Biomedical subjects
Publications and source records attributed to R B Jones.
The drawbacks of using the concepts of models in discussing the problems of disabled people are discussed. It is suggested that the terms "impairment", "disability", and "handicap" can unify the different models and enhance the position of people with disabilities in society.
Ten cadaver specimens were used to study the effect of distal fibular resection and ligamentous repair on ankle laxity. The distal fibula was resected sequentially at three levels. Talar tilt and anterior drawer were measured on stress radiographs after resection and then after ligament repair. Sequential resection of the distal fibula caused a progressive increase in talar tilt and anterior drawer at each cut level (p < 0.5), regardless of whether the ligaments were repaired or not. Ligament repair significantly decreased talar tilt at cuts above the ATFL insertion and decreased anterior drawer at cuts at the tibiotalar level, but these values did not approach control values.
The Internet is a rich source of health information but it is not as accessible as many claim. This paper brings together three projects to illustrate technical and cost barriers and some options to overcome them. (1) A survey amongst a representative sample of 180 patients in rural Spain showed a marked age gradient in computer access. None over the age of 50 had, and less than 10% planned, access to the Internet whereas a quarter were prepared to use health centre based touchscreen kiosks. (2) Half the commonly used search engines did not include the two most relevant websites for Glasgow colorectal cancer patients in the first ten documents listed, showing the difficulty facing patients in finding relevant information. Selection of information would help patients avoid being overwhelmed with information. (3) One method to improve accessibility is to download websites to kiosks but two projects showed that considerable work is required to reformat the information. Public access computing, such as kiosks, could help make the Internet more accessible. We discuss whether Web sites which structure their information according to method of access, place and person provide a way forward.
Explore the source record for details and available documents.
Boron neutron capture therapy (BNCT) is based on a nuclear capture reaction that occurs when boron-10, a stable isotope, is irradiated with low energy neutrons to produce high-energy alpha particles and recoiling lithium-7 nuclei. The purpose of the present study was to determine what urinary metabolites, if any, could be detected in patients with brain tumors who were given sodium borocaptate (BSH), a drug that has been used clinically for BNCT. BSH was infused intravenously over a 1-h time period at doses of 26.5, 44.1, or 88.2 mg/kg of body weight to patients with high-grade brain tumors. Electrospray ionization mass spectrometry has been used to investigate possible urinary metabolites of BSH. Chemical and instrument conditions were established to detect BSH and its possible metabolites in both positive and negative electrospray ionization modes. Using this methodology, boronated ions were found in patients' urine samples that appeared to be consistent with the following chemical structures: BSH sulfenic acid (BSOH), BSH sulfinic acid (BSO(2)H), BSH disulfide (BSSB), BSH thiosulfinate (BSOSB), and a BSH-S-cysteine conjugate (BSH-CYS). Although BSH has been used clinically for BNCT since the late 1960s, this is the first report of specific biotransformation products following administration to patients. Further studies will be required to determine both the biological significance of these metabolites and whether any of these accumulate in significant amounts in brain tumors.
OBJECTIVES: The aim was to assess the content, validity and reproducibility of web-based questionnaires, for a study on osteoporosis prevention among young British women. Twenty-two questionnaires to assess knowledge, self-efficacy, physical activity, calcium intake, health beliefs and stages of change relevant to osteoporosis prevention were identified. Nine were selected and modified to compensate for cultural differences, to suit young women, for completion on the Web. DESIGN: Subjects were recruited by e-mail and asked to complete the web-based questionnaires. Subjects completed the questionnaires again, on paper and were asked to assess the content validity, at least seven days later. SETTING: University of Glasgow, Scotland. SUBJECTS: Sixteen female students and staff aged 19-49. RESULTS: The questionnaires' reproducibility, as measured by the intraclass correlation coefficient was significant at p < 0.01 and acceptable, i.e. above 0.70 for knowledge, 0.85; for self-efficacy, 0.72; for exercise stage of change, 0.79; for exercise benefits, 0.89 and for exercise barriers, 0.82. The intraclass correlation coefficient was significant at p < 0.01 for health belief, 0.43, for weight-bearing physical activity, 0.67, for calcium barriers, 0.48, for 'others around you', 0.65, for calcium stage of change, 0.50 and for calcium intake, 0.56. The intraclass correlation coefficient was not significant for calcium benefits. CONCLUSIONS: Assessing content validity was valuable in ensuring questionnaires were relevant and interpreted correctly by the sample population. Nine web-based questionnaires suitable for, and validated with, young British women are now available for use as outcome measures in studies of health education to prevent osteoporosis.
Exons IIIb and IIIc of the FGFR2 gene are alternatively spliced in a mutually exclusive manner in different cell types. A switch from expression of FGFR2IIIb to FGFR2IIIc accompanies the transition of nonmalignant rat prostate tumor epithelial cells (DTE) to cells comprising malignant AT3 tumors. Here we used transfection of minigenes with and without alterations in reading frame and with and without introns to examine how translation affects observed FGFR2 splice products. We observed that nonsense mutations in other than the last exon led to a dramatic reduction in mRNA that is abrogated by removal of downstream introns in both DTE and AT3 cells. The mRNA, devoid of both IIIb and IIIc exons (C1-C2), is a major splice product from minigenes lacking an intron downstream of the second common exon C2. From these observations, we suggest that repression of exon IIIc and activation of exon IIIb inclusion in DTE cells lead to the generation of both C1-IIIb-C2 and C1-C2 products. However, the C1-C2 product from the native gene is degraded due to a frameshift and a premature termination codon caused by splicing C1 and C2 together. Derepression of exon IIIc and repression of exon IIIb lead to the generation of both C1-IIIc-C2 and C1-C2 products in AT3 cells, but the C1-C2 product is degraded. The C1-IIIb-IIIc-C2 mRNA containing a premature termination codon in exon IIIc was present, but at apparently trace levels in both cell types. The nonsense-mediated mRNA decay pathway and cell type-dependent rates of inclusion of exons IIIb and IIIc result in the mutually exclusive expression of FGFR2IIIb and IIIc.
Mitochondrial proton leak in rat muscle is responsible for approx. 15% of the standard metabolic rate, so its modulation could be important in regulating metabolic efficiency. We report in the present paper that physiological concentrations of AMP (K(0.5)=80 microM) increase the resting respiration rate and double the proton conductance of rat skeletal-muscle mitochondria. This effect is specific for AMP. AMP also doubles proton conductance in skeletal-muscle mitochondria from an ectotherm (the frog Rana temporaria), suggesting that AMP activation is not primarily for thermogenesis. AMP activation in rat muscle mitochondria is unchanged when uncoupling protein-3 is doubled by starvation, indicating that this protein is not involved in the AMP effect. AMP activation is, however, abolished by inhibitors and substrates of the adenine nucleotide translocase (ANT), suggesting that this carrier (possibly the ANT1 isoform) mediates AMP activation. AMP activation of ANT could be important for physiological regulation of metabolic rate.
Heparan sulfate-regulated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes. Fibroblast growth factor has been implicated in the definition of liver from foregut endoderm where FGFR4 is expressed and stimulation of hepatocyte DNA synthesis in vitro. Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normally in response to partial hepatectomy. However, the FGFR4 (-/-) mice exhibited depleted gallbladders, an elevated bile acid pool and elevated excretion of bile acids. Cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase, the limiting enzyme for bile acid synthesis, was elevated, unresponsive to dietary cholesterol, but repressed normally by dietary cholate. Expression pattern and cholate-dependent, cholesterol-induced hepatomegaly in the FGFR4 (-/-) mice suggested that activation of receptor interacting protein 140, a co-repressor of feed-forward activator liver X receptor alpha, may mediate the negative regulation of cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase transcription by FGFR4 and cholate. The results demonstrate that transmembrane sensors interface with metabolite-controlled transcription networks and suggest that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for cell structures and signal transduction.
Behavioral and adrenocortical responses to repeated mechanical restraint were compared in 28-day-old to 31-day-old male Japanese quail from two genetic lines divergently selected for reduced (low stress, LS) or exaggerated (high stress, HS) plasma corticosterone (C) responses to brief immobilization. Restraint in a metal crush cage for 5 min elicited immobility and silence in all the birds. Circulating C levels were considerably higher in quail of both lines following restraint than in the undisturbed controls of either line. As expected, both the behavioral and physiological effects were more pronounced in HS than in LS birds. Struggling increased with repeated restraint in HS and LS quail, thus suggesting behavioral habituation to the stressor in both lines. On the other hand, a line effect on the pattern of adrenocortical responses was revealed upon subtracting the change in plasma C concentrations from Day 1 to Day 4 in the undisturbed controls from the corresponding change in restrained birds. Thus, unlike LS quail, in which there were no detectable effects of repeated restraint, the adrenocortical responses of HS birds showed evidence of experience-dependent sensitization. Our results demonstrate the importance of the background genome in determining the patterns of the behavioral and adrenocortical responses elicited by repeated exposure to stressful stimulation. The present results and those of previous studies could be explained in one or both of two ways: that underlying fearfulness is lower in LS than HS quail or that they adopt active or passive coping strategies, respectively. Our findings may also have important implications for poultry welfare and productivity. @ 2000 Elsevier Science Inc.
The purpose of this review is to analyze the current status of high-dose chemotherapy (HDCT) with autologous stem cell transplantation for patients with breast cancer. Current results from the major prospective phase 2 and phase 3 trials in metastatic breast cancer (MBC) and high-risk primary breast cancer (HRPBC) are reviewed. Prognostic factors and future research directions are also discussed. The encouraging results of phase 2 trials suggested a benefit for HDCT in HRPBC and some categories of patients with MBC. Some investigators have argued that patient selection might have been a critical factor in those studies. Recently reported randomized trials in patients with chemosensitive MBC have included only small numbers of patients in complete remission and thus have not adequately addressed the relative value of HDCT versus maintenance standard-dose chemotherapy in this patient subset. Although initial results of 2 studies have been reported, most randomized phase 3 studies of HDCT in HRPBC require longer follow-up before definitive conclusions can be made about its efficacy in this setting. We conclude that the role of HDCT for HRPBC or MBC patients has not yet been fully defined. Longer follow-up of the ongoing randomized trials is necessary, and their mature results will help clarify this important question. In the meantime, it is imperative that research continues, to enhance the efficacy of the procedure. This may come through incorporating more active drugs into HDCT regimens and combining HDCT with novel strategies aimed at eradication of posttransplantation minimal residual disease.
We retrospectively evaluated 443 breast cancer patients treated with high-dose cyclophosphamide, cisplatin, and BCNU (STAMP-I) with autologous stem cell support to characterize the cardiac toxicity of this regimen. Patients had stage II-III (n = 243) or stage IV (n = 200) breast cancer. We observed an overall 5.1% incidence of cardiac complications, both clinical and subclinical, in the whole group: 4.9% in stage II-III and 5.5% in stage IV patients. Clinical cardiomyopathy (CMP) was observed in 1.6% of stage II-III patients (1 case of fatal grade 5 toxicity and 3 cases of grade 3 CMP) and in 3.5% of patients with stage IV disease (1 case of grade 4 and 6 cases of grade 3). The incidence of cardiac toxicity did not differ significantly between the groups. Prior radiation therapy to the mediastinum or left chest wall (P = .001) and advanced age (P = .01) were independent predictors of an increased risk of the appearance of this complication. No pharmacodynamic correlation was observed between any of the 3 drugs and cardiac toxicity.
D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study investigates the effect of D-pinitol on glucose homeostasis in animal models of diabetes, and on glucose transport by cultured muscle cells. Plasma glucose concentrations were measured in normal, obese-diabetic (ob/ob) and streptozotocin (STZ)-diabetic mice after oral (p.o.) and intraperitoneal (i.p.) administration of D-pinitol. Glucose transport was measured in L6 rat muscle cells by 2-deoxyglucose (2DG) uptake. In STZ-diabetic mice, 100 mg kg(-1) p.o. D-pinitol acutely decreased the hyperglycaemia (by 22% at 6 h). A similar decrease in plasma glucose (by 21%) was observed after 100 mg kg(-1) i.p. D-pinitol. Insulin concentrations and the rate of insulin-induced (1 unit kg(-1) actrapid i.p.) glucose disappearance were not altered by 100 mg kg(-1) p.o. D-pinitol. Chronic administration of D-pinitol (100 mg kg(-1) i.p. twice daily for 11 days) to STZ-diabetic mice maintained a reduction in plasma glucose concentrations from about 14 to 10 mmol l(-1). In normal non-diabetic and severely insulin resistant ob/ob mice, 100 mg kg(-1) p.o. D-pinitol did not significantly affect plasma glucose or insulin during acute studies. Incubation of L6 muscle cells with D-pinitol (10(-3) M) increased basal 2DG uptake by 41% after 10 min and by 34% after 4 h. The effect of D-pinitol was inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. D-pinitol did not increase insulin-stimulated 2DG uptake by L6 cells. The data support the view that D-pinitol can exert an insulin-like effect to improve glycaemic control in hypoinsulinaemic STZ-diabetic mice. D-pinitol may act via a post-receptor pathway of insulin action affecting glucose uptake.
Tacrolimus is increasingly used for graft-versus-host disease (GVHD) prophylaxis and therapy in the allogeneic stem cell transplant (allo-SCT) setting. Pancreatitis, previously described as a side-effect of cyclosporine, has not been reported in allo-SCT recipients receiving tacrolimus. We present here a case of acute pancreatitis in a 28-year-old patient with chronic myelogenous leukemia (CML) who received an unrelated umbilical cord blood transplant (UCBT) and tacrolimus for GVHD prophylaxis. On day +31 post-transplant, she developed severe acute pancreatitis with multiorgan failure, from which she recovered completely. Tacrolimus was the probable cause of pancreatitis in this patient.
Between January and June 1998, postgraduate and undergraduate students from seven centres participated in a discussion of suicide from a public health perspective, using a listserver on the Internet. Most contributions were in English but a few were in Spanish with subsequent translation. Eighteen out of 32 students responding to evaluation, found the module worthwhile and their learning objectives were met. After making a few modifications to procedures resulting from the evaluation, further rounds of discussion were started in October 1998. International discussion groups using listservers on the Internet provide a new and apparently effective method of education.
Significant evidence suggests that Chlamydia pneumoniae has a major role in occlusive vascular disease. Vascular access thrombosis in chronic hemodialysis patients is a frequent problem; the underlying pathological state is stenosis caused by endothelial hyperplasia. There is presently no literature concerning C pneumoniae in vascular access thrombosis. We embarked on a study to evaluate the possible role of C pneumoniae in access failure. Ten consecutive patients with thrombosed polytetrafluoroethylene (PTFE) conduit arteriovenous fistulae undergoing surgical thrombectomy and revision were studied. We sought to detect C pneumoniae using both culture and polymerase chain reaction (PCR) methods. An excisional biopsy of the stenotic vein segment just above the anastomosis with the PTFE graft was obtained at surgery. Vein samples weighing at least 30 mg were aseptically placed in transport media and stored at 4 degrees C for up to 24 hours. The samples then were sonicated, inoculated in Hep-2 cell culture vials containing confluent monolayers, and passaged three times over 2 weeks. Detection was by direct fluorescent antibody staining. Both culture and PCR were performed in an active chlamydia research laboratory. None of the 10 samples was positive for C pneumoniae by culture or PCR. Based on our preliminary pilot study, we do not believe C pneumoniae has a major role in endothelial hyperplasia and consequent graft loss in the hemodialysis patients we studied.
PURPOSE: Although the high incidence of skeletal, neural, and other ocular problems has been identified in previous reports of large cohorts of patients with Duane syndrome, there has not been any documentation of anomalies in close relatives. Patients with Duane syndrome have a greater than 50% incidence of associated abnormalities that include deafness, other ocular anomalies, cranial nerve palsies, and skeletal abnormalities. This study was undertaken to review the experience of our strabismus service with patients who have Duane retraction syndrome (DRS) and to delineate the associated anomalies in them and their first-degree relatives. METHODS: A prospective study of all patients with Duane syndrome who were seen at the strabismus service at Moorfields Eye Hospital has been ongoing for the last 4 years. All patients were assessed for the presence of ophthalmologic features of DRS and then referred to the pediatric service for a physical and neurologic examination. First-degree relatives were also examined, and a family pedigree was generated. RESULTS: We have evaluated 68 patients with DRS, of which 60.2% were female patients. The left eye was involved at a ratio of 4:1 in unilateral cases. The number of bilateral cases was 57.3%. Among the patients with DRS, 46% had first-degree relatives with associated abnormalities. CONCLUSIONS: The high incidence of associated anomalies in patients and first-degree relatives may suggest that a common genetic defect is responsible. This has to be confirmed with molecular genetic studies, which were not performed on these families because of a lack of available resources. However, our findings may indicate that the inheritance of Duane syndrome is much higher than the 10% previously reported, if any congenital abnormality is accepted as DRS associated. Children with Duane syndrome may benefit from a full medical assessment, in view of the frequency of other abnormalities, and so may their siblings.
BACKGROUND: Proliferative diabetic retinopathy (PDR), a prevalent late-stage complication of diabetes, is associated with severe visual loss. The objectives of this report were to estimate the incidence of and risk factors for PDR using routinely collected data from a clinical information system at University Hospital Nottingham for insulin- and non-insulin-dependent (insulin-treated and non-insulin-treated) diabetes separately. We also attempted to assess the risk of blindness in these diabetes clinic attenders. METHODS: During a mean (standard deviation (SD)) follow-up period of 5.1 (2.9) (range 0.5-12.4) years, 3482 diabetic patients (1915 male and 1567 female) from three outpatient clinics at University Hospital, Nottingham were examined. The mean (SD) age of the participants was 49.3 (17.9) years with a mean duration of diabetes of 7.1 (8.7) years at registration. RESULTS: Among the 3482 patients who attended the clinic at least twice in the period 1979-1992, and who were free of PDR at registration, the overall incidence of PDR was 16.2 per 1000 person-years, based on 17,618 person-years of follow-up. The incidence rate of PDR was nearly three times as high among patients with non-proliferative diabetic retinopathy (NPDR) as in those without any retinopathy (42.1 vs. 15.0 per 1000 person-years). Based on a Cox's Proportional Hazards Model, significant independent predictors of PDR recorded at baseline were glycosylated haemoglobin (HbA1), systolic blood pressure, and longer duration of diabetes for patients without PDR or any retinopathy among insulin-dependent patients. Longer duration of diabetes was the only independent predictor of PDR for patients without PDR or any retinopathy in both insulin- and non-insulin-treated non-insulin-dependent patients. These clinic-based data clearly indicate the higher risk of PDR in non-insulin-dependent patients. Gender, age, BMI, creatinine, proteinuria and cigarette smoking, had no significant independent association with PDR when other covariates were considered in all groups. The risk of blindness was greater among those with PDR than those with NPDR in all three types of diabetes, but was substantial even for those without retinopathy. CONCLUSION: These data are of value in identifying those diabetes clinic attenders who may be most at risk.