Biomedical subjects
A Smith
Publications and source records attributed to A Smith.
Observation of assembly of fluorescent Si nanoparticles under the influence of electric current.
A silicon substrate patterned by an oxide is immersed in an alcohol solution of low-doped 1-nm Si nanoparticles. Reverse biasing draws particles to the substrate, mostly along the conducting current paths. Scanning electron and fluorescence microscopy show a tree-like network on the substrate. Avoidance of closed loops and preference for an angle of branching of 90 degrees-120 degrees are observed. The building block of the tree network is not individual particles but spherical particle aggregates approximately 150 nm in diameter.
What can wound fluids tell us about the venous ulcer microenvironment?
Research into the healing of venous leg ulcers is increasing as they are a common problem. The wound fluid bathing an ulcer is thought to reflect the wound microenvironment, and the properties of wound fluids have been studied in attempts to find ways to promote healing. After a brief summary of normal wound healing, this article reviews some of the research that has been carried out on venous ulcer wound fluid, with respect to its biochemistry, proteolytic nature, growth factor profile, and effects on cell cultures. Some of the problems and pitfalls inherent in performing and interpreting wound fluid studies are discussed. Finally, a proposal is made for standardizing research on wound fluids that would improve comparisons between different studies.
Meniscofemoral ligaments revisited. Anatomical study, age correlation and clinical implications.
The meniscofemoral ligaments were studied in 84 fresh-frozen knees from 49 cadavers. Combined anterior and posterior approaches were used to identify the ligaments. In total, 78 specimens (93%) contained at least one meniscofemoral ligament. The anterior meniscofemoral ligament (aMFL) was present in 62 specimens (74%), and the posterior meniscofemoral ligament (pMFL) in 58 (69%). The 42 specimens (50%) in which both ligaments were present were from a significantly younger population than that with one MFL or none (p < 0.05). Several anatomical variations were identified, including oblique fibres of the posterior cruciate ligament (PCL), which were seen in 16 specimens (19%). These were termed the 'false pMFL'. The high incidence of MFLs and their anatomical variations should be borne in mind during arthroscopic and radiological examination of the PCL. It is important to recognise the oblique fibres of the PCL on MRI in order to avoid wrongly identifying them as either a pMFL or a tear of the lateral meniscus. The increased incidence of MFLs in younger donors suggests that they degenerate with age.
Intraoperative measurement of knee kinematics in reconstruction of the anterior cruciate ligament.
Our objectives were to establish the envelope of passive movement and to demonstrate the kinematic behaviour of the knee during standard clinical tests before and after reconstruction of the anterior cruciate ligament (ACL). An electromagnetic device was used to measure movement of the joint during surgery. Reconstruction of the ACL significantly reduced the overall envelope of tibial rotation (10 degrees to 90 degrees flexion), moved this envelope into external rotation from 0 degrees to 20 degrees flexion, and reduced the anterior position of the tibial plateau (5 degrees to 30 degrees flexion) (p < 0.05 for all). During the pivot-shift test in early flexion there was progressive anterior tibial subluxation with internal rotation. These subluxations reversed suddenly around a mean position of 36 +/- 9 degrees of flexion of the knee and consisted of an external tibial rotation of 13 +/- 8 degrees combined with a posterior tibial translation of 12 +/- 8 mm. This abnormal movement was abolished after reconstruction of the ACL.
Description and simulation of an active imaging technique utilizing two speckle fields: root reconstructors.
Quasi-monochromatic light will form laser speckle upon reflection from a rough object. This laser speckle provides information about the shape of the illuminated object. Further information can be obtained if two colors of coherent light are used, provided that the colors are sufficiently close in wavelength that the interference is also measurable. It is shown that no more than two intensities of two speckle patterns and their interference are required to produce an unambiguous band-limited image of an object, to within an overall spatial translation of the image, in the absence of measurement errors and in the case where all roots of both fields and their complex conjugates are distinct. This result is proven with a root-matching technique, which treats the electric fields as polynomials in the pupil plane, the coefficients of which form the desired complex object. Several root-matching algorithms are developed and tested. These algorithms are generally slow and sensitive to noise. So motivated, several other techniques are applied to the problem, including phase retrieval, expectation maximization, and probability maximization in a sequel paper [J. Opt. Soc. Am. A 19, 458 (2002)]. The phase-retrieval and expectation-maximization techniques proved to be most effective for reconstructions of complex objects larger than 10 pixels across.
Description and simulation of an active imaging technique utilizing two speckle fields: iterative reconstructors.
Quasi-monochromatic light will form laser speckle upon reflection from a rough object. This laser speckle provides information about the shape of the illuminated object. In a prior paper [J. Opt. Soc. Am. A 19, 444 (2002)], it was shown that two intensities of two speckle patterns and their interference are sufficient to produce an unambiguous (except for object translation) band-limited image of the object, based on a root-matching technique described therein, in the absence of measurement error and in the case of distinct roots of the field polynomials and their complex conjugates. On the other hand, algorithms based on the root-matching technique are found to be slow and sensitive to noise. So motivated, several other techniques are applied to the problem, including phase retrieval, expectation maximization, and statistical maximization. The phase-retrieval and expectation-maximization techniques proved to be most effective for reconstructions of complex objects larger than 10 pixels across, and high-quality images were formed by using three independent sets of two-field data (three frames of two-wavelength data), each comprising two speckle intensity patterns and their interference. Two additional results of note are reported. First, the expectation-maximization algorithm produced relatively good images when three or more frames each of only one speckle intensity pattern (data at just one wavelength) were used and second, the phase-retrieval algorithm when only the object autocorrelation was used also produced relatively good images for the chosen test object.
Efficacy of oral sulfadimethoxine against two gregarine parasites, Protomagalhaensia granulosae and Gregarina cubensis (Apicomplexa: Eugregarinida), infecting the Death's Head cockroach, Blaberus discoidalis.
Gregarines are common parasites of insects in culture, but no effective chemotherapeutic or prophylactic control protocol has been demonstrated. Sulfadimethoxine was administered in 5- and 7-day treatments to Death's Head cockroaches (Blaberus discoidalis) infected with Gregarina cubensis and Protomagalhaensia granulosae to test the efficacy of this sulfonamide against gregarine infection. Sulfadimethoxine significantly reduced the mean intensity of both G. cubensis and P. granulosae. Sulfadimethoxine treatment reduced gregarine intensity by 80% to 85% but had no significant effect on gametocyst production, suggesting that sulfonamide toxicity is directed primarily at sporozoites, trophozoites, and perhaps young gamonts. The possible use of sulfadimethoxine to produce gregarine-free insect cultures and the potential utility of gregarines as target organisms for screening pharmacologically active compounds for use against other intestinal apicomplexans are discussed.
Tuberculosis in the Republic of Ireland at the end of the 1990s.
There has been limited detailed epidemiological data available on tuberculosis in the Republic of Ireland. The 1998 and 1999 National TB Reports produced by the National Disease Surveillance Centre presented disaggregate national data describing in detail the epidemiology of TB in the Republic of Ireland. Individual case notifications were collated by health boards, forwarded to NDSC where they were entered onto a national TB database and then analysed using Epi-Info. There were 893 cases of TB notified in 1998-1999. It was more common in older age groups and men. 50% of cases occurred in those less than 45 years, an indication of considerable ongoing transmission of tuberculosis. Regional variation in the rate of TB exists and a relatively small proportion of cases occurred in foreign-born patients. TB in HIV positive patients was not common and MDR-TB has also been observed. TB has not disappeared from the Republic of Ireland. Treatment, contact tracing and surveillance need to be maintained and preferably enhanced.
Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation.
BACKGROUND: Successful engraftment of hematopoietic stem cells from unrelated donors is influenced by disparities between the donor and recipient for HLA-A, B, and C alleles. Disparities between HLA sequence polymorphisms that are serologically detectable are termed antigen mismatches, whereas those that can be identified only by DNA-based typing methods are termed allele mismatches. Whether both kinds of polymorphisms are important in transplantation is not known. We tested the hypothesis that allele mismatches that are detectable only at the DNA level are less immunogenic than those that are serologically detectable and thereby are associated with a lower risk of graft failure after hematopoietic-cell transplantation METHODS: We used DNA sequencing to define the HLA-A, B, and C alleles in 471 patients who received bone marrow from unrelated donors for the treatment of chronic myeloid leukemia after myeloablative conditioning therapy. The odds ratios for graft failure were determined for recipients of transplants from donors with a single class I allele mismatch, a single class I antigen mismatch, or two or more class I mismatches, as compared with those with no mismatch RESULTS: A single HLA allele mismatch did not increase the risk of graft failure, whereas a single antigen mismatch significantly increased the risk. The risk was also increased if the recipient was HLA homozygous at the mismatched class I locus or if the donor had two or more class I mismatches CONCLUSIONS: HLA class I antigen mismatches that are serologically detectable confer an enhanced risk of graft failure after hematopoietic-cell transplantation. Transplants from donors with a single class I allele mismatch that is not serologically detectable may be used without an increased risk of graft failure.
Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1.
Dysregulation of imprinted genes on human chromosome 11p15 has been implicated in Beckwith-Wiedemann syndrome (BWS), an overgrowth syndrome associated with congenital malformations and tumor predisposition. The molecular basis of BWS is complex and heterogeneous. The syndrome is associated with alterations in two distinct imprinting domains on 11p15: a telomeric domain containing the H19 and IGF2 genes and a centromeric domain including the KCNQ1OT1 and CDKNIC genes. It has been postulated that disorders of imprinting in the telomeric domain are associated with overgrowth and cancer predisposition, whereas those in the centromeric domain involve malformations but not tumor development. In this study of 125 BWS cases, we confirm the association of tumors with constitutional defects in the 11p15 telomeric domain; six of 21 BWS cases with uniparental disomy (UPD) of 11p15 developed tumors and one of three of the rare BWS subtype with hypermethylation of the H19 gene developed tumors. Most importantly, we find that five of 32 individuals with BWS and imprinting defects in the centromeric domain developed embryonal tumors. Furthermore, the type of tumors observed in BWS cases with telomeric defects are different from those seen in BWS cases with defects limited to the centromeric domain. Whereas Wilms' tumor was the most frequent tumor seen in BWS cases with UPD for 11p15 or H19 hypermethylation, none of the embryonal tumors with imprinting defects at KCNQ1OT1 was a Wilms' tumor. This suggests that distinct tumor predisposition profiles result from dysregulation of the telomeric domain versus the centromeric domain and that these imprinting defects activate distinct genetic pathways for embryonal tumorigenesis.
Validating automated screening for psychological distress by means of computer touchscreens for use in routine oncology practice.
The aim of the study was to confirm the validity of using touchscreen computers for screening for clinically significant levels of distress among cancer patients in routine oncology practice. The Hospital Anxiety and Depression Scale (HADS), EORTC Quality of Life questionnaire (QLQ-C30), Mental Health Inventory-MHI5 and a Concerns Checklist were administered via touchscreen computer to 172 chemotherapy out-patients, twice, 2-4 weeks apart. A standard psychiatric interview (Present State Examination - PSE) was conducted within a week of the second assessment. On interview, 23% of patients were identified as 'cases'. Using the available data (questionnaires, sociodemographic details, self-reported past psychiatric history), the best screening strategy combined scores from MHI-5 and HADS from a single time-point with the following rules: if MHI-5 < 11 = non-case; if MHI-5 > or = 11 then use HADS; then, if HADS > or = 9 = 'case' (sensitivity 85%; specificity 71%; misclassification rate 26%; positive predictive value 47%). The computerized screening system enabled data to be collected, scored, collated and reported in real time to identify patients who warrant further clinical assessment. It offers the potential for improving 'case' detection in routine oncology practice while reducing the burden of questions put to 'non-cases'. Further work is needed to develop optimal choice of screening questions for this purpose.
Search for the familon via B(+/-) --> pi+/-X(0), B(+/-) --> K(+/-)X(0), and B(0) --> K(0)(S)X(0) decays.
We have searched for the two-body decay of the B meson to a light pseudoscalar meson h = pi(+/-),K+/-,K(0)(S) and a massless neutral feebly interacting particle X(0) such as the familon, the Nambu-Goldstone boson associated with a spontaneously broken global family symmetry. We find no significant signal by analyzing a data sample containing 9.7x10(6) BBbar mesons collected with the CLEO detector at the Cornell Electron Storage Ring, and set 90% C.L. upper limits italicB(B(+/-) --> h(+/-)X(0)) = 4.9x10(-5) and italicB(B(0) --> K(0)(S)X(0)) = 5.3x10(-5). These limits correspond to a lower bound of approximately 10(8) GeV on the family symmetry breaking scale with vector coupling involving the third generation of quarks.
Hydroxyurea does not enhance the anti-HIV activity of low-dose tenofovir disoproxil fumarate.
Tenofovir disoproxil fumarate (DF) is an adenosine analogue with significant activity against HIV-1. Hydroxyurea decreases the intracellular concentrations of deoxyadenosine triphosphate, the active metabolite of adenosine. We therefore tested the hypothesis that hydroxyurea could enhance the anti-HIV activity of low-dose tenofovir in vivo. Eight patients received tenofovir DF, 75 mg, plus hydroxyurea, 500 mg bid, for 28 days. Changes in plasma HIV RNA levels were compared with a previously studied cohort of patients treated with tenofovir DF, 75 mg once daily ( n = 8), or tenofovir placebo ( n = 12). The median change in HIV RNA levels after 28 days of continuous treatment was -0.01 log(10) copies/ml for tenofovir placebo, -0.33 log(10) copies/ml for tenofovir 75 mg once daily, and -0.22 log(10) copies RNA/ml for tenofovir plus hydroxyurea. The difference between placebo and tenofovir-treated groups was significant ( p <.05); however, the difference between the tenofovir and tenofovir plus hydroxyurea groups was not significant ( p =.90). We conclude that hydroxyurea does not significantly enhance the antiviral activity of low-dose tenofovir.
Pneumoperitoneum augmented tumor invasiveness is abolished by matrix metalloproteinase blockade.
BACKGROUND: Certain surgical strategies, including Helium (He) and carbon dioxide (CO2) insufflation in laparoscopy, have been shown to induce a hypoxic environment. This may have a significant effect on the invasive capacity of tumor cells and may be a factor in the incidence of port-site metastases seen in patients following laparoscopic resection for malignancy. METHODS: A colon adenocarcinoma cell line (SW1222) was exposed to an in vitro pneumoperitoneum of CO2 or He at 3 mmHg or left in normal growth conditions (control). After a 4-hour exposure to an in vitro pneumoperitoneum, the ability of the cells to invade through 8.0-microm Transwell filters coated with Matrigel was analyzed by colorimetric MTS assay and by direct staining of the filters. The effect of the addition of a known blocker of matrix metalloproteinases (MMPs), 1,10-phenanthroline (1,10-P), was investigated. RESULTS: Cells exposed to an in vitro pneumoperitoneum demonstrate significantly increased invasive capacity compared to the control set, without loss of viability (He vs control, p <0.001; CO2 vs control, p <0.001). This augmented capacity is abolished by the addition of 1,10-P (p <0.01). CONCLUSION: Exposure of a colonic adenocarcinoma cell line to either a CO2 or He pneumoperitoneum causes an increase in tumor cell invasiveness, which is abolished by the presence of a known inhibitor of MMPs. This suggests that MMPs have an important role in the metastatic potential of tumors exposed to a hypoxic operative environment.
Preoperative assessment: from tribalism to cooperation.
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Patient passports would alert doctors to previous bone marrow transplantation.
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