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Biomedical subjects

J McGee

Publications and source records attributed to J McGee.

At least 19 recordsLinked to original sources

Physical management of spasticity.

Physical management of people with spasticity is a complex task requiring the collaborative work of a multidisciplinary team. This article reviews some of the most commonly used treatment techniques and theories that lay the framework for the physical management of spasticity. Most crucial to the management of the person with spasticity is the skillful application of the techniques and theories discussed. Given the complexity in the standardized evaluation of children with spasticity, it is recommended that existing outcome measures or standardized scales be applied wherever possible as an adjunct tool to the clinician's assessment and interventions. One must recognize the benefits of such scales and their limitations. Therefore, it is recommended that further development of standardized assessments be supported by funding agencies to develop both quantitative and qualitative measurement tools that will address the particular needs of the person with spasticity. Review of the literature supports the many interventions that are listed; however, further research is recommended by the consensus group.

Adolescent↗

Transperineal and transvaginal sonography of perianal inflammatory disease.

OBJECTIVE: Perianal infection arises in small intersphincteric anal glands predominantly located at the dentate line. Documentation of fluid collections and the relationship of inflammatory tracts to the sphincter mechanism is important for surgical treatment. Transanal sonography for assessment of perianal inflammatory disease is limited because placement of the rigid probe into the anal canal does not allow assessment of disease in the perineal region. The purpose of this study was to validate the use of transperineal sonography in men and both transvaginal and transperineal sonography in women for evaluation of perianal inflammatory disease. SUBJECTS AND METHODS: Fifty-four patients, 28 men and 26 women, were imaged with transperineal and a combination of transperineal and transvaginal sonography, respectively. All patients were examined in the supine lithotomy and left lateral position with a transvaginal 8-to 4-MHz probe or a linear 12- to 7-MHz transducer. All fluid collections, sinus tracts, and fistulas were described by their location in relation to the sphincter mechanism and perineum. RESULTS: Forty-six of 54 patients had perianal fistulas or sinus tracts: 33 transphincteric, seven intersphincteric, and six extrasphincteric. Fifteen patients had an associated abscess. In the eight remaining patients, there were two anovaginal fistulas, one rectovaginal fistula, one prolapsed internal hemorrhoid, two perianal complex masses, and two vascular perianal or perirectal inflammatory masses. Twenty-six patients underwent surgical procedures involving the anorectal canal or perirectal region, and of these, preoperative sonographic findings were confirmed in 22 (85%) of 26 patients. Three patients refused surgery, and six are awaiting surgery at this writing. Fifteen patients were treated conservatively. CONCLUSION: Transperineal and transvaginal sonography are accurate, painless, and cost-effective methods for documenting perianal fluid collections and fistulas or sinus tracts or both.

Abscess↗

Wound botulism in California, 1951-1998: recent epidemic in heroin injectors.

California has reported most of the world's wound botulism (WB) cases and nearly three-fourths of the cases reported in the United States. We reviewed the clinical, epidemiologic, and laboratory features of WB. From the first case in 1951, through 1998, a total of 127 cases were identified-93 in the last 5 years. The dramatic increase has been due to an epidemic (of WB) in people who inject black tar heroin. Whereas early cases of WB occurred after gross trauma, all but 1 of the last 102 cases occurred in drug users, primarily those who inject drugs subcutaneously ("skin poppers"). Cases are occurring disproportionately in Hispanics and women. Misdiagnosis and diagnostic delays of up to 64 days have occurred. This unprecedented, ongoing epidemic is now being reported in other states. We discuss the clinical and laboratory features that distinguish botulism from conditions that can mimic it, the relative yield of various diagnostic laboratory tests for botulism, and its treatment.

Adolescent↗

Afferent innervation of outer and inner hair cells is normal in neonatally de-efferented cats.

It has been hypothesized that normal pruning of exuberant branching of afferent neurons in the developing cochlea is caused by the arrival of the olivocochlear efferent neurons and the resulting competition for synaptic sites on hair cells. This hypothesis was supported by a report that afferent innervation density on mature outer hair cells (OHCs) is elevated in animals deefferented at birth, before the olivocochlear system reaches the outer hair cell area (Pujol and Carlier [1982] Dev. Brain Res. 3:151-154). In the current study, this claim was evaluated quantitatively at the electron microscopic level in four cats that were de-efferented at birth and allowed to survive for 6-11 months. A semiserial section analysis of 156 OHCs from de-efferented and normal ears showed that, although de-efferentation essentially was complete in all four cases, the number and distribution of afferent terminals on OHCs was indistinguishable from normal, and the morphology of afferent synapses was normal in both the inner hair cell area and the OHC area. Thus, the postnatal presence of an efferent system is not required for the normal development of cochlear afferent innervation, and the synaptic competition hypothesis is not supported.

Afferent Pathways↗

SHP-2 can suppress transformation induced by platelet-derived growth factor.

Signaling by either the type alpha or type beta receptors of platelet-derived growth factor occurs by phosphorylation of at least 10 intra-cytoplasmic tyrosine residues and their subsequent association of secondary signaling molecules with Src homology 2 (SH2) domains. Although the role of several of these secondary signaling molecules in mitogenesis has become increasingly clear, their roles in morphological transformation are not as well defined. Here we present evidence that the SHP-2 phosphatase which associates with Tyr 1009 of the type beta receptor and Tyr 720 of the type alpha receptor may suppress transformation induced by the PDGF B chain. Cotransfection of a dominant negative mutant of the SHP-2 gene and the PDGF B chain gene into mouse fibroblasts that only poorly formed foci with the PDGF B chain alone resulted in larger and more prominent foci. Furthermore, introduction of a wild-type copy of the SHP-2 gene into a tumor cell line, U-87MG, which relies on PDGF expression to form foci in vitro, caused a reversion of phenotype.

3T3 Cells↗

The manifestation and nursing management of agitation in institutionalised residents with dementia.

This participatory action research study is the first formal research study undertaken by nurses in a nursing development unit. The study emerged as the result of nurses brainstorming issues that they perceived to be problematic in their nursing practice and their unit environment. The nurses of the psycho-geriatric nursing development unit, Wallsend Aged Care Facility, New South Wales, Australia identified that the management of agitated behaviour manifested by their severely demented clients was a major challenge in their practice. As a result, a pilot participatory action research study was designed to measure how agitation manifested, to measure the severity of agitation and to identify current nursing practices used to manage it and their outcome. Results of the study demonstrated that nurse actions triggered the majority of most highly rated episodes of agitated behaviour in this group of elderly residents, and that the majority of these nurse actions related to those involved in carrying out activities of daily living for the residents.

Aged↗

Variable pulmonary responses from exposure to concentrated ambient air particles in a rat model of bronchitis.

Chronic bronchitis may be considered a risk factor in particulate matter (PM)-induced morbidity. We hypothesized that a rat model of human bronchitis would be more susceptible to the pulmonary effects of concentrated ambient particles (CAPs) from Research Triangle Park, NC. Bronchitis was induced in male Sprague-Dawley rats (90-100 days of age) by exposure to 200 ppm sulfur dioxide (SO2), 6 h/day x 5 days/week x 6 weeks. One day following the last SO2 exposure, both healthy (air-exposed) and bronchitic (SO2-exposed) rats were exposed to filtered air (three healthy; four bronchitic) or CAPs (five healthy; four bronchitic) by whole-body inhalation, 6 h/day x 2 or 3 days. Pulmonary injury was determined either immediately (0h) or 18 h following final CAPs exposure. The study protocol involving 0 h time point was repeated four times (study #A, November, 1997; #B, February, 1998; #C and #D, May, 1998), whereas the study protocol involving 18 h time point was done only once (#F). In an additional study (#E), rats were exposed to residual oil fly ash (ROFA), approximately 1 mg/ m(3)x6 h/day x 3 days to mimic the CAPs protocol (February, 1998). The rats allowed 18 h recovery following CAPs exposure (#F) did not depict any CAPs-related differences in bronchoalveolar lavage fluid (BALF) injury markers. Of the four CAPs studies conducted (0 h time point), the first (#A) study (approximately 650 microg/m3 CAPs) revealed significant changes in the lungs of CAPs-exposed bronchitic rats compared to the clean air controls. These rats had increased BALF protein, albumin, N-acetyl glutaminidase (NAG) activity and neutrophils. The second (#B) study (approximately 475 microg/m3 CAPs) did not reveal any significant effects of CAPs on BALF parameters. Study protocols #C (approximately 869 microg/m3 CAPs) and #D (approximately 907 microg/m3 CAPs) revealed only moderate increases in the above mentioned BALF parameters in bronchitic rats exposed to CAPs. Pulmonary histologic evaluation of studies #A, #C, #D, and #F revealed marginally higher congestion and perivascular cellularity in CAPs-exposed bronchitic rats. Healthy and bronchitic rats exposed to ROFA (approximately 1 mg/m3) did not show significant pulmonary injury (#E). Analysis of leachable elemental components of CAPs revealed the presence of sulfur, zinc, manganese, and iron. There was an apparent lack of association between pulmonary injury and CAPs concentration, or its leachable sulfate or elemental content. In summary, real-time atmospheric PM may result in pulmonary injury, particularly in susceptible models. However, the variability observed in pulmonary responses to CAPs emphasizes the need to conduct repeated studies, perhaps in relation to the season, as composition of CAPs may vary. Additionally, potential variability in pathology of induced bronchitis or other lung disease may decrease the ability to distinguish toxic injury due to PM.

Acetylglucosaminidase↗

Contributions of ion conductances to the onset responses of octopus cells in the ventral cochlear nucleus: simulation results.

The onset response pattern displayed by octopus cells has been attributed to intrinsic membrane properties, low membrane impedance, and/or synaptic inputs. Although the importance of a low membrane impedance generally is acknowledged as an essential component, views differ on the role that ion channels play in producing the onset response. In this study, we use a computer model to investigate the contributions of ion channels to the responses of octopus cells. Simulations using current ramps indicate that, during the "ramp-up" stage, the membrane depolarizes, activating a low-threshold K(+) channel, K(LT), which increases membrane conductance and dynamically increases the current required to evoke an action potential. As a result, the model is sensitive to the rate that membrane potential changes when initiating an action potential. Results obtained when experimentally recorded spike trains of auditory-nerve fibers served as model inputs (simulating acoustic stimulation) demonstrate that a model with K(LT) conductance as the dominant conductance produces realistic onset response patterns. Systematically replacing the K(LT) conductance by a h-type conductance (which corresponds to a hyperpolarization-activated inward rectifier current, I(h)) or by a leakage conductance reduces the model's sensitivity to rate of change in membrane potential, and the model's response to "acoustic stimulation" becomes more chopper-like. Increasing the h-type conductance while maintaining a large K(LT) conductance causes an increase in threshold to both current steps and acoustic stimulation but does not significantly affect the model's sensitivity to rate of change in membrane potential and the onset response pattern under acoustic stimulation. These findings support the idea that K(LT), which is activated during depolarization, is the primary membrane conductance determining the response properties of octopus cells, and its dynamic role cannot be provided by a static membrane conductance. On the other hand, I(h), which is activated during hyperpolarization, does not play a large role in the basic onset response pattern but may regulate response threshold through its contribution to the membrane conductance.

Acoustic Stimulation↗

Clostridium difficile colitis associated with infant botulism: near-fatal case analogous to Hirschsprung's enterocolitis.

We present the first five reported cases of Clostridium difficile-associated diarrhea (CDAD) in children with infant botulism caused by Clostridium botulinum. We compare two fulminant cases of colitis in children with colonic stasis, the first caused by infant botulism and the second caused by Hirschsprung's disease. In both children, colitis was accompanied by hypovolemia, hypotension, profuse ascites, pulmonary effusion, restrictive pulmonary disease, and femoral-caval thrombosis. Laboratory findings included pronounced leukocytosis, hypoalbuminemia, hyponatremia, coagulopathy, and, when examined in the child with infant botulism, detection of C. difficile toxin in ascites. CDAD recurred in both children, even though difficile cytotoxin was undetectable in stool after prolonged initial therapy. Four children who had both infant botulism and milder CDAD also are described. Colonic stasis, whether acquired, as in infant botulism, or congenital, as in Hirschsprung's disease, may contribute to the susceptibility to and the severity of CDAD.

Botulism↗

Making survey results easy to report to consumers: how reporting needs guided survey design in CAHPS. Consumer Assessment of Health Plans Study.

OBJECTIVES: CAHPS is designed to report information about health care quality from the consumer perspective. Enrollees are surveyed about their experiences with their health plan and medical care, and results are reported to other consumers choosing among health plans. Based on survey instruments designed to elicit reliable and valid information about health plan experiences from plan enrollees, the aim of the CAHPS team was to design a series of reporting products that present survey results so that consumers find the information understandable, meaningful, and useful in choosing among health plans. METHODS: Design of the survey instruments and reporting products were closely linked. The approach to reporting was based on previous research on consumers' information interests and needs in evaluating and choosing among plans. Cognitive tests were conducted with consumers to get their reactions to mock-ups of various approaches to reporting CAHPS survey results. RESULTS: Findings from previous research and cognitive testing, together with feedback from various experts and the public, were used to modify the survey questions, response options, and reporting formats to make it easier for consumers to understand and use reports. Changes included dropping topics of less interest to consumers, changing question wordings that were hard to understand, minimizing the number of different response categories, and revising questions to make them easier to group together for purposes of reporting. CONCLUSIONS: The CAHPS focus on reporting results to consumers presented an unusual challenge for survey design, requiring close coordination between instrument design and report development to produce a survey and reporting kit that serves consumers' information needs.

Adult↗

Long-term effects of sectioning the olivocochlear bundle in neonatal cats.

The olivocochlear bundle (OCB) was cut in neonatal cats to evaluate its role in the development of normal cochlear function. Approximately 1 year after deefferentation, acute auditory nerve fiber (ANF) recordings were made from lesioned animals, lesion shams, and normal controls. The degree of deefferentation was quantified via light microscopic evaluation of the density of OCB fascicles in the tunnel of Corti, and selected cases were analyzed via electron microscopy. In the most successful cases, the deefferentation was virtually complete. ANFs from successfully lesioned animals exhibited significant pathophysiology compared with normals and with other animals in which the surgery failed to interrupt the OCB. Thresholds at the characteristic frequency (CF), the frequency at which ANFs are most sensitive, were elevated across the CF range, with maximal effects for CFs in the 10 kHz region. Frequency threshold or tuning curves displayed reduction of tip-to-tail ratios (the difference between CF and low-frequency "tail" thresholds) and decreased sharpness of tuning. These pathological changes are generally associated with outer hair cell (OHC) damage. However, light microscopic histological analysis showed minimal hair cell loss and no significant differences between normal and deefferented groups. Spontaneous discharge rates (SRs) were lower than normal; however, those fibers with the highest SRs remained more sensitive than those with lower SRs. Findings suggest that the interaction between OC efferents and OHCs early in development may be critical for full expression of active mechanical processes.

Age Factors↗

Wound botulism associated with black tar heroin among injecting drug users.

CONTEXT: Wound botulism (WB) is a potentially lethal, descending, flaccid, paralysis that results when spores of Clostridium botulinum germinate in a wound and elaborate neurotoxin. Since 1988, California has experienced a dramatic increase in WB associated with injecting "black tar" heroin (BTH), a dark, tarry form of the drug. OBJECTIVE: To identify risk factors for WB among injecting drug users (IDUs). DESIGN: Case-control study based on data from in-person and telephone interviews. PARTICIPANTS: Case patients (n=26) were IDUs who developed WB from January 1994 through February 1996. Controls (n=110) were IDUs newly enrolled in methadone detoxification programs in 4 counties. MAIN OUTCOME MEASURES: Factors associated with the development of WB. RESULTS: Among the 26 patients, the median age was 41.5 years, 15 (58%) were women, 14 (54%) were non-Hispanic white, 11 (42%) were Hispanic, and none were positive for the human immunodeficiency virus. Nearly all participants (96% of patients and 97% of controls) injected BTH, and the mean cumulative dose of BTH used per month was similar for patients and controls (27 g and 31 g, respectively; P=.6). Patients were more likely than controls to inject drugs subcutaneously or intramuscularly (92% vs 44%, P<.001) and used this route of drug administration more times per month (mean, 67 vs 24, P<.001), with a greater cumulative monthly dose of BTH (22.3 g vs 6.3 g, P<.001). A dose-response relationship was observed between the monthly cumulative dose of BTH injected subcutaneously or intramuscularly and the development of WB (chi2 for linear trend, 26.5; P<.001). In the final regression model, subcutaneous or intramuscular injection of BTH was the only behavior associated with WB among IDUs (odds ratio, 13.7; 95% confidence interval, 3.0-63.0). The risk for development of WB was not affected by cleaning the skin, cleaning injection paraphernalia, or sharing needles. CONCLUSIONS: Injection of BTH intramuscularly or subcutaneously is the primary risk factor for the development of WB. Physicians in the western United States, where BTH is widely used, should be aware of the potential for WB to occur among IDUs.

Adult↗

Pulmonary responses to oil fly ash particles in the rat differ by virtue of their specific soluble metals.

Occupational exposure to residual oil fly ash (ROFA) particulate has been associated with adverse respiratory health effects in humans. We hypothesized that ROFA collected at different sites within an oil burning power plant, by virtue of its differing metal and sulfate composition, will induce differential lung injury. Ten ROFA samples collected at various sites within a power plant were analyzed for water- and 1.0 M HCl-leachable arsenic (As), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), zinc (Zn), and sulfur by inductively coupled plasma-atomic emission spectroscopy. All ROFA samples contained variable amounts of leachable (water-extractable) and 1.0 M HCl-extractable Fe, V, and/or Ni. All other metals, except Zn (ROFA No. 1 contained 3.43 and No. 3, 6.35 micrograms/mg Zn), were present in negligible quantities (< 1.0 microgram/mg) in the water extract. In vivo pulmonary injury from exposure to whole saline suspensions of these ROFA was evaluated. Male, SD rats (60 days old) were intratracheally instilled with either saline or saline suspension of whole ROFA (< 3.0 mass median aerodynamic diameter) at three concentrations (0.833, 3.33, or 8.33 mg/kg). After 24 h, lungs were lavaged and bronchoalveolar lavage fluid (BALF) was analyzed for cellular influx and protein content as well as lactate dehydrogenase (LDH) and N-acetyl glucosaminidase (NAG) activity and total hemoglobin as indicators of lung injury. ROFA-induced increases in BALF protein and LDH, but not neutrophilic inflammation, were associated with its water-leachable total metal, Ni, Fe, and sulfate content. However, the neutrophilic response following ROFA exposure was positively correlated with its water-leachable V content. Modest lung injury was observed with the ROFA samples which contained the smallest amounts of water-leachable metals. The ability of ROFA to induce oxidative burst in alveolar macrophage (AM) was determined in vitro using a chemiluminescence (CL) assay. AM CL signals in vitro were greatest with ROFA containing primarily soluble V and were less with ROFA containing Ni plus V. In summary, ROFA-induced in vivo acute pulmonary inflammation appears to be associated with its water-leachable V content; however, protein leakage appears to be associated with its water-leachable Ni content. ROFA-induced in vitro activation of AM was highest with ROFA containing leachable V but not with Ni plus V, suggesting that the potency and the mechanism of pulmonary injury will differ between emissions containing V and Ni.

Animals↗

Ultrastructural, physiological, and molecular defects in the inner ear of a gene-knockout mouse model for autosomal Alport syndrome.

The cochleae from a COL4A3-deficient mouse line were examined for defects that might shed light on the molecular mechanism of otopathology observed in humans with Alport syndrome. At the light microscopic level no obvious defects were observed. Immunohistochemical analysis using antibodies specific for the basement membrane collagen chains revealed the absence of the COL4A3 and COL4A4 chains throughout the membranous labyrinth. The COL4A5 chain was absent from all cochlear basement membranes except those in the vessels of the stria vascularis. Expression of the COL4A1 and COL4A2 chains was unchanged in the mutant. Electron microscopic examination of the cochlear basement membranes revealed significant thinning of the basement membrane running from the spiral limbus, down the inner sulcus, across the basilar membrane and up to the spiral prominence. Basement membranes that normally ensheathe the root cells were not detectable. In contrast, the basement membranes surrounding the vessels of the stria vascularis were significantly thickened in the mutant. This was associated with endothelial cell swelling and a marked decrease in internal capillary diameter. In severe cases, pathology was observed in the marginal cells with a loss of basolateral infoldings. Immunohistochemical analysis of the strial vessels revealed an increase in entactin and collagen COL4A1 and COL4A2 chains. Auditory-evoked brainstem response measurements suggest a small increase in thresholds across all frequencies when successive measurements on individual mutant mice were examined between 6 and 8 postnatal weeks. Combined, these results illustrate changes in the basement membranes of the strial vessels that bear resemblance to Alport glomerular basement membrane pathology. A closer look at this compartment in human Alport biopsy specimen may be warranted.

Animals↗

Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus.

The principal role of ionotropic glutamate receptors in the transmission and processing of information in the auditory pathway has been investigated extensively. In contrast, little is known about the functional contribution of the G-protein-coupled metabotropic glutamate receptors (mGluRs), although their anatomic location suggests that they exercise a significant influence on auditory processing. To investigate this issue, sound-evoked responses were obtained from single auditory neurons in the cochlear nuclear complex of anesthetized cats and gerbils, and metabotropic ligands were administered locally through microionophoretic pipettes. In general, microionophoresis of the mGluR agonists, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous and sound-evoked discharge rates. However, activation and recovery times were significantly longer than those observed for ionotropic agonists, such as N-methyl--aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, consistent with the recruitment of a second-messenger system. The efficacy of mGluR agonists was diminished after administration of the mGluR antagonist, (+)-alpha-methyl-4-carboxyphenylglycine, consistent with a selective action at metabotropic recognition sites. In contrast, two distinct changes were observed after the mGluR agonist had been discontinued for several minutes. Approximately 50% of neurons exhibited a chronic depression of sound-evoked discharge rate reminiscent of long-term depression, a cellular property observed in other systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the sound-evoked response similar to the cellular phenomenon of long-term potentiation. These findings suggest that mGluR activation has a profound influence on the gain of primary afferent driven activity in the caudal cochlear nucleus.

Acoustic Stimulation↗