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Biomedical subjects

J R Williams

Publications and source records attributed to J R Williams.

At least 19 recordsLinked to original sources
PubMed2001

IUdR polymers for combined continuous low-dose rate and high-dose rate sensitization of experimental human malignant gliomas.

Local polymeric delivery enhances IUdR radiosensitization of human malignant gliomas (MG). The combined low-dose rate (LDR) (0.03 Gy/h) and fractionated high-dose rate (HDR) treatments result in cures of experimental MGs. To enhance efficacy, we combined polymeric IUdR delivery, LDR, and HDR for treatments of both subcutaneous and intracranial MGs. In vitro: Cells (U251 MG) were trypsinized and replated in triplicate 1 day prior to LDR irradiation in media either without (control) or with 10 microM IUdR. After 72 hr, LDR irradiation cells were acutely irradiated (1.1 Gy/min) with increasing (0, 1.25, 2.5, 5.0, or 10 Gy) single doses. Implantable IUdR polymers [(poly(bis(p-carboxyphenoxy)-propane) (PCPP): sebaic acid (PCPP:SA), 20:80] (50% loading; 10 mg) were synthesized. In vivo: For flank vs. intracranial tumors, mice had 6 x 10(6) subcutaneous vs. 2 x 10(5) intracranial cells. For intracranial or subcutaneous MGs, mice had intratumoral blank (empty) vs. IUdR polymer treatments. One day after implantation, mice had immediate external LDR (3 cGy/h x 3 days total body irradiation) or HDR (2 Gy BID x 4 days to tumor site) or concurrent treatments. For the in vitro IUdR treatments, LDR resulted in a striking increase in cell-killing when combined with HDR. For the in vivo LDR treatments of flank tumors, the growth delay was greater for the IUdR vs. blank polymer treatments. For the combined LDR and HDR, the IUdR treatments resulted in a dramatic decrease in tumor volumes. On day 60 the log V/V0 were -1.7 +/- 0.22 for combined LDR + HDR + IUdR polymer (P < 0.05 vs. combined LDR + HDR + blank polymer). Survival for the intracranial controls was 22.9 +/- 1.2 days. For the blank polymer + LDR vs. blank polymer + LDR + HDR treatments, survival was 25.3 +/- 1.7 (P = NS) vs. 48.1 +/- 3.5 days (P < 0.05). For IUdR polymer + LDR treatment survival was 27.3 +/- 2.3 days (P = NS). The most striking improvement in survival followed the IUdR polymer + LDR + HDR treatment: 66.0 + 6.4 days (P < 0.05 vs. blank polymer + LDR + HDR). The polymeric IUdR delivery plus combined continuous LDR and HDR treatments results in growth delay and improved survival in animals bearing the MG xenografts. This treatment may hold promise for the treatment of human MGs.

Animals↗
PubMed2001

Composition dependence of the nucleation energy of iron antimonides from modulated elemental reactants.

Modulated elemental reactants containing iron and antimony were found to react at low temperature (T < 200 degrees C) forming either FeSb(2) or FeSb(3) depending on both the layer thicknesses and the overall composition of the initial reactant. For films containing 75% antimony and 25% iron, the metastable compound FeSb(3) was observed to nucleate and grow if the layer thickness was below approximately 35 A. Above this critical thickness for the modulation, annealing led to the formation of FeSb(2). This, combined with low-angle diffraction data, suggests that the initial interdiffusion between iron and antimony layers in an elementally modulated reactant results in the formation of an amorphous reaction intermediate if the layering thickness is less than 35 A. For modulated reactants with composition between 70 and 90 atomic % antimony and below this critical layer thickness, the metastable compound FeSb(3) formed. In more iron-rich modulated reactants FeSb(2) nucleates. The nucleation temperature and the nucleation energy of FeSb(3) were found to be a function of the composition of the amorphous intermediate, while those of FeSb(2) were found to be relatively independent of composition.

Journal Article↗
PubMed2001

Which primary shoulder and elbow replacement? A review of the results of prostheses available in the UK.

To assist surgeons select a suitable prosthesis, we have undertaken a detailed review of all shoulder and elbow replacements currently marketed in the UK. Twenty shoulder and 8 elbow implants, manufactured by 16 companies, have been identified. Twelve of the shoulder and one of the elbow implants have been introduced or modified in the last 8 years and have no clinical results published in peer-reviewed journals. Only the Biomodular, Bipolar, Copeland, Isoelastic, Neer hemi, Neer II, Roper-Day and Select shoulders accounting for less than 40% of the UK shoulder market, possess published results. The Capitello-condylar, Coonrad-Morrey, GSB III, Kudo, Liverpool, Roper-Tuke and Souter-Strathclyde elbows all have published results. These account for over 95% of all UK elbow replacements. The implications of these findings in an era of evidence-based medicine is discussed. Reviewing the clinical results should be of primary importance in the selection of a suitable prosthesis. Implants with a proven long-term record must represent the 'gold standard'. New or modified implants should only be used if they are part of a properly conducted clinical trial.

Arthroplasty, Replacement↗
PubMed2000

Craniofacial resection for paranasal sinus cancers.

BACKGROUND: Combined anterior craniofacial resection (CFR) has been in use for more than 25 years. The advent of the free revascularized tissue transfer flap in l980 permitted safe resection of tumors that had spread beyond the confines of the paranasal sinuses with immediate reconstruction of the sino-orbital cranial defect. The purpose of this study was to examine the outcomes and morbidity of a management policy of primary CFR and postoperative radiotherapy for paranasal sinus cancers infiltrating the skull base over a 21-year period. METHODS: Seventy-three patients with paranasal sinus cancers were treated at the Prince of Wales Hospital between l975 and l996. All were newly diagnosed with the exception of one patient who had received radiotherapy elsewhere 5 years earlier. Only 22% were early lesions and 31% were advanced (more than six sites involved). There were 59 men and 14 women. The mean age was 57 years. All but two patients had a performance status of either 0 or 1. Orbital exenteration was performed in 31 patients. Since l980, all major defects were reconstructed with free tissue transfer flaps. RESULTS: The 5-year cancer-specific survival (CSS) for the 73 patients was 69%, which was unchanged at 10 years. Twenty two patients died from or with their index cancer. An additional 11 patients died from unrelated causes. The actuarial overall survival (OS) at 5 and 10 years was 61% and 48%, respectively. The 5-year recurrence-free rate was 59%. The CSS for the three dominant pathologic conditions were adenocarcinoma 70%, squamous cancer 51%, and olfactory neuroblastoma 84%. The difference was not significant; however, there was a significant difference in OS, with olfactory neuroblastoma having the best prognosis. Orbital involvement, radiologic evidence of skull base erosion, and involvement of the infratemporal fossa were not poor prognostic indicators. Patients with a performance status of 0 had improved OS. There was no operative mortality. CONCLUSIONS: An aggressive policy of combined CFR and postoperative radiotherapy with free-flap reconstruction for large defects gave survival results that were comparable to less-advanced lesions and superior to many other treatment alternatives. There was a high exenteration rate (42%). Squamous cancers were associated with the greatest morbidity and poorest OS.

Adult↗
PubMed2000

The effects of dehydroepiandrosterone on carcinogenesis, obesity, the immune system, and aging.

With the passage of the U.S. Dietary Supplement Health and Education Act of 1994, dehydroepiandrosterone (DHEA, 5-androsten-3beta-ol-17-one) has become widely available, and a large and growing market has developed for this "fountain of youth." DHEA has been shown to have significant beneficial effects in animals, which may lead to clinical uses in man. Historically, the U.S. Food and Drug Administration removed DHEA from the over-the-counter market in 1985 because there was no support for the health claims that were made for this product. Almost all of the biological data was on animals and there was a lack of demonstrated efficacy in humans. Recently there have been a number of small clinical trials in humans but the results have not been as positive as in the animal tests. This review will be restricted to the effects of DHEA on carcinogenesis, obesity, the immune system, and aging. Four hypotheses have been proposed to explain the underlying biochemical mechanism(s) by which DHEA exerts its beneficial properties. The first is based on the inhibitory effect of DHEA on mammalian glucose-6-phosphate dehydrogenase. This mechanism can explain the antiinitiation and antipromotion steps in some cases of carcinogenesis. The second biochemical mechanism involves the induction of peroxisomes and peroxisome-associated enzymes. The third explanation is that DHEA works in a similar fashion to the known anticarcinogenic action of food restriction. An antiglucocorticoid mechanism has also been suggested. A hypothesis for the increase followed by the decrease in the levels of DHEA with age is proposed. A number of new synthetic DHEA analogs have been synthesized and tested. They offer the best hope for the development of a clinically useful drug based on the properties of DHEA.

Aging↗
PubMed2000

Is impaired outcome following a first manic episode due to mood-incongruent psychosis?

BACKGROUND: Mood-incongruent psychosis during the course of bipolar disorder has been associated with poor outcome. However, it remains unknown whether this is secondary to persistent affective or psychotic symptoms or both. METHOD: Fifty patients with bipolar disorder between the ages of 16 and 45 years were recruited during their first psychiatric hospitalization for mania. These patients were evaluated using structured and semi-structured clinical instruments then followed longitudinally. Outcomes during the first eight months of follow-up were compared between patients with mood-incongruent psychosis and those without (i.e., patients with mood-congruent psychosis or no psychosis) during the index manic episode. Specifically, ratings of the percent of weeks during follow-up with psychosis and affective syndromes and symptoms, as well as ratings of global outcome (GAF), were compared. RESULTS: Patients with mood-incongruent psychosis at the index hospitalization exhibited significantly more weeks during follow-up with both mood-incongruent and mood-congruent psychotic symptoms than patients without mood-incongruent psychosis. Mood-incongruent psychosis was also associated with poorer overall functioning during the outcome interval. The groups did not differ in the percent of weeks with affective syndromes or symptoms. Treatment during follow-up did not differ between groups and was not associated with outcome variables in general. CONCLUSION: Mood-incongruent psychosis that occurs during the first manic episode appears to predict an increased likelihood of persistent psychotic symptoms during the subsequent eight months. This persistence of psychosis is associated with a worse overall course of illness as compared to patients without mood-incongruent psychosis. LIMITATIONS: These results apply to a relatively short outcome period and are from a single center.

Adolescent↗
PubMed2000

Analysis of MIR-18 results for physical and biological dosimetry: radiation shielding effectiveness in LEO.

We compare models of radiation transport and biological response to physical and biological dosimetry results from astronauts on the Mir space station. Transport models are shown to be in good agreement with physical measurements and indicate that the ratio of equivalent dose from the Galactic Cosmic Rays (GCR) to protons is about 3/2:1 and that this ratio will increase for exposures to internal organs. Two biological response models are used to compare to the Mir biodosimetry for chromosome aberration in lymphocyte cells; a track-structure model and the linear-quadratic model with linear energy transfer (LET) dependent weighting coefficients. These models are fit to in vitro data for aberration formation in human lymphocytes by photons and charged particles. Both models are found to be in reasonable agreement with data for aberrations in lymphocytes of Mir crew members: however there are differences between the use of LET dependent weighting factors and track structure models for assigning radiation quality factors. The major difference in the models is the increased effectiveness predicted by the track model for low charge and energy ions with LET near 10 keV/micrometers. The results of our calculations indicate that aluminum shielding, although providing important mitigation of the effects of trapped radiation, provides no protective effect from the galactic cosmic rays (GCR) in low-earth orbit (LEO) using either equivalent dose or the number of chromosome aberrations as a measure until about 100 g/cm 2 of material is used.

Chromosome Aberrations↗
PubMed2000

Sequence variations within PrfA DNA binding sites and effects on Listeria monocytogenes virulence gene expression.

Reporter gene fusions were used to investigate the contributions of PrfA DNA binding sites to Listeria monocytogenes virulence gene expression. Our results suggest that the DNA sequence of PrfA binding sites determines the levels of expression of certain virulence genes, such as hly and mpl. Other virulence genes, such as actA and plcB, may depend upon additional factors for full regulation of gene expression.

Bacterial Proteins↗
PubMed2000

Maternal thyroid deficiency and pregnancy complications: implications for population screening.

OBJECTIVE: To examine the relation between certain pregnancy complications and thyroid stimulating hormone (TSH) measurements in a cohort of pregnant women. METHODS: TSH was measured in sera obtained from women during the second trimester as part of routine prenatal care. Information was then collected about vaginal bleeding, premature delivery, low birthweight, abruptio placentae, pregnancy induced hypertension, need for cesarean section, low Apgar scores, and fetal and neonatal death. RESULTS: Among 9403 women with singleton pregnancies, TSH measurements were 6 mU/l or greater in 209 (2.2%). The rate of fetal death was significantly higher in those pregnancies (3.8%) than in the women with TSH less than 6 mU/l (0.9%, odds ratio 4.4, 95% confidence interval 1.9-9.5). Other pregnancy complications did not occur more frequently. CONCLUSION: From the second trimester onward, the major adverse obstetrical outcome associated with raised TSH in the general population is an increased rate of fetal death. If thyroid replacement treatment avoided this problem this would be another reason to consider population screening.

Adult↗
PubMed2000

Measurement of dose in panoramic dental radiology.

The National Radiological Protection Board (NRPB) has recommended the introduction of dose-width product (DWP) for the measurement of patient dose in panoramic dental radiology and has proposed a reference level of 65 mGy mm for adult exposures. This paper describes a method for measuring DWP and dose-area product (DAP) using thermoluminescent dosemeters (TLDs). The technique was used on 16 sets with a range of exposure settings. The mean value of DWP was 14% higher than the mean value reported from a survey by the NRPB. This difference is most likely to be caused by systematic variations due to measurement method. The average DAP for a standard adult examination was shown to be 11.3 cGy cm2. Data are presented so that the DAP can be derived from the exposure factors (tube current and operating potential) and beam area. Based on published data for effective dose, it is estimated that the DAP to effective dose conversion factor is approximately 0.06 mSv(Gy cm2)-1. The average DAP value (11.3 cGy cm2) can be compared with the average value for intraoral radiography (9.3 cGy cm2) based on the NRPB survey of entrance surface doses assuming 6 cm circular collimation.

Humans↗
PubMed2000

Interobserver and intraobserver variation in classification systems for fractures of the distal humerus.

We assessed the inter- and intraobserver variation in classification systems for fractures of the distal humerus. Three orthopaedic trauma consultants, three trauma registrars and three consultant musculoskeletal radiologists independently classified 33 sets of radiographs of such fractures on two occasions, each using three separate systems. For interobserver variation, the Riseborough and Radin system produced 'moderate' agreement (kappa = 0.513), but half of the fractures were not classifiable by this system. For the complete AO system, agreement was 'fair' (kappa = 0.343), but if only AO type and group or AO type alone was used, agreement improved to 'moderate' and 'substantial', respectively (kappa = 0.52 and 0.66). Agreement for the system of Jupiter and Mehne was 'fair' (kappa = 0.295). Similar levels of intraobserver variation were found. Systems of classification are useful in decision-making and evaluation of outcome only if there is agreement and consistency among observers. Our study casts doubt on these aspects of the systems currently available for fractures of the distal humerus.

Classification↗
PubMed2000

Examination of factor structure for the consumers' responses to the Value Consciousness Scale.

The psychometric properties of the Value Consciousness Scale developed by Lichtenstein, Netemeyer, and Burton in 1990 were examined in a retail grocery study (N = 497). Original assessment of scale properties was undertaken using two convenience samples in a nonretail setting and additional scale performance has been documented by the scale authors. This study furthers previous research by (1) examining performance on the items in the retail grocery setting and (2) utilizing an appropriately rigorous sampling procedure. A confirmatory factor analysis indicated that the Value Consciousness Scale does not exhibit unidimensional properties, and one must be cautious if this scale is used in applications of market segmentation until further clarification can be provided.

Consumer Behavior↗
PubMed2000

The American Medical Association and physician performance measurement: information for improving patient care.

The American Medical Association convenes clinical experts from national medical specialty societies and experts in methodology and data collection to develop physician clinical performance measures. These measures, derived from established clinical recommendations, are intended to facilitate continuous quality improvement by physicians. Through notification and education about their performance, physicians can determine if, and where, changes are needed to improve patient care. Other approaches to physician performance measurement that seek to externally compare physicians should be viewed with caution because of one or more methodological concerns. The medical profession is committed to engaging physicians in performance measurement for quality improvement.

American Medical Association↗
PubMed2000

Digital health care: where health care, information technology, and the Internet converge.

The digital health care industry applies information technologies to facilitate communications, commerce, transactions, business problem solving, and enhanced decision making for one or more groups that supply, consume, or finance health care services and products. The variation among companies is significant, but each one attempts to leverage information technology to drive sustainable evolutionary change. In an overview of the industry, a framework is provided to understand the maze of business plans.

Computer Security↗