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Biomedical subjects

D Dunn

Publications and source records attributed to D Dunn.

At least 19 recordsLinked to original sources

$250 for a life.

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Acute Disease

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

Prostitutes and their clients: a Gambian survey.

The social backgrounds and working behaviour of 248 prostitutes in urban and rural areas of The Gambia were investigated. Prostitutes were found to be highly mobile, moving frequently between a number of working locations in The Gambia and neighbouring Senegal, from which most of them originated. The educational level of prostitutes and the standard of living of their natal families were above average. Prostitutes worked on average four days a week and had between two and three clients a night. Condoms were used in up to 80% of contacts. 795 clients of prostitutes were interviewed and found to be on average of low educational and occupational status. Half were non-Gambian and most were currently travelling or living away from home.

Abortion, Therapeutic

Esophagogastric ring: why and when we see it, and what it implies: a radiologic-pathologic correlation.

Schatzki first reported a ring-like structure at the esophagogastric mucosal junction in 1953. There is still no uniform agreement as to its exact location, etiology, or clinical importance. We found an esophagogastric ring in 15% to 18% of 22,368 patients having routine upper gastrointestinal examinations. It was present only in patients with cephalad displacement of the esophagogastric junction and only in those who had sharply and circumferentially marginated transition of esophagogastric mucosal junction. It is postulated that the esophagus shortens on vagal stimulation by contracture of the longitudinal esophageal muscle, which causes a mucosal infolding at the esophagogastric junction. In a small group of these patients, fibrosis apparently develops in this region and results in a fixed organic circumferential diaphragm, which may cause obstructive symptoms. These concepts affect therapeutic alternatives.

Barium Sulfate

Pediatric renal transplants--results with sequential immunosuppression.

Cyclosporine has improved the results of renal transplantation. In 1984, we began using it as part of a sequential immunosuppression protocol (MALG, AZA, P, and delayed administration of CsA) in our pediatric renal transplant recipients. We studied the outcome of the 131 pediatric renal transplants (less than or equal to 18 years of age at transplant) performed at our institution between June 1984 and March 1991. We compared these results with the 144 similar transplants performed since January 1980 that did not involve CsA immunosuppression. In the sequential immunosuppression group, there were 97 primary (74%) (26 [27%] cadaver, 71 [73%] living donor [LD]) and 34 (26%) retransplant (23 [68%] CAD, 11 [32%]) recipients. Age at transplant (mean +/- SD) was 7.4 +/- 5.5. Overall, 1-year actuarial graft survival was 93%; 1-year patient survival was 100%. The mean number of hospital readmissions was 3.0 +/- 3.5; 26 (20%) were readmission-free. The mean number of rejection episodes was .87 +/- 1.3 per patient; 73 (56%) were rejection-free. Importantly, LD (vs. CAD) recipients had fewer rejection episodes (P = 0.06). In the first post-transplant year, the serum creatinine level was significantly lower in primary (vs. retransplant) recipients and in LD (vs. CAD) recipients (P less than 0.05). In the 144 patients not receiving CsA, there were 129 (90%) primary (27 CAD, 102 LD) and 15 (10%) retransplant (7 CAD, 8 LD) recipients. Age at transplant was 6.9 +/- 5.3 years. The 1-year actuarial graft survival rate was 82%; the 1-year patient survival rate was 94%. The mean number of hospital readmissions was 3.3 +/- 2.3; 5 (8%) were readmission-free. The mean number of rejection episodes was 1.2 +/- 1.5; 27 (45%) were rejection-free. There was no difference in the serum creatinine level based on donor source or transplant number. Sequential immunosuppression has significantly improved patient (P = 0.003) and graft survival (P = 0.004) rates. Comparing sequential vs. non-CsA immunosuppression, there was no difference in the number of readmissions (P = 0.47), number of rejection episodes (P = 0.17), or serum creatinine level. The number of rejection-free patients was significantly lower in LD (vs. CAD) recipients (P less than 0.05). There was no evidence of progressive deterioration in renal function in the sequential (vs. non-CsA) recipients.

Adolescent

Alpha-1-protease inhibitor in bronchial asthma: phenotypes and biochemical characteristics.

The prevalence of the different phenotypes of alpha 1-protease inhibitor (alpha 1PI) was investigated in a group of 90 asthmatic patients and compared with that of a control group of 240 individuals representing the general population. The M2M2 phenotype occurred more frequently in the asthmatic group (p = 0.015). Plasma samples of 51 of the asthmatic patients randomly selected from the different phenotype groups identified were studied for the absolute plasma values of alpha 1-PI and the inhibitory capacity of plasma for porcine pancreatic elastase, and compared with those from 21 nonasthmatic individuals of the M1M1 phenotype. Although the asthmatic patients had higher absolute alpha 1PI values (p = 0.04), the plasma elastase inhibitory capacity was markedly reduced compared with the nonasthmatic subjects (p = 0.01). The functional efficiency of alpha 1PI from asthmatic patients of the M1M1, M1M2, and M2M2 phenotypes was significantly decreased compared with that of the nonasthmatic M1M1 individuals. Functional deficiency of alpha 1PI may be important in the pathogenesis of the inflammatory process that characterizes bronchial asthma.

Adult

Osteoblastoma response to chemotherapy.

An 8-year-old boy had an osteoblastoma of the body of C2. After attempted excision, the tumor recurred rapidly and massively. The tumor shrank progressively after treatment with high-dose methotrexate, doxorubicin, and cisplatin. The patient has stopped treatment and been stable for 33 months. Surgical excision remains the treatment of choice for osteoblastoma. Chemotherapy may be useful in selected patients with a recurrent, aggressive tumor or in patients with surgically inaccessible disease.

Bone Neoplasms

Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium.

A well recognized feature of the immune response to parasitic helminth infections, including schistosomiasis, is the production of large amounts of specific and nonspecific IgE1,2. Immunological pathways involving IgE can lead to damage to the developing schistosomulum and it has been suggested that responses involving IgE could have evolved as protection against helminth infections. There has been no epidemiological evidence to support this idea and the only significant IgE responses known in man are those involved in the pathogenesis of allergic disease. Here we measure serological response during reinfection with S. haematobium and demonstrate that IgE antibodies in man can be beneficial. Our results support the hypothesis that the slow build-up of IgE to high levels and the early production of IgG4 antibodies, which may block IgE pathways are responsible for delaying the development of protective immunity to S. haematobium.

Adolescent

Risk factors for second renal allografts immunosuppressed with cyclosporine.

Second renal allograft survival rates are lower than those of primary allografts. For recipients immunosuppressed with azathioprine, prednisone, and Minnesota ALG (conventional immunosuppression), risk factors associated with decreased second graft survival have been identified: age greater than 40, cadaver donor, less than 6 months between primary graft loss and retransplantation, duration of primary graft function (6 months or 1 year, depending on the study), high peak panel-reactive antibody, number of human leukocyte antigen mismatches, and delayed graft function. In this study, we used a multivariate analysis to identify risk factors associated with decreased second graft survival in patients who did or did not receive cyclosporine. Results were compared with primary graft survival rates. Risk factors for patients receiving conventional immunosuppression were: (a) primary graft loss caused by rejection greater than or equal to 6 months (P = 0.01 vs. either rejection less than 6 months or nonimmunologic loss); (b) cadaver donor (P = 0.005 vs. living related); and (c) interval between primary graft loss and retransplantation of greater than or equal to 6 months (P = 0.05 vs. less than 6 months). For CsA, risk factors that most decreased second graft survival were: (a) primary graft loss caused by rejection less than 6 months (P = 0.11 vs. nonimmunologic loss); (b) conventional immunosuppression for the primary graft (P = 0.08 vs. CsA immunosuppression); and (c) a peak PRA of greater than or equal to 21 (P = 0.14 vs. peak PRA of 1-20). For second graft recipients immunosuppressed with CsA, primary graft loss to either rejection greater than 6 months posttransplant or nonimmunologic causes was not a risk factor for second graft survival. These data extend the recent reports of other investigators by identifying risk factors for retransplant recipients treated with CsA and by demonstrating that subgroups of patients in the retransplant population can be retransplanted without additional risk (i.e., their second graft survival rates are similar to primary graft survival rates). This may become more important if, in the future, organ distribution is based on graft survival data. If so, our data would support retransplantation in patients who are immunosuppressed with CsA, especially those who lost their primary graft to either rejection greater than or equal to 6 months posttransplant or nonimmunologic causes; who receive living related grafts; and who have a peak PRA of 1-20.

Adult

The haematology of homozygous sickle cell disease after the age of 40 years.

Haematological indices have been studied in 181 patients with homozygous sickle cell (SS) disease aged 40-73 years. Cross-sectional analyses in 5-year age bands indicated age-related decreases in HbF (males only), total haemoglobin and platelet counts. Longitudinal studies within individuals confirmed the downward age-related trend in haemoglobin and platelets and also revealed a falling reticulocyte count, most significant when expressed as absolute values. Total nucleated cells also fell although the decline was significant only in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to patients with normal creatinine levels. The mechanism of this bone marrow failure is currently unknown.

Adult

Expression of MHC class II antigens by conjunctival epithelial cells in trachoma: implications concerning the pathogenesis of blinding disease.

In an attempt to understand the pathogenesis of corneal changes and conjunctival scarring in trachoma, which are responsible for blindness in some 7 million people worldwide, the surface expression of major histocompatibility complex class II antigens on conjunctival epithelial cells was sought in patients with different clinical features of the disease. Class II expression was significantly associated with active (inflammatory) trachoma, but an independent association with corneal pannus or conjunctival scarring could not be shown. Longitudinal data suggest that class II expression may antedate clinically active disease and persist after it has resolved.

Adolescent

HIV-2-induced immunosuppression among asymptomatic West African prostitutes: evidence that HIV-2 is pathogenic, but less so than HIV-1.

Two hundred and forty-one prostitutes working in The Gambia were tested for retroviral infections and their immune system evaluated. Sixty-three were seropositive for HIV-2 only, five for HIV-1 only and six for both HIV-1 and HIV-2 (26.1, 2.1 and 2.5%, respectively). When compared to seronegative individuals, the 63 women infected with HIV-2 clearly had an abnormal immune system, with significantly lower CD4+ and higher CD8+ lymphocyte counts and percentages, lower CD4+:CD8+ ratios, lower CD25+ (activated) lymphocyte counts, and lower lymphocyte proliferation responses after stimulation with phytohaemagglutinin, purified protein derivative (PPD), Candida or pokeweed mitogen, and higher levels of neopterin and beta 2-microglobulin. However, when the HIV-2-seropositive prostitutes were compared with the five women infected with HIV-1, the former were less abnormal, with significantly higher CD4+ percentages and CD4+:CD8+ ratios and lower CD8+ percentages and counts. Immunological anomalies were seen in five women known to have been infected with HIV-2 for less than 17 months. Coinfection with HTLV-1 resulted in more severe immunological alterations than infection with HIV-2 alone.

Acquired Immunodeficiency Syndrome