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Biomedical subjects

P Rose

Publications and source records attributed to P Rose.

At least 19 recordsLinked to original sources
PubMed2006

High D-dimer levels at presentation in patients with venous thromboembolism is a marker of adverse clinical outcomes.

Qualitative D-dimer results, together with clinical probability scores, are well established in the diagnosis of venous thromboembolism (VTE). The predictive value of quantitative D-dimer levels for various clinical outcomes in VTE patients is not fully understood. D-dimer levels obtained at presentation were analysed in 699 (360 men; 339 women) VTE patients for survival and occurrence of malignancy. Patients were followed for a median of 23 months. 17.2% patients had a D-dimer level >8000 ng FEU/mlat presentation, which was associated with decreased overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001). 25.4% patients had malignancy and 4% subsequently developed malignancy following VTE. 29.9% of patients with VTE and malignancy had a D-dimer level >8 mg/l when compared with 13.4% of patients with VTE without malignancy (P < 0.001). 50% of patients who developed subsequent malignancy following VTE had a presentation D-dimer >8000 ng FEU/mlas compared with 13.3% of patients with VTE with out malignancy (P = 0.009). In conclusion, D-dimer >8000 ng FEU/ml at presentation in patients with VTE is a marker of poor OS, EFS and underlying malignancy. Consideration of screening for malignancy is recommended in patients with VTE with a presentation D-dimer >8000 ng FEU/ml and age >60 years.

Adolescent↗
PubMed2005

Prevalence and incidence of adults consulting for shoulder conditions in UK primary care; patterns of diagnosis and referral.

OBJECTIVES: To estimate the national prevalence and incidence of adults consulting for a shoulder condition and to investigate patterns of diagnosis, treatment, consultation and referral 3 yr after initial presentation. METHODS: Prevalence and incidence rates were estimated for 658469 patients aged 18 and over in the year 2000 using a primary care database, the IMS Disease Analyzer-Mediplus UK. A cohort of 9215 incident cases was followed-up prospectively for 3 yr beyond the initial consultation. RESULTS: The annual prevalence and incidence of people consulting for a shoulder condition was 2.36% [95% confidence interval (CI) 2.32-2.40%] and 1.47% (95% CI 1.44-1.50%), respectively. Prevalence increased linearly with age whilst incidence peaked at around 50 yr then remained static at around 2%. Around half of the incident cases consulted once only, while 13.6% were still consulting with a shoulder problem during the third year of follow-up. During the 3 yr following initial presentation, 22.4% of patients were referred to secondary care, 30.8% were prescribed non-steroidal anti-inflammatory drugs and 10.6% were given an injection by their general practitioner (GP). GPs tended to use a limited number of generalized codes when recording a diagnosis; just five of 426 possible Read codes relating to shoulder conditions accounted for 74.6% of the diagnoses of new cases recorded by GPs. CONCLUSIONS: The prevalence of people consulting for shoulder problems in primary care is substantially lower than community-based estimates of shoulder pain. Most referrals occur within 3 months of initial presentation, but only a minority of patients are referred to orthopaedic specialists or rheumatologists. GPs may lack confidence in applying precise diagnoses to shoulder conditions.

Adolescent↗
PubMed2005

Gas chromatographic, mass spectrometric and stable carbon isotopic investigations of organic residues of plant oils and animal fats employed as illuminants in archaeological lamps from Egypt.

Man's use of illuminants in lamps or as torches to extend the working day and range of environments accessible to him would have been a major technological advance in human civilisation. The most obvious evidence for this in the archaeological record comes from pottery and stone vessels showing sooting due to the use of a wick in conjunction with a lipid-based fuel or illuminant. A wide range of potential fuels would have been exploited depending upon availability and burning requirements. Reported herein are the results of chemical investigations of a number of lamps recovered from excavations of the site of Qasr Ibrim, Egypt. Gas chromatographic, mass spectrometric and stable carbon isotopic analyses of both free (solvent extractable) and 'bound'(released from solvent extracted pottery by base treatment) lipids have revealed a wide range of saturated fatty acids, hydroxy fatty acids and alpha, omega-dicarboxylic acids. Examination of the distributions of compounds and comparisons with the fatty acid compositions of modern plant oils have allowed a range of fats and oils to be recognised. Specific illuminants identified include Brassicaceae (Cruciferae) seed oil (most likely radish oil, Raphanus sativus), castor oil (from Ricinus communis), animal fat, with less diagnostic distributions and delta(13)C values being consistent with low stearic acid plant oils, such as linseed (Linum usitatissimum) or sesame (Sesamum indicum) oils. The identifications of the various oils and fats are supported by parallel investigations of illuminant residues produced by burning various oils in replica pottery lamps. The findings are entirely consistent with the classical writers including Strabo, Pliny and Theophrastrus.

Archaeology↗
PubMed2005

Assessment of the Lequesne index of severity for osteoarthritis of the hip in an elderly population.

OBJECTIVE: To assess the measurement properties of the Lequesne index of severity for osteoarthritis of the hip (LISOH) together with its overall usefulness with reference to the original stated aims. METHOD: Postal questionnaire was sent to a random sample of 5500 Oxfordshire residents, aged 65 and above. Respondents with hip symptoms at baseline (but without verification of a diagnosis) were sent an identical follow-up questionnaire 12 months later. The questionnaire included a general health section, including the Short Form-36 survey, and a hip section which began with a screening question about hip pain. Respondents who reported having a prolonged episode of hip pain were asked to complete the LISOH. RESULTS: At baseline, response rate of 66.3% (3341/5039) was obtained from eligible participants; 19.2% (610/3175) of respondents reported having hip pain. Internal reliability (Cronbach's alpha) was 0.84 (95% CI: 0.81-0.86) for all 11 items of the LISOH; however, factor analysis identified two factors (sub-scales): "function and mobility" and "pain and discomfort". Rasch analysis revealed that the two factors were only unidimensional when applied to sub-groups of respondents. Convergent validity of the LISOH was questionable, as the "function and mobility" factor was more highly correlated with SF-36 bodily pain score than was the "pain and discomfort" factor. The assessment of sensitivity over time was problematic due to changing patterns of symptomatic weight-bearing joints over time. CONCLUSIONS: The current study identifies major limitations with the LISOH--particularly if used as a single composite measure.

Aged↗
PubMed2005

Successful treatment of a patient with chronic lymphocytic leukaemia (CLL) presenting with bony metastases with aggressive antibody and chemotherapy.

Osteolytic lesions are rare in chronic lymphocytic leukaemia (CLL) and thought to result from Richter's transformation or metastatic disease from nonlymphoid malignancies. We report a patient who presented with a large femoral metastatic lesion and hypercalcaemia caused by CLL itself. Complete remission of CLL with resolution of the osteolytic lesion was achieved with rituximab and cyclophosphamide, adriamycin, oncovin and prednisolone [CHOP (R-CHOP)] combination chemotherapy.

Aged, 80 and over↗
PubMed2004

Epidemiology of hip and knee pain and its impact on overall health status in older adults.

OBJECTIVES: To obtain prevalence rates of hip and knee pain in elderly people and compare combinations of symptoms with overall health status. METHODS: We performed a cross-sectional postal survey of a random sample of 5500 Oxfordshire residents aged 65 yr and older. Prevalence estimates were based on the screening question: 'During the past 12 months, have you had pain in or around either of your hip/knee joints on most days for one month or longer?' Overall health status was assessed with the SF-36 questionnaire. RESULTS: The response rate was 66.3% (3341/5039 eligible people), and was highest (approximately reverse similar 72%) for the 65-74 yr age-group. The percentage reporting hip pain was 19.2% [95% confidence interval (CI) 17.9-20.6], and 32.6% (95% CI 31.0-34.3) reported knee pain. The percentage reporting hip and knee pain was 11.3%, and 40.7% reported hip or knee pain. Less than half (48%) of the symptomatic respondents had unilateral problems affecting one hip or knee joint only. SF-36 scores worsened as the number of symptomatic hip and knee joints increased (P<0.001 for physical function, physical role limitation and bodily pain). CONCLUSIONS: Patterns of hip and knee symptoms are complex in older people. Amongst the symptomatic, most have more than one hip/knee affected. This has implications for treatment and health status measurement. In the absence of hip and knee symptoms, general health status scores of elderly people are similar to those of people aged under 65 yr.

Aged↗
PubMed2004

The effects of selective cytokine inhibitory drugs (CC-10004 and CC-1088) on VEGF and IL-6 expression and apoptosis in myeloma and endothelial cell co-cultures.

Myeloma cells and human umbilical vein endothelial cells (HUVECs) were co-cultured to model in vitro the interactions between myeloma and endothelium, and treated with thalidomide and two selective cytokine inhibitory drugs (SelCIDs, phosphodiesterase-4 inhibitors). Flow cytometry and enzyme-linked immunosorbent assay were used to assess production of two key cytokines--vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6)--and apoptosis in co-cultured HUVECs and myeloma cells. VEGF was produced by both myeloma cells and HUVECs, while IL-6 was almost exclusively produced by endothelial cells. In co-culture, there was significant up-regulation of VEGF and IL-6 production compared with the sum of separate myeloma and endothelial cell cultures. SelCIDs markedly inhibited production of both cytokines in co-cultures, with CC-10004 being more potent than CC-1088. In addition, SelCIDs induced myeloma cell apoptosis. Apoptosis in co-cultured myeloma cells was significantly lower than in those cultured separately, suggesting that co-culture partially protected myeloma cells from drug-induced apoptosis. This protective effect was probably due to IL-6 produced by endothelial cells in co-culture as addition of anti-IL-6 neutralizing antibody, but not anti-VEGF antibody, abrogated it. In conclusion, SelCIDs can exert their anti-myeloma activity through two mechanisms, i.e. inhibition of VEGF and IL-6 production by interacting myeloma and endothelium and induction of myeloma cell apoptosis.

Angiogenesis Inhibitors↗
PubMed2003

beta-Phenylethyl isothiocyanate-mediated apoptosis in hepatoma HepG2 cells.

beta-Phenylethyl isothiocyanate (PEITC) is a promising chemoprotective compound that is routinely consumed in the diet as its glucosinolate precursor. Previous studies have shown that PEITC can inhibit phase I enzymes and induce phase II detoxification enzymes along with apoptosis in vitro. The detailed mechanisms involved in the apoptotic cascade, however, have not been elucidated. In the present study, we demonstrate that PEITC can induce apoptosis in hepatoma HepG2 cells in a concentration- and time-dependant manner as determined by TUNEL positive and SubG1 population analysis. Caspase-3-like activity and poly(ADP-ribosyl)polymerase cleavage increased during treatment with 20 microM PEITC; high concentrations, however, induced necrosis. Pre-treatment with Z-VAD-FMK and the caspase-3-specific inhibitor Ac-DEVD-CHO prevented PEITC-induced apoptosis, as determined by caspase-3-like activity and DNA fragmentation. Additional investigations also showed that at concentrations of 5-10 microM PEITC, DNA synthesis was inhibited and G2/M phase cell cycle arrest occurred, correlating with an alteration in cyclin B1 and p34(cdc2) protein levels. Furthermore, we also demonstrate a concentration- and time-dependant burst of superoxide (O2*-) in PEITC-treated cells. However, pre- and co-treatment with the free radical scavengers Trolox, ascorbate, mannitol, uric acid and the superoxide mimetic manganese (III) tetrakis (N-methyl-2-pyridyl) porphyrin failed to prevent PEITC-mediated apoptosis. Taken together, these results suggest that PEITC potently induces apoptosis and cell cycle arrest in HepG2 cells and that the generation of reactive oxygen species appears to be a secondary effect.

Anticarcinogenic Agents↗
PubMed2003

Acute arterial thrombosis in acute promyelocytic leukaemia.

INTRODUCTION: Localized large vessel thrombosis in acute leukaemia is rare, haemorrhagic complications being more common. METHOD: We present a patient with acute promyelocytic leukaemia (APL) presenting with an acutely ischaemic lower limb. Large vessel thrombosis is a rare presentation of APL. We reviewed the literature on the coagulopathy of APL and discuss the pathology and current treatment options. DISCUSSION: Disordered haemostasis is typical of acute promyelocytic leukaemia (FAB M3) and relates to the intrinsic properties of the blast cells as well as thrombocytopenia from bone marrow involvement. Expression of procoagulants, stimulation of cytokines and alterations in endothelial cell anticoagulant properties initiate a disseminated intravascular coagulation (DIC) resulting in the typical clinical and laboratory findings in APL. The promyelocytes are characterized by the balanced reciprocal translocation between chromosomes 15 and 17. All-trans-retinoic acid (ATRA) induces differentiation in these cells, revolutionizing the treatment of APL. CONCLUSION: Unexpected limb ischaemia in a young, apparently healthy patient might be the presenting symptom of an underlying haematological disorder such as APL. A thorough haematological investigation should be performed prior to contemplating surgery. New treatment strategies based on knowledge of the molecular biology of APL has improved the prognosis of patients suffering from APL.

Amputation, Surgical↗
PubMed2003

A targeted approach significantly increases the identification rate of patients with undiagnosed haemochromatosis.

OBJECTIVE: To determine the optimal means of identifying patients with undiagnosed haemochromatosis. DESIGN: Case-control study where cases are defined by the presence of specific clinical diagnoses or symptoms. SETTING: Primary care patients were recruited from three Oxfordshire practices and secondary care patients were recruited from those patients attending specialist clinics in Amiens University Hospital. SUBJECTS: A total of 569 patients recruited via hospital clinics and 60 primary care patients (recruited from 4022 consultations) presenting with the following haemochromatosis associated conditions, diabetes, arthralgia/chronic fatigue, osteoporosis or arthropathy were studied. The control group, a total of 991 healthy volunteers, were recruited through a Health Appraisal Centre. Patients and controls were included in the study if they or their family members had not previously been diagnosed with hereditary haemochromatosis. MAIN OUTCOME MEASURES: Serum ferritin concentration, transferrin saturation (Tsat) and presence of HFE mutations, C282Y and H63D. The check-up in controls consisted of a questionnaire, clinical examination, biochemical tests and screening for the presence of the C282Y and H63D mutations. RESULTS: Patient groups presenting with unstable diabetes or chronic fatigue and arthralgia together with a raised serum ferritin concentration showed an enrichment in the haemochromatosis-associated genotype HH/YY, odds ratio (OR) = 40.1, confidence interval (CI) = 8.0-202.1 and OR = 103, CI = 22.9-469.7, respectively. CONCLUSION: Patients presenting to hospital clinics with haemochromatosis associated conditions should be screened biochemically for iron overload. Only those with a serum ferritin >300 microg L-1 or Tsat >40% should subsequently go on to be genotyped for HFE mutations. The patients at greatest risk of having undiagnosed haemochromatosis are those presenting with unstable diabetes, or fatigue and/or arthralgia in the absence of any other explanation.

Adult↗
PubMed2003

Co-digestion of primary sewage sludge and industrial wastewater under anaerobic sulphate reducing conditions: enzymatic profiles in a recycling sludge bed reactor.

The first stage in the degradation and recycling of primary sewage sludge and particulate organic matter is the solubilisation and enhanced hydrolysis of complex polymeric organic carbon structures associated with the anaerobic sulphidogenic environment. Solubilization of complex carbon substrates provides the primary reaction in the BioSURE Process, and is effected in the recycling sludge bed reactor (RSBR). During the process of anaerobic digestion, macromolecules are broken down into simpler low molecular weight compounds in the presence of extracellular enzymes. Though hydrolysis of the complex carbon sources was enhanced under biosulphidogenic conditions, no studies have examined the role of enzymes and the enzymatic profiles in the RSBR. To investigate the overall enzymology in the RSBR variations in COD, pH, sulphate, sulphite and sulphide concentrations, carbohydrates, protein and activities of glucosidases, proteases and lipases were studied over 50 days in the reactor at three different depths: 0-16 cm; 16-32 cm; 32-50 cm. While the pH profile remained fairly constant between 6.9 and 7.3 the sulphate and sulphide levels, as expected, changed dramatically as sulphate reduction took place. Proteases, lipases and glucosidases all showed enhanced activity with depth in the bioreactor. It is suggested that the increased sulphide concentration generated during the sulphate reduction process stimulates the enzymes, leading to enhanced solubilisation of primary sewage sludge.

Bacteria, Anaerobic↗
PubMed2002

Development of isothiocyanate-enriched broccoli, and its enhanced ability to induce phase 2 detoxification enzymes in mammalian cells.

Broccoli florets contain low levels of 3-methylsuphinylpropyl and 4-methylsulphinylbutyl glucosinolates. Following tissue disruption, these glucosinolates are hydrolysed to the corresponding isothiocyanates (ITCs), which have been associated with anticarcinogenic activity through a number of physiological mechanisms including the induction of phase II detoxification enzymes and apoptosis. In this paper, we describe the development of ITC-enriched broccoli through the introgression of three small segments of the genome of Brassica villosa, a wild relative of broccoli, each containing a quantitative trait locus (QTL), into a broccoli genetic background, via marker-assisted selection and analysis of glucosinolates in the florets of backcross populations. Epistatic and heterotic effects of these QTLs are described. The ITC-enriched broccoli had 80-times the ability to induce quinone reductase (a standard assay of phase II induction potential) when compared to standard commercial broccoli, due both to an increase in the precursor glucosinolates and a greater conversion of these into ITCs.

Anticarcinogenic Agents↗
PubMed2002

Multiple cutaneous plasmacytomas following an autologous peripheral stem cell transplant.

We describe the unusual development of multiple cutaneous plasmacytomas following treatment of IgA lambda myeloma with myeloablative therapy and a peripheral blood stem cell autograft. Cutaneous metastatic spread was evident despite bone marrow remission. Treatment with an autograft may have contributed to the cutaneous relapse.

Hematopoietic Stem Cell Transplantation↗