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Persistent pain as a disease entity: implications for clinical management.

Pain has often been regarded merely as a symptom that serves as a passive warning signal of an underlying disease process. Using this model, the goal of treatment has been to identify and address the pathology causing pain in the expectation that this would lead to its resolution. However, there is accumulating evidence to indicate that persistent pain cannot be regarded as a passive symptom. Continuing nociceptive inputs result in a multitude of consequences that impact on the individual, ranging from changes in receptor function to mood dysfunction, inappropriate cognitions, and social disruption. These changes that occur as a consequence of continuing nociceptive inputs argue for the consideration of persistent pain as a disease entity in its own right. As with any disease, the extent of these changes is largely determined by the internal and external environments in which they occur. Thus genetic, psychological and social factors may all contribute to the perception and expression of persistent pain. Optimal outcomes in the management of persistent pain may be achieved not simply by attempting to remove the cause of the pain, but by addressing both the consequences and contributors that together comprise the disease of persistent pain.

Chronic Disease↗

Evidence for a persistent Na+ conductance in neurons of the gastric mill rhythm generator of spiny lobsters.

Evidence for a persistent Na+ conductance was obtained in identified motor neurons of the gastric mill network in the stomatogastric ganglion of the spiny lobster Panulirus interruptus. The cells studied were the lateral gastric and lateral posterior gastric motor neurons, which in vivo control chewing movements of the lateral teeth of the gastric mill. We examined basic cellular properties in the quiescent network of the isolated stomatogastric ganglion. In current-clamp recordings, we found two types of evidence for a persistent Na+ conductance. First, tetrodotoxin-sensitive inward rectification occurred during depolarization from rest to spike threshold. Second, 5 mmol l-1 tetraethylammonium (a K+ channel blocker) induced plateau potentials that persisted in the presence of Mn2+ or a low [Ca2+]0 but were blocked by a low [Na+]0 or 100 nmol l-1 tetrodotoxin. The plateau potentials could drive trains of fast spikes in the motor axon and strong transmitter release at central output synapses within the ganglion. This conductance probably corresponds to the persistent Na+ current, INaP, described in cultured stomatogastric neurons and in neurons from several other preparations. During normal neuronal activity, it may contribute to the prolonged plateau depolarizations and long spike trains typical of motor neuronal activity during gastric rhythm generation. Persistent inward currents of this type are likely to be important in neurons that must fire prolonged bursts in cycle after cycle of rhythmical activity.

Animals↗

Gone but not forgotten: the lingering effects of intermediate-term memory on the persistence of long-term memory.

Aerial respiratory behaviour can be operantly conditioned in Lymnaea stagnalis and, depending on the interval between the training sessions, memories of significantly different durations are produced. In naïve snails, a 15 min training procedure with a 30 min interval between three training sessions results in memory that persists for only 3 h (intermediate-term memory, ITM); whilst if the three 15 min training sessions are separated by a 1 h interval memory persists for 48 h (long-term memory, LTM). We found that if ITM training preceded LTM training, then LTM would persist for 24 h longer. This augmenting effect on LTM persistence could be demonstrated for up to 5 h following the last ITM training session, even though ITM was not observed at that time. However, if LTM training ensued 8 h after the last ITM training session, an augmented LTM did not occur. Extinguishing the memory produced by the ITM training procedure also prevented augmentation of LTM. That is, if an extinction procedure was given to the snails after the ITM training procedure, LTM did not persist longer than 48 h. Thus, at the behavioural level, ITM and LTM are interconnected.

Animals↗

Pharmacological cardioversion of persistent atrial fibrillation with and without a history of drug-resistant paroxysmal atrial fibrillation.

BACKGROUND: Suppression by antiarrhythmic drugs of the maintenance mechanisms could convert persistent atrial fibrillation (AF) to sinus rhythm (SR). Whether a history of drug-resistant paroxysmal AF (PAF) would affect the outcome of pharmacological conversion of persistent AF by bepridil or in combination with aprindine was evaluated in the present study. METHODS AND RESULTS: The study group comprised 51 consecutive patients (24 men, 61+/-8 years) undergoing pharmacological conversion of persistent AF lasting >1 month. Drug-resistant PAF was defined as AF and at least 2 ineffective antiarrhythmic drugs for suppression of AF recurrence. Fast Fourier transform analysis of fibrillation waves was used to measure fibrillation cycle length (FCL) from the peak frequency. Fifteen patients had a history of drug-resistant PAF (Group I), and the remaining 36 did not (Group II) before diagnosis of persistent AF. Ten patients (67%) in Group I and 26 patients (72%) in Group II were restored to SR by bepridil alone or in combination with aprindine after 29+/-15 days of drug administration. Before conversion to SR, bepridil increased the FCL more in Group II than in Group I. During a 12-month follow-up period, 4 of 10 patients in Group I and 2 of 26 patients in Group II (p<0.01) had recurrence of persistent AF with bepridil alone or in combination with aprindine. CONCLUSIONS: A history of drug-resistant PAF does not affect the efficacy of pharmacological conversion by bepridil or in combination with aprindine. However, recurrence of AF was significantly higher in patients with such a history.

Anti-Arrhythmia Agents↗

Effects of coronary artery bypass surgery on regions showing persistent defects in thallium myocardial images.

The indications for revascularization surgery and its effects on myocardial regions showing persistent defects in thallium myocardial images are controversial. The effects of aortocoronary bypass surgery on myocardial perfusion and wall motion in the regions with persistent defects were evaluated in 47 patients with thallium-201 single photon emission computed tomography and left ventriculography. In areas showing persistent thallium defects preoperatively the rate of improvement of perfusion was only 24% by postoperative thallium imaging, and 57% by wall motion analysis. These results were significantly inferior to those of regions with transient defects, which were 84% and 82%, respectively. A persistent defect may not be a definitive marker of a non-viable scar, but the results of surgery on such regions were unsatisfactory. It is concluded, therefore, that revascuralization surgery in regions with persistent defects is not always recommended and that the indications for surgery should be individually determined with operative risk balanced against benefits.

Adult↗

Correlation between particle size, in vivo particle persistence, and lung injury.

Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the lung and may correlate with adverse pulmonary effects. We investigated such correlations using a model involving TiO2 particles of two particle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle types in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals compared to the larger-sized particles. In the postexposure period (up to 1 year) retention in the alveolar space per se was not different between fine and ultrafine TiO2. However, the following differences between the particle types were noted: a significantly different total pulmonary retention, both quantitatively (significantly prolonged retention of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macrophage function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and effects was observed. A comparison of the adverse reactions with dosimetric parameters of TiO2 in different lung compartments in the postexposure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment.

Administration, Inhalation↗

Induction of mucosal disease in cattle persistently infected with noncytopathic bovine viral diarrhea-mucosal disease virus by superinfection with cytopathic bovine viral diarrhea-mucosal disease virus.

Three head of cattle persistently infected with noncytopathic bovine viral diarrhea-mucosal disease virus (ncBVD-MDV) were superinfected naturally or experimentally with cytopathic bovine viral diarrhea-mucosal disease virus (cBVD-MDV). In the naturally superinfected case, one animal manifested pyrexia and severe diarrhea, and died without developing antibodies to cBVD-MDV. However, another animal survived with only continual slight anorexia and pyrexia, and developed strong resistance to the superinfected strain. In the experimental cases, induction of MD was unsuccessful in two persistently infected cattle when superinfected with cBVD-MDV antigenically heterologous for persistently infected ncBVD-MDV. They also developed antibodies to the cBVD-MDV strain with which they had been infected. After 6 months, these cattle were infected again with a cBVD-MDV strain different from that used in the previous experiment. One animal infected with this strain, which was antigenically homologous to the persistently infected strain, died after developing MD symptoms without developing antibodies to the infecting strain. It is suggested that the antigenic relationship between the persistent ncBVD-MDV and the superinfected cBVD-MDV was an important factor in developing MD.

Animals↗

Heterogeneity of airway inflammation in persistent asthma : evidence of neutrophilic inflammation and increased sputum interleukin-8.

STUDY OBJECTIVES: To identify the characteristics of airway inflammation in persistent asthma and to examine the role of neutrophilic inflammation in noneosinophilic persistent asthma. METHODS: Nonsmoking adults (n = 56) with persistent asthma and healthy control subjects (n = 8) underwent hypertonic saline solution challenge and sputum induction. Selected sputum portions were dispersed with dithiothreitol and assayed for total cell count, cellular differential, supernatant eosinophil cationic protein (ECP), myeloperoxidase, and interleukin (IL)-8. RESULTS: We identified two distinct inflammatory patterns. Typical eosinophilic inflammation occurred in 41% of subjects, whereas the remainder exhibited noneosinophilic asthma (59%). Both neutrophil percentage and absolute neutrophil counts were increased in subjects with noneosinophilic asthma (64%, 283 x 10(6)/mL) compared to eosinophilic asthma (14%, 41 x 10(6)/mL) and control subjects (34%, 49 x 10(6)/mL; p = 0.0001). Myeloperoxidase was elevated in both noneosinophilic (280 ng/mL) and eosinophilic groups (254 ng/mL) compared with control subjects (82 ng/mL; p = 0.002). Sputum IL-8 levels were highest in subjects with noneosinophilic asthma (45 ng/mL) compared to eosinophilic asthma (9.6 ng/mL) and control subjects (3.5 ng/mL; p = 0.0001). Neutrophils correlated with IL-8 levels (r = 0.72). ECP was highest in subjects with eosinophilic asthma (2,685 ng/mL) compared with noneosinophilic asthma (1,081 ng/mL) and control subjects (110 ng/mL; p = 0.0001). CONCLUSION: Induced-sputum analysis in persistent asthma identifies two different inflammatory patterns. The most common pattern is noneosinophilic, associated with a neutrophil influx and activation, which may be mediated by IL-8 secretion. There is heterogeneity of airway inflammation in persistent asthma, which indicates differing mechanisms and may impact on treatment responses.

Adult↗

Left superior vena cava persistence in patients undergoing pacemaker or cardioverter-defibrillator implantation: a 10-year experience.

OBJECTIVE: The persistence of a left superior vena cava (LSVC) has been observed in 0.3% of the general population as established by autopsy. In the adult population, it is an important anatomic finding if a left superior approach to the heart is considered. The aim of the study was to evaluate the prevalence of a LSVC in patients undergoing pacemaker (PM) and cardioverter-defibrillator (CD) implantation. DESIGN: We observed the prevalence of LSVC during a 10-year period; each patient undergoing PM or transvenous CD implantation received a left cephalic/left subclavian venous approach to the heart. With this technique, LSVC persistence is easily diagnosed during lead placement. RESULTS: A total of 1,139 patients consecutively underwent PM implantation during 10 years: 4 patients had persistent LSCV (0.34%). Among 115 patients undergoing CD implantation, 2 patients with LSVC (1.7%) were observed. Overall LSVC persistence was found in 6 of 1,254 patients (0.47%). Two patients, one of whom had no right superior vena cava (RSVC), received a left-sided PM, whereas two other patients received right-sided devices. Both CD patients received a left-sided active-can device: the first patient with a right-sided lead tunneled to the left pectoral pocket, as a result of poor catheter handling through the LSVC and coronary sinus, and the second patient with a screw-in lead from LSVC. Long-term follow-up of these patients (average +/- SD, 41 +/- 26 months) revealed absence of lead dislodgment and appropriate device function regardless of lead implantation site. CONCLUSIONS: Persistence of LSVC in adults undergoing PM/CD implantation is similar to that of the general population (0.47% in our study). The left-sided implant can be achieved by stylet shaping and by use of active fixation leads in most patients, with a reliable outcome at short term in addition to appropriate device performance at follow-up. Assessment of the RSVC is advisable when planning a right-sided implantation, since a minority of patients lacks this vessel.

Defibrillators, Implantable↗

Unsuspected loss of lung elastic recoil in chronic persistent asthma.

STUDY OBJECTIVES: To investigate the progression and mechanism(s) for fixed maximum expiratory airflow (max) limitation in patients with chronic persistent asthma. METHODS: When optimally treated and in clinically stable condition, we studied 21 asthmatic patients and classified them into three groups based on the severity of expiratory airflow limitation: (1) group A included 5 asthmatic patients (four women; mean +/- SD age, 51 +/- 17 years) with mild persistent asthma (FEV(1) > 80% predicted) with serial FEV(1) measurements obtained prior to the present study for 16 +/- 4 years; (2) group B included 11 asthmatic patients (three women; mean age, 64 +/- 11 years) with moderate persistent asthma (FEV(1) of 60 to 80% predicted) with serial FEV(1) measurements for 12 +/- 4 years; and (3) group C included 5 asthmatic patients (three women; mean age, 55 +/- 16 years) with severe persistent asthma (FEV(1) < 60% predicted) with serial FEV(1) measurements for 11 plus minus 5 years. RESULTS: Lung CT indicated no or trivial emphysema, and diffusion was normal in all asthmatics. There was a marked loss of lung elastic recoil at total lung capacity (TLC) in all asthmatic patients in group B (16 +/- 4 cm H(2)O) and group C (15 +/- 5 cm H(2)O), but none or minimal in group A (22 +/- 1 cm H(2)O) [p < 0.01], and loss of elastic recoil accounted for 34% and 50% of decreased maximal expiratory airflow (max) at 80% and 70% TLC, respectively. Comparison with previous longitudinal data indicated individual asthmatics when in clinically stable condition remained predominantly in the same FEV(1) percent predicted classification group as in the current study. CONCLUSION: Patients with chronic moderate and severe persistent asthma, despite optimal therapy, have reduced max for many years in part due to (early?) loss of lung elastic recoil from unknown mechanism(s). This challenges current concept of airway remodeling.

Aged↗

Relation of beta2-adrenoceptor polymorphisms at codons 16 and 27 to persistence of asthma symptoms after the onset of puberty.

BACKGROUND: It has long been recognized that many children with asthma outgrow the disease after the onset of puberty, but little is known about genetic factors influencing this outcome. OBJECTIVES: The aim of the present study was to determine whether the polymorphisms at codons 16 and 27 of the beta2-adrenoceptor are significant predictors of the persistence of asthma during adolescence. DESIGN AND PARTICIPANTS: We used data from the prospective Tucson Children's Respiratory Study. Children were genotyped for the polymorphisms at codons 16 and 27. The presence of wheezing/asthma was assessed by questionnaire from age 6 years up to the reported onset of puberty (prepubertal period) and after the onset of puberty up to age 16 years (adolescence). RESULTS: Among children who wheezed in the prepubertal period (n = 168), subjects homozygous for Gly at codon 16 were at significantly increased risk for persistent wheezing after puberty, as compared with carriers of the other genotypes (relative risk [RR], 1.43; 95% confidence interval [CI], 1.06 to 1.92; p = 0.019). This relation was present among boys (RR, 2.17; 95% CI, 1.41 to 3.36) but not girls (RR, 0.85; 95% CI, 0.55 to 1.30), and increased linearly according to the frequency of wheezing episodes after the onset of puberty. These findings persisted after adjusting for ethnicity and other potential confounders and after selecting only white children. The polymorphism at codon 27 showed no relation with risk for persistent wheezing. CONCLUSIONS: This study provides evidence for a strong gender-specific effect of the Gly16 polymorphism on the persistence of asthma after the onset of puberty.

Adolescent↗

Are factors at diagnosis of growth hormone deficiency in childhood associated with persistence of growth hormone deficiency into adult life?

A proportion of children with growth hormone deficiency (GHD) have persistence of GHD as young adults. To date, no markers have been shown in childhood to have predictive value in determining persistence of GHD into adult life. We examined the hypothesis in 31 patients that variables present at the time of diagnosis of childhood-onset GHD, or those related to the early response to growth hormone (GH) therapy, are associated with the likelihood of persistence of GHD. The results show that, as previously demonstrated, children with GHD are more likely to have persistent severe GHD in adult life when the diagnosis is associated with other pituitary hormone deficiencies (p = 0.02), abnormal pituitary neuroimaging (p = 0.003), induced puberty (p = 0.001), early age of diagnosis (p = 0.03) and lower peak GH response at the first dynamic GH test in childhood (p = 0.02). However, there are no associations of persistent severe GHD with the pattern of pretreatment growth or growth response to GH treatment in the initial phase.

Adult↗

Persistence and problem-solving skills in young male alcoholics.

This study compares the level of persistence between 31 inpatient alcoholic males and 31 abstinent or light social drinking males matched on age, education, socioeconomic status and estimated premorbid IQ. An unsolvable anagram and diagram were selected as measures of persistence. Results indicated that alcoholics persisted for significantly shorter periods of time on both measures than their matched controls. However, there were no significant group differences on two measures from the Wisconsin Card Sorting Test (set shifting and set maintenance). Persistence measures from the unsolvable tasks were not significantly correlated with the set maintenance score of the Wisconsin Card Sorting Test. Possible explanations are considered for these findings of persistence deficits without problem-solving impairments among young alcoholics.

Adult↗

Persistent disease after surgery for primary hyperparathyroidism: the long-term outcome.

OBJECTIVE: Nineteen patients with persistent primary hyperparathyroidism were investigated to evaluate their clinical and laboratory status a long time after treatment was ended. The risk of persistent disease and need for extensive surgery for cure, i.e. more than two neck operations, or mediastinal exploration, was also evaluated. DESIGN: The medical records of 896 consecutive patients operated on for primary hyperparathyroidism were scrutinised at follow-up, a mean of 10.3 Years after surgery. Data on state of health, medication, bone fractures and other diagnoses were collected by use of a questionnaire. There were 600 patients still alive, among whom 13 had persistent disease and they were compared with 509 patients who were cured and without any suspicion of recurrent disease, according to laboratory examination. RESULTS: Serum calcium and creatinine values had with few exceptions remained stable over the Years. In five patients, serum calcium levels were within the normal range at follow-up. Still, all 19 patients were considered hyperparathyroid. They had substantial cardiovascular morbidity, and their state of health was not as good as that of the patients who were surgically cured. After one operation, 5.5% (95% confidence interval (CI) 4.0-7.2%) had persistent disease, and 2.1% after reoperation. Extensive surgery for cure was performed in 2% of the patients (95% CI 1.1-3.2%). CONCLUSIONS: We found that the state of health was significantly better for patients with cured primary hyperparathyroidism than for patients with persistent disease, but serious deterioration of laboratory values was uncommon. The result of the present study supports surgical treatment.

Calcium↗

Ovarian carbonyl reductase activity in rats at persistent oestrus.

Age-related changes and effects of gonadotrophins on ovarian carbonyl reductase (CR) of virgin female Wistar-Imamichi rats were investigated. In mature rats ovarian CR is an LH-dependent oxidoreductase and is closely involved in the periovulatory process. After 8 months of age, all of the rats exhibited persistent oestrus and the ovarian mass was significantly decreased, whereas 4- and 5-month-old rats showed the regular 4 day oestrous cycles and ovulation occurred. The ovarian CR activity towards four substrates declined steeply consistent with persistent oestrus and the enzyme activity for each substrate at 15 months of age was 1.4-53.7% lower than at 4 months of age. The ovarian CR concentration measured by western blot analysis was also lower at 8 months of age. Equine chorionic gonadotrophin (eCG) and hCG were administered to 10- and 15-month-old rats at persistent oestrus to examine whether the ovarian CR in rats at persistent oestrus is influenced by gonadotrophins. Treatment with hCG not only increased ovarian CR activity and its concentration but also caused ovulation at both ages. The immunoreactivity to anti-ovarian CR antibody in the theca cells of the hCG-treated ovary was greater than that of the control ovary. Equine(e) CG did not stimulate ovarian CR activity in rats at persistent oestrus, although ovarian mass of 10-month-old rats was increased after administration of 50 iu of eCG. These results indicate that changes in ovarian CR with ageing are related to the transition of regular oestrous cyclicity to acyclicity and that the expression of ovarian CR markedly decreased in aged rats is stimulated by hCG.

Aging↗

Persistence of anti-zonae pellucidae antibodies following a single inoculation of porcine zonae pellucidae in the domestic equine.

In this study of equids, we investigated the antibody response and the effect on the estrous cycle following a single inoculation of porcine zonae pellucidae (pZP) employing controlled-release methodology. We also investigated the use of two different water-soluble adjuvants as an alternative to oil-based adjuvants. Twenty-seven domestic mares were inoculated with various formulations of pZP and adjuvant. We showed that the anti-pZP antibodies generated as a result of the inoculations persisted for at least 43 weeks (length of the study). Of the various formulations used in the study, pZP and QS-21 water-soluble adjuvant, administered in combination with an emulsified preparation of pZP and Freund's Complete Adjuvant generated a significantly (P < 0.05) higher titer of anti-pZP antibodies when compared with other formulations employing the water-soluble adjuvant, Carbopol. Hormone analyses for cyclicity indicated a high incidence and extended duration of persistent corpora lutea among the treated mares. The positive control group of mares receiving two standard inoculations of pZP and Freund's Complete and Incomplete Adjuvants, as well as the placebo group of mares injected with QS-21 only, also exhibited high incidences of persistent corpora lutea. However, all mares eventually returned to normal cyclicity. The basis for the high incidence and extended duration of persistent corpora lutea was unexplained. The results demonstrate for the first time the persistent generation of anti-pZP antibodies following a single inoculation of pZP incorporated into a controlled-released preparation in the horse. This study further suggests that a single inoculation of pZP sequestered in a controlled-release lactide-glycolide polymer may serve as an alternative to traditional two-inoculation protocols for contraception investigations in the equine.

Acrylic Resins↗

Prospective study of persistence and excretion of human herpesvirus-6 in patients with exanthem subitum and their parents.

OBJECTIVE: To elucidate persistence of human herpesvirus-6 (HHV-6) in the blood and excretion of the virus into several body fluids of patients with exanthem subitum (ES), and to examine serologic and virologic findings of the parents caring for the patients in the family setting. MATERIALS AND METHODS: During a 15-month period, 20 infants from 20 families (11 boys and 9 girls; mean age, 7.7 months; range, 4-11 months) with primary HHV-6 infection and a typical clinical course of ES, and 15 parents from the 20 families (2 males and 13 females; mean age, 28.2 years; range, 21-34 years) were enrolled in the study and examined clinically and virologically. Primary infection with HHV-6 was confirmed by isolation of the virus from peripheral blood mononuclear cells (MNCs), and seroconversion or a significant increase in the antibody titers to HHV-6 by a neutralization test. Viral persistence or excretion was examined by amplifying the viral deoxyribonucleic acid (DNA) in serially collected peripheral blood MNCs, plasma, saliva, stool, and urine samples with a nested polymerase chain reaction method. Data on saliva from the parents were compared with those of 21 age-matched controls. RESULTS: Twenty infants with virologically confirmed ES had HHV-6 DNA in MNCs persistently during and after the disease but in plasma only in the first 5 days of ES. The viral DNA was also detected persistently or intermittently in saliva and stool during and after the disease but rarely in urine. On the other hand, the 15 parents examined of the 20 infants had no HHV-6 viremia nor viral DNA in peripheral blood MNCs and plasma except 1, but half of them excreted viral DNA in saliva during and after ES. The frequency of excretion of viral DNA into saliva was not significantly different from that of 21 control parents. Only 1 of the 15 showed a fourfold increase in antibody titers to HHV-6 after possible exposure from their children. CONCLUSIONS: After systemic replication of HHV-6 in the blood of patients with ES during the first 5 days of the disease, the virus is excreted into saliva and stool persistently or intermittently but rarely into urine. The presence of HHV-6 DNA in plasma suggested active infection with the virus. Excretion of the virus into the saliva of infants with ES and their parents suggests the source and transmission route of infection with HHV-6.

Adult↗

Otorrhea in young children after tympanostomy-tube placement for persistent middle-ear effusion: prevalence, incidence, and duration.

OBJECTIVE: To characterize the occurrence of tube otorrhea after tympanostomy-tube placement (TTP) for persistent middle-ear effusion (MEE) in a group of otherwise healthy infants and young children. METHODS: In a long-term, prospective study of child development in relation to early-life otitis media, we enrolled by 2 months of age healthy infants who presented for primary care at 1 of 2 urban hospitals or 1 of 2 small-town/rural and 4 suburban private pediatric group practices. We monitored their middle-ear status closely. Children who developed persistent MEE of specified durations within the first 3 years of life became eligible for random assignment to undergo TTP either promptly or after an extended period if MEE persisted. The present report concerns 173 randomly assigned children who underwent bilateral TTP between ages 6 and 36 months and were followed for at least 6 months thereafter. Episodes of tube otorrhea were treated with oral antimicrobial drugs and, if persistent, with ototopical medication. RESULTS: Socioeconomic status, as estimated from maternal education and type of health insurance, was lowest at the urban sites and highest at the suburban sites. The tenure of the 230 tubes that were extruded during the observation period ranged from 19 days to 38.5 months (mean = 13.8 months; median = 13.5 months). During the first 18 months after TTP, the proportion of children who had tubes in place and who developed 1 or more episodes of otorrhea increased progressively, reaching 74.8% after 12 months and 83.0% after 18 months. The mean number of episodes per child was 0.79 in the first 6 months, 1.50 in the first 12 months, 2.17 in the first 18 months, and 2.82 in the first 24 months. Overall, otorrhea occurred earliest and was most prevalent among urban children and occurred latest and was least prevalent among suburban children. The mean estimated duration of episodes of tube otorrhea was 16.0 days (standard deviation = 16.9 days), the median was 10 days, and the range was 3 to 131 days. The duration was >30 days in 13.2% of the episodes. Six of the 173 children (3.5%) developed on 1 or more occasions tube otorrhea that failed to improve satisfactorily with conventional outpatient management. Five of these children were hospitalized to receive parenteral antibiotic treatment, 1 child twice and 1 three times, and 1 also underwent tube removal. The sixth child underwent tube removal as an outpatient. CONCLUSIONS: Tube otorrhea is a common and often recurrent and/or stubborn problem in young children who have undergone tube placement for persistent MEE. The extent of the problem seems to be related inversely to socioeconomic status. Tube otorrhea does not always respond satisfactorily to outpatient management and for resolution may require parenteral antimicrobial treatment and/or tube removal.

Anti-Bacterial Agents↗