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Thomas Johnson

Publications and source records attributed to Thomas Johnson.

At least 19 recordsLinked to original sources
PubMed2006

Management of stinging insect hypersensitivity: a 5-year retrospective medical record review.

BACKGROUND: The Joint Task Force on Practice Parameters for Allergy and Immunology recommends that patients with a history of a systemic reaction to an insect sting be educated on ways to avoid insect stings, carry injectable epinephrine for emergency self-treatment, undergo specific IgE testing for stinging insect sensitivity, and be considered for immunotherapy. OBJECTIVE: To review frontline providers' documented care and recommendations for imported fire ant and flying insect hypersensitivity reactions. METHODS: A retrospective medical record review was performed of emergency department and primary care clinic visits between November 1, 1999, and November 30, 2004. Using International Classification of Diseases, Ninth Revision, codes, medical records were selected for review to identify patients with potential insect hypersensitivity. RESULTS: A total of 769 medical records from patients who experienced an insect sting were reviewed. Of 120 patients with a systemic reaction, 66 (55.0%) received a prescription for injectable epinephrine, and 14 (11.7%) were given information regarding avoidance of the offending insect. Forty-seven patients with systemic reactions (39.2%) were referred to an allergist. Of 28 patients who kept their appointments and underwent skin testing, 3 had negative results and 25 (89%) had positive results and were advised to start immunotherapy. CONCLUSION: Adherence to the stinging insect hypersensitivity practice parameter recommendations is poor. Many patients who have experienced a systemic reaction after an insect sting and have sought medical care are not afforded an opportunity for potentially lifesaving therapy.

Adolescent↗
PubMed2006

Genomewide scan and fine mapping of quantitative trait loci for intraocular pressure on 5q and 14q in West Africans.

PURPOSE: High intraocular pressure (IOP) is a major risk factor for glaucoma, one of the leading causes of blindness worldwide. Because it has been demonstrated that African populations are at increased risk for glaucoma, the authors investigated the genetic basis of IOP in a sample of West Africans with type 2 diabetes (T2D) from Ghana and Nigeria. METHODS: Genomewide linkage analysis was conducted for loci linked to IOP (measured by applanation tonometry) in 244 affected sibling pairs with T2D using 372 autosomal short-tandem repeat markers at an average spacing of 9 cM. RESULTS: Multipoint variance components linkage analyses revealed suggestive linkage on chromosome 5 (5q22) with a logarithm of odds (LOD) score of 2.50 (nominal P = 0.0003; empiric P = 0.0004) and on chromosome 14 (14q22) with an LOD score of 2.95 (nominal P = 0.0001; empiric P = 0.0003). Fine mapping at a marker density of 2 cM in the 5q region confirmed the linkage signal, with an increase in peak LOD score to 4.91. CONCLUSIONS: The strong signal on chromosome 5 lies in the region in which a novel gene, WDR36, in the GLC1G locus was recently identified as causative for adult-onset primary open-angle glaucoma and provides additional evidence that chromosome 5 contains susceptibility loci for glaucoma in multiple human populations. The evidence provided in this study is particularly important given the evolutionary history of these West African populations and the recent ancestral relationship to African Americans-a population with one of the highest rates of diabetes and associated complications (including glaucoma) in the world.

Chromosome Mapping↗
PubMed2006

Prognostic outcomes after the initiation of an electronic telemedicine intensive care unit (eICU) in a rural health system.

APACHE (Acute Physiology and Chronic Health Evaluation) mortality predictions and other outcomes are reported after the initiation of a telemedicine intensivist staffing program to monitor the intensive care unit patients of a rural health system. Mortality, length of ICU stay, and length of hospital stay were significantly less than predicted. Length of stay was identical to one year previously in the largest hospital reported, but the case mix index of severity had increased. More severely ill patients were being treated without increase in length of stay.

APACHE↗
PubMed2005

Cellular transfection to deliver alanine-glyoxylate aminotransferase to hepatocytes: a rational gene therapy for primary hyperoxaluria-1 (PH-1).

BACKGROUND: Primary hyperoxaluria-type 1 (PH-1) is a rare autosomal recessive disorder of glyoxalate metabolism caused by deficiency in the liver-specific peroxisomal enzyme alanine-glyoxalate transaminase 1 (AGT) resulting in the increased oxidation of glyoxalate to oxalate. Accumulation of oxalate in the kidney and other soft tissues results in loss of renal function and significant morbidity. The present treatment options offer some relief in the short term, but they are not completely successful. In the present study, we tested the feasibility of corrective gene therapy for this metabolic disorder. METHODS: A cDNA library was made from HepG2 cells. PCR primers were designed for the AGT sequence with modifications to preclude mistargeting during gene delivery. Amplified AGT cDNA was cloned as a fusion protein with green fluorescent protein (GFP) using the vector EGFP-C1 (Clontech) for monitoring subcellular distribution. Sequence and expression of the fusion protein was verified. Fusion protein vectors were transfected into hepatocytes by liposomal transfection. AGT expression and subcellular distribution was monitored by GFP fluorescence. RESULTS: HepG2 cells express full-length mRNA coding for AGT as confirmed by insert size as well as sequence determination. Selective primers allowed us to generate a modified recombinant GFP-AGT fusion protein. Cellular transfections with Lipofectamine resulted in transfection efficiencies of 60-90%. The recombinant AGT did localize to peroxisomes as monitored by GFP fluorescence. CONCLUSIONS: The results demonstrate preliminary in vitro feasibility data for AGT transfection into the hepatocytes. To the best of our knowledge, this is the first study to attempt recombinant AGT gene therapy for treatment of primary hyperoxaluria-1.

Cells, Cultured↗
PubMed2005

A genome wide quantitative trait linkage analysis for serum lipids in type 2 diabetes in an African population.

Lipid abnormalities are strongly linked with coronary heart disease and are common in type 2 diabetes. However, little is known about the genetic determinants of serum lipids in African populations. An autosomal genome scan was performed for linkage to five plasma lipid phenotypes (total cholesterol, triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and VLDL-cholesterol (VLDL-C)) in the Africa-America Diabetes Mellitus (AADM) study. Two hundred and ninety-five affected sibling pairs with type 2 diabetes mellitus enrolled from Ghana and Nigeria were genotyped for 390 microsatellite markers with an average inter-marker distance of 9cM. Multipoint variance components linkage analysis showed that HDL-C had a LOD score of 4.34 near marker D7S3061 and 3.00 near marker D7S513. Some clustering of linkage evidence to several lipid phenotypes was observed on chromosomes 5 (LDL-C, total cholesterol, VLDL-C), chromosome 7 (HDL-C, TG) and chromosome 19 (total cholesterol, LDL-C, TG). Principal component analysis of the five phenotypes yielded two factors, one (TG, HDL-C and VLDL) of which was linked to QTLs on chromosomes 2, 5 and 7, while the other (total cholesterol and LDL-C) was linked to a different set of QTLs on chromosomes 2, 5 and 18. Several of these regions have been reported to be linked to lipids in other studies. Follow up investigations are warranted in view of the central role serum lipids play in the aetiopathogenesis of cardiovascular disease.

Adult↗
PubMed2005

Combination glutathione and anthocyanins as an alternative for skin care during external-beam radiation.

OBJECTIVE: Radiation dermatitis during therapy for breast malignancy can cause significant morbidity and delay treatment. RayGel (reduced glutathione and anthocyanins; Integrative Therapies, Portland, OR) appears to decrease this skin reaction, prompting us to undertake an objective evaluation of RayGel's effectiveness. METHODS: Patients undergoing whole breast external-beam irradiation were randomized to treatment with placebo or RayGel. Patients and investigators/staff were blinded to treatment assignment. Skin reaction was documented by photograph and severity scale. RESULTS: Thirty-two patients were enrolled. Thirty patients were randomized to receive placebo (n = 15) or RayGel (n = 15). Scores were calculated by percent of breast skin involved and grade of reaction. The group receiving RayGel had a lower average score, 93.7, versus the placebo group, 123.3. CONCLUSION: RayGel provides skin protection during radiation therapy, superior to that observed with standard skin care and placebo. This formula may reduce discomfort associated with breast irradiation and thereby allow more consistent completion of radiation courses for the treatment of breast cancer.

Anthocyanins↗
PubMed2005

Calpain-10 gene polymorphisms and type 2 diabetes in West Africans: the Africa America Diabetes Mellitus (AADM) Study.

PURPOSE: To investigate whether the three single nucleotide polymorphisms (SNPs), SNP-43, -56, and -63 of CAPN10 were associated with type 2 diabetes in a West African cohort. METHODS: A total of 347 diabetic subjects and 148 unaffected controls from four ethnic groups in two West African countries were enrolled in this study. After genotyping three SNPs of CAPN10 and one SNP from CYP19, the allele, genotype, and haplotype frequencies as well as the odds ratios were calculated to test their association with type 2 diabetes. RESULTS: None of the alleles or genotypes was associated with type 2 diabetes. Although statistical analysis indicated that haplotype 221 was associated with type 2 diabetes (OR, 3.765; 95% CI, 1.577-8.989) in the two ethnic groups of Nigeria, the same haplotype did not show any association with type 2 diabetes in the two ethnic groups in Ghana (OR, 0.906; 95% CI, 0.322-2.552). CONCLUSION: Considering the relatively low frequency of haplotype 221 and that none of the haplotypes including 221 was associated with any of the diabetes-related quantitative traits tested, it is concluded that SNP-43, -56, and -63 of the CAPN10 gene variants may play a limited role in the risk of type 2 diabetes risks in this cohort of West Africans.

Alleles↗
PubMed2005

The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim.

Previously, we showed that the proteasome inhibitor bortezomib/Velcade (formerly PS-341) synergizes with the protein tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL), a ligand for certain death receptors, to induce apoptosis in cell lines derived from prostate and colon cancers. Because apoptosis is often triggered by BH3-only proteins of the Bcl-2 family, we have explored the hypothesis that bortezomib contributes to the apoptosis by up-regulating their levels. Indeed, bortezomib induced increases of Bik and/or Bim in multiple cell lines but not notably of two other BH3-only proteins (Puma and Bid) nor other family members (Bax, Bak, Bcl-2, and Bcl-xL). The increase in Bik levels seems to reflect inhibition by bortezomib of its proteasome-mediated degradation. Importantly, both Bik and Bim seem central to the proapoptotic function of bortezomib, because mouse embryo fibroblasts in which the genes for both Bik and Bim had been disrupted were refractory to its cytotoxic action. Similarly, the synergy between bortezomib and TRAIL in killing human prostate cancer cells was impaired in cells in which both Bik and Bim were down-regulated by RNA interference. Further evidence that bortezomib acts through the mitochondrial pathway regulated by the Bcl-2 family is that deficiency for APAF-1, which acts downstream of Bcl-2, also blocked its apoptotic effect. These results implicate BH3-only proteins, in particular both Bik and Bim, as important mediators of the antitumor action of bortezomib and establish their role in its enhancement of TRAIL-induced apoptosis.

Animals↗
PubMed2004

Oncogenic Ras sensitizes normal human cells to tumor necrosis factor-alpha-related apoptosis-inducing ligand-induced apoptosis.

Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces apoptosis in tumor cells but rarely kills normal ones. To determine how normal human cells acquire TRAIL-sensitive phenotype during the process of malignant transformation, we used an experimental system that allows for controlled conversion of human cells from normal to cancerous by introduction of several genes. Human embryonic kidney cells and foreskin fibroblasts were first immortalized by combination of the early region of simian virus 40 and telomerase and then were transformed with oncogenic Ras. Both normal and immortalized cells were resistant to TRAIL-induced apoptosis, whereas Ras-transformed cells were susceptible. Ras transformation enhanced TRAIL-induced activation of caspase 8 by increasing its recruitment to TRAIL receptors. The proapoptotic effects of Ras could be reversed by mutations in its effector loop or by inhibitors of either farnesyl transferase or mitogen-activated protein kinase kinase. The expression of constitutively activated mitogen-activated protein kinase kinase 1 enhanced caspase 8 recruitment and sensitized immortalized human embryonic kidney cells to TRAIL-induced death. These results indicate that in normal human cells the TRAIL-induced apoptotic signal is blocked at the level of caspase 8 recruitment and that this block can be eliminated by Ras transformation, involving activation of the mitogen-activated protein kinase pathway.

Apoptosis↗
PubMed2004

A genome-wide search for type 2 diabetes susceptibility genes in West Africans: the Africa America Diabetes Mellitus (AADM) Study.

The incidence of type 2 diabetes is growing rapidly, not only in developed countries but also worldwide. We chose to study type 2 diabetes in West Africa, where diabetes is less common than in the U.S., reasoning that in an environment where calories are less abundant, incident cases of type 2 diabetes might carry a proportionately greater genetic component. Through the Africa America Diabetes Mellitus (AADM) study, we carried out a genome-wide linkage analysis of type 2 diabetes in a cohort of 343 affected sibling pairs (691 individuals) enrolled from five West African centers in two countries (Ghana: Accra and Kumasi; Nigeria: Enugu, Ibadan, and Lagos). A total of 390 polymorphic markers were genotyped, and multipoint linkage analysis was conducted using the GENEHUNTER-PLUS and ASM programs. Suggestive evidence of linkage was observed in four regions on three chromosomes (12, 19, and 20). The two largest logarithm of odds scores of 2.63 and 1.92 for chromosomes 20q13.3 and 12q24, respectively, are particularly interesting because these regions have been reported to harbor diabetes susceptibility genes in several other populations and ethnic groups. Given the history of forced migration of West African populations during the slave trade, these results should have considerable relevance to the study of type 2 diabetes in African Americans.

Africa, Western↗
PubMed2003

Routine genotyping of human papillomavirus samples in Denmark.

In order to examine a sensitive unbiased consensus PCR with routine sequencing for HPV typing, we analysed Danish male and female patients suspected of having an HPV infection. We used the well-characterised nested PCR setting with MY09/MY11 and GP5+/GP6+ primers, followed by routine cycle sequencing. Of 1283 clinical samples from female patients based on suspected HPV infection, we found 379 (29%) negatives and 894 (70%) positives. Samples containing >5000 HPV copies/ml were genotyped by sequencing. Of the 552 HPV genotyped samples from women >15 years of age, 398 were characterised as high-risk types and the remaining 154 as low-risk types. The most commonly found high-risk types were HPV-16, HPV-31, HPV-33, HPV-18, HPV-58, and HPV-52, and the most commonly found low-risk types were HPV-6, HPV-53 and HPV-11. In addition, we observed that other typing assays could not perform as sensitively or accurately as the nested PCR/cycle sequencing method used in this study. For instance, 87 out of 552 genotyped samples could not have been typed correctly in the Hybrid Capture II assay. Of these 87 samples, 46 (53%) were considered as high-risk types.

Adolescent↗
PubMed2003

Prevalence and determinants of diabetic retinopathy and cataracts in West African type 2 diabetes patients.

OBJECTIVE: To quantify the prevalence of, and risk factors for, diabetic retinopathy and cataracts in patients with type 2 diabetes, and their spouse controls, enrolled from 5 centers in 2 West African countries (Ghana and Nigeria). METHOD: The analysis cohort was made up of 840 subjects with type 2 diabetes, and their 191 unaffected spouse controls, who were enrolled and examined in Lagos, Enugu, and Ibadan, in Nigeria, and in Accra and Kumasi, in Ghana. A diagnosis of diabetic retinopathy was made only where a participant had a minimum of one microaneurysm in any field, as well as exhibiting hemorrhages (dot, blot, or flame shaped), and maculopathy (with or without clinically significant edema). RESULTS: Average duration of diabetes was 7.0 years, and mean age at diagnosis was 46.5 years. Prevalence of diabetic retinopathy was 17.9%. Cataracts were present in 44.9% of the patients with type 2 diabetes, and in 18.3% of spouse controls. The risk of developing retinopathy increased more than 3-fold for patients at the highest fasting plasma glucose (FPG) level (OR=3.4; 95% CI, 1.8-6.3), compared to patients at the lowest FPG level. The odds ratios for persons with diabetes for 10 years or more, compared to persons with diabetes for less than 5 years, was 7.3 (95% CI, 4.3-12.3) for retinopathy, and 2.6 (95% CI, 1.5-4.5) for cataracts. CONCLUSIONS: Cataracts were a more important cause of vision impairment than was diabetic retinopathy in this cohort. The prevalence of cataracts in patients with diabetes was more than twice that of their spouse controls, indicating that type 2 diabetes is an important risk factor for cataract formation. Individuals who developed type 2 diabetes at an earlier age were more likely to develop both diabetic retinopathy and cataracts. A strong positive association was observed between FPG level, duration of diabetes, and risk of retinopathy and cataracts. The low prevalence of retinopathy and cataracts observed within the first 5 years of diagnosis of diabetes in this cohort, suggests that intensive blood glucose control may reduce the risk of the development and progression of retinopathy and cataracts. In this regard, early eye examination, preferably at first presentation of elevated blood glucose, is highly recommended.

Adult↗
PubMed2003

[Stent-based local delivery of therapeutic adenovirus effectively reduces neointimal proliferation in porcine coronaries].

OBJECTIVE: To find an effective means for delivering therapeutic genes of Tissue inhibitor of metalloproteinase-3 (TIMP-3) to the target sites of the dilated coronary artery for the purpose of preventing restenosis of the injured artery. METHODS: A stainless steel stent coated with a high-molecular-mass polymer phosphorylocholine, after treatment with recombinant replication-defective adenovirus designated as RAD TIMP-3, was implanted into the coronary arteries of 7 pigs (therapy group). Another 7 pigs serving as the control group received implantation of uncoated stent. In both groups, coronary artery angiography was performed before withdrawal of intubation and 28 days after the implantation. For the purpose of planimetric analysis, the stented coronary arteries were isolated and fixed followed by resin embedding. Six sections were obtained for each stent for morphological assessment. RESULTS: The lumen diameter of the therapy group was 2.32+/-0.18 mm, significantly greater than that of the control group (1.79+/-0.31 mm, P=0.014). The neointimal thickness was smaller in the therapy group (0.34+/-0.17 mm vs 0.81+/-0.32 mm, P=0.0 059). CONCLUSIONS: The stent with biosynthetic coating effectively promotes TIMP3 AdV transduction and transcription, which effectively reduces neointimal proliferation, thus confirming its role in the prevention of in-stent restenosis. This maneuver may offer an alternative to conventional drug coatings for preventing restenosis.

Adenoviridae↗
PubMed2003

A data-driven approach for extracting "the most specific term" for ontology development.

We present a data-driven approach to extract the "most specific" terms relevant to an ontology of functioning, disability and health. The algorithm is a combination of statistical and linguistic approaches. The statistical filter is based on the frequency of the content words in a given text string; the linguistic heuristic is an extension of existing algorithms but goes beyond noun phrases and is formulated as a "complete syntactic node". Thus, it can be applied to any syntactic node of interest in the particular domain. Two test sets were marked by three experts. Test set 1 is a well-constructed text from pain abstracts; test set 2 is actual medical reports. Results are reported as recall, precision, F-score and rate of valid terms in false positives. A limitation of the current research is the relatively small test set.

Algorithms↗
PubMed2002

A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults.

STUDY OBJECTIVE: We sought to compare the efficacy and safety of nebulized magnesium sulfate (MgSO(4)) plus albuterol with that of albuterol alone in adult patients with mild-to-moderate acute asthma exacerbations. METHODS: Patients were randomized to receive nebulized MgSO(4) (384 mg in 6 mL of sterile water) or an equal volume of placebo (normal saline solution) in a double-blind fashion after each dose of nebulized albuterol administered (2.5 mg/3 mL) every 20 minutes for the first hour of the study. Spirometry was performed at baseline and every 20 minutes for 2 hours. Monitoring for safety included vital signs, pulse oximetry, and serum magnesium levels. Improvement in percent predicted forced expiratory volume in 1 second was chosen as a primary efficacy end point. RESULTS: Among 74 patients enrolled, 37 were randomized to each of 2 study groups. There were no statistically or clinically significant differences between the 2 study groups in percent predicted forced expiratory volume in 1 second at any point during the trial or overall. There were no significant differences in vital signs, pulse oximetry, or serum magnesium levels at any point during the study. CONCLUSION: The combination of nebulized MgSO(4) and albuterol provides no benefit in addition to that provided by therapy with albuterol in adult patients with mild-to-moderate asthma exacerbations. The efficacy of nebulized MgSO(4) in patients with severe asthma exacerbations remains unknown.

Administration, Inhalation↗
PubMed2002

Dose-intense ifosfamide/doxorubicin/cisplatin based chemotherapy for osteosarcoma in adults.

The efficacy of neoadjuvant and adjuvant chemotherapy has been clearly established in the treatment of osteosarcoma; however, the most active regimen remains to be identified. This prospective study evaluated the efficacy and toxicity of a dose-intense ifosfamide, doxorubicin, and cisplatin-based neoadjuvant regimen in adults with osteosarcoma. We prospectively treated 20 patients with osteogenic sarcoma with two cycles of ifosfamide/doxorubicin followed by two cycles of doxorubicin/cisplatin every 2 weeks. Surgical specimens were analyzed for percent tumor necrosis. Patients who demonstrated a "good response" (GR) to chemotherapy received the same combination postoperatively at a lower dose rate. Patients who demonstrated a "poor response" (PR) received four cycles of high-dose methotrexate alternating with two cycles of ifosfamide/etoposide and two cycles of cisplatin/etoposide after the surgery. Neoadjuvant chemotherapy was well tolerated with moderate hematologic toxicity. Twelve of 19 evaluable patients (63%) were treated according to the GR arm and 7 according to the PR arm. At median follow-up of 5.5 years, disease-free survival (DFS) and overall survival (OS) are 68% and 74%, respectively. Patients treated on the GR arm had DFS and OS of 75% and 83%, respectively, whereas patients on the PR arm had DFS and OS of 57%. Intensive neoadjuvant chemotherapy is effective and moderately well tolerated in patients with de novo osteosarcoma. The outcome data suggest that lack of a near complete response to preoperative chemotherapy reflects inherent biologic resistance to chemotherapy and hence a poor prognosis.

Adult↗
PubMed2002

Rates of discontinuation and change of glaucoma therapy in a managed care setting.

BACKGROUND: Comparing discontinuation and change rates of glaucoma pharmacotherapies provides insight as to which agents perform more effectively. OBJECTIVE: To quantify the rates of discontinuation and change of different glaucoma therapies. METHODS: This retrospective, observational study using managed care administrative claims data included patients who were between 20 and 64 years of age and received at least 1 prescription for 1 of the following glaucoma agents as monotherapy: betaxolol, brimonidine, latanoprost, or timolol. Patients receiving any glaucoma medication during the 180 days prior to their index prescription were excluded, as were those who did not have continuous plan enrollment during this period. The primary outcome measures were the discontinuation and change (switching/adding on) of the index glaucoma medication. Rates of discontinuation and change were compared using a proportional hazard model. RESULTS: A total of 1006 patients comprised the final study population. Approximately 62% of patients discontinued their index glaucoma medication, and 18% of patients changed to a different therapy within 18 months of starting therapy. Among those discontinuing therapy, latanoprost patients remained on therapy the longest (mean: 217 days) compared to other study cohorts (range: 182 to 184 days). Compared with latanoprost, patients initiated on any of the other agents were more likely to discontinue or change therapy. CONCLUSIONS: This study indicates that latanoprost therapy results in a lower rate of discontinuation or change compared to patients started on betaxolol, brimonidine, or timolol.

Adult↗