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M R Smith

Publications and source records attributed to M R Smith.

At least 19 recordsLinked to original sources
PubMed2006

Is correction necessary when clinically determining quantitative cerebral perfusion parameters from multi-slice dynamic susceptibility contrast MR studies?

Several groups have modified the standard singular value decomposition (SVD) algorithm to produce delay-insensitive cerebral blood flow (CBF) estimates from dynamic susceptibility contrast (DSC) perfusion studies. However, new dependences of CBF estimates on bolus arrival times and slice position in multi-slice studies have been recently recognized. These conflicting findings can be reconciled by accounting for several experimental and algorithmic factors. Using simulation and clinical studies, the non-simultaneous measurement of arterial and tissue concentration curves (relative slice position) in a multi-slice study is shown to affect time-related perfusion parameters, e.g. arterial-tissue-delay measurements. However, the current clinical impact of relative slice position on amplitude-related perfusion parameters, e.g. CBF, can be expected to be small unless any of the following conditions are present individually or in combination: (a) high concentration curve signal-to-noise ratios, (b) small tissue mean transit times, (c) narrow arterial input functions or (d) low temporal resolution of the DSC image sequence. Recent improvements in magnetic resonance (MR) technology can easily be expected to lead to scenarios where these effects become increasingly important sources of inaccuracy for all perfusion parameter estimates. We show that using Fourier interpolated (high temporal resolution) residue functions reduces the systematic error of the perfusion parameters obtained from multi-slice studies.

Brain↗
PubMed2006

Regulation of osteoblast gene expression and phenotype by polylactide-fatty acid surfaces.

Cell function is influenced by surface structure and molecules. Molecules that enhance cellular differentiation can be applied to tissue scaffold surfaces to stimulate endogenous tissue regeneration. The application of this approach to bone implants yields surfaces coated with factors (proteins, peptides, etc...) that promote the differentiation of osteoblasts, the cells that make bone. Increased bone formation leads to increased healing and union of the implant with endogenous bone. To obtain better control over surface coating we developed PLLA copolymers with allyl (PLLA-co-DAG) and 3-hydroxypropyl (PLLA-co-HP) side chains to which we can attach functional groups. Given the potential of fatty acids being able to incorporate into lipid bilayers and/or influence gene expression, we grafted different fatty acid side chains to PLLA-co-HP by esterifying the corresponding fatty acids with the PLLA-co-HP 3-hydroxypropyl side chains. The effects of the polymer modifications on osteoblasts were then evaluated. While cellular morphology differed between surface coatings, they did not reflect changes in cellular phenotype. Changes in gene expression were most evident with arachidonate and 3-hydroxypropyl side-chains which exhibited osteoblast differentiating capabilities. Linoleate, myristate, oleate, and stearate ester side-chains did not have a significant influence on osteoblast phenotype. Growth characteristics of osteoblasts did not differ between the fatty acid copolymer films, although cells grown on PLLA-co-HP exhibited a trend toward increased growth. Taken together our findings demonstrate that surface fatty acid composition can impact osteoblast phenotype.

Animals↗
PubMed2004

Removing the effect of SVD algorithmic artifacts present in quantitative MR perfusion studies.

Quantitative cerebral blood flow (CBF) values can be obtained from dynamic susceptibility contrast (DSC) MR perfusion studies using the standard singular value decomposition (sSVD) deconvolution algorithm. Reports in the literature from simulation and in vivo studies suggest that CBF estimates obtained using sSVD deconvolution depend on the arterial-tissue delay (ATD). By contrast, Fourier transform (FT) deconvolution produces CBF estimates that are independent of ATD. The diagnostic reliability of quantitative CBF measurements to define areas of normal tissue flow and tissue at risk is brought into doubt by such gross sensitivity to the specifics of the deconvolution approach. This variation of CBF values with ATD is shown to be an artifact associated with the current implementation of the sSVD deconvolution algorithm. A reformulated version of the SVD deconvolution algorithm (rSVD) is presented and compared to the standard SVD algorithm through simulation and patient case studies.

Algorithms↗
PubMed2004

Finasteride and bicalutamide as primary hormonal therapy in patients with advanced adenocarcinoma of the prostate.

BACKGROUND: Medical or surgical castration is effective in advanced prostate cancer but with profound side-effects, particularly on sexual function. Effective, less toxic therapies are needed. This study examined whether the addition of finasteride to high-dose bicalutamide enhanced disease control, as measured by additional decreases in serum prostate-specific antigen (PSA). PATIENTS AND METHODS: Forty-one patients with advanced prostate cancer received bicalutamide (150 mg/day). Finasteride (5 mg/day) was added at first PSA nadir. Serum PSA was measured every 2 weeks until disease progression. Questionnaires were administered to assess sexual function. RESULTS: Median follow-up is 3.9 years. At the first PSA nadir, median decrease in PSA from baseline was 96.5%. Thirty of 41 patients (73%) achieved a second PSA nadir and median decrease of 98.5% from baseline. Median time to each nadir was 3.7 and 5.8 weeks, respectively. Median time to treatment failure was 21.3 months. Toxicities were minor, including gynecomastia. Seventeen of 29 (59%) and 12 of 24 (50%) men had normal sex drive at baseline and at second PSA nadir, respectively. One-third of men had spontaneous erection at both time points. CONCLUSION: Finasteride provides additional intracellular androgen blockade when added to bicalutamide. Duration of control is comparable to castration, with preserved sexual function in some patients.

Adenocarcinoma↗
PubMed2004

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

Animals↗
PubMed2003

Barking up the wrong tree? A survey of dog bite wound management.

OBJECTIVES: Several trials have been published examining the role of antibiotics in dog bite wound management. A meta-analysis of these suggests that there is very little benefit to routine antibiotic prescription in these patients. All papers however incorporated rigorous wound care regimens involving large volume irrigation. METHODS: The authors undertook a telephone survey to investigate wound care and prescribing practice in bite wound management in accident and emergency and minor injury units in the Yorkshire region. RESULTS: Twenty one departments were contacted. Only 10% of departments routinely irrigate these wounds. Antibiotics are prescribed routinely in 71%. CONCLUSIONS: Management of dog bite wounds would not seem to be evidence based in most departments in this sample.

Animals↗
PubMed2001

Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer.

BACKGROUND: Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist. METHODS: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study. RESULTS: In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02). CONCLUSIONS: Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist.

Aged↗
PubMed2001

Regioselective aromatic borylation in an inert solvent.

[reaction: see text]. A protocol for performing Rh catalyzed aromatic borylations in cyclohexane has been devised. Borylation at the 5-position of several 1,3-substituted aromatic species ranging from electron-rich (1,3-(NMe(2))(2)C(6)H(4)) to electron-deficient (1,3-(CF(3))(2)C(6)H(4)) yields the corresponding aryl boronate esters. Veratrole was selectively borylated at the 4-position, thus extending regioselectivity to 1,2-substituted benzenes. Selective borylation at the 3-position of an N-protected pyrrole has also been demonstrated, providing a valuable reagent for cross-coupling reactions in a single step.

Anisoles↗
PubMed2001

Low bone mineral density in hormone-naïve men with prostate carcinoma.

BACKGROUND: The objective of this study was to determine the prevalence of low bone mineral density in men with prostate carcinoma and no history of androgen-deprivation therapy. METHODS: The authors conducted a cross-sectional study in 41 hormone-naïve men with locally advanced, lymph node positive, or recurrent prostate carcinoma and no radiographic evidence of bone metastases. Bone mineral density of the total hip, posterior-anterior (PA) lumbar spine, and lateral lumbar spine was determined by dual-energy X-ray absorptiometry (DXA) using a densitometer. Trabecular bone mineral density of the lumbar spine was determined by quantitative computed tomography (QCT). Bone mineral density results were expressed in standard deviation units relative to young adult men (T score) and relative to age-matched men (Z score). RESULTS: Fourteen of 41 men (34%; 95% confidence interval [95% CI], 20-51%) had T scores < -1.0 at one or more skeletal sites by DXA, 12 of 41 men (29%; 95% CI, 16-42%) had T scores between -1.0 and -2.5, and 2 of 41 men (5%; 95% CI, 1-17%) had T scores < -2.5. Thirty-nine of 41 men (95%; 95% CI, 83-99%) had T scores < -1.0 by QCT, 13 of 41 men (31%; 95% CI 18-48%) had T scores between -1.0 and -2.5, and 26 of 41 men (63%; 95% CI, 47-78%) had T scores < -2.5. T scores for trabecular bone mineral density of the lumbar spine were significantly lower than T scores for either the total hip (P < 0.001) or the PA lumbar spine (P < 0.001). The mean Z score for trabecular bone mineral density of the lumbar spine was -0.7 +/- 0.9. Hypogonadism, hypovitaminosis D, and dietary calcium intakes below the Recommended Daily Allowance were observed in 20%, and 17%, and 59% of study participants, respectively. CONCLUSIONS: Many hormone-naïve men with prostate carcinoma have low bone mineral density. QCT is a more sensitive method than DXA for diagnosing low bone mineral density in this patient population. Trabecular bone mineral density is lower than expected for age and risk factors for osteoporosis are common.

Age Factors↗
PubMed2001

Non-destructive quantitation of spermine in human prostate tissue samples using HRMAS 1H NMR spectroscopy at 9.4 T.

We present the results of a study of human prostate specimens evaluated by high resolution magic angle spinning (1)H nuclear magnetic resonance (NMR) spectroscopy at 400 MHz (9.4 T) and by quantitative histopathology. We demonstrate that NMR and pathology data can be obtained from the same intact specimens, and report for the first time a linear correlation between the NMR measured concentration of spermine, a proposed endogenous inhibitor to prostate cancer growth, and the volume percentage of normal prostatic epithelial cells as quantified by histopathology. Our results show that NMR may serve as a critical tool for the investigation of the inhibitory mechanism of spermine in human subjects.

Humans↗
PubMed2001

Lead poisoning of waterfowl by contaminated sediment in the Coeur d'Alene River.

The Coeur d'Alene River basin in Idaho has been contaminated by mine tailings that have impaired the health of wildlife since the early 1900s. In other parts of the world, virtually all lead poisoning of waterfowl is caused by the ingestion of manmade lead artifacts, primarily spent lead shotshell pellets or, occasionally, fishing sinkers. However, in the Coeur d'Alene River basin in Idaho, nonartifactual lead poisoning was the ultimate cause of death of most of 219 (77%) of 285 waterfowl carcasses that had been found sick or dead from 1992 through 1997. The majority of these 219 waterfowl (172 tundra swans [Cygnus columbianus], 33 Canada geese [Branta canadensis], and 14 other species) were poisoned by ingesting river sediment that was contaminated with lead. The next most common cause of death (20 instances, 7%) was lead poisoning accompanied by ingested shotshell pellets. The remaining 46 waterfowl succumbed to trauma, infectious diseases (aspergillosis, avian cholera, tuberculosis), or miscellaneous problems, or the cause of death was not determined.

Animals↗
PubMed2001

Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: a preliminary report.

Effective treatment options for high-risk localized prostate cancer are limited. Patients at high risk for recurrence include those with biopsy Gleason scores of 8 to 10, prostate specific antigen (PSA) levels > 20 ng/mL, and clinical stage T3 disease. Docetaxel chemotherapy is active in hormone-refractory prostate cancer, either combined with estramustine or used as a single agent. To determine if systemic therapy can improve the outcome of radical prostatectomy in men with high-risk localized prostate cancer, we are undertaking a pilot phase II clinical trial of weekly docetaxel at 36 mg/m(2) for up to 6 months, followed by surgery. Patients are monitored with weekly visits, monthly digital rectal examinations, PSA measurement, and testosterone tests, and endorectal magnetic resonance imaging done at baseline, after two cycles, and again after six cycles. To date, 15 patients have been enrolled, and 70 cycles of chemotherapy have been administered. Toxicity has been mostly grade 1 in intensity, and fatigue has been the most common grade 2 toxicity reported. The primary endpoint of the trial is measurement of pathologic complete response rate, for which data are not yet available. Recruitment to the trial is ongoing.

Adenocarcinoma↗
PubMed2001

A gain-of-function mutation in the sodium channel gene Scn2a results in seizures and behavioral abnormalities.

The GAL879-881QQQ mutation in the cytoplasmic S4-S5 linker of domain 2 of the rat brain IIA sodium channel (Na(v)1.2) results in slowed inactivation and increased persistent current when expressed in Xenopus oocytes. The neuron-specific enolase promoter was used to direct in vivo expression of the mutated channel in transgenic mice. Three transgenic lines exhibited seizures, and line Q54 was characterized in detail. The seizures in these mice began at two months of age and were accompanied by behavioral arrest and stereotyped repetitive behaviors. Continuous electroencephalogram monitoring detected focal seizure activity in the hippocampus, which in some instances generalized to involve the cortex. Hippocampal CA1 neurons isolated from presymptomatic Q54 mice exhibited increased persistent sodium current which may underlie hyperexcitability in the hippocampus. During the progression of the disorder there was extensive cell loss and gliosis within the hippocampus in areas CA1, CA2, CA3 and the hilus. The lifespan of Q54 mice was shortened and only 25% of the mice survived beyond six months of age. Four independent transgenic lines expressing the wild-type sodium channel were examined and did not exhibit any abnormalities. The transgenic Q54 mice provide a genetic model that will be useful for testing the effect of pharmacological intervention on progression of seizures caused by sodium channel dysfunction. The human ortholog, SCN2A, is a candidate gene for seizure disorders mapped to chromosome 2q22-24.

Animals↗
PubMed2001

Complementary and alternative therapies for advanced prostate cancer.

This article reviews complementary and alternative therapies for advanced prostate cancer. This is not a comprehensive survey of nontraditional therapies for prostate cancer. Rather, this review focuses on alternative and complementary therapies with published studies to evaluate efficacy and safety. Three areas are addressed: alternative forms of hormonal therapy, management of side effects of hormonal therapy, and management of skeletal complications.

Acupuncture↗