Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “persistent”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources
PubMed2004

Divide and conquer: how object files adapt when a persisting object splits into two.

Coherent visual experience requires not only segmenting incoming visual input into a structured scene of objects, but also binding discrete views of objects into dynamic representations that persist across time and motion. However, surprisingly little work has explored the principles that guide the construction and maintenance of such persisting object representations. What causes a part of the visual field to be treated as the same object over time? In the cognitive development literature, a key principle of object persistence is cohesion: An object must always maintain a single bounded contour. Here we demonstrate for the first time that mechanisms of adult midlevel vision are affected by cohesion violations. Using the object-file framework, we tested whether object-specific preview benefits-a hallmark of persisting object representations-are obtained for dynamic objects that split into two during their motion. We found that these preview benefits do not fully persist through such cohesion violations without incurring significant performance costs. These results illustrate how cohesion is employed as a constraint that guides the maintenance of object representations in adult midlevel vision.

Cognition↗
PubMed2003

Patterns of over-the-counter nicotine gum use: persistent use and concurrent smoking.

AIMS: To examine the occurrence of persistent use (i.e. use beyond 12 weeks) and concurrent use of nicotine gum with cigarettes among consumers who purchase nicotine gum over-the-counter (OTC). DESIGN: Assessment of gum use was conducted in the context of a smoking cessation trial among smokers who purchased Nicorette gum and enrolled in the optional Committed Quitters smoking cessation program. Eligible participants were contacted by telephone 6 weeks and 12 weeks following their self-selected target quit date. Those who reported gum use at 12 weeks were contacted again at week 24. PARTICIPANTS: A total of 2655 current smokers who purchased nicotine gum and enrolled in a clinical efficacy trial of the Committed Quitters program. MEASUREMENTS: Detailed information on smoking and gum use, including frequency of use, amount used and reasons for use was obtained at each of the three follow-up assessments. FINDINGS: At the 24-week assessment, 6% of participants reported current use of nicotine gum (i.e. persistent use). Those engaging in persistent use averaged 4.7 (SD = 2.5) days of gum use per week and 3.2 (SD = 3.5) pieces of gum per day. Sixty-six per cent of persistent users reported at week 24 that they were not currently smoking, and 67% of persistent users reported they were using gum to establish or maintain abstinence. At the 6-, 12- and 24-week assessments, 14%, 10% and 2% of participants, respectively, reported current use of nicotine gum and current cigarette smoking (i.e. concurrent users). Those concurrent users reported at the 12-week follow-up that they did so an average of 4.4 (SD = 2.1) days per week, that they chewed an average of 2.6 (SD = 3.5) pieces of nicotine gum per day and that they smoked an average of 8.7 (SD = 8.6) cigarettes per day. CONCLUSION: Extended use of nicotine gum is rare. Concurrent use with cigarettes is uncommon. In both cases, the amount of gum use is small. OTC marketing of nicotine gum does not appear to have increased use contrary to labeling nor resulted in patterns of use that should warrant clinical or public health concerns.

Adult↗
PubMed2005

Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters.

BACKGROUND: Staphylococcus aureus has important implications for the pathogenesis of atopic dermatitis (AD). In some patients S. aureus can be eradicated from the skin during anti-inflammatory treatment, while in others bacterial colonization is persistent. Potential mechanisms and features of these two distinct groups of patients are not known. OBJECTIVE: Accordingly, we studied relationships between the ability to eliminate S. aureus during an anti-inflammatory treatment and selected clinical and immunological features. METHODS: Quantitative assessment of S. aureus on the skin, in nasal vestibule and throat, serum IgE levels, CD4/CD8 T-cell ratio, lymphocyte proliferation and phagocyte oxidative burst were determined during the exacerbation and after 4 and 12 weeks of the treatment using topical steroid and oral antihistamine in 34 patients with AD. RESULTS: S. aureus was found on the skin of all 34 patients during exacerbation. Disease severity scoring of atopic dermatitis (SCORAD) correlated with the density of bacteria. Treatment with oral antihistamine and topical steroid resulted in a significant alleviation of symptoms, which correlated with the elimination of S. aureus from the skin in 70% of patients. In the remaining 30% of patients, dense (more than 10(10)/cm2) S. aureus skin colonization, persisted despite the treatment. Patients with persistent S. aureus presented with higher serum IgE levels, lower lymphocyte proliferation in response to staphylococcal enterotoxin B, phytohaemagluttinin and anti-CD3. Persistence of S. aureus was more common in men. CONCLUSIONS: Patients with AD differ in the ability to clear S. aureus from the skin during anti-inflammatory treatment, which appears to be related to the abnormalities in immunological parameters. Local antibiotic therapy should be considered only in patients with persistent S. aureus colonization.

Administration, Topical↗
PubMed2005

Persistence of Escherichia coli O157 on farm surfaces under different environmental conditions.

AIMS: To compare the persistence of Escherichia coli O157 on a variety of common faecally contaminated farmyard material surfaces (wood and steel) under different moisture and temperature regimes. METHODS AND RESULTS: Samples of field-conditioned farmyard materials (galvanized steel and wood) were cut into pieces and contaminated with fresh cattle faeces inoculated with nontoxigenic E. coli O157 (strain 3704). Thereafter, they were stored at four different environmental conditions; with temperature (5 and 20 degrees C) and moisture (moist or dry) as variables. Transfer of the pathogen to hands from the surfaces was also evaluated. Escherichia coli O157 numbers declined over time on all surfaces albeit at different rates according to the sample material and environmental conditions. Persistence was greatest on moist wood samples under cooler temperatures with large population numbers remaining after 28 days. Desiccation of surfaces resulted in a more rapid decline in E. coli O157 populations under both temperature regimes. Substantial numbers of colonies may also potentially be transferred to human hands from the surfaces during brief contact. CONCLUSIONS: When environmental conditions are favourable, E. coli O157 may persist for considerable times on a range of surfaces. However, when exposed to higher temperatures and dehydration, survival is notably decreased. Overall, bacterial persistence was significantly greater on wood samples relative to steel. SIGNIFICANCE AND IMPACT OF THE STUDY: Escherichia coli O157 is a prevalent pathogen, common in ruminant faeces. Contact with contaminated faeces may lead to human infection, resulting in possible severe illness. Although our study used only one strain of bacteria, our findings indicates that E. coli O157 has the potential to persist for long periods of time on gates, stiles and other farmyard surfaces under a range of environmental conditions. These farmyard surfaces therefore pose a potential infection pathway particularly where there is a high risk of direct human contact (e.g. child petting zoos, open farms).

Animal Husbandry↗
PubMedDate not supplied

Persistent childhood diarrhoea: patterns, pathogenesis and prevention.

With improved management of acute episodes of infectious diarrhoea, increased attention is now being given to persistent diarrhoea and its nutritional consequences and associated mortality. Risk factors for the development of persistent diarrhoea include young age, malnutrition, impaired immune function, recent introduction of milk feedings, prior antimicrobial therapy and infection with pathogenic strains of Escherichia coli. Descriptive epidemiology indicates that 3-20% of episodes of acute diarrhoea in children in developing countries become persistent and cause about one-third to one-half of all deaths from diarrhoea. Environmental factors may be very important in causing persistent diarrhoea: these include undernutrition combined with the impact of living in highly contaminated environments and their effects on gastrointestinal microecology. Development of effective preventive strategies will depend on improved understanding of causes and pathogenesis of persistent diarrhoea.

Acute Disease↗
PubMed2006

An early event in the herpes simplex virus type-2 replication cycle is sufficient to induce Chlamydia trachomatis persistence.

Epidemiological studies have demonstrated that co-infections of herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis occur in vivo. Data from a tissue culture model of C. trachomatis/HSV-2 co-infection indicate that viral co-infection stimulates the formation of persistent chlamydiae. Transmission electron microscopic (TEM) analyses demonstrated that in both HeLa and HEC-1B cells, co-infection caused developing chlamydiae to exhibit swollen, aberrantly shaped reticulate bodies (RBs), characteristically observed in persistence. Additionally, HSV-2 co-infection suppressed production of infectious chlamydial elementary bodies (EBs) in both host cell types. Co-infection with HSV type 1 (HSV-1) produced similar morphologic alterations and abrogated infectious EB production. These data indicate that virus-induced chlamydial persistence was neither host cell- nor virus strain-specific. Purification of crude HSV-2 stocks demonstrated that viral particles were required for coinfection-induced chlamydial persistence to occur. Finally, co-infection with either UV-inactivated, replication-incompetent virus or replication-competent HSV-2 in the presence of cyclohexamide reduced chlamydial infectivity without altering chlamydial genomic DNA accumulation. These data demonstrate that productive viral replication is not required for the induction of chlamydial persistence and suggest that HSV attachment and entry can provide the necessary stimulus to alter C. trachomatis development.

Animals↗
PubMed2005

Persistent and occasional nocturnal enuresis in orthotopic urinary diversion: is there a urodynamic difference?

OBJECTIVE: To establish urodynamic criteria differentiating between men with a radical cystoprostatectomy and ileal neobladder who are persistently enuretic and those who are occasionally enuretic. PATIENTS AND METHODS: Fifty enuretic men at least 1 year after a radical cystoprostatectomy and ileal neobladder (hemi-Kock or 'W' neobladders) were divided into two groups according to the persistence of their complaint; 17 men were persistently enuretic (nightly) and 33 were occasionally enuretic (<3 episodes/week). Both groups were compared with 50 fully continent men with similar reservoirs. Uroflowmetry, enterocystometry and urethral pressure profilometry were carried out according to International Continence Society standards and terminology. RESULTS: Both enuretic groups had significantly higher residual urine volumes, pressure at mid-capacity and at maximum enterocystometric capacity, amplitude of uninhibited contractions, and lower compliance than continent men. Men with occasional enuresis also had a significantly higher frequency and duration of uninhibited contractions than continent men. Men with persistent enuresis had significantly lower average and maximum urinary flow rates than continent men, and significantly lower functional urethral length and maximum urethral pressure. Uroflowmetric and urethral pressure differences were dissimilar between men with occasional enuresis and controls. CONCLUSION: Enuretic men had significantly higher residual urine volumes and enterocystometric pressure variables than continent men. Men with persistent enuresis had significantly lower flow rates and less urethral resistance. Pharmacological inhibition of reservoir contraction and/or management of residual urine by clean intermittent catheterization before sleep might cure occasional enuresis.

Chronic Disease↗
PubMed2004

Significance of hepatitis C virus coinfection with persistently normal alanine aminotransferase levels in HIV-1-infected patients.

OBJECTIVES: To assess the prevalence of chronic hepatitis C virus (HCV) infection with persistently normal alanine aminotransferase (ALT) levels in HIV-1-infected patients, together with its clinical, biological and histological characteristics and predictive factors. METHODS: We retrospectively studied all HCV/HIV-coinfected patients treated in our Infectious Diseases Department, for whom data on both HIV and HCV infection were available. We compared the demographic characteristics and parameters of HIV and HCV infection between cases, defined by persistently normal ALT levels (<45 IU/L) and detectable serum HCV-RNA (determined by PCR), and controls with high ALT levels and HCV PCR positivity during the previous 3 years. RESULTS: Among the 815 HIV-infected patients assessed for this study, 179 (22%) were HCV-coinfected, of whom 155 were eligible for this analysis. Of these 155 HCV-coinfected patients, 137 (88%) were HCV-PCR-positive, of whom 39 (28.5%) had persistently normal ALT levels (cases) and 98 (71.5%) had high ALT levels (controls). Relative to controls, cases had a significantly lower fibrosis score and a lower fibrosis progression rate (2.2 vs. 1.3, P=0.004; 0.3 vs. 0.2, P=0.006, respectively). Three factors associated with persistently normal ALT levels were identified, namely: HBsAg negativity (P=0.003), HCV genotype 4 (P=0.01) and female sex (P=0.05). CONCLUSION: Persistently normal ALT levels may be considered as a marker of slow HCV disease progression in HIV-coinfected patients, with significantly less severe hepatic lesions.

Adult↗
PubMed1999

Nitric oxide increases persistent sodium current in rat hippocampal neurons.

1. The effects of nitric oxide (NO) donors on whole-cell, TTX-sensitive sodium currents and single sodium channels in excised patches were examined in rat hippocampal neurons. The whole-cell sodium current consisted of a large transient component (INa,t) and a smaller, inactivation-resistant, persistent component (INa,p). 2. In acutely dissociated neurons, the amplitude of the whole-cell INa, p increased by 60-80 % within a few minutes of exposure to either of two NO donors, sodium nitroprusside (SNP, 100 microM) or S-nitroso-N-acetyl-DL-penicillamine (SNAP, 100 microM). 3. The amplitude of INa,t was not changed significantly by the same concentrations of SNP and SNAP, indicating that NO had a selective effect on INa,p. 4. Both NO donors significantly increased the mean persistent current in excised inside-out patches from cultured hippocampal neurons. SNP at 10-100 microM increased average mean persistent current at a pipette potential (Vp) of +30 mV from -0.010 +/- 0.014 pA (control) to -2.91 +/- 1.41 pA (n = 10). SNAP at 3-100 microM increased the average mean inward current in six inside-out patches from -0.07 +/- 0.02 to -0.30 +/- 0.08 pA (Vp = +30 mV). 5. The increase in persistent Na+ channel activity recorded in inside-out patches in the presence of SNP or SNAP could be reversed by the reducing agent dithiothreitol (DTT, 2-5 mM) or by lidocaine (1-10 microM). 6. The average mean current recorded in the presence of SNP was 10-fold higher than that elicited by SNAP. The time delay before an increase was observed was shorter with SNP (4.0 +/- 0.8 min, n = 8) than with SNAP (8.4 +/- 1.6 min, n = 7). 7. A component of the SNP molecule added on its own, 5 mM sodium cyanide (NaCN), increased mean current in excised inside-out patches (Vp = +30 mV) from -0.06 +/- 0.04 to -0.58 +/- 0.21 pA (n = 19). This increase in channel activity could be blocked by 10 microM lidocaine and 2-5 mM DTT. 8. These results suggest that NO may directly increase the activity of neuronal persistent Na+ channels, but not transient Na+ channels, through an oxidizing action directly on the channel protein or on a closely associated regulatory protein in the plasma membrane.

Animals↗
PubMed2000

Oxygen-sensing persistent sodium channels in rat hippocampus.

1. Persistent sodium channel activity was recorded before and during hypoxia from cell-attached and inside-out patches obtained from cultured hippocampal neurons at a pipette potential (Vp) of +30 mV. Average mean current (IU) of these channels was very low under normoxic conditions and was similar in cell-attached and excised inside-out patches (-0.018 +/- 0.010 and -0.025 +/- 0.008 pA, respectively, n = 24). 2. Hypoxia increased the activity of persistent sodium channels in 10 cell-attached patches (IU increased from -0. 026 +/- 0.016 pA in control to -0.156 +/- 0.034 pA during hypoxia, n = 4, P = 0.013). The increased persistent sodium channel activity was most prominent at a VP between +70 and +30 mV (membrane potential, Vm = -70 to -30 mV) and could be blocked by lidocaine, TTX or R56865 (n = 5). Sodium cyanide (NaCN, 5 mM; 0.5-5 min) increased persistent sodium channel activity in cell-attached patches (n = 3) in a similar manner. 3. Hypoxia also increased sodium channel activity in inside-out patches from hippocampal neurons. Within 2-4 min of exposure to hypoxia, I had increased 9-fold to -0. 18 +/- 0.04 pA (n = 21, P = 0.001). Sodium channel activity increased further with longer exposures to hypoxia. 4. The hypoxia-induced sodium channel activity in inside-out patches could be inhibited by exposure to 10-100 microM lidocaine applied via the bath solution (I = -0.03 +/- 0.01 pA, n = 8) or by perfusion of the pipette tip with 1 microM TTX (I = -0.01 +/- 0.01 pA, n = 3). 5. The reducing agent dithiothreitol (DTT, 2-5 mM) rapidly abolished the increase in sodium channel activity caused by hypoxia in excised patches (I = -0.01 +/- 0.01 pA, n = 4). Similarly, reduced glutathione (GSH, 5-20 mM) also reversed the hypoxia-induced increase in sodium channel activity (IU = -0.02 +/- 0.02 pA, n = 5). 6. These results suggest that persistent sodium channels in neurons can sense O2 levels in excised patches of plasma membrane. Hypoxia triggers an increase in sodium channel activity. The redox reaction involved in increasing the sodium channel activity probably occurs in an auxiliary regulatory protein, co-localized in the plasma membrane.

Anesthetics, Local↗
PubMed1992

The cytological detection of persistent cervical intraepithelial neoplasia after local ablative treatment: a comparison of sampling devices.

OBJECTIVE: To determine whether the cytological detection of persistent cervical intraepithelial neoplasia (CIN) after local ablative treatment is improved by the use of sampling devices other than the Ayre's spatula. DESIGN: A randomized controlled study. SETTING: Lothian Area Colposcopy Clinic. SUBJECTS: 856 patients who had received local therapy (CO2 laser or cold coagulation) for CIN II or III between 9 and 30 months earlier. INTERVENTION: Each patient had three consecutive cervical smears taken, one with the Ayre's spatula, one with either the Aylesbury, the Rocket or the Multispatula device, and finally one with the Cytobrush. The allocation of which spatula and the order of the first two was randomized. Each patient had a colposcopic examination immediately after the smears were taken. MAIN OUTCOME MEASURES: A comparison of the detection of histologically proven persistent CIN by the Ayre's spatula with the detection of persistent disease by alternative sampling devices. RESULTS: Of the 856 patients 130 had histologically proven persistent CIN. Another 98 had suspicious findings on colposcopy but punch biopsies reported as histologically normal. Of the remaining patients with normal colposcopy 130 were randomly selected to form a control group. The cervical smears from these 358 women were reported. Significantly fewer Ayre's samples contained endocervical cells than Aylesbury samples (47% vs 59%, difference 12%; 95% CI 3%-21%; P less than 0.001), Rocket samples (47% vs 67%; difference 20%, 95% CI; 12%-32%; P less than 0.001) or Multispatula samples (47% vs 76%; difference 29%, 95% CI 19-38%; P less than 0.001). When punch biopsies contained CIN, dyskaryotic cells were seen in 10% of Ayre's samples, 4.3% of Aylesbury samples, 8.3% of Rocket samples, and in no smear taken with the Multispatula. Obtaining a third smear with the Cytobrush did not substantially improve the detection rate of dyskaryosis. Neither the order of use of the spatulas, the form of initial treatment nor the size of the transformation zone had any apparent effect on the cytological detection of persistent CIN. CONCLUSIONS: We recommend that surveillance of patients who have received local ablative therapy for CIN should be by both cytology and colposcopy, and that cytological samples should be obtained using the Ayre's spatula.

Carcinoma in Situ↗
PubMed1994

Persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy.

OBJECTIVE: A 16 year review of persistent gestational trophoblastic tumour when the antecedent pregnancy was a partial hydatidiform mole. DESIGN: Cases of persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy were reviewed for the period 1976 to 1992. DNA ploidy was analysed by flow cytometry. SETTING: A University Hospital which is a reference centre for gestational trophoblastic tumour. SUBJECTS: The case notes of 207 women with persistent gestational trophoblastic tumour were reviewed. MAIN OUTCOME MEASURES: A rise (or failure to fall) of beta hCG titre, or sign of metastasis. RESULTS: Six (2.9%) women had partial hydatidiform mole as the antecedent pregnancy and all were initially judged to be low risk. However, two developed pulmonary metastasis; one woman developed persistent gestational trophoblastic tumour shortly after a hysterotomy, and none developed choriocarcinoma. The geometric mean of serum beta hCG concentrations at the initiation of chemotherapy was 868 mIU/ml (95% CI 114-1524). Of the six women, one achieved remission after total abdominal hysterectomy, and five after chemotherapy. The mean interval from starting treatment to remission was 68 days (95% CI 27.9-108.0). The initial beta hCG titre and interval were not statistically different from those found in cases of persistent gestational trophoblastic tumour when the antecedent pregnancy was not partial hydatidiform mole. Of the six, the DNA content was triploid in three and diploid in two. One of the two diploid cases required multiple courses of chemotherapy to achieve remission. CONCLUSION: Partial hydatidiform mole can have malignant sequelae and can develop very soon after treatment. Its DNA content can be either diploid or triploid, the lungs being the most common site of metastasis. After evacuation of partial hydatidiform mole, immediate chest X-ray and regular follow up of the serum beta hCG level is necessary.

Adult↗
PubMed1998

Persistent keratoacanthoma: challenges in management.

BACKGROUND: Keratoacanthoma is a common cutaneous neoplasm, although the persistent form is less common and often more difficult to manage. Multiple treatment approaches have been attempted with variable efficacy. Establishing the diagnosis and selecting a treatment plan for persistent keratoacanthoma is often challenging. OBJECTIVE: Our purpose is to describe the difficulty one may encounter in the diagnosis and treatment of persistent keratoacanthoma. Hopefully, review of this clinical conundrum may facilitate the management of the reader's future patients. METHODS: We describe a case of persistent keratoacanthoma where the diagnosis was initially elusive and the management challenging. Our thought process during each stage of diagnosis and management is described in the form of "issues" with references to the appropriate literature. RESULTS: After several diagnostic and therapeutic interventions, successful treatment was achieved with administration of oral isotretinoin. Long-term remission continued as the dosage was tapered. CONCLUSION: Persistent keratoacanthoma may be challenging to diagnose and manage, presenting a clinical conundrum. Careful review of the clinicopathologic presentation and an understanding of the various treatment options may result in a successful outcome.

Administration, Oral↗
PubMed1996

Prevalence and persistence of sleep complaints in a rural older community sample: the MoVIES project.

OBJECTIVES: To determine the prevalence and 2-year persistence of subjective sleep complaints in a rural older population. DESIGN: A prospective epidemiological study of an age-stratified random community sample. SETTING: The mid-Monongahela Valley, a rural area of Southwestern Pennsylvania. PARTICIPANTS: A total of 1050 individuals with a mean age of 74.4 years (range, 66-97; SD = 5.5); 57.2% were women. MEASUREMENTS: Subjective responses to questions about sleep complaints, classified as "never" experienced versus "sometimes" or "usually"; these questions reflected difficulty falling asleep (DFA), sleep continuity disturbance (SCD), early morning awakening (EMA), and uncontrollable daytime somnolence (DaSom). Subjects were also asked about snoring. Frequencies of these complaints were used to calculate their prevalence; those who remained in the study 2 years later were asked the same questions again to determine the persistence of sleep complaints. On the first occasions, subjects were also asked for "usual" estimates of how long they took to fall asleep, how many times they wakened during the night, and how many hours of sleep they obtained per night. RESULTS: With regard to prevalence, 385 (36.7%) subjects reported DFA, 301 (28.7%) reported SCD, 201 (19.1%) reported EMA, and 198 individuals (18.9%) reported DaSom. Of those who knew whether they snored, 334 (40.0%) reported snoring loudly during sleep. Within the age range of this group, age was not associated with complaints of insomnia or somnolence; however, older age was associated with a significantly lower prevalence of snoring (P < .001). All three insomnia complaints were significantly more common among women (P < .001). Snoring was significantly more common among men (P < .005), but there was no gender difference in DaSom. With regard to subjective estimates, of those reporting DFA, 49.2% reported that sleep latency exceeded an hour; of those reporting SCD, 26.2% reported waking three or more times per night; and of the entire sample, 11.8% reported 5 hours or less, whereas 12.7% reported 9 to 12 hours, of sleep per night. Approximately 2 years later, among those who had reported insomnia previously and participated in the follow-up wave, the persistence of DFA was 74.9%, that of SCD 68.9%, that of EMA 47.3%, and that of known snoring was 59.6%. The persistence of DaSom, however, was only 5.7%; only DaSom was significantly (P = .049) associated with mortality. CONCLUSIONS: Sleep complaints were common among these older individuals. Because these data were collected prospectively, they also provide objective evidence that insomnia is relatively persistent or chronic among older adults. This finding has implications for the diagnosis and long-term management of sleep disorders in older people. Derivation from a random community-based sample rather than from samples of patients or volunteers makes these data more generalizable to the general older population. Finally, these data describe a rural older populations, a group which, in general, is medically underserved and understudied.

Aged↗
PubMed2005

Minimum conditions of major histocompatibility complex compatibility and recipient immune compromise required to establish donor white blood cell persistence in a murine transfusion model.

BACKGROUND: In some patients multiply transfused to treat severe trauma, white blood cells (WBCs) from a single blood donor can persist for years, constituting up to 5 percent of all circulating WBCs. The immunologic mechanisms responsible for this are not known but, if understood, might allow manipulation of the human immune system to induce microchimerism for a variety of therapeutic purposes. To better characterize these mechanisms, a murine transfusion model was developed with a panel of immunologic knockouts as transfusion recipients. By conducting a systematic series of transfusion experiments, the purpose was to determine which recipient immune cell population, when abrogated, could lead to prolonged survival of donor cells (microchimerism). STUDY DESIGN AND METHODS: Blood was transfused from normal donors to knockout recipients in syngeneic, allogeneic, and xenogeneic settings. Donor WBC survival was evaluated by quantitative polymerase chain reaction, and recipient lymphocyte subsets by fluorescence-activated cell sorting. RESULTS: In the syngeneic setting, donor WBCs persisted in C2ta, RAG-1, and TCR knockout recipients. Allogeneic donor WBCs persisted in RAG-2 and RAG-2/Common gamma knockout recipients. Xenogeneic donor WBCs required RAG-2/Common gamma and RAG-2/Pfp double knockouts to persist. CONCLUSION: It is concluded that donor-recipient major histocompatibility complex (MHC) concordance alone is not sufficient to achieve microchimerism. Further, the degree of recipient immune compromise necessary to achieve persistent microchimerism is directly proportional to the degree of donor-recipient MHC disparity.

Animals↗
PubMed2004

Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway.

BACKGROUND: Thrombin promotes angiogenesis and cell proliferation in cancer. Whether thrombin turnover influences cancer incidence is unknown. OBJECTIVES: To explore the relation between the status of the coagulant pathway and cancer incidence by population survey. METHODS: Of 4,009 middle-aged men clinically free of malignancy, 3052 (76.1%) were recruited. Measurements of hemostatic status were made annually for 4 years, and follow-up for morbidity and mortality was maintained thereafter. Persistent activation of the coagulant pathway was diagnosed when prothrombin fragment 1+2 and fibrinopeptide A concentrations exceeded the upper quartiles of the population distribution in two consecutive annual examinations. Cancer incidence rates in men developing persistent activation (taking the time of onset of activation as baseline) were compared with those in men remaining free of this condition. RESULTS: Persistent activation of the hemostatic pathway was a distinct entity found in 111 men [43 expected by chance alone (P <0.001)], and associated with activation throughout the coagulation pathway. Total mortality (/1000 person-years) was higher in those with persistent activation than in others (17.1 and 9.7, respectively, P=0.015), owing to a higher mortality from all cancers (11.3 and 5.1, respectively, P=0.01), due in turn largely to a higher mortality from cancers of the digestive tract (6.3 and 1.9, respectively, P=0.004). Trends were similar for non-fatal cancers. CONCLUSIONS: Persistent activation of the coagulant pathway plays a role in the preclinical phase of cancer and is associated with an increased incidence of clinical malignancy, especially of the digestive tract.

Coagulants↗
PubMed2006

Persistence of procoagulant surface expression on activated human platelets: involvement of apoptosis and aminophospholipid translocase activity.

BACKGROUND: Activated platelets express a procoagulant surface when the asymmetric distribution of membrane phospholipids is scrambled, leading to phosphatidylserine (PS) exposure. PS expression, associated with apoptosis in nucleated cells, would be expected to be reversed by aminophospholipid translocase (APLT) activity. OBJECTIVE: To determine whether the procoagulant surface of activated platelets persists after it forms; to examine whether PS expression on platelets is associated with loss of mitochondrial inner membrane potential (DeltaPsi(m)), a hallmark of apoptosis; and to investigate the role of APLT in persistence of PS expression. METHODS: Platelets were stimulated with thrombin, collagen, a combination of both, or the Ca(2+)-ionophore A23187. Up to 4 h after activation, procoagulant surface expression was measured by annexin A5 binding by flow cytometry and by a prothrombinase assay. Flow cytometry was also used to measure PS expression concurrently with DeltaPsi(m) collapse, using CMXRos. APLT activity in annexin A5-negative and -positive platelets was measured flow cytometrically as the percent of 1-palmitoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]caproyl]-sn-glycero-3-phosphatidylserine (NBD-PS) translocated from the outer to the inner membrane leaflet. RESULTS AND CONCLUSIONS: Procoagulant surface expression on activated platelets persisted in vitro for at least 4 h; if such persistence occurs in vivo, there are important implications for the propagation of thrombosis. With the physiological stimuli, only 10-20% of the activated platelets expressed PS on their surface, and of these, only a portion exhibited DeltaPsi(m) collapse, indicating that PS expression can be associated with platelet apoptosis, but can also occur independently. APLT activity was very low in the PS-expressing platelet subpopulation for up to 4 h after activation, indicating that the persistence of a procoagulant surface may be attributed, at least in part, to this reduced APLT activity.

Apoptosis↗
PubMed1997

Persisting corneal oedema following intracapsular cataract extraction.

PURPOSE: The purpose of this study was to reveal the frequency of persisting corneal oedema following intracapsular cataract extraction and at the same time to examine whether the survival rate after penetrating keratoplasty due to this diagnosis differs from the survival rate following penetrating keratoplasty due to primary Fuchs' endothelial dystrophy. METHODS AND MATERIAL: A series of 2455 eyes underwent intracapsular cataract extraction between January 1, 1986 and December 31, 1988, at the Department of Ophthalmology, Arhus University Hospital. The medical files were examined to study the frequency of persisting corneal oedema. Patients with persisting corneal oedema were offered penetrating keratoplasty and the survival rate following this procedure was calculated. RESULTS: The frequency of pseudophakic persisting corneal oedema was 5.3% in the group of patients who underwent intracapsular cataract extraction. The survival of the following corneal transplantation was 54% after 2 years of follow-up. This is a low survival rate compared to the survival rate in primary Fuchs' endothelial dystrophy, but there is a similarity to this disease in a development of a slowly progressive oedema in 17% compared to 13% in primary Fuchs' endothelial dystrophy. CONCLUSION: 5.3% of a group of patients who underwent intracapsular cataract extraction developed persisting corneal oedema within a 5 to 7-year follow-up period. When these patients underwent penetrating keratoplasty the survival rate of the graft was 54% after 2 years of follow-up.

Cataract Extraction↗