Biomedical subjects

Michael D Mills

Publications and source records attributed to Michael D Mills.

8 recordsLinked to original sources

PubMed2006

Schwann cell-like differentiation by adult oligodendrocyte precursor cells following engraftment into the demyelinated spinal cord is BMP-dependent.

The development of remyelinating strategies designed to enhance recruitment and differentiation of endogenous precursor cells available to a site of demyelination in the adult spinal cord will require a fundamental understanding of the potential for adult spinal cord precursor cells to remyelinate as well as an insight into epigenetic cues that regulate their mobilization and differentiation. The ability of embryonic and postnatal neural precursor cell transplants to remyelinate the adult central nervous system is well documented, while no transplantation studies to date have examined the remyelinating potential of adult spinal-cord-derived oligodendrocyte precursor cells (adult OPCs). In the present study, we demonstrate that, when transplanted subacutely into spinal ethidium bromide/X-irradiated (EB-X) lesions, adult OPCs display a limited capacity for oligodendrocyte remyelination. Interestingly, the glia-free environment of EB lesions promotes engrafted adult OPCs to differentiate primarily into cells with immunophenotypic and ultrastructural characteristics of myelinating Schwann cells (SCs). Astrocytes modulate this potential, as evidenced by the demonstration that SC-like differentiation is blocked when adult OPCs are co-transplanted with astrocytes. We further show that inhibition of bone morphogenetic protein (BMP) signaling through noggin overexpression by engrafted adult OPCs is sufficient to block SC-like differentiation within EB-X lesions. Present data suggest that the macroglial-free environment of acute EB lesions in the ventrolateral funiculus is inhibitory to adult spinal cord-derived OPC differentiation into remyelinating oligodendrocytes, while the presence of BMPs and absence of noggin promotes SC-like differentiation, thereby unmasking a surprising lineage fate for these cells.

Animals↗

PubMed2006

Lipid exudation following plaque radiotherapy for posterior uveal melanoma.

PURPOSE: To investigate factors associated with lipid exudation after plaque radiotherapy for uveal melanoma. DESIGN: Retrospective interventional case series. METHODS: Records of 139 consecutive uveal melanoma patients treated with I-125 plaque radiotherapy were reviewed. Lipid exudation was the major outcome measured. RESULTS: Lipid exudation was detected in 19 patients (13.7%). Mean time from plaque therapy to lipid exudation was 10 months (range, 3-23 months). Lipid exudation was associated with younger patient age (P = .0002), increased low-density lipoprotein (P = .004), decreased high-density lipoprotein (P = .026), increased tumor thickness (P = .024), and exudative retinal detachment (P = .016). Patients with lipid exudation had worse visual outcome (P < .0001) and increased neovascular glaucoma (P = .01). CONCLUSIONS: Lipid exudation after plaque radiotherapy for uveal melanoma is associated with poor ocular outcome. Factors associated with this lipid exudation are distinct from those associated with radiation retinopathy, and they may suggest interventions to combat this complication.

Brachytherapy↗

PubMed2006

Intraoperative radiation therapy using mobile electron linear accelerators: report of AAPM Radiation Therapy Committee Task Group No. 72.

Intraoperative radiation therapy (IORT) has been customarily performed either in a shielded operating suite located in the operating room (OR) or in a shielded treatment room located within the Department of Radiation Oncology. In both cases, this cancer treatment modality uses stationary linear accelerators. With the development of new technology, mobile linear accelerators have recently become available for IORT. Mobility offers flexibility in treatment location and is leading to a renewed interest in IORT. These mobile accelerator units, which can be transported any day of use to almost any location within a hospital setting, are assembled in a nondedicated environment and used to deliver IORT. Numerous aspects of the design of these new units differ from that of conventional linear accelerators. The scope of this Task Group (TG-72) will focus on items that particularly apply to mobile IORT electron systems. More specifically, the charges to this Task Group are to (i) identify the key differences between stationary and mobile electron linear accelerators used for IORT, (ii) describe and recommend the implementation of an IORT program within the OR environment, (iii) present and discuss radiation protection issues and consequences of working within a nondedicated radiotherapy environment, (iv) describe and recommend the acceptance and machine commissioning of items that are specific to mobile electron linear accelerators, and (v) design and recommend an efficient quality assurance program for mobile systems.

Electrons↗

PubMed2005

Management of endogenous fungal endophthalmitis with voriconazole and caspofungin.

PURPOSE: Voriconazole, a new generation triazole, has been shown to achieve therapeutic intraocular levels after oral administration. Caspofungin is the first approved agent from a new class of antifungals, the echinocandins. This series describes experience at two centers using these novel antifungals to treat endogenous fungal endophthalmitis. DESIGN: Retrospective review. METHODS: Treatment of five patients with Candida endophthalmitis are reviewed. Postmortem intraocular voriconazole concentrations on a sixth patient are presented as well. RESULTS: All patients had systemic cultures positive for Candida species. Three patients had prompt resolution of intraocular mycosis with intravenous and oral voriconazole, caspofungin, or both. The fourth patient with bilateral disease responded well to i.v. voriconazole and caspofungin but had a recurrence when discharged on oral voriconazole and i.v. caspofungin. This patient had a bowel resection with an ileostomy; therefore, absorption of oral voriconazole may have been inadequate. Bilateral amphotericin B intravitreal injection ultimately treated this patient. The fifth patient received 100 microg/0.1 ml of intravitreal voriconazole (final vitreous concentration approximately 25 microg/ml) followed by oral voriconazole and responded favorably. Our sixth patient had multisystem failure and passed away 1 week after initiating intravenous voriconazole for non-ocular candidemia. Postmortem HPLC analysis of the aqueous and vitreous revealed voriconazole concentrations of 1.52 microg/ml and 1.12 microg/ml, respectively (MIC90 of Candida albicans is 0.06 microg/ml). CONCLUSIONS: Voriconazole and caspofungin appear to be powerful weapons to add to the existing armamentarium against fungal endophthalmitis. Further studies are warranted to define precisely the role of these new agents alone or in combination with other antifungals.

Administration, Oral↗

PubMed2004

Complex interactions between native and invasive fish: the simultaneous effects of multiple negative interactions.

We suggest that the ultimate outcome of interactions between native species and invasive species (extinction or coexistence) depends on the number of simultaneous negative interactions (competition and predation), which depends on relative body sizes of the species. Multiple simultaneous interactions may constrain the ability of native species to trade fitness components (i.e., reduced growth for reduced risk of predation) causing a spiral to extinction. We found evidence for five types of interactions between the adults and juveniles of introduced western mosquitofish (Gambusia affinis) and the juveniles of native least chub (Iotichthys phlegethontis). We added ten large (23-28 mm) and seven small (9-13 mm) young-of-the-year (YOY) least chub to replicate enclosures with zero, low, and high densities of mosquitofish in a desert spring ecosystem. Treatments with mosquitofish reduced the average survival of least chub by one-third. No small YOY least chub survived in enclosures with high mosquitofish densities. We also performed two laboratory experiments to determine mortality to predation, aggressiveness, and habitat selection of least chub in the presence of mosquitofish. Mean mortality of least chub due to predation by large mosquitofish was 69.7% over a 3-h trial. Least chub were less aggressive, selected protected habitats (Potamogeton spp.), and were more stationary in the presence of mosquitofish where the dominance hierarchy was large mosquitofish>>large least chub approximately small mosquitofish>>small least chub. Least chub juveniles appear to be figuratively caught in a vice. Rapid growth to a size refuge could reduce the risk of predation, but the simultaneous effects of competition decreased least chub growth and prolonged the period when juveniles were vulnerable to mosquitofish predation.

Analysis of Variance↗

PubMed2003

Reimbursement versus effort in medical physics practice in radiation oncology.

The changes in health care reimbursement have the potential to affect the availability of quality medical physicist service in patient care. A survey was conducted by the AAPM Professional Council and the ACMP to collect cost information for special medical physics consultation, CPT4-77370 and continuing medical physics, CPT4-77336. The data collected from the survey was compared to current reimbursement schemes for a number of special procedures. Under varying reimbursement schemes, the costs of the medical physics services provided cannot be recaptured by the institution. It remains important for medical physicists to assess our utilization of resources and allocation to each of the services we provide and to understand the implications of policy changes at the federal and local levels.

Data Collection↗

PubMed2002

Functional redundancy of ventral spinal locomotor pathways.

Identification of long tracts responsible for the initiation of spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. Pathways derived from the mesencephalic locomotor region and pontomedullary medial reticular formation responsible for fictive locomotion in decerebrate preparations project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the ventrolateral funiculus (VLF). However, white matter regions critical for spontaneous over-ground locomotion remain unclear because cats, monkeys, and humans display varying degrees of locomotor recovery after ventral SCIs. We studied the contributions of myelinated tracts in the VLF and ventral columns (VC) to spontaneous over-ground locomotion in the adult rat using demyelinating lesions. Animals received ethidium bromide plus photon irradiation producing discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, VC, VLF-VC, or complete ventral white matter (CV). Behavior [open-field Basso, Beattie, and Bresnahan (BBB) scores and grid walking] and transcranial magnetic motor-evoked potentials (tcMMEP) were studied at 1, 2, and 4 weeks after lesion. VLF lesions resulted in complete loss or severe attenuation of tcMMEPs, with mean BBB scores of 18.0, and no grid walking deficits. VC lesions produced behavior similar to VLF-lesioned animals but did not significantly affect tcMMEPs. VC-VLF and CV lesions resulted in complete loss of tcMMEP signals with mean BBB scores of 12.7 and 6.5, respectively. Our data support a diffuse arrangement of axons within the ventral white matter that may comprise a system of multiple descending pathways subserving spontaneous over-ground locomotion in the intact animal.

Animals↗

PubMed2002

Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat.

Identification of long tracts responsible for spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. We recently demonstrated that extensive demyelination of adult rat thoracic ventral columns, ventromedial, and ventrolateral white matter produces persistent, significant open-field hindlimb locomotor deficits. Locomotor movements resulting from stimulation of the pontomedullary locomotor region are inhibited by dorsolateral funiculus (DLF) lesions suggesting that important pathways for locomotion may also exist in the dorsal white matter. However, dorsal hemisections that interrupt dorsal columns/dorsal corticospinal tract (DC/CST) and DLF pathways do not produce persistent, severe locomotor deficits in the adult rat. We studied the contributions of myelinated tracts in the DLF and DC/CST to overground locomotion following complete conduction blockade of axons in the ventrolateral funiculus (VLF), a region important for locomotor movements and for transcranial magnetic motor-evoked potentials (tcMMEP). Animals received ethidium bromide plus photon irradiation to produce discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, combined VLF + DLF, or combined VLF + DC/CST. Open-field BBB scores and tcMMEPs were studied at 1, 2, 3, and 4 weeks postlesion. VLF lesions resulted in mean BBB scores of 17 at 4 weeks. VLF + DC/CST and VLF + DLF lesions resulted in mean BBB scores of 15.9 and 11.1, respectively. TcMMEPs were absent in all lesion types confirming VLF conduction blockade throughout the study. Our data indicate that significant contributions to locomotion from myelinated pathways within the rat DLF can be revealed when combined with simultaneous compromise of the VLF.

Animals↗