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Biomedical subjects

K M Miller

Publications and source records attributed to K M Miller.

At least 37 records · Page 2Linked to original sources
PubMed2000

Approach to colon polyps in the elderly.

Colorectal cancer is a common but potentially preventable disease. Nearly all colorectal cancers are thought to arise from adenomatous polyps. The conclusions from the National Polyp Study strongly support the concept that the removal of polyps may prevent the future development of colorectal cancer. With the growing acceptance of screening for colorectal cancer, many elderly patients with adenomatous polyps will be discovered. Because increasing age is a powerful determinant of a higher prevalence of colonic neoplasia in asymptomatic individuals, physicians will need to be prepared to make informed decisions regarding the treatment of elderly patients with colonic polyps. The literature is reviewed and guidelines are formed regarding the optimal surveillance interval for patients with colonic polyps. The age at which surveillance and screening for colorectal neoplasia should stop is also reviewed. Conclusions are based on the currently available data.

Aged↗
PubMed1999

Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy.

OBJECTIVE: To determine the expression pattern and cellular source of matrix metalloproteinases (MMPs) in chronic inflammatory demyelinating polyneuropathy (CIDP) and nonsystemic vasculitic neuropathy (NSVN). BACKGROUND: MMPs are endopeptidases involved in tissue destruction and infiltration by immune cells in multiple sclerosis and Guillain-Barré syndrome. Enzyme inhibitors of MMPs attenuate clinical symptoms in corresponding animal models of these diseases. MMP inhibition may therefore be a novel approach for the treatment of CIDP and NSVN. However, the spectrum of MMPs expressed in chronic inflammatory neuropathies has not been established. METHODS: The expression of MMP-2, MMP-3, MMP-7, and MMP-9 in T cells, macrophages, and stromal cells in CIDP, NSVN, and noninflammatory neuropathies (NIN) was quantitated by immunohistochemistry. Results were correlated with clinical and electrophysiologic findings. RESULTS: The production of MMP-2 and MMP-9 is increased in nerve tissue in CIDP and NSVN compared with NIN. T cells are the predominant source of MMP-2 and MMP-9 in CIDP and NSVN, whereas macrophages contribute only to a minor extent. Stromal cells of the perineurium/epineurium are an additional source of MMP-2 in NSVN, but not in CIDP. Expression of MMP-3 and MMP-7 was not detectable in CIDP or NSVN. Expression of MMP-2 and MMP-9 did not correlate with clinical disease activity and electrophysiologic measurements. CONCLUSIONS: The upregulation of MMP-2 and MMP-9 is a specific feature of CIDP and NSVN, and selective inhibitors of these enzymes could be used to prevent inflammatory tissue damage. The similar increase of MMP-2 and MMP-9 in both demyelinating (CIDP) and nondemyelinating (NSVN) neuropathies raises doubts about whether MMPs play a primary role in demyelination.

Adult↗
PubMed1999

A central role for astrocytes in the inflammatory response to beta-amyloid; chemokines, cytokines and reactive oxygen species are produced.

Alzheimer's disease (AD) is the commonest form of adult onset dementia and is characterised neuropathologically by the accumulation of plaques containing beta-amyloid (A beta) fibrils, reactive astrocytes, activated microglia, and leukocytes. A beta plays a role in the pathology of AD by directly causing neuronal cytotoxicity and stimulating microglia to secrete cytokines and reactive oxygen species (ROS) which also damage neurons. Here, we demonstrate that A beta activates astrocytes and oligodendrocytes (the most common cell types in the brain) to produce chemokines, in particular MCP-1 and RANTES, which serve as potent in vitro microglial and macrophage chemoattractants. Furthermore, we have shown that A beta activates astrocytes to upregulate pro-inflammatory cytokine expression and enhances the production of ROS. We propose therefore that A beta-mediated astrocyte activation initiates an inflammatory cascade which could be targeted for therapeutic intervention in AD.

Alzheimer Disease↗
PubMed1999

Randomized clinical comparison of Healon GV and Viscoat.

PURPOSE: To compare the ability of Healon GV (sodium hyaluronate 1.4%) and Viscoat (sodium chondroitin sulfate 4.0%-sodium hyaluronate 3.0%) to protect the corneal endothelium during endocapsular phacoemulsification and foldable intraocular lens (IOL) implantation. SETTING: A small ophthalmology group practice. METHODS: One hundred forty patients were randomized, 70 per group, in a prospective, partially masked study of cataract surgery using Healon GV or Viscoat. One ophthalmologist performed all surgery. Primary outcome variables were the 2 week postoperative changes in corneal thickness, endothelial cell density, mean endothelial cell size, and endothelial cell hexagonality. Several secondary variables were measured, and an analysis of the statistical power of the study was performed. RESULTS: There were no statistically significant differences between groups in terms of age (P = .856), cataract density (P = .117), preoperative best corrected visual acuity (BCVA) (P = .892), postoperative BCVA (P = .969), amount of viscoelastic material used during surgery (P = .444), amount of irrigating solution used (P = .125), or phacoemulsification time (P = .088). It took longer to remove the Viscoat than the Healon GV (P < .001), and total operating time for the Viscoat group was longer (P < .001). Two weeks after surgery, there were no significant differences between groups in corneal thickness (P = .362), endothelial cell density (P = .351), or mean endothelial cell size (P = .610). However, Viscoat preserved the hexagonal shape of endothelial cells slightly better than Healon GV (P = .043). The study had sufficient power to detect clinically significant differences in corneal thickness, endothelial cell density, and endothelial cell size. CONCLUSIONS: Healon GV and Viscoat were comparable in their ability to protect the corneal endothelium during endocapsular phacoemulsification and foldable IOL implantation. Results may vary, however, if phacoemulsification is performed anterior to the iris plane.

Aged↗
PubMed1999

Use of a preanesthetic video for facilitation of parental education and anxiolysis before pediatric ambulatory surgery.

UNLABELLED: In this study, we evaluated the effects of viewing an educational videotape about pediatric anesthesia on measures of parental knowledge of anesthesia and preoperative anxiety using a randomized, controlled design. During their routine preoperative visit, 85 parents of children scheduled to undergo ambulatory surgical procedures under general anesthesia were randomized to view either the experimental videotape about pediatric anesthesia or a control videotape with no medical content. Before and immediately after viewing the assigned videotape, parents completed measures of situational anxiety (State-Trait Anxiety Inventory-State), preoperative anxiety and need for information (Amsterdam Preoperative Anxiety and Information Scale), and anesthesia knowledge (Standard Anesthesia Learning Test). Repeated-measures analyses of variance showed that parents who viewed the experimental videotape showed a significant increase in anesthesia knowledge (P < 0.022) and a significant reduction in their state of anxiety (P < 0.031), anesthesia-specific anxiety, and need for information (P < 0.0001) compared with the control group. These results demonstrated that viewing a preoperative educational videotape about pediatric anesthesia can provide immediate educational and anxiolytic benefits for parents of children undergoing ambulatory surgery. The duration of these benefits remains to be determined. IMPLICATIONS: In this study, we demonstrated the benefits of viewing an educational videotape about pediatric anesthesia on measures of parental knowledge of anesthesia and preoperative anxiety using a randomized, controlled design. We found that videotape viewing facilitated preoperative preparation and lessened preoperative anxiety.

Ambulatory Surgical Procedures↗
PubMed1999

Validation of measures of parents' preoperative anxiety and anesthesia knowledge.

UNLABELLED: Parents' anxiety about their children's anesthesia may adversely affect the children's outcomes and compromise the quality of informed consent. Studies of these issues have been limited by the lack of validated measures of parental anxiety and knowledge surrounding anesthesia. In the present study, we evaluated psychometric properties of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the Standard Anesthesia Learning Test (SALT) among 85 parents who participated in an evaluation of the effects of a videotape about pediatric anesthesia. The results supported the internal consistency, test-retest reliability, and concurrent validity of both instruments and documented the equivalence of two forms of the SALT. Factor analysis supported the previously demonstrated factor structure of the APAIS, further confirming its construct validity. We conclude that the APAIS and SALT are reliable and valid measures of parental anxiety and knowledge of pediatric anesthesia that can be used for clinical and research purposes. IMPLICATIONS: This study verified the reliability and validity of two questionnaires for measuring parents' knowledge and anxiety about pediatric anesthesia. These questionnaires can be used in further research on factors affecting parental anxiety and knowledge before their children's surgery.

Ambulatory Surgical Procedures↗
PubMed1999

Denaturing gradient gel electrophoresis (DGGE): a rapid and sensitive technique to screen nucleotide sequence variation in populations.

We describe a rapid and sensitive method for the detection of nucleotide sequence variation that can be used for large-scale screening of population markers. Denaturing gradient gel electrophoresis (DGGE) detects sequence variants of amplified fragments by the differences in their melting behavior. DGGE detects most single-base substitutions when carried out on products amplified with a primer to which a GC clamp has been added. Although DGGE has been primarily used for the detection of limited numbers of single-base mutations in disease studies, it offers great potential for use in population analysis of genetic markers with greater levels of sequence variation. The methodology described was developed to identify the number and distribution of MHC class I alpha 1 alleles among chinook salmon (Oncorhynchus tshawytscha) populations. DGGE detects 28 of 31 identified alpha 1 sequences, which differ by between 1 and 16 nucleotides and a two-codon indel. By creating a network of control alleles, 22-23 of the MHC alleles can be resolved rapidly and accurately by a single gel run condition, and 27 alleles can be resolved by two gel run conditions. This techniques has been used in surveys scoring alleles from two MHC markers (class I alpha 1 and alpha 2) in 20,000 individuals of chinook and coho (O. kisutch) salmon. A single person in our laboratory now analyzes 160 salmon from one MHC locus per day with DGGE.

Alleles↗
PubMed1998

Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS.

In an experimentally-induced DTH model of MS, we examined mRNA and protein expression of a range of MMPs and of TNFalpha to establish the contribution that individual MMPs might make to the pathogenesis. In control rat brain, mRNA for all of the MMPs examined was detectable. However, by immunohistochemistry, only MMP-2 could be detected. In the DTH lesions, significant increases in the level of mRNA expression were observed for MMP-7, MMP-8, MMP-12, and TNFalpha. Where expression of MMP mRNA was increased, there was a corresponding increase in protein expression detected by immunohistochemistry. To determine whether the upregulated MMPs could invoke destructive events in the CNS, highly purified activated MMP-7, MMP-8, and MMP-9 were stereotaxically injected into the brain parenchyma. All provoked recruitment of leukocytes and BBB breakdown. In addition, MMPs 7 and 9 induced loss of myelin staining. In conclusion, specific MMPs are upregulated in DTH lesions; for the most part, measurement of mRNA was a predictor of increased protein expression. From our injections of MMPs, it is clear that the upregulated MMPs in the DTH lesions could participate in the disruption of the BBB, leukocyte recruitment, and tissue damage.

Animals↗
PubMed1998

Determination of transport parameters of permeant substrates of the vesicular amine transporter.

Biological transport of moderately permeant compounds is obscured by diffusion of the compounds back across the membrane, so characterization of the transport of such compounds requires correction for permeability. A relatively simple method for determining kinetic parameters for moderately permeant compounds is presented here. After evaluating a compound's apparent permeability coefficient, its steady-state uptake is measured as a function of concentration. By comparing the concentration dependence of uptake measured both in the presence and in the absence of a complete inhibitor of the transporter, K(m) and Vmax for transport of that substrate may be calculated. When used to analyze transport of tyramine and hydroxyephedrine by the vesicular amine transporter, this method yields results consistent with other methods and with values for analogous impermeant substrates. In bovine adrenal chromaffin vesicles, tyramine and (-)erythro-hydroxyephedrine have apparent permeability coefficients of 4.7 +/- 1.0 x 10(-9) and 1.1 +/- 0.4 x 10(-8) cm/s, respectively. Values for K(m) are 15 +/- 9 and 34 +/- 14 microM and for Vmax are 1.3 +/- 0.2 and 1.4 +/- 0.9 nmol/min.mg of membrane protein, respectively.

Adrenal Medulla↗
PubMed1998

Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors.

The proinflammatory Th1 cytokine, tumor necrosis factor-alpha (TNF alpha), the cell death signaling molecule FasL, and several extracellular matrix degrading metalloproteinases have been implicated in the pathogenesis of multiple sclerosis (MS). The latter enzymes, as well as TNF alpha-converting enzyme and FasL-converting enzyme, can be blocked by matrix metalloproteinase inhibitors (MMPIs). In this study, we show that a potent MMPI was clinically effective in an animal model for MS, experimental autoimmune encephalomyelitis (EAE) in the SJL/J mouse. Efficacy was remarkable, as indicated by blocking and reversal of acute disease and reduced number of relapses and diminished mean cumulative disease score in chronic relapsing animals. Also, demyelination and glial scarring were significantly decreased in MMPI-treated mice with chronic relapsing EAE, as was central nervous system gene expression for TNF alpha and fasL. It is interesting that expression of the beneficial cytokine interleukin-4 (IL-4) was increased, and IL-4 was expressed on glial cells. The relevance of these compounds for MS was underscored by their ability to specifically inhibit TNF alpha shedding and cytotoxicity of myelin-autoreactive human cytotoxic CD4+ T-cell clones. This is the first report to show a positive effect by MMPIs on chronic relapsing EAE, its central nervous system cytokine profile, and on TNF alpha shedding by human myelin-autoreactive T cells.

Animals↗
PubMed1998

Phacoemulsification and lens implantation after pars plana vitrectomy.

OBJECTIVE: This study aimed to describe the intraoperative and postoperative complications and visual acuity outcomes of patients undergoing Kelman phacoemulsification (KPE) and intraocular lens (IOL) implantation after pars plana vitrectomy (PPV). DESIGN: The study design was a retrospective review of a consecutive surgical series. PARTICIPANTS: Forty-four eyes of 43 patients who underwent surgery at the Jules Stein Eye Institute, Los Angeles, California, or Advanced Vision Care, West Hills, California, were studied. INTERVENTION: Office records, referring retina specialists' records, and operative reports were reviewed for demographic information, indications for PPV, preoperative cataract severity, unplanned intraoperative events and complications, early and late postoperative complications, and postoperative visual acuities. MAIN OUTCOME MEASURES: Complications and postoperative visual acuities were measured. RESULTS: The mean interval from PPV to KPE was 20 months. The mean interval from KPE to final examination was 19 months. Primary indications for PPV included development of a macular epiretinal membrane, macular hole, proliferative diabetic retinopathy, retinal detachment, vitreous abscess, and vitreous hemorrhage. The degree of nuclear sclerosis in postvitrectomy eyes was greater than that in typical cataract eyes (P = 0.00002). The most common intraoperative problem was the discovery of a posterior capsule plaque. In a few cases, surgery was made difficult by unusual fluctuations in anterior chamber depth and lens zonule instability. The most common early postoperative complication was corneal edema; the most common late complication was the need for neodymium:YAG (Nd:YAG) laser posterior capsulotomy. An IOL was implanted in every eye. There were no retinal detachments. Median visual acuity improved from 20/125 before cataract surgery to 20/40 6 weeks after surgery to 20/30 on final examination. Visual acuity of 20/40 or better was achieved by 63.6% of eyes at 6 weeks and by 72.7% of eyes by final examination. CONCLUSIONS: Kelman phacoemulsification and IOL implantation can be performed safely after PPV. Intraoperative and postoperative complications are uncommon. Pre-existing posterior segment pathology limits the ultimate improvement in visual acuity, but substantial gains in visual acuity are realized by most patients.

Adult↗
PubMed1998

Intraocular pressure change after sutureless phacoemulsification and foldable posterior chamber lens implantation.

PURPOSE: To investigate the effect on intraocular pressure (IOP) of sutureless scleral and corneal tunnel Kelman phacoemulsification (KPE) with foldable posterior chamber intraocular lens (IOL) implantation. SETTING: Jules Stein Eye Institute, Los Angeles, California, USA. METHODS: Preoperative and postoperative (1 and 6 weeks and 6 to 8 months) IOP measurements of 385 consecutive eyes having uneventful phacoemulsification and foldable posterior chamber IOL implantation were reviewed retrospectively. A subset of 193 eyes for which no IOP measurements were missing at any follow-up were analyzed separately. RESULTS: Mean preoperative IOP was 15.8 mm Hg +/- 0.2 (+/- SE). It dropped postoperatively by 1.3 +/- 0.2 mm Hg at 1 week (P < .001), 2.5 +/- 0.2 mm Hg at 6 weeks (P < .001), and 2.2 +/- 0.2 mm Hg at 6 to 8 months (P < .001). Mean preoperative IOP for the subset without missing data was 16.0 +/- 0.3 mm Hg. It decreased by 1.1 +/- 0.3 mm Hg at 1 week (P < .001), 2.3 +/- 0.2 mm Hg at 6 weeks (P < .001), and 2.2 +/- 0.2 mm Hg at 6 to 8 months (P < .001). Wound construction (scleral versus corneal tunnel), anesthesia type (topical versus posterior orbital injection), the eye operated on, and patient age and sex did not significantly influence the postoperative pressure change. Patients with a preoperative diagnosis of glaucoma had significantly higher 1 week postoperative IOPs; however, the differences were statistically insignificant at 6 weeks and 6 to 8 months. CONCLUSION: Sutureless KPE with foldable posterior chamber IOL implantation lowered IOP by 1.1 to 2.5 mm Hg for the 6 months immediately following surgery. Glaucoma patients had a statistically significant initial rise in IOP at 1 week.

Adult↗
PubMed1998

Phacoemulsification and lens implantation in patients treated with aspirin or warfarin.

PURPOSE: To determine the incidence and nature of hemorrhagic complications in patients having phacoemulsification and foldable intraocular lens (IOL) implantation while taking aspirin or warfarin. SETTING: The Jules Stein Eye Institute, University of California at Los Angeles School of Medicine, Los Angeles, California, USA. METHODS: This retrospective study reviewed the charts from the practice of 1 ophthalmic surgeon. The type of medication, dosage, indication for anticoagulant therapy, type of incision, type of anesthesia, and intraoperative and postoperative hemorrhagic complications were recorded. RESULTS: Sixty-two patients (82 eyes) taking aspirin and 25 patients (31 eyes) taking warfarin were identified. Seven eyes in the aspirin group (8.5%) and 3 in the warfarin group (9.7%) experienced subconjunctival hemorrhages. Eight of the 10 subconjunctival hemorrhages occurred in eyes with scleral incisions. The remaining 2 occurred in eyes with corneal incisions. No eye developed lid ecchymosis, retrobulbar hemorrhage, hyphema, or suprachoroidal hemorrhage. CONCLUSIONS: Phacoemulsification with foldable IOL implantation was performed safely in patients taking aspirin or warfarin. Subconjunctival hemorrhage was the most common hemorrhagic complication.

Anticoagulants↗
PubMed1998

Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis.

Matrix metalloproteinases (MMPs) are a family of endopeptidases capable of enzymatic digestion of subendothelial basement membrane and other components of the extracellular matrix. Expression of MMP-2, -3, -7 and -9 is increased around multiple sclerosis plaques and in brain tissue in experimental allergic encephalomyelitis. To measure quantitatively the expression of these MMPs and their endogenous inhibitors (TIMP-1 and -2), we analysed samples from 52 patients with relapsing-remitting and primary progressive multiple sclerosis by ELISA (enzyme-linked immunosorbent assay) and substrate-gel electrophoresis (zymography). MMP-9 was increased over controls in 100% of relapsing-remitting multiple sclerosis cases, with similar levels detected in relapses and clinically stable phases of disease. In primary progressive multiple sclerosis, MMP-9 was increased in 57% of CSF samples, but concentrations were below those encountered in the relapsing-remitting form. The selective upregulation of MMP-9 suggests that T-cells and macrophages invading the brain parenchyma and the CSF space are the predominant source of MMP-9 in multiple sclerosis. TIMPs and other MMPs (MMP-2 and -3) were not upregulated or not detectable (MMP-7) in CSF of patients with relapsing-remitting and primary progressive multiple sclerosis. The sustained increase of MMP-9 in clinically stable multiple sclerosis supports the concept that multiple sclerosis is associated with ongoing proteolysis that may result in progressive tissue damage. The selective inhibition of MMP-9 could be a useful approach for the prevention of disease progression in multiple sclerosis.

Cerebrospinal Fluid↗