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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Multiple organ dysfunction syndrome: a narrative review.

PURPOSE: To review multiple organ dysfunction syndrome with respect to: 1) clinical measurement systems; 2) molecular mechanisms; and 3) therapeutic directions based upon molecular mechanisms. METHODS: The Medline, Cochrane, and Best Evidence databases (1996 to 2000), conference proceedings, bibliographies of review articles were searched for relevant articles. Key index words were multiple organ failure, multiple system organ dysfunction, sepsis, septic shock, shock, systemic inflammatory response syndrome. Outcomes prospectively defined were death and physiological reversal of end organ failure. RESULTS: Multiple organ dysfunction/failure (MODS) is the most common cause for death in intensive care units. The recognition of this syndrome in the last 30 yr may be due to advances in early resuscitation unmasking these delayed sequelae in those that would have died previously. Multiple organ dysfunction occurs after shock of varied etiologies and may be the result of unbridled systemic inflammation. As yet, therapy directed to prevent or improve MODS has not dramatically altered outcomes. CONCLUSION: Multiple organ dysfunction may serve as useful measure of disease severity for risk adjustment and outcome marker for quality of care and therapy provided. Anesthesiologists treating shock patients will note the subsequent development of MODS in the critical care unit and may be required to provide anesthetic support to these patients.

Humans↗
PubMed2001

Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung cancer.

BACKGROUND: Neoadjuvant chemotherapy before resection is the standard of care for stage IIIA non-small cell lung cancer in many institutions. Further, neoadjuvant therapy is being studied in earlier stage lung cancer and may be applied more broadly in the future. There is little information about the effect of preoperative chemotherapy on the perioperative complications and mortality after lung resection. METHODS: All patients undergoing anatomic resection after neoadjuvant chemotherapy by a single surgeon at a single institution were compared with patients undergoing similar resections without preoperative chemotherapy. Complications were analyzed as life-threatening (pneumonia, emergency surgery, transfer to the intensive care unit, or intubation), major (prolonging hospital stay but not necessarily dangerous), and minor. The incidence of life-threatening complications, major complications, reintubation, tracheostomy, and mortality were analyzed to determine whether neoadjuvant chemotherapy might have an effect on these complications. Mortality was defined as hospital mortality. Two-tailed Student's t test was used to analyze differences in means and chi2 to determine differences in proportions. Differences less than 0.05 were considered significant. RESULTS: Thirty-four patients underwent resection after neoadjuvant chemotherapy, and 67 patients underwent resection without preoperative therapy. No differences between the two groups in age, pulmonary function, or comorbid diseases were found. The patients receiving chemotherapy did have a more advanced stage (2.52 versus 1.55, p < 0.0001). Striking increases were found in incidence of life-threatening complications (6.0% versus 26.5%, p = 0.0036), major complications (19.4% versus 47.1%, p = 0.0037), reintubation (3.0% versus 17.6%, p = 0.0093), and tracheostomy (0% versus 11.8%, p = 0.0042) in those patients who received preoperative chemotherapy. There was no hospital mortality. However, 2 (neoadjuvant) patients died within 90 days after discharge from the hospital of pneumonia and pulmonary embolus. This difference was also significant (0% versus 5.89%, p = 0.045). CONCLUSIONS: Neoadjuvant carboplatin and Taxol increased the perioperative life-threatening complications in this cohort of patients compared with a similar cohort undergoing operations by the same surgeon in the same institution. The most common life-threatening complication in patients receiving induction chemotherapy was the failure to respond to antibiotics given for pneumonia. Strategies to prevent these complications will be important, especially if chemotherapy before resection becomes the standard for earlier stages of non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Cloning and characterization of Rhesus monkey neuropeptide Y receptor subtypes.

Neuropeptide Y (NPY) is a 36 amino acid peptide that is abundant in the brain and peripheral nervous system. NPY has a variety of effects when administered into the brain including a pronounced feeding effect, anxiolysis, regulation of neuroendocrine axes and inhibition of neurotransmitter release. These effects are mediated by up to 6 G protein coupled receptors designated Y1, Y2, Y3, Y4, Y5 and y6. To better understand the phylogeny and pharmacology of NPY in non-human primates, we have cloned and expressed the NPY Y1, Y2 and Y5 receptor subtypes from the Rhesus monkey. No cDNA sequence encoding a Y4 receptor was found suggesting substantial sequence differences when compared to the human sequence. Comparison of these sequences with those from human indicated strong sequence conservation of Y1, Y2 and Y5 between the two species. The displacement of (125)I-PYY binding to the Rhesus monkey and human receptors by various peptides was compared to evaluate the pharmacology of the two species. Similar pharmacologies were noted across the species at the various receptor subtypes. These results indicate the Rhesus monkey and human NPY receptor subtypes have a close amino acid sequence conservation and that the peptide recognition domains are conserved as well.

Amino Acid Sequence↗
PubMed2001

Contrast-enhanced power Doppler imaging of normal and decreased blood flow in canine prostates.

The purpose of this study was to investigate if Sonazoid, a new ultrasound (US) contrast agent, can improve the delineation of areas with normal and decreased blood flow in the prostate. Sonazoid was administered in the dose range of 0.00625-0.0375 microL microbubbles/kg into five anaesthetised mongrel adult male dogs. Transrectal power Doppler imaging of the prostate was performed in 2-D and 3-D with a C9-5 end-fire probe, using an HDI 3000 scanner. An area of decreased blood flow was created by inducing tissue ablation with a CL60 laser system, to mimic an avascular lesion. A subjective assessment of the intraprostatic vessels and the prostate vascular architecture was performed, with and without Sonazoid, before and after inducing the abnormal site. Visibility of the prostate blood flow improved following Sonazoid injection (p < 0.001). A symmetric, radial vascular pattern was identified in the normal prostate prior to tissue ablation, but only on the enhanced images. After tissue ablation, a disturbance of the normal vascular pattern and identification of areas with lack of blood flow was possible, following Sonazoid injection. Furthermore, the location and size of these areas were verified in all dogs by gross histology examination. Sonazoid enhances the visibility of the prostate vascular architecture and improves, thereby the delineation of areas with normal and decreased blood flow.

Animals↗
PubMed2001

Tissue distribution and measurement of cartilage oligomeric matrix protein in patients with magnetic resonance imaging-detected bone bruises after acute anterior cruciate ligament tears.

Histologic and immunostaining analyses were performed on articular cartilage/subchondral bone biopsy specimens overlying MRI-detected bone bruises in 12 patients with anterior cruciate ligament (ACL) tears. Staining with toluidine blue for proteoglycan revealed loss of staining from the superficial portion of the articular cartilage. Immunostaining for cartilage oligomeric matrix protein (COMP) showed an increased staining in the superficial matrix of the articular cartilage. Using polyclonal antisera against COMP, the authors performed a competitive enzyme-linked immunosorbent assay (ELISA) on the synovial fluid from the injured and uninjured knees. There was an approximately 10-fold higher synovial fluid COMP levels in injured knees. The COMP levels were greater in those patients who had synovial fluid samples harvested closer to the date of initial injury. Western blot analysis of the synovial fluid showed an increased presence of COMP degradation fragments from injured knees. These results are indicative of a significant injury to the articular cartilage, and may represent preclinical posttraumatic osteoarthritic lesions.

Adolescent↗
PubMed2001

The week, inherited in neonatal human twins, found also in geomagnetic pulsations in isolated Antarctica.

About 7-day (circaseptan) components, found at different levels of organization, notably in relation to growth, regeneration, repair and development, are often viewed as reflecting no more than the 7-day societal schedule, ample evidence for a built-in feature notwithstanding. Herein, we resolve circaseptans in geomagnetic pulsations recorded by a stand-alone magnetometer residing in Antarctica, far away from societal influences. Human physiological data, collected in the neonatal intensive care unit, show by intra-class correlation analysis that the nonlinearly assessed circaseptan period of heart rate, diastolic blood pressure and body weight is more similar between same-gender twins than among twin pairs, lending additional support for the endogenicity of circaseptans. Like circadians, about-weekly features in environmental variables such as geomagnetic pulsations were genetically acquired in the course of evolution.

Activity Cycles↗
PubMed2001

Panel-based pain management in primary care. a pilot study.

Although pain is an extremely common symptom presenting to primary care physicians, it frequently is not optimally managed. The purpose of this feasibility study was to develop and pilot-test an efficient, rapid assessment and management approach for pain in busy community practices. The intervention utilized the Dartmouth COOP Clinical Improvement System (DCCIS) and a telephone-based, nurse-educator intervention. Patients from four primary care practices in rural New Hampshire and Vermont were screened by mail for the presence of persistent pain. Patients with mild to severe pain were randomized to either the usual care control group (n = 383) or the intervention group (n = 320). Patients who reported pain but no psychosocial problems received a summary of identified problems and targeted educational material via mail (DCCIS). Patients who reported pain and psychosocial problems received the DCCIS intervention and calls from a nurse-educator who provided pain self-management strategies and a problem-solving approach for psychosocial problems. Post-treatment evaluation revealed that patients in the intervention group scored significantly better on the Pain, Physical, Emotional, and Social subscales of the SF-36 and on the total score of the Functional Interference Scale, as compared to a usual care control group. Feasibility and acceptability of the approach were demonstrated; however, the conclusions based on analyses of the post-treatment outcomes were tempered by baseline imbalances across groups.

Feasibility Studies↗
PubMed2001

Characterisation of the long terminal repeat regions of South African human immunodeficiency virus type 1 isolates.

The 5' long terminal repeat (LTR) region of the integrated proviral human immunodeficiency virus type I (HIV-1) template encodes cis-acting sequences for cellular proteins that are responsible for initiating viral transcription. The objective of this study was to analyse the LTR regions of isolates from a broad spectrum of South African HIV-1 infected individuals to (i) determine if sequence diversity was sufficient to allow for subtyping on the basis of this region, and (ii) to note any specific or unusual alterations in promoter binding motifs that may be common to this group of isolates or specific HIV-1 subtypes within this group. A total of 60 isolates were subtyped by heteroduplex mobility assay (HMA) and by phylogenetic analysis, using both the env and gag regions. Phylogenetic relatedness within the LTR region demonstrated the suitability of this region for use in HIV-1 subtype designation. The presence of additional NF-kappaB binding elements as well as altered USF binding sites were features common to subtype C HIV-1 isolates. Although the biological relevance of these alterations within the HIV-1 LTR with respect to viral replicative capacity and patient disease progression is unknown, there is strong support to suggest that in the presence of these features, there is increased gene transcription in subtype C isolates, and that this would be further increased in the presence of secondary infection.

Base Sequence↗
PubMed2001

Distribution of the human immunodeficiency virus coreceptors CXCR4 and CCR5 on leukocytes of persons with human immunodeficiency virus type 1 infection and pulmonary tuberculosis: implications for pathogenesis.

Expression of CXCR4 was significantly reduced from normal on all cell subsets of persons with pulmonary tuberculosis (TB group), with HIV-1 infection (HIV group), and those with both infections (HIV/TB group), except for on monocytes in the HIV group. The reductions were most notable in the two TB groups. Interestingly, the duration of antituberculosis treatment was significantly negatively correlated with the expression of CXCR4 on CD4+ and CD8+CD45RO+ cells, monocytes and NK cells, viral load, and proportions of CD38-expressing CD8+ lymphocytes, in HIV/TB patients. By contrast, CCR5 expression on most cell subsets analyzed was increased in all the disease groups, except for on monocytes in the two TB groups. There was no change in CCR5 expression on CD4+ cells when based on the disease groupings. However, higher proportions of CD4+CD45RA+ and CD8+ lymphocytes as well as B cells expressing CCR5 correlated with advancing HIV-1 disease, as did decreased proportions of CXCR4-expressing CD4+CD45RA+ cells.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy.

Replicating adenoviruses may prove to be effective anticancer agents if they can be engineered to selectively destroy tumor cells. We have constructed a virus (01/PEME) containing a novel regulatory circuit in which p53-dependent expression of an antagonist of the E2F transcription factor inhibits viral replication in normal cells. In tumor cells, however, the combination of p53 pathway defects and deregulated E2F allows replication of 01/PEME at near wild-type levels. The re-engineered virus also showed significantly enhanced efficacy compared with extensively studied E1b-deleted viruses such as dl1520 in human xenograft tumor models.

Adenoviridae↗
PubMed2001

Are keloids really "gli-loids"?: High-level expression of gli-1 oncogene in keloids.

BACKGROUND: Keloids are a common lesion arising from sites of previous trauma and are a considerable source of morbidity because of continued growth of lesions, pruritus, and physical appearance. They consist of mesenchymal cells embedded in a stroma of disordered collagen matrix. Clinically, keloids are distinguished from scars in that keloids demonstrate continued growth over the borders of the original injury. Keloids appear with increased frequency in patients of African and Asian descent. Currently, no entirely satisfactory method of treatment exists for these lesions. Recently, a patient who was enrolled in a clinical trial of topical tacrolimus for atopic dermatitis applied this drug to a keloid and noted clearing. OBJECTIVE: Based on this clinical observation and the observation that rapamycin, a chemically similar compound to tacrolimus, is known to inhibit signaling from the gli-1 oncogene, we examined keloids and scars for expression of Gli-1 protein. METHODS: Skin sections from keloids and scars were examined by immunohistochemical staining for gli-1. To further confirm the presence of gli-1 expression in keloids, reverse transcriptase-polymerase chain reaction was carried out. RESULTS: Expression of gli-1 was strongly elevated in keloids compared with scars. CONCLUSION: These results provide a rationale for the treatment of keloids with topical rapamycin analogs, including tacrolimus. Clinical trials of topical tacrolimus are warranted.

DNA↗
PubMed2001

Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160).

OBJECTIVE: The rate of complete resection (50%) and the 5-year survival (30%) for non-small cell lung carcinomas of the superior sulcus have not changed for 40 years. Recently, combined modality therapy has improved outcome in other subsets of locally advanced non-small cell lung carcinoma. This trial tested the feasibility of induction chemoradiation and surgical resection in non-small cell lung carcinoma of the superior sulcus with the ultimate aim of improving resectability and survival. METHODS: Patients with mediastinoscopy-negative T3-4 N0-1 superior sulcus non-small cell lung carcinoma received 2 cycles of cisplatin and etoposide chemotherapy concurrent with 45 Gy of radiation. Patients with stable or responding disease underwent thoracotomy 3 to 5 weeks later. All patients received 2 more cycles of chemotherapy and were followed up by serial radiographs and scans. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed for significance by Cox regression analysis. RESULTS: From April 1995 to September 1999, 111 eligible patients (77 men, 34 women) were entered in the study, including 80 (72.1%) with T3 and 31 with T4 tumors. Induction therapy was completed as planned in 102 (92%) patients. There were 3 treatment-related deaths (2.7%). Cytopenia was the main grade 3 to 4 toxicity. Of 95 patients eligible for surgery, 83 underwent thoracotomy, 2 (2.4%) died postoperatively, and 76 (92%) had a complete resection. Fifty-four (65%) thoracotomy specimens showed either a pathologic complete response or minimal microscopic disease. The 2-year survival was 55% for all eligible patients and 70% for patients who had a complete resection. To date, survival is not significantly influenced by patient sex, T status, or pathologic response. CONCLUSIONS: (1) This combined modality treatment is feasible in a multi-institutional setting; (2) the pathologic complete response rates were high; and (3) resectability and overall survival were improved compared with historical experience, especially for T4 tumors, which usually have a grim prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Cardiac surgery increases the activity of matrix metalloproteinases and nitric oxide synthase in human hearts.

OBJECTIVES: Heart function is variably impaired after cardiopulmonary bypass. We hypothesized that, similar to other myocardial injury states, cardiopulmonary bypass leads to enhanced activity of nitric oxide synthase and matrix metalloproteinases. METHODS: We obtained right atrial biopsy specimens and plasma samples at the onset and termination of cardiopulmonary bypass in 10 patients. Biopsy specimens were analyzed for nitric oxide synthase activity by using a citrulline assay, whereas plasma and tissue were analyzed for matrix metalloproteinase-9 and matrix metalloproteinase-2 activity by using zymography. Tissue inhibitor of metalloproteinase-4 was analyzed by means of Western blotting. The cellular expression of inducible nitric oxide, endothelial nitric oxide synthase, matrix metalloproteinase-2, and matrix metalloproteinase-9 was determined in right atrial biopsy samples from 3 additional patients by using the appropriate conjugated antibodies. RESULTS: Nitric oxide synthase activity increased from the beginning to the end of bypass (4.46 +/- 1.07 vs 16.77 +/- 4.86 pmol citrulline/mg of protein per minute, respectively; P =.018). Pro-matrix metalloproteinase-9 activity increased in hearts (199 +/- 41 vs 660 +/- 177 density units/mg protein; P =.008) and plasma (14.1 +/- 4.6 vs 52.2 +/- 5.9 density units/mg protein; P =.008). Pro-matrix metalloproteinase-2 activity increased in the heart (201 +/- 23 vs 310 +/- 35 density units/mg protein, P <.05) but not in plasma. Tissue inhibitor of metalloproteinase-4 expression in the heart decreased (1574 +/- 280 vs 864 +/- 153 density units, P =.014). CONCLUSIONS: Cardiopulmonary bypass activates enzymes mediating acute inflammation and organ injury (ie, nitric oxide synthase, matrix metalloproteinase-9, and matrix metalloproteinase-2). Decreased tissue inhibitor of metalloproteinase-4 expression allows relatively unopposed increases in matrix metalloproteinase tissue activity. We postulate that these changes play a role in the pathogenesis of heart dysfunction after bypass surgery.

Aged↗
PubMed2001

Increased prostatic lysophosphatidylcholine acyltransferase activity in human prostate cancer: a marker for malignancy.

PURPOSE: Phospholipase A2 and lysophosphatidylcholine acyltransferase (LAT) constitute a deacylation-reacylation cycle that incorporates arachidonic acid into the lipid membrane. In a preliminary report we found increased LAT activity in malignant prostate tissue. We measured LAT activity in prostate tissue from a large number of patients undergoing prostatectomy. MATERIALS AND METHODS: Prostate tissue from 93 patients undergoing radical prostatectomy for prostate carcinoma, 14 undergoing cystoprostatectomy for bladder cancer, 55 undergoing transurethral resection for benign prostatic hyperplasia and 11 with prostate cancer undergoing transurethral resection for relief of obstructive symptoms was analyzed for LAT activity. RESULTS: In radical prostatectomy specimens using oleoyl coenzyme A as substrate mean increase in LAT activity between malignant and benign portions of the same specimen was 0.68 +/- 0.12 nmol./mg. protein per minute (p <0.00001). In all radical prostatectomy specimens analyzed LAT activity was 43% higher in the malignant than benign portions (2.25 +/- 0.15 versus 1.57 +/- 0.11 nmol./mg. protein per minute, p <0.001). In the 10 benign prostate specimens obtained from cystoprostatectomy mean LAT activity was 1.12 +/- 0.18 nmol./mg. protein per minute, which was significantly lower than that of benign portions of radical prostatectomy (p <0.05). LAT activity in benign cystoprostatectomy specimens was significantly higher than that in the 50 benign transurethral resection specimens (0.54 +/- 0.05, p <0.01), possibly due to heat damage in transurethral resection specimens during collection. However, LAT activity in transurethral resection specimens from patients with known prostate cancer was similarly increased. Similar results were obtained using arachidonoyl coenzyme A. CONCLUSIONS: We demonstrated increased LAT activity in malignant tissue from patients with prostate cancer. Thus, the deacylation-acylation remodeling cycle may be enhanced to provide more arachidonic acid to meet the demand for prostaglandin E2 synthesis in malignant tissue.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed2001

Baclofen overdose in two siblings.

Baclofen is a muscle relaxant used in both adults and children with neuromuscular disorders to control spasticity. In children, relatively few cases of overdose have been previously reported. We report two cases of baclofen overdose occurring in two siblings. One sibling with cerebral palsy was being treated with baclofen at the time of overdose. Both cases presented with severe respiratory depression requiring mechanical ventilation. Serum baclofen concentrations from both children were significantly elevated. We also review the published literature on baclofen overdose in children and adolescents. These cases emphasize the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member.

Baclofen↗