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Biomedical subjects

D Cooper

Publications and source records attributed to D Cooper.

At least 91 records · Page 5Linked to original sources

Lymphomatoid granulomatosis of the skin and lung. An angiocentric T-cell-rich B-cell lymphoproliferative disorder.

OBJECTIVE: To test the recent hypothesis that lymphomatoid granulomatosis (LYG) is a clonal B-cell proliferative process related to Epstein-Barr virus (EBV). BACKGROUND AND DESIGN: Historically, LYG has been classified as an angiocentric T-cell lymphoproliferative disorder. To further characterize LYG in the skin, we analyzed for EBV RNA in lymphocytes using in situ hybridization, coupled with colabeling for B-cell and T-cell markers. Clonality of lymphocytes was assessed by polymerase chain reaction using primers for immunoglobulin heavy chain genes and T-cell receptor beta and gamma genes. SETTING: Academic referral center. PATIENTS: In a 5-year retrospective review, we identified 4 patients with classic clinical and pathologic features of LYG in skin and lung, and tissue available from both sites. MAIN OUTCOME MEASURES: The presence or absence of EBV RNA and clonal gene rearrangements in cutaneous and pulmonary lesions of LYG. RESULTS: Biopsy specimens of skin and lung in all patients revealed angiocentric infiltrates predominantly composed of T lymphocytes. Epstein-Barr virus RNA was identified in the skin of 1 patient and the lung of 3 patients, and was restricted to B cells. Polymerase chain reaction revealed clonal immunoglobulin heavy chain gene rearrangements and no clonal rearrangement of T-cell receptor genes in skin and lung tissue of all patients. CONCLUSIONS: At least some examples of LYG in the skin and lung are characterized by a clonal proliferation of B lymphocytes, some of which contain EBV RNA. The B cells are typically scarce and may be obscured by striking angiocentric T-cell infiltrates.

Adult↗

Cervical cytology screening--knowledge, attitudes and practice in a peri-urban settlement.

AIM: To determine the knowledge, attitudes and practice of women living in peri-urban settlements with regard to screening for cervical cancer. METHOD: A community-based questionnaire survey of 165 women living in a defined area of Khayelitsha, a peri-urban settlement on the outskirts of Cape Town. RESULTS: Two hundred households were visited, with a response rate of 84%. Median age of respondents was 27.5 years. The majority of interviewees were married (53.3%), unemployed (61.5%), had an educational status of standard 4 or less (58.1%) and had been living in Cape Town for 4 years or more (64.3%). The median parity was 2 (range 0-11). Most interviewees were currently using contraception (52.4%). One-third (35.4%; 95% CI 28.1-42.7%) of interviewees had heard of the Pap smear. Of these women, most had obtained their information from the midwife obstetric unit (MOU), and this was the most commonly reported facility where Pap tests were known to be done. The majority of interviewees did not regard the test (or the prospect thereof) as embarrassing (88.4%), painful (89.1%) or harmful (90.9%), and indicated that they would have the test done (89.1%). The most important reason for choice of where the test should be done was proximity to place of residence (83.9%). More than one-third of interviewees reported having had a Pap test (37.2%; 95% CI 28.8-44.8%). The most common reason for not having had a test was that the interviewee had never heard of it (81.3%). Most had undergone the test at a MOU (65.6%), where it had been part of an antenatal work-up (80.3%). Fewer than half of the interviewees who had undergone a test knew the result of their test. CONCLUSION: The antenatal, obstetric and family planning services in the area have been effective, to a limited extent, in providing information and conducting screening. However, these services are missing many opportunities to fulfill this function, and knowledge and practice of cervical cytology screening in this community are poor. With the implementation of a rational policy for screening in this area there is the potential to achieve good coverage.

Adolescent↗

Transendothelial migration of neutrophils involves integrin-associated protein (CD47).

Inflammation is a primary pathological process. The development of an inflammatory reaction involves the movement of white blood cells through the endothelial lining of blood vessels into tissues. This process of transendothelial cell migration of neutrophils has been shown to involve neutrophil beta 2 integrins (CD18) and endothelial cell platelet-endothelium cell adhesion molecules (PECAM-1; CD31). We now show that F(ab')2 fragments of the monoclonal antibody B6H12 against integrin-associated protein (IAP) blocks the transendothelial migration of neutrophils stimulated by an exogenous gradient of the chemokine interleukin 8 (IL-8; 60% inhibition), by the chemotactic peptide N-formyl-methionylleucylphenylalanine (FMLP; 76% inhibition), or by the activation of the endothelium by the cytokine tumor necrosis factor alpha (98% inhibition). The antibody has two mechanisms of action: on neutrophils it prevents the chemotactic response to IL-8 and FMLP, and on endothelium it prevents an unknown but IL-8-independent process. Blocking antibodies to IAP do not alter the expression of adhesion proteins or production of IL-8 by endothelial cells, and thus the inhibition of neutrophil transendothelial migration is selective. These data implicate IAP as the third molecule essential for neutrophil migration through endothelium into sites of inflammation.

Antibodies, Monoclonal↗

Typing of Legionella pneumophila serogroup 1 isolates by degenerate (D-)RAPD fingerprinting.

A new method to identify clonal strains of pathogenic bacteria has been developed recently in this laboratory. The method utilizes degenerate random amplified polymorphic DNA primers (D-RAPD) to amplify random fragments in crude bacterial lysates, generating reproducible DNA banding profiles or fingerprints. We use this method to type outbreak and non-outbreak isolates of Legionella pneumophila serogroup 1 from four hospitals near to, and affiliated with the University of Pittsburgh Medical Center. Patient isolates from a large outbreak, and nearly half of the contemporaneous environmental isolates showed the same DNA profile. Other isolates derived from non-outbreak patients showed easily distinguishable profiles. Other Legionella isolates collected between 1984 and 1994 were also analysed by this method. Our studies demonstrate that four strains were common among patient and environmental isolates at the four hospitals. These strains were also found to be different from a limited number of isolates from outside the Pittsburgh area. Because of its speed, simplicity and powerful discriminating ability, we believe that the D-RAPD approach provides epidemiologists and hospital infection control teams with a powerful tool in their efforts in analysing and terminating infection outbreaks.

Bacterial Typing Techniques↗

Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy.

Pain from oral mucositis afflicts from 40% to 70% of patients receiving chemotherapy or radiation therapy. Current methods of clinical pain management (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oral capsaicin to provide temporary relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers, desensitizes some neurons and has provided moderate pain relief when applied to the skin surface. Oral capsaicin in a candy (taffy) vehicle produced substantial pain reduction in 11 patients with oral mucositis pain from cancer therapy. However, this pain relief was not complete for most patients and was only temporary. Additional research is needed to fully utilize the properties of capsaicin desensitization and thus optimize analgesia.

Administration, Oral↗

P-selectin interacts with a beta 2-integrin to enhance phagocytosis.

P-selectin is an adhesion molecule for myeloid cells that seems to be essential for the development of cellular inflammatory responses. We show that adhesion of neutrophils to purified and recombinant P-selectin enhances the phagocytosis of unopsonized zymosan particles as judged by the number of cells ingesting particles (30.2 +/- 5.8 vs 14.5 +/- 4.0, p = 0.002) and the number of particles ingested per cell (percentage increase 58.3 +/- 4.4%. p = 0.0002). The enhanced phagocytosis was inhibited by Abs to CD18 or CD11b, suggesting that P-selectin alters beta 2-integrin function. The enhancement was only seen in the presence of cations allowing the integrin to assume a particular extracellular conformation. Furthermore, P-selectin, although not altering the total expression of CD18 on neutrophils, significantly increased the binding of mAb 24, which detects an activation-dependent epitope. Our results support a signaling role for P-selectin in influencing beta 2-integrin function.

Animals↗

Acute cauda equina syndrome. Diagnostic advantage of MRI.

Speed and completeness are vital in the radiographic evaluation of an acute cauda equina syndrome presentation to maximize its resolution with rapid appropriate surgical intervention. Magnetic resonance imaging provides the optimal method for non-invasive evaluation.

Acute Disease↗

Vocational integration services in community mental health: professionals' perceptions of training needs.

Vocational integration in mental health is part of a national initiative to make quality, community-based work a possibility for persons with psychiatric disabilities. While effective delivery of these services requires trained staff, preparing professionals to provide relevant vocationally oriented services is complex and challenging. This study examines perceived priority training needs in vocational integration services from the perspectives of professionals in mental health, rehabilitation, and education organizations in Mississippi. Findings suggest that vocational integration activities are perceived differently across organizations and across occupational specialties. Implications for staff development in community support and psychosocial rehabilitation programs are discussed.

Community Mental Health Services↗

Dental needs of pre-retirement and retired people in an inner-city area.

Perceived and normative dental needs were assessed for people of pre-retirement (55-64 years) and retirement age (65-74 years) in Camberwell, London, using a postal questionnaire and dental examination. Of the pre-retirement group, 77% were dentate compared with 65% in the older cohort. The younger age-group were more likely to believe teeth were more important and to perceive a need for dental care. People who attended for the examination were more likely to perceive a need for (64% and 15% respectively) and want treatment (39% and 17%) than non-examinees. Also, they were more likely to be unhappy with their appearance (43% and 20%) and to be in pain (42% and 21%). Treatment need was similar for both groups with regard to restorative and extraction needs. However, the retirement group were more likely to have deep periodontal pockets (33% and 8%) and a greater normative need for denture care.

Aged↗

Sustained cellular immune responses to Borrelia burgdorferi: lack of correlation with clinical presentation and serology.

Fifty-one patients with erythema migrans were followed up prospectively with serial clinical evaluations, serologic determinations for antiborrelial antibodies, and lymphocyte stimulation responses to Borrelia burgdorferi antigens to determine (i) the factors associated with sustained cellular immune responses and (ii) whether lymphocyte stimulation is a good indicator of prior exposure to B. burgdorferi in patients treated early after erythema migrans. Positive lymphocyte stimulation responses ( > 2 standard deviations above normal control values) were found in 15 (29%) of 51 patients 3 months after treatment for erythema migrans and in 8 (18%) of 44 patients 1 year posttreatment. Heightened lymphocyte responses were not associated with the number or duration of erythema migrans lesions prior to treatment, the mean size of the largest erythema migrans lesion, or the number of symptoms at the time of presentation. The development of Jarisch-Herxheimer reaction, choice of antibiotic, and clinical outcome also were not associated with a positive lymphoproliferation assay result. Changes in the lymphocyte stimulation indices between the two time points assessed (3 months and 1 year posttreatment) also did not correlate with the above variables. When serologic results and lymphoproliferative responses were evaluated as categorical or continuous variables, there were no correlations between values. One year after treatment for early Lyme disease, lymphocyte reactivity is not a good indicator of prior infection with B. burgdorferi.

Adult↗

Ductus arteriosus smooth muscle cell migration on collagen: dependence on laminin and its receptors.

During permanent closure of the ductus arteriosus, smooth muscle cells migrate through the extracellular matrix (ECM) to form intimal mounds that occlude the vessel's lumen. Smooth muscle cells (SMC) migrate over surfaces coated with collagen in vitro. During the migration SMC also synthesize fibronectin (FN) and laminin (LN). Antibodies against FN and LN inhibit migration on collagen by 30% and 67%, respectively. Because of the apparent importance of LN in migration, we examined how SMC interact with LN and LN fragments (P1, E8, P1', E1', E3, E4, and G). Ductus SMC adhere to high concentrations of LN and two fragments of the molecule: P1 and E8. They use a unique set of integrin receptors to bind to LN (alpha 1 beta 1, alpha 6 beta 1 and alpha v beta 3), to P1 (alpha 1 beta 1, alpha v beta 3), and to E8 (alpha 6 beta 1, alpha v beta 3). The alpha v beta 3 integrin binds to the P1 fragment of LN in an RGD peptide-dependent manner, and to the E8 fragment in an RGD-independent manner; the RGD site on the P1 fragment probably is not available to the cell in intact LN. Antibodies against beta 1 integrins completely inhibit SMC adhesion to LN; antibodies against the alpha v beta 3 integrin do not block SMC adhesion to LN, but do prevent cell spreading. LN is also capable of interfering with SMC adhesion to other ECM components. The antiadhesive effect of LN is located in the E1' domain. Both exogenous and endogenous LN increase SMC motility on collagen I. The locomotion-promoting activity of LN resides in the E1' antiadhesive domain, and not in its adhesive (P1, E8) domains. LN causes a decrease in the number of focal contacts on collagen I. This might enable SMC to alter their mobility as they move through the extracellular matrix to occlude the ductus arteriosus lumen.

Amino Acid Sequence↗

Polymerase chain reaction amplification of culture supernatants for rapid detection of Borrelia burgdorferi.

A combination of culture and polymerase chain reaction (PCR) amplification was employed to detect Borrelia burgdorferi in in vitro cultures of skin biopsy specimens. Spirochetes were observed by microscopic examination in 56% (20/36) of the cultures from patients with erythema migrans who had not received prior antibiotic treatment. No growth of Borrelia burgdorferi was detected in control cultures or those from patients who had received antibiotics. PCR analysis of culture supernatants agreed with microscopic evaluation in 50/51 evaluable cultures tested (both positive and negative). At two weeks of incubation Borrelia burgdorferi could be detected by PCR in 19/20 cultures (95%) compared to 14/20 (70%) by visual inspection. This study indicates that a combined culture-PCR test for detection of Borrelia burgdorferi is more rapid and specific than culture alone.

Borrelia burgdorferi Group↗

Failure to isolate Borrelia burgdorferi after antimicrobial therapy in culture-documented Lyme borreliosis associated with erythema migrans: report of a prospective study.

BACKGROUND: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment. A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment. METHODS: Skin biopsies were performed in patients with EM and cultured for B. burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture-positive patients after the completion of antimicrobial therapy. RESULTS: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria. Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001). The only other identified factor associated with successful recovery of B. burgdorferi was shorter duration of EM. When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01). B. burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy. Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart. CONCLUSIONS: After brief courses of antibiotics, B. burgdorferi appears to be rapidly eliminated from the skin at EM sites. The ability to recover B. burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time.

Adult↗

AIDS-associated Kaposi's sarcoma in Romanian children.

BACKGROUND: Kaposi's sarcoma (KS) is commonly associated with the acquired immunodeficiency syndrome (AIDS) in adults. Little is known regarding its occurrence in children. OBJECTIVE: Our purpose was to report the clinical and epidemiologic characteristics of KS in three Romanian children with AIDS and to compare them with previously reported AIDS-associated KS in children. METHODS: This was a clinicopathologic study and computer-based literature review. RESULTS: All three Romanian children had skin involvement; two had involvement of lymph nodes and internal organs. All had acquired human immunodeficiency virus (HIV) infection postnatally. Including these children, 33 cases of AIDS-associated KS in children have been reported. Thirteen of 30 evaluable patients had acquired HIV infection postnatally; nine of these children (69%) had cutaneous involvement by KS. A perinatal route of transmission was present in the remaining 17 cases; only two of these children (12%) with KS had cutaneous involvement. No case was noted in which intravenous drug use was the sole parental HIV risk factor. CONCLUSION: The data support the contention that KS is caused by a second infectious agent prevalent only in certain HIV-infected populations. Children of parents in high-risk groups for KS and children who acquire HIV via contaminated blood or blood products are at highest risk for KS. The route of acquisition of HIV infection may also be associated with different clinical manifestations of KS in children.

Acquired Immunodeficiency Syndrome↗

NMR studies of diffusional water permeability of red blood cells from macropodid marsupials (kangaroos and wallabies).

1. The water permeabilities of the red blood cell (RBC) membranes of five species of macropodid marsupials were monitored by using a Mn(2+)-doping 1H nuclear magnetic resonance (NMR) technique. 2. Since this appears to be the first time that this type of measurement at 400 MHz for 1H has been reported, an analysis of instrumental parameters influencing the estimated value of the water exchange time (Te), and of the diffusional water permeability (Pd), was performed on samples of human RBC. 3. It was found that a short interpulse delay in the Carr-Purcell-Meiboom-Gill pulse sequence had to be used (around 100 microseconds) to avoid an underestimation of the relaxation times, that occurred as the result of molecular diffusion through non-uniform local magnetic fields in and around the cells. 4. There were no significant differences, in the water permeabilities of the RBC membranes, between the five species (Macropus rufogriseus, M. parma, M. eugenii, M. parryi and Wallabia bicolor). 5. There were also no significant differences between various colonies of M. eugenii living in different habitats. 6. The average values of Pd were 9.1 x 10(-3) cm/sec at 24.6 degrees C, 10.4 x 10(-3) cm/sec at 30 degrees C, 12.6 x 10(-3) cm/sec at 37 degrees C, and 14.7 x 10(-3) cm/sec at 42.1 degrees C; these were more than twice as high as those for human RBC. 7. In agreement with the high water permeability the RBC of macropodids displayed a relatively low activation energy of water diffusion across their membranes, approximately 21 kJ/mol, compared with 25 kJ/mol for human RBC.

Animals↗