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D Dunn

Publications and source records attributed to D Dunn.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Increased production of nitric oxide in the immediate and late asthmatic responses in models of guinea pig experimental asthma].

Nitric oxide is produced in mammalian airways by constitutive and inducible nitric oxide synthase, and endogenous nitric oxide can be detected as exhaled gas. Patients with asthma have large numbers of airway epithelial cells and inflammatory cells that contain nitric oxide synthase, and nitric oxide levels in exhaled air are high during immediate asthmatic responses. To examine the dynamics of nitric oxide synthase in the tracheas of guinea pigs, cumulative dose-response studies of 5-HT were done on tracheal strips, in the presence or absence of arginine and its analogues. This assay indicated that relative the activity of nitric oxide synthase was greater 6 hr after the challenge than immediately after, which suggests that nitric oxide is involved in the pathogenesis of bronchial asthma attacks.

Animals↗
PubMed1994

Chemoprophylaxis with oral ciprofloxacin in ovarian cancer patients receiving taxol.

The purpose of this study was to review the clinical outcomes and cost of administration of a prophylactic antibiotic compared to G-CSF for the prevention of neutropenic morbidity associated with taxol. The study group was composed of 62 patients with ovarian cancer who received a 24-h infusion of a taxol-based regimen at doses less than or equal to 175 mg/m2 between June 1992 and April 1994. The records were retrospectively reviewed and the patients were grouped and analyzed according to the management of their myelosuppression. Group I patients (n = 29) were observed until their absolute neutrophil count (ANC) was less than 500/microliters and then were placed on ciprofloxacin 500 mg orally twice a day until their ANC was 1,000/microliters. Group II patients (n = 15) received G-CSF from Day 2 until the ANC was greater than 10,000/microliters beginning with their first cycle. Group III patients (n = 18) received their taxol regimen without either ciprofloxacin or G-CSF. Two hundred eighty-two taxol-based chemotherapy cycles were administered to these 62 patients. There was no statistically significant difference between the groups concerning disease status as measured by age, stage, performance status, dose intensity, or number of previous regimens. There were two episodes of febrile neutropenia in Group I and three episodes in Group II. Group III had 15 episodes of febrile neutropenia. The estimated cost of the different prophylactic regimens was $5,215.00 for Group I versus $104,000.00 for G-CSF in Group II. Within the three groups, there were 27 patients with an episode of febrile neutropenia (n = 20) or prolonged myelosuppression (n = 7) that were followed for an additional 104 taxol cycles. Twenty-four of these patients received G-CSF prophylaxis with intermittent ciprofloxacin and three received only ciprofloxacin. There were eight more episodes of febrile neutropenia in the patients receiving G-CSF. There were no additional febrile episodes on cycles prophylaxed with ciprofloxacin. There was no septic mortality. For patients receiving a 24 h infusion of taxol at doses less than 175 mg/m2, ciprofloxacin given through the ANC nadir may be effective in preventing febrile morbidity. A prospective randomized trial is underway to evaluate this approach.

Administration, Oral↗
PubMed1994

T-cell lines derived from lesional skin of lichen planus patients contain a distinctive population of T-cell receptor gamma delta-bearing cells.

Lichen planus is characterized by a dense infiltrate of T lymphocytes at the dermoepidermal junction. To determine the phenotypic and functional characteristics of the infiltrating lymphocytes, T-cell lines from normal and lesional skin from the same patients with lichen planus were established by culture with interleukin 2 followed by stimulation every 14 d with phytohemagglutinin and irradiated allogeneic feeder cells. Resultant T-cell lines were immunophenotyped by staining with monoclonal antibodies and their reactivity tested by determining their cytolytic activity to selected targets. T-cell lines from 13 lesional and nine normal biopsy specimens were studied. T-cell lines from normal skin were 61% CD4+ and 32% CD8+, whereas lines from lesional skin had significantly fewer CD4+ cells (13%) and more CD8+ cells (62%). T-cell lines from lesional skin contained a distinctive population of gamma delta T cells that was rarely present in lines derived from normal skin. We were able to culture gamma delta T cells out of the lesional skin of 12 of 13 patients. In these 12 patients, lesional T-cell lines were 17% gamma delta+ (range 2% to 47%). Only one T-cell line from normal skin contained significant numbers of gamma delta T cells. The gamma delta population from lesional skin was commonly V delta 1J delta 1+. These results suggest that CD8+ and TCR gamma delta+ T lymphocytes may be involved in the development or the maintenance of lichen planus.

Cell Line↗
PubMed1994

Laparoscopic cholecystectomy in England and Wales: results of an audit by the Royal College of Surgeons of England.

The results of an audit of open and laparoscopic cholecystectomy conducted by the Comparative Audit Service of The Royal College of Surgeons of England are presented. Data were submitted by 124 consultant surgeons on 3319 attempted laparoscopic and by 227 consultant surgeons on 8035 open cholecystectomies performed in England and Wales during the 2 years 1990 and 1991. These were contrasted with 9322 attempted laparoscopic cholecystectomies reported in 21 series reported in the world literature between 1991 and 1992, and with five other nations' audit studies. Among attempted laparoscopic cases, conversion to an open procedure was necessary in 175/3319 (5.2%) of cases and overall mortality was 0.15% (5/3319). Major complications were reported in 2.1% and minor complications in 5.9% of cases. Bile duct injury was reported to be significantly more common after attempted laparoscopic cholecystectomy (11/3319, 0.33%) than after open cholecystectomy (4/8035, 0.06%) (95% confidence intervals -0.48 to 0.08), but it was not significantly different from that reported for laparoscopic cholecystectomy in the combined world literature (28/9322, 0.3%) (95% confidence intervals -0.19 to 0.25). Most systemic complications were significantly more common after open cholecystectomy. For open cholecystectomy, the mortality was 55/8035 (0.76%), with major complications reported in 3.2% and minor complications in 9.8% of patients. Adoption of the laparoscopic approach was associated with a four-fifths reduction in the mortality of cholecystectomy, and a 40% reduction in the overall complication rate when compared with the open operation. While laparoscopic cholecystectomy has an impressively low mortality and morbidity profile during the first 2 years of its introduction into the UK, prevention of bile duct injury is the most important issue to be addressed in all laparoscopic cholecystectomy training programmes.

Bile Ducts↗
PubMed1993

Replication and tropism of human immunodeficiency virus type 1 as predictors of disease outcome in infants with vertically acquired infection.

In a series of 97 infants born to mothers who were seropositive for human immunodeficiency virus type 1 (HIV-1), 18 were identified as infected within the first 60 days of life on the basis of viral culture and polymerase chain reaction findings. We studied viral burden in vivo by quantitative polymerase chain reaction and the in vitro replication pattern of the HIV-1 infecting strain by culturing patient cells with normal phytohemagglutinin-stimulated peripheral blood mononuclear cells. According to the lag phase before p24 antigen detection and the level of p24 production on peripheral blood mononuclear cells, HIV-1 isolates from these patients were classified as rapid/high (R/H), slow/high (S/H), and slow/low (S/L). The pattern of HIV-1 replication in vitro was significantly associated with the viral burden in vivo; the range of HIV-1 copies per 10(5) peripheral blood mononuclear cells was 10 to 38, 44 to 314, and 360 to 947 in children with isolates of the S/L, S/H, and R/H types, respectively. Viral tropism was assessed by culturing patient cells under end-point dilution conditions with either CD4+ T-lymphocytes or monocyte-derived macrophages. We found that children with S/L isolates harbored mainly monocytotropic variants; all infants with S/H or R/H isolates had T-lymphotropic variants and, in 7 of 11 cases, monocytotropic or amphitropic variants. All children with R/H isolates had HIV-related symptoms by the age of 4 months, and five had acquired immunodeficiency syndrome by the age of 1 year. At 1 year of age, four and no infants with S/H or S/L isolates, respectively, had HIV-1-related symptoms (p < 0.001), and none had acquired immunodeficiency syndrome (p = 0.006).

CD4-Positive T-Lymphocytes↗
PubMed1993

Estimating the rate of mother-to-child transmission of HIV. Report of a workshop on methodological issues Ghent (Belgium), 17-20 February 1992. The Working Group on Mother-to-Child Transmission of HIV.

PURPOSE: In the last 8 years, numerous cohort studies have been conducted to estimate the rate of mother-to-child transmission (MTCT) of HIV. Many of these have faced problems in data collection and analysis, making it difficult to compare transmission rates between studies. This workshop on methodological aspects of the study of MTCT of HIV-1 was held in Ghent (Belgium) in February 1992. STUDY SELECTION AND DATA EXTRACTION: Fourteen teams of investigators participated, representing studies from Central (five) and Eastern Africa (three), Europe (two), Haiti (one) and the United States (three). A critical evaluation of the projects was carried out, under four headings: (1) enrollment and follow-up procedures, (2) diagnostic criteria and case definitions, (3) measurement and comparison of MTCT rates and (4) determinants of transmission. RESULTS OF DATA ANALYSIS: Reported transmission rates ranged from 13 to 32% in industrialized countries and from 25 to 48% in developing countries. However, no direct comparisons could be made because methods of calculation differed from study to study. Based on this review, a common methodology was developed. Agreement was reached on definitions of HIV-related signs/symptoms, paediatric AIDS and HIV-related deaths. A classification system of children born to HIV-1-infected mothers according to their probable HIV infection status during the first 15 months of life, allowed the elaboration of a direct method of computation of the transmission rate and of an indirect method for studies with a comparison group of children born to HIV-seronegative mothers. This standardized approach was subsequently applied to selected data sets. CONCLUSIONS: The methodology can now be applied to all studies with sufficient follow-up and comparisons made between transmission rates. This step is essential for assessing determinants of transmission and for the development of a common approach for the evaluation of interventions aimed at reducing or interrupting MTCT of HIV.

Adult↗
PubMed1993

The use of mycophenolate mofetil (RS-61443) in human heart transplant recipients.

Mycophenolate mofetil is a potent inhibitor of de novo guanine nucleotide synthesis that selectively blocks lymphocyte proliferative responses. In animal models, mycophenolate mofetil has been shown to prolong allograft survival, reverse ongoing rejection, and induce strain-specific tolerance. To assess the safety and efficacy of mycophenolate mofetil in cardiac transplantation, 30 recipients with mild rejection were enrolled in an 8-week phase I trial. Mycophenolate mofetil in doses from 500 to 3000 mg/day orally was substituted for azathioprine, while baseline cyclosporine levels and corticosteroid doses were maintained. Rejection resolved in the majority of patients, with a significant decrease in mean biopsy score. By protocol, mycophenolate mofetil was discontinued in 4 patients due to persistent mild rejection, and in 4 patients due to progression to moderate rejection. The rate of progression to moderate rejection compared favorably with that observed in patients with mild rejection maintained on azathioprine without augmentation of immunosuppression. Significant increases were observed in hematocrit, total white blood cell count, and absolute neutrophil count. Absolute lymphocyte count remained unchanged. No nephrotoxicity or hepatotoxicity was observed. Gastrointestinal side effects prompted discontinuation of mycophenolate mofetil in one patient. Two major infections occurred. Mycophenolate mofetil remained well tolerated during long-term maintenance immunosuppression, with a rate of rejection similar to that in patients receiving azathioprine. We conclude that mycophenolate mofetil is safe and well tolerated in cardiac transplant recipients, is less myelosuppressive than azathioprine, and appears to be at least equipotent to azathioprine.

Adult↗
PubMed1993

Etiology of hypoferremia in a recently sedentary Kalahari village.

To determine the etiology of hypoferremia in recently sedentary hunter-gatherers, a community located in the Kalahari Desert of Botswana was studied. Iron profiles of 106 Basarwa (Bushmen, San) volunteers were examined. Hematocrits were measured in the field. The remaining blood was processed for transportation to a research medical laboratory for further studies. Subnormal serum iron values were present, depending on the subpopulation, in 50-52% of the volunteers. Transferrin saturation was subnormal in 35-49% of those tested. The absence of subnormal serum ferritin levels indicates that dietary iron deficiency is not the cause of the hypoferremia. Instead, serum ferritin was greater than 50 micrograms/l (a level indicative of anemia of chronic disease/inflammation) in 92% of the hypoferremic adult Basarwa. We suggest that by depriving microbes of needed iron, the frequency of the anemia of infections and chronic disease in this population might be a response to, and defense against, a chronically high pathogen load in a community that has not yet incorporated sanitation practices appropriate for sedentary aggregations.

Adolescent↗
PubMed1992

$250 for a life.

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Acute Disease↗
PubMed1992

A controlled trial of ganciclovir to prevent cytomegalovirus disease after heart transplantation.

BACKGROUND: Because of the immunosuppression required, heart-transplant recipients frequently have complications caused by cytomegalovirus (CMV), including pneumonia, esophagitis, gastritis, and a syndrome of fever, hepatitis, and leukopenia. We undertook a controlled trial to evaluate the prophylactic administration of ganciclovir to prevent CMV-induced disease after heart transplantation. METHODS: This randomized, double-blind, placebo-controlled trial was conducted at four centers. Before randomization, the patients were stratified into two groups: those who were seropositive for CMV before transplantation and those who were seronegative but who received hearts from seropositive donors. Ganciclovir was given intravenously at a dose of 5 mg per kilogram of body weight every 12 hours from postoperative day 1 through day 14, then at a dose of 6 mg per kilogram each day for 5 days per week until day 28. RESULTS: Among the seropositive patients, CMV illness occurred during the first 120 days after heart transplantation in 26 of 56 patients given placebo (46 percent), as compared with 5 of 56 patients treated with ganciclovir (9 percent) (P less than 0.001). Among 37 seronegative patients, CMV illness was frequent in both groups (placebo, 29 percent; ganciclovir, 35 percent; P not significant). From day 15 through day 60, the patients who took ganciclovir had significantly fewer urine cultures positive for CMV, but by day 90 there was no difference. More of the ganciclovir-treated patients had serum creatinine concentrations greater than or equal to 221 mumol per liter (2.5 mg per deciliter) (18 percent vs. 4 percent in the placebo group), but those elevations were transient. CONCLUSIONS: The prophylactic administration of ganciclovir after heart transplantation is safe, and in CMV-seropositive patients it reduces the incidence of CMV-induced illness.

Adolescent↗