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Biomedical subjects

Peter Johnson

Publications and source records attributed to Peter Johnson.

At least 19 recordsLinked to original sources
PubMed2006

The relationship between threat appraisal and social constraints in cancer survivors and their spouses.

: Social constraints stem from unsupportive social environments and are associated with reluctance to discuss stressor-related thoughts and feelings. Support deterioration and erosion models provide a framework for explaining how a cancer patient's threat appraisal contributes to a spouse's inadvertent constraint on the patient's emotional expression. Also, based on social comparison theory and the convoy model, a discrepancy in threat appraisal between patient and spouse may create social constraints. Contrary to social cognitive processing theories, we hypothesized that threat appraisals may be an antecedent of social constraints, rather than a consequence. Cancer patients (n=75) and their spouses (n=75) completed questionnaires assessing cancer-related threat appraisals and perceived spousal social constraints at two time points. Cross-lagged panel design results suggested that patient appraisal precedes and predicts patients' perception of social constraints. However, patient and spouse appraisals did not significantly interact in predicting spousal constraints. Limitations and implications are discussed.

Adult↗
PubMed2006

The clinical outcome and toxicity of high-dose chemotherapy and autologous stem cell transplantation in patients with myeloma or amyloid and severe renal impairment: a British Society of Blood and Marrow Transplantation study.

The outcome of high-dose chemotherapy (HDT) was evaluated retrospectively in 27 patients with myeloma and four patients with AL amyloidosis with severe renal impairment. Twenty-three patients were receiving dialysis and the rest had a creatinine clearance of <20 ml/min. The median melphalan dose was 140 mg/m2 (range: 60-200 mg/m2), but 10 patients (37%) received 200 mg/m2. Myeloid and platelet engraftment were similar to that seen in patients without renal failure. Five of 27 patients died of transplant-related toxicity before the day 100. Twenty of 27 patients had a response (70%). The median time to disease progression was 32 months (range: 6-54 months) and the median time to best response was 6.5 months. Four of 17 evaluable patients (24%) became dialysis-independent at a median of 5 months post-HDT/stem cell transplantation. At a median follow-up of 70 months, 7/23 patients with myeloma were alive but three of these seven patients had progressive disease. Two of the four patients with amyloidosis have survived. HDT is feasible in these patients and results in 5-year survival in about one-third of patients.

Adult↗
PubMed2006

Eradication of common pathogens at days 2, 3 and 4 of moxifloxacin therapy in patients with acute bacterial sinusitis.

BACKGROUND: Acute bacterial sinusitis (ABS) is a common infection in clinical practice. Data on time to bacteriologic eradication after antimicrobial therapy are lacking for most agents, but are necessary in order to optimize therapy. This was a prospective, single-arm, open-label, multicenter study to determine the time to bacteriologic eradication in ABS patients (maxillary sinusitis) treated with moxifloxacin. METHODS: Adult patients with radiologically and clinically confirmed ABS received once-daily moxifloxacin 400 mg for 10 days. Middle meatus secretion sampling was performed using nasal endoscopy pre-therapy, and repeated on 3 consecutive days during treatment. Target enrollment was 30 bacteriologically evaluable patients (pre-therapy culture positive for Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and evaluable cultures for at least Day 2 and Day 3 during therapy visits), including at least 10 each with S. pneumoniae or H. influenzae. RESULTS: Of 192 patients enrolled, 42 were bacteriologically evaluable, with 48 pathogens isolated. Moxifloxacin was started on Day 1. Baseline bacteria were eradicated in 35/42 (83.3%) patients by day 2, 42/42 (100%) patients by day 3, and 41/42 (97.6%) patients by day 4. In terms of individual pathogens, 12/18 S. pneumoniae, 22/23 H. influenzae and 7/7 M. catarrhalis were eradicated by day 2 (total 41/48; 85.4%), and 18/18 S. pneumoniae and 23/23 H. influenzae were eradicated by day 3. On Day 4, S. pneumoniae was isolated from a patient who had negative cultures on Days 2 and 3. Thus, the Day 4 eradication rate was 47/48 (97.9%). Clinical success was achieved in 36/38 (94.7%) patients at the test of cure visit. CONCLUSION: In patients with ABS (maxillary sinusitis), moxifloxacin 400 mg once daily for 10 days resulted in eradication of baseline bacteria in 83.3% of patients by Day 2, 100% by Day 3 and 97.6% by Day 4.

Journal Article↗
PubMed2006

Erythrocyte and plasma protein modification in alcoholism: a possible role of acetaldehyde.

Analysis of the oxidative modification of plasma and erythrocyte ghost proteins of chronic alcoholic subjects and healthy non-alcoholics has been performed. It was found that increased levels of protein carbonyls in both plasma and erythrocyte ghosts from alcoholic subjects occurred in comparison to the levels found in preparations from non-alcoholics. Plasma proteins from alcoholic subjects did not show evidence of cross-linking, although plasma protein concentration and composition were changed. In alcoholic subjects who displayed no evidence of abnormal erythrocyte morphology no cross-linking of erythrocyte ghost proteins was detectable, whereas the ghosts obtained from alcoholic subjects who displayed morphologically abnormal erythrocytes contained cross-linked proteins. The in vitro treatment with acetaldehyde of erythrocytes from non-alcoholics caused increased levels of protein carbonyls and cross-linking products in erythrocyte ghost preparations which were similar to those found in severe alcoholics. It is concluded that chronic alcohol consumption can cause abnormal erythrocyte morphology and increased erythrocyte fragility as a result of oxidation and cross-linking of erythrocyte ghost proteins. These effects can be ascribed, in part, to exposure of erythrocytes to circulatory acetaldehyde which is a product of ethanol metabolism.

Acetaldehyde↗
PubMed2006

Phase I study of vinflunine administered as a 10-minute infusion on days 1 and 8 every 3 weeks.

Vinflunine is a novel vinca alkaloid developed through the selective modification of vinorelbine using super-acidic chemistry. In preclinical testing, vinflunine demonstrated significantly enhanced anti-tumour activity in human tumour xenograft models when compared to its parent compound. A phase I study was conducted to evaluate the safety and toxicity of vinflunine administered as a 10 minute intravenous infusion on days 1 and 8 every three weeks. Sixteen patients with advanced solid tumours were treated. Two of four patients experienced dose limiting toxicities (DLT) at 190 mg/m2 and this was established as the maximum tolerated dose (MTD). At the MTD, the DLT of vinflunine consisted of constipation and neutropenia. Fatigue was notable but not dose limiting. No objective responses were observed. A dose of 170 mg/m2 given on a day 1 and 8 schedule every three weeks would be suitable for future studies.

Adult↗
PubMed2006

Predicting erythroid response to recombinant erythropoietin plus granulocyte colony-stimulating factor therapy following a single subcutaneous bolus in patients with myelodysplasia.

We randomized 21 patients with low-risk myelodysplastic syndromes (MDS) to receive a single subcutaneous bolus of recombinant erythropoietin (epoietin) +/- granulocyte-colony stimulating factor (G-CSF), or placebo and monitored erythropoietic response over 7 days. In this small study, the reticulocyte response at day 7 was highly predictive of subsequent response to a therapeutic trial of epoietin + G-CSF.

Drug Administration Schedule↗
PubMed2005

Hypoxia-inducible factor 1 proteomics and diving adaptations in ringed seal.

The putative amino acid sequence of ringed seal (Phoca hispida) hypoxia-inducible factor 1alpha (HIF-1alpha) derived from DNA sequence analysis of the single-copy gene has been investigated. The rationale for these studies was to determine the reasons for the presence of HIF-1alpha at relatively high levels in seal tissues, and its possible role in protection against diving-related oxidative damage. Sequence analysis indicated that the bHLH/PAS and TAD functional domains are very similar to those in terrestrial mammals, although there were significant sequence differences between the mouse and seal proteins in a region of the ODD domain. Some of these results indicate that seal HIF-1alpha protein can bind HIF-Ibeta, DNA, transcriptional coactivators, and von Hippel-Lindau protein (pVHL). The presence of HIF-1alpha in seal tissues was not related to the absence of pVHL, which was found to be present in all seal tissues examined. It is concluded that seal HIF-1alpha may act as a transcriptional activator and that its presence in seal tissues is probably not caused by its inability to interact with pVHL. It is suggested that seal HIF-1 may serve two functions in the postdiving period, namely, to attenuate ischemia/reperfusion-induced oxidative stress and to allow efficient lung reinflation.

Amino Acid Sequence↗
PubMed2005

Emerging evidence for a similar role of glutamate receptors in the nervous and immune systems.

The role of glutamate receptors in synaptic transmission and excitotoxicity in the nervous system is well established. Recent evidence has emerged that glutamatergic mechanisms also exist in a wide variety of non-neuronal cells. In the case of thymocytes and lymphocytes, several types of glutamate receptor are expressed which can induce functional changes. This review focuses on the cellular function of NMDA-activated ionotropic and groups I and III metabotropic glutamate receptors in lymphocytes. Levels of exogenous and endogenous circulatory agonists and antagonists for lymphocyte glutamate receptors, notably homocysteine metabolites, are markedly increased in certain disease states and may be involved in disorders of the immune system. In addition to glutamate and aspartate, these compounds are active at glutamate receptors and increase the excitotoxic effects of glutamate in both neurons and lymphocytes. Increased levels of compounds acting at glutamate receptors may be risk factors for organ damage, for example in both heart and kidney disease. We conclude that glutamate is involved in signaling in immunocompetent cells and that the expression of both ionotropic and metabotropic glutamate receptors may have regulatory functions in immunocompetent cells, as well as in the nervous system. In addition, glutamate may serve as a signaling agent between the immune and nervous systems.

Animals↗
PubMed2004

Rodent lymphocytes express functionally active glutamate receptors.

RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate receptors are expressed in rodent lymphocytes. Flow cytometry showed that activation of iGluR NR1 by N-methyl-D-aspartate (NMDA) increased intracellular free calcium and reactive oxygen species (ROS) levels and activated caspase-3. The latter effect was attenuated by the NMDA antagonist, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), by the antioxidant N-acetylcysteine and by cyclosporin A. Treatment with L-2-amino-4-phosphonobutyric acid (L-AP4), an mGluR Group III agonist, increased lymphocyte ROS levels but to a lower extent than did NMDA. Activation of lymphocytes with both NMDA and L-AP4 caused a synergistic increase in ROS levels and induced necrotic cellular death without elevating the caspase-3 activation observed in the presence of NMDA alone. These results show that lymphocyte iGluR NR1 and mGluR Group III receptors may be involved in controlling rodent lymphocyte functions and longevity as they regulate events in cell proliferation, maturation, and death.

Aminobutyrates↗
PubMed2004

DNA vaccines to attack cancer.

Delivery of antigens by injection of the encoding DNA allows access to multiple antigen-presenting pathways. Knowledge of immunological processes can therefore be used to modify construct design to induce selected effector functions. Expression can be directed to specific intracellular sites, and additional genes can be fused or codelivered to amplify responses. Therapeutic vaccination against cancer adds a requirement to overcome tolerance and to activate a weakened immune repertoire. Induction of CD4(+) T helper cells is critical for both antibody and T cell effector responses. To activate immunity against tumor antigens, we fused the tumor-derived sequences to genes encoding microbial proteins. This strategy engages T helper cells from the large antimicrobial repertoire for linked help for inducing antibody against cell-surface tumor antigens. The principle of linked T cell help also holds for induction of epitope-specific antitumor CD8(+) T cells, but the microbial sequence has to be minimized to avoid competition with tumor antigens. Epitope-specific DNA vaccination leads to powerful antitumor attack and can activate immunity from a profoundly tolerized repertoire. Vaccine designs validated in preclinical models are now in clinical trial with immune responses detected against both tumor antigens and fused microbial antigens. DNA priming is highly efficient, but boosting may benefit from increased antigen expression. Physical methods including electroporation provide increased expression without introducing additional competing antigens. A wide range of cancers can be targeted, and objective assays of response will determine efficacy.

Animals↗
PubMed2004

C/EBPalpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo.

CCAAT enhancer binding protein-alpha (C/EBPalpha) inhibits proliferation in multiple cell types; therefore, we evaluated whether C/EBPalpha-deficient hematopoietic progenitor cells (HPCs) have an increased proliferative potential in vitro and in vivo. In this study we demonstrate that C/EBPalpha(-/-) fetal liver (FL) progenitors are hyperproliferative, show decreased differentiation potential, and show increased self-renewal capacity in response to hematopoietic growth factors (HGFs). There are fewer committed bipotential progenitors in C/EBPalpha(-/-) FL, whereas multipotential progenitors are unaffected. HGF-dependent progenitor cell lines can be derived by directly culturing C/EBPalpha(-/-) FL cells in vitro Hyperproliferative spleen colonies and myelodysplastic syndrome (MDS) are observed in mice reconstituted with C/EBPalpha(-/-) FL cells, indicating progenitor hyperproliferation in vitro and in vivo. C/EBPalpha(-/-) FL lacked macrophage progenitors in vitro and had impaired ability to generate macrophages in vivo. These findings show that C/EBPalpha deficiency results in hyperproliferation of HPCs and a block in the ability of multipotential progenitors to differentiate into bipotential granulocyte/macrophage progenitors and their progeny.

Animals↗
PubMed2004

Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation.

BACKGROUND: Dysregulated fibroblast proliferation is thought to play an important role in the progression of bronchiolitis obliterans (BO) after lung transplantation. Augmented immunosuppression is often used to treat BO. We investigated the effect of methylprednisolone (mPRED), cyclosporine A (CsA), tacrolimus (FK506), azathioprine (AZA), mycophenolate mofetil (MMF), and everolimus (rapamycin derivative [RAD]) on the proliferative capacity of fibroblasts cultured from transbronchial biopsies of lung transplant recipients. METHODS: Primary cultures of human lung fibroblasts were obtained from 14 transbronchial biopsies of lung transplant recipients. Subconfluent cells were serum starved for 24 hr followed by growth stimulation in the presence or absence of the respective drug in six concentrations ranging as follows: 0.01 to 100 mg/L for mPRED; 0.01 to 50 mg/L for CsA and AZA; 0.001 to 5 mg/L for FK506 and MMF; and 0.00001 to 1 mg/L for RAD. Proliferation was quantified by [3H]thymidine incorporation and direct cell count. A toxic drug effect was excluded by trypan blue. RESULTS: Drug concentrations (mg/L) causing a 50% inhibition of fibroblast proliferation were mPRED 4; CsA 20; FK506 0.3; AZA 7; MMF 0.3; and RAD 0.0006. Drug concentrations (mg/L) causing inhibition of fetal bovine serum-induced proliferation were mPRED 60; CsA 45; FK506 3; AZA 35; MMF 1; and RAD 0.003. CONCLUSIONS: RAD and MMF were the most potent antifibroproliferative drugs and were effective at concentrations achieved clinically, supporting their use for the treatment of patients with early BO. Our method holds promise as an in vitro model to assess the likely in vivo responses of human lung fibroblasts to specific immunosuppressive drugs.

Adult↗
PubMed2004

Efficacy and tolerability of moxifloxacin in the treatment of acute bacterial sinusitis caused by penicillin-resistant Streptococcus pneumoniae: a pooled analysis.

BACKGROUND: Penicillin-resistant Streptococcus pneumoniae (PRSP) has become a relatively common pathogen in upper and lower respiratory tract infections, including acute bacterial sinusitis (ABS). OBJECTIVE: The goal of this analysis was to assess the efficacy and tolerability of moxifloxacin in the treatment of ABS caused by penicillin-sensitive S pneumoniae (PSSP) and PRSP METHODS: Two prospective, multicenter, open-label, noncomparative US trials of moxifloxacin were included in this pooled analysis. All patients received oral moxifloxacin 400 mg once daily for 7 to 10 days. Minimum inhibitory concentrations (MICs) of moxifloxacin and penicillin were determined using the E-test and standard broth-microdilution methods. The primary end point was clinical success at the test-of-cure visit (21-37 days after completion of therapy) in patients with a positive pretherapy sinus culture. Data are presented for patients with ABS caused by both PSSP and PRSP RESULTS: Of 806 patients enrolled in the 2 studies, 146 had microbiologically confirmed bacterial infection. Sixty-nine patients had ABS caused by S pneumoniae, including 15 confirmed cases of PRSP infection. The majority of the 69 clinically evaluable patients were white (n = 63) and female (n = 46), and the mean age of this population was 43 years. Investigators categorized the episode of ABS as severe in 26 (37.7%) of clinically evaluable patients and of moderate severity in the remainder (62.3% [43]); however, most patients (78.3% [54/69]) reported >/=1 severe symptom. The episode of ABS was classified as severe in 8 (53.3%) of the 15 patients with PRSP infection. Clinical and bacteriologic success at the test-of-cure visit was achieved in 93.3% (14/15) of patients with PRSP infection, compared with 88.4% (61/69) of all patients infected with S pneumoniae regardless of penicillin susceptibility. Moxifloxacin MICs against the 15 PRSP strains ranged from 0.06 to 0.25 microg/mL. Data from 805 patients were available for tolerability analysis. The most commonly occurring adverse events were nausea, headache, and diarrhea. Generally, adverse events were mild to moderate. None of the 6 serious adverse events reported were considered related to moxifloxacin therapy. CONCLUSION: In this small cohort of patients, moxifloxacin provided clinical and bacteriologic cures in the majority of patients with ABS caused by PRSP, including those with severe sinusitis.

Acute Disease↗
PubMed2004

Written emotional disclosure buffers the effects of social constraints on distress among cancer patients.

The aims of the present study were to examine whether written emotional disclosure would reduce distress among cancer patients and whether it would buffer the effects of high levels of social constraint (negative social responses to patients' expressions of emotion regarding their cancer) on distress. Cancer patients (N=104) were randomly assigned to write about their emotions regarding their cancer 20 min a day for 3 days or to write about a nonemotional topic. They completed questionnaires at baseline and 6 months postintervention. Results showed that written disclosure buffered the effects of social constraints on stress at the 6-month follow-up and that avoidance partly mediated these effects. The present data reinforce the notion that interventions should be tailored to patients' needs.

Adaptation, Psychological↗
PubMed2004

Hypoxia-Inducible Factor in ringed seal (Phoca hispida) tissues.

Tissue hypoxia and ischemia-reperfusion pose a dangerous situation for oxidative stress. However, diving mammals and birds show pronounced resistance to oxidative injury under such conditions, which are a consequence of selective vasoconstriction during a dive. As the function of Hypoxia-Inducible Factor-1alpha (HIF-1alpha) in protection against and adaptation to hypoxia has been recognized in terrestrial animals, we have investigated the genomics and expression of this protein in ringed seal (Phoca hispida) in order to determine if it may play a protective role in this diving mammal. PCR studies using primers based on sequences from mouse HIF-1alpha exons 3, 4, 5, 6, 9, 10, 11, 12 and 15 showed that DNA from seal lung generated PCR products similar to those from mouse DNA. These studies have established that a putative HIF-1alpha gene exists in the seal genome that appears to have a similar but not identical sequence to the mouse gene. Seal lung and skeletal muscle tissues showed the highest relative levels of HIF-1alpha protein expression, with heart muscle showing significantly lower levels, and levels of HIF-1beta protein expression paralleled this situation. Analysis of oxidized cellular protein levels indicated that seal lung and heart muscle had the lowest levels of oxidized proteins. Thus, as seal lung tissue had the highest level of HIF-1alpha protein expression and the second lowest level of protein oxidation, this suggests that HIF-1alpha expression may have an important protective effect in this tissue in diving mammals. Our results support the hypothesis that HIF-1alpha expression is dependent on both tissue-specific energy requirements and adequate metabolic supply-to-demand ratio. Combined, the evidence available suggests that diving mammals have an overall anticipatory response to avoid the ill effects of dive-associated ischemia-reperfusion which may involve the HIF-1 system.

Animals↗
PubMed2004

Nurse midwifery.

Explore the source record for details and available documents.

Career Choice↗
PubMed2003

General utilities of multislice tomography in the cardiac field.

OBJECTS: To show all cardiac evaluations multislice computed tomography (MSCT) can perform. METHODS: MSCTs were performed on an MSCT scanner (Mx8000; Philips Medical Systems) with enhanced contrast acquisition. The reconstructed images were sent to a workstation for multiplanar reconstruction, volume rendering, and 3-D reconstruction. A total of 140 patients were studied with MSCT and conventional angiography (CA) to assess coronary artery stenosis. 30 of these patients were also evaluated by intravascular ultrasound (IVUS) for plaque characterization. A group of 20 patients were studied with MSCT, gated single-photon emission computed tomography (SPECT), and echocardiography for myocardial perfusion test and volumetric analysis. RESULTS: The results of MSCT versus CA showed a sensitivity of 79.2% and a specificity of 93.7%, whereas for MSCT versus IVUS the sensitivity was 84.4% and the specificity 91.6%. A total of 156 plaques were detected by both methods. 105 (67%) were soft, 14 (24%) were fibrous and 37 (9%) were calcified. In the evaluation of myocardial perfusion, the cardiac software showed a sensitivity of 55% and a specificity of 80%. However, general evaluation disclosed a sensitivity of 88.5% and a specificity of 96.4%. The volumetric analysis showed a good correlation between MSCT and echocardiography for end-systolic volume (ESV), rS = 0.874, and end-diastolic volume (EDV), rS = 0.828. There was also a good correlation for the evaluation of the left ventricular anatomy: septal wall rS = 0.96, posterior wall rS = 0.81, and diameter of left ventricle rS = 0.69. CONCLUSION: Nowadays, MSCT allows different cardiologic evaluations with the same acquisition as that for the coronary arteries. These data show a general view of the patient providing information that is obtained by the hand of multiple cardiologic methods such as DA, IVUS, gated SPECT, and echocardiography.

Angina Pectoris↗