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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

Doppler ultrasound of the uterine arteries: the importance of bilateral notching in the prediction of pre-eclampsia, placental abruption or delivery of a small-for-gestational-age baby.

The use of Doppler studies of the uterine arteries in the prediction of pre-eclampsia and intrauterine growth retardation has had mixed success. The introduction of color Doppler imaging and the use of the "notch' to define an abnormal waveform have helped to improve the predictive value of uterine artery Doppler screening. The aim of this study was to evaluate the use of uterine artery Doppler in a group of women of mixed race and parity. This study was a prospective, cross-sectional analysis of 1326 unselected women who were screened with continuous wave uterine Doppler at 19-21 weeks, as part of a fetal anomaly/dating scan. A total of 214 women with abnormal uterine artery waveforms (notching) were referred for assessment at 24 weeks; 191 attended and had color Doppler imaging/pulsed Doppler studies of both uterine arteries. Data from 185 pregnancies were suitable for analysis. There were abnormal uterine Doppler findings (uni- or bilateral notching) in 110 patients at 24 weeks; 48 had bilateral notching. The sensitivity of notching for the prediction of proteinuric pregnancy-induced hypertension (PPIH) was similar in primiparas (76.9%), multiparas (77.7%), African-Caribbean women (82.6%) and Caucasian women (71.4%). The sensitivity of bilateral notching for the prediction of PPIH requiring delivery before 34 weeks was 81.2%, and 57.6% for babies small for gestational age (SGA), with positive predictive values of 27% (PPIH), 31.2% (SGA) and 37.5% (any complication). Patients with persistent bilateral notching are particularly at risk of developing PPIH or delivering an SGA baby before 34 weeks' gestation; they warrant increased surveillance, and may be a group that could benefit from prophylactic therapies.

Abruptio Placentae↗

Phase I/II trial of filgrastim (r-metHuG-CSF), CEOP chemotherapy and antiretroviral therapy in HIV-related non-Hodgkin's lymphoma.

BACKGROUND: A phase I/II trial determined the maximum tolerated dose (MTD) of CEOP for AIDS-related non-Hodgkin's lymphoma (NHL) with concurrent filgrastim and antiretroviral therapy. PATIENTS AND METHODS: Fourteen AIDS-NHL patients, chemotherapy naïve and ECOG performance status < 2 received filgrastim 1.0 microgram/kg s.c. daily for 3-7 days to assess neutrophil response, followed by CEOP with filgrastim support 10 micrograms/kg s.c. daily, day 2-14, continued if the absolute neutrophil count (ANC) < 1.2 x 10(9)/l. Two CEOP dose cohorts were used: cohort 1 (5 patients) - cyclophosphamide (C) 500 mg/m2, epirubicin (E) 37.5 mg/m2, vincristine (O) 2 mg and prednisolone (P) 75 mg/m2 daily on days 1-5; cohort 2 (9 patients) - C 750 mg/m2, E 50 mg/m2, same doses of O and P. Antiretroviral therapy was maintained (zidovudine-10, ddI-3, both-1). RESULTS: In cohort 1, 4/5 patients received at least 3 courses of CEOP with one complete response after five cycles and four progressions. Four have died (3-21 months after entry) with 1 alive at 40 months. Dose limiting toxicity (DLT - grade IV febrile neutropenia in cycle 1) occurred in 1 patient. In cohort 2, 5/9 completed > or = 5 cycles with 6 complete responses, 1 partial response and 2 progressions, 6 deaths and 3 alive at > 33 months. DLT (evaluable in 8 patients) occurred in two patients. Median survival for both cohorts was 17 months. Mean relative dose intensity was > 85%. CONCLUSIONS: The dosages of CEOP in cohort 1 defined the MTD however, the cohort 2 doses with filgrastim and antiretroviral therapy gave an encouraging response, acceptable toxicities and merit further study.

Adult↗

Toombak-associated oral mucosal lesions in Sudanese show a low prevalence of epithelial dysplasia.

Clinical (n = 281) and histopathological (n = 141) characteristics of toombak-associated oral mucosal lesions detected in an epidemiological study in northern Sudan in 1992/93 are described. The lesional site in the majority of toombak users was the anterior lower labial groove and the lower labial mucosa. 4 degrees (1-4) of clinical severity of lesions, similar to those used to characterise Swedish snuff-dipper's lesion, were applied. An association between the severity of mucosal lesions and a longer lifetime duration (> 10 years) of toombak use was found, but the severity was not related to the daily frequency of the habit. Parakeratosis, pale surface staining of the epithelium and basal cell hyperplasia were commonly observed, but epithelial dysplasia was infrequent (10/141). The most significant observation was a PAS-positive amorphous deposit between the lamina propria and the submucosa, found in 25/141 biopsies. The clinical and histopathological features of toombak lesions are closely similar to Swedish moist snuff-dipper's lesions and this may reflect the high alkalinity of these products, resulting in an alkaline burn on the oral mucosa following chronic exposure. The low prevalence of epithelial dysplasia implies a low risk of malignant transformation. Nevertheless, the high concentrations of tobacco-specific nitrosamines present in toombak, and the high prevalence of oral cancer in Sudan, mandate biopsy and careful histopathological analysis of any such lesions detected in habitues.

Adolescent↗

Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans.

We investigated the appearance and evolution of immunoglobulin M (IgM) and IgG antibodies to Borrelia burgdorferi in 46 patients with culture-proven erythema migrans (EM). All patients received antimicrobial treatment and were prospectively evaluated for up to 1 year. A total of 257 serially collected serum samples were tested by commercial IgG-IgM enzyme-linked immunosorbent assay and separate IgM and IgG immunoblots (IBs). At the baseline, 33% of the patients had a positive ELISA result and 43% of the patients had a positive IgM IB result by using the criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors for the interpretation of IB results. Positive serology at the baseline and the rate of seroconversion correlated directly with disease duration and/or evidence of dissemination prior to treatment. At days 8 to 14 after the baseline, 91% of patients had a positive ELISA result and/or IgM IB result. Peak IgM antibody levels were seen at this time in patients with localized or disseminated disease. The most frequent IgM bands at the baseline and the peak were of 24 kDa (OspC), 41 kDa, and 37 kDa. Although 89% of the patients developed IgG antibodies as determined at a follow-up examination, only 22% were positive by the IgG IB criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors. The persistence of antibodies was directly related to disease duration and/or dissemination prior to treatment. Since IgM antibodies to the 24- and 41-kDa antigens remained detectable for long periods, 38% of IgM IBs were still positive at 1 year postbaseline. IgM to antigens of 39, 58, 60, 66, or 93 kDa, conversely, were most often seen in sera obtained within 1 month postbaseline. Their presence may be of assistance in confirming a recent infection with B. burgdorferi in individuals living in areas where Lyme disease is endemic.

Antibodies, Bacterial↗

Molecular typing of Borrelia burgdorferi from Lyme disease patients by PCR-restriction fragment length polymorphism analysis.

Ninety-three Borrelia burgdorferi isolates obtained from erythema migrans lesions or blood of Lyme disease patients in Westchester County, N.Y., between 1991 and 1994 were characterized by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the 16S-23S rRNA gene spacer. All isolates could be classified into three distinct RFLP types. Among the 82 skin biopsy isolates studied, 21 (25.6%) were type 1, 37 (45.1%) were type 2, and 21 (25.6%) were type 3. Three (3.7%) cultures contained a mixture of two isolates with distinct RFLP types. The 11 isolates cultured from blood showed a similar predominance of RFLP type 2 (6 of 11; 54.5%) relative to types 1 (2 of 11; 18.2%) and 3 (3 of 11; 27.3%). For one patient both skin and blood isolates were cultured, and RFLP analysis revealed that these isolates differed from one another. This study demonstrates that there is genotypic heterogeneity in B. burgdorferi strains infecting Lyme disease patients, and this typing approach may allow differentiation of isolates with various degrees of pathogenic potential.

Bacterial Typing Techniques↗

Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the lung.

Immunohistochemical expression of p53, bcl-2, CD44 standard (CD44S), and the v6 isoform of CD44 (CD44v6) proteins were studied in 14 typical carcinoid tumors (TCs), 11 atypical carcinoids (ACs), and eight small cell carcinomas (SCLCs) in an attempt to use these markers of mutational events and cellular adhesion to discriminate neoplasms demonstrating neuroendocrine differentiation. p53 and bcl-2 overexpression were associated with more aggressive neuroendocrine cell types. p53 nuclear staining was weakly positive in 21% of the TCs, whereas strong nuclear staining was seen in 64% of the ACs and 88% of the SCLCs (P = 0.0047). bcl-2 was present in 21% of the TCs, 91% of the ACs, and 100% of the SCLCs (P = 0.0001). In contrast, CD44S and CD44v6 were inversely correlated with more aggressive types of neuroendocrine tumors. CD44S expression was moderate to strong in all of the TCs and 91% of the ACs but in only 37% of the SCLCs (P = 0.0018). There was no correlation between expression of these markers and tumor size or nodal status, although loss of CD44v6 was associated with lymph node metastases in the TC group only. In the spectrum of neuroendocrine tumors of the lung, p53 and bcl-2 overexpression correlates with more aggressive histologic cell types. The decreasing CD44S expression in AC and SCLC is similar to findings in cancer of the colon and in non-small cell carcinoma of the lung, where loss of CD44S is associated with poor prognosis. In AC and SCLC, but not in cancer of the colon, loss of CD44v6 correlates with more aggressive neoplasms and might correlate with lymph node metastases in TCs.

Adult↗

The static-charge-sensitive bed in the monitoring of respiration during sleep in infants and young children.

The performance of the static-charge-sensitive bed (SCSB) in the monitoring of nocturnal breathing was studied in 22 infants and young children at the mean age of 24 weeks (SD 24, range 1-79 weeks). The conventional polysomnogram (PSG) was used as a reference method. Episodes of central apnoea were detected with high sensitivity by the SCSB. Episodes of obstructive apnoea and obstructive parts of mixed apnoea were not identified. When the SCSB recordings were scored with the airflow signal some mixed events were identified, but the detection of obstructive apnoea episodes remained poor. Partial upper airway obstruction increased the amount of SCSB spiking (high-frequency components of breathing), which may have diagnostic value. In conclusion, the SCSB enables simple, non-invasive detection of central apnoea episodes, periodic breathing and the behavioural state of the child.

Analysis of Variance↗

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↗