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Biomedical subjects

T Morrow

Publications and source records attributed to T Morrow.

At least 19 recordsLinked to original sources
PubMed2001

Hearing rehabilitation using the BAHA bone-anchored hearing aid: results in 40 patients.

OBJECTIVE: This study evaluates the U.S. experience with the first 40 patients who have undergone audiologic rehabilitation using the BAHA bone-anchored hearing aid. STUDY DESIGN: This study is a multicenter, nonblinded, retrospective case series. SETTING: Twelve tertiary referral medical centers in the United States. PATIENTS: Eligibility for BAHA implantation included patients with a hearing loss and an inability to tolerate a conventional hearing aid, with bone-conduction pure tone average levels at 60 dB or less at 0.5, 1, 2, and 4 kHz. INTERVENTION: Patients who met audiologic and clinical criteria were implanted with the Bone-Anchored Hearing Aid (BAHA, Entific Corp., Gothenburg, Sweden). MAIN OUTCOME MEASURES: Preoperative air- and bone-conduction thresholds and air-bone gap; postoperative BAHA-aided thresholds; hearing improvement as a result of implantation; implantation complications; and patient satisfaction. RESULTS: The most common indications for implantation included chronic otitis media or draining ears (18 patients) and external auditory canal stenosis or aural atresia (7 patients). Overall, each patient had an average improvement of 32+/-19 dB with the use of the BAHA. Closure of the air-bone gap to within 10 dB of the preoperative bone-conduction thresholds (postoperative BAHA-aided threshold vs. preoperative bone-conduction threshold) occurred in 32 patients (80%), whereas closure to within 5 dB occurred in 24 patients (60%). Twelve patients (30%) demonstrated 'overclosure' of the preoperative bone-conduction threshold of the better hearing ear. Complications were limited to local infection and inflammation at the implant site in three patients, and failure to osseointegrate in one patient. Patient response to the implant was uniformly satisfactory. Only one patient reported dissatisfaction with the device. CONCLUSIONS: The BAHA bone-anchored hearing aid provides a reliable and predictable adjunct for auditory rehabilitation in appropriately selected patients, offering a means of dramatically improving hearing thresholds in patients with conductive or mixed hearing loss who are otherwise unable to benefit from traditional hearing aids.

Acoustic Stimulation↗
PubMed2001

Sequential specification of neurons and glia by developmentally regulated extracellular factors.

Cortical progenitor cells give rise to neurons during embryonic development and to glia after birth. While lineage studies indicate that multipotent progenitor cells are capable of generating both neurons and glia, the role of extracellular signals in regulating the sequential differentiation of these cells is poorly understood. To investigate how factors in the developing cortex might influence cell fate, we developed a cortical slice overlay assay in which cortical progenitor cells are cultured over cortical slices from different developmental stages. We find that embryonic cortical progenitors cultured over embryonic cortical slices differentiate into neurons and those cultured over postnatal cortical slices differentiate into glia, suggesting that the fate of embryonic progenitors can be influenced by developmentally regulated signals. In contrast, postnatal progenitor cells differentiate into glial cells when cultured over either embryonic or postnatal cortical slices. Clonal analysis indicates that the postnatal cortex produces a diffusible factor that induces progenitor cells to adopt glial fates at the expense of neuronal fates. The effects of the postnatal cortical signals on glial cell differentiation are mimicked by FGF2 and CNTF, which induce glial fate specification and terminal glial differentiation respectively. These observations indicate that cell fate specification and terminal differentiation can be independently regulated and suggest that the sequential generation of neurons and glia in the cortex is regulated by a developmental increase in gliogenic signals.

Animals↗
PubMed2001

Putting to use a clinical guideline for treating tobacco dependency.

The issuance last year of the U.S. Public Health Services' clinical guideline for treating tobacco use and dependency offered managed care a tool that could help them achieve the Healthy People 2010 goals of cutting adult smoking rates in half. The authors describe how the guidelines approach this difficult public health issue.

Adolescent↗
PubMed2000

Semaphorin 3A is a chemoattractant for cortical apical dendrites.

The apical dendrites of pyramidal neurons integrate inputs from various cortical layers and are central to information processing. Here we show that the growth of apical dendrites towards the pial surface is regulated by a diffusible chemoattractant present at high levels near the marginal zone. A major component of this signal is semaphorin 3A (Sema3A), which was previously characterized as a chemorepellant for cortical axons. Soluble guanylate cyclase is asymmetrically localized to the developing apical dendrite, and is required for the chemoattractive effect of Sema3A. Thus the asymmetric localization of soluble guanylate cyclase confers distinct Sema3A responses to axons and dendrites. These observations reveal a mechanism by which a single chemotropic signal can pattern both axons and dendrites during development.

Animals↗
PubMed2000

Roundtable discussion: Part I--Epidemiologic, demographic, and treatment challenges in hypertension.

Hypertension is one of the most pervasive medical disorders in this country. As the nation's population ages, the number of patients with hypertension can be expected to rise substantially. On December 9, 1999, a panel of managed care medical directors, pharmacy directors, clinicians, and health economists convened in Irvine, Texas to discuss aspects of hypertension management and economic analysis. This roundtable is presented in three parts, including (1) a summary of the challenges of hypertension management from the point of view of the clinician, (2) the introduction of a pharmacoeconomic model of hypertension management, and (3) a discussion of how health plans approach this insidious disorder.

Aged↗
PubMed2000

Roundtable discussion: Part II--Development of a pharmacoeconomic model in hypertension.

Antihypertensive medications are targeted by most health plans as a major cost center. However, the efficacy of these medications, their side effects, and their resulting ability to prevent serious long-term complications must be factored into the value equation. To illustrate the possible economic effects of a single antihypertensive agent's inclusion on a health plan's drug formulary, an innovative pharmacoeconomic model was developed. In this portion of the roundtable, the design, results, and caveats of this model are discussed.

Antihypertensive Agents↗
PubMed2000

Roundtable discussion: Part III--Hypertension management in health plans.

In the final section of the roundtable discussion, participants describe how their individual managed care plans approach hypertension from the standpoints of disease management targeting, strategies to combat noncompliance, and how these plans utilize pharmacoeconomic information in drug formulary decision making.

Antihypertensive Agents↗
PubMed2000

Management of menopause: a new HEDIS measure and an opportunity for health plans.

A new measurement was added to the 2000 Health Plan Employer Data and Information Set (HEDIS) in June. The "management of menopause" measure allows health plans an opportunity to better serve a segment of the population that has traditionally been overlooked. The authors describe in detail the new HEDIS measurement criteria and how they represent an opportunity for health plans to better meet the needs of their perimenopausal enrollees.

Counseling↗
PubMed1995

Occupational asthma caused by automated salmon processing.

Within 3 months of the opening of a salmon-processing plant in the UK, some workers complained of symptoms suggestive of occupational asthma. A survey of all 291 employees identified 24 (8.2%) with occupational asthma. The employees worked near machines which generated respirable aerosols containing salmon-serum proteins. The IgE response to these proteins was associated with occupational asthma (p < 0.001), with increasing severity of symptoms (p < 0.001), and with working distance from the aerosol source (p = 0.037). The main factor which predisposed to IgE-antibody production and asthma was cigarette smoking (p < 0.001), whereas atopy and a previous allergic history did not. The affected employees were reallocated to a low-exposure worksite and factory ventilation was improved. Eleven showed significant clinical and pulmonary function improvement, and continued in employment. Thirteen who still had symptoms were advised to leave, thereafter becoming symptom-free, and regaining normal respiratory function. Early recognition of symptoms and prompt action to reduce aerosol exposure avoided the long-term reduction in pulmonary functions often associated with occupational asthma.

Adult↗
PubMed1995

A two-centre study for the evaluation and validation of an animal model for the assessment of the potential of small molecular weight chemicals to cause respiratory allergy.

This study evaluated a single intradermal injection model in the guinea pig with subsequent inhalation challenge and serological analysis as a method to predict the potential of chemicals to induce respiratory allergy. Four known respiratory allergens (trimellitic anhydride, diphenyl methane diisocyanate, phthalic anhydride and toluene diisocyanate (TDI)) were screened by two industrial research laboratories using this protocol. Dinitrochlorobenzene, a potent contact allergen, was included as a negative control material. In both laboratories, the respiratory allergens, but not the contact allergen, induced high titre antigen-specific antibodies in treated animals. The inhalation challenge results were similar in both laboratories but were less conclusive in that exposure to free TDI failed to induce pulmonary responses, probably because it fails to penetrate to the deep lung in sufficient concentration. Although the assay shows promise as a means of identifying chemical respiratory sensitisers, its use as a routine screen for the prediction of the ability of materials to induce respiratory allergy in man is probably questionable.

Administration, Inhalation↗
PubMed1994

Ig heavy chain protein controls B cell development by regulating germ-line transcription and retargeting V(D)J recombination.

The membrane-associated form of Ig heavy chain (mu) protein has been implicated as a critical regulator of B cell development. Mutant mice unable to produce the membrane form of mu protein fail to produce mature B cells. Splenic B cells from mice transgenic for a functionally rearranged Ig mu gene show a marked decrease in endogenous heavy chain gene rearrangement. We have analyzed the effects of a human mu transgene on the regulation of V(D)J recombination during B cell development in the mouse fetal liver. We found that mu transgenic and wild-type littermate mice begin kappa light chain gene rearrangement at the same time during development but the transgenic mice show a striking increase in the frequency of kappa gene rearrangement. The transgenic mice also show an increase in the levels of a germ-line kappa gene transcript known to be associated with kappa gene rearrangement. D-to-JH heavy chain gene rearrangement is unaffected throughout development by the presence of the mu transgene. Endogenous heavy chain gene V-to-DJH rearrangement occurs with similar frequency in transgenic and nontransgenic fetal livers during midgestation but is reduced in late gestation mu transgenic fetal liver. We show that this decrease in rearrangement is associated with a decrease in unrearranged VH gene transcription. Furthermore, we show that changes in the frequencies of rearranged kappa and mu genes are accompanied by changes in the frequencies of dsDNA breaks, a V(D)J recombination reaction intermediate associated with each of these loci. We propose that membrane-associated mu protein regulates B cell development by signaling a change in the pattern of unrearranged Ig gene transcriptional activity, thereby retargeting the V(D)J recombinase.

Alleles↗
PubMed1994

Respiratory allergy: hazard identification and risk assessment.

Various chemicals and proteins of industrial importance are known to cause respiratory allergy, with occupational asthma being the most important manifestation of the disease. This paper describes clinical syndromes, mechanisms associated with occupational respiratory hypersensitivity, and methods available currently for the prospective identification of potential respiratory allergens. Certain classes of chemicals are commonly associated with occupational respiratory allergy. There is insufficient information, however, to predict respiratory sensitization potential from analysis of structure alone, although reactivity with proteins is likely to be relevant. As yet there exist no fully validated or widely applied predictive methods or internationally harmonized guidelines. The most promising predictive animal methods are the mouse IgE test and guinea pig models. Work in mice has focused upon events occurring during the induction phase of sensitization following primary encounter with the test chemical. In contrast, guinea pig models have been used primarily to identify respiratory allergens (chemicals or proteins) as a function of elicitation reactions induced in previously sensitized animals. Given the possible serious health manifestations of respiratory allergy, early identification of respiratory sensitizers is urgently required. The two methods should, as a priority, be developed further and the production of a detailed protocol for these methods be undertaken to facilitate further validation. Together, this information will allow for two types of risk assessment associated with respiratory allergy: the risk that exposure to a material will (1) induce sensitization in an individual and (2) elicit allergic reactions in a previously sensitized individual.

Allergens↗
PubMed1993

Double-strand signal sequence breaks in V(D)J recombination are blunt, 5'-phosphorylated, RAG-dependent, and cell cycle regulated.

Immunoglobulin and T-cell receptor genes are assembled during lymphocyte development by a novel, highly regulated series of gene rearrangement reactions known as V(D)J recombination. All rearranging loci are flanked by conserved heptamer-nonamer recombination signal sequences. Gene rearrangement results in the imprecise fusion of coding sequences and the precise fusion of signal sequences. DNA molecules with double-stranded breaks near signal sequences have been detected in cells undergoing V(D)J recombination of the TCR delta locus. We have devised a ligation-mediated PCR assay that detects broken-ended molecules in purified genomic DNA. Using this assay we found that DNA breaks occurring precisely at the signal sequence-coding sequence junction are a general feature of V(D)J recombination, appearing in association with each type of rearranging immunoglobulin gene segment. We show that a significant fraction of these broken ends are blunt and 5'-phosphorylated. In addition, detection of these broken-ended signal sequences is dependent on the activity of RAG-1 and RAG-2, and is restricted to the G0/G1 phase of the cell cycle. The pattern of broken-ended molecules detected in cells at various stages of development reflects the activity of the V(D)J recombinase at different loci during B- and T-cell development.

Aging↗
PubMed1992

The purification of B-cell precursors from mouse fetal liver.

Lymphocyte progenitor cells isolated on sequential days of gestation from mouse fetal liver represent distinct stages in B cell development. We have utilized polymerase chain reaction (PCR)-based assays to detect immunoglobulin (Ig) gene rearrangement and flow cytometry to assay cell surface markers following fractionation based on the differential expression of the B cell-specific phosphatase CD45 (B220). The purification of B220+ cells from day 17 fetal liver resulted in a 10-fold enrichment of cells which had undergone gene rearrangement events. We have also shown that day 13 fetal liver cells activate successive Ig gene rearrangements during short-term culture in the presence of fetal calf serum (FCS), interleukin-3 (IL3), and interleukin-7 (IL7). However, partially purified lymphocyte precursors fail to activate Ig gene rearrangement in culture unless they are cultured in the presence of a stromal cell line.

Animals↗