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Biomedical subjects

Bruce R Lindgren

Publications and source records attributed to Bruce R Lindgren.

11 recordsLinked to original sources

Chronic and recurrent otitis media: a genome scan for susceptibility loci.

Otitis media (OM) is the most common childhood disease. Almost all children experience at least one episode, but morbidity is greatest in children who experience chronic/recurrent OM (COME/ROM). There is mounting evidence that COME/ROM clusters in families and exhibits substantial heritability. Subjects who had tympanostomy tube surgery for COME/ROM (probands) and their families were recruited for the present study, and an ear examination was performed, without knowledge of the subject's history, to determine presence of OM sequelae. In addition, tympanometric testing was performed at three frequencies (226, 630 or 710, and 1,400 Hz) to detect abnormal middle-ear mechanics, and hearing was screened at 20 dB for the speech frequencies. Of these families, 121 had at least two individuals who had received the diagnosis of COME/ROM (364 affected and genotyped individuals), of whom 238 affected and informative relative pairs were used for analyses. Single-point nonparametric linkage analysis provided evidence of linkage of COME/ROM to chromosome 10q at marker D10S212 (LOD 3.78; P=3.0 x 10(-5)) and to chromosome 19q at marker D19S254 (LOD 2.61; P=5.3 x 10(-4)). Analyses conditional on support for linkage at chromosomes 10q and 19q resulted in a significant increase in LOD score support on chromosome 3p (between markers D3S4545 and D3S1259). These results suggest that risk of COME/ROM is determined by interactions between genes that reside in several candidate regions of the genome and are probably modulated by other environmental risk factors.

Acoustic Impedance Tests↗

Racial diversity with high nucleated cell counts and CD34 counts achieved in a national network of cord blood banks.

Banked, unrelated, partially HLA-matched, umbilical cord blood is an alternative stem cell source for patients in need of transplantation therapy who lack traditionally matched donors. A presumed advantage of cord blood is the ability to increase recruitment of donors of minority ethnic backgrounds. The American Red Cross Cord Blood Program was established in 1999 with 6 banks and 10 collection sites throughout the country. Cord blood donors self-report racial designations on questionnaires, and donor race was collected from each site. Postprocessing nucleated cell counts and CD34(+) counts were obtained on the cord blood units, and results from each racial group (white, black, Asian, Hispanic, and Native American) were compared in the natural logarithmic scale by using analysis of variance. A total of 18878 donors consented: 64% white, 16% black, 12% Hispanic, 4% Asian, 1% Native American, and 3% other. The Detroit area consented the highest percentage of black donors (87%), San Diego consented the highest percentage of Hispanic donors (59%), and Oakland consented the highest percentage of Asian donors (15%). Seven thousand eight hundred sixty-six cord blood units have been banked for transplantation. The mean preprocessing nucleated cell count was 1220 x 10(6) (range, 327-7300 x 10(6)). There was no difference among racial groups when controlled for site (P =.395). The mean CD34(+) count was 3.28 x 10(6). Blacks had a significantly lower CD34(+) count than the other racial/ethnic groups in the Midwest, Northwest, and North Carolina collection sites. A racially diverse cord blood bank can be achieved. Nucleated cell counts were similar among the different racial/ethnic groups. CD34(+) counts were lower for blacks in some collection sites.

Antigens, CD34↗

Cochlear changes in chronic otitis media.

OBJECTIVES/HYPOTHESIS: The objective was to describe the morphological changes in the cochlea in chronic otitis media. STUDY DESIGN: Retrospective human temporal bone analysis. METHODS: Fifteen temporal bones with unilateral chronic otitis media were selected and compared with contralateral normal temporal bones. Standard cytocochleograms and spiral ganglion cell reconstructions were performed on all temporal bones. Spiral ligament was divided into four segments according to the locations of different types of fibrocytes. The average loss of fibrocytes in each segment was estimated. Morphometric measurements of areas of stria vascularis and spiral ligament were made in all turns of the cochlea on mid modiolar sections. RESULTS: Loss of outer and inner hair cells was common in the basal turn of the cochlea in temporal bones with chronic otitis media compared with control ears. There was no difference in the number of spiral ganglion cells in the chronic otitis media and contralateral ears. The areas of stria vascularis and spiral ligament in the basal turn decreased significantly in the ears with chronic otitis media compared with control ears. There were no significant differences between the ears with chronic otitis media and the contralateral ears for any of the regions characterized by the presence of types I-IV fibrocytes. CONCLUSION: The results of the study are consistent with the hypothesis that chronic otitis media causes cochlear disease.

Adolescent↗

Some statistical methods for investigating the date of birth as a disease indicator.

Some methods of temporal statistics are presented and proposed for investigating the date of birth as a disease predictor. A subject's birthday is proposed to be used as a continuous variable with a circular distribution, a special type of interval scale without a true zero point. Three types of endpoints are then considered: a dichotomous endpoint; a continuous endpoint; and time-to-event. A study of otitis media is used for illustration. We found, for example, that children born in late winter to early spring tend to have higher cord blood pneumococcal antibody concentration and lower risk of disease as compared to those born in summer to early fall perhaps due largely to exposure to indoor pollution by pregnant mothers.

Antibodies, Bacterial↗

Chronic otitis media with effusion sequelae in children treated with tubes.

OBJECTIVE: To determine incidence and prevalence of middle ear sequelae and abnormal tympanometry results among children with chronic otitis media with effusion (OME) who received standard treatment with tympanostomy tubes. DESIGN: Prospective cohort study. SETTING: Community clinic and academic medical center. Patients A total of 140 children followed up for 8 years after tube treatment. MAIN OUTCOME MEASURES: Tympanic membrane perforation, atrophy, retraction, hearing loss, myringosclerosis, low static admittance (SA) and broad-peaked tympanogram, high SA and narrow-peaked tympanogram, and negative tympanometric peak pressure. RESULTS: Annual incidence of sequelae was typically greater during 3 to 5 years than 6 to 8 years of follow-up. Greatest increases in incidence during the 5-year follow-up were for atrophy (67%), high SA and narrow-peaked tympanogram (70%), and retraction pocket (47%). Prevalence of these sequelae also increased over time, whereas low SA and broad-peaked tympanogram and negative tympanometric peak pressure decreased during follow-up. Sequela tended to become bilateral over time, and concordance of different sequelae in the same ear was low (kappa, 0.05-0.42). CONCLUSIONS: Annual incidence of sequelae decreased during follow-up. This finding parallels decreasing incidence of OME and tube placement as children mature and demonstrates that sequelae are more likely to develop during active acute and chronic OME. The cumulative effect of incidence resulted in few ears free of sequelae by 8 years of follow-up. Based on this cohort of healthy children with OME, although the risk of sequelae decreased over time, functional and morphologic sequelae were prevalent and may put children at risk for continuing middle ear problems as they grow into adolescence and adulthood.

Acoustic Impedance Tests↗

Reduced small artery but not large artery elasticity is an independent risk marker for cardiovascular events.

BACKGROUND: Atherosclerosis begins in the arterial wall, with endothelial dysfunction accompanied by functional and structural changes that influence arterial stiffness. Pulse contour analysis provides an assessment of compliance or elasticity of the large conduit arteries (C(1)) and small microcirculatory arteries (C(2)). In this study, the predictive value of reduced elasticity of these arteries was evaluated by follow-up of subjects who underwent pulse contour analysis at the University of Minnesota. METHODS: Questionnaires were sent to 870 subjects who had radial artery pulse wave analysis performed between 1993 and 1999 using a noninvasive sensor, parameter estimating algorithm and modified Windkessel model of the circulation. Responses from 419 subjects >19 years of age reported on any cardiovascular events including death, myocardial infarction, stroke, transient ischemic attacks, angina, or coronary or peripheral vascular interventional procedures. RESULTS: Of the subjects, 168 (41%) reported one or more cardiovascular events. Events were more common in those with elevated blood pressure, elevated cholesterol, diabetes, and family history of events. Age, reduced C(1), and reduced C(2) were univariate predictors of events. After adjusting for age, a 2-unit decrease in C(2) remained a significant predictor (odds ratio 1.50, P <.001), whereas C(1) was no longer predictive. CONCLUSION: Reduced small artery elasticity, which is a measure of endothelial dysfunction, is significantly associated with cardiovascular events independent of age.

Arteries↗

Left- versus right-hand tracking performance by right-handed boys and girls: examination of performance asymmetry.

This study compared left- versus right-hand performance within healthy, right-handed, 8- or 9-yr.-old boys and girls on a finger-movement tracking task. 38 boys and 38 girls were randomly assigned to use either the left hand first and right hand second or vice versa in tracking a sine wave target with extension and flexion movements of the index finger. The data were analyzed with a three-way analysis of variance with repeated measures followed by pair-wise comparisons with a Bonferroni correction. Analysis yielded a significant hand x test interaction and a significant improvement for subjects tracking with the right hand on Test 1 and left hand on Test 2. No significant change occurred for subjects tracking with the left hand on Test 1 and right hand on Test 2. No interaction was observed with sex as a factor. This study suggests that asymmetry of performance favoring the left hand occurs in right-handed boys and girls during finger-movement tracking.

Child↗

Effects of long-term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys.

OBJECTIVE: To determine the effects of long-term estrogen replacement therapy (ERT) on the severity of osteoarthritis (OA) of the knee joint in surgically postmenopausal (bilaterally ovariectomized) female monkeys. A secondary aim was to evaluate the effect of soy phytoestrogen (SPE) treatment on the severity of OA. METHODS: Feral adult female cynomolgus macaques were ovariectomized bilaterally and then randomly divided into 3 age- and weight-matched treatment groups. For 3 years, the first group received ERT with conjugated equine estrogens, the second group received SPE, and the third group received no treatment (controls). At necropsy, histologic lesions of OA were graded, and the area and thickness of cartilage and subchondral bone were measured. The data were summarized by principal components analysis, and the resulting factors and individual variables were compared using analysis of variance and analysis of covariance (age and weight as covariates). RESULTS: Cartilage lesions of OA were significantly less severe in the animals given ERT compared with those in the control group. This treatment effect remained significant when adjusted for age and weight. The factor representing subchondral bone was significantly higher, but the number of osteophytes was lower, in the ERT group compared with the control group. SPE treatment had no significant effect on cartilage or bone lesions of OA. CONCLUSION: These results demonstrate that long-term ERT significantly reduces the severity of OA lesions in this animal model.

Animals↗

Discectomy strategies for lumbar disc herniation: results of the LAPDOG trial.

Since its introduction in the 1970s percutaneous treatment of lumbar disc herniation has been an attractive concept that has been the object of technical development and clinical application throughout the world. Little scientific evaluation of the efficacy and effectiveness of the procedure has been done. To estimate the success rates of automated percutaneous and conventional discectomy in comparable patients and to document the resource consumption of patients treated in these ways, a multicenter randomized clinical trial designed to compare both treatment efficacy and cost-effectiveness of automated percutaneous discectomy and conventional discectomy in adult patients with no prior lumbar spinal surgery, no coexistent lumbar spinal disease, unilateral single level lumbar radiculopathy with images confirming disc herniation at the appropriate level. In the course of the trial important technical advances allowing epidural extraction of free-fragment disc herniation was incorporated into the trial. It was not possible to enroll the required number of patients to complete the trial. Of 5735 screened patients, 95 were eligible and 36 were enrolled. Two elected watchful waiting and did not have any surgical procedure. Eight patients were lost to follow-up. Among the 27 evaluable patients, 41% of the percutaneous discectomy patients and 40% of the conventional discectomy patients were assessed as achieving "success" on the primary outcome measure. No clinical trial of any percutaneous discectomy technique provides definitive evidence supporting the efficacy or effectiveness of the procedure. Such evidence should be required by patients to whom such procedures are proposed and those who are asked to pay for them.

Adult↗

Discectomy strategies for lumbar disc herniation: study design and implications for clinical research.

Although previous studies have found automated percutaneous discectomy and epidural percutaneous discectomy to be less efficacious than conventional discectomy, these percutaneous procedures may be effective and cost-effective as a first surgical treatment for herniated lumbar disc. Percutaneous procedures for herniated lumbar disc continue to be performed throughout the world without definitive evidence of efficacy or effectiveness. The objective of this article is to report the design considerations and final design of a study with the following objectives: (1) to estimate the efficacy of automated percutaneous and conventional discectomy in treating single level herniated lumbar discs in comparable patient populations, and (2) to test the hypothesis that the use of percutaneous discectomy as the first surgical procedure in such patients would result in less cost and fewer complications than utilizing conventional discectomy as the first procedure. A multicenter randomized clinical trial was designed that followed published eligibility criteria closely, allowed flexibility in timing of surgery (while collecting natural history information on patients identified before electing surgery), incorporated adjustments for newly developed technology and accommodated the unusual demands of assessing a procedure acknowledged to have inferior medical outcomes when compared to conventional therapy but which offered potential advantages in cost and safety. The study was successfully designed and funded. In its implementation we experienced several obstacles that may affect the success of other clinical trials. Despite using established eligibility criteria, our patient enrollment was lower than expected. Academic health centers and traditional research settings are seeing fewer patients who would be eligible for discectomy; private clinical centers are treating eligible patients but lack the incentives to participate in clinical research. Automated percutaneous discectomy and epidural percutaneous discectomy are widely performed procedures and, despite the aforementioned obstacles, their efficacy and cost-effectiveness need to be scientifically evaluated if we are committed to delivering appropriate patient care.

Cost-Benefit Analysis↗

Health locus of control and adherence with home spirometry use in lung transplant recipients.

Home monitoring is an effective tool that can be used to promote the health of lung transplant recipients, but only if the recipients transmit data to the healthcare team. This study examines the relationship of the Multidimensional Health Locus of Control scale to adherence with home spirometry use. Form C of this scale was mailed to 139 eligible lung and heart-lung transplant recipients. Eighty-three respondents returned the questionnaire. The respondents were on average 4 years older and had greater adherence than nonrespondents. Men tended to score higher than women on all the subscales. These scales were not related to type of transplant or underlying disease. Adherence was also unrelated to the Multidimensional Health Locus of Control scale, with little difference in adherence across persons with various levels of the health locus of control subscales.

Female↗