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PubMed2003

Drug prescriptions after acute myocardial infarction: dosage, compliance, and persistence.

BACKGROUND: Although it has been well documented that aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and lipid-lowering drugs are under-prescribed for patients with acute myocardial infarction (Am Heart J 2003;145:438-44.), few studies have examined dosage and long-term compliance and persistence patterns for the use of these drugs after AMI. METHODS: Using Quebec administrative data on all elderly (aged > or =65 years) survivors of hospital admissions for AMI between 1996 and 1998 (n = 14,057), we studied the discharge prescriptions, dosages, patient compliance, and persistence during this period for aspirin, beta-blockers, ACE inhibitors, and lipid-lowering drugs. RESULTS: Rates of discharge medications were suboptimal (aspirin 65%, beta-blockers 54%, ACE inhibitors 45%, lipid-lowering drugs 21%). Most patients with prescriptions for aspirin and ACE inhibitors were prescribed dosages equivalent to those administered in clinical trials (99% and 88%, respectively). In contrast, only 20% of patients with beta-blocker prescriptions and 48% of patients with lipid-lowering drug prescriptions were prescribed clinical trial doses. For patients with discharge prescriptions, 1-year compliance rates were high (aspirin 74%, beta-blockers 74%, ACE inhibitors 70%, lipid-lowering drugs 84%), as were the 1-year persistence rates (aspirin 71%, beta-blockers 72%, ACE inhibitors 69%, lipid-lowering drugs 80%). CONCLUSION: Although cardiac drugs are under-prescribed to patients with AMI, once prescribed, patients are likely to adhere to these prescriptions, with high rates of compliance and persistence.

Acute Disease↗
PubMed2000

Increased expression of major basic protein (MBP) and interleukin-5(IL-5) in middle ear biopsy specimens from atopic patients with persistent otitis media with effusion.

BACKGROUND: Molecular biologic evidence to support an etiologic role for allergy in the pathogenesis of persistent otitis media with effusion (OME) is lacking. OBJECTIVE: The goal of this article was to document expression of allergy-associated Th-2-type cytokines and inflammatory cells in the middle ear mucosa of children with persistent OME. METHODS: With immunocytochemistry (CD3, major basic protein) and in situ hybridization (interleukin-5 mRNA), middle ear biopsy specimens from 7 children with persistent OME were stained. Nonatopic stapedectomy patients with no history of otitis media served as controls (n = 7). RESULTS: There was a statistically significant (P< 0.05) difference in expression of CD3, major basic protein, and interleukin-5 between experimental and control subjects. All 8 OME patients proved to be atopic by ELISA testing. CONCLUSIONS: Type I allergy involving a Th-2-type cytokine and cellular profile may be a contributing factor in the persistence of OME in atopic children. SIGNIFICANCE: The middle ear may serve as a target organ for allergic inflammation, suggesting that appropriate allergy management may be a useful adjunct to the management of OME.

Biopsy↗
PubMed2000

Second-look laparotomy after modified posterior exenteration: patterns of persistence and recurrence in patients with stage III and stage IV ovarian cancer.

OBJECTIVE: The purpose of this study was to determine patterns of persistence and recurrence in patients with advanced ovarian cancer (stage IIIC and stage IV) after modified posterior exenteration. STUDY DESIGN: Retrospective chart review was used to determine patterns of persistence and recurrence of disease in patients undergoing modified posterior exenteration. From January 1, 1987, to September 15, 1998, 151 of 212 (71.2%) patients undergoing modified posterior exenteration in addition to other cytoreductive surgical procedures for stage IIIC and stage IV ovarian cancer underwent second-look laparotomy. The average age of the patients was 60.3 years (range, 20.3-86.3). A total of 207 of the 212 (97.6%) had grade 2 or 3 disease. Papillary serous carcinoma (113/212; 53.3%) and adenocarcinoma (75/212; 35.4%) were the most frequent cell types encountered. After initial cytoreductive surgery, minimal disease (<5 mm) was present in 206 of the 212 (96.2%) patients with 153 of 212 (72.2%) having no visible residual disease. There were 4 (1.9%) postoperative deaths. In 13 patients (6.1%) progressive disease was noted. Second-look laparotomy was not undertaken in 61 of the 212 (28%) patients. Fluid for cytologic testing was obtained from all four intra-abdominal quadrants, and biopsies of previously noted sites of disease were performed, in addition to random biopsies of diaphragmatic peritoneum, colonic gutters, and pelvic peritoneum. If present, the retroperitoneal lymph nodes were resected; biopsy specimens of these sites were obtained if there was no evidence of intraperitoneal disease. RESULTS: Findings at second-look laparotomy were negative for cancer in 85 of 151 (56.3%) and positive for cancer in 66 of 151 (43.7%). Only 8 of 151 (5.3%) patients had persistent disease in the pelvis. In the remainder (58/151; 38.4%) disease was found either in the upper abdomen or in the bowel mesentery. Recurrence was documented in the upper abdomen only (71/212; 33.5%), upper abdomen and pelvis (18/212; 8.5%), multiple sites excluding the pelvis (22/212; 10.4%), pelvis only (2/212; 0. 9%), chest alone (5/212; 2.4%), head alone (4/212; 1.9%), or groin alone (2/212; 0.9%). Median survival in the overall group was 51.1 months, with estimated 5- and 10-year survival rates of 44.2% and 32. 9%, respectively. CONCLUSIONS: Modified posterior exenteration is an effective surgical means of eliminating pelvic disease in patients with advanced ovarian cancer. Results of second-look laparotomy confirmed that only 8 of 151 (5.3%) had persistent disease in the pelvis.

Adult↗
PubMed2003

A case of chronic herpes gestationis: persistent disease or conversion to bullous pemphigoid?

We report the case of a 38-year-old woman with herpes gestationis (HG) persistent for 26 months postpartum with typical erythematous-edematous grouped lesions associated with vesicles, blisters, and scaled crusts on most parts of her body. Despite high doses of oral prednisolone, azathioprine, and dapsone, and a trial of 5 plasmaphereses, the disease has persisted to date. Histopathologic examination of lesional skin showed subepidermal blisters, focal basal cell necrosis, and a dermal inflammatory infiltrate including many eosinophils. Direct immunofluorescence showed linear C3 staining in the basement membrane zone and the complement fixation test demonstrated circulating antibasement membrane zone antibodies at a low titer (1:80). HLA typing demonstrated an A2, A24, B35, B52, DR4,5, DR13,15, DRW52,53 phenotype. We present this case as chronic persistent HG and discuss the differential diagnosis between chronic persistent HG and HG evolving to bullous pemphigoid, together with a careful examination of similar cases reported in literature.

Adult↗
PubMed1979

The effect of spatial frequency and contrast on visual persistence.

The visual persistence of sinusoidal gratings of varying spatial frequency and contrast was measured. It was found that the persistence of low-contrast gratings was longer than that of high-contrast stimuli for all spatial frequencies investigated. At higher contrast levels of 1 and 4 cycles deg-1 gratings, a tendency for persistence to be independent of contrast was observed. For 12 cycles deg-1 gratings, however, persistence continued to decrease with increasing contrast. These results are compared with recently published data on other temporal responses, and are discussed in terms of the different properties of sustained and transient channels.

Afterimage↗
PubMed1996

Cortical dynamics of boundary segmentation and reset: persistence, afterimages, and residual traces.

In previous work with a neural-network model of boundary segmentation and reset, the percept of persistence was linked to the duration of a boundary segmentation after stimulus offset. In particular, the model simulated the decrease of persistence duration with an increase in stimulus duration and luminance. Further evidence is revealed for the neural mechanisms involved in the theory. Simulations show that the model reset signals generate orientational afterimages, such as the MacKay effect, when the reset signals can be grouped by a subsequent boundary segmentation that generates illusory contours through them. Simulations also show that the same mechanisms explain properties of residual traces, which increase in duration with stimulus duration and luminance. The model hereby discloses previously unsuspected mechanistic links between data about persistence and afterimages, and helps to clarify the sometimes controversial issues surrounding distinctions between persistence, residual traces, and afterimages.

Afterimage↗
PubMed2004

Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections.

Persistent viral infections causing serious diseases derive, primarily, from altered function of the immune system. Knowledge of the very complex composition and function of the innate and adaptive branches of the immune system is essential to understanding persistent infection. The best solution to the problem of persistent infection is by prevention using prophylactic vaccines. Hit and run viruses evade immune destruction by infecting new hosts and rarely persist. Hit and stay viruses evade immune control by sequestration, blockade of antigen presentation, cytokine escape, evasion of natural killer cell activities, escape from apoptosis, and antigenic change. Twelve prophylactic vaccines against hit and run agents exist, and there are only three vaccines against hit and stay viruses, all of which are of DNA composition. Several new vaccines against hit and stay viruses are feasible, but protective vaccines against RNA HIV and hepatitis C agents are highly unlikely, short of a major breakthrough. Therapeutic vaccines are very improbable without a magnitude of favorable new discoveries. In the meantime, antiviral chemotherapy, chemotherapy/prophylactic vaccination, and short interfering RNA silencing are worthy of intense investigation.

Antibodies, Viral↗
PubMed2002

Antigen-specific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia.

Purified protein derivative (PPD) skin testing is used to identify persons infected with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immune responses to Mtb. However, lack of skin induration to intradermal injection of PPD or PPD anergy is observed in a subset of patients with active tuberculosis (TB). To investigate the sensitivity and persistence of PPD reactivity and its in vitro correlates during active TB disease and after successful chemotherapy, we evaluated the distribution of skin size induration after intradermal injection of PPD among 364 pulmonary TB patients in Cambodia. A subset of 25 pulmonary TB patients who had a positive skin reaction to mumps and/or candida antigens showed persistent anergy to PPD after successful completion of TB therapy. Strikingly, in vitro stimulation of T cells from persistently anergic TB patients with mumps but not PPD resulted in T cell proliferation, and lower levels of IL-2 and IFN-gamma and higher levels of IL-10 were detected in PPD-stimulated cellular cultures from PPD-anergic as compared with PPD-reactive pulmonary TB patients. These results show that anergy to PPD is antigen-specific and persistent in a subset of immunocompetent pulmonary TB patients and is characterized by antigen-specific impaired T cell proliferative responses and a distinct pattern of cytokine production including reduced levels of IL-2.

Adult↗
PubMed1982

Persistent infection of Friend erythroleukemia cells with vaccinia virus.

Cultures of murine Friend erythroleukemia (FL) cells, which are chronically infected with leukemia virus, were inoculated with vaccinia virus. The yield of vaccinia virus was determined by assaying plaque-forming units in mouse L2 cells, and the yield of leukemia virus was determined by measuring reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) activity released into the culture fluid. Although no facilitation of one virus by the other was detected, persistently infected cultures were established. Electron microscopic examination revealed the presence of vaccinia and leukemia viruses in the same cell. The permanent lines of cells persistently infected with vaccinia were designated FLvac. Their morphology, growth rate, cloning efficiency, and ability to respond to the induction of erythrodifferentiation by treatment with dimethyl sulfoxide were not appreciably altered as compared to the parental FL cells. However, the persistently infected cells showed a marked decrease in tumorigenicity when assayed in DBA/2 mice. The infectious virus produced by FLvac cells and by L2 cells were indistinguishable as judged by restriction endonuclease patterns of virion DNA, structural proteins, and the activities of two virion-associated DNases. The yield of infectious vaccinia virus from FLvac cells generally declined after about 60 serial passages. Although some cell lines no longer yield infectious virus, they are resistant to challenge with vaccinia at concentrations that are cytolytic for L2 cells. The mechanism responsible for the establishment of the persistent infection remains unclear because defective particles, interferon production, and temperature-sensitive mutants have not been detected.

Animals↗
PubMed1993

Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro.

An in vitro cell culture system was used to study the effect of interferon gamma (IFN-gamma) on Chlamydia trachomatis growth and differentiation. The effect of IFN-gamma on chlamydiae was dose-dependent. IFN-gamma at 2 ng/ml completely inhibited chlamydial growth and differentiation; however, persistent infection was established when chlamydiae were cultured with IFN-gamma at 0.2 ng/ml. Persistent infection was characterized by the development of noninfectious atypical chlamydial forms from which infectious progeny could be recovered only when IFN-gamma was removed from the culture system. Analysis of persistently infected cells by immunofluorescent microscopy and immunoblotting with specific antibodies revealed that the atypical chlamydial forms had near-normal levels of the 60-kDa heat shock protein, an immunopathologic antigen, and a paucity of the major outer membrane protein, a protective antigen. Furthermore, steady-state levels of other outer membrane constituents, such as the 60-kDa cysteine-rich outer membrane protein and lipopolysaccharide, were greatly reduced. If IFN-gamma causes similar events to occur in vivo, then persistently infected cells could augment the pathogenesis of the chronic inflammatory sequelae that follow chlamydial infection by serving as depots of antigen capable of stimulating a sustained inflammatory response.

Antibodies, Bacterial↗
PubMed1994

Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection.

Live proliferation-competent and irradiated proliferation-incompetent L5178 murine lymphoma cells (Eb cell line) were compared for their potency to induce systemic anti-tumor immunity in syngeneic DBA/2 mice. The tumorigenic potential in vivo of live Eb cells was suppressed through local secretion of interleukin 4 (IL4) or alternatively by injection of parental cells at a site refractory to tumor growth. Inoculation of nontumorigenic doses of live Eb or Eb-IL4 cells led to long-lasting specific and systemic T-cell-mediated antitumor response requiring both CD4+ and CD8+ T lymphocytes. Irradiated cells offered only limited short-term protection, which could be marginally improved by IL4. The more effective protection offered by vaccination with live tumor cells correlated with rapid migration and persistence of tumor cells in the bone marrow of host animals after tumor cell inoculation. In contrast, irradiated Eb-lacZ cells had a short persistence. Tumor cells recovered from the bone marrow of host animals injected with live Eb-IL4 cells still expressed IL4. These observations indicate that in the course of vaccination with live Eb or Eb-IL4 cells, a fraction of these cells escaped destruction by host mechanisms and persisted in a dormant state in the bone marrow for long periods of time. Persistence of dormant tumor in the bone marrow correlated with the duration of anti-tumor immunity.

Animals↗
PubMed1994

Rapid cell variation can determine the establishment of a persistent viral infection.

Evidence for a mechanism of initiation of viral persistence in which the cell, and not the virus, plays a critical role has been obtained using the important animal pathogen foot-and-mouth disease virus (FMDV). We have developed a virulence assay consisting of quantification of the ability of virus to kill cells and of cells to divide in the presence of virus and to initiate a carrier state. Cells were cured of FMDV at early times following a cytolytic infection of BHK-21 monolayers with FMDV. When cured cells were subjected to the virulence assay they showed an increased ability to survive a second infection by FMDV but not by other RNA viruses. This altered phenotype was maintained as a stable genetic trait. When the virus present in such early surviving cells was used to infect BHK-21 cells, it proved to be as virulent as the initial cytolytic FMDV and, furthermore, its ability to kill BHK-21 cells increased upon replication in the surviving cells. Both the level of genetic heterogeneity and the rate of evolution of FMDV were similar to those previously documented during acute and persistent FMDV infections. The results suggest that, in contrast to most other viral systems, the critical element in the establishment of a persistent infection of BHK-21 cells with FMDV is the ability of the host cells to vary genetically and phenotypically, which promotes selection of cells with increased resistance to virus. The possible relevance of this mechanism to viral persistence in vivo is discussed.

Animals↗
PubMed1999

Distinct neurochemical features of acute and persistent pain.

To address the neurochemistry of the mechanisms that underlie the development of acute and persistent pain, our laboratory has been studying mice with deletions of gene products that have been implicated in nociceptive processing. We have recently raised mice with a deletion of the preprotachykinin-A gene, which encodes the peptides substance P (SP) and neurokinin A (NKA). These studies have identified a specific behavioral phenotype in which the animals do not detect a window of "pain" intensities; this window cuts across thermal, mechanical, and chemical modalities. The lowered thermal and mechanical withdrawal thresholds that are produced by tissue or nerve injury, however, were still present in the mutant mice. Thus, the behavioral manifestations of threshold changes in nociceptive processing in the setting of injury do not appear to require SP or NKA. To identify relevant neurochemical factors downstream of the primary afferent, we are also studying the dorsal horn second messenger systems that underlie the development of tissue and nerve injury-induced persistent pain states. We have recently implicated the gamma isoform of protein kinase C (PKCgamma) in the development of nerve injury-induced neuropathic pain. Acute pain processing, by contrast, is intact in the PKCgamma-null mice. Taken together, these studies emphasize that there is a distinct neurochemistry of acute and persistent pain. Persistent pain should be considered a disease state of the nervous system, not merely a prolonged acute pain symptom of some other disease conditions.

Acute Disease↗
PubMed1999

Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice.

Lymphocytic choriomeningitis virus (LCMV), strain WE, is a non-cytopathic RNA virus that is highly adapted to its natural host, the mouse. Acute infection of adult mice leads to generalized virus spread, followed by cytotoxic T lymphocyte-mediated virus clearance below the detection levels of conventional assays within 2-3 weeks. Indirect evidence had suggested that virus or viral antigen might persist in the immune mouse. Here we demonstrate LCMV-WE persistence at low levels after infection with 10(2) or 10(6) plaque-forming units, shown as viral genome, viral antigen, and replicative virus using sensitive in vitro and in vivo assays. The finding that LCMV-WE persists in the face of apparently intact immune responses resembles the situation in some viral (hepatitis B and C, HIV) and bacterial (tuberculosis, leprosy) infections in humans; the results are relevant to the understanding not only of other murine and human persistent viral infections but also of protective immunological memory by "infection immunity."

Animals↗
PubMed2000

Borna disease virus persistent infection activates mitogen-activated protein kinase and blocks neuronal differentiation of PC12 cells.

Persistence of Borna disease virus (BDV) in the central nervous system causes damage to specific neuronal populations. BDV is noncytopathic, and the mechanisms underlying neuronal pathology are not well understood. One hypothesis is that infection affects the response of neurons to factors that are crucial for their proliferation, differentiation, or survival. To test this hypothesis, we analyzed the response of PC12 cells persistently infected with BDV to the neurotrophin nerve growth factor (NGF). PC12 is a neural crest-derived cell line that exhibits features of neuronal differentiation in response to NGF. We report that persistence of BDV led to a progressive change of phenotype of PC12 cells and blocked neurite outgrowth in response to NGF. Infection down-regulated the expression of synaptophysin and growth-associated protein-43, two molecules involved in neuronal plasticity, as well as the expression of the chromaffin-specific gene tyrosine hydroxylase. We showed that the block in response to NGF was due in part to the down-regulation of NGF receptors. Moreover, although BDV caused constitutive activation of the ERK1/2 pathway, activated ERKs were not translocated to the nucleus efficiently. These observations may account for the absence of neuronal differentiation of persistently infected PC12 cells treated with NGF.

Animals↗
PubMed2002

Indocyanine green-mediated photothrombosis as a new technique of treatment for persistent central serous chorioretinopathy.

PURPOSE: To evaluate the potential benefit and complications of indocyanine green-mediated photothrombosis (IMP) in the management of patients with persistent central serous chorioretinopathy (CSC). METHODS: Interventional noncomparative case series. Eleven patients with CSC presenting with persistent subretinal fluid in optical coherence tomography (OCT) four months after presentation and decrease in visual acuity (VA) were submitted to a single IMP session with 2 mg/kg body weight ICG and application of 5.6 W/cm(2) light at 810 nm. A continuous follow-up was provided with best-corrected ETDRS VA assessment, and angiographic and OCT documentation 72 hours before and at 2 days, 1 and 2 weeks, 1, 3, 6, and 12 months after treatment. RESULTS: Pretreatment VA levels ranged from 20/32 - 1 to 20/100 (mean, 20/63 + 2 [logMAR equivalent, 0.460 +/- 0.155]); post treatment levels ranged from 20/25 - 2 to 20/20 (mean, 20/20 - 2 [logMAR equivalent, 0.038 +/- 0.048]). Ten out of eleven patients presented with VA levels of >/=20/25 2 weeks after treatment; the mean logMAR VA change of 0.345 at that time was statistically significant (p < 0.05, Friedman test). OCT disclosed resolution of persistent subretinal fluid in all eyes. No recurrence was observed after 12 months of follow-up. Complications included transient retinal whitening in two patients, and associated occlusion of retinal capillaries in one. CONCLUSIONS: Photothrombosis using low-intensity 810 nm light to direct laser energy continuously at the active leakage sites after intravenous ICG infusion induced rapid VA recovery in patients with persistent CSC; accordingly, restoration of the macular architecture was evidenced on OCT, and no recurrence was noted 12 months after IMP.

Adult↗
PubMed1998

Conditioned flavour aversions in sheep: the relationship between the dose rate of a secondary plant compound and the acquisition and persistence of aversions.

Within the overall objective of whether ruminants are able to form conditioned aversions (CFA) toward a food flavour associated with the administration of an aversive stimulus which occurs naturally in food plants (oxalic acid, OA), two specific objectives were tested: (1) whether the rate and degree of formation of CFA are dependent on the dose rate of OA administered and (2) whether the persistence of formed CFA depends on the previous dose rate of OA. Sheep were conditioned to associate the specific flavour of one of two novel foods with either the oral administration of OA or equivalent placebos. Four dose rates of OA were tested (0.06, 0.12, 0.18 and 0.24 g/kg sheep live weight per d), with twelve sheep per dose. Each conditioning period lasted for 8 d and was repeated four times. At the end of each conditioning period the preference for the two flavours was measured in short-term, 20 min preference tests. The persistence of the CFA was measured at 0, 7, 21 and 49 d after the completion of the conditioning phase with long-term, 3 h preference tests. The results of the experiment indicated that: (1) the rate and degree of formation of CFA were dependent on the rate of administration of OA; (2) sheep required repeated exposures to the lower dose rates of OA in order to develop CFA and these CFA did not persist in the absence of continual reinforcement; (3) CFA to the higher dose rates of OA were developed after as little as one exposure and persisted over a period of at least 7 weeks. These findings are consistent with the expectation that ruminants should be able to select a diet which minimizes the risk of consumption of potentially harmful foods, whilst at the same time maintaining a degree of flexibility in their feeding behaviour.

Administration, Oral↗
PubMed2006

Persistent geotropic nystagmus--a different kind of cupular pathology and its localizing signs.

CONCLUSION: A persistent geotropic positional nystagmus indicates a dysfunction in the lateral semicircular canal with a cupula of less specific weight than the surrounding endolymph. It is possible to determine the side of the affected cupula by recording the nystagmus pattern in yaw and pitch plane. OBJECTIVES: To identify the clinical features in patients with a persistent geotropic positional nystagmus, establish lateralizing signs and relate the findings to a pathophysiologic mechanism. PATIENTS AND METHODS: Six patients with acute onset vertigo of a peripheral origin and persistent geotropic nystagmus were examined with videonystagmoscopy and the nystagmus characteristics in different positions of the head in yaw and pitch plane were studied. RESULTS: Besides the persistent geotropic nystagmus, a zero zone was found with no nystagmus, beyond which the nystagmus changed direction when the head of the patient in supine position was gradually rotated from side to side. The zero zone was present when the head was turned slightly towards one side and is thought to represent a position where the affected cupula is aligned with the gravitational vertical. With the head bent forwards the nystagmus direction was to the non-affected side and when the head was bent backwards to the affected side.

Adult↗