hypoventilation in ALS/MND patients.

There is still no consensus as to which physiologic marker should be used as a trigger for the initiation of non-invasive positive pressure ventilation (NPPV) in patients with amyotrophic lateral sclerosis (ALS). Current practice parameters recommend that the decision to begin treatment be based upon forced vital capacity (FVC) measurements. A prospective, randomized study was performed in 20 ALS patients who had an FVC of 70-100%. Patients received baseline assessments including: ALS functional rating scale-respiratory version (ALSFRS-R), pulmonary symptom scale, Short form 36 (SF-36), FVC%, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and nocturnal oximetry. Patients were randomized to receive NPPV based upon nocturnal oximetry studies suggesting oxygen desaturation <90% for one cumulative minute ("early intervention") or a FVC <50% ("standard of care"). At enrollment, there was no significant correlation between FVC% and the ALSFRS-R, symptom score, MEP, MIP, or duration of nocturnal desaturation <90%. An increase in the vitality subscale of the SF-36 was demonstrated in 5/6 patients randomized to "early intervention" with NPPV. Our data indicate that FVC% correlates poorly with respiratory symptoms and suggests that MIP and nocturnal oximetry may be more sensitive measures of early respiratory insufficiency. In addition, intervention with NPPV earlier than our current standard of care may result in improved quality of life.

Disease Progression↗
PubMed2001

NHS reorganisation. Cause and effect.

In a survey of 304 chief executives, three-quarters felt the Shifting the Balance reorganisation would delay the delivery of the NHS plan over the next year. A quarter felt the delay would be severe. 55 per cent expressed negative views about the reorganisation. On average, chief executives were spending a quarter of their time implementing the reforms. Almost half were concerned about PCTs' ability to cope with an enlarged set of responsibilities. More than half (59 per cent) of chief executives thought their job would change as the result of the reorganisation. A quarter thought they were less likely to be working in the NHS.

Administrative Personnel↗
PubMed2001

Primary care. Getting in on the act.

A three-year in-depth evaluation of 12 PCG/Ts shows that much remains to be done in terms of commissioning. PCG/Ts need to be more active in tackling poor performance. Further delegation of responsibilities from health authorities to PCTs will be a challenge, given their reluctance to tackle service changes. GPs tend to dominate board meetings. More resources are needed for management support.

Decision Making, Organizational↗
PubMed2001

A novel phosphotyrosine mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine (Cpp): exploitation in the design of nonpeptide inhibitors of pp60(Src) SH2 domain.

The novel phosphotyrosine (pTyr) mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine (Cpp) has been designed and incorporated into a series of nonpeptide inhibitors of the SH2 domain of pp60(c-Src) (Src) tyrosine kinase. A 2.2 A X-ray crystal structure of 1a bound to a mutant form of Lck SH2 domain provides insight regarding the structure-activity relationships and supports the design concept of this new pTyr mimetic.

Animals↗