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Biomedical subjects

C Campbell

Publications and source records attributed to C Campbell.

At least 127 records · Page 7Linked to original sources

Emergency care in Namibia.

Namibia is a sparsely populated nation in southwest Africa. A state-run health service provides care to most of the population. The geography and population distribution dictate the delivery systems for prehospital and emergency care. A state-run ambulance service provides basic patient transportation to the state-run hospitals. There is no 911 system. Two private aeromedical companies in Namibia provide the full range of ground and aeromedical treatment, diver rescue, and helicopter and fixed-wing transport services. The scope of care includes cricothyrotomies, chest tubes, and rapid-sequence intubation. Equipment is modern and virtually identical to what is used in the United States. There are no emergency physicians in Namibia. General medical officers are the backbone of the state-run health service. General medical officers assigned to cover the ED are called casualty officers. No specialized training beyond internship is required, and assignments to casualty are viewed as temporary until better positions become available. Only the largest state hospital in the capital has a dedicated, 24-hour emergency staff. The private prehospital care/transport systems are well organized and sophisticated. Formal efforts should be undertaken to develop ties with our colleagues in Namibia. Potential areas for collaboration include injury surveillance and prevention, field trauma resuscitation, and prehospital care.

Air Ambulances↗

Plasmablastic lymphoma: a new subcategory of human immunodeficiency virus-related non-Hodgkin's lymphoma.

A patient with human immunodeficiency virus-related non-Hodgkin's lymphoma arising in the oral cavity is reported. The tumour had an unusual immunohistochemical profile that was negative for leucocyte common antigen and the B-cell antigen CD20 but positive for the plasma cell-reactive antibody VS38c. The features of this type of tumour, which has recently been categorized, are presented and discussed.

Adult↗

Predicting depression in women: the role of past and present vulnerability.

BACKGROUND: A prospective study, covering just over a 1-year period, sought to confirm an earlier finding that around 40% of women who experience a severe life event in the presence of two ongoing psychosocial vulnerability factors, (negative close relationships and low self-esteem) will develop a major depressive episode. Distal risk factors were examined to see if they improved prediction. METHODS: A population sample of 105 mainly working-class mothers with vulnerability and without depression were interviewed three times over a 14-month period to date the occurrence of severe life events and onset of major depression. Degree of vulnerability was assessed at first contact together with distal risk in terms of childhood neglect/abuse and any earlier episodes of depression. RESULTS: Thirty-seven per cent of these vulnerable women became depressed in the study period. The majority experienced a severe life event, and of these, 48% had onsets. Contrary to expectation, risk was only a little less among those with just one of the two vulnerability factors. Two-thirds of women with an onset had been depressed in previous years. Although this was associated with increased risk, the effect was greatest for those who had experienced an episode before age 20. A relationship between childhood neglect/abuse and onset was entirely accounted for by such early depression. CONCLUSION: An aetiological model of depression outlined in earlier research was confined with a new factor of teenage depression shown to increase risk of onset.

Adolescent↗

A phase I-II study of bi-weekly paclitaxel as first-line treatment in metastatic breast cancer.

BACKGROUND: Single-agent bi-weekly paclitaxel was studied as first-line metastatic treatment for breast cancer in a phase I-II trial. PATIENTS AND METHODS: Thirty-eight women with metastatic breast cancer were enrolled. Thirty-seven are evaluable for toxicity, 35 for response. RESULTS: The MTD was defined at 160 mg/m2 q two weeks with dose limiting toxicity in two patients consisting of hematological toxicity (1) and neurotoxicity (2). Twenty patients were treated at 150 mg/m2, the recommended dose. Response rates were two CRs and nine PRs (overall 61%) at the RD of 150 mg/m2 and three CRs and 11 PRs for an overall RR of 67% for the two top doses. CONCLUSIONS: The good drug tolerance, response rates, and convenience over weekly treatment suggest this may be a worthwhile regimen.

Adult↗

Nucleolin promotes homologous DNA pairing in vitro.

We purified to near homogeneity a previously identified 100 kDa mammalian homologous DNA pairing protein. The purified 100 kDa protein also catalyzed high levels of cell-free homologous DNA recombination activity. This ATP-dependent activity was capable of forming conservative recombinant products between two circular, double-stranded DNA molecules. We were unable to detect any DNA polymerase, DNA ligase, or 5' or 3' exonuclease activity associated with this purified material. The purified 100 kDa protein bound silver nitrate as well as a monoclonal antibody specific for nucleolin. A recombinant protein comprised of the Escherichia coli maltos-ebinding protein fused to the carboxyl-terminal two-thirds of human nucleolin possessed homologous DNA pairing activity. These data indicate that the 100 kDa homologous DNA pairing protein is nucleolin. The observation that nucleolin can carry out homologous DNA strand pairing in vitro raises the prospect that it may function similarly in vivo.

Base Pairing↗

Corneal aberrations, monocular diplopia, and ghost images: analysis using corneal topographical data.

Corneal irregularities can create conditions in which monocular diplopia, "ghost images," and multiple images of various types occur, thus degrading vision. For these secondary images to occur, corneal irregularities must create areas which form: (1) images which are displaced from the primary image; (2) sufficiently focused images; and (3) images which have sufficient contrast to be noticed in the presence of the primary image. Criteria necessary to satisfy these three conditions using measurable data are developed. The concept of a differential deflection field is introduced, and a method to create this field using corneal topography data is developed. It is shown how to use differential deflection field data to assess if conditions necessary for creating secondary images will occur in cases of corneal distortion.

Algorithms↗

Reduced Ca2+ uptake by mitochondria in pyruvate dehydrogenase-deficient human diploid fibroblasts.

Physiological and pathological Ca2+ loads are thought to be taken up by mitochondria via a process dependent on aerobic metabolism. We sought to determine whether human diploid fibroblasts from a patient with an inherited defect in pyruvate dehydrogenase (PDH) exhibit a decreased ability to sequester cytosolic Ca2+ into mitochondria. Mobilization of Ca2+ stores with bradykinin (BK) increased the cytosolic Ca2+ concentration ([Ca2+]c) to comparable levels in control and PDH-deficient fibroblasts. In normal fibroblasts transfected with plasmid DNA encoding mitochondrion-targeted apoaequorin, BK elicited an increase in Ca2(+)-dependent aequorin luminescence corresponding to an increase in the mitochondrial Ca2+ concentration ([Ca2+]mt) of 2.0 +/- 0.2 microM. The mitochondrial uncoupling agent carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone blocked the BK-induced [Ca2+]mt increase, although it did not affect the [Ca2+]c transient. Basal [Ca2+]c and [Ca2+]mt in control and PDH-deficient cells were similar. However, confocal imaging of the potential-sensitive dye JC-1 indicated that the percentage of highly polarized mitochondria was reduced from 30 +/- 1% in normal cells to 19 +/- 2% in the PDH-deficient fibroblasts. BK-elicited [Ca2+]mt transients in PDH-deficient cells were reduced to 4% of control, indicating that PDH-deficient mitochondria have a decreased ability to take up cytosolic Ca2+. Thus cells with compromised aerobic metabolism have a reduced capacity to sequester Ca2+.

Aequorin↗

Optical isolation of portions of a wave front.

A criterion is established for determining when portions of a wave front can be said to be optically isolated from the rest of the wave front in the sense that they can subsequently be treated separately when one is considering the formation of images. The subarea of the wave front is treated as a separate aperture, and it is said to be isolated if diffraction maxima for the majority of the wave front fall at or beyond the first minima for the subarea. An illustrative example employing two circular unequal-diameter apertures is presented. A method is given for identifying portions of wave front that may be optically isolated; the method uses the technique of fitting a reference surface to the actual wave front and then finding what is defined as the differential deflection of the actual surface with respect to the reference surface at all locations. Subpopulations of locations with similar differential deflection values, sufficient numbers, and sufficient differential deflection are candidates for area of optical isolation.

Light↗

Efficacy of an oral vaccinia-rabies glycoprotein recombinant vaccine in controlling epidemic raccoon rabies in New Jersey.

A field trial to evaluate the efficacy of an oral vaccinia-rabies glycoprotein recombinant virus vaccine in controlling epidemic raccoon (Procyon lotor) rabies was conducted by distributing 180,816 doses (10(8.2)TCID50/ml) of vaccine in wax ampules within fish-meal polymer baits at a rate of 64 doses/km2/treatment throughout a 552 km2 area, forming an 18 km wide band across the northern Cape May Peninsula of New Jersey (USA). Vaccination treatments were conducted in the spring and fall between May 1992 and October 1994 from a helicopter along ecotones and from motor vehicles along roads. Vaccine-laden baits were removed by animals from tracking stations within 3 wk and 61% of the identifiable tracks were those of raccoons. Tetracycline incorporated in the baits as a biomarker was detected in 155 (73%) of the vaccination area raccoons following the fall 1993 and spring 1994 vaccinations. Eleven (61%) of the raccoons sampled in the same time period seroconverted (> or = 0.5 IU) in response to rabies virus glycoprotein. A raccoon diagnosed with rabies from the northern border of the vaccination area on 30 April 1993 provided the first evidence that the barrier was being challenged by the rabies epidemic. The prevalence of rabies in raccoons from the vaccination area for the first year (10%, n = 96) and second year (8%, n = 61) of challenge was reduced more than six-fold by vaccination compared to unvaccinated raccoons from northern adjacent surveillance areas during the corresponding first (65%, n = 189) and second years (53%, n = 43). Vaccination also effectively reduced by three-fold the rate at which the epidemic moved through the raccoon population (15 km/yr). The breach of the vaccination area resulted in a resumption of the high rate (43 km/yr) of epidemic movement and a significant nine-fold increase in rabies prevalence (77%, n = 47). The maximum linear movement (12.9 km) among five ear-tagged rabid raccoons in the study area was significantly greater than that of 19 normal radio-collared raccoons (2.58 km) in the area. These large movements of rabid raccoons, together with relocation of nuisance raccoons, spillover of raccoon rabies in skunks (Mephitis mephitis) and other species, insufficient funding and a decision to discontinue the program in 1994 (which could have resulted in insufficient population immunity among raccoons in the vaccination area) may have contributed to the eventual breach of the barrier.

Administration, Oral↗

Understanding the epidemic of HIV in South Africa. Analysis of the antenatal clinic survey data.

OBJECTIVES: To investigate the magnitude and the time course of the HIV epidemic in the provinces of South Africa from the antenatal clinic HIV surveys. DESIGN: We analysed the data on the provincial prevalences of HIV infection from 1990 to 1996 using maximum likelihood methods to determine the intrinsic growth rate and probable asymptotic prevalence of HIV among women attending antenatal clinics. SUBJECTS: Women attending antenatal clinics and included in the national HIV prevalence surveys conducted by the Department of Health. RESULTS: 1. In KwaZulu-Natal the epidemic is likely to peak at a prevalence of about 23% (95% confidence interval (CI) 19-36%). 2. The intrinsic doubling time does not differ significantly among the provinces. 3. The average length of the intrinsic doubling time is 12.0 months (95% CI 11.3-12.8 months). 4. The force of infection is approximately 1.00/year at age 16 years and declines at a rate of about 5% per year of age above 16 years. CONCLUSIONS: South Africa is likely to experience one of the worst HIV epidemics in Africa. The lack of statistically significant differences between the growth rates of the epidemic in the various provinces constrains the possible explanations that can be advanced to explain the time course of the epidemic and may in part be a consequence of migrancy. The intrinsic growth rate is higher than previous estimates and it is possible that in those provinces where the prevalence is still low it will eventually reach the same levels as in KwaZulu-Natal.

Acquired Immunodeficiency Syndrome↗

Elevated homologous recombination activity in fanconi anemia fibroblasts.

It is widely believed that Fanconi anemia cells possess a reduced ability to repair inter-strand DNA cross-links. While the mechanism through which inter-strand DNA cross-links are removed from mammalian chromosomes is unknown, these lesions are repaired via homologous recombination in lower eukaryotes and bacteria. Based on the hypothesis that a similar mechanism of DNA repair functions in mammalian somatic cells, we measured homologous recombination activity in diploid fibroblasts from healthy donors, and Fanconi anemia patients. Somewhat surprisingly, homologous recombination levels in nuclear protein extracts prepared from Fanconi anemia cells were nearly 100-fold higher than in extracts prepared from control cells. We observed a similar increase in the activity of a 100-kDa homologous DNA pairing protein in extracts from Fanconi anemia cells. Transfection studies confirmed that plasmid homologous recombination levels in intact Fanconi anemia cells were substantially elevated, compared with control cells. These results suggest that inappropriately elevated levels of homologous recombination activity may contribute to the genomic instability and cancer predisposition that characterize Fanconi anemia.

Cell Nucleus↗

Blockade of CD28/B7 co-stimulation by mCTLA4-Hgamma1 inhibits antigen-induced lung eosinophilia but not Th2 cell development or recruitment in the lung.

We have studied the role of the CD28/B7 co-stimulatory pathway in the development of a Th2-type lung immune response. Mice injected two or three times intraperitoneally with ovalbumin in alum adjuvant and then re-exposed to the same antigen by intranasal (i.n.) inoculation show infiltration of the lung tissue and appearance in the broncho-alveolar lavage (BAL) fluid of significant numbers of eosinophils and lymphocytes, in a pattern which is reminiscent of asthmatic inflammation. The accumulation of eosinophils in the airways is completely dependent on interleukin (IL)-5 secretion by CD4+ T cells. We have used mice transgenic for a soluble form of murine CTLA-4 (mCTLA4-Hgamma1) which binds to B7 molecules on antigen-presenting cells, thereby preventing their interaction with T cell-expressed CD28. mCTLA4-Hgamma1-transgenic mice immunized intraperitoneally and challenged i.n. with ovalbumin failed to generate any eosinophil infiltration, suggesting that little or no IL-5 was secreted in the lungs of these mice. In contrast with the complete lack of eosinophils, the numbers and phenotypes of infiltrating lymphocytes were comparable in the lungs of mCTLA4-Hgamma1-transgenic and normal mice. Also, lung lymphocytes from immunized mCTLA4-Hgamma1-transgenic and normal mice could be shown to secrete comparable amounts of IL-4 and IL-5 when stimulated in culture in the absence of mCTLA4-Hgamma1. We conclude that mCTLA4-Hgamma1 can efficiently block the production of IL-5 during in vivo responses and inhibit eosinophil recruitment, but that it does not block the development of CD4+ T cells into Th2 cells with the potential to secrete IL-5.

Abatacept↗

Kinetics of splenocyte interleukin-4 production after injury and lethal endotoxin challenge.

Cytokine aberrations may contribute to sepsis-associated mortality after trauma. We have previously documented that IL-10 (a Th-2 cytokine) is downregulated after tissue trauma, and the administration of exogenous IL-10 improved survival and anti-IL-10 antibody increased lethality in a murine injury-lethal endotox-emia model. IL-4 activates the Th-2 subset of T cells, and functions in a paracrine manner to inhibit proinflammatory cytokine synthesis. The purpose of this study was to investigate the kinetics of IL-4 production in this murine trauma-sepsis model. Mice (n = 50) were randomized to five groups: Control, Femur Fracture (FFx), FFx-lipopolysaccharide (LPS), FFx-LPS-IL10, and FFx-LPS-Anti-IL10. LPS (400 micrograms ip) was administered 4 days after FFx to induce lethal sepsis. IL-10 (0.5 microgram ip) or anti-IL-10 (100 micrograms IP) was administered at resuscitation, 30 min after LPS. IL-4 production was measured in ex vivo splenocyte culture supernatants at 24-hr intervals. Splenocyte IL-4 production was significantly upregulated in the FFx-LPS group that received anti-IL-10; maximal IL-4 production was on Day 5, with a greater than sevenfold increase compared to all other groups. A transient early rise in IL-4 production was noted in the FFx-LPS group that received exogenous IL-10; however, a subsequent rapid decline was documented. Treatment with anti-IL-10 antibody after FFx injury and septic challenge with LPS is associated with an upregulation of splenocyte IL-4 synthesis, as well as an increase in mortality in this murine model. IL-4 and IL-10 interaction postinjury may profoundly influence monocyte activation, cell-mediated immunity, and the subsequent host immune response to infection.

Animals↗

Migrancy, masculine identities and AIDS: the psychosocial context of HIV transmission on the South African gold mines.

Levels of HIV infection are particularly high amongst migrant workers in sub-Saharan Africa. This paper presents a case study of one such vulnerable group of migrants-underground workers on the South African gold mines-and highlights the psychosocial context of HIV transmission in the mining setting. On the assumption that social identities serve as an important influence on peoples' sexual behaviour, the study examines the way in which miners construct their social identities within the parameters of their particular living and working conditions. It also identifies some of the key narratives used by miners to make sense of their experience in the realms of health, ill-health, HIV and sexuality. Masculinity emerged as a leading narrative in informants' accounts of their working life, health and sexuality, and the paper examines the way in which the construction of masculine identities renders miners particularly vulnerable to HIV. The implications of these findings for HIV educational interventions are discussed.

Gender Identity↗