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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 19 recordsLinked to original sources
PubMed2007

Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants.

Mutations in SNCA and LRRK2 genes, encoding alpha-synuclein and leucine-rich repeat kinase 2, respectively, cause autosomal dominant Parkinson's disease (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have also been identified in sporadic PD (sPD). We studied 55 unrelated patients with AdPD, 235 patients with sPD, and 235 healthy age- and gender-matched controls all of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by direct sequencing. SNCA gene dosage analysis was also performed for AdPD using quantitative duplex polymerase chain reaction of genomic DNA. In addition, we investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no missense mutations or multiplications in the SNCA gene. Here we report two novel variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two patients with AdPD that was not present in controls. We identified only one patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are present in AdPD and sPD patients of Greek origin.

Adult↗
PubMed2005

An economic evaluation of phosphorus recovery as struvite from digester supernatant.

Phosphorus can be recovered from wastewater through crystallisation of struvite, MgNH(4)PO(4).6H(2)O. Approximately 1 kg of struvite can be crystallised from 100 m(3) of wastewater. Crystallisation is profitable compared to chemical and biological removal of phosphorus due to savings from the reduction in (i) chemicals used for precipitation and sludge disposal; and (ii) downtime for cleaning unwanted struvite formed during chemical and biological removal. The struvite produced annually from a wastewater treatment plant that processed 100 m3/d, would be sufficient to apply on 2.6 ha of arable land, as fertilizer. If struvite were to be recovered from wastewater treatment plants worldwide, 0.63 million tons of phosphorus (as P(2)O(5)) could be harvested annually, reducing phosphate rock mining by 1.6%. Therefore, this technology could provide opportunities to recover phosphorus sustainably from waste streams and preserve phosphorus reserves.

Biodegradation, Environmental↗
PubMed2005

Fetal hemoglobin induction by the histone deacetylase inhibitor, scriptaid.

Many different classes of drugs induce fetal hemoglobin (HbF) including histone deacetylase (HDAC) inhibitors such as butyrate and trichostatin A. Although these agents induce gamma-globin expression in culture many are ineffective in vivo, therefore research efforts continue to identify clinically useful fetal globin inducers. We and others demonstrated a role for p38 mitogen activated protein kinase (MAPK) in gamma-globin promoter activation by HDAC inhibitors. In this study we determined the ability of scriptaid, a novel HDAC inhibitor, to induce gamma-globin expression via p38 MAPK signaling. Scriptaid induced gamma-globin in K562 cells and human erythroid progenitors. Furthermore the p38-selective inhibitor SB203580 completely reversed the ability of scriptaid to induce HbF. To test the potential efficacy of scriptaid in humans, in vivo studies were completed in beta-YAC transgenic mice where the gamma-gene is completely silenced. Scriptaid induced reticulocytosis and human gamma-globin mRNA synthesis. At a concentration of 1 mg/kg/day given by intraperitoneal injections twice weekly we observed a significant 1.8-fold increase in gamma-globin mRNA transcripts. The potential for scriptaid as a treatment option for sickle cell disease will be discussed.

Anemia, Sickle Cell↗
PubMed2005

Human papillomavirus infection in women who develop high-grade cervical intraepithelial neoplasia or cervical cancer: a case-control study in the UK.

Human papillomavirus (HPV) testing might identify older women who could be withdrawn from the cervical screening programme, or require less frequent screening. A case-control study using the United Kingdom cervical screening population was set up to help address this issue. Cases comprised 575 women who developed cervical intraepithelial neoplasia (CIN) grade 2 or worse over a 13-year period following a cytologically normal baseline smear, and were stratified by age group ('under 20', '20-39' and 40 years or over). Controls (n=601) were women who remained disease free over this interval and were the same age on average as cases. DNA was extracted from the baseline smears and tested for HPV by PCR using GP5+/6+ consensus primers. HPV+ samples were tested for HPV types 16 and 18 using specific PCR primers. In all, 27.0% of cases tested positive for HPV at baseline, compared with 15.4% of controls (odds ratio (OR)=2.00; 95% confidence interval (CI), 1.50-2.68). Among women aged 40 years or over, the OR for HPV 16 was 8.95 (95% CI, 2.63-30.4). These results support the need for further cervical screening of HPV- older women, as many of the cases were HPV- at baseline.

Adult↗
PubMed2005

Cardiac diverticulum with pericardial effusion: report of two new cases treated by in-utero pericardiocentesis and a review of the literature.

Congenital cardiac diverticula are rare abnormalities that may occur as isolated malformations. They are often associated with pericardial effusions, which may cause both pulmonary hypoplasia and progressive fetal hydrops. Few cases are reported in fetal life. Mount Sinai Hospital, Toronto, has previously reported two cases of cardiac diverticula complicated with pericardial effusion successfully treated in utero with aspiration of the pericardial fluid. Here a further two cases of isolated apical right ventricular diverticula with large pericardial effusion, one diagnosed at 16 weeks and another at 13 weeks' gestation are described. In-utero drainage of pericardial effusion was performed once in each case at 16 and 14 weeks' gestation, respectively, with good neonatal outcome. Both had normal karyotype and there was no evidence of maternal or fetal infection. The pericardial effusion did not recur in either case. Given the otherwise favorable prognosis for this lesion, and the excellent response in these cases, prenatal pericardiocentesis should be considered in similar cases.

Adolescent↗
PubMed2005

Predictive value of pretransplant inflammatory markers in renal allograft survival and rejection in children.

Pretransplant (pre-Tx) inflammation has been associated with acute rejection (AR) in adult Tx recipients. Our study was performed to determine whether a single pre-Tx serum C-reactive protein (CRP), Neopterin (Neo), and IL-12 determination could predict outcome in pediatric renal Tx recipients. Pre-Tx sera from 51 children transplanted between 1985 and 2000 were analyzed for serum CRP, Neo, and IL-12 for correlation with Tx-related variables. Endpoints were graft loss and AR. Kaplan-Meier and log-rank statistics were used to compare rejection-free and overall graft survival at different quartiles for each marker. Cox regression analysis was performed to determine the independent effects of various pre-Tx variables on the endpoints. The mean age of the children at Tx was 11 years. The mean CRP, Neo, and IL-12 were 1.3 mg/L, 1.78 ng/mL and 123 pg/mL, respectively. At last-follow-up (mean 4.9 years after Tx), 50% of the children had experienced AR and 29% had lost their grafts. The mean CRP, Neo, and IL-12 were not different between the patients with versus without AR or graft loss (P > .4 for all). Neither rejection-free survival nor graft survival was affected by CRP, Neo, or IL-12 quartiles (log-rank test). Cox regression analysis demonstrated no predictive value of any marker on the outcomes. Unlike adults, a single pre-Tx determination of inflammatory markers was not predictive of AR or graft loss in children. The pathogenesis of AR may be different in children with a lesser contribution of alloantigen-independent factors such as chronic infections.

Analysis of Variance↗
PubMed2005

Efficacy of oral isotretinoin in the control of skin and nasal colonization by antibiotic-resistant propionibacteria in patients with acne.

BACKGROUND: Skin colonization by antibiotic-resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy. OBJECTIVE: To assess the efficacy of oral isotretinoin in the control of antibiotic-resistant propionibacteria. METHODS: Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic-resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne-prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic-resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics. RESULTS: After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline-resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic-resistant strains from any site. Post-treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post-treatment at the two centres were similar but not identical. CONCLUSIONS: Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic-resistant propionibacteria. However, viable populations of resistant isolates persisted post-treatment at multiple sites. Novel methods are required to eradicate antibiotic-resistant propionibacteria completely, especially from the nasal reservoir.

Acne Vulgaris↗
PubMed2005

Anatomy of a patient safety event: a pediatric patient safety taxonomy.

BACKGROUND: Idiosyncratic terminology and frameworks in the study of patient safety have been tolerated but are increasingly problematic. Agreement on standard language and frameworks is needed for optimal improvement and dissemination of knowledge about patient safety. METHODS: Patient safety events were assessed using critical incident analysis, a method used to classify risks that has been more recently applied to medicine. Clinician interviews and clinician reports to a web based reporting system were used for analysis of hospital based and ambulatory care events, respectively. Events were classified independently by three investigators. RESULTS: A pediatric patient safety taxonomy, relevant to both hospital based and ambulatory pediatric care, was developed from the analysis of 122 hospital based and 144 ambulatory care events. It is composed of four main categories: (1) problem type; (2) domain of medicine; (3) contributing factors in the patient (child-specific), environment (latent conditions) and care providers (human factors); and (4) outcome or result of the event and level of harm. A classification of preventive mechanisms was also developed. Inter-rater reliability of classifications ranged from 72% to 86% for sub-categories of the taxonomy. CONCLUSIONS: This patient safety taxonomy reflects the nature of events that occur in both pediatric hospital based and ambulatory care settings. It is flexible in its construction, permits analysis to begin at any point, and depicts the relationships and interactions of elements of an event.

Ambulatory Care↗
PubMed2005

Communication failures in patient sign-out and suggestions for improvement: a critical incident analysis.

BACKGROUND: The transfer of care for hospitalized patients between inpatient physicians is routinely mediated through written and verbal communication or "sign-out". This study aims to describe how communication failures during this process can lead to patient harm. METHODS: In interviews employing critical incident technique, first year resident physicians (interns) described (1) any adverse events or near misses due to suboptimal preceding patient sign-out; (2) the worst event due to suboptimal sign-out in which they were involved; and (3) suggestions to improve sign-out. All data were analyzed and categorized using the constant comparative method with independent review by three researchers. RESULTS: Twenty six interns caring for 82 patients were interviewed after receiving sign-out from another intern. Twenty five discrete incidents, all the result of communication failures during the preceding patient sign-out, and 21 worst events were described. Inter-rater agreement for categorization was high (kappa 0.78-1.00). Omitted content (such as medications, active problems, pending tests) or failure-prone communication processes (such as lack of face-to-face discussion) emerged as major categories of failed communication. In nearly all cases these failures led to uncertainty during decisions on patient care. Uncertainty may result in inefficient or suboptimal care such as repeat or unnecessary tests. Interns desired thorough but relevant face-to-face verbal sign-outs that reviewed anticipated issues. They preferred legible, accurate, updated, written sign-out sheets that included standard patient content such as code status or active and anticipated medical problems. CONCLUSION: Communication failures during sign-out often lead to uncertainty in decisions on patient care. These may result in inefficient or suboptimal care leading to patient harm.

Chicago↗
PubMed2005

Expression of mesothelial markers in malignant mesotheliomas: an immunohistochemical evaluation of 173 cases.

OBJECTIVE: To see the distribution of Calretinin, thrombomodulin, CK5/6 and HBME-1 markers in various subtypes of mesotheliomas and extend the published data on this topic. The positivity of adenocarcinoma specific markers (CEA and BerEP4) in malignant mesotheliomas have also been evaluated. METHODS: Various markers in 173 cases of malignant mesotheliomas received over a period of 8 years were evaluated by immunohistochemistry. RESULTS: In majority of malignant mesotheliomas i.e., epithelioid and biphasic types, the positive staining patterns complement the gold standard histologic diagnosis. However, in a small minority mainly sarcomatoid variant, heavy reliance cannot be placed on these markers. CEA and BerEP4 are useful negative markers of mesotheliomas, although occasionally these are positive in clear cut mesotheliomas. CONCLUSIONS: Specificity of various markers in malignant mesotheliomas should be assessed according to histologic subtypes. The existing generation of markers is not reliable in diagnosis of sarcomatoid mesotheliomas. Fortunately this forms only a small group of mesothelial malignancy. In common epithelioid and biphasic variants calretinin, thrombomodulin, CK5/6, HBME-1 are sensitive positive markers whereas CEA and BerEP4 are negative markers of malignant mesotheliomas.

Antigens, Neoplasm↗
PubMed2004

The Opportunity Rover's Athena science investigation at Meridiani Planum, Mars.

The Mars Exploration Rover Opportunity has investigated the landing site in Eagle crater and the nearby plains within Meridiani Planum. The soils consist of fine-grained basaltic sand and a surface lag of hematite-rich spherules, spherule fragments, and other granules. Wind ripples are common. Underlying the thin soil layer, and exposed within small impact craters and troughs, are flat-lying sedimentary rocks. These rocks are finely laminated, are rich in sulfur, and contain abundant sulfate salts. Small-scale cross-lamination in some locations provides evidence for deposition in flowing liquid water. We interpret the rocks to be a mixture of chemical and siliciclastic sediments formed by episodic inundation by shallow surface water, followed by evaporation, exposure, and desiccation. Hematite-rich spherules are embedded in the rock and eroding from them. We interpret these spherules to be concretions formed by postdepositional diagenesis, again involving liquid water.

Atmosphere↗
PubMed2004

A dose-finding and pharmacokinetic study of the matrix metalloproteinase inhibitor MMI270 (previously termed CGS27023A) with 5-FU and folinic acid.

The orally bioavailable matrix metalloproteinase inhibitor MMI270 reduces tumour growth metastasis in preclinical models. We assessed the feasibility and pharmacokinetic interactions of combining MMI270 with 5-fluorouracil (5-FU) and folinic acid (FA). Entered into the study were 33 patients with advanced colorectal cancer. They received FA 200 mg/m2 over 2 h followed by 5-FU 400 mg/m2 over 15 min and 5-FU 600 mg/m2 over 22 h on days 1 and 2 of a 14-day cycle. MMI270 commenced with the second cycle at either 50 mg once daily, 150 mg three times daily or 300 mg twice daily. No dose-limiting toxicity was observed at any MMI270 dose level. Ten patients (61%) experienced joint symptoms independent of MMI270 dose, leading to interruption, modification, or discontinuation of treatment in seven patients (23%). MMI270 did not alter 5-FU pharmacokinetics. Six patients had a partial response and seven had stable disease. 5-FU/FA with MMI270 at a dose of 300 mg twice daily is well tolerated. MMI270 has no significant effect on 5-FU pharmacokinetics.

Administration, Oral↗
PubMed2004

SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies.

The authors recently have shown that triplication of the alpha-synuclein gene (SNCA) can cause Parkinson disease (PD) and diffuse Lewy body disease within the same kindred. The authors assessed 101 familial PD probands, 325 sporadic PD cases, 65 patients with dementia with Lewy bodies, and 366 neurologically normal control subjects for SNCA multiplication. The authors did not identify any subjects with multiplication of SNCA and conclude this mutation is a rare cause of disease.

Adult↗
PubMed2004

Localization and physical properties experiments conducted by Spirit at Gusev Crater.

The precise location and relative elevation of Spirit during its traverses from the Columbia Memorial station to Bonneville crater were determined with bundle-adjusted retrievals from rover wheel turns, suspension and tilt angles, and overlapping images. Physical properties experiments show a decrease of 0.2% per Mars solar day in solar cell output resulting from deposition of airborne dust, cohesive soil-like deposits in plains and hollows, bright and dark rock coatings, and relatively weak volcanic rocks of basaltic composition. Volcanic, impact, aeolian, and water-related processes produced the encountered landforms and materials.

Extraterrestrial Environment↗
PubMed2004

Wind-related processes detected by the Spirit Rover at Gusev Crater, Mars.

Wind-abraded rocks, ripples, drifts, and other deposits of windblown sediments are seen at the Columbia Memorial Station where the Spirit rover landed. Orientations of these features suggest formative winds from the north-northwest, consistent with predictions from atmospheric models of afternoon winds in Gusev Crater. Cuttings from the rover Rock Abrasion Tool are asymmetrically distributed toward the south-southeast, suggesting active winds from the north-northwest at the time (midday) of the abrasion operations. Characteristics of some rocks, such as a two-toned appearance, suggest that they were possibly buried and exhumed on the order of 5 to 60 centimeters by wind deflation, depending on location.

Evolution, Planetary↗