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Biomedical subjects

P Leonard

Publications and source records attributed to P Leonard.

At least 19 recordsLinked to original sources
PubMed2005

[HIV seroprevalence among tuberculosis patients in Nkembo Hospital, Libreville, Gabon. Short note].

There are nearly 31,000 HIV infected patients in Gabon. In Libreville, the capital, the prevalence is estimated at 7.7%. About 2627 tuberculosis patients, all types included, have been notified in 2001 to the World Health Organization of which 43% of smear positive new cases. The co-infection HIV-TB worsens the overall prognosis of our patients. The objective of our study is to determine the HIV seroprevalence among our tuberculosis patients. It is a cross-sectional study conducted between June 25th and August 31th 2001. All patients are new or relapse tuberculosis cases. There is no difference between the types of tuberculosis. The diagnosis was clinical, radiological and based on smear AFB sputum (according to the Ziehl Neelsen method). The patients agreed orally for HIV testing. We made two tests: a rapid one followed by Elisa if positive. 358 patients were examined among them 141 women and 217 men. The M/F sex ratio was 1.53 and the average age 32 years. Proportion of new patients reached 61%. Ninety seven per cent of patients suffered from a pulmonary tuberculosis, 58% smear positive and 26% were HIV-1 positive. According to this status, no statistical difference was notified towards sex, types of disease or patients and the smear sputum results.

Adult↗
PubMed2004

Wavelet analysis of pulse oximeter waveform permits identification of unwell children.

BACKGROUND: Children who are unwell often display signs of circulatory compromise. It has been observed that pronounced changes occur in the appearance of the photoplethysmogram (pulse oximeter tracing) in these children. The aim of the study was to discover if wavelet transforms can identify more subtle changes in the photoplethysmogram of children who are unwell. METHODS: Photoplethysmograms were obtained from children attending a paediatric accident and emergency department with clinical features suggestive of significant bacterial illness or circulatory compromise. Photoplethysmograms were also obtained from a control group of well children. Wavelet transforms were applied to the traces in an attempt to separate the two groups. RESULTS: 20 traces were obtained from unwell children and 12 from controls. Analysis of the entropy of the wavelet transform of the photoplethysmogram allows the differentiation of unwell children from controls (p = 0.00002). CONCLUSIONS: Wavelet transform of the photoplethysmogram offers the possibility of a rapid non-invasive method of screening children for significant illness.

Blood Gas Monitoring, Transcutaneous↗
PubMed2004

A questionnaire survey of stress and bullying in doctors undertaking research.

BACKGROUND: Research is an increasingly important aspect of higher medical training for many doctors. Studies investigating sources of stress, isolation, and workplace bullying have not previously sought information in this setting. METHODS: An internet based questionnaire survey of doctors undertaking research (n = 259) was conducted to examine stressors and levels of job satisfaction in this potentially vulnerable group. In order to assess overall levels of satisfaction, we asked whether doctors would recommend their research post to a colleague. RESULTS: There was a statistically significant association between those who would not recommend their post to a colleague and those who had difficulties in arranging funding and in writing up (p<0.001). Further significant correlations were found between dissatisfaction with the post and lack of help, support, and advice from supervisors and colleagues, wanting to change supervisors, experience of the major categories of workplace bullying, and having an inadequate clinical commitment (p<0.001). When the significant variables were entered into a multivariate analysis, the results showed that dissatisfaction was associated with wanting to change supervisors and with a threat to professional status. CONCLUSIONS: Stress and bullying are common in doctors undertaking research. These findings have important implications for medical training and for doctors choosing research projects. Setting up systems of support may have important benefits.

Attitude of Health Personnel↗
PubMed2003

Gene expression array profile of human osteosarcoma.

The aims of this pilot study were to determine whether needle and open biopsies from osteosarcoma (OS) provide sufficient quality of mRNA for cDNA array analyses to gain insights into the expression profile of OS. A total of 22 samples collected from OS were used for array analyses. A primary cell culture was also established from one of the OS biopsies. Total RNA was extracted and probes were generated for cDNA arrays. cDNA probes were made for all the 22 samples. Two of these samples were needle core bone biopsies. Statistical analysis confirmed the reliability of array data obtained in 16 of the 22 samples. Known genes involved in bone metabolism and osteosarcoma were identified as highly expressed, and the putative new marker Ezrin was also identified. Confirmatory immunohistochemical staining using the Ezrin antibody was performed in a selection of samples.

Adolescent↗
PubMed2003

How do blood cultures sent from a paediatric accident and emergency department influence subsequent clinical management?

OBJECTIVES: To determine the clinical impact of positive results from blood cultures sent from a busy paediatric accident and emergency department. METHODS: All children who attended the department over a seven month period and had blood culture investigations were identified. Case notes of patients who had any growth on blood culture were reviewed to determine whether the organism was felt to be pathogenic and how the result affected clinical management. RESULTS: 1159 children had blood cultures sent, 26 of these grew an organism that was felt to be pathogenic. However, only five significantly influenced clinical management. CONCLUSIONS: Blood cultures sent from an accident and emergency department rarely influence clinical management. A more focused approach to bacteriological investigation is recommended.

Adolescent↗
PubMed2003

Standard pulse oximeters can be used to monitor respiratory rate.

BACKGROUND: One of the most important limitations of standard pulse oximeters is the inability to detect changes in respiratory rate until oxygenation is affected. This study sought to determine if analysis of the plethysmogram by wavelet transforms would enable the determination of changes in respiratory rate at an earlier stage. METHODS: Ten healthy adult volunteers were monitored, breathing at baseline and predetermined respiratory rates, using a standard pulse oximeter. Photo-plethysmograms captured in an attached lap top computer were then analysed using wavelet transforms. RESULTS: Determination of baseline respiratory rate and subsequent changes including apnoea were easily identified. COMMENT: Wavelet transforms permit the accurate determination of respiratory rate by a standard pulse oximeter.

Humans↗
PubMed2002

Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer.

We investigated the activity of irinotecan given with a more convenient modified bimonthly de Gramont regimen of bolus and infusional 5-fluorouracil [IrMdG] in advanced or metastatic colorectal cancer in the first and second line setting. Irinotecan 180 mg m(-2) was infused over 90 min. L-folinic acid 175 mg or d,l folinic acid 350 mg was given over 2 h followed by a bolus of 5-fluorouracil (400 mg m(-2)) and a 46 h continuous infusion of 5-fluorouracil (2.4-2.8 g m(-2)). Forty-six previously untreated patients (Group A) and 36 who had received 5-fluorouracil for metastatic disease (Group B) were recruited. Seventy-eight patients were evaluable for response. A partial response was seen in 13 out of 43 (30% [95%CI 28.1-31.9%]) in Group A and 8/35 (23% [95% CI 17.9-28.1%]) in Group B. 40% (95%CI 38.1-41.9%) of Group A and 26% (95% CI 20.9-31.1%) of Group B patients achieved disease stabilisation. The median progression free survival from the start of this treatment was 7 months (95% CI 4.4-9.6 months) in Group A and 5 months (95% CI 2.8-7.2 months) in Group B. Median overall survival was 14 months (95% CI 9.0-18.9) in Group A and 11 months (95% CI 5.9-16.1) in Group B. Grade 3-4 toxicity in both treatment groups were similar; leucopenia 17% and diarrhoea 7-8%. Grade 3-4 mucositis was not seen and severe alopecia affected only three patients. IrMdG is an active and well-tolerated regimen for both the first and second line treatment of advanced colorectal cancer.

Adult↗
PubMed2002

[Morphological and metabolic abnormalities related to antiretroviral therapy].

The long term use of antiretroviral therapy is associated with metabolic and morphological abnormalities named lipodystrophy. The understanding of its epidemiology is in progress. NRTIs and Pls are involved in the origin of these abnormalities. So, NRTIs inhibit mitochondrial gamma polymerase and induce body fat distribution disorders. PIs interfere with lipid metabolism, leading to hyperlipidaemia and insulin resistance symptomatology. The diagnosis is made by clinical (far wasting or accumulation, or mixed syndrome) and biological signs (hyperlipidaemia, hyperglycaemia, hyperlactacidaemia). Radiological exams can quantify morphological abnormalities. The management consists in drug substitution, diet and exercise, and corrective drugs. Plastic surgery can be useful.

Adipose Tissue↗
PubMed2002

Prevalence of obesity, lipid and glucose abnormalities in outpatients prescribed clozapine.

Individuals with schizophrenia have standardised mortality rates which are double that of the general population. In addition to suicide, high rates of cardiovascular and respiratory disease contribute to this raised mortality rate. Although clozapine has been reported to improve psychotic symptoms and decrease suicide rates, attention has recently focussed on its potential to increase cardiovascular risk factors including obesity, dyslipidemia and diabetes mellitus. This study aimed to ascertain the prevalence of these risk factors in a cohort of Irish outpatients treated with clozapine.

Adolescent↗
PubMed2001

Neo-adjuvant therapy improves resectability rates for colorectal liver metastases.

PURPOSE: Liver resection improves survival in selected patients with colorectal liver metastases. However, the majority of patients with colorectal liver metastases have inoperable disease at presentation. Neo-adjuvant therapy (systemic or regional chemotherapy and interstitial laser therapy) used singly or in combination may convert a selected group of patients with irresectable liver metastases into an operable state. PATIENTS AND METHODS: We report a series of patients with initially inoperable multiple colorectal liver metastases who became operable after neo-adjuvant therapy. Operability was defined as unilateral disease limited to the liver. Twelve patients (7 female, 5 male, median age 57 years, range 38-69 years) with multiple inoperable colorectal liver metastases (8 synchronous, 4 metachronous) were initially treated with systemic chemotherapy (n = 7), hepatic arterial chemotherapy (n = 2) and chemotherapy plus interstitial laser therapy (n = 3). RESULTS: In all cases, a significant response was achieved which enabled subsequent liver resection to be undertaken. There was only one postoperative complication (8%) and no peri-operative deaths. 3 patients were operated on within the last 12 months and are still alive. Of the remainder, 1 died within 1 year with recurrent disease. The remaining patients have a median survival of 2.5 years, range 1.39-4 years. CONCLUSIONS: These results are similar to those reported for patients undergoing resection for operable metastases without neo-adjuvant therapy. Aggressive multimodality treatment of colorectal liver metastases in specialised centres may improve the resectability rates and survival in a selected group of patients.

Adult↗
PubMed2000

The influence of modified purine bases on the stability of parallel DNA.

The stability of the parallel-stranded (ps) DNA duplexes is increased when the dA-residues are replaced by the 7-substituted 7-deaza-2'-deoxyadenosine derivatives 3a,b or the dG-residues by the 8-aza-7-deazapurine 2'-deoxynucleosides 6 and 7a,b. Also the N-7-glycosylated adenine 5 forms stable base pairs in ps-DNA while it destabilizes oligonucleotide duplexes with antiparallel chain orientation. The presence of a 2-amino group as in compound 4b is critical for the DNA-structure, leading to a much greater destabilization of the ps-hybrids than of aps-DNA.

Base Sequence↗
PubMed2000

Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes.

PURPOSE: To design, synthesize, and test synthetic glycopeptide-based delivery systems for gene targeting to hepatocytes by systemic administration. METHODS: All peptides were synthesized by the solid phase method developed using Fmoc chemistry on a peptide synthesizer. The binding of galactosylated peptides to HepG2 cells and accessibility of the galactose residues on particle surface was demonstrated by a competition assay using 125I-labeled asialoorosomucoid and RCA lectin agglutination assay, respectively. DNA plasmid encoding chloramphenicol acetyl transferase (CAT) gene was complexed with a tri-galactosylated peptide (GM245.3) or tri-galactosylated lipopeptide (GM246.3) in the presence of an endosomolytic peptide (GM225.1) or endosomolytic lipopeptide (GM227.3) to obtain DNA particles of 100-150 nm in size. The plasmid/peptide complexes were added to HepG2 cell cultures or intravenously administered by tail vein injection into normal mice or rats. Plasmid uptake and expression was quantified by qPCR and ELISA, respectively. RESULTS: Multiple antennary glycopeptides that have the ability to condense and deliver DNA plasmid to hepatocytes were synthesized and complexed with DNA plasmid to obtain colloidally stable DNA/peptide complexes. Addition of DNA/GM245.3/GM225.1 peptide complexes (1:3:1 (-/+/-)) to HepG2 cell cultures yielded CAT expression in transfected cells. The transfection efficiency was significantly reduced in the absence of galactose ligand or removal of endosomolytic peptide. Intravenous administration of DNA/GM245.3 peptide complexes (1:0.5 (-/+)) into the tail vein of normal rats yielded DNA uptake in the liver. Substitution of GM245.3 by galactosylated lipopeptide GM246.3 resulted in more stable DNA particles, and a 10-fold enhancement in liver plasmid uptake. CAT expression was detectable in liver following intravenous administration of DNA/GM246.3 complexes. Addition of endosomolytic lipopeptide GM227.3 into the complexes (DNA/ GM246.3/GM227.3 (1:0.5:1 (-/+/-))) yielded a 5-fold increase in CAT expression. Liver expression was 8-fold and 40-fold higher than lung and spleen, respectively, and localized in the hepatocytes only. The transfection efficiency in liver was enhanced by increasing DNA dose and injection volume. The plasmid uptake and expression in liver using DNA/GM246.3/GM227.3 complexes was 100-200-fold higher than DNA formulated in glucose. Tissue examination and serum biochemistry did not show any adverse effect of the DNA/GM246.3/ GM227.3 (1:0.5:1 (-/+/-)) complexes after intravenous delivery. CONCLUSIONS: Gene targeting to hepatocytes was achieved by systemic administration of a well-tolerated synthetic glycopeptide-based delivery system. The transfection efficiency of this glycopeptide delivery system was dependent on peptide structure, endosomolytic activity, colloidal particle stability, and injection volume.

Amino Acid Sequence↗
PubMed2000

Cationic lipid-based delivery system for systemic cancer gene therapy.

A cationic lipid-based gene delivery system composed of N-[(1-(2,3-dioleyloxy)propyl)]-N-N-N-trimethylammonium chloride and cholesterol, at a 4:1 molar ratio, was developed for systemic administration. Plasmid biodistribution and expression were characterized in syngeneic mouse tumor model squamous cell carcinoma VII cells. A reporter gene expression plasmid was used for biodistribution of plasmid and expression. The results showed that lungs and primary tumors were transfected. Fluorescence microscopy showed that fluorescent-labeled transfection complexes were passively targeted to the tumor vasculature and that the endothelial cells internalized the plasmid. Transgene expression was characterized based on duration of expression and dosing schedule. In vivo gene transfer with an interleukin-12 expression plasmid yielded protein levels in blood, lungs, and primary tumor after intravenous administration. Efficacy studies showed that 15 microg of interleukin-12 plasmid was sufficient to produce a gene-specific inhibition of primary tumor growth. These results characterize the vascularity of the tumor model, characterize the in vivo gene transfer properties of the plasmid-based gene delivery system, and show that the transgene expression level was sufficient to elicit a biological response by inhibiting tumor growth.

Animals↗
PubMed1998

Biodistribution and gene expression of lipid/plasmid complexes after systemic administration.

The objectives of this study were to investigate the influence of physicochemical properties of lipid/plasmid complexes on in vivo gene transfer and biodistribution characteristics. Formulations based on 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and novel biodegradable cationic lipids, such as ethyl dioleoyl phosphatidylcholine (EDOPC), ethyl palmitoyl myristyl phosphatidylcholine (EPMPC), myristyl myristoyl carnitine ester (MMCE), and oleyl oleoyl L-carnitine ester (DOLCE), were assessed for gene expression after tail vein injection of lipid/plasmid complexes in mice. Gene expression was influenced by cationic lipid structure, cationic lipid-to-colipid molar ratios, plasmid-to-lipid charge ratios, and precondensation liposome size. Detectable levels of human growth hormone (hGH) in serum, human factor IX (hFIX) in plasma, and chloramphenicol acetyltransferase (CAT) in the lung and liver were observed with positively charged lipid/plasmid complexes prepared from 400-nm extruded liposomes with a cationic lipid-to-colipid ratio of 4:1 (mol/mol). Intravenous administration of lipid/CAT plasmid complexes resulted in distribution of plasmid DNA mainly to the lung at 15 min after injection. Plasmid DNA accumulation in the liver increased with time up to 24 hr postinjection. There was a 10-fold decrease in the amount of plasmid DNA in the lung at 15 min after injection, when the lipid/plasmid complex charge ratio was decreased from 3:1 to 0.5:1 (+/-). Bright fluorescent aggregates were evident in in vivo-transfected lung with the positively charged pCMV-CAT/DOLCE:dioleyl phosphatidylethanolamine (DOPE) (1:1, mol/mol) complexes, while more discrete punctate fluorescence was observed with a 4:1 molar ratio of cationic lipid:colipid formulations. Preinjection of polyanions such as plasmid, dextran sulfate, polycytidic acid, and polyinosinic acid decreased hGH expression, whereas the preinjection of both positively charged and neutral liposomes had no effect on hGH serum levels. Of the cationic lipids tested, DOLCE was found to be the most effective potentially biodegradable cationic lipid. A correlation between gene expression and cationic lipid:colipid ratios and lipid-to-plasmid charge ratio was also observed for DOTMA- and DOLCE-based formulations.

Animals↗
PubMed1997

Parallel-stranded duplexes and quartet assemblies formed by oligonucleotides containing isoguanine.

Oligonucleotides with isoguanine-cytosine base pairs form duplexes with parallel chain orientation. This strong base pair dictates the strand polarity when additional dA-dT or N7Ad-dT pairs are present. The same is observed for the isocytosine-guanine pair. Quartet structures are built by the self-assembly of oligonucleotides containing short runs of isoguanine or 7-deazaisoguanine. New base pairs between isoguanine or guanine and 5-aza-7-deazaguanine are presented.

Base Composition↗