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Biomedical subjects

L Reed

Publications and source records attributed to L Reed.

At least 19 recordsLinked to original sources

Changes in foot function with the use of Root and Blake orthoses.

This study examined the effects of two designs of rigid foot orthoses on plantar pressure measurements and identified differences between the devices. While wearing modified Root- and Blake-style orthoses, 27 subjects were examined with the Electrodynogram (EDG) in-shoe pressure measurement system. Reliability testing was performed on the EDG data. Significant changes were observed in the temporal parameters of gait when subjects wore the orthoses. When the devices were used, the duration of some of the components of stance phase was altered, and the initiation of loading beneath the medial forefoot was delayed. A reduction in the total duration of loading at discrete sites beneath the heel and forefoot was also observed. The effects of the two orthoses were similar, with only small differences observed between the devices.

Adolescent↗

Radioimmunotherapy of a human lung cancer xenograft with monoclonal antibody RS7: evaluation of (177)Lu and comparison of its efficacy with that of (90)Y and residualizing (131)I.

UNLABELLED: Tumor targeting and therapeutic efficacy of (177)Lu-labeled monoclonal antibody (mAb) RS7 (antiepithelial glycoprotein-1) was evaluated in a human nonsmall cell lung carcinoma xenograft model. The potential of (177)Lu-labeled RS7 was compared with that of RS7 labeled with (90)Y and a residualizing form of (131)I. METHODS: A 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) conjugate of RS7 was used for radiolabeling with (177)Lu-acetate or (88/90)Y-acetate. Biodistribution and therapy studies were conducted in nude mice with subcutaneous Calu-3 xenografts. Therapy studies were performed using the maximal tolerated doses (MTDs) of (90)Y-DOTA-RS7 (3.9 MBq [105 microCi]) and (177)Lu-DOTA-RS7 (10.2 MBq [275 microCi]) and compared with the data obtained using the MTD (13.0 MBq [350 microCi]) of a residualizing form of (131)I-RS7. RESULTS: Radiolabeling of RS7-DOTA conjugate with (177)Lu-acetate was facile. (177)Lu-DOTA-RS7 displayed biodistribution results that were nearly identical to that of the (88)Y analog in a paired-label study. The mean percentage injected doses per gram (%ID/g) for (177)Lu-RS7 and (88)Y-RS7 (in parentheses) in tumor were 38.3 %ID/g (39.1 %ID/g), 63.0 %ID/g (66.0 %ID/g), 63.0 %ID/g (65.8 %ID/g), and 34.0 %ID/g (34.9 %ID/g) on days 1, 3, 7, and 14, respectively. Elimination of established tumors, with an initial mean tumor volume of 0.24 cm(3), was shown using doses of (177)Lu-DOTA-RS7 ranging from 5.6 to 9.3 MBq (150--250 microCi) per nude mouse, with no significant difference in response rate noted between the doses in this range. Specificity of the therapeutic effect was shown in an isotype-matched control experiment, in which (177)Lu-DOTA-RS7 was markedly more effective than the (177)Lu-DOTA control antibody. A comparison of the therapeutic efficacies of (177)Lu-DOTA-RS7 and (90)Y-DOTA-RS7, using mice with established tumors with an initial mean tumor volume of 0.85 cm(3), indicated similar tumor growth inhibition and similar tumor regrowth profiles. The therapy data were similar to those obtained with residualizing (131)I-RS7 obtained at the same time. CONCLUSION: (177)Lu-RS7 is an effective radioimmunoconjugate for radioimmunotherapy. With its radiophysical properties similar to those of (131)I, coupled with its facile and stable attachment to mAb, (177)Lu promises to be an alternative to (131)I, and a complement to (90)Y, in radioimmunotherapy.

Animals↗

Brain trauma in aged transgenic mice induces regression of established abeta deposits.

Traumatic brain injury (TBI) increases susceptibility to Alzheimer's disease (AD), but it is not known if TBI affects the progression of AD. To address this question, we studied the neuropathological consequences of TBI in transgenic (TG) mice with a mutant human Abeta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter resulting in overexpression of mutant APP (V717F), elevated brain Abeta levels, and AD-like amyloidosis. Since brain Abeta deposits first appear in 6-month-old TG (PDAPP) mice and accumulate with age, 2-year-old PDAPP and wild-type (WT) mice were subjected to controlled cortical impact (CCI) TBI or sham treatment. At 1, 9, and 16 weeks after TBI, neuron loss, gliosis, and atrophy were most prominent near the CCI site in PDAPP and WT mice. However, there also was a remarkable regression in the Abeta amyloid plaque burden in the hippocampus ipsilateral to TBI compared to the contralateral hippocampus of the PDAPP mice by 16 weeks postinjury. Thus, these data suggest that previously accumulated Abeta plaques resulting from progressive amyloidosis in the AD brain also may be reversible.

Aging↗

Changes in patterns of 24-hr heart rate variability after kidney and kidney-pancreas transplant.

BACKGROUND: Transplantation has been shown to improve cardiorespiratory reflex measures of autonomic function. However, there are limited data on how kidney or kidney-pancreas transplantation influence continuous autonomic modulation of heart rate and the clinical utility of 24-hr heart rate variability (HRV) monitoring. METHODS: Ninety nondiabetic kidney and 30 diabetic kidney-pancreas transplant recipients underwent 24-hr Holter monitoring before and again at 6 and 12 months posttransplantation. Tapes were submitted for determination of HRV including interbeat variability (the proportion of adjacent R-R intervals having a difference <50 msec, the SD of all R-R intervals for the entire recording, and the SD of the averages of R-R intervals calculated over 5-min blocks for the entire recording) which is associated with vagal function, sudden death, and circadian function, respectively. Power spectral analysis quantified total neural, sympathetic, and parasympathetic modulation of the heart in ln(msec2). RESULTS: Nondiabetic kidney recipients showed improvement (P< or =0.05) in the SD of the averages of R-R intervals calculated over 5-min blocks (83.2 vs. 95.7 msec) and the SD of all R-R intervals (94.5 vs. 104.4 msec) by 6 months and all groups showed improvement by 12 months. Kidney-pancreas recipients also showed improved total neural (4.35 vs. 4.64) and sympathetic modulation (2.70 vs. 3.13). Kidney-pancreas recipients had significantly poorer values for each measure (P< or =0.05) at all time points. CONCLUSIONS: Cardiac autonomic neuropathy arises in the presence of uremia and diabetes, with severe dysfunction seen when these conditions occur concomitantly. Improvement in cardiac autonomic function follows both kidney and kidney-pancreas transplantation with more pronounced improvement in the circadian measures. Therefore, circadian measures of 24-hr HRV could be used to monitor the restoration of cardiac autonomic function.

Adult↗

Integrating the Internet into health administration education: a report from AUPHA's Faculty Internet integration task force.

HRSA funded a survey to determine what Internet resources would be most useful to AUPHA membership. This manuscript describes the Internet-intensive survey methodology, reports the survey results, and lists the task force recommendations. The task force used sequential questionnaires posted on the Web to gather both potentially useful Internet resource ideas and membership perceptions of the importance of each idea. Resources recommended by survey participants and the Task Force members emphasized potential improvements to the AUPHA and AUPHA-member Web pages.

Data Collection↗

Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17.

Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms. Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.

Alternative Splicing↗

Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17.

Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21-22. These hereditary disorders are known collectively as frontotemporal dementia (FTD) and parkinsonism linked to chromosome 17 (FTDP-17). Although the clinical features and associated regional variations in the neuronal loss observed in different FTDP-17 kindreds are diverse, the diagnostic lesions of FTDP-17 brains are tau-rich filaments in the cytoplasm of specific subpopulations of neurons and glial cells. The microtubule associated protein (tau) gene is located on chromosome 17q21-22. For these reasons, we investigated the possibility that PPND and other FTDP-17 syndromes might be caused by mutations in the tau gene. Two missense mutations in exon 10 of the tau gene that segregate with disease, Asn279(Lys) in the PPND kindred and Pro301(Leu) in four other FTDP-17 kindreds, were found. A third mutation was found in the intron adjacent to the 3' splice site of exon 10 in patients from another FTDP-17 family. Transcripts that contain exon 10 encode tau isoforms with four microtubule (MT)-binding repeats (4Rtau) as opposed to tau isoforms with three MT-binding repeats (3Rtau). The insoluble tau aggregates isolated from brains of patients with each mutation were analyzed by immunoblotting using tau-specific antibodies. For each of three mutations, abnormal tau with an apparent Mr of 64 and 69 was observed. The dephosphorylated material comigrated with tau isoforms containing exon 10 having four MT-binding repeats but not with 3Rtau. Thus, the brains of patients with both the missense mutations and the splice junction mutation contain aggregates of insoluble 4Rtau in filamentous inclusions, which may lead to neurodegeneration.

Adult↗

Frequency of 22q11 deletions in patients with conotruncal defects.

OBJECTIVES: This study was designed to determine the frequency of 22q11 deletions in a large, prospectively ascertained sample of patients with conotruncal defects and to evaluate the deletion frequency when additional cardiac findings are also considered. BACKGROUND: Chromosome 22q11 deletions are present in the majority of patients with DiGeorge, velocardiofacial and conotruncal anomaly face syndromes in which conotruncal defects are a cardinal feature. Previous studies suggest that a substantial number of patients with congenital heart disease have a 22q11 deletion. METHODS: Two hundred fifty-one patients with conotruncal defects were prospectively enrolled into the study and screened for the presence of a 22q11 deletion. RESULTS: Deletions were found in 50.0% with interrupted aortic arch (IAA), 34.5% of patients with truncus arteriosus (TA), and 15.9% with tetralogy of Fallot (TOF). Two of 6 patients with a posterior malalignment type ventricular septal defect (PMVSD) and only 1 of 20 patients with double outlet right ventricle were found to have a 22q11 deletion. None of the 45 patients with transposition of the great arteries had a deletion. The frequency of 22q11 deletions was higher in patients with anomalies of the pulmonary arteries, aortic arch or its major branches as compared to patients with a normal left aortic arch regardless of intracardiac anatomy. CONCLUSIONS: A substantial proportion of patients with IAA, TA, TOF and PMVSD have a deletion of chromosome 22q11. Deletions are more common in patients with aortic arch or vessel anomalies. These results begin to define guidelines for deletion screening of patients with conotruncal defects.

Aorta, Thoracic↗

Diagnosis and initial management of blunt pancreatic trauma: guidelines from a multiinstitutional review.

OBJECTIVE: The authors' objective was to resolve the current controversies surrounding the diagnosis and management of blunt pancreatic trauma (BPT). SUMMARY BACKGROUND DATA: The diagnosis of BPT is notoriously difficult: serum amylase has been claimed to be neither sensitive nor specific, and recent anecdotal reports have suggested a role for computed tomography. The therapy of BPT has been controversial, with some suggesting selective observation and others advocating immediate exploration to prevent a delay-induced escalation in morbidity and death. METHODS: The authors conducted a retrospective chart review of documented BPT from six institutions, using a standardized binary data form composed of 187 items and 237 data fields. RESULTS: A significant correlation between pancreas-specific morbidity and injury to the main pancreatic duct (MPD) was noted. Patients requiring delayed surgical intervention after an unsuccessful period of observation demonstrated notably higher pancreas-specific mortality and morbidity rates, principally because of the incidence of unrecognized injuries to the MPD. Although detection of MPD injuries by computed tomography was no better than flipping a coin, endoscopic pancreatography was accurate in each of the five cases in which it was used. CONCLUSIONS: The principal cause of pancreas-specific morbidity after BPT is injury to the MPD. Parenchymal pancreatic injuries not involving the ductal system rarely result in pancreas-specific morbidity or death. Delay in recognizing MPD injury leads to increased mortality and morbidity rates. CT is unreliable in diagnosing MPD injury and should not be used to guide therapy. Initial selection of patients with isolated BPT for observation or surgery can be based on the determination of MPD integrity.

Cholangiopancreatography, Endoscopic Retrograde↗

Adverse patient occurrences as a measure of nursing care quality.

OBJECTIVE: The purpose of this study was to describe relationships among adverse patient occurrences aggregated at the unit level of measurement. Relationships between adverse occurrences and a patient acuity measure were also described. BACKGROUND: Adverse patient occurrence data have been traditionally a major indicator of quality care in hospitals; however, few studies have examined relationships among these indicators or the usefulness of these indicators for assessing the quality of nursing care. METHODS: A correlational design was used to examine and describe patterns of relationships among in-patient units in a tertiary care hospital. The results demonstrated positive correlations between medication error rates and patient falls; these adverse occurrences correlated negatively with pressure ulcers, infections, patient complaints, and death. Pressure ulcers, infections, patient complaints and death intercorrelated positively and also related positively to patient acuity levels. RESULTS: An examination of these same rates for a subset of units with similar patient acuity levels revealed that most of the interrelationships among the entire set of adverse occurrence indicators were positive. When patient acuity was taken into account, these adverse outcomes appeared to indicate some common underlying characteristic of the units, such as quality of nursing care. CONCLUSIONS: This study suggests a relationship between the adverse occurrences that were correlated (pressure ulcers, patient complaints, infection, and death) and the severity of patient illness. Medication error rates and patient fall rates were not correlated with patient acuity and are more likely to indicate quality of nursing care across all types of units.

Accidental Falls↗

Pharmaceutical practice management.

BACKGROUND: Being accomplished in the short span of 21 years the number of states granting therapeutic optometric privileges has now reached 50. Since health care reform is also expanding, optometrists' prescribing responsibilities will probably increase in proportion to their clinical demands. PURPOSE: In addition to clinical expertise, optometrists should possess practical knowledge about pharmaceutical industry practices and the effects of managed care. This article addresses issues such as drug pricing and distribution, reimbursement, and patient costs, which can affect pharmaceutical dispensing. CONCLUSION: Optometrists should become aware of "nonclinical" prescribing influences that can affect patients. By doing so, they can make informed decisions about the products they prescribe, to ensure optimum patient care and compliance.

Drug Costs↗

Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome).

OBJECTIVE: To investigate the association of polyarthritis and chromosome 22q11.2 deletions. METHODS: Eighty patients with chromosome 22q11.2 deletion syndrome followed up at The Children's Hospital of Philadelphia were examined for evidence of arthropathy or arthritis. Patients with chromosome 22q11.2 deletion syndrome and polyarthritis underwent laboratory evaluations of immunologic function to determine the relationship of their immunodeficiency to the polyarthritis. RESULTS: The prevalence of polyarthritis in patients with chromosome 22q11.2 deletion syndrome was markedly increased over the prevalence of polyarticular juvenile rheumatoid arthritis (JRA) in the general population. All 3 patients with polyarthritis had evidence of impaired T cell function. Two of the patients with polyarthritis also had IgA deficiency. CONCLUSION: The chromosome 22q11.2 deletion syndrome represents a primary T cell disorder which can be associated with a JRA-like polyarthritis. All 3 patients with polyarthritis had evidence of more extensive immunoregulatory derangements than those typically seen in patients with chromosome 22q11.2 deletion, and these derangements may have predisposed to the development of polyarthritis.

Arthritis↗

Perceptual and behavioral manifestations of the Chronic Illness and Recovery models among clinical transplant coordinators.

This descriptive, qualitative study examines manifestations of the Chronic Illness and Recovery models among clinical transplant coordinators. Data collected through focused group interviews revealed that the Chronic Illness model fosters patient dependency, education about the illness itself, a perception that transplantation does not change the chronic nature of illness, a view of patients as socioeconomically disadvantaged and dependent on the transplant center, and the use of reactive approaches to care. In contrast, the Recovery model encourages patient independence, limits coordinators' protective feelings toward patients, provides education for life tasks, perceives patients as socioeconomically advantaged people capable of managing their own lives, and conducts patient care in a proactive manner.

Attitude of Health Personnel↗