Biomedical subjects

R Will

Publications and source records attributed to R Will.

At least 19 recordsLinked to original sources

PubMed2006

PATRIC: the VBI PathoSystems Resource Integration Center.

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.

Bioterrorism↗

PubMed2005

What are cancer patients' preferences about treatment at the end of life, and who should start talking about it? A comparison with healthy people and medical staff.

GOALS OF THE WORK: In order to strengthen cancer patients' autonomy and to improve quality of palliative care, it is necessary to know what are the patients' preferences for treatment at the end of life, whether they accept the idea of advance directives, and who should initiate the process of fulfilling such a document. PATIENTS AND METHODS: We compared cancer patients' preferences with respect to particular treatment options at the end of life, acceptance of the idea of advance directives, and preferences for whom should initiate writing such a document with that of healthy controls, nursing staff, and physicians (n=100 each group) using a structured questionnaire. RESULTS: Cancer patients wanted treatment with antibiotics and infringing treatments such as chemotherapy and dialysis significantly more often than healthy controls, nursing staff, and physicians (p<0.01 and p<0.001, respectively). Determinants associated with the wish to opt for these treatments were reduced health condition and older age. The groups did not differ with respect to their acceptance of advance directives; 58-75% of all those surveyed wanted their physicians to initiate a discussion about writing such a document if they thought it appropriate. CONCLUSIONS: Cancer patients' preferences for treatment at the end of life significantly differ compared to other groups. Oncologists should initiate a discussion about an advance directive when/if the course of the illness seems to make this appropriate, which corresponds to the wish of the majority of cancer patients, healthy controls, and medical staff.

Adult↗

PubMed2005

Would they follow what has been laid down? Cancer patients' and healthy controls' views on adherence to advance directives compared to medical staff.

UNLABELLED: Advance directives are propagated as instruments to maintain patients' autonomy in case they can no longer decide for themselves. It has been never been examined whether patients' and healthy persons themselves are inclined to adhere to these documents. Patients' and healthy persons' views on whether instructions laid down in advance directives should be followed because that is (or is not) "the right thing to do", not because one is legally obliged to do so, were studied and compared with that of medical staff. METHOD: Vignette study presenting five cases. Cancer patients, healthy persons, nursing staff and physicians (n = 100 in each group) were interviewed. An adherence score was calculated (maximum value 5). The adherence score is found to be low in all groups, yet lowest in patients (1.55; standard deviation 1.13) and healthy controls (1.60; 1.37). The scores are significantly different between nursing staff on the one hand and patients and healthy controls on the other (p < 0.005 and p < 0.05, respectively), and between doctors and patients (p < 0.05). Interviewees who want these documents to be followed tend to live alone and to have already written an advance directive. CONCLUSIONS: Cancer patients and healthy persons widely disregard instructions laid down in advance directives and consider them less binding than physicians and nursing staff do. Only a minority tends to adhere more to advance directives. To improve decision-making at the end of life when patients are no longer able to decide for themselves alternative concepts, such as advanced care planning, should be considered.

Adult↗

PubMed2005

Attitudes towards and barriers to writing advance directives amongst cancer patients, healthy controls, and medical staff.

OBJECTIVES: After years of public discussion too little is still known about willingness to accept the idea of writing an advance directive among various groups of people in EU countries. We investigated knowledge about and willingness to accept such a directive in cancer patients, healthy controls, physicians, and nursing staff in Germany. METHODS: Cancer patients, healthy controls, nursing staff, and physicians (n = 100 in each group) were surveyed by means of a structured questionnaire. RESULTS: Only 18% and 19% of the patients and healthy controls respectively, and 10% of the medical staff had written an advance directive. However, 50-81% of those surveyed indicated that they wished to write one. This intention was associated with deteriorating health (p < 0.001). Only 29% of the healthy controls and 43% of the patients knew about the possibility of appointing a health care proxy. A majority in all groups believed that advance directives may influence the course of treatment (79-85%), yet half of those surveyed in all groups fear that patients could be pressurised into writing an advance directive, and 38-65% thought that relatives could abuse such documents. CONCLUSIONS: Only a minority of the participants had written an advance directive and knew about the possibility of authorizing a health care proxy. Deteriorating health was associated with increasing willingness to make a directive. Despite a majority belief that advance directives may influence treatment at the end of life, other factors limit their employment, such as fear of abuse.

Adult↗

PubMed2004

A phase II study of Rituximab in rheumatoid arthritis patients with recurrent disease following haematopoietic stem cell transplantation.

Haematopoietic stem cell transplantation (HSCT) has been used recently as an effective therapy in patients with resistant rheumatoid arthritis (RA). Although disease control occurs in the majority of cases, recurrence is common, often coinciding with B-cell reconstitution. We hypothesized that Rituximab, a monoclonal anti-CD20 antibody, would have activity in this group of patients. We treated 10 RA patients (8F:2M, median age 46.5 years), who had recurrent disease post HSCT. All patients received two doses of Rituximab 1 g, 2 weeks apart with no major adverse sequelae and were followed for 12 months. A total of eight out of 10 patients experienced major clinical responses as measured by the American College of Rheumatology (ACR) criteria, with 50-70% improvement in disease parameters. Responses were equivalent to previous responses attained with HSCT. Disease responses were maximal at 4-8 months post Rituximab and correlated with B-cell lymphopenia and a reduction of rheumatoid factor titre. Disease recurrence occurred in 6/9 responders within 12 months and four patients were subsequently retreated, with major responses again attained. This study provides further evidence that B-cell depletion leads to a significant improvement in disease activity in patients with severe RA and provides data for future trials of HSCT and Rituximab therapy.

Adult↗

PubMed2002

Sensory features of variant Creutzfeldt-Jakob disease.

OBJECTIVE: Sensory symptoms are a prominent feature of variant Creutzfeldt-Jakob disease (vCJD), occurring at an early stage of the illness. They are persistent and can be troublesome. Here, they are described in detail and a possible anatomical basis is discussed. METHODS: The first 50 cases of vCJD confirmed by the National CJD Surveillance Unit (NCJDSU) were reviewed. Where possible the patients and their relatives were interviewed and case notes were examined. The presence and nature of sensory symptoms and signs were noted. Results of investigation and types of treatment offered were also reviewed. RESULTS: Of 50 definite cases, 64 % had persistent sensory symptoms, 16 % had no sensory symptoms and 18 % were uncertain. In 2 % there was insufficient information. Of the 32 with definite symptoms, 31 % were symptomatic from the onset of the illness. The symptoms were varied and some patients complained of more than one type of symptom. Limb pain was described in 63 % cases. This was the most common symptom and was often non-specific and poorly localised, usually occurring in the lower limbs. Other symptoms included cold feelings (25 % patients), dysaesthesia (28 % patients), paraesthesia (31 % patients) and numbness (25 % patients). The symptoms were lateralised in 31 % of patients. CONCLUSIONS: Sensory symptoms are a prominent feature of vCJD, occurring in nearly two thirds of cases. They may help distinguish variant from sporadic CJD. They are likely to be of thalamic origin but the recognised MRI changes in vCJD do not correlate with the presence or absence of sensory symptoms. Neuropathological changes in the thalamus, however, show marked astrocytosis and neuronal loss.

Creutzfeldt-Jakob Syndrome↗

PubMed2002

Interleukin-1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid arthritis.

OBJECTIVE: To determine whether interleukin-1 alpha and 1 beta gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1 beta and rheumatoid arthritis (RA) motif gene. METHODS: IL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1 alpha-889 and IL-1 beta + 3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1 beta 2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data. RESULTS: There was no significant difference in the frequency and carriage rate of IL-1 alpha polymorphisms between RA patients and the controls. The beta 2/2 genotype of IL-1 beta was more common in female RA patients compared with controls (P = 0.001). A lower carriage rate of IL-1 beta 2 occurred in male RA patients (P = 0.001). A higher carriage rate of IL-1 alpha 2 is associated with a higher ESR (P = 0.008), HAQ score (P = 0.03), and vit-D3 (P < 0.001), but conversely a lower SJC (p = 0.002), a lower RF (P = 0.002) and a lower BMD at the lumbar spine (P = 0.001). A higher frequency of IL-1 alpha 1 is associated with a lower CRP value (P = 0.009). An increased IL-1 beta 2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P < 0.001), ESR (P < 0.001) and pain score (P = 0.001) and a higher BMD at the lumbar spine (P = 0.007), lower vit-D3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1 beta allele 2 at same time did not contribute to disease activity. CONCLUSION: Polymorphisms of the IL-beta gene may affect the RA occurrence. Carriage of IL-1 beta 2 polymorphisms is associated with more active disease in RA and the presence of both the IL-1 alpha 2 and the IL-1 beta 1 allele in RA influences bone resorption.

Alleles↗

PubMed2001

Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom.

The size of the variant Creutzfeldt-Jakob Disease (vCJD) epidemic in the United Kingdom is a major public health concern and a subject of speculation. The cases are young (mean age = 28). Assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.7 years [95% confidence interval (CI): 12.4 to 23.2] and that the total number of cases will be 205 (upper limit of the 95% CI: 403).

Adolescent↗

PubMed2001

Changing a single amino acid in the N-terminus of murine PrP alters TSE incubation time across three species barriers.

The PrP gene of the host exerts a major influence over the outcome of transmissible spongiform encephalopathy (TSE) disease, but the mechanism by which this is achieved is not understood. We have introduced a specific mutation into the endogenous murine PrP gene using gene targeting to produce transgenic mice with a single amino acid alteration (proline to leucine) at amino acid position 101 in their PrP protein (P101L). The effect of this alteration on incubation time, targeting and PrP(Sc) formation has been studied in TSE-infected animals. Transgenic mice carrying the P101L mutation in PrP have remarkable differences in incubation time and targeting of central nervous system pathology compared with wild-type littermates, following inoculation with infectivity from human, hamster, sheep and murine sources. This single mutation can alter incubation time across three species barriers in a strain-dependent manner. These findings suggest a critical role for the structurally 'flexible' region of PrP in agent replication and targeting of TSE pathology.

Amino Acid Sequence↗

PubMed2000

European surveillance on Creutzfeldt-Jakob disease: a case-control study for medical risk factors.

Medical risk factors for Creutzfeldt-Jakob disease (CJD) were analyzed in a prospective ongoing case-control study based on European CJD surveillance. Detailed data on past and recent medical history were analyzed in 405 cases and controls matched by sex, age, and hospital. Data were correlated with polymorphism at codon 129 of the prion protein gene. Our analysis did not support a number of previously reported associations and failed to identify any common medical risk factor for CJD. Although not statistically significant, brain surgery was associated with an increased risk of CJD. A detailed medical history should be obtained in every suspected CJD case in order to identify iatrogenic sources of CJD.

Adult↗

PubMed2000

Recurrent clear cell hidradenoma of the foot.

BACKGROUND: Clear cell hidradenoma is an uncommon neoplasm without established optimal treatment. OBJECTIVE: Using Mohs micrographic surgery, a recurrent clear cell hidradenoma of the right foot was treated. METHODS: Case report and literature review. RESULTS: Two stages of Mohs micrographic surgery and subsequent repair successfully treated the recurrent clear cell hidradenoma. No recurrence of the neoplasm has been observed at 11 months follow-up. CONCLUSION: Optimal treatment of clear cell hidradenoma is unestablished. Adequate primary local excision is essential. Mohs micrographic surgery should be considered for treatment, especially on recurrent tumors in critical locations.

Acrospiroma↗

PubMed2000

Effect of different daytime and night-time temperature regimes on the foliar respiration of Pinus taeda: predicting the effect of variable temperature on acclimation.

The objectives of this study were to determine the acclimation of loblolly pine (Pinus taeda L.) foliar respiration to different night-time low temperatures, daytime high temperatures, and daily mean temperatures, and then to use the responses of temperature acclimation to various temperature regimes to predict acclimation under fluctuating temperatures. Experiments were conducted on two-year-old seedlings in growth chambers using different combinations of day and night-time temperatures. The first experiment exposed trees to 22/22, 29/22, 22/15, and 29/15 degrees C day/night (d/n). When measured at a common temperature (15, 22 or 29 degrees C), respiration rates were lower for trees exposed to higher treatment temperatures and acclimation was influenced by both day and night-time temperature. However, the extent of acclimation did not relate to mean temperature, i.e. respiration rates measured at a common temperature ranked as follows for seedlings exposed to different temperature regimes, 22/15>22/22>29/15 congruent with29/22 degrees C d/n. Rather, acclimation of foliar respiration was linearly related to mean daily respiration rate, where mean daily respiration rate is the average of the respiration rates measured at the day and night-time treatment temperatures. The discrepancy between mean daily respiration rate and mean daily temperature occurred because respiration increased exponentially with increasing temperature. In a second experiment, the same seedlings were exposed to 22/22, 15/15, 25.5/18.5, and 25.5/15 degrees C d/n to test the relationship between mean daily respiration rate and acclimation. As in the first experiment, acclimation was linearly related to mean daily respiration rate. The concept of effective acclimation temperature, which is the temperature at which the mean daily respiration rate occurs, was derived from these results as a means to predict the extent that foliar respiration acclimates to treatment temperature.

Adaptation, Physiological↗

PubMed2000

Ankylosing spondylitis and the shoulder: commonly involved but infrequently disabling.

OBJECTIVE: To undertake 2 independent studies of shoulder involvement in patients with ankylosing spondylitis (AS) and assess the frequency of shoulder pain, stiffness, and loss of movement and function. To evaluate and correlate shoulder symptoms, function, range of movement, and radiology. METHODS: A cross sectional design was used in both studies. In Study A, a self-administered questionnaire was sent to members of the National Ankylosing Spondylitis Society of the UK and patients attending the Royal National Hospital for Rheumatic Diseases. In Study B, a clinical assessment of 88 patients with AS was undertaken that included a radiological assessment of 26 consecutive patients. RESULTS: In Study A, 15.2% and 13.8% of subjects had severe/very severe shoulder pain or stiffness, respectively. In Study B the corresponding findings were 9.6% and 17.6%. Patient reported disability associated with shoulder involvement was uncommon. Study A revealed that patients with severe/very severe shoulder pain were more likely to have significant hip and knee involvement. Significant shoulder involvement appears to be as common as involvement of the hip joint. In Study B radiological changes were common, being present in 31% of patients, but were often minor. There was a significant correlation between the sum of the stiffness, abduction, and flexion scores for both shoulders and the total radiological score (r = 0.87; p<0.001). CONCLUSION: The results suggest that shoulder symptoms and loss of shoulder mobility are common in patients with AS, and correlate with higher pain scores and influence of AS on their lives as assessed by the Arthritis Impact Measurement Scale, but are rarely disabling. Involvement of the shoulder joint in AS correlates with involvement of other peripheral joints as well as the extent of radiographic change on shoulder radiographs.

Adult↗

PubMed1999

Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans.

There is growing concern that bovine spongiform encephalopathy (BSE) may have passed from cattle to humans. We report here that transgenic (Tg) mice expressing bovine (Bo) prion protein (PrP) serially propagate BSE prions and that there is no species barrier for transmission from cattle to Tg(BoPrP) mice. These same mice were also highly susceptible to a new variant of Creutzfeldt-Jakob disease (nvCJD) and natural sheep scrapie. The incubation times (approximately 250 days), neuropathology, and disease-causing PrP isoforms in Tg(BoPrP)Prnp(0/0) mice inoculated with nvCJD and BSE brain extracts were indistinguishable and differed dramatically from those seen in these mice injected with natural scrapie prions. Our findings provide the most compelling evidence to date that prions from cattle with BSE have infected humans and caused fatal neurodegeneration.

Animals↗

PubMed1999

A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy.

A mutation equivalent to P102L in the human PrP gene, associated with Gerstmann-Straussler syndrome (GSS), has been introduced into the murine PrP gene by gene targeting. Mice homozygous for this mutation (101LL) showed no spontaneous transmissible spongiform encephalopathy (TSE) disease, but had incubation times dramatically different from wild-type mice following inoculation with different TSE sources. Inoculation with GSS produced disease in 101LL mice in 288 days. Disease was transmitted from these mice to both wild-type (226 days) and 101LL mice (148 days). In contrast, 101LL mice infected with ME7 had prolonged incubation times (338 days) compared with wild-type mice (161 days). The 101L mutation does not, therefore, produce any spontaneous genetic disease in mice but significantly alters the incubation time of TSE infection. Additionally, a rapid TSE transmission was demonstrated despite extremely low levels of disease-associated PrP.

Alleles↗

PubMed1999

[Colony stimulating factors in polychemotherapy of testicular tumors. A comparison between G-CSF and GM-CSF].

Colony-stimulating factors (CSF) are frequently used in cases of cytostatic therapy of patients with testicular cancer assuming that they support hematopoietic recovery and, thus, shorten duration of neutropenia as well as reduce infections. Currently, G-CSF and GM-CSF are clinically used. In the present study efficacy and toxicity of these two drugs were investigated and compared in patients with testicular cancer treated by standard chemotherapy. Studying 83 chemotherapy cycles applied to 31 patients with advanced germ cell tumors the effectivity and the side effects of the two CSF were examined by questioning, clinical evaluation, and blood chemistry studies. G-CSF (480 micrograms subcutaneously (s.c.)) were used in 55 and GM-CSF (400 micrograms s.c.) in 28 chemotherapeutic cycles. The indications consisted in the treatment of leukocytopenia on the one hand and in the prophylaxis in subsequent cycles on the other hand. No difference between the two CSF could be found either with regard to postponement of the next cycle (G-CSF: 6.8 vs. GM-CSF: 7.3 days), or to the number of injections per cycle (G-CSF: 8 vs. GM-CSF: 12.5), or to the leukocyte (G-CSF: 2.1 vs. GM-CSF: 1.6 x 10(3)/microliter) or platelet nadir (G-CSF: 0.5 vs. GM-CSF: 0.5 x 10(5)/microliter; mean values of all cycles, respectively). Both CSF did not seem to influence the production of platelets. However, a difference between the two CSF was demonstrated with respect to the toxicity. Frequency (G-CSF: 38.5% vs. GM-CSF: 69.3%) as well as intensity of side effects causing a change of the drug (G-CSF: n = 1 vs. GM-CSF: n = 7) were lower in the case of G-CSF. In conclusion, these data demonstrate no difference was seen between G-CSF and GM-CSF with respect to the efficacy in patients with testicular cancer treated by standard chemotherapy. However, the use of G-CSF seems to be associated with lower toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

New variant Creutzfeldt-Jakob disease.

New variant Creutzfeldt-Jakob disease is a novel human spongiform encephalopathy with a consistent clinico-pathological phenotype. Epidemiological evidence indicates that this disease is occurring almost exclusively in the UK, where there has been an epidemic of spongiform encephalopathy in the cattle population. Current evidence strongly supports the hypothesis that there is a causal link between bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease.

Animals↗

PubMed1999

Three year followup of bone mineral density change in premenopausal women with systemic lupus erythematosus.

OBJECTIVE: To measure the change in bone mineral density (BMD, g/cm2) in a female population with systemic lupus erythematosus (SLE) over 3 years, to identify factors predictive of bone loss, including the role of corticosteroid and disease related variables, and to determine the predictive value of urinary collagen crosslinks for bone loss. METHODS: All premenopausal women with SLE who participated in a cross sectional study of BMD in 1994 were invited to undergo a standardized interview, examination, medical record review, and BMD measurement of the lumbar spine and femoral neck by dual energy x-ray absorptiometry. RESULTS: Thirty-two women participated with a mean (SEM) age of 35.2 (1.5) years, duration of SLE of 7.0 (0.8) years, and mean (range) time to followup of 3.2 (2.9-3.4) years. Twenty-one subjects were exposed to corticosteroids during the study period with a mean (range) daily dose of prednisolone of 11.1 (2.8-22.9) mg. There was no significant change over the 3 years in BMD at the lumbar spine (1.161+/-0.122 vs. 1.169+/-0.022; p = 0.39) or femoral neck (0.944+/-0.023 vs. 0.955+/-0.020; p = 0.47) for the group as a whole, or when subjects were divided according to corticosteroid exposure. However, in the corticosteroid exposed subgroup, patients treated with > or = 7.5 mg/day (n = 14) lost lumbar spine BMD (-0.50%/yr) in contrast to those receiving <7.5 mg/day, who gained 1.06%/yr (p = 0.02). Furthermore, no participant receiving <7.5 mg/day lost lumbar spine BMD, while 57% of patients receiving > or =7.5 mg/day lost lumbar spine BMD (p = 0.01). In the corticosteroid exposed subgroup only, subjects who did not exercise regularly lost femoral neck BMD, while those who did gained femoral neck BMD (-0.54%/yr vs. 1.39%/yr; p = 0.02). Disease related variables (disease severity, activity, duration, functional capacity) and baseline urinary collagen crosslink levels were not predictive of BMD change. CONCLUSION: Loss of lumbar spine and femoral neck BMD in this premenopausal female SLE population was minimal for the group as a whole; however, a daily dose of prednisolone of > or =7.5 mg was associated with loss of lumbar spine BMD. In corticosteroid exposed patients, regular exercise was protective of femoral neck BMD loss. A single baseline measurement of urinary collagen crosslinks was not predictive of bone loss.

Absorptiometry, Photon↗