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PubMed2003

Linear accelerator-based stereotactic radiosurgery for limited, locally persistent, and recurrent nasopharyngeal carcinoma: efficacy and complications.

PURPOSE: To evaluate the efficacy and complication of linear accelerator-based stereotactic radiosurgery (SRS) when used as salvage treatment for early-stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy (RT). MATERIALS AND METHODS: Between March 1998 and June 2001, 18 patients (15 men and 3 women; median age 46 years, range 32-84) with locally persistent or recurrent NPC confined to the nasopharynx (rT1) or with limited extension to the nasal fossa or parapharyngeal space (rT2) were treated by SRS. Thirteen patients had rT1 disease and 5 had rT2 disease. Most patients had disease not amenable to surgery or brachytherapy. All patients had undergone previous radical RT. Persistent disease was defined as tumor relapse within 4 months of completion of primary RT, and recurrence as tumor relapse beyond 4 months. Seven patients were treated for persistent disease, eight for a first recurrence, and three for a second recurrence. SRS was performed using multiple noncoplanar arcs of photons delivered to the target volume, which was defined by axial CT at a 3 mm thickness, supplemented by MRI in selected patients (67%). The median target volume was 5.3 cm(3) (range 2.2-16.9). The median SRS dose was 12.5 Gy (range 11-14) delivered to the 80% isodose line. All patients underwent serial nasopharyngoscopy and imaging after SRS. The median follow-up was 26 months (range 11-48). RESULTS: After SRS, 16 (89%) of 18 patients had complete regression of tumor as assessed by nasopharyngoscopy and biopsy. Four patients with an initial complete response to SRS subsequently developed local relapse again, with one recurrence developing outside the target volume 8 months after SRS and three within the target volume at 6-26 months after SRS. Two patients with local disease controlled by SRS developed relapse in other sites (neck node and liver metastases). The actuarial 2-year local control rate after SRS was 72%. Patients treated for persistent disease had a better local control rate (100%; 7 of 7) than those treated for recurrent disease (46%; 5 of 11). Patients with rT1 disease also had a better outcome after SRS compared with those with rT2 disease, with a control rate of 77% (10 of 13) for rT1 disease and 40% (2 of 5) for rT2 disease. Treatments were well tolerated, with no acute side effects. One patient had radiologic evidence of temporal lobe necrosis, although the right temporal lobe had already received a high dose during prior RT. That patient also developed additional local recurrence and liver metastases and died. The actuarial 2-year survival rate was 86%. CONCLUSIONS: Our preliminary results indicate that SRS is an effective treatment modality for persistent and recurrent early-stage NPC, with early control rates comparable to other salvage treatments such as brachytherapy and nasopharyngectomy. A modest SRS dose at 12.5 Gy also appears to be effective and is associated with minimal morbidities. More clinical experience and longer follow-up are needed to validate our results and to address fully the role of SRS in salvaging local failures of NPC.

Adult↗
PubMed2001

Doxorubicin-induced persistent oxidative stress to cardiac myocytes.

We recently reported a cardioselective and cumulative oxidation of cardiac mitochondrial DNA (mtDNA) following subchronic administration of doxorubicin to rats. The mtDNA adducts persist for up to 5 weeks after cessation of doxorubicin treatment. Since the evidence suggests that this persistence of mtDNA adducts cannot be attributed to a lack of repair and replication, we investigated whether it might reflect a long-lasting stimulation of free radical-mediated adduct formation. Male Sprague-Dawley rats received weekly s.c. injections of either doxorubicin (2 mg/kg) or an equivalent volume of saline. Cardiac myocytes isolated from rats following 6 weekly injections of doxorubicin expressed a much higher rate of reactive oxygen species (ROS) formation compared to saline controls. This higher rate of ROS formation persisted for 5 weeks following the last injection. Associated with this was a persistent depression of GSH in heart tissue, while protein-thiol content was not markedly altered. These data suggest that the accumulation and persistence of oxidized mtDNA may be due, not to the stability of the adducts, but to some as yet undefined toxic lesion that causes long-lasting stimulation of ROS generation by doxorubicin. This persistent generation of ROS may contribute to the cumulative and irreversible cardiotoxicity observed clinically with the drug.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Endocrine profiles of cows undergoing extended lactation in relation to the control of lactation persistency.

We conducted an experiment in dairy cows investigating the effects of calving season, milking frequency and nutrition on lactation persistency. Cows calved in the Spring (n=12) or Winter (n=12). Commencing in lactation week 9 one udder-half of each cow was milked thrice-daily and half of each calving group received additional concentrate at a fixed rate of 3kg per day above that of the control cows. As reported elsewhere, between lactation weeks 9 and 33 persistency (measured as the slope of decline in milk yield) was significantly improved by frequent milking (P<0.001), by calving in the Winter (P<0.001) and by additional concentrate (P<0.05). The cows were rebred after week 33. When analysis of persistency was extended up to week 20 of the recurring pregnancy only the frequency effect remained significant. Persistency was unaffected by the pregnancy up until pregnancy week 20 but was then greatly reduced (P<0.001). In this paper we report hormone concentrations. GH was unaffected by nutrition but was consistently elevated in the Winter calving group relative to the Spring. IGF1 and prolactin were both unaffected by nutrition and calving season, IGF1 tended to increase as lactation progressed but changes in prolactin were related to time of year more than stage of lactation. Insulin was not affected by nutrition and was lower in Winter calvers, but only during early lactation. Prior to rebreeding, lactation persistency was correlated (slightly) with [GH] but not with [IGF1] or [insulin] and was correlated significantly with changes in GH, IGF1 (both positive) and insulin (negative). In conclusion, whilst bovine lactation persistency is plastic and amenable to beneficial manipulation, the details of its endocrine control remain to be elucidated.

Animals↗
PubMed2002

Molecular bases of long-term memories: a question of persistence.

The most distinctive attribute of long-term memory is persistence over time. New studies have uncovered many aspects of the molecular and cellular biology of synaptic plasticity, and the acquisition and consolidation of memory, which are thought to depend on synaptic plasticity. Much less, however, is known about the molecular and cellular biology of long-term memory persistence. Recent findings in the field are construed within the conceptual framework that proposes that consolidation and persistence of long-term memories require modulation of gene expression, which can culminate in synaptic remodeling. Whether modulation of gene expression, and particularly the ensuing morphological plasticity of the synapse, is permissive, causal or sufficient for the materialization and persistence of the long-term trace is, as yet, undetermined. How persistent is persistence? Renewed interest is focused on the possibility that some long-term memories consolidate anew with retrieval, and could, under certain conditions, become transiently shaky in this period of reconsolidation.

Animals↗
PubMed1999

Embolotherapy of persistent endoleaks after endovascular repair of abdominal aortic aneurysm with the ancure-endovascular technologies endograft system.

PURPOSE: Endoleak is a potential complication after endovascular repair of abdominal aortic aneurysm (AAA). It may result in continued growth of the aneurysm and potentially result in aneurysm rupture. The authors present their experience with embolotherapy in patients with persistent perigraft flow treated with the Ancure-Endovascular Technologies endograft system. MATERIALS AND METHODS: Between February 1996 and August 1998, 54 patients underwent successful repair of AAA with use of the Ancure system. All underwent operative angiography and discharge computed tomography (CT). Follow-up included CT at 6, 12, and 24 months, and CT was also performed at 3 months if an endoleak was present on the discharge CT. Persistent endoleak was defined as perigraft flow still present on the 6-month CT. Seven of 21 initial endoleaks persisted at 6 months. Six patients returned for embolization of the perigraft space and outflow vessels including lumbar arteries and the inferior mesenteric artery (IMA). RESULTS: Five of the six patients had leaks from the proximal (n = 1) or distal attachment sites (n = 4) of the Ancure system with outflow into lumbar arteries and/or the IMA; one leak was caused by retrograde IMA flow. The six patients underwent nine embolization procedures with only one minor complication. Follow-up CT showed complete resolution of endoleak and decrease in size of the aneurysm sac in all patients. CONCLUSIONS: Although endoleak is commonly seen initially with the Ancure system, persistent leak occurred in 13% of the patients in the study. Persistent flow in most patients arises from a graft attachment site combined with patent outflow vessels such as the IMA or lumbar arteries. Persistent endoleaks can be effectively and safely embolized with use of a combination of coil embolization of the perigraft space and embolization of outflow vessels. Such intervention resulted in a decrease in size of the aneurysm sac.

Aged↗
PubMed2002

Persistent air-leak following pulmonary resection.

Air leaks are an unavoidable complication of pulmonary resection. The definition of a persistent air leak is arbitrary and may even be irrelevant in solving the problem. Persistent air leaks are more common in patients with severe COPD, and preoperative interventions are ineffective in reducing their prevalence. Meticulous surgical technique and care in handling and resection of the pulmonary parenchyma are essential in preventing persistent air leaks. Buttressing parenchymal staple lines and creating a pleural tent or pneumoperitoneum should be reserved for patients at risk for persistent air leaks. The use of currently available sealants is ineffective for the treatment of this complication. To stop persistent air leaks, early cessation of suction and placing chest tubes to an underwater seal is more effective than continuous suction. The management of persistent air leaks may require provocative chest tube clamping and permissive chest tube removal or patient discharge from the hospital with a chest tube and a Heimlich valve.

Chest Tubes↗
PubMed2002

Chlamydia trachomatis genes whose products are related to energy metabolism are expressed differentially in active vs. persistent infection.

The Chlamydia trachomatis genome encodes glycolysis and pentose phosphate pathway enzymes, two ATP/ADP exchange proteins, and other energy transduction-related components. We asked if and when chlamydial genes specifying products related to energy transduction are expressed during active vs. persistent infection in in vitro models and in synovia from Chlamydia-associated arthritis patients. Hep-2 cells infected with K serovar were harvested from 0-48 h post-infection (active infection). Human monocytes identically infected were harvested at 1, 2, 3, 5 days post-infection (persistent). RNA from each preparation and from synovial samples PCR-positive/-negative for Chlamydia DNA was subjected to RT-PCR targeting (a) chlamydial primary rRNA transcripts and adt1 mRNA, (b) chlamydial mRNA encoding enzymes of the glycolysis (pyk, gap, pgk) and pentose phosphate (gnd, tal) pathways, the TCA cycle (mdhC, fumC), electron transport system (cydA, cydB), and sigma factors (rpoD, rpsD, rpoN). Primary rRNA transcripts and adt1 mRNA were present in each infected preparation and patient sample; controls were negative for chlamydial RNA. In infected Hep-2 cells, all energy transduction-related genes were expressed by approximately 11 h post-infection. In monocytes, pyk, gap, pgk, gnd, tal, cydA mRNA were present in 1-2-day-infected cells but absent at 3 days and after; cydB, mdhC, fumC were expressed through 5 days post-infection. RT-PCR targeting mRNA from sigma factor genes indicated that lack of these gene products cannot explain selective transcriptional down-regulation during persistence. Analyses of RNA from synovial tissues mirrored those from the monocyte system. These data suggest that in the first phase of active chlamydial infection, ADP/ATP exchange provides energy required for metabolism; in active growth, glycolysis supplements host ATP. In persistence host, rather than bacterially produced, ATP is the primary energy source. Metabolic rate in persistent C. trachomatis is lower than in actively growing cells, as judged from assays for relative chlamydial primary rRNA transcript levels in persistent vs. actively growing cells.

Adenosine Triphosphate↗
PubMed2003

Psychoendocrine antecedents of persistent first-episode major depression in adolescents: a community-based longitudinal enquiry.

BACKGROUND: This longitudinal study investigated whether patterns of cortisol and DHEA that precede the onset of an episode of major depression influence time to recovery in a community ascertained sample of adolescents meeting DSM-IV criteria for major depression. METHOD: Sixty adolescents aged 12 to 16 at high risk for psychiatric disorders were followed for 24 months. At 12 months, 30 had experienced an episode of major depression and 30 had not. The second follow-up repeated the psychiatric evaluations with all participants completing the Kiddie-SADS Schedule for Schizophrenia and Affective Disorders. Hormone characteristics and self-reports completed at entry (the Mood and Feelings questionnaire and the Ruminations scale) together with intervening undesirable life events in the 12 months prior to onset, were used to determine the best pattern of psychosocial and endocrine features to predict persistent major depression. RESULTS: Compared to the never depressed (N = 30) and remitted adolescents (N = 19), persistently depressed cases (N = 11) had a raised morning cortisol/DHEA ratio at entry. Only persistent cases had higher levels of self-reported depressive symptoms and ruminations at entry compared to never depressed. There was no difference in exposure to undesirable life events before onset of disorder between remitted and persistent groups. Logistic regression techniques showed that only the cortisol/DHEA ratio predicted persistence. CONCLUSIONS: In community adolescents at high risk for psychiatric disorder persistent major depression may be distinguished from sporadic forms by the 08.00 h salivary cortisol/DHEA ratio prior to onset.

Adolescent↗
PubMed1985

Multiple-dose vials: persistence of bacterial contaminants and infection control implications.

Due to sporadic infections attributed to contaminated multiple-dose medication vials (MDV), some authorities have suggested discarding all MDV within 24 hours. We inoculated 11 commonly used medications with suspensions of 10 bacterial species previously associated with contaminated parenteral solutions and determined microbial persistence at both room and refrigerator temperature. At 22 degrees C, atropine, curare, folic acid, NPH insulin and triamcinolone did not allow microbial persistence beyond 4 hours. Lidocaine and heparin were sterile by 24 hours. Regular insulin, immune serum globulin, and myochrysine allowed persistence for up to 7 days. At 4 degrees C, bacterial persistence was significantly prolonged for all medications including those MDV requiring refrigeration. No organisms proliferated; however, F. meningosepticum and P. maltophilia were particularly persistent at both temperatures. The risk of persistent MDV contamination appears to be dependent upon specific pharmaceutical, microbe and storage temperature interactions. Recommendations for the refrigeration of MDV medications may require reevaluation on a product-by-product basis.

Bacteria↗
PubMed1999

Persistence of the left superior caval vein: can it potentiate obstructive lesions of the left ventricle?

Recent evidence has suggested that persistence of the left superior caval vein is associated with a high incidence of obstructive lesions of the left heart. To shed more light on this issue 1085 patients with congenital heart disease were studied retrospectively, with the aim of estimating the prevalence of a persistent left superior caval vein and its associated anomalies, focusing attention on obstructive lesions in the left and right ventricles. Patients with isomerism of the atrial appendages, or hypoplastic left heart syndrome, were excluded. A persisting left superior caval vein was present in 57 patients (5.2%). The overall incidence of obstructive lesions of the left heart was higher in patients with than in those without a persistent left superior caval vein (31.6 versus 7.8%,p < 0.001). Relative hypoplasia of the left ventricle was also higher in patients with persistent left superior caval vein (14 versus 0.8%, p < 0.001). The obstructive lesions found in the left heart, compared with the number in those without a left caval vein, were: mitral stenosis, 5.2 versus 0.7%; subaortic stenosis, 5.3 versus 0.9%; aortic coarctation, 17.5 versus 5.8% (p < 0.01); all of these in association, 3.5 versus 0.4%. In contrast, the incidence of obstructive lesions of the right heart was similar in the two groups of patients. It is concluded that persistence of the left superior caval vein can perturb the normal development of the left ventricle, being strongly associated with obstructions to left ventricular inflow and outflow.

Aortic Coarctation↗
PubMed2000

Persistence of volatile compounds in the breath after their consumption in aqueous solutions.

The persistence of volatile compounds in the breath was monitored after their consumption in aqueous solutions. Factors studied were variation in volatile release patterns between panelists, effect of adding hydroxy propyl methyl cellulose (HPMC), and differences among compounds. For any given compound, the extent of volatile persistence was broadly similar for all panelists. Adding HPMC at concentrations in excess of c did not substantially affect persistence. The largest differences in persistence were observed when compounds were compared (>20-fold). The differences were modeled using a quantitative structure property relationship approach, based on the persistence data from 41 compounds. Major components of the model were terms that described the hydrophobicity and vapor pressure of a molecule. The model was validated with a test set, which showed that there was a significant correlation between persistence predicted by the model and the actual values observed.

Adult↗
PubMed2001

High levels of urinary eosinophil protein X in young asthmatic children predict persistent atopic asthma.

Levels of urinary eosinophil protein X (U-EPX) and eosinophil counts were measured in 32 children (12-36 months of age) who were hospitalized for acute asthma, and the U-EPX levels were measured in 20 healthy children of the same age. The ability of these parameters to predict persistent asthma (at least one wheezing episode during the last 6 months) and atopic asthma (a positive skin-prick test [SPT]), was evaluated at a follow-up 2 years later. On admission, levels of U-EPX were higher in children with asthma (median: 120 microg/mmol of creatinine; quartiles: 67-123 microg/mmol of creatinine) than in controls (60 microg/mmol of creatinine, 38-74 microg/mmol of creatinine; p< 0.001). The U-EPX level was higher in those with persistent atopic asthma at follow-up (173 microg/mmol of creatinine, 123-196 microg/mmol of creatinine, n = 16), than in those with persistent non-atopic asthma (73 microg/mmol creatinine, 46-105 microg/mmol of creatinine, n = 8; p< 0.05), and higher than in those with transient asthma (no symptoms at follow-up) (106 microg/mmol creatinine; 42-167 microg/mmol of creatinine, n = 8; p< 0.05). By multiple logistic regression analysis, U-EPX was the only parameter able to predict persistent atopic asthma; eosinophil counts, parental atopy, age or gender could not. Parental atopy was the only parameter predictive for persistent asthma, regardless of atopic status. In conclusion, levels of U-EPX, but not eosinophil counts, measured in young children hospitalized with acute asthma can predict the persistence of atopic asthma 2 years later.

Antiviral Agents↗
PubMed2000

Relative persistence of behavior: a fundamental measure of relative reinforcing effects.

Relative persistence of behavior is measured in terms of rates of behavior at a higher schedule value divided by rates of behavior at a lower schedule value and then multiplied by 100 to express the result as a percentage. Relative persistence of behavior is a direct function of reinforcer size over a broad range of values. In 1 study, food was the reinforcer; however, in most studies of persistence, drug reinforcers were used, and the drugs were taken orally or intravenously. A variety of reinforcing drugs were studied: barbiturates, opioids, psychomotor stimulants, a dissociative anesthetic, and alcohol. Both ratio and interval schedules were used to study relative persistence of behavior in human participants, male and female rhesus monkeys (Macaca mulatta), and rats. Thus, studies of persistence are based on results of an extensive set of conditions. The results support the proposition that relative persistence of behavior is a fundamental measure of relative reinforcing effects.

Animals↗
PubMed1991

Effects of display luminance, stimulus meaningfulness, and probe duration on visible and schematic persistence.

Partial report performance is conceived of as consisting of two independent sources of information: visible persistence and schematic persistence. Following the work of Di Lollo and Dixon (1988), these two sources of information were separated experimentally by varying interstimulus interval and stimulus onset asynchrony independently. In the present experiment we asked whether visible persistence and schematic persistence would be affected by display luminance, stimulus meaningfulness, or probe duration. The results were fit accurately by an extension of the Di Lollo and Dixon independent-decay model in which display luminance affected visible persistence but stimulus meaningfulness and probe duration affected neither form of persistence directly.

Adult↗
PubMed2026

Microbiome features associated with persistent intestinal carriages of Escherichia coli ST131 in a Southeast Asian cohort study.

Escherichia coli sequence-type 131 (ST131) is the dominant global extraintestinal pathogen capable of asymptomatic intestinal carriage and sustained household transmission, challenging infection control. Despite its clinical significance, the ecological determinants of gut persistence remain poorly understood. We performed shotgun metagenomics on fecal samples to investigate gut microbiome features associated with ST131-positive samples, distinct host carrier statuses (persistent, intermittent and non-carriers) and household risks in a study of a Southeast Asian cohort. Here, we show that ST131 carriage was associated with compositional shifts without reducing species alpha-diversity. Regression analyses identified depletion of commensal taxa and the 1,5-anhydrofructose degradation pathway in ST131-positive samples. Persistent carriers exhibited highly perturbed microbiome enriched with pathobionts, aerobactin- and lipopolysaccharide (LPS)-biosynthesis pathways. Comparing household risk groups to control, revealed that biotin biosynthesis and 1,5-anhydrofructose degradation may influence ST131 co-colonization through both direct and indirect mechanisms. Machine learning analyses identified metabolic pathways as stronger discriminators of persistent carriage than taxonomic features. Genomic-resolved analysis of clinical ST131 isolates revealed conserved genes for iron-acquisition, LPS and antibiotic resistance determinants. Overall, while commensals and metabolism may influence initial ST131 colonization, persistent carriage is associated with specific microbial and metabolic adaptations, providing potential targets to limit intestinal ST131 persistence.

Humans↗
PubMed1983

Recovery and persistence of stuttering among relatives of stutterers.

Recovery and persistence of stuttering were examined in the first-degree relatives of a large group of adult persistent stutters. The percentage of recovered individuals reported in these families supports the hypothesis that recovered and persistent stuttering are not independent disorders. Sex and type of relative were significant variables in the distributions of recovery and persistence of stuttering. Handedness in male subjects and birth order did not distinguish between recovered and persistent stutterers. Female recovered stutterers had significantly earlier ages of stuttering onset than the other groups (male recovered stutterers and male and female persistent stutterers). Female recovered stutterers also tended to recover earlier than male recovered stutterers, and the durations of stuttering symptoms were similar in both sexes.

Adolescent↗
PubMed2002

High persistence of statin use in a Danish population: compliance study 1993-1998.

AIMS: Several studies have found that compliance with lipid-lowering drug (LLD) treatment is low. However, the results of these studies were based on crude measures of compliance. The aim of this study was to describe compliance with statin treatment by analysing prescription patterns on an individual level in a population-based prescription database over a 6 year period. METHODS: For incident statin users, all prescriptions for statins and drugs indicating cardiovascular disease or diabetes were retrieved from the OPED prescription database covering a population of about 470,000 inhabitants. Treatment was considered discontinued if the interval between two prescriptions exceeded number of tablets prescribed, plus 30 days. Compliance was assessed in terms of persistence and continuity. Persistence was defined as the period from the first prescription date to the date of discontinuation. Continuity was defined as the number of days with treatment (=number of tablets) divided by the total number of days in the period of persistence. RESULTS: 11% of the study cohort only received a single statin prescription. Survival analyses revealed a median persistence of 41 months. Less than 15% of the patients had more than 20% days without therapy within the period of persistence. Patients under 45 years without drug indicators of cardiovascular disease or diabetes presented the lowest compliance. CONCLUSIONS: The study showed good compliance with statin treatment in terms of persistence and continuity. A high percentage of the youngest patients, however, seemed to discontinue treatment before obtaining the full benefit in terms of decreased risk of coronary heart morbidity and mortality.

Adolescent↗
PubMed1998

Links between maternal care and persistent infant crying in the early months.

A community sample was screened to select three groups of infants and their mothers according to how much the babies cried at 6 weeks of age, the peak age for infant crying. The three groups--of moderate (n = 55), evening (n = 38) and persistent criers (n = 67) and their mothers--were assessed by diary, observation and questionnaire measures of mother and infant characteristics and interactions at 6 weeks and 5 months of infant age. At 6 weeks, mothers of persistent criers spent more time interacting with and physically stimulating their babies. Below-optimum maternal sensitivity/affection was linked to moderately increased crying in the infants overall. However, most mothers of persistent criers showed optimum sensitivity and affection, while no significant links between maternal sensitivity/affection and infant crying were found in the persistent crying group. By 5 months, when infant crying declined, the range and size of differences between mothers of persistent criers and other mothers declined. Home observations and a standard play measure failed to show group differences in maternal sensitivity, affection and intrusiveness at this age. The findings show that persistent infant crying in the early months often occurs in spite of high quality maternal care, so that in most cases the crying is probably not due to inadequate parenting. The need to distinguish general community cases from those at social or medical risk is emphasized and the findings' implications for professionals are discussed.

Adult↗