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Biomedical subjects

R A Cox

Publications and source records attributed to R A Cox.

At least 19 recordsLinked to original sources
PubMed2006

The role of the bronchial circulation in the acute lung injury resulting from burn and smoke inhalation.

Smoke inhalation in burn patients is a serious medical problem around the world. Inhalation injury increases mortality in addition to increasing infections, ventilator-days, and hospital stays. There are also large numbers of patients subjected to smoke inhalation without burns from cooking fires, burning crops and forest fires. The injury results in a fall in arterial oxygenation as a result of airway blockade, increased pulmonary transvascular fluid flux and loss of hypoxic pulmonary vasoconstriction. The changes in cardiopulmonary function are mediated at least in part by reactive oxygen and nitrogen species. Nitric oxide (NO) is generated by both inducible and constitutive isoforms of nitric oxide synthase (NOS). NO combines with superoxide to form reactive nitrogen species such as peroxynitrite. These reactive nitrogen species can be detected by measuring their reaction products such as 3-nitrotyrosine. The latter is elevated in the airway following smoke/burn injury. The control of NO formation involves poly (ADP ribose) polymerase (PARP) and its ability to up-regulate the activity of nuclear transcription factors through ribosylation. Present data also support a major role for the bronchial circulation in the injury since blockade of bronchial blood flow will also minimize the pulmonary injury. The data suggest that cytotoxins or activated cells are formed in the airway and carried to the parenchyma. These materials cause the formation of oedema and a reduction of PaO(2).

Acute Disease↗
PubMed2002

Loss of cytomegalovirus-specific immunological memory in a patient with thymoma.

Cytomegalovirus (CMV) retinitis is a re-activation infection associated with severely impaired T cell-mediated immunity. We describe a patient with long-standing Crohn's disease and thymoma who developed severe CMV retinitis. While thymoma can be associated with impaired humoral immunity and a quantitative CD4+ T helper cell deficiency, these were not evident in our patient. However, more detailed investigation of anti-CMV responses showed absence of specific T cell responses to CMV antigen. Normal CMV seropositive controls have detectable proliferation and interferon-gamma production by T cells in response to stimulation with CMV antigen, but this was absent in this patient both during the acute infection and in convalescence. Other measures of T cell function were normal. Since CMV retinitis is due to reactivation of latent CMV infection, it appears that selective loss of CMV-specific immunity had occurred, perhaps secondary to a thymoma. The causes of thymoma-associated immune impairment are not understood, but this case demonstrates that selective defects can occur in the absence of global T cell impairment. Opportunistic infections should therefore be suspected in patients with thymoma even in the absence of quantitative immune deficiencies.

Aged↗
PubMed2002

Characterization of an rRNA operon (rrnB) of Mycobacterium fortuitum and other mycobacterial species: implications for the classification of mycobacteria.

Mycobacteria are thought to have either one or two rRNA operons per genome. All mycobacteria investigated to date have an operon, designated rrnA, located downstream from the murA gene. We report that Mycobacteriun fortuitum has a second rrn operon, designated rrnB, which is located downstream from the tyrS gene; tyrS is very close to the 3' end of a gene (3-mag) coding for 3-methylpurine-DNA-glycosylase. The second rrn operon of Mycobacterium smegmatis was shown to have a similar organization, namely, 5' 3-mag-tyrS-rrnB 3'. The rrnB operon of M. fortuitum was found to have a single dedicated promoter. During exponential growth in a rich medium, the rrnB and rrnA operons were the major and minor contributors, respectively, to pre-rRNA synthesis. Genomic DNA was isolated from eight other fast-growing mycobacterial species. Samples were investigated by Southern blot analysis using probes for murA, tyrS, and 16S rRNA sequences. The results revealed that both rrnA and rrnB operons were present in each species. The results form the basis for a proposed new scheme for the classification of mycobacteria. The approach, which is phylogenetic in concept, is based on particular properties of the rrn operons of a cell, namely, the number per genome and a feature of 16S rRNA gene sequences.

Base Sequence↗
PubMed2002

Clinical and microbiological features of Haemophilus influenzae vulvovaginitis in young girls.

AIMS: To define the clinical and microbiological features of vulvovaginitis in prepubertal girls whose genital swabs yielded Haemophilus influenzae. METHODS: Laboratory based study and retrospective collection of clinical data from the requesting doctors. RESULTS: Thirty eight isolates of non-capsulate Haemophilus influenzae and one of H parainfluenzae were isolated from 32 girls aged 18 months to 11 years. No other pathogens, such as beta haemolytic streptococci or yeasts, were present with H influenzae. The most common biotype was biotype II, comprising 57% of the 26 isolates biotyped. Six children had more than one episode of vulvovaginitis caused by H influenzae and a total of 14 children had recurrent vaginal symptoms. CONCLUSION: Children who have H influenzae vulvovaginitis are at risk of recurrent symptoms. Biotype II is the one most commonly associated with this condition.

Anti-Bacterial Agents↗
PubMed2001

An outbreak of Pseudomonas aeruginosa infection associated with contaminated urodynamic equipment.

Seven patients developed Pseudomonas aeruginosa urinary tract infections following urodynamic studies, over a two-month period. One patient developed septicaemia and meningitis and died following rupture of a berry aneurysm. Two others required hospital admission for intravenous antibiotic treatment. Pseudomonas aeruginosa was isolated from a pressure dome which covered the pressure transducer of the urodynamic system used for assessing bladder pressure. The device packaging carried the symbol designating this as a 'single use' product, but as an economy measure, a local decision had been taken to change the device monthly.

Cross Infection↗
PubMed2001

The use of palivizumab monoclonal antibody to control an outbreak of respiratory syncytial virus infection in a special care baby unit.

An outbreak of respiratory syncytial virus (RSV) infection affected seven premature infants in a special care baby unit during November and December 1999. Conventional infection control measures (cohorting infected babies, strict reinforcement of the use of gloves and aprons, emphasis on hand disinfection) failed to prevent spread. Palivizumab, a respiratory syncytial virus monoclonal antibody, was given to eight high-risk preterm infants. There were no further cases of RSV in the unit and none of the babies given palivizumab developed RSV. One baby who acquired RSV during the outbreak (and who was not given palivizumab) was subsequently admitted to hospital with another episode of RSV bronchiolitis. The role of palivizumab in the control of hospital outbreaks of RSV infection merits further investigation.

Antibodies, Monoclonal↗
PubMed2001

Young dyspeptic patients: with a test-and-treat policy, are the benefits of decreased symptom severity and oesophago-gastric-duodenoscopy workload sustained?

OBJECTIVES: To examine the symptom severity and requirement for oesophago-gastro-duodenoscopy (OGD) in young dyspeptic patients 2 years after serological testing for Helicobacter pylori, and to compare the outcomes of seronegative patients with those of seropositive patients. DESIGN: Long-term follow-up study of 232 participants from our previous trial. METHODS: Telephone assessment of patients' symptom severity, scored using a previously validated questionnaire; return of patients for OGD determined using local patient administration system (PAS); and review of medical case notes. RESULTS: Dyspepsia symptom severity of both seronegative and seropositive patients remained reduced compared with initial scores at time of trial recruitment. Symptom severity of seropositive patients was significantly lower than that of seronegative patients (P< 0.001). Seventeen additional patients returned for OGD between six months and two years after the start of the serological study. As 61 of the original 232 study patients returned for OGD within the first six month follow-up period, a total of 78 individuals (34%) had OGD during the two years following the study. Thus, 66% of the original participants avoided OGD. CONCLUSIONS: This study of non-invasive testing for H. pylori in young dyspeptic patients has demonstrated an improvement in symptom severity and a substantial reduction in OGD workload over a 2-year period.

Adult↗
PubMed2000

Comparative morphology of the marrow sac.

Electron microscopic techniques have been used to profile the morphologies of marrow sacs in different laboratory species. These structures all comprise a condensed layer of overlapping fibroblast-like stromal cells and apparently confine the medullary and endosteal osteoblast/lining cells to separate histiotypic compartments. There were some variations in the morphology of the sac cells in the different species. In rats, cats, and sheep, scanning electron microscopy (SEM) showed a seamless arrangement of marrow sac cells which resembled a thin, flat simple squamous epithelium; they displayed few intercellular cytoplasmic processes. In the rabbit and pigeon, the sac comprised a more woven, multilayered fabric of broadly elongate flat fibroblast-like cells which displayed numerous intercellular processes. Transmission electron microscopy (TEM) showed that all marrow sac cells were attenuated with elongated nuclei, a few small round mitochondria, and a sparse rough endoplasmic reticulum. In the majority of animals, the sac was one to two cell layers thick. The rabbit and pigeon sacs were multilayered, and never less than three to four cells deep. The cell layers were not closely apposed. Tight or gap junctions were absent at the points of intercellular contact. These morphological results suggest that marrow sacs are common elements of the vertebrate skeleton with species specific morphologies.

Animals↗
PubMed2000

The crystal structure of NusB from Mycobacterium tuberculosis.

Both prokaryotes and eukaryotes regulate transcription through mechanisms that suppress termination signals. An antitermination mechanism was first characterized in bacteriophage lambda. Bacteria have analogous machinery that regulates ribosomal RNA transcription and employs host factors, called the N-utilizing (where N stands for the phage lambda N protein) substances (Nus), NusA, NusB, NusE and NusG. Here we report the crystal structure of NusB from Mycobacterium tuberculosis, the bacterium that causes tuberculosis in humans. This molecule shares a similar tertiary structure with the related Escherichia coli protein but adopts a different quaternary organization. We show that, unlike the E. coli homolog, M. tuberculosis NusB is dimeric both in solution and in the crystal. These data help provide a framework for understanding the structural and biological function of NusB in the prokaryotic transcriptional antitermination complex.

Amino Acid Motifs↗
PubMed2000

Crystallization and preliminary X-ray diffraction studies on the N-utilizing substance-B (NusB) from Mycobacterium tuberculosis.

N-utilizing substance B (NusB) is a protein which forms part of a complex assembly in transcriptional antitermination in Mycobacterium tuberculosis. It forms a heterodimer with the product of the NusE gene (identical to the ribosomal protein S10) and mediates the process of transcriptional antitermination by forming the core complex with the nut site of the ribosomal RNA along with other protein factors. NusB has been cloned and overexpressed in Escherichia coli and crystallized using the hanging-drop vapour-diffusion method. The space group is P2(1)2(1)2(1), with unit-cell parameters a = 46.6, b = 64.2, c = 90.1 A. A native data set complete to 1.6 A resolution has been collected from a single crystal.

Amino Acid Sequence↗
PubMed2000

Surgical versus interventional procedures in patients with multivessel coronary artery disease.

OBJECTIVE: This study examined the clinical characteristics, risk factors, indications and post-intervention complications of patients with multivessel coronary artery disease (CAD) submitted to either percutaneous transluminal coronary angioplasty (PTCA) and/or stent placement versus isolated coronary artery bypass grafting (CABG). BACKGROUND: Several studies have examined the relative safety and outcome of patients submitted to those interventional procedures compared to CABG. Limited information is available regarding that subject in Puerto Rico. METHODS: We performed a retrospective analysis of the clinical, angiographic, operative, interventional, post-operative and post-interventional data of patients submitted to those procedures in our institution from January 1998 to August 1998. There were 53 patients in the interventional group and 206 patients in the CAGB group. Comparison of quantitative variables by procedure was based on Student t test or Mann-Whitney-Wilcoxon test; categorical variables were compared using Pearson's chi-square or Fisher's exact test. RESULTS: There were no significant differences in age, body surface area, or cardiac risk factors. The most common pre-existing cardiovascular diagnosis was unstable angina. Three-vessel disease was the most common angiographic finding among CABG patients (61.7%). Two-vessel disease without left anterior descending coronary artery obstruction was significantly more common in the PTCA/Stent patients (58.5%). The vast majority (97.6%) of patients in the PTCA/Stent group and 52.4% of the CABG group had two-vessel intervention. A significantly higher frequency of complications occurred in the CABG group. However, the incidence of major complications, in both groups was not statistically different. Atrial arrhythmias were significantly more frequent in the CABG group. CONCLUSION: A larger prospective study should be conducted in order to corroborate these preliminary findings and seek effective solution to any identifiable problem.

Angioplasty, Balloon, Coronary↗
PubMed2000

Gender differences in clinical outcome after coronary stenting.

OBJECTIVE: The purpose of this study was to determine the effect of gender differences in the clinical outcome of women and men submitted to coronary stenting at our institution. BACKGROUND: Studies regarding gender differences in outcome after invasive coronary interventions have revealed conflicting data regarding risk for complications. Some studies have pointed to female gender as a predictor of mortality and complications after those procedures. To our knowledge no such evaluation has been performed in our country. METHODS: We reviewed the medical records, cardiac catheterization and procedural data of 205 men and 122 women referred to our section that underwent coronary stenting at the Cardiovascular Center of Puerto Rico and the Caribbean from July 1, 1998 to March 30, 1999. The clinical and procedural characteristics and the immediate procedure-related complications were analyzed. Clinical events during the six-month period after the procedure were evaluated in patients that returned for follow-up to the section. Student's t-test or Mann-Whitney-Wilcoxon, when appropriate, was used to compare continuous data. The chi-square test or Fisher's exact test, was employed to compare categorical data. RESULTS: The initial procedural success and the frequency of early complications were comparable to those informed in the medical literature and not statistically significant between genders. The only statistically significant gender differences in outcome occurred in men who had higher re-hospitalization and re-intervention rates in the six-month period after the procedure. A lower mean ejection fraction and higher previous history of myocardial infarction and cigarette smoking in this group could have been related to the higher complication rate. CONCLUSION: Although the sample examined is small, its findings point to the need of a larger prospective study to further explore the possibility that the previously reported differences in outcome in men and women submitted to interventional procedures would have a stronger relation to clinical factors than to the direct effect of gender.

Cardiac Surgical Procedures↗
PubMed1999

Protein synthesis in the plastid of Plasmodium falciparum.

The plastid organelle of malarial and other apicomplexan parasites contains ribosome-like particles as well as a genome dedicated largely to specifying components of a protein expression system. We have identified plastid ribosomes using hybridization studies and show that in erythrocytic stages of Plasmodium falciparum a subset of polysomes carries plastid-specified rRNAs and mRNA, supporting the idea that protein synthesis is active in the plastid.

Animals↗
PubMed1999

Methicillin-resistant Staphylococcus aureus colonization in nursing home residents: a prevalence study in Northamptonshire.

A prevalence study of methicillin-resistant Staphylococcus aureus (MRSA) colonization was carried out in 17 nursing homes in Northamptonshire over a 20-month period. Thirteen of 275 residents swabbed (4.7%) were found to be colonized and six of the 17 homes (35%) had colonized residents. Only two homes had more than one colonized resident. Individual risk factors for colonization were gender (male) and the presence of skin ulcers and sores. There were no significant risk factors identified for homes. Spread may have occurred in the two homes which had more than one colonized resident. Both these homes had the epidemic strain EMRSA-15 whereas three of the four homes with a single colonized resident had EMRSA-16. It is suggested that homes with residents colonized with EMRSA-16 may be able to prevent spread by adherence to good infection control procedures but that this may not be adequate to prevent spread of EMRSA-15.

Adult↗
PubMed1999

Coadministration of interleukin 12 expression vector with antigen 2 cDNA enhances induction of protective immunity against Coccidioides immitis.

Interleukin 12 (IL-12) plays an important role in the induction of protective immunity against cancer and infectious diseases. In this study we asked whether IL-12 cDNA could increase the protective capacity of the antigen 2 (Ag2) gene vaccine in experimental coccidioidomycosis. Coimmunization of BALB/c mice with a single-chain IL-12 cDNA (p40-L-p35) and Ag2 cDNA, both subcloned into the pVR1012 plasmid, significantly enhanced protection against systemic challenge with 2,500 arthroconidia, as evidenced by a greater-than-1.3-log-unit reduction in the fungal load in the lungs and spleens compared to mice receiving the pVR1012 vector alone, Ag2 cDNA alone, or IL-12 cDNA alone. The enhanced protection was associated with increased gamma interferon secretion; production of immunoglobulin G2a (IgG2a), IgG2b, and IgG3 antibodies to Coccidioides immitis antigen; and the influx of CD4(+) and CD8(+) T cells in lungs and spleens. When challenged by the pulmonary route, mice covaccinated with Ag2 cDNA and IL-12 cDNA were not protected at the lung level but did show a significant reduction in the fungal load in their livers and spleens compared to mice vaccinated with Ag2 cDNA or IL-12 cDNA alone. These results suggest that IL-12 acts as a therapeutic adjuvant to enhance Ag2 cDNA-induced protective immunity against experimental coccidioidomycosis through the induction of Th1-associated immune responses.

Animals↗