Presumed consent or contracting out.
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Cadaver↗
Biomedical subjects
J Harris
Publications and source records attributed to J Harris.
Report of the Sixth International Workshop on Human Chromosome 11 Mapping 1998. Nice, France, May 2-5, 1998.
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Animals↗
A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis.
This study aimed to investigate whether there was a difference in outcome related to histologic pattern in cryptogenic fibrosing alveolitis (CFA) and to see whether there were correlations between clinical and radiologic findings and histology. One hundred thirteen lung biopsies from consecutive patients taken for the diagnosis of diffuse lung disease were reviewed and reclassified using the Katzenstein and Myers criteria for interstitial pneumonias. Patients lacking full investigational data at presentation and those with conditions predisposing to lung fibrosis were excluded, leaving 15 patients diagnosed with nonspecific interstitial pneumonia (NSIP) and 15 with usual interstitial pneumonia (UIP). Clinical and radiologic findings at presentation and serial lung function information and survival status in November 1998 were compared for the two groups. Survival was found to be significantly greater in the NSIP group compared with the UIP group (p < 0.001). This could not be explained by differences in treatment. Patients with UIP showed a progressive deterioration in lung function whereas those with NSIP remained stable. CT scans of patients with UIP showed more fibrosis than those of patients with NSIP (p < 0.011). A histologic diagnosis of NSIP is associated with a better prognosis than UIP. This subclassification of CFA is clinically useful.
Adult↗
Domestic aeroallergen exposures among infants in an English town.
A multicentre, prospective cohort study of childhood asthma was established in three European countries; the purpose of the project is the examination of factors which modify the relationship between allergen exposure in infant life and subsequent atopy and asthma. Dust samples were collected from the homes of 643 infants in a single town in the UK (the first cohort) and assayed for house dust mites (Der p 1) and cat allergen (Fel d 1) concentrations by enzyme-linked immunosorbent assay. A questionnaire with potential relevance to the development of atopy and asthma was completed. A wide variation in exposure to both allergens was observed. Carpeted, double-glazed or damp living rooms, and those sampled in the winter months, had higher levels of Der p 1, but these features did not predict Fel d 1 concentrations. Measures of high home occupancy were positively related to Der p 1 concentrations; and inversely with levels of Fel d 1, a finding which could not be explained by cat ownership. Homes in which one or more persons smoked had significantly lower concentrations of Der p 1, but not Fel d 1. There were no consistent differences in allergen levels between homes where one or more parent or sibling was either atopic or asthmatic. These findings indicate complex interactions among domestic, behavioural and seasonal factors and early allergen exposure in British children.
Air Pollution, Indoor↗
The nuclear receptor corepressor N-CoR regulates differentiation: N-CoR directly interacts with MyoD.
Classical ligand-activated nuclear receptors (e.g. thyroid hormone receptor, retinoic acid receptor), orphan nuclear receptors (e.g. Rev-erbAalpha/beta), Mad/Max bHLH (basic helix loop helix)-LZ proteins, and oncoproteins, PLZF and LAZ3/BCL6, bind DNA and silence transcription by recruiting a repressor complex that contains N-CoR (nuclear receptor corepressor)/SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), Sin3A/B, and HDAc-1/-2 proteins. The function of the corepressor, N-CoR, in the process of cellular differentiation and coupled phenotypic acquisition, has not been investigated. We examined the functional role of N-CoR in myogenesis (muscle differentiation), an ideal paradigm for the analysis of the determinative events that govern the cell's decision to divide or differentiate. We observed that the mRNA encoding N-CoR was suppressed as proliferating myoblasts exited the cell cycle, and formed morphologically and biochemically differentiated myotubes. Exogenous expression of N-CoR (but not RIP13) in myogenic cells ablated 1) myogenic differentiation, 2) the expression of the myoD gene family that encode the myogenic specific bHLH proteins, and 3) the crucial cell cycle regulator, p21Waf-1/Cip-1 mRNA. Furthermore, N-CoR expression efficiently inhibits the myoD-mediated myogenic conversion of pluripotential C3H10T1/2 cells. We demonstrate that MyoD-mediated transactivation and activity are repressed by N-CoR. The mechanism involves direct interactions between MyoD and N-CoR; moreover, the interaction was dependent on the amino-terminal repression domain (RD1) of N-CoR and the bHLH region of MyoD. Trichostatin A treatment significantly stimulated the activity of MyoD by approximately 10-fold and inhibited the ability of N-CoR to repress MyoD-mediated transactivation, consistent with the involvement of the corepressor and the recruitment of a histone deacteylase activity in the process. This work demonstrates that the corepressor N-CoR is a key regulator of MyoD activity and mammalian differentiation, and that N-CoR has a multifaceted role in myogenesis.
Animals↗
Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I.
Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro. We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 microg/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading. Marrow cells were flushed from the femur and cultured at the same initial density for up to 21 days. PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared with cultures from vehicle-treated rats. PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor. We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone. These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.
Animals↗
Endotension: an explanation for continued AAA growth after successful endoluminal repair.
PURPOSE: To present and analyze several cases that illustrate persistent sac pressurization following endovascular abdominal aortic aneurysm (AAA) repair. METHODS AND RESULTS: Four patients with successful endovascular AAA exclusion presented in follow-up with an expanding aneurysm. Two had initial sac diameter decrease, but by 18 and 24 months, respectively, the AAA had enlarged and become pulsatile. There was no endoleak evident, but the proximal attachment stents had mig rated distally in both cases. One patient developed endoleak with aneurysm expansion at 6 months; contained rupture occurred at 12 months. The last case had slowly evolving aneurysm expansion over 36 months but no endoleak. All endografts were removed and successfully replaced with conventional grafts. Intrasac thrombus was implicated as the means of pressure transmission that precipitated AAA expansion in these cases. CONCLUSIONS: Excluded AAAs can increase in size owing to persistent or recurrent pressurization (endotension) of the sac even when there is no evidence of endoleak. One proposed mechanism is pressure transmission via thrombus that lines the attachment site. Endotension may also represent an indiscernible, very low flow endoleak that allows blood to clot at the source of leakage.
Aged↗
The principles of medical ethics and medical research.
In this paper I discuss the application of the principles of medical ethics and of medical research to the case of children and others whose consent to treatment and to research is problematic. Public health depends substantially on the possibility of ongoing research into all conditions which affect the health of the people. Constraints on this research are therefore a public health issue. Moreover and more importantly the possibility of predictive testing and indeed of screening for health-relevant conditions is an important public health tool, and limitations on the use of this tool are of great significance to public health medicine. Having considered the particular problems created by research and predictive testing on children for late-onset conditions I go on to discuss research on those whose consent is problematic more generally. I conclude with radical recommendations for the reform of The Declaration of Helsinki and of the International Ethics Guidelines for Biomedical Research Involving Human Subjects, prepared by the Council for International Organizations of Medical Sciences (CIOMS).
Adult↗
Combined effect of nisin and moderate heat on destruction of Listeria monocytogenes in cold-pack lobster meat.
The combined effect of nisin and moderate heat to increase the killing of Listeria monocytogenes in cans of "cold-pack" lobster was investigated. Adding nisin at a level of 25 mg/kg of can contents to the brine surrounding the lobster, in combination with a heat process giving internal can temperatures of 60 degrees C for 5 min and 65 degrees C for 2 min, resulted in decimal reductions of inoculated L. monocytogenes of 3 to 5 logs, whereas heat or nisin alone resulted in decimal reductions of 1 to 3 logs. Such a reduced heat process to that currently commercially used (65.5 degrees C for 13 to 18 min, depending on the can size) results in significant reduction in drained weight loss, thus allowing considerable cost savings to the lobster-processing industry.
Animals↗
Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET.
BACKGROUND: Amplified DNA probes provide powerful tools for the detection of infectious diseases, cancer, and genetic diseases. Commercially available amplification systems suffer from low throughput and require decontamination schemes, significant hands-on time, and specially trained laboratory staff. Our objective was to develop a DNA probe system to overcome these limitations. METHODS: We developed a DNA probe system, the BDProbeTecTMET, based on simultaneous strand displacement amplification and real-time fluorescence detection. The system uses sealed microwells to minimize the release of amplicons to the environment. To avoid the need for specially trained labor, the system uses a simple workflow with predispensed reagent devices; a programmable, expandable-spacing pipettor; and the 96-microwell format. Amplification and detection time was 1 h, with potential throughput up to 564 patient results per shift. We tested 122 total patient specimens obtained from a family practice clinic with the BD ProbeTecET and the Abbott LCx(R) amplified system for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Based on reportable results, the BDProbeTecET results for both organisms were 100% sensitive and 100% specific relative to the LCx. CONCLUSIONS: The BDProbeTecET is an easy-to-use, high-throughput, closed amplification system for the detection of nucleic acid from C. trachomatis and N. gonorrhoeae and other organisms.
Chlamydia trachomatis↗
Precious fertility and third-trimester tests.
Are some pregnancies more 'precious' than others? Should amniocentesis be offered late in pregnancy with the possibility looming of a late abortion, and if such tests should be offered, to whom and in what circumstances should this be done? These are some of the important ethical questions raised in the paper by Shalev et al. (1999). In what follows, an analysis and resolution will be offered for all these important issues.
Amniocentesis↗
Experience using radio frequency laptops to access the electronic medical record in exam rooms.
Kaiser Permanente, Northwest, evaluated the use of laptop computers to access our existing comprehensive Electronic Medical Record in exam rooms via a wireless radiofrequency (RF) network. Eleven of 22 clinicians who were offered the laptops successfully adopted their use in the exam room. These clinicians were able to increase their exam room time with the patient by almost 4 minutes (25%), apparently without lengthening their overall work day. Patient response to exam room computing was overwhelmingly positive. The RF network response time was similar to the hardwired network. Problems cited by some laptop users and many of the eleven non-adopters included battery issues, different equipment layout and function, and inadequate training. IT support needs for the RF laptops were two to four times greater than for hardwired desktops. Addressing the reliability and training issues should increase clinician acceptance, making a successful general roll-out for exam room computing more likely.
Computer Communication Networks↗
Salaries keep the bills paid.
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Data Collection↗
Ethical genetic research on human subjects.
Since the Nuremberg trials and the Nazi doctors trial following World War II, international ethics protocols have emerged designed to protect human subjects from the atrocities of medical experimentation that were literally routine under the Nazis. Some of the apparent "lessons" from the Nazi period have been encapsulated in the Declaration of Helsinki, perhaps the leading medical ethics protocol. This paper argues that these protocols have not been notably conducive to human welfare or to the protection of human rights in the field of human genetics research. The paper proposes new protocols and a new approach to the ethics of research on human subjects.
Access to Information↗
Systematic review of trials comparing antibiotic with placebo for acute cough in adults. Quality scores showed poor agreement.
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Adult↗
Safety and immunogenicity of a candidate therapeutic vaccine, p24 virus-like particle, combined with zidovudine, in asymptomatic subjects. Community HIV Research Network Investigators.
OBJECTIVES: To evaluate the impact of therapeutic immunization with p24 virus-like particle (VLP) and zidovudine (ZDV) on p24 antibody titre (primary endpoint), CD4+ cell counts, cellular responses to the immunogen and recall antigens, and viral load (secondary endpoints) in subjects with asymptomatic HIV infection and CD4+ counts greater than 400 x 10(6) cells/l. DESIGN: A double dummy, double-blind randomized placebo-controlled Phase II trial of the therapeutic vaccine p24-VLP, with or without ZDV. METHODS: ZDV-naive subjects were randomized to one of three groups for 6 months: group A, ZDV 200 mg three times daily plus intramuscular administration of alum adjuvant monthly; group B, ZDV 200 mg three times daily plus p24-VLP (500 microg) in intramuscular alum monthly; group C, placebo capsules plus p24-VLP (500 microg) in intramuscular alum monthly. Subjects were followed for a further 6 months. RESULTS: Sixty-one patients received vaccinations. The mean CD4+ cell counts pretherapy for groups A, B, and C were 605 +/- 25, 668 +/- 43, and 583 +/- 30 x 10(6) cells/l, respectively. Treatment was well tolerated. At both 24 and 52 weeks there were no significant differences between the treatment groups in terms of antibody responses to p24, CD4+ or CD8+ cell counts, viral load, T-cell responses to p24, p17, recall antigen or mitogen, or markers of immune activation, despite induction of antibody and proliferative responses to the carrier protein of the vaccine. CONCLUSION: Vaccination with p24-VLP was well tolerated. p24-VLP either alone or in combination with ZDV did not significantly alter either antibody or proliferative responses to p24, or CD4+ cell number, immune activation or viral load over 12 months.
AIDS Vaccines↗
Associated malformations in infants and fetuses with upper or lower neural tube defects.
The paper describes associated malformations in infants born with neural tube defects (N = 3,809) from three large malformation registers and in fetuses aborted because of a diagnosed neural tube defect (N = 748) from two of the registers. In infants, upper spina bifida and encephalocele are more often associated with non-neural malformations than anencephaly or lower spina bifida. Aborted fetuses with spina bifida or encephalocele have associated malformations registered more often than infants with those neural tube defects, but the opposite is true for anencephaly. The degree of detail of the investigation of an aborted specimen or a perinatally dead infant will contribute to such differences but they can also depend on the fact that prenatal detection may be facilitated by the simultaneous presence of other malformations like body wall defects. Also, fetuses with many malformations may be more prone to abort spontaneously late in pregnancy. Variable prenatal diagnosis may, therefore, explain population differences in the pattern of associated malformations. The type of associated malformation differs with the level of the neural tube defect: this could be due to different causal mechanisms or be a question of cranio-caudal level and/or timing. For limb reduction defects, however, we did not find any association between upper limb and upper neural tube defects or lower limb and lower neural tube defects. These findings together with other epidemiological data support the idea that upper and lower neural tube defects may have different significance in epidemiological studies and should be treated separately.
Abnormalities, Multiple↗
All-trans retinoic acid blocks the antiproliferative prodifferentiating actions of 1,25-dihydroxyvitamin D3 in normal human keratinocytes.
1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] and all-trans retinoic acid (RA), the active metabolites of vitamins D and A respectively, regulate the proliferation and differentiation of keratinocytes. Both the vitamin D receptor (VDR) and the retinoic acid receptor family (RAR) bind to DNA response elements as heterodimers with the retinoic X receptor (RXR), suggesting that there are pathways of action that are shared by both compounds. Therefore, we examined the interactions of 1,25(OH)2D3 and RA upon the proliferation and differentiation of normal human keratinocytes (NHK) and of a squamous cell carcinoma cell line, SCC4. Although both 1,25(OH)2D3 and RA were each able to inhibit NHK proliferation in a dose-dependent manner, when they were administered in combination, proliferation was stimulated, suggesting mutual antagonism. In contrast, SCC4 cells proved insensitive in terms of proliferation to 1,25(OH)2D3 and to all but the highest concentration (10(-6) M) of RA. 1,25(OH)2D3 exerted a biphasic effect on transglutaminase (TGase) and involucrin (INV) mRNA levels, with maximal stimulation at 10(-9) M. RA inhibited TGase and INV mRNA levels and antagonized the stimulation by 1,25(OH)2D3. A similar pattern was observed for TGase protein, but, RA, which, by itself, reduced INV, markedly enhanced the ability of 1,25(OH)2D3 to raise INV levels, possibly by inhibiting 1,25(OH)2D3-stimulated TGase activity and cross-linking of soluble INV into the insoluble cornified envelope (CE). Thus, in NHK cells, RA antagonizes the antiproliferative prodifferentiating actions of 1,25(OH)2D3, but assessment of a single marker, such as INV protein, may be misleading.
Calcitriol↗