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PubMed1994

Persistence of Pneumocystis carinii in patients with AIDS receiving chemoprophylaxis.

Pneumocystis carinii organisms have been shown to persist throughout therapy in the majority of patients with Pneumocystis carinii pneumonia (PCP). This study evaluated the relationship between persistence of organisms and recurrence of disease, and the effect of chemoprophylaxis on bronchoalveolar lavage specimens. Seven patients receiving PCP chemoprophylaxis underwent serial bronchoalveolar lavage (BAL) examinations at 1, 4, and 7 mo after recovery from a first episode of PCP. Specimens were examined for persistent organisms with Gomori's methenamine silver stain and immunofluorescent antibody staining. There were no persistent organisms 1 mo after completion of antimicrobial treatment in six of the seven patients. The one patient with persistent organisms demonstrated clearance of organisms by 4 mo and had no recurrence of PCP. One patient had a recurrence of PCP at 4 mo, after a negative 1-mo BAL. We conclude that a positive BAL result by silver stain or immunofluorescent antibody staining more than a month after ending treatment may indicate clinical recurrence of PCP and not just persistence of nonpathologic cysts. These findings suggest that recurrences of PCP are more likely due to new infection than to relapse of prior disease.

AIDS-Related Opportunistic Infections↗
PubMed1998

Airway inflammation in mild intermittent and in persistent asthma.

The severity of asthma can be graded from mild intermittent to severe persistent. Airway inflammation is a feature of persistent asthma. We compared several markers of inflammation in mucosal biopsies and bronchoalveolar lavage fluid (BAL fluid) from 12 healthy control subjects, 24 patients with intermittent asthma, and 18 patients with mild-to-moderate persistent asthma. Epithelial shedding, eosinophil (EG2-positive cells), and activated T-cell (UCHL1) counts in biopsies, and ECP levels in BAL fluids were significantly increased in patients with intermittent asthma by comparison with control subjects and this increase was significantly greater for patients with persistent asthma. Alveolar macrophage activation (percentage of hypodense cells) and the thickness of the basement membrane were significantly increased in asthmatic subjects as compared with controls but there was no difference between the two asthmatic groups. Hyaluronic acid levels in BAL fluids were significantly increased in patients with persistent asthma by comparison with control subjects and patients with intermittent asthma. Mast cell numbers (toluidine blue) in biopsies and histamine or levels in BAL fluids were similar in the three groups. This study shows that airways inflammation is present in patients with intermittent asthma but to a lesser extent than in patients with persistent asthma.

Adult↗
PubMed1998

Changes in levels of viremia in cattle persistently infected with bovine viral diarrhea virus.

Virus isolation and serum neutralizing antibody titers were determined over a period of time from samples collected from animals persistently infected with bovine viral diarrhea virus (BVDV). To evaluate over time the ability to detect BVDV by virus isolation from serum or white blood cell preparations, 4 persistently infected calves were monitored from birth until 70 days of age. In 3 of 4 persistently infected calves, virus isolation from serum and white blood cells was negative until approximately 42 days of age, when colostral antibody had declined. The level of viremia in 7 adult (> 12 months) persistently infected animals decreased by 1 10-fold dilution over at least a 2-year period. The level of viremia became undetectable by virus isolation from serum in 1 of the 7 animals examined. This decline was associated with the development of virus neutralizing antibody. Although the level of viremia is fairly stable within persistently infected animals, the presence of specific neutralizing antibody may affect the ability to isolate BVDV. These findings are important when considering diagnostic testing to identify persistently infected animals by virus isolation.

Animals↗
PubMed2026

CSNK1E sustains stemlike drug persistence in diffuse large B-cell lymphoma.

Relapsed or refractory (R/R) disease occurs in up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) following first-line immunochemotherapy. However, the molecular mechanisms underlying drug persistence remain incompletely defined. In this study, we performed single-cell RNA and B-cell receptor sequencing on paired diagnostic and R/R samples from 8 patients who were either treatment-refractory or relapsed after remission, and validated our findings in 3 independent patient cohorts. We found that drug-persistent cells exhibited a transcriptional profile indicative of a less-differentiated state and adopted a memory B-cell-like program with enhanced stemlike properties, which correlated with unfavorable clinical outcomes across multiple DLBCL cohorts. Functionally, drug-persistent cells showed significantly increased in vitro clonogenicity and in vivo tumor-initiating capacity. Mechanistically, the WNT signaling regulator casein kinase 1ɛ (CSNK1E) was upregulated in these stemlike drug-persistent cells, in part through the activation of the A proliferation-inducing ligand (APRIL)-TNFRSF13B axis. Notably, CSNK1E inhibition impaired the growth and tumor-initiating capacity of drug-persistent cells and potentiated the efficacy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based treatment, both in vitro and in vivo. Together, our study reveals the stemlike transcriptional and functional properties of drug-persistent cells, and identifies CSNK1E as a critical mediator and therapeutic vulnerability that may improve the efficacy of standard immunochemotherapy in DLBCL.

Lymphoma, Large B-Cell, Diffuse↗
PubMed2002

Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia.

We determined the prognostic importance of morphologically identifiable persistent disease at day 15 and days 22 to 25 of remission induction in childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2 consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations on day 15 (+/- 1 day) and 218 on days 22 to 25 (+/- 1 day). Fifty-seven patients (14%) had persistent lymphoblasts (> or = 1%) in the BM on day 15 and 27 patients (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free survival (EFS) was significantly worse for patients with lymphoblasts on day 15 (40% +/- 6%) or on days 22 to 25 (4% +/- 3%) as compared to those without lymphoblasts on these dates (78% +/- 2% and 76% +/- 2%, respectively, P <.001 for both comparisons). A worse prognosis was observed even for patients with a low percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS = 56% +/- 8%) or days 22 to 25 (5-year EFS = 0%) compared to those without morphologically identifiable persistent lymphoblasts at these times (P <.001 for both comparisons). The prognostic impact of persistent lymphoblasts on both dates remained significant after adjusting for other known risk factors, including treatment protocol, age, white blood cell count, DNA index, cell lineage, and central nervous system status, and National Cancer Institute/Rome criteria simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of remission induction was associated with a poor prognosis and on days 22 to 25 signified a particularly dismal outcome; these very high-risk patients require novel or more intensive therapy to improve outcome.

Blast Crisis↗
PubMed1982

The synthesis of prostaglandins from persistent proliferative endometrium.

The pattern of prostaglandins (PGs) synthesized by persistent proliferative endometrium of women with excessive menstrual bleeding (greater than 50 ml) associated with anovulatory cycles was compared to endometrium collected from women with normal menstrual blood loss (less than 50 ml). Levels of PGF2 alpha in normal and persistent proliferative endometrium were lower than the levels of PGF2 alpha found in normal secretory endometrium (P less than 0.005 for both normal and persistent proliferative endometria). When incubated with exogenous [1-14C]arachidonic acid (9.1 nmol), normal secretory endometrium synthesized more PGF2 alpha and PGE2 than did normal proliferative endometrium, but the amounts of PGF2 alpha and PGE2 released by persistent proliferative endometrium were similar to those obtained by normal secretory endometrium. These findings suggest that persistent proliferative and normal secretory endometria have the same PG synthetase activity, and that the low endogenous concentrations of PGF2 alpha in the former arise from a lack of endogenous precursor. PGF2 alpha has predominantly vasoconstricting properties, and a reduced capacity to synthesize this PG by persistent proliferative endometrium may result in excessive menstrual bleeding, as was suggested by the inverse correlation between the ratio of the endogenous concentrations of PGF2 alpha and PGE and the menstrual blood loss (r = -0.7; P less than 0.005; n = 26).

Adult↗
PubMedDate not supplied

Self-reported nonadherence with antiretroviral drugs predicts persistent condition.

PURPOSE: To assess variables predictive of nonadherence persisting over time in HIV-infected people treated with highly active antiretroviral therapy. METHOD: Prospective study of consecutive HIV-infected patients who were prescribed ritonavir- or indinavir-containing regimens in a university-based HIV clinic in Rome. A patient questionnaire assessing knowledge of treatment regimen, adherence behavior, reasons for taking and missing therapy, factors influencing adherence, and health behaviors was administered at baseline and 1 year later. A predose protease inhibitor plasma level was measured concurrently. Persistent nonadherence was defined as patient self-reported nonadherence both at enrollment and at follow-up questionnaires. RESULTS: From April 1998 to July 1998, 140 patients were enrolled into the study. At follow-up, 10% remained persistently nonadherent, and 15% of the previously adherent patients became nonadherent. On bivariate analysis, being less than 35 years old (odds ratio [OR] 8.9; 95% CI 1.8-43.1; p =.002), self-reporting nonadherence at enrollment (OR 14.5; 95% CI 3.5-5.8; p <.001), and having experienced "a fair amount" or "a lot" of vomiting (OR 11.1;95% CI 1.6-74.7; p =.02) or pruritus (OR 16.4; 95% CI 2.6-102.8; p =.004) during the 4 weeks before enrollment were significantly correlated to persistent nonadherence. CONCLUSION: Previous self-reported nonadherence was a strong predictor of persistent nonadherence during follow-up. Moreover, being of younger age and self-reporting vomiting or pruritus were also associated with a higher risk of nonadherence persisting over time.

Adult↗
PubMed1999

The significance of the persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis.

STUDY OBJECTIVES: Identification of acid-fast bacilli (AFB) in the sputum smear at the completion of tuberculosis therapy is in some settings considered evidence of treatment failure. However, some patients with pulmonary tuberculosis (TB) will have positive smear results with negative sputum culture results at the end of therapy. The objectives of this study were to estimate the prevalence of persisting positive sputum smear results in patients with TB and to identify characteristics that distinguish patients with persistently positive sputum smear results who also had negative sputum culture results from patients identified as treatment failures. DESIGN: A population-based, historical cohort study with nested case control study. SETTING: British Columbia Division of Tuberculosis Control central case registry. PATIENTS: All 428 patients with culture-proven pulmonary TB in British Columbia over 7 years with sputum that was positive for AFB. METHODS: Review of laboratory data of all 428 patients, as well as clinical data of a subset of 30 patients with persistently positive smear results beyond 20 weeks. RESULTS: Sputum smears were positive for AFB in 205 patients (48%) at 4 weeks, in 30 patients (7%) at 20 weeks, and in 12 patients (3%) at 36 weeks. Of the patients with smear results that were persistently positive at 20 weeks, 23 (77%) had negative sputum culture results and 7 (23%) had positive sputum culture results (ie, they were treatment failures). Patients identified as treatment failures had more localized disease as shown on chest radiographs, had less radiographic improvement at follow-up, had a higher prevalence of drug resistance, and were less compliant with medications than patients with persistently positive smear results and negative culture results. No subject with a negative culture result relapsed over the 6- to 48-month observation period. CONCLUSION: Sputum that is persistently positive for AFB in patients in developed countries is more likely to be associated with negative culture results than with treatment failure.

Adult↗
PubMed2001

Symptomatic persistent post-coronary artery bypass graft pleural effusions requiring operative treatment : clinical and histologic features.

BACKGROUND: More than 85% of patients develop pleural effusions after coronary artery bypass grafting (CABG). Although the majority resolve spontaneously, post-CABG effusions can persist. The cause of these persistent effusions is unknown, and the histology of the pleural changes has seldom been reported. OBJECTIVES: To describe the patient characteristics and pathologic condition of the pleural tissues in patients with persistent post-CABG effusions. SUBJECTS: Eight patients with persistent post-CABG effusions who underwent thoracoscopy or thoracotomy over a 2-year period by one thoracic surgeon. These eight patients were selected as having undergone CABG > 2 months before their thoracic surgery and had no other identifiable causes of effusion. RESULTS: The median time from CABG to pleural surgery was 132 days (range, 74 to 2,258 days). The median left ventricular ejection fraction was 57% (range, 15 to 70%). All patients were dyspneic and had large (> or = 25% of the hemithorax) effusions on chest radiograph. All effusions persisted after two or more thoracenteses. Pleural effusion was left sided in three patients and bilateral in five patients. Pleural fluid was characterized by lymphocytosis (82 to 99%). Four of the eight patients had a visceral peel and trapped lung requiring decortication. Seven of the eight biopsy specimens showed pleural thickening characterized by dense fibrous tissues with associated mononuclear cell infiltration, while the eighth biopsy specimen showed only clotted blood. The degree of inflammation and fibrosis correlated with the interval between CABG and pleural surgery. Early post-CABG patients displayed more inflammation, with abundant lymphocytes in nodular configuration deep in the fibrous tissues away from the surface. Abundant keratin-positive, spindle-shaped cells were present in the fibrous tissues. Late cases showed predominantly mature fibrosis. CONCLUSIONS: Persistent post-CABG effusion can occur. Pleural fluids and pleural tissue in early-stage lesions were characterized by lymphocytosis. With time, the inflammatory changes were replaced by fibrosis that resulted in dyspnea and, at times, trapped lungs requiring surgical intervention.

Aged↗
PubMed2024

Molecular Analysis of Persistent and Recurrent Barrett's Esophagus in the Setting of Endoscopic Therapy.

INTRODUCTION: Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease. METHODS: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups. RESULTS: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations. DISCUSSION: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.

Humans↗
PubMed1987

Prostaglandin F2 alpha and oxytocin release during persistence of the corpus luteum in sheep.

Oxytocin (OT), progesterone and prostaglandin F2 alpha (PGF2 alpha) concentrations were measured in the utero-ovarian vein (UOV) of ewes which displayed persistence of the corpus luteum (CL). During the period of expected luteolysis, the frequency of OT and PGF2 alpha pulses in the UOV was significantly (P less than 0.005 for both) lower in ewes with persistent CLs, compared with ewes that underwent normal luteal regression. In contrast, the amplitude of both OT and PGF2 alpha pulses was similar in both groups of animals. It is suggested that persistence of the CL resulted from a decreased PGF2 alpha pulse frequency, which may have arisen from a decreased frequency of stimulation by OT. In two persistent CL ewes, however, it appeared that a failure at the level of the uterus may have contributed to the observed decrease in PGF2 alpha release. Although a PGF2 alpha analogue (Lutalyse) infusion into the uterine vein of two ewes with persistent CLs failed to induced luteolysis, it did stimulate a large release of OT into the UOV. This suggests that persistent CLs maybe more resistant to PGF2 alpha and, that at day 22 post-oestrus, these CLs are capable of releasing large quantities of OT into the UOV.

Animals↗
PubMed2003

Persistent insomnia is a predictor of hypertension in Japanese male workers.

Insomnia is one of the most common complaints at worksites, as well as in the general population. This study aims to assess the effect of insomnia on the development of hypertension in Japanese male workers. Using the annual health examination database of a Japanese telecommunication company, eligible middle-aged male participants in the 1994 health examination were followed up until 1998 or the development of hypertension (either initiation of antihypertensive therapy or a systolic blood pressure > or = 140 mmHg and/or a diastolic blood pressure > or = 90 mmHg). The effect of difficulty initiating sleep (DIS) was assessed with a DIS dataset (n=4,794), which included non-DIS (n=4,602) and persistent-DIS (n=192) subjects. That of difficulty maintaining sleep (DMS) was assessed with a DMS dataset (n=4,443), which included non-DMS (n=4,157) and persistent-DMS (n=286) subjects. The incidence of hypertension among persistent-DIS (40.1%; 130.7 per 1,000 person-yr) was significantly higher than that among non-DIS (30.6%; 89.9 per 1,000 person-yr). The incidence of hypertension among persistent-DMS (42.3%; 136.7 per 1,000 person-yr) was significantly higher than that among non-DMS (30.7%; 90.8 per 1,000 person-yr). After adjusting for potential confounding factors (i.e. age, body mass index, smoking, alcohol drinking, and job stress), persistent complaints of DIS and DMS were significantly associated with an increased risk of hypertension (OR=1.96; 95%CI: 1.42-2.70 and OR=1.88; 95%CI: 1.45-2.45, respectively). Persistent insomnia may be a useful predictor of hypertension in Japanese male workers.

Adult↗
PubMed2004

Effects of childhood socioeconomic circumstances on persistent smoking.

OBJECTIVES: We investigated whether socioeconomic circumstances at different life stages influence persistent smoking. METHODS: We followed a British birth cohort (all births between March 3 and 9, 1958) for 41 years to examine the influence of childhood and adulthood socioeconomic position on persistent smoking in adulthood (n = 6541). RESULTS: Persistent smoking (19% of participants, n = 1216) showed strong social gradients with both childhood and adulthood socioeconomic measures. Among men, the association with childhood socioeconomic circumstances was no longer significant after we adjusted for adulthood socioeconomic circumstances; however, among women, the adjusted odds of persistent smoking increased by 8% for each unit increase across a 16-point childhood score. CONCLUSIONS: Childhood socioeconomic circumstances predicted persistent smoking among women in our cohort, a finding that highlights the importance of influences on the development of persistent smoking across the life course.

Adolescent↗
PubMed2000

[Persistent diarrhea]

INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding.

Journal Article↗
PubMed1999

Persistence of depressive symptoms in diabetic adults.

OBJECTIVE: To determine the level and pattern of persistent depressive symptoms among adults with diabetes and identify factors associated with increased risk of being persistently depressed. RESEARCH DESIGN AND METHODS: A self-report depression symptom inventory was administered to 245 patients at two initial time points--the beginning and end of a comprehensive outpatient diabetes education program--and at 6-month follow-up. RESULTS: Only 13% of subjects were persistently depressed (i.e., exceeded the criterion for depression symptoms at all three time points). The rate of being depressed at follow-up was 10% for those negative for depression symptoms at either of the initial time points, 36% for those positive at one initial time point, and 73% for those positive at both initial time points (P < 0.0001). Those at increased risk for being persistently depressed were those who did not graduate from high school, had more than two complications of diabetes, and were not treated with insulin. CONCLUSIONS: Persistent depressive symptomatology is present in a substantial number of diabetic adults and can be effectively predicted using simple screening instruments during initial contacts. Risk factors for being persistently depressed only partly overlap those for transient depressive symptoms and represent a possible biological dimension.

Adult↗
PubMed1987

Effects of persistency and production on the genetic parameters of milk and fat yield in Israeli-Holsteins.

Herd-years of Israeli-Holsteins were stratified into three groups by two criteria: mean annualized milk yield [365 (total lactations yield/calving interval)] and mean persistency, estimated as the ratio of daily milk production at the 5th mo postpartum to daily production during the postpartum peak period. The latter was taken as an indication of the relative environmental stress on the cow. Primi- and multiparous cows were analyzed separately. Genetic parameters were estimated for annualized milk and fat production at each production and persistency group. Heritabilities increased with a rise in production for both primiparous and multiparous cows, but the effect was greater for multiparous cows. Even though persistency and production were correlated, no clear trends were evident for stratification by persistency; thus, a relationship between stress and heritability was not established. Genetic correlations among stratification groups were between .7 and .9 for persistency and between .6 and .86 for production; thus, sire x environmental interaction was greater for production than for persistency stratification. Production in a given year can be used as a criterion for selecting herds to test progeny of young sires in the following year.

Animals↗
PubMed1991

Duration of visible persistence in relation to stimulus complexity.

Visible persistence refers to the phenomenal impression that a stimulus is still present after its offset. A dispute exists whether visible persistence is due to temporal sluggishness in the visual pathway (neural hypothesis) or whether it is a byproduct of information-extraction processes under cognitive control (process hypothesis). This was investigated by manipulating stimulus complexity in five temporal integration experiments and one recognition memory experiment. According to the process hypothesis, complex stimuli should persist longer than simple stimuli because they require more information extraction. This prediction was not confirmed; in all six experiments, complexity was found to have no reliable effect on the duration of visible persistence. By contrast, and in accordance with earlier findings, complexity was shown to have a significant effect on a short-lived, nonvisible form of memory known as schematic persistenc. This pattern of results supports two major conclusions: First, that the effects of complexity reported in earlier research were probably on schematic--rather than visible--persistence; and second, that visible persistence must be regarded as a residual neural trace of an extinguished stimulus, rather than as a byproduct of information-extraction processes.

Adult↗
PubMedDate not supplied

Toddlers' persistence in the emerging occupations of functional play and self-feeding.

OBJECTIVE: This descriptive study explores motivation of toddlers who are typically developing to persist with challenging occupations. METHOD: The persistence of 33 children, 12 to 19 months of age (M = 15.7 months), in functional play and self-feeding with a utensil was examined through videotape analysis of on-task behaviors. RESULTS: A modest correlation was demonstrated between the percentages of on-task time in the two conditions (r = .44, p < .01). Although chronological age was not associated with persistence, participants' age-equivalent fine motor scores were correlated with persistence with challenging toys (r = .39, p < .03) but not with self-feeding with a utensil. Having an older sibling was associated with longer periods of functional play, t(32) = 3.02, p < .005, but the amount the parent urged the child to eat with a utensil was not associated with persistence in self-feeding. CONCLUSION: The modest association between on-task time for functional play and self-feeding with a utensil reveals that factors other than urge to meet perceptual motor challenges lead to children's persistence. The results reinforce the importance of considering not only challenging activities, but also the experienced meaning that elicits optimal effort and, thus, learning.

Feeding Behavior↗