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PubMed2003

Persistent pain and depression: a biopsychosocial perspective.

This review highlights recent research findings on the relationship between persistent pain and depression and discusses the implications of these findings for future research in persons who suffer from both pain and depression. First, we briefly discuss advances in theories of pain that underscore the important role that depression can play in the chronic pain experience. Second, we discuss depression in persons suffering from chronic pain from a biopsychosocial perspective that takes into account both biological and psychosocial mechanisms linking pain and depression. Third, we address biomedical, psychosocial, and combined medical-psychosocial approaches to treatment in persons with persistent pain and depression. We conclude by highlighting future directions for research related to screening and diagnosis of depression in persons having persistent pain, treatment of comorbid pain and depression, and individual and subgroup differences in the experience of persistent pain and depression.

Depression↗
PubMed2001

Hippocampal neurons exhibit both persistent Ca2+ influx and impairment of Ca2+ sequestration/extrusion mechanisms following excitotoxic glutamate exposure.

Exposure of neurons to glutamate is an essential element of neuronal function, producing transient elevations in free intracellular calcium ([Ca2+]i) that are required for normal physiological processes. However, prolonged elevations in [Ca2+]i have been observed following glutamate excitotoxicity and have been implicated in the pathophysiology of delayed neuronal cell death. In the current study, we utilized indo-1 and fura-2ff Ca2+ imaging techniques to determine if glutamate-induced prolonged elevations in [Ca2+]i were due to persistent influx of extracellular Ca2+ or from impairment of neuronal Ca2+ extrusion/sequestration mechanisms. By experimentally removing Ca2+ from the extracellular solution following glutamate exposure, influx of Ca2+ into the neurons was severely attenuated. We observed that brief glutamate exposures (<5 min, 50 microM glutamate) resulted in a Ca2+ influx that continued after the removal of glutamate. The Ca2+ influx was reversible, and the cell was able to effectively restore [Ca2+]i to resting levels. Longer, excitotoxic glutamate exposures (> or = 5 min) generated a Ca2+ influx that continued for the duration of the recording period (>1 h). This persistent Ca2+ influx was not primarily mediated through traditionally recognized Ca2+ channels such as glutamate receptor-operated channels or voltage-gated Ca2+ channels. In addition to the persistent Ca2+ influx, longer glutamate exposures also produced a lasting disruption of Ca2+ extrusion/sequestration mechanisms, impairing the ability of the neuron to restore resting [Ca2+]i. These data suggest that glutamate-induced protracted [Ca2+]i elevations result from at least two independent, simultaneously occurring alterations in neuronal Ca2+ physiology, including a persistent Ca2+ influx and damage to Ca2+ regulation mechanisms.

Animals↗
PubMed2001

Lesion and electrical stimulation of the ventral tegmental area modify persistent nociceptive behavior in the rat.

The ventral tegmental area (VTA) has been traditionally related with the control of motor responses. However, some studies show that this area is also involved in the processing of nociceptive information. It has been reported that this nucleus participates in the dissociative analgesia phenomenon. In the few works where electrical stimulation and lesion of the VTA have been performed, evaluated with persistent or chronic pain related behaviors, contradictory results have been obtained. Thus, a more detailed analysis of the role of the VTA in persistent pain is needed. Two series of experiments were performed: lesions of this nucleus were done with radiofrequency, (bilaterally at two points per side using a temperature range from 50 to 80 degrees C), and the VTA was electrically stimulated (10 min daily over 5 days, 2 ms rectangular pulses at 100 Hz during 1 s every 5 s) using two different schemes:10 min before the induction of the nociceptive stimulus and 90 min after the induction of the nociceptive stimulus. The latter allowed us to distinguish if the VTA electrical stimulation had a distinctive antinociceptive effect when applied before or after the induction of the nociceptive stimulus on a persistent pain related behavioral response in the rat, the self injury behavior (SIB). Our results showed that VTA lesions enhanced the occurrence of SIB; while activation of this same nucleus by electrical stimulation after the nociceptive stimulus, but not before, facilitates the analgesic process, expressed as a 1 day delay in SIB onset. These results indicate that the VTA is a brain structure that plays a key role in the processing and modulation of persistent pain information. Data are discussed in terms of the relationship of the VTA with the affective component of pain.

Analgesia↗
PubMed1999

Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation.

OBJECTIVE: Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS: Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (> 8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Cox's MAZE surgery (n = 12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression. RESULTS: L-type calcium channel alpha 1 and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (-57%, p = 0.01 and -28%, p = 0.04, respectively) and protein contents (-43%, p = 0.02 and -28%, p = 0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF. CONCLUSIONS: Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF.

Aged↗
PubMed1997

Intracervical and fundal administration of levonorgestrel for contraception: endometrial thickness, patterns of bleeding, and persisting ovarian follicles.

OBJECTIVE(S): To study the prevalence of persisting ovarian follicles and to assess the endometrial changes and patterns of vaginal bleeding over 1 year of use of a 20 micrograms/24 h levonorgestrel-releasing intracervical contraceptive device. DESIGN: Prospective, randomized study. SETTING: Two family planning clinics in Helsinki, Finland. PATIENT(S): Women requesting intrauterine hormonal contraception. INTERVENTION(S): Insertion of a levonorgestrel-releasing intracervical contraceptive device into the cervical canal (group 1, n = 151) or fundally into the uterine cavity (group 2, n = 147) for contraception. MAIN OUTCOME MEASURE(S): Transvaginal ultrasonography of the ovaries and endometrium at insertion and 3, 6, and 12 months after insertion. Data on bleeding were collected using menstrual diary cards. RESULTS: Persisting ovarian follicles were found in < 8% of women. In both groups, the amount of endometrial tissue decreased significantly in 3 months. The incidence of amenorrhea during the 1st year was higher in the fundal insertion group. CONCLUSION(S): The number of persisting follicles was low. Follicles resolved within 6 to 8 weeks. No association was found between persisting follicles and problems of bleeding. Compared with intracervical insertion, fundal insertion resulted in more uniform endometrial suppression and fewer days of bleeding and spotting.

Adult↗
PubMed2000

Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels.

BACKGROUND & AIMS: Some patients with serum hepatitis C virus (HCV) have persistently normal aminotransferase (ALT) levels and are affected by cirrhosis. This study prospectively evaluated progression of the disease in a group of anti-HCV-positive patients with persistently normal ALT levels. METHODS: Thirty-seven subjects were studied. Each subject underwent liver biopsy at baseline and after 5 years of follow-up. At baseline, serum samples were tested for genotypes and HCV RNA load. ALT levels and serum HCV RNA were tested every other month and every 6 months, respectively. Patients with increased ALT were discharged from the study and treated with IFN. Five years after the end of IFN therapy, a liver biopsy was performed. RESULTS: Liver biopsy at baseline showed chronic hepatitis in 34 patients and normal histology in 3 patients, 2 of whom were negative for HCV RNA and 1 positive. HCV genotypes were distributed as follows: 2a, 56%; 1b, 41%; and 1a, 3%. At the end of 7-year follow-up, 73% of the patients still had normal ALT values. Liver histology after 5 years was comparable to that observed at entry to study. CONCLUSIONS: Most patients with persistently normal ALT serum levels have very mild chronic hepatitis. However, healthy anti-HCV-positive subjects exist. In patients with HCV-related chronic hepatitis associated with persistently normal ALT levels, the grade of disease activity does not increase over years and progression to cirrhosis is slow or absent.

Adult↗
PubMedDate not supplied

Second formant transitions in fluent speech of persistent and recovered preschool children who stutter.

UNLABELLED: This study investigated frequency change and duration of the second formant (F2) transitions in perceptually fluent speech samples recorded close to stuttering onset in preschool age children. Comparisons were made among 10 children known to eventually persist in stuttering, 10 who eventually recovered from stuttering, and 10 normally fluent controls. All were enrolled in the longitudinal Stuttering Research Project at the University of Illinois. Subjects fluently repeated standard experimental sentences. The same 36 perceptually fluent target segments (syllables embedded in words) from each subject's repeated sentences were analyzed. The syllables were divided into three phonetic categories based on their initial consonant: bilabial, alveolar, and velar placement. The frequency change and duration of F2 transitions were analyzed for each of the target CV segments. F2 transition onset and offset frequencies and their interval (duration) were measured for each utterance. Data indicate that near stuttering onset, children whose stuttering eventually persisted demonstrated significantly smaller frequency change than that of the recovered group. It is suggested that the F2 transitions should continue to be investigated as a possible predictor of stuttering pathways. LEARNING OUTCOMES: (1) Readers will learn about studies regarding second formant transition related to stuttering. (2) Readers will learn about differences between children who persist in stuttering and those who recover from stuttering. (3) Readers will learn about research concerned with early identification of risk criteria in persistent stuttering.

Child, Preschool↗
PubMed1995

pH heterogeneity in aged hypertensive rat hearts distinguishes reperfused from persistently ischemic myocardium.

Myocardium reperfused following ischemia may contain regions that are adequately perfused but temporarily dysfunctional or metabolically abnormal, and regions that are persistently ischemic. By examining heterogeneity in the inorganic phosphate (Pi) resonance in 31P NMR spectra obtained for isolated perfused young v old hypertensive rat hearts made globally ischemic and then reperfused, areas of persistent intracellular acidosis (pHi about 6) were distinguished from recovering tissue (pHi about 7). The extent of persistent regional acidosis reported by Pi heterogeneity in the 31P NMR spectrum of the reperfused heart correlates well with (1) whole heart flow deficit measured as coronary flow, (2) the decrease in extracellular (primarily vascular) 23Na NMR resonance area measured using 23Na NMR and shift reagent, and (3) regional flow deficits identified using perfusate-borne dye markers. Persistent intracellular acidosis during reperfusion was observed only in the hearts of aged hypertensive rats, confirming that the vasculature of these animals is more susceptible to ischemic injury than both younger hypertensive rats and age-matched controls. The portion of the heart that is reperfused following only 16 min of global ischemia is metabolically abnormal, showing incomplete recovery of ATP and pH.

Adenosine Triphosphate↗
PubMed1993

Effect of nitric oxide on the survival rate and incidence of lung injury in newborn lambs with persistent pulmonary hypertension.

We previously showed that inhaling nitric oxide (NO) for up to 30 minutes selectively dilates the pulmonary circulation and improves oxygenation in newborn lambs with persistent pulmonary hypertension. In the current study we determined whether inhaling NO for 23 hours increased the survival rate of newborn lambs with persistent pulmonary hypertension, oxidized hemoglobin to methemoglobin, or damaged the lungs. Persistent pulmonary hypertension was created in newborn lambs by ligating the ductus arteriosus 13 days before delivery. Six lambs were randomly selected to breathe NO at 80 parts per million for 23 hours, and 7 control lambs were untreated. Each lamb was delivered at 135 days of gestation (term is 146 days), and the lungs were ventilated at a fraction of inspired oxygen of 0.92. Each of the control lambs died before the end of the study, whereas only one of the NO-treated lambs died (p < or = 0.05). Arterial oxygen tension was greater in the NO-treated lambs by 15 minutes after delivery (63 +/- 17 vs 14 +/- 4 mm Hg). Oxygen tension increased with time in the NO-treated lambs. Inhaled NO increased the concentration of methemoglobin, but this concentration reached a plateau at 3.0% +/- 0.4%. There was evidence of early airway damage in both groups of lambs but no difference between the groups. We conclude that inhaled NO increased survival rates without increasing the incidence of acute lung injury in newborn lambs with persistent pulmonary hypertension.

Animals↗
PubMed1987

Persistence of sleep disturbances in preschool children.

The purpose of our study was to determine if common sleep disturbances in young children, such as night waking and bedtime struggle, tend to persist; if they are related to environmental stress factors and are accompanied by other behavior problems; and if their persistence is related to other factors. Sixty children aged 15 to 48 months (mean age 26.4 months) were studied by interviewing their mothers initially and after 3 years. Children with and without sleep disturbances were compared, with the latter serving as the control group. Twenty-five (42%: night waking, 22%; bedtime struggle, 13%; both night waking and bedtime struggle, 7%) of 60 children had sleep disturbances at the initial interview, and of these 25 children, 21 (84%) had persistence of sleep disturbances after 3 years, persistent sleep disturbances had a significant relationship with increased frequency of stress factors in the environment (P less than 0.01). Other generalized behavior difficulties were present in 30% of sleep-disturbed and 19% of non-sleep-disturbed children (P = NS). Co-sleeping (sleeping with a parent or sibling) was noted more frequently in sleep-disturbed (34%) than in non-sleep-disturbed (16%) children. Twenty percent of the mothers at initial interview and 30% at 3-year follow-up perceived their child's sleep disturbances as stressful to them and to their family life. Early identification of the child with sleep disturbances and timely intervention would help both the child and the family.

Child Behavior Disorders↗
PubMed2003

Thresholds for disease persistence in models for tick-borne infections including non-viraemic transmission, extended feeding and tick aggregation.

Lyme disease and Tick-Borne Encephalitis (TBE) are two emergent tick-borne diseases transmitted by the widely distributed European tick Ixodes ricinus. The life cycle of the vector and the number of hosts involved requires the development of complex models which consider different routes of pathogen transmission including those occurring between ticks that co-feed on the same host. Hence, we consider here a general model for tick-borne infections. We assumed ticks feed on two types of host species, one competent for viraemic transmission of infection, the second incompetent but included a third transmission route through non-viraemic transmission between ticks co-feeding on the same host. Since a blood meal lasts for several days these routes could lead to interesting nonlinearities in transmission rates, which may have important effects.We derive an explicit formula for the threshold for disease persistence in the case of viraemic transmission, also for the case of viraemic and non-viraemic transmission. From this formula, the effect of parameters on the persistence of infection can be determined. When only viraemic transmission occurs, we confirm that, while the density of the competent host has always a positive effect on infection persistence, the density of the incompetent host may have either a positive effect, by amplifying tick population, or a negative ("dilution") effect, by wasting tick bites on an incompetent host. With non-viraemic transmission, the "dilution" effect becomes less relevant. On the other hand, if the nonlinearity due to extended feeding is included, the dilution effect always occurs, but often at unrealistically high host densities. Finally, we incorporated the effects of tick aggregation on the hosts and correlation of tick stages and found that both had an important effect on infection persistence, if non-viraemic transmission occurred.

Animals↗
PubMed2000

Mitochondrial ultrastructure and density in a primate model of persistent tardive dyskinesia.

The use of neuroleptic drugs to treat schizophrenia is almost invariably associated with extrapyramidal movement disorders. One of these disorders, tardive dyskinesia (TD), can persist long after neuroleptic withdrawal suggesting that permanent neurological damage is produced. However, there appears to be no convincing pathology of TD and its pathogenesis remains unknown. Findings that neuroleptics interfere with normal mitochondrial function and produce mitochondrial ultrastructural changes in the basal ganglia of patients and animals suggest that mitochondrial dysfunction plays a role in TD. We have established a model for persistent TD in baboons that appears to involve compromised mitochondrial function. In this study, we evaluated two animals treated for 41 weeks with a derivative of haloperidol and two treated with vehicle only. Treatment was then withdrawn and the animals observed for a further 17-18 weeks. Treated animals developed abnormal orofacial signs that were consistent with TD. These symptoms persisted during the drug-free period. The animals were euthanased, the brains perfused-fixed then post-fixed in 4% paraformaldehyde and the caudate and putamen prepared for electron microscopy. Regardless of whether mitochondria were located in neural soma, excitatory terminals, glia or in non-somal neuropil there was no consistent difference either in size or number between treated and control animals. Thus, even if mitochondria in striatal neurons undergo ultrastructural alterations during neuroleptic therapy, these changes do not persist after drug withdrawal.

Animals↗
PubMed2000

Theoretical analysis of the amplification of synaptic potentials by small clusters of persistent sodium channels in dendrites.

We extend on the work developed by R.R. Poznanski and J. Bell from a linearized somatic persistent sodium current source to a non-linear representation of the dendritic Na(+)P current source associated with a small number of persistent sodium channels. The main objective is to investigate the modulation in the amplification of excitatory postsynaptic potentials (EPSPs) in dendrites studded with persistent sodium channels. The relation between membrane potential (V) and persistent sodium current density (I(NaP)) is approximated heuristically with a sigmoidal function and the resultant cable equation is solved analytically using a regular perturbation expansion and Green's function techniques. The transient simulated (non-evoked) response is found as a result of current injection in the form of synaptically induced voltage change located at a distance from the recording site in a cable with a uniform distribution of ion channel densities per unit length of cable (the so-called 'hot-spots') and with the conductance of each hot-spot (i.e., number of channels per hot-spot) assumed to be a constant. The results show an amplification in the observed EPSPs to be compatible with the experimentally derived estimates, and in addition a saturation in the amplification is observed indicating an optimum number of ionic channels.

Animals↗
PubMed2001

Low level viral persistence after infection with LCMV: a quantitative insight through numerical bifurcation analysis.

Many important viruses persist at very low levels in the body in the face of host immunity, and may influence the maintenance of this state of 'infection immunity'. To analyse low level viral persistence in quantitative terms, we use a mathematical model of antiviral cytotoxic T lymphocyte (CTL) response to lymphocytic choriomeningitis virus (LCMV). This model, described by a non-linear system of delay differential equations (DDEs), is studied using numerical bifurcation analysis techniques for DDEs. Domains where low level LCMV coexistence with CTL memory is possible, either as an equilibrium state or an oscillatory pattern, are identified in spaces of the model parameters characterising the interaction between virus and CTL populations. Our analysis suggests that the coexistence of replication competent virus below the conventional detection limit (of about 100 pfu per spleen) in the immune host as an equilibrium state requires the per day relative growth rate of the virus population to decrease at least 5-fold compared to the acute phase of infection. Oscillatory patterns in the dynamics of persisting LCMV and CTL memory, with virus population varying between 1 and 100 pfu per spleen, are possible within quite narrow intervals of the rates of virus growth and precursor CTL population death. Whereas the virus replication rate appears to determine the stability of the low level virus persistence, it does not affect the steady-state level of the viral population, except for very low values.

Animals↗
PubMed2004

[Persistent primitive trigeminal artery associated with brain cavernoma. Case report].

Among cases of embryonic carotid-basilar anastomosis which may persist after birth, persistent trigeminal artery is the most common. It has been associated with a wide variety of intracranial abnormalities. We are unaware of any other reported association with cavernoma. We report a young woman who experienced seizures following spontaneous abortion. A CT scan disclosed a right frontal hematoma. MRI revealed a cavernoma associated with a persistent trigeminal artery. The cavernoma was removed through a frontal approach. The aim of the present case is to report another type of lesion fortuitously associated with a persistent trigeminal artery.

Adult↗
PubMed1999

Predictors of persistence of adnexal masses in pregnancy.

OBJECTIVE: To determine factors predicting the persistence of sonographically identified adnexal masses in pregnancy. METHODS: All patients from March 1988 to April 1993 diagnosed with an adnexal mass by obstetric sonography were reviewed. Examinations had been entered prospectively into our sonography database. Follow-up data were collected from the database, from hospital and pathology department records, and from interviews with referring obstetricians. Adnexal masses were characterized by size, sonographic appearance, and anatomic site. Persistence of the masses was determined by subsequent sonography, operative findings, or postpartum physical examinations. RESULTS: The rate of adnexal masses during pregnancy was 2.3% (432 of 18,391). Complete follow-up was available for 422 of 432. Most of the adnexal masses (76%; 320 of 422) were simple cysts with a mean diameter less than 5 cm. The remainder of the masses were simple or complex, measuring 5 cm or more in diameter. Seventy of 102 large or complex masses resolved. By multivariate analysis, the best predictors for persistence of these masses were complex appearance on sonography and size of the mass (P < .05 for both categories). CONCLUSION: Most adnexal masses identified by sonography during pregnancy were small, simple cysts that did not pose a risk to the pregnancy. Even the majority of large or sonographically complex masses resolved. The best predictors of persistence of the masses were sonographic appearance and size.

Adnexal Diseases↗
PubMed2000

Persistent intrahepatic right umbilical vein in the fetus: a benign anatomic variant.

OBJECTIVE: To evaluate outcomes of fetuses with antepartum sonographic diagnoses of persistent intrahepatic right umbilical veins. METHODS: A detailed fetal sonographic examination was done in 30,240 consecutive pregnancies at 14-26 weeks' gestation. High- and low-risk pregnancies were included and persistent right umbilical veins specifically were recorded. RESULTS: Sixty-nine fetuses had persistent intrahepatic right umbilical veins, of which 60 had no additional sonographic abnormalities, four had transient nuchal findings, and four had minor anomalies or anatomic variants. Only one of the 69 fetuses had a major anomaly (diaphragmatic hernia), and died after surgery. The remaining 68 fetuses were normal and healthy after birth. CONCLUSION: Persistent intrahepatic right umbilical vein is a fetal anatomic variant that is not rare and usually associated with a favorable outcome.

Female↗
PubMed2000

Persistent stress-induced elevations of urinary corticosterone in rats.

Exposure of rats to inescapable stressors (IS) results in persistent elevations in plasma corticosterone (CORT), which are selective to the trough of the circadian rhythm. Although affective disorders (depression, anxiety) in humans are also characterized by persistent hypothalamic-pituitary-adrenal axis (HPAA) activation, the predominant measure of HPAA activation in clinical studies is 24-h urinary cortisol. To facilitate interspecies comparisons regarding the persistent effects of stress on HPAA activity, we compared the effects of IS on plasma and urinary CORT in rats. Male Sprague-Dawley rats were exposed to three 2-h sessions of IS (40, 2.0 mA tailshocks) or remained in their home cages. The 24-h urine samples were collected daily from 2 days prior to stress to 5 days after stressor cessation, then weekly for 3 weeks. In addition, plasma samples were obtained at 08:00 (trough) and 20:00 hours (peak) for the first 3 days after stressor cessation and weekly for 3 weeks thereafter. Consistent with our earlier work, plasma CORT elevations were apparent in the trough, but not the peak samples for 3 days after stressor cessation. The 24-h urinary CORT levels were elevated during stressor exposure, and remained elevated for 3 days after stressor cessation. Persistent stress-induced urinary CORT elevations in rats are reminiscent of the clinical HPAA abnormalities described for major depression and affective disorders.

Animals↗