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Persistence of intracranial diastolic flow in transcranial Doppler sonography exploration of patients in brain death.

OBJECTIVE: The persistence of cerebral blood flow (CBF) in patients with whole brain death (BD) diagnosis is an unusual phenomenon. We describe patients with whole BD diagnosed despite persistence of intracranial blood flow on transcranial Doppler sonography (TDS). MATERIALS AND METHODS: From January 2001 to December 2002, we reviewed the records of 11 patients. Etiology of BD was craniocephalic trauma in 2 cases, schemic cerebrovascular accident (CVA) in 4 cases, Hemorrhagic CVA in 3 cases, subaracnoid hemorrhage in 1 case, and acute hydrocephalus in 1 case. Six patients had a cerebral decompressive mechanism. In all patients, TDS was used to confirm BD after clinical diagnosis. Additionally, all patients underwent an electroencephalogram (EEG). In 3 patients cerebral angiography (CA) and in 2 others radionuclide angiography (RA) with Tc99m HMPAO were done. RESULTS: All TDS studies showed persistent telediastolic positive flow in at least 1 artery. Because the TDS did not confirm the clinical diagnosis of BD, EEG tests were performed showing silence of bioelectrical activity. Those cases showed CA or RA results with a complete absence of CBF. CONCLUSION: The TDS technique directly evaluates the intracranial but not the intracerebral circulation. For this reason, during the BD diagnosis for patients with previous decompressive techniques, it was possible to find persistence of intracranial telediastolic flow using TDS. In those cases, it is advisable to use other tests to confirm the clinical diagnosis of BD.

Adult↗

Blood rheology in deep venous thrombosis--relation to persistent and transient risk factors.

INTRODUCTION: The risk of recurrence in patients with symptomatic deep venous thrombosis (DVT) is higher in patients with persistent risk factors than in patients with transient risk factors. The purpose of this prospective study was to investigate the course of rheological variables in patients with DVT up to 1 year after the acute event in relation to risk factors. PATIENTS AND METHODS: In 37 patients with proven DVT plasma fibrinogen, plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit and platelet aggregation were studied in the acute phase, at 6 weeks and at 12 months. RESULTS: In the acute phase, patients had higher fibrinogen (medians and ranges; 450 [270-611] vs. 247 [170-340] mg/dl, p < 0.01), plasma viscosity (1.67 [1.48-1.96] vs. 1.60 [1.50-1.70] mPa s, p < 0.01), red cell aggregation (9.76 [5.87-12.66] vs. 5.66 [3.67-8.46] arbitrary units; p < 0.01) and whole blood viscosity (5.78 [5.61-5.87] vs. 5.59 [5.27-5.9] mPa s, p < 0.01), but lower hematocrit (40 [32-46] vs. 45 [38-50]%, p < 0.01) and platelet aggregation (by epinephrine: 41 [13-85] vs. 79 [29-91]%, (p < 0.01) than controls. During the 1-year follow-up, fibrinogen, plasma viscosity, red cell aggregation and whole blood viscosity constantly decreased, whereas hematocrit and platelet aggregation increased in the total of patients (all p < 0.01). Subgroup analysis according to risk factors showed that at 12 months patients with persistent risk factors (N = 21) had higher plasma fibrinogen (357 [235-450] vs. 247 [214-335] mg/dl, p < 0.01), plasma viscosity (1.65 [1.50-1.80] vs. 1.59 [1.42-1.77] mPa s, p < 0.05) and red cell aggregation (7.82 [6.0-11.3] vs. 6.3 [5.2-7.1] arb. units, p < 0.01) than patients with transient risk factors (N = 16). Compared with controls, these variables were increased in patients with persistent risk factors (all p < 0.01), but not in patients with transient risk factors (all n.s.). CONCLUSION: In patients with persistent risk factors rheological changes are still present 1 year after acute DVT, whereas in patients with transient risk factors blood rheology returns to normal. Further studies are needed to clarify whether blood rheology might be helpful to identify patients at high risk of recurrence.

Adult↗

Carpal tunnel syndrome due to thrombosed persisting median artery. A case report.

Surgical intervention for carpal tunnel syndrome in a seventy year old woman revealed thrombosis of a double persisting median artery. The persisting median artery is a rare anomaly and its association with a thrombotic process to cause carpal tunnel syndrome is even rarer. Carpal tunnel syndrome is a widely-known phenomenon about which much has been written in the medical literature. A persisting median artery accompanying the nerve into the carpal tunnel is uncommon, occurring in only about 10% of such cases (Pecket, 1973) and thrombosis of such an artery as a cause for carpal tunnel syndrome is very rare (Burnham, 1963; DeAbreu & Godoy Moreira, 1958). We describe a case in which thrombosis is a double persisting median artery was discovered to be the cause of carpal tunnel syndrome at operation.

Aged↗

The effects of CO2 pneumoperitoneum on the survival of women with persistent metastatic ovarian cancer.

OBJECTIVES: The effects of CO(2) pneumoperitoneum on the survival of women with metastatic ovarian cancer have not been documented. We sought to describe the survival of women with persistent stage III-IV ovarian cancer as documented by positive second-look laparoscopy or laparotomy and to see whether the laparoscopic approach with CO(2) pneumoperitoneum has a negative effect on overall survival. METHODS: We conducted a retrospective review of all patients with FIGO stage III-IV invasive epithelial ovarian cancer who were found to have persistent disease at second-look surgery. All patients underwent primary surgery followed by intravenous chemotherapy and were clinically without evidence of disease prior to second-look surgery. Second-look laparoscopy began to be utilized regularly in 1994. The selection of the second-look surgical approach depended on the surgeon's discretion. CO(2) pneumoperitoneum was utilized for all laparoscopic cases with the maximum intra-abdominal pressure maintained at 15 mm Hg. Patients received a variety of additional intravenous, intraperitoneal, or oral chemotherapy following positive second-look surgery. RESULTS: Between 6/1/91 and 6/30/02, 289 patients were found to have persistent ovarian/peritoneal cancer at second look. Second-look operations included 131 (45%) transperitoneal laparoscopies and 139 (48%) laparotomies. Nineteen (7%) patients underwent laparoscopy followed immediately by laparotomy. The mean age, stage distribution, histology, grade, and size of residual disease at second look did not differ between the two groups. The median overall survival for patients who underwent laparoscopy, 41.1 months (95% CI, 33.2-58.1), did not significantly differ from that of the laparotomy group, 38.8 months (95% CI, 31.9-44.2) (P = 0.742). CONCLUSIONS: Transperitoneal laparoscopy with CO(2) pneumoperitoneum does not appear to reduce the overall survival of women with persistent metastatic intra-abdominal carcinoma of ovarian/peritoneal origin. The overall survival appears to be independent of the second-look surgical approach.

Carbon Dioxide↗

Group II mGluR receptor agonists are effective in persistent and neuropathic pain models in rats.

The involvement of Group II metabotropic receptors in acute and persistent pain states was evaluated in several in vivo models of pain with selective and potent Group II metabotropic glutamate (mGlu) 2,3 agonists. LY354740, LY379268 and LY389795 attenuated late-phase paw-licking pain behavior in a dose-dependent manner in the formalin model of persistent pain. Effects occurred in the absence of overt neuromuscular deficits as measured by performance in the rotorod test for ataxia. The effects of LY354740 and LY379268 were also stereoselective. The order of potency of the agonists was LY389795>LY379268>LY354740. The attenuation of licking behavior by LY379268 (3 mg/kg) in the formalin model was reversed by a potent and selective mGlu2,3 receptor antagonist, LY341495 (1 mg/kg). In the L5/L6 spinal nerve ligation model of neuropathic pain in rats, LY379268 significantly reversed mechanical allodynia behavior in a dose-related manner. In contrast, LY379268 had no significant effects on the tail flick test or paw withdrawal test of acute thermal nociceptive function. These results support the involvement of Group II mGlu2,3 receptors in persistent pain mechanisms and suggest the potential utility of selective Group II mGlu agonists for the treatment of persistent pain.

Animals↗

Efficacy of budesonide inhalation suspension in infants and young children with persistent asthma. Budesonide Inhalation Suspension Study Group.

This paper reviews the results from 3 randomized, double-blind, placebo-controlled, multicenter studies that assessed the efficacy and safety of once- and twice-daily dosing of budesonide inhalation suspension (BIS) in infants and young children with persistent asthma. In children with mild persistent asthma that was previously treated with bronchodilators or noncorticosteroid anti-inflammatory agents (study A), nighttime and daytime asthma symptoms were significantly improved in 0.25-mg once daily, 0.5-mg once daily, and 1.0-mg once daily BIS treatment groups compared with placebo (P </=. 05). Rescue medications were used significantly less in all BIS groups (approximately 2 days of every 14 days) compared with placebo (P <.05). The proportion of patients who discontinued this therapy because of worsening asthma was greater in the placebo group than in the BIS groups, with the difference between placebo (23%) and the 1. 0-mg BIS group (13%) being statistically significant (P =.020). All BIS doses except 0.5 mg once daily showed nonsignificant numeric improvement in morning and evening peak expiratory flow (PEF) compared with placebo. In children with asthma that was previously treated with inhaled corticosteroids (study B), BIS doses of 0.25 mg, 0.5 mg, and 1.0 mg twice daily resulted in significant improvements in nighttime symptoms scores versus placebo (P </=.026). Rescue medications were used significantly less in all BIS groups (approximately 2.5 to 3.5 days of every 14 days) compared with placebo (P </=.032). The proportion of patients receiving placebo who discontinued therapy because of worsening asthma symptoms (36%) was significantly greater compared with the BIS groups (9%; P </=. 015). Morning PEF levels were significantly greater in each BIS group compared with placebo (P </=.03). For evening PEF levels, all BIS treatment groups showed numeric improvements compared with placebo; the 0.25-mg twice daily budesonide group showed statistically significant improvement (P <.05). In children with moderate persistent asthma that was previously maintained either on bronchodilators or inhaled corticosteroids (study C), nighttime asthma symptoms significantly improved in the 0.25-mg twice daily, 0. 5-mg twice daily, and 1.0-mg once daily BIS groups compared with placebo (P <.01); there was a numeric improvement for the 0.25-mg once daily treatment group. Rescue medications were used significantly less in all BIS groups (approximately 2 to 3 days of every 14 days) compared with placebo (P </=.014). The proportion of patients who discontinued treatment because of worsening of asthma symptoms was greater in the placebo group than in the BIS groups; the difference between 0.25-mg twice daily group (13%) and the placebo group (26%) was statistically significant (P =.029). All BIS doses showed numeric improvement in morning PEF levels, and statistically significant improvements were observed in the 0.25-mg twice daily, 0.5-mg twice daily, and 1.0-mg once daily groups compared with placebo (P <.03). Significant improvements in evening PEF levels were observed for each BIS treatment group (P </=.034), except for the 1.0-mg once daily group. Overall, the 3 studies show that once- and twice-daily dosing of BIS effectively relieves asthma symptoms and improves pulmonary function in infants and young children with mild-to-severe persistent asthma.

Administration, Inhalation↗

Uterine clearance and resistance to persistent endometritis in the mare.

The objective of this article is to review the role of uterine defense mechanisms in natural resistance to chronic or persistent endometritis. A breakdown of uterine physical clearance mechanisms is currently believed to play a major role in susceptibility to persistent endometritis. Mares with increased susceptibility to persistent endometritis have impaired myometrial contractility in response to an acute inflammation, resulting in an accumulation of fluid and inflammatory products within the uterine lumen. The origin of this defect remains unknown. Recent studies have demonstrated that spermatozoa trigger PMN chemotaxis into the uterine lumen. This observation suggests that a transient endometritis is a normal physiological response to breeding. However, in mares with impaired uterine defense mechanisms, the condition may develop into a persistent endometritis and subsequent subfertility. In contrast to spermatozoa, seminal plasma has a suppressive effect on complement activation and PMN chemotaxis (65). The exact role of seminal components in breeding-induced inflammation needs further investigation.

Animals↗

Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial.

BACKGROUND: Although inhaled glucocorticosteroids are recommended for persistent asthma, their long-term effect on recent onset, mild, persistent asthma has yet to be established. METHODS: We did a randomised, double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids. Patients aged 5-66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications. The daily budesonide dose was 400 microg, or 200 microg for children younger than 11 years. The primary outcome was time to first severe asthma-related event, and analysis was by intention to treat. FINDINGS: 198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation; hazard ratio 0.56 (95% CI 0.45-0.71, p<0.0001). Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo. Compared with placebo, budesonide increased postbronchodilator forced expiratory volume in 1 s (FEV1) from baseline by 1.48% (p<0.0001) after 1 year and by 0.88% (p=0.0005) after 3 years (expressed as percent of the predicted value). The corresponding increase in prebronchodilator FEV1 was 2.24% after 1 year and 1.71% after 3 years (p<0.0001 at both timepoints). The effect of treatment on all outcome variables was independent of the baseline lung function (prebronchodilator or postbronchodilator) or baseline medication. In children younger than 11 years, 3-year growth was reduced in the budesonide group by 1.34 cm. The reduction was greatest in the first year of treatment (0.58 cm) than years 2 and 3 (0.43 cm and 0.33 cm, respectively). INTERPRETATION: Long-term, once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset.

Administration, Topical↗

Chronic relapsing pericarditis and dilated cardiomyopathy: serological evidence of persistent enterovirus infection.

By means of two different IgM-capture assays, enterovirus-specific IgM responses were shown in 9 of 14 (64%) patients with chronic relapsing pericarditis. This finding suggests persistent enterovirus infection, particularly coxsackie B virus infection. IgM responses persisted for at least 1 year and for up to 10 years after onset of symptoms. In contrast, patients with acute enterovirus infections, including acute pericarditis, had transient responses. Among patients with acute pericarditis, the level of IgM antibody was significantly higher in those who subsequently relapsed (mean 1.21, range 0.6-2.0 optical density [OD] units) than in those who did not (0.4, 0.2-0.9 OD units; p less than 0.01). Of 86 patients with dilated cardiomyopathy, 28 (33%) showed enterovirus-specific IgM responses which were present for up to 19 months before transplantation and persisted up to 4 years afterwards. Although the distribution of HLA types in these patients was similar to that in the general population, the frequency of the HLA A2 haplotype was significantly higher in those who were IgM positive. IgM antibody was significantly more common in those who had had symptoms for longer than a year before transplantation than in those with a shorter duration of symptoms (1 of 21 vs 8 of 23; p less than 0.02). Persistent virus-specific serum IgA responses were also shown in patients with chronic cardiac disease.

Acute Disease↗

Persistence and differentiation of HTLV-I-transformed immature T-cells in HTLV-I carrier rabbits.

Two T-cell lines with immature phenotypes, CD4-8- and CD4+8+, were found among HTLV-I-transformed T-cell lines obtained during experiments using a rabbit model of adult T-cell leukemia. Persistence and differentiation of these clones in vivo were examined by retrospectively analysing a series of cell lines from individual animals and by adoptive transfer of these cells into syngeneic hosts. The double negative cell line did not differentiate and remained double negative in adoptive transfer into neonates and in long-term in vitro culture, while the double positive cell line differentiated both in vivo and in vitro into CD8+ cell, as if the fate of this cell line had been predetermined. Cells of the same clone as this double positive cell line persisted for more than one year in the peripheral blood of the animal. Long-term persistence was not observed for five cell lines of CD4 single positive phenotype, which were obtained from another carrier rabbit. These results suggested that HTLV-I-transformed immature T-cells persist in neonatally infected carriers, continuously giving rise to mature T-cells harboring HTLV-I.

Animals↗

Patient compliance and persistence with antihyperglycemic drug regimens: evaluation of a medicaid patient population with type 2 diabetes mellitus.

BACKGROUND: Drug use patterns among patients with type 2 diabetes mellitus have been studied in the general population but not specifically in the Medicaid population. OBJECTIVE: The purpose of this study was to examine antihyperglycemic drug use patterns among Medicaid recipients with type 2 diabetes and assess patients' persistence and compliance with different antihyperglycemic drug regimens. METHODS: Pharmaceutical claims data from Medi-Cal for January 1996 through September 1998 were analyzed to investigate antihyperglycemic drug use patterns over a 1-year and 2-year period. Prescription refill data were examined to assess patient compliance and persistence. RESULTS: Of the 37,431 patients in the 1-year follow-up cohort, 79.6% started antihyperglycemic treatment with monotherapy (ie, drug therapy with a single class of antihyperglycemic medication), 14.5% with insulin alone, 3.9% with polytherapy (ie, drug therapy with > or = 2 classes of medication other than insulin), and 2.1% with insulin plus another therapy. Of the patients receiving monotherapy, 85.3% were taking a sulfonylurea, 14.0% were taking metformin, and 0.7% were taking another agent. In the 1-year follow-up, 55.5% of patients taking metformin alone, 67.2% of those taking sulfonylurea alone, and 83.9% of those taking metformin plus sulfonylurea (M + S) did not undergo any modification of their regimen (except discontinuation of therapy). Among these patients, those taking metformin or sulfonylurea alone had approximately 65% more days of continuous (or persistent) treatment (129 and 128 days, respectively) per patient per year than did patients taking polytherapy (78 days). In addition, sulfonylurea or metformin monotherapy was associated with a 36% higher compliance rate than M + S polytherapy (177 days vs 130 days). CONCLUSION: Simple 1-drug antihyperglycemic regimens were associated with better compliance and persistence (as measured by prescription refill data) than more complex multiple-drug regimens among patients with type 2 diabetes in the Medi-Cal population.

Adult↗

[Persistant mucosal ulcerations: a rare complication of toxic epidermal necrolysis].

INTRODUCTION: Sequels can be observed in toxic epidermal necrolysis. Persistence of mucosal ulcerations is not a classical complication of this disease. We describe two case reports of mucous membrane ulcerations (oral and genital) which have remained many months after the acute phase of toxic epidermal necrolysis. CASE REPORTS: Case 1. A little girl, 9 years old, was referred for a chronic and painful ulceration of the vulva that had appeared 9 months earlier during a toxic epidermal necrolysis. She presented a clearly crircumscribed vestibular ulceration. The mucosal biopsy was refused by the family. The genital erosion persisted more than one year after the acute phase. Case 2. A 73 year-old man was referred for a persistent and clearly circumscribed lingual ulceration, 9 cm in diameter. This chronic ulceration had appeared 3 months earlier, during the acute phase of a toxic epidermal necrolysis. The skin biopsy specimen, with histologic and direct immunofluorescence analysis, did not disclose any specific anomalies. After a period of clinical observation, intralesional injections of corticosteroids were decided and ulceration progressively decreased in 13 months. DISCUSSION: Complications of toxic epidermal necrolysis mainly occur at the acute phase. The most well documented sequelae are ophthalmological lesions. The most frequent cutaneous sequelae are cutaneous pigmentary changes and nail dystrophy. We report two observations of persistent mucous membrane erosions many months after the acute phase of toxic epidermal necrolysis. The pathophysiology of this complication, is rarely described and still remains unclear.

Aged↗

Persistent endophthalmitis after intravitreal antimicrobial therapy.

PURPOSE: To assess the frequency of persistent infection after injection of intravitreal antimicrobials as therapy for endophthalmitis and to determine if persistent infection influences the final visual outcome after treatment. METHODS: In a series of 42 eyes with culture-positive endophthalmitis of various types, the authors performed a second vitreous culture and injection of antimicrobial agents in 22 eyes. Repeat cultures were obtained 3 to 8 days after initial therapy in 20 of the 22 eyes. RESULTS: Twelve of the 22 eyes were persistently culture-positive. Organisms identified in the persistently culture-positive eyes included staphylococcal species (n = 4), Streptococcus (n = 4), Serratia (n = 1), Propionibacterium acnes (n = 1), and fungi (n = 2). Eyes in which the initial antimicrobial therapy failed to eradicate a bacterial infection had a worse outcome than those that were culture-negative on repeat sampling. Final visual acuity of 20/200 or better after repeat injection was attained in 4 of the 12 culture-positive eyes. CONCLUSION: A single injection of intravitreal antimicrobial agents may be insufficient to cure some cases of endophthalmitis, and a second injection should be considered in some circumstances.

Adolescent↗

Evaluating persistent and recurrent choroidal neovascularization. The role of indocyanine green angiography.

OBJECTIVE: To evaluate the clinical utility of routinely using indocyanine green angiography (ICGA) with fluorescein angiography (FA) in detecting persistent or recurrent choroidal neovascularization (CNV). DESIGN: Prospective, consecutive case series. PARTICIPANTS: Twenty-four eyes of 21 patients with exudative age-related macular degeneration (AMD) that had conventional laser treatment for CNV were examined. INTERVENTION: Fluorescein angiography and ICGA were performed together on all eligible eyes at the first post-treatment visit and all subsequent follow-up visits in which persistent or recurrent CNV was suspected clinically. MAIN OUTCOME MEASURES: Choroidal neovascularization detection and delineation by each angiographic technique were measured. RESULTS: Of the 54 FA-ICGA study pairs performed over a 20-month investigation period, FA showed well-defined, ill-defined, and no CNV in 10 (19%), 19 (35%), and 25 (46%) eyes, respectively. Indocyanine green angiography had a high concordance rate at 70% and 88% when persistent or recurrent CNV was well-defined and absent, respectively, on FA and rarely added additional, clinically useful information in these settings, particularly in the former presentation. Of the 29 eyes that showed some evidence of CNV by FA, the neovascular complex was ill-defined in 19 (66%) eyes. When CNV was ill-defined by FA, the corresponding ICGA showed well-defined CNV in 9 (47%) of 19 eyes, in 5 of which the CNV was nonsubfoveal in location. CONCLUSIONS: Persistent or recurrent CNV in AMD was frequently ill-defined by FA. Indocyanine green angiography was a valuable adjunct to FA by better delineating CNV in this specific setting. However, ICGA was not useful when the post-treatment FA showed well-defined CNV. Furthermore, ICGA was not helpful when the first post-treatment FA was negative and there were no ophthalmoscopic signs of exudation.

Aged↗

Photocoagulation and fluid-gas exchange to treat persistent macular holes after prior vitrectomy. A pilot study.

OBJECTIVE: This study aimed to determine the efficacy of photocoagulation to the retinal pigment epithelial (RPE) cells and fluid-gas exchange (FGX) in the treatment of persistent macular holes. DESIGN: A clinical trial. PARTICIPANTS: Thirteen eyes of 12 patients who had undergone photocoagulation to the RPE and FGX for persistent macular holes after initial vitrectomy and gas tamponade were examined. All eyes had persistent full-thickness macular holes (diameter range, 290-820 microns; 610 +/- 190, mean +/- standard deviation) and no vitreous cortex around the holes on biomicroscopic examination. INTERVENTION: Argon laser photocoagulation was applied to the RPE in the hole bed, and FGX with 20% sulfur hexafluoride was then performed, followed by 2 weeks with the patient in a prone position. The follow-up period of the patients ranged from 3 to 18 months (10.2 +/- 4.2; mean +/- standard deviation). MAIN OUTCOME MEASURES: Anatomic success and final visual outcome were measured. RESULTS: Macular holes were closed successfully after treatment in 12 (92%) of 13 eyes, and visual acuity improved 2 or more lines in 6 eyes (46%). Two eyes (15%) attained visual acuities of 20/40 or better, and seven eyes (54%) attained 20/67 or better visual acuity. There were no intraoperative complications. Cataract formation or progression was recognized during follow-up in five (83%) of six phakic eyes. CONCLUSIONS: Although this study includes only a small number of patients, it suggests that photocoagulation and FGX can be effective in the treatment of persistent macular holes.

Aged↗

Eustachian tube function in older children and adults with persistent otitis media.

OBJECTIVE: Otitis media (OM) is most common in infants and young children. Despite a dramatic reduction in its incidence after the age of six, the disease still occurs in older children, adolescents, and may even persist into adulthood. The goal of this study was to identify characteristics of eustachian tube (ET) function in an older population which may underlie their persistent OM. METHODS: Following a medical history and a head and neck examination, 38 subjects over 6 years of age (64 ears) had their ET function assessed with the forced-response test (FRT). Parameters derived from this test included opening and closing pressures as well as steady-state and active resistances. RESULTS: Adenoidectomy had previously been performed in 71% of the sample. Clinically, 5% of these subjects had evidence of nasopharyngeal inflammation. The distributions of closing pressure and steady-state resistance were very similar to the distributions of the historic normal controls. The distributions of opening pressure and active resistance were highly skewed relative to the control sample. All study subjects had either abnormal opening pressures or high active resistance, with 79% having both abnormalities. CONCLUSIONS: If nasopharyngeal inflammation and hypertrophied adenoids are significantly correlated to ET dysfunction and persistent OM, this sample should be free of middle-ear (ME) disease. However, these individuals suffer persistent OM due to ET dysfunction characterized by high opening pressures and high active resistances. The abnormalities underlying these skewed forced-response parameters must be identified and corrected if we are going to alleviate the ME disease in these and similar patients.

Acoustic Impedance Tests↗

Persistence of benzo[a]pyrene--DNA adducts in hematopoietic tissues and blood of the mummichog, Fundulus heteroclitus.

The formation and persistence of benzo[a]pyrene (B[a]P)-DNA adducts were investigated in blood, liver and two hematopoietic tissues (anterior kidney and spleen) of the mummichog (Fundulus heteroclitus). Fish were injected with a single, sublethal dose of B[a]P (12 mg/kg body weight) and sampled from 8 to 96 days post-injection. 32P-Postlabeling analysis and storage phosphor imaging were used to resolve and quantify hydrophobic DNA adducts. One major DNA adduct was present in each of the examined tissues at all sampling times. This adduct had similar chromatographic characteristics to those of the adduct standard, 7R,8S,9S-trihydroxy-10S-(N(2)-deoxyguanosyl-3'-phosphate)-7,8,9,10-tetrahydro-benzo[a]pyrene (B[a]PDE-dG). Minor DNA adduct spots, representing less than 2% of the total DNA adducts, were observed in some liver, anterior kidney and spleen samples for up to 32 days post-injection. The B[a]P-DNA adducts reached maximal levels at 32 days post-injection and persisted for at least 96 days in all examined tissues. B[a]P-DNA adduct levels were significantly higher in the liver and anterior kidney than in the spleen from 16 to 96 days (P<0.001), although liver and anterior kidney DNA adduct levels were not significantly different at any time. This is the first controlled study to demonstrate the formation and persistence of B[a]P-DNA adducts in hematopoietic tissues and blood of fishes exposed to the prototypical polycyclic aromatic hydrocarbon, B[a]P. Although persistent DNA adducts are generally recognized as potential initiators of carcinogenic processes, adducts in these vital tissues may also lead to disruption of physiological functions such defense mechanisms and hematopoiesis.

Animals↗

Tissue differences, dose-response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L) exposed to benzo[a]pyrene.

Baltic Sea blue mussels (Mytilus edulis) were experimentally exposed to the genotoxic model substance benzo[a]pyrene (B[a]P) to study DNA adduct formation. The specific aims were (a). to examine where in the mussels the DNA adducts were formed, in gills or digestive gland; (b). to study the dose-response relationship between B[a]P exposure and DNA adduct formation; and (c). to examine the persistence of the formed adducts. A Scope for growth (SFG) study was also run to compare physiological responses of the mussels with the degree of DNA adduct formation. In an initial dose-response experiment, the mussels were exposed to 0, 5, 50, and 100 microg/l of tritium labelled B[a]P under semi-static conditions for 4 days, and thereafter the bioaccumulation of B[a]P and DNA adduct formation in different tissues was determined using liquid scintillation counting and 32P-postlabelling analysis, respectively. In a following exposure-depuration experiment, mussels were exposed to 17 microg/l of radiolabelled B[a]P under semi-static conditions for 6 days. B[a]P accumulation and DNA adduct formation were determined during the exposure, and B[a]P elimination and persistence of DNA adducts were studied during 28 days of depuration in uncontaminated water. The results revealed large tissue differences in DNA adduct formation. DNA adduct levels were not elevated in the digestive gland of the mussels at any exposure concentration (0-100 microg/l), even though the highest B[a]P tissue concentrations were found in the digestive gland (1.0+/-0.1 mg B[a]P/g tissue dry wt at 100 microg/l, mean+/-SE, n=12). DNA adducts were on the other hand formed in the gills, with the highest levels found in mussels exposed to 50 and 100 microg B[a]P/l, and a dose dependent increase in adduct levels (from 1.6 to 5.9 nmol adducts/mol nucleotides) from 0 to 50 microg B[a]P/l. In gills, DNA adduct levels increased with time during the 6-day exposure period in the exposure-depuration experiment, and then persisted for at least 2 weeks after exposure cessation while B[a]P tissue levels exhibited a rapid decrease (half-life of 8 days). No significant differences were observed in SFG between the control and exposed groups. Since DNA adducts exhibited a relatively high persistence in gills compared to B[a]P tissue concentrations, they seem to be a more integrated measure of genotoxic exposure than only chemical analysis of the contaminant bioaccumulation. The results also suggest that if using analysis of DNA adducts in M. edulis for monitoring purposes, analysis of gills in addition to the more commonly used digestive gland should be taken into consideration.

Animals↗