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D Dunn

Publications and source records attributed to D Dunn.

At least 19 recordsLinked to original sources
PubMed2006

Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T cells express high levels of the Th1-chemokine receptor CC chemokine receptor 5 (CCR5), which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA-affected sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly undertransmitted to children with early-onset JRA (P<0.01). C-1835T was genotyped in 424 additional simplex and multiplex families. CCR5-1835T allele was undertransmitted in the cohort of all probands with JRA (P<0.02), as well as in those with early-onset (P<0.01) or pauciarticular JRA (P<0.05). Another variant, a 32-bp deletion in the open reading frame of CCR5 (CCR5-Delta32) was also tested in approximately 700 simplex and multiplex families. CCR5-Delta32 was also significantly undertransmitted to probands with early-onset JRA (P<0.05). Both variants are in regions under natural selection, and result in functional consequences. Our results suggest these CCR5 variants are protective against early-onset JRA.

Arthritis, Juvenile↗
PubMed2005

Experience with minimally invasive esophagectomy.

BACKGROUND: Minimally invasive esophagectomy (MIE) is an evolving surgical alternative to traditional open esophagectomy. Despite considerable technical challenges, it was hypothesized that MIE could be performed effectively by surgeons experienced in open esophageal resection and advanced laparoscopic surgery. The authors report their experience with 25 patients who underwent MIE for esophageal disease. METHODS: A multidisciplinary esophageal cancer team evaluated all the patients enrolled in this institutional review board-approved retrospective review study. Over an 18-month period, 25 consecutive patients (22 men and 3 women; mean age, 62 years; range, 48-77 years) with resectable esophageal cancer underwent MIE. Six patients were treated with neoadjuvant chemoradiotherapy. The preoperative diagnoses were adenocarcinoma (64%, n = 16), high-grade dysplasia (20%, n = 5), and squamous cell cancer (16%, n = 4). The outcomes evaluated included operative course, hospital and intensive care unit lengths of stay, pathologic stage, morbidity, and mortality. RESULTS: Two patients required conversion to open esophagectomy. Operative mortality was 4% (n = 1). The mean operative time was 350 min (range, 300-480), and the average blood loss was 200 ml. The patients remained ventilated for a median of 12 h, and the median intensive care unit utilization was 1 day. The median hospital length of stay was 9 days (range, 6-33 days). Major complications occurred in 32% of the patients. The anastomotic leak rate was 12%. Minor pulmonary complications occurred in 32% and atrial fibrillation in 16% of the patients. An anastomotic stricture developed in 24% of all the patients. One patient showed a positive proximal margin in the final pathology results. CONCLUSIONS: Minimally invasive esophagectomy is a technically challenging procedure that can be performed safely at the Virginia Piper Cancer Institute. Optimal results require appropriate patient selection and a multidisciplinary team experienced in the management of esophageal cancer.

Adenocarcinoma↗
PubMed2003

Influence of allogeneic blood transfusion on clinical outcome during radiotherapy for cancer of the uterine cervix.

Anemia has long been reported to adversely affect the efficacy of radiation treatment in cervical cancer. On the basis of these findings, many radiation oncologists routinely use blood transfusions with the intent to maintain hemoglobin above specified levels during radiation therapy. However, allogeneic blood transfusions have been previously linked with biological and clinical phenomena correlated with immune suppression. In this study we have analyzed the effects of blood transfusion on the outcome of 130 patients with stage-IIB and -III cervical carcinomas treated with external radiation and intracavitary brachytherapy with or without concomitant platinum administration at the University of Arkansas for Medical Sciences between 1990 and 1999. With the exception of hemoglobin and hematocrit levels at the onset of treatment between the transfused and untransfused groups (p < 0.001), the distribution of age, histology, total radiation dose and duration of treatment were not significantly different between the 2 groups of stage-IIB and -III patients. Among the 45 stage-IIB patients who received blood during radiation treatment, there were 31 deaths (68.8%), compared with 14 (31.8%) among the 44 patients who did not receive blood (p > 0.05). Among the 30 stage-III patients who received blood during radiation treatment, there were 27 deaths (90%), compared with 6 (54%) among the 11 patients who did not receive blood (p > 0.11). In multivariate analysis of survival, there was a significant difference due to transfusion with a risk ratio (RR) of 2.6 (95% CI 1.6, 4.2; p < 0.001) after adjusting for no chemotherapy (RR = 2.2, 95% CI 1.4, 3.5; p < 0.001), considering all patients collectively, stage-IIB patients only (RR = 1.9, 95% CI 1.1, 3.3; p < 0.01), and stage-III patients only (RR = 3.2, 95% CI 1.2, 8.7; p < 0.02). These results suggest that routine blood transfusion of anemic cervical cancer patients does not improve outcome and may represent an independent variable predictive of diminished survival during primary radiation treatment for cervical cancer. Prospective randomized studies are strongly warranted to confirm this hypothesis.

Adult↗
PubMed2003

Cervical spondyloptosis caused by an aneurysmal bone cyst: a case report.

STUDY DESIGN: The case of an 11-year-old patient with an aneurysmal bone cyst at C7, cervical spondyloptosis, and scoliosis of the lumbar spine is reported. OBJECTIVE: To describe an unusual presentation of aneurysmal bone cyst causing painless cervical spondyloptosis. SUMMARY OF BACKGROUND DATA: Aneurysmal bone cysts of the cervical spine are rare. There has never been a reported case of cervical dislocation by an aneurysmal bone cyst. This case highlights the potentially devastating effects that can be caused by benign tumors in the vertebral column. METHODS: The history, clinical examination, imaging findings, and treatment are reviewed. RESULTS: The patient was treated with a single-stage combined posteroanteroposterior operation to resect the tumor, reduce the cervicothoracic dislocation, and create a three-column stabilization of the spine. The results were satisfactory, with an improvement in neurology. CONCLUSIONS: Aneurysmal bone cysts should be considered in the etiology of complicated scoliosis. Patients with a benign clinical history should be investigated at an early stage using appropriate imaging. Surgery is the treatment of choice when stability of the spine is compromised and neurologic signs are present.

Bone Cysts, Aneurysmal↗
PubMed2001

Ecological comparison of the risks of mother-to-child transmission and clinical manifestations of congenital toxoplasmosis according to prenatal treatment protocol.

We compared the relative risks of mother-to-child transmission of Toxoplasma gondii and clinical manifestations due to congenital toxoplasmosis associated with intensive prenatal treatment in Lyon and Austria, short term treatment in 51% of Dutch women, and no treatment in Danish women. For each cohort, relative risks were standardized for gestation at seroconversion. In total, 856 mother-child pairs were studied: 549 in Lyon, 133 in Austria, 123 in Denmark and 51 in The Netherlands. The relative risk for mother-to-child transmission compared to Lyon was 1.24 (95% CI: 0.88, 1.59) in Austria; 0.59 (0.41, 0.81) in Denmark; and 0.65 (0.37, 1.01) in The Netherlands. Relative risks for clinical manifestations compared with Lyon (adjusted for follow-up to age 3 years) were: Austria 0.19 (0.04, 0.51); Denmark 0.60 (0.13, 1.08); and The Netherlands 1.46 (0.51, 2.72). There was no clear evidence that the risk of transmission or of clinical manifestations was lowest in centres with the most intensive prenatal treatment.

Anti-Bacterial Agents↗
PubMed2001

Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones.

Because of the insensitivity of the Ham test, paroxysmal nocturnal haemoglobinuria (PNH) has been inaccurately viewed as a late clonal complication of aplastic anaemia (AA). To clarify the relationship between PNH and marrow failure, we tested for the presence of glycosylphosphatidyl-anchored protein-deficient (GPI-AP) granulocytes in large cohorts of patients with AA, myelodysplasia (MDS), and pure haemolytic PNH. A PNH clone was detected in 32% of new AA patients and 18% of MDS patients. In serial studies, this proportion did not change up to 15 years after diagnosis, suggesting that expansion of aberrant cells is an early event (i.e. prior to initial presentation). For all patients with a PNH clone, on average 14% of PNH granulocytes were found on presentation and 37% at 10 years. Patients with PNH but without cytopenia showed higher percentages of GPI-AP-deficient cells than did those with the AA/PNH syndrome. After immunosuppression, there was no change in the contribution of PNH clone to blood production, arguing against the "immune-escape" theory in PNH. Clinically, a high proportion of GPI-AP-deficient cells correlated with marrow hypercellularity. GPI-AP-deficient cells were similarly present in patients with and without karyotypic abnormalities. Our results indicate that the GPI-AP-deficient clones show quantitative and kinetic differences between classic haemolytic PNH and PNH with marrow failure, in which the evolution rate is low later in the course of the disease.

Adult↗
PubMed2000

Treating glaucoma.

Explore the source record for details and available documents.

Antibiotics, Antineoplastic↗
PubMed2000

Evidence of recent lateral gene transfer among hyperthermophilic archaea.

A total of 153 nucleotide differences were found over a contiguous 16 kb region between two hyperthermophilic Archaea, Pyrococcus furiosus and Thermococcus litoralis. The 16 kb region in P. furiosus is flanked by insertion sequence (IS) elements with inverted and direct repeats. Both IS elements contain a single open reading frame (ORF) encoding a putative protein of 233 amino acids identified as a transposase. This 16 kb region has the features of a typical bacterial composite transposon and represents a possible mechanism for lateral gene transfer between Archaea or possibly between Archaea and Bacteria. A total of 23 homologous IS elements was found in the genome sequence of P. furiosus, whereas no full-length IS elements were identified in the genomes of Pyrococcus abyssi and Pyrococcus horikoshii. Only one IS element was found in T. litoralis. In P. furiosus and T. litoralis, the 16 kb region contains an ABC transport system for maltose and trehalose that was characterized biochemically for T. litoralis. Regulation of expression studies showed that the malE gene, located on the transposon, and the encoded trehalose/maltose-binding protein (TMBP) are induced in the presence of maltose and trehalose in both P. furiosus and T. litoralis. The implications of transposition as a mechanism for lateral gene transfer among Archaea are discussed.

Amino Acid Sequence↗
PubMed2000

Ultra-high throughput screen of two-million-member combinatorial compound collection in a miniaturized, 1536-well assay format.

Results of a complete survey of the more than 2-million-member Pharmacopeia compound collection in a 1536-well microvolume screening assay format are reported. A complete technology platform, enabling the performance of ultra-high throughput screening in a miniaturized 1536-well assay format, has been assembled and utilized. The platform consists of tools for performing microvolume assays, including assay plates, liquid handlers, optical imagers, and data management software. A fluorogenic screening assay for inhibition of a protease enzyme target was designed and developed using this platform. The assay was used to perform a survey screen of the Pharmacopeia compound collection for active inhibitors of the target enzyme. The results from the survey demonstrate the successful implementation of the ultra-high throughout platform for routine screening purposes. Performance of the assay in the miniaturized format is equivalent to that of a standard 96-well assay, showing the same dependence on kinetic parameters and ability to measure enzyme inhibition. The survey screen identified an active class of compounds within the Pharmacopeia compound collection. These results were confirmed using a standard 96-well assay.

Chemistry, Pharmaceutical↗
PubMed2000

Chronic regional pain syndrome, type 1: Part I.

Chronic regional pain syndrome refers to a class of disorders thought to involve common neuropathic and clinical features. These disorders usually are caused by injury, and they manifest in pain and sensory changes that are disproportionate in intensity, distribution, and duration to the underlying pathology. The result of these injuries is significant impairment of motor function over time. This article is divided into two parts. Part I discusses background information such as pain, pathophysiology, diagnosis, clinical stages, and the most common treatment modality, sympathetic nerve blocks. Part II, discusses alternate treatment modalities, such as sympathectomy, physical therapy, stimulators, trigger point injections, acupuncture, tourniquet effects, placebo effects, and amputation.

Autonomic Nerve Block↗
PubMed1999

Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counselling.

BACKGROUND: Women who acquire toxoplasmosis infection during pregnancy (in most cases detected through serological screening) require counselling about the risk of congenital infection and its clinical sequelae. Reliable estimates of risk are not currently available. We undertook an analysis of data from women referred to the toxoplasmosis reference laboratory, Lyon, France, between 1987 and 1995. METHODS: Information was collected from clinical notes kept at the laboratory and, where necessary, from the relevant obstetrician or paediatrician via telephone. Methods were developed to derive estimates of the risk of congenital toxoplasmosis by exact duration of gestation at maternal seroconversion. FINDINGS: We analysed obstetric and paediatric data on 603 confirmed maternal toxoplasmosis infections. At least 564 women received antiparasitic drugs according to a standard protocol. Congenital infection status was ascertained in 554 cases, and infected children were followed-up for a median of 54 months. The overall maternal-fetal transmission rate was 29% (95% CI 25-33), which masked a sharp increase in risk with duration of gestation from 6% at 13 weeks to 72% at 36 weeks. However, fetuses infected in early pregnancy were much more likely to show clinical signs of infection. These effects counterbalance, and women who seroconverted at 24-30 weeks of gestation carried the highest risk (10%) of having a congenitally infected child with early clinical signs who was thus at risk of long-term complications. INTERPRETATION: This information will assist the clinical counselling of pregnant women diagnosed with acute toxoplasmosis and may guide individual decisions on investigative and therapeutic options. Further studies are required to determine the long-term risks of clinical symptoms and disability due to congenital toxoplasmosis.

Adult↗
PubMed1999

Diagnosis of congenital toxoplasmosis at birth: what is the value of testing for IgM and IgA?

UNLABELLED: Recommendations vary on the best combination of tests to use for the diagnosis of subclinical congenital toxoplasmosis at birth. The diagnostic accuracy of IgM and IgA tests was assessed in the context of routine clinical practice on 233 newborns with congenital toxoplasmosis and 661 healthy controls. IgM/IgA sensibility and specificity were compared in cord and postnatal samples. Both tests were considerably more specific in neonatal blood (IgM: 98%; IgA: 100%) than in cordblood (IgM: 85%; IgA: 88%). Sensitivity for IgM and IgA was not significantly different in neonatal blood (61% and 60%, respectively) and cord blood (67% and 54%, respectively). Combining IgM and IgA increased the overall sensitivity to 73% without any significant loss in specificity (98%). The influence of the date of maternal infection on the sensitivity and negative predictive value was also clearly demonstrated. CONCLUSION: Because of their relatively low cost compared to more sophisticated methods, IgM and IgA tests should remain the main method for the routine diagnosis of congenital toxoplasmosis although follow up is essential to identify the Ca. 25% of infected children who are missed at birth on the basis of these tests.

Agglutination Tests↗
PubMed1999

Sequence heterogeneity of the ferripyoverdine uptake (fpvA), but not the ferric uptake regulator (fur), genes among strains of the fluorescent pseudomonads Pseudomonas aeruginosa, Pseudomonas aureofaciens, Pseudomonas fluorescens and Pseudomonas putida.

Pseudomonas aeruginosa, Pseudomonas aureofaciens, Pseudomonas fluorescens and Pseudomonas putida are of importance to medicine, agriculture and biocycling. These microbes acquire ferric ion via the use of the siderophores pyochelin and the family known as the pyoverdines or pseudobactins. The ferric uptake regulator (fur) gene is responsible, at least in part, for the regulation of siderophore synthesis and uptake in P. aeruginosa. To determine whether the organisms contain single or multiple homologues of the siderophore-related genes fpvA (ferripyoverdine uptake) and fur, and whether these homologues displayed sequence heterogeneity, their chromosomal DNAs were probed with fur and fpvA sequences. As a representative of a non-fluorescent pseudomonad, the bacterium Burkholderia (Pseudomonas) cepacia was also examined. The pseudomonads all contained fpvA- and fur-like homologues, and heterogeneity was observed among the different species. The presence of two or more fpvA-like genes is indicated in all of the fluorescent pseudomonads surveyed. In contrast, B. cepacia DNA either did not hybridize to these probes, or did so only very weakly, suggesting that fur- and fpvA-like homologues are either absent or significantly different in B. cepacia compared to the fluorescent pseudomonads examined.

Bacterial Outer Membrane Proteins↗